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Conserved domains on  [gi|945225|gb|AAA74451|]
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guanylyl cyclase [Homo sapiens]

Protein Classification

retinal guanylyl cyclase 2( domain architecture ID 11570903)

retinal guanylyl cyclase 2 may play a specific role in rods and/or cones of photoreceptors, its activity appears modulated by the calmodulin-like Ca(2+)-binding protein GCAP2

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
PBP1_sensory_GC_DEF-like cd06371
ligand-binding domain of membrane guanylyl cyclases (GC-D, GC-E, and GC-F) that are ...
54-435 0e+00

ligand-binding domain of membrane guanylyl cyclases (GC-D, GC-E, and GC-F) that are specifically expressed in sensory tissues; This group includes the ligand-binding domain of membrane guanylyl cyclases (GC-D, GC-E, and GC-F) that are specifically expressed in sensory tissues. They share a similar topology with an N-terminal extracellular ligand-binding domain, a single transmembrane domain, and a C-terminal cytosolic region that contains kinase-like and catalytic domains. GC-D is specifically expressed in a subpopulation of olfactory sensory neurons. GC-E and GC-F are colocalized within the same photoreceptor cells of the retina and have important roles in phototransduction. Unlike the other family members, GC-E and GC-F have no known extracellular ligands. Instead, they are activated under low calcium conditions by guanylyl cyclase activating proteins called GCAPs. GC-D expressing neurons have been implicated in pheromone detection and GC-D is phylogenetically more similar to the Ca2+-regulated GC-E and GC-F than to receptor GC-A, -B and -C which are activated by peptide ligands. Moreover, these olfactory GCs and retinal GCs share characteristic sequence similarity in a regulatory domain that is involved in the binding of GCAPs, suggesting GC-D activity may be regulated by an unknown extracellular ligand and intracellular Ca2+. Rodent GC-D-expressing neurons have been implicated in pheromone detection and were recently shown to respond to atmospheric CO2 which is an olfactory stimulus for many invertebrates and regulates some insect innate behavior, such as the location of food and hosts.


:

Pssm-ID: 380594 [Multi-domain]  Cd Length: 379  Bit Score: 753.38  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225     54 KIGVVGPWACDSLFSKALPEVAARLAIERINRDPSFDLSYSFEYVILNEDCQTSRALSSFISHHQMASGFIGPTNPGYCE 133
Cdd:cd06371    1 KVGVVGPWTCDPIFAKALPDLAARLAVSRINKDPSLDLGYWFDYVILPEDCETSKALAAFSSAEGRASGFVGPVNPGYCE 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    134 AASLLGNSWDKGIFSWACVNYELDnkiSYPTFSRTLPSPIRVLVTVMKYFQWAHAGVISSDEDIWVHTANRVASALRSHG 213
Cdd:cd06371   81 AASLLAQEWDKALFSWGCVNHELN---SYPTFARTLPPPADVLYTVLRYFRWAHVAVVSSPQDLWVETGRELASALRARG 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    214 LPVGVVLTTGQDSQSMRKALQRIHQADRIRIIIMCMHSALIGGETQMHLLECAHDLKMTDGTYVFVPYDALLYSLPYKHT 293
Cdd:cd06371  158 LPVGLVTSMEPSDSGAREALKRIRDADRVRVVIMCMHSVLIGGEEQRTLLEAAHDMGLTDGSYVFVPYDTLLYSLPYKHE 237
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    294 PYQVLRNNPKLREAYDAVLTITVESQEKTFYQAFTEAAARGEIPEKLEFDQVSPLFGTIYNSIYFIAQAMNNAMKENGQA 373
Cdd:cd06371  238 PYAVLRNNSKLRRAYDAVLTITMESPEGSFYEAFRRAQERGELPSDLDPEQVSPLFGTIYNSIYLLAGAVENARAAGGGV 317
                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 945225    374 GAASLVQHSRNMQFHGFNQLMRTDSNGNGISEYVILDTNLKEWELHSTYTVDMEMELLRFGG 435
Cdd:cd06371  318 SGASLARHARNAQFPGFNQLLRTDSGGNGQPSYVILDTDGKGWRLFPTYTLDMTTGLLRFLG 379
PKc_like super family cl21453
Protein Kinases, catalytic domain; The protein kinase superfamily is mainly composed of the ...
545-815 2.64e-138

Protein Kinases, catalytic domain; The protein kinase superfamily is mainly composed of the catalytic domains of serine/threonine-specific and tyrosine-specific protein kinases. It also includes RIO kinases, which are atypical serine protein kinases, aminoglycoside phosphotransferases, and choline kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to hydroxyl groups in specific substrates such as serine, threonine, or tyrosine residues of proteins.


The actual alignment was detected with superfamily member cd14043:

Pssm-ID: 473864 [Multi-domain]  Cd Length: 267  Bit Score: 417.96  E-value: 2.64e-138
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    545 RLSFSSGSLTPATYENSNIAiYEGDWVWLKKFSLGDFGDlksIKSRASDVFEMMKDLRHENINPLLGFFYDSGMFAIVTE 624
Cdd:cd14043    1 PSSPSSTSSVNATSSNTGVA-YEGDWVWLKKFPGGSHTE---LRPSTKNVFSKLRELRHENVNLFLGLFVDCGILAIVSE 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    625 FCSRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGFNDILEMLRLSEEE 704
Cdd:cd14043   77 HCSRGSLEDLLRNDDMKLDWMFKSSLLLDLIKGMRYLHHRGIVHGRLKSRNCVVDGRFVLKITDYGYNEILEAQNLPLPE 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    705 SSMEELLWTAPELLRAPRGSRLGSFAGDVYSFAIIMQEVMVRGTPFCMMDLPAQEIINRLKKPPPVYRPVVPPEHAPPEC 784
Cdd:cd14043  157 PAPEELLWTAPELLRDPRLERRGTFPGDVFSFAIIMQEVIVRGAPYCMLGLSPEEIIEKVRSPPPLCRPSVSMDQAPLEC 236
                        250       260       270
                 ....*....|....*....|....*....|.
gi 945225    785 LQLMKQCWAEAAEQRPTFDEIFNQFKTFNKG 815
Cdd:cd14043  237 IQLMKQCWSEAPERRPTFDQIFDQFKSINKG 267
CYCc smart00044
Adenylyl- / guanylyl cyclase, catalytic domain; Present in two copies in mammalian adenylyl ...
848-1040 1.02e-91

Adenylyl- / guanylyl cyclase, catalytic domain; Present in two copies in mammalian adenylyl cyclases. Eubacterial homologues are known. Two residues (Asn, Arg) are thought to be involved in catalysis. These cyclases have important roles in a diverse range of cellular processes.


:

Pssm-ID: 214485  Cd Length: 194  Bit Score: 291.47  E-value: 1.02e-91
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225       848 IEKQKTEKLLTQMLPPSVAESLK-KGCTVEPEGFDLVTLYFSDIVGFTTISAMSEPIEVVDLLNDLYTLFDAIIGSHDVY 926
Cdd:smart00044    1 EEKKKTDRLLDQLLPASVAEQLKrGGSPVPAESYDNVTILFSDIVGFTSLCSTSTPEQVVNLLNDLYSRFDQIIDRHGGY 80
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225       927 KVETIGDAYMVASGLPKRNGSRHAAEIANMSLDILSSVGTFKMRHmPEVPVRIRIGLHSGPVVAGVVGLTMPRYCLFGDT 1006
Cdd:smart00044   81 KVKTIGDAYMVASGLPEEALVDHAELIADEALDMVEELKTVLVQH-REEGLRVRIGIHTGPVVAGVVGIRMPRYCLFGDT 159
                           170       180       190
                    ....*....|....*....|....*....|....
gi 945225      1007 VNTASRMESTGLPYRIHVSLSTVTILQNLSEGYE 1040
Cdd:smart00044  160 VNLASRMESAGDPGQIQVSEETYSLLARRGGQFV 193
HNOBA super family cl06648
Heme NO binding associated; The HNOBA domain is found associated with the HNOB domain and ...
824-869 2.33e-08

Heme NO binding associated; The HNOBA domain is found associated with the HNOB domain and pfam00211 in soluble cyclases and signalling proteins. The HNOB domain is predicted to function as a heme-dependent sensor for gaseous ligands, and transduce diverse downstream signals, in both bacteria and animals.


The actual alignment was detected with superfamily member pfam07701:

Pssm-ID: 462234  Cd Length: 214  Bit Score: 55.66  E-value: 2.33e-08
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 945225      824 MLRMLEQYSSNLEDLirerTEELEIEKQKTEKLLTQMLPPSVAESL 869
Cdd:pfam07701  173 ALDQLEQKSAELEES----MRELEEEKKKTDELLYSMLPKSVADRL 214
 
Name Accession Description Interval E-value
PBP1_sensory_GC_DEF-like cd06371
ligand-binding domain of membrane guanylyl cyclases (GC-D, GC-E, and GC-F) that are ...
54-435 0e+00

ligand-binding domain of membrane guanylyl cyclases (GC-D, GC-E, and GC-F) that are specifically expressed in sensory tissues; This group includes the ligand-binding domain of membrane guanylyl cyclases (GC-D, GC-E, and GC-F) that are specifically expressed in sensory tissues. They share a similar topology with an N-terminal extracellular ligand-binding domain, a single transmembrane domain, and a C-terminal cytosolic region that contains kinase-like and catalytic domains. GC-D is specifically expressed in a subpopulation of olfactory sensory neurons. GC-E and GC-F are colocalized within the same photoreceptor cells of the retina and have important roles in phototransduction. Unlike the other family members, GC-E and GC-F have no known extracellular ligands. Instead, they are activated under low calcium conditions by guanylyl cyclase activating proteins called GCAPs. GC-D expressing neurons have been implicated in pheromone detection and GC-D is phylogenetically more similar to the Ca2+-regulated GC-E and GC-F than to receptor GC-A, -B and -C which are activated by peptide ligands. Moreover, these olfactory GCs and retinal GCs share characteristic sequence similarity in a regulatory domain that is involved in the binding of GCAPs, suggesting GC-D activity may be regulated by an unknown extracellular ligand and intracellular Ca2+. Rodent GC-D-expressing neurons have been implicated in pheromone detection and were recently shown to respond to atmospheric CO2 which is an olfactory stimulus for many invertebrates and regulates some insect innate behavior, such as the location of food and hosts.


Pssm-ID: 380594 [Multi-domain]  Cd Length: 379  Bit Score: 753.38  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225     54 KIGVVGPWACDSLFSKALPEVAARLAIERINRDPSFDLSYSFEYVILNEDCQTSRALSSFISHHQMASGFIGPTNPGYCE 133
Cdd:cd06371    1 KVGVVGPWTCDPIFAKALPDLAARLAVSRINKDPSLDLGYWFDYVILPEDCETSKALAAFSSAEGRASGFVGPVNPGYCE 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    134 AASLLGNSWDKGIFSWACVNYELDnkiSYPTFSRTLPSPIRVLVTVMKYFQWAHAGVISSDEDIWVHTANRVASALRSHG 213
Cdd:cd06371   81 AASLLAQEWDKALFSWGCVNHELN---SYPTFARTLPPPADVLYTVLRYFRWAHVAVVSSPQDLWVETGRELASALRARG 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    214 LPVGVVLTTGQDSQSMRKALQRIHQADRIRIIIMCMHSALIGGETQMHLLECAHDLKMTDGTYVFVPYDALLYSLPYKHT 293
Cdd:cd06371  158 LPVGLVTSMEPSDSGAREALKRIRDADRVRVVIMCMHSVLIGGEEQRTLLEAAHDMGLTDGSYVFVPYDTLLYSLPYKHE 237
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    294 PYQVLRNNPKLREAYDAVLTITVESQEKTFYQAFTEAAARGEIPEKLEFDQVSPLFGTIYNSIYFIAQAMNNAMKENGQA 373
Cdd:cd06371  238 PYAVLRNNSKLRRAYDAVLTITMESPEGSFYEAFRRAQERGELPSDLDPEQVSPLFGTIYNSIYLLAGAVENARAAGGGV 317
                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 945225    374 GAASLVQHSRNMQFHGFNQLMRTDSNGNGISEYVILDTNLKEWELHSTYTVDMEMELLRFGG 435
Cdd:cd06371  318 SGASLARHARNAQFPGFNQLLRTDSGGNGQPSYVILDTDGKGWRLFPTYTLDMTTGLLRFLG 379
PK_GC-2D cd14043
Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-2D; The pseudokinase domain ...
545-815 2.64e-138

Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-2D; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding. GC-2D is allso called Retinal Guanylyl Cyclase 1 (RETGC-1) or Rod Outer Segment membrane Guanylate Cyclase (ROS-GC). It is found in the photoreceptors of the retina where it anchors the reciprocal feedback loop between calcium and cGMP, which regulates the dark, light, and recovery phases in phototransduction. It is also found in other sensory neurons and may be a universal transduction component that plays a role in the perception of all senses. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC-2D subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270945 [Multi-domain]  Cd Length: 267  Bit Score: 417.96  E-value: 2.64e-138
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    545 RLSFSSGSLTPATYENSNIAiYEGDWVWLKKFSLGDFGDlksIKSRASDVFEMMKDLRHENINPLLGFFYDSGMFAIVTE 624
Cdd:cd14043    1 PSSPSSTSSVNATSSNTGVA-YEGDWVWLKKFPGGSHTE---LRPSTKNVFSKLRELRHENVNLFLGLFVDCGILAIVSE 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    625 FCSRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGFNDILEMLRLSEEE 704
Cdd:cd14043   77 HCSRGSLEDLLRNDDMKLDWMFKSSLLLDLIKGMRYLHHRGIVHGRLKSRNCVVDGRFVLKITDYGYNEILEAQNLPLPE 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    705 SSMEELLWTAPELLRAPRGSRLGSFAGDVYSFAIIMQEVMVRGTPFCMMDLPAQEIINRLKKPPPVYRPVVPPEHAPPEC 784
Cdd:cd14043  157 PAPEELLWTAPELLRDPRLERRGTFPGDVFSFAIIMQEVIVRGAPYCMLGLSPEEIIEKVRSPPPLCRPSVSMDQAPLEC 236
                        250       260       270
                 ....*....|....*....|....*....|.
gi 945225    785 LQLMKQCWAEAAEQRPTFDEIFNQFKTFNKG 815
Cdd:cd14043  237 IQLMKQCWSEAPERRPTFDQIFDQFKSINKG 267
CYCc smart00044
Adenylyl- / guanylyl cyclase, catalytic domain; Present in two copies in mammalian adenylyl ...
848-1040 1.02e-91

Adenylyl- / guanylyl cyclase, catalytic domain; Present in two copies in mammalian adenylyl cyclases. Eubacterial homologues are known. Two residues (Asn, Arg) are thought to be involved in catalysis. These cyclases have important roles in a diverse range of cellular processes.


Pssm-ID: 214485  Cd Length: 194  Bit Score: 291.47  E-value: 1.02e-91
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225       848 IEKQKTEKLLTQMLPPSVAESLK-KGCTVEPEGFDLVTLYFSDIVGFTTISAMSEPIEVVDLLNDLYTLFDAIIGSHDVY 926
Cdd:smart00044    1 EEKKKTDRLLDQLLPASVAEQLKrGGSPVPAESYDNVTILFSDIVGFTSLCSTSTPEQVVNLLNDLYSRFDQIIDRHGGY 80
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225       927 KVETIGDAYMVASGLPKRNGSRHAAEIANMSLDILSSVGTFKMRHmPEVPVRIRIGLHSGPVVAGVVGLTMPRYCLFGDT 1006
Cdd:smart00044   81 KVKTIGDAYMVASGLPEEALVDHAELIADEALDMVEELKTVLVQH-REEGLRVRIGIHTGPVVAGVVGIRMPRYCLFGDT 159
                           170       180       190
                    ....*....|....*....|....*....|....
gi 945225      1007 VNTASRMESTGLPYRIHVSLSTVTILQNLSEGYE 1040
Cdd:smart00044  160 VNLASRMESAGDPGQIQVSEETYSLLARRGGQFV 193
Guanylate_cyc pfam00211
Adenylate and Guanylate cyclase catalytic domain;
875-1062 6.56e-80

Adenylate and Guanylate cyclase catalytic domain;


Pssm-ID: 425528  Cd Length: 183  Bit Score: 259.10  E-value: 6.56e-80
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225      875 VEPEGFDLVTLYFSDIVGFTTISAMSEPIEVVDLLNDLYTLFDAIIGSHDVYKVETIGDAYMVASGLPkRNGSRHAAEIA 954
Cdd:pfam00211    1 VYAQPYDNVTILFADIVGFTALSSRHSPEQVVRLLNELYTRFDRLLDKHKVYKVKTIGDAYMVVSGLP-EPSPAHARKIA 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225      955 NMSLDILSSVGTFKMRHMPevPVRIRIGLHSGPVVAGVVGLTMPRYCLFGDTVNTASRMESTGLPYRIHVSLSTVTILQN 1034
Cdd:pfam00211   80 EMALDMLEAIGEVNVESSE--GLRVRVGIHTGPVVAGVIGARMPRYDLWGNTVNLASRMESTGVPGKIHVSEETYRLLKT 157
                          170       180
                   ....*....|....*....|....*...
gi 945225     1035 lsEGYEVELRGRTELKGKGTEETFWLIG 1062
Cdd:pfam00211  158 --EGFEFTERGEIEVKGKGKMKTYFLNG 183
ANF_receptor pfam01094
Receptor family ligand binding region; This family includes extracellular ligand binding ...
71-412 1.02e-74

Receptor family ligand binding region; This family includes extracellular ligand binding domains of a wide range of receptors. This family also includes the bacterial amino acid binding proteins of known structure.


Pssm-ID: 460062 [Multi-domain]  Cd Length: 347  Bit Score: 251.15  E-value: 1.02e-74
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225       71 LPEVAARLAIERINRDPSFDLSYSFEYVILNEDCQTSRALSSFISHHQ-MASGFIGPTNPGYCEAASLLGNSWDKGIFSW 149
Cdd:pfam01094    1 LVLLAVRLAVEDINADPGLLPGTKLEYIILDTCCDPSLALAAALDLLKgEVVAIIGPSCSSVASAVASLANEWKVPLISY 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225      150 ACVNYELDNKISYPTFSRTLPS---PIRVLVTVMKYFQWAHAGVISSDEDIWVHTANRVASALRSHGLPVGVVLTTGQ-- 224
Cdd:pfam01094   81 GSTSPALSDLNRYPTFLRTTPSdtsQADAIVDILKHFGWKRVALIYSDDDYGESGLQALEDALRERGIRVAYKAVIPPaq 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225      225 -DSQSMRKALQRIHQadRIRIIIMCMHSaliggETQMHLLECAHDLKMTDGTYVFVPYDALLYSLPYKHTPYqvlrnnpk 303
Cdd:pfam01094  161 dDDEIARKLLKEVKS--RARVIVVCCSS-----ETARRLLKAARELGMMGEGYVWIATDGLTTSLVILNPST-------- 225
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225      304 lREAYDAVLTITVESQEKTFYQAFTE--AAARGEIPEKLEFDQVSPLFgTIYNSIYFIAQAMNNAMKENGQ--------- 372
Cdd:pfam01094  226 -LEAAGGVLGFRLHPPDSPEFSEFFWekLSDEKELYENLGGLPVSYGA-LAYDAVYLLAHALHNLLRDDKPgracgalgp 303
                          330       340       350       360
                   ....*....|....*....|....*....|....*....|..
gi 945225      373 -AGAASLVQHSRNMQFHGFNQLMRTDSNGNGIS-EYVILDTN 412
Cdd:pfam01094  304 wNGGQKLLRYLKNVNFTGLTGNVQFDENGDRINpDYDILNLN 345
CHD cd07302
cyclase homology domain; Catalytic domains of the mononucleotidyl cyclases (MNC's), also ...
883-1060 2.94e-65

cyclase homology domain; Catalytic domains of the mononucleotidyl cyclases (MNC's), also called cyclase homology domains (CHDs), are part of the class III nucleotidyl cyclases. This class includes eukaryotic and prokaryotic adenylate cyclases (AC's) and guanylate cyclases (GC's). They seem to share a common catalytic mechanism in their requirement for two magnesium ions to bind the polyphosphate moiety of the nucleotide.


Pssm-ID: 143636 [Multi-domain]  Cd Length: 177  Bit Score: 217.83  E-value: 2.94e-65
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    883 VTLYFSDIVGFTTISAMSEPIEVVDLLNDLYTLFDAIIGSHDVYKVETIGDAYMVASGLPKRNGsRHAAEIANMSLDILS 962
Cdd:cd07302    2 VTVLFADIVGFTALSERLGPEELVELLNEYFSAFDEIIERHGGTVDKTIGDAVMAVFGLPGAHE-DHAERAVRAALEMQE 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    963 SVGTFKMRHMPEVPVRIRIGLHSGPVVAGVVGLTMPRYCLFGDTVNTASRMESTGLPYRIHVSLSTVTILQNlsEGYEVE 1042
Cdd:cd07302   81 ALAELNAEREGGPPLRLRIGIHTGPVVAGVVGSERPEYTVIGDTVNLAARLESLAKPGQILVSEATYELLGD--AGFEFE 158
                        170
                 ....*....|....*....
gi 945225   1043 LRGRTELKGK-GTEETFWL 1060
Cdd:cd07302  159 ELGEVELKGKsGPVRVYRL 177
AcyC COG2114
Adenylate cyclase, class 3 [Signal transduction mechanisms];
820-1065 5.67e-48

Adenylate cyclase, class 3 [Signal transduction mechanisms];


Pssm-ID: 441717 [Multi-domain]  Cd Length: 407  Bit Score: 176.92  E-value: 5.67e-48
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    820 IIDSMLRMLEQYSSNLEDLIRERTEELEIEKQKTEKLLTQMLPPSVAESLKKGCTVEPEG--FDLVTLYFSDIVGFTTIS 897
Cdd:COG2114  158 VALLLLALLLLLLLLLLLALLLLLLLALRERERLRDLLGRYLPPEVAERLLAGGEELRLGgeRREVTVLFADIVGFTALS 237
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    898 AMSEPIEVVDLLNDLYTLFDAIIGSHDVYKVETIGDAYMVASGLPKRNGSrHAAEIANMSLDILSSVGTF--KMRHMPEV 975
Cdd:COG2114  238 ERLGPEELVELLNRYFSAMVEIIERHGGTVDKFIGDGVMAVFGAPVARED-HAERAVRAALAMQEALAELnaELPAEGGP 316
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    976 PVRIRIGLHSGPVVAGVVGLTMPR-YCLFGDTVNTASRMESTGLPYRIHVSLSTVtilQNLSEGYEVELRGRTELKGKGT 1054
Cdd:COG2114  317 PLRVRIGIHTGEVVVGNIGSEDRLdYTVIGDTVNLAARLESLAKPGEILVSEATY---DLLRDRFEFRELGEVRLKGKAE 393
                        250
                 ....*....|..
gi 945225   1055 E-ETFWLIGKKG 1065
Cdd:COG2114  394 PvEVYELLGAKE 405
TyrKc smart00219
Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.
585-809 1.22e-37

Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.


Pssm-ID: 197581 [Multi-domain]  Cd Length: 257  Bit Score: 141.90  E-value: 1.22e-37
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225       585 KSIKSRASDV--------FEMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKLDWMFKSSLLLDLIK 656
Cdd:smart00219   34 KTLKEDASEQqieeflreARIMRKLDHPNVVKLLGVCTEEEPLYIVMEYMEGGDLLSYLRKNRPKLSLSDLLSFALQIAR 113
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225       657 GMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGfndileMLRLSEEESSMEELL------WTAPELLRaprgSRLGSFA 730
Cdd:smart00219  114 GMEYLESKNFIHRDLAARNCLVGENLVVKISDFG------LSRDLYDDDYYRKRGgklpirWMAPESLK----EGKFTSK 183
                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225       731 GDVYSFAIIMQEVMVRG-TPFCmmDLPAQEIINRLKKpppvYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEIFNQF 809
Cdd:smart00219  184 SDVWSFGVLLWEIFTLGeQPYP--GMSNEEVLEYLKN----GYRLPQPPNCPPELYDLMLQCWAEDPEDRPTFSELVEIL 257
PK_Tyr_Ser-Thr pfam07714
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ...
596-809 2.84e-37

Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyze the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyze the reverse process. Protein kinases fall into three broad classes, characterized with respect to substrate specificity; Serine/threonine-protein kinases, tyrosine-protein kinases, and dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins). This entry represents the catalytic domain found in a number of serine/threonine- and tyrosine-protein kinases. It does not include the catalytic domain of dual specificity kinases.


Pssm-ID: 462242 [Multi-domain]  Cd Length: 258  Bit Score: 141.09  E-value: 2.84e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225      596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRN 675
Cdd:pfam07714   53 SIMKKLDHPNIVKLLGVCTQGEPLYIVTEYMPGGDLLDFLRKHKRKLTLKDLLSMALQIAKGMEYLESKNFVHRDLAARN 132
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225      676 CVVDGRFVLKVTDYG-FNDILEMLRLSEEESSMEELLWTAPELLRAprgsRLGSFAGDVYSFAIIMQEVMVRG-TPFCmm 753
Cdd:pfam07714  133 CLVSENLVVKISDFGlSRDIYDDDYYRKRGGGKLPIKWMAPESLKD----GKFTSKSDVWSFGVLLWEIFTLGeQPYP-- 206
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 945225      754 DLPAQEIINRLKKpppvYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEIFNQF 809
Cdd:pfam07714  207 GMSNEEVLEFLED----GYRLPQPENCPDELYDLMKQCWAYDPEDRPTFSELVEDL 258
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
596-750 9.27e-11

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 65.42  E-value: 9.27e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILtNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRN 675
Cdd:COG0515   59 RALARLNHPNIVRVYDVGEEDGRPYLVMEYVEGESLADLL-RRRGPLPPAEALRILAQLAEALAAAHAAGIVHRDIKPAN 137
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 945225    676 CVVDGRFVLKVTDYGFNDILEMLRLSEEESSMEELLWTAPELLrapRGSRLGsFAGDVYSFAIIMQEVMVRGTPF 750
Cdd:COG0515  138 ILLTPDGRVKLIDFGIARALGGATLTQTGTVVGTPGYMAPEQA---RGEPVD-PRSDVYSLGVTLYELLTGRPPF 208
PHA02988 PHA02988
hypothetical protein; Provisional
558-812 1.69e-08

hypothetical protein; Provisional


Pssm-ID: 165291 [Multi-domain]  Cd Length: 283  Bit Score: 57.06  E-value: 1.69e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225     558 YENSNIAIYEGDW----VWLKKFSlGDFGDLKSIKSRASDVFEMMKDLRHENINPLLGFFYDSG----MFAIVTEFCSRG 629
Cdd:PHA02988   29 KENDQNSIYKGIFnnkeVIIRTFK-KFHKGHKVLIDITENEIKNLRRIDSNNILKIYGFIIDIVddlpRLSLILEYCTRG 107
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225     630 SLEDILTNQDvKLDWMFKSSLLLDLIKGMKYLH-HREFVHGRLKSRNCVVDGRFVLKVTDYGfndiLEMLRLSEEESSME 708
Cdd:PHA02988  108 YLREVLDKEK-DLSFKTKLDMAIDCCKGLYNLYkYTNKPYKNLTSVSFLVTENYKLKIICHG----LEKILSSPPFKNVN 182
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225     709 ELLWTAPELLRAPRGSRLgsFAGDVYSFAIIMQEVMVRGTPFCMMDlpAQEIINRLKKpppvyrpVVPPEHAPPECLQLM 788
Cdd:PHA02988  183 FMVYFSYKMLNDIFSEYT--IKDDIYSLGVVLWEIFTGKIPFENLT--TKEIYDLIIN-------KNNSLKLPLDCPLEI 251
                         250       260
                  ....*....|....*....|....*...
gi 945225     789 K----QCWAEAAEQRPTFDEIFNQFKTF 812
Cdd:PHA02988  252 KciveACTSHDSIKRPNIKEILYNLSLY 279
HNOBA pfam07701
Heme NO binding associated; The HNOBA domain is found associated with the HNOB domain and ...
824-869 2.33e-08

Heme NO binding associated; The HNOBA domain is found associated with the HNOB domain and pfam00211 in soluble cyclases and signalling proteins. The HNOB domain is predicted to function as a heme-dependent sensor for gaseous ligands, and transduce diverse downstream signals, in both bacteria and animals.


Pssm-ID: 462234  Cd Length: 214  Bit Score: 55.66  E-value: 2.33e-08
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 945225      824 MLRMLEQYSSNLEDLirerTEELEIEKQKTEKLLTQMLPPSVAESL 869
Cdd:pfam07701  173 ALDQLEQKSAELEES----MRELEEEKKKTDELLYSMLPKSVADRL 214
LivK COG0683
ABC-type branched-chain amino acid transport system, periplasmic component [Amino acid ...
52-409 1.58e-05

ABC-type branched-chain amino acid transport system, periplasmic component [Amino acid transport and metabolism];


Pssm-ID: 440447 [Multi-domain]  Cd Length: 314  Bit Score: 48.39  E-value: 1.58e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225     52 PYKIGVV----GPWAcdsLFSKALpEVAARLAIERINRDPSFdLSYSFEYVILNEDCQTSRALS---SFISHHQmASGFI 124
Cdd:COG0683    3 PIKIGVLlpltGPYA---ALGQPI-KNGAELAVEEINAAGGV-LGRKIELVVEDDASDPDTAVAaarKLIDQDK-VDAIV 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    125 GPTNPGYCEAASLLGNswDKGI--FSWACVNYELDNKISYPTFSRTLPSP---IRVLVTVMKY-FQWAHAGVISSDEDIW 198
Cdd:COG0683   77 GPLSSGVALAVAPVAE--EAGVplISPSATAPALTGPECSPYVFRTAPSDaqqAEALADYLAKkLGAKKVALLYDDYAYG 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    199 VHTANRVASALRSHGLPVGVVLTTGQDSQSMRKALQRIHQADririiimcmhsaliggetqmhllecahdlkmtdgtyvf 278
Cdd:COG0683  155 QGLAAAFKAALKAAGGEVVGEEYYPPGTTDFSAQLTKIKAAG-------------------------------------- 196
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    279 vPyDALLYSLPYKHTPyQVLRNnpkLREA-YDAVLTitvesqeKTFYQAFTEAAARgeipeklefdQVSPLFGTIYNSIY 357
Cdd:COG0683  197 -P-DAVFLAGYGGDAA-LFIKQ---AREAgLKGPLN-------KAFVKAYKAKYGR----------EPSSYAAAGYDAAL 253
                        330       340       350       360       370
                 ....*....|....*....|....*....|....*....|....*....|..
gi 945225    358 FIAQAMNNAMKENGQAGAASLvqhsRNMQFHGFNQLMRTDSNGNGISEYVIL 409
Cdd:COG0683  254 LLAEAIEKAGSTDREAVRDAL----EGLKFDGVTGPITFDPDGQGVQPVYIV 301
 
Name Accession Description Interval E-value
PBP1_sensory_GC_DEF-like cd06371
ligand-binding domain of membrane guanylyl cyclases (GC-D, GC-E, and GC-F) that are ...
54-435 0e+00

ligand-binding domain of membrane guanylyl cyclases (GC-D, GC-E, and GC-F) that are specifically expressed in sensory tissues; This group includes the ligand-binding domain of membrane guanylyl cyclases (GC-D, GC-E, and GC-F) that are specifically expressed in sensory tissues. They share a similar topology with an N-terminal extracellular ligand-binding domain, a single transmembrane domain, and a C-terminal cytosolic region that contains kinase-like and catalytic domains. GC-D is specifically expressed in a subpopulation of olfactory sensory neurons. GC-E and GC-F are colocalized within the same photoreceptor cells of the retina and have important roles in phototransduction. Unlike the other family members, GC-E and GC-F have no known extracellular ligands. Instead, they are activated under low calcium conditions by guanylyl cyclase activating proteins called GCAPs. GC-D expressing neurons have been implicated in pheromone detection and GC-D is phylogenetically more similar to the Ca2+-regulated GC-E and GC-F than to receptor GC-A, -B and -C which are activated by peptide ligands. Moreover, these olfactory GCs and retinal GCs share characteristic sequence similarity in a regulatory domain that is involved in the binding of GCAPs, suggesting GC-D activity may be regulated by an unknown extracellular ligand and intracellular Ca2+. Rodent GC-D-expressing neurons have been implicated in pheromone detection and were recently shown to respond to atmospheric CO2 which is an olfactory stimulus for many invertebrates and regulates some insect innate behavior, such as the location of food and hosts.


Pssm-ID: 380594 [Multi-domain]  Cd Length: 379  Bit Score: 753.38  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225     54 KIGVVGPWACDSLFSKALPEVAARLAIERINRDPSFDLSYSFEYVILNEDCQTSRALSSFISHHQMASGFIGPTNPGYCE 133
Cdd:cd06371    1 KVGVVGPWTCDPIFAKALPDLAARLAVSRINKDPSLDLGYWFDYVILPEDCETSKALAAFSSAEGRASGFVGPVNPGYCE 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    134 AASLLGNSWDKGIFSWACVNYELDnkiSYPTFSRTLPSPIRVLVTVMKYFQWAHAGVISSDEDIWVHTANRVASALRSHG 213
Cdd:cd06371   81 AASLLAQEWDKALFSWGCVNHELN---SYPTFARTLPPPADVLYTVLRYFRWAHVAVVSSPQDLWVETGRELASALRARG 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    214 LPVGVVLTTGQDSQSMRKALQRIHQADRIRIIIMCMHSALIGGETQMHLLECAHDLKMTDGTYVFVPYDALLYSLPYKHT 293
Cdd:cd06371  158 LPVGLVTSMEPSDSGAREALKRIRDADRVRVVIMCMHSVLIGGEEQRTLLEAAHDMGLTDGSYVFVPYDTLLYSLPYKHE 237
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    294 PYQVLRNNPKLREAYDAVLTITVESQEKTFYQAFTEAAARGEIPEKLEFDQVSPLFGTIYNSIYFIAQAMNNAMKENGQA 373
Cdd:cd06371  238 PYAVLRNNSKLRRAYDAVLTITMESPEGSFYEAFRRAQERGELPSDLDPEQVSPLFGTIYNSIYLLAGAVENARAAGGGV 317
                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 945225    374 GAASLVQHSRNMQFHGFNQLMRTDSNGNGISEYVILDTNLKEWELHSTYTVDMEMELLRFGG 435
Cdd:cd06371  318 SGASLARHARNAQFPGFNQLLRTDSGGNGQPSYVILDTDGKGWRLFPTYTLDMTTGLLRFLG 379
PK_GC-2D cd14043
Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-2D; The pseudokinase domain ...
545-815 2.64e-138

Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-2D; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding. GC-2D is allso called Retinal Guanylyl Cyclase 1 (RETGC-1) or Rod Outer Segment membrane Guanylate Cyclase (ROS-GC). It is found in the photoreceptors of the retina where it anchors the reciprocal feedback loop between calcium and cGMP, which regulates the dark, light, and recovery phases in phototransduction. It is also found in other sensory neurons and may be a universal transduction component that plays a role in the perception of all senses. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC-2D subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270945 [Multi-domain]  Cd Length: 267  Bit Score: 417.96  E-value: 2.64e-138
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    545 RLSFSSGSLTPATYENSNIAiYEGDWVWLKKFSLGDFGDlksIKSRASDVFEMMKDLRHENINPLLGFFYDSGMFAIVTE 624
Cdd:cd14043    1 PSSPSSTSSVNATSSNTGVA-YEGDWVWLKKFPGGSHTE---LRPSTKNVFSKLRELRHENVNLFLGLFVDCGILAIVSE 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    625 FCSRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGFNDILEMLRLSEEE 704
Cdd:cd14043   77 HCSRGSLEDLLRNDDMKLDWMFKSSLLLDLIKGMRYLHHRGIVHGRLKSRNCVVDGRFVLKITDYGYNEILEAQNLPLPE 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    705 SSMEELLWTAPELLRAPRGSRLGSFAGDVYSFAIIMQEVMVRGTPFCMMDLPAQEIINRLKKPPPVYRPVVPPEHAPPEC 784
Cdd:cd14043  157 PAPEELLWTAPELLRDPRLERRGTFPGDVFSFAIIMQEVIVRGAPYCMLGLSPEEIIEKVRSPPPLCRPSVSMDQAPLEC 236
                        250       260       270
                 ....*....|....*....|....*....|.
gi 945225    785 LQLMKQCWAEAAEQRPTFDEIFNQFKTFNKG 815
Cdd:cd14043  237 IQLMKQCWSEAPERRPTFDQIFDQFKSINKG 267
CYCc smart00044
Adenylyl- / guanylyl cyclase, catalytic domain; Present in two copies in mammalian adenylyl ...
848-1040 1.02e-91

Adenylyl- / guanylyl cyclase, catalytic domain; Present in two copies in mammalian adenylyl cyclases. Eubacterial homologues are known. Two residues (Asn, Arg) are thought to be involved in catalysis. These cyclases have important roles in a diverse range of cellular processes.


Pssm-ID: 214485  Cd Length: 194  Bit Score: 291.47  E-value: 1.02e-91
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225       848 IEKQKTEKLLTQMLPPSVAESLK-KGCTVEPEGFDLVTLYFSDIVGFTTISAMSEPIEVVDLLNDLYTLFDAIIGSHDVY 926
Cdd:smart00044    1 EEKKKTDRLLDQLLPASVAEQLKrGGSPVPAESYDNVTILFSDIVGFTSLCSTSTPEQVVNLLNDLYSRFDQIIDRHGGY 80
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225       927 KVETIGDAYMVASGLPKRNGSRHAAEIANMSLDILSSVGTFKMRHmPEVPVRIRIGLHSGPVVAGVVGLTMPRYCLFGDT 1006
Cdd:smart00044   81 KVKTIGDAYMVASGLPEEALVDHAELIADEALDMVEELKTVLVQH-REEGLRVRIGIHTGPVVAGVVGIRMPRYCLFGDT 159
                           170       180       190
                    ....*....|....*....|....*....|....
gi 945225      1007 VNTASRMESTGLPYRIHVSLSTVTILQNLSEGYE 1040
Cdd:smart00044  160 VNLASRMESAGDPGQIQVSEETYSLLARRGGQFV 193
Guanylate_cyc pfam00211
Adenylate and Guanylate cyclase catalytic domain;
875-1062 6.56e-80

Adenylate and Guanylate cyclase catalytic domain;


Pssm-ID: 425528  Cd Length: 183  Bit Score: 259.10  E-value: 6.56e-80
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225      875 VEPEGFDLVTLYFSDIVGFTTISAMSEPIEVVDLLNDLYTLFDAIIGSHDVYKVETIGDAYMVASGLPkRNGSRHAAEIA 954
Cdd:pfam00211    1 VYAQPYDNVTILFADIVGFTALSSRHSPEQVVRLLNELYTRFDRLLDKHKVYKVKTIGDAYMVVSGLP-EPSPAHARKIA 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225      955 NMSLDILSSVGTFKMRHMPevPVRIRIGLHSGPVVAGVVGLTMPRYCLFGDTVNTASRMESTGLPYRIHVSLSTVTILQN 1034
Cdd:pfam00211   80 EMALDMLEAIGEVNVESSE--GLRVRVGIHTGPVVAGVIGARMPRYDLWGNTVNLASRMESTGVPGKIHVSEETYRLLKT 157
                          170       180
                   ....*....|....*....|....*...
gi 945225     1035 lsEGYEVELRGRTELKGKGTEETFWLIG 1062
Cdd:pfam00211  158 --EGFEFTERGEIEVKGKGKMKTYFLNG 183
PBP1_NPR_GC-like cd06352
ligand-binding domain of membrane guanylyl-cyclase receptors; Ligand-binding domain of ...
54-433 5.57e-78

ligand-binding domain of membrane guanylyl-cyclase receptors; Ligand-binding domain of membrane guanylyl-cyclase receptors. Membrane guanylyl cyclases (GC) have a single membrane-spanning region and are activated by endogenous and exogenous peptides. This family can be divided into three major subfamilies: the natriuretic peptide receptors (NPRs), sensory organ-specific membrane GCs, and the enterotoxin/guanylin receptors. The binding of peptide ligands to the receptor results in the activation of the cytosolic catalytic domain. Three types of NPRs have been cloned from mammalian tissues: NPR-A/GC-A, NPR-B/ GC-B, and NPR-C. In addition, two of the GCs, GC-D and GC-G, appear to be pseudogenes in humans. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are produced in the heart, and both bind to the NPR-A. NPR-C, also termed the clearance receptor, binds each of the natriuretic peptides and can alter circulating levels of these peptides. The ligand binding domain of the NPRs exhibits strong structural similarity to the type 1 periplasmic binding fold protein family.


Pssm-ID: 380575 [Multi-domain]  Cd Length: 391  Bit Score: 261.52  E-value: 5.57e-78
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225     54 KIGVVGPWACDSL-FSKALPEVAARLAIERINRDPSFDLSYSFEYVILNEDCQTSRALSSFIS--HHQMASGFIGPTNPG 130
Cdd:cd06352    1 KVGVLAPSNSQSLpVGYARSAPAIDIAIERINSEGLLLPGFNFEFTYRDSCCDESEAVGAAADliYKRNVDVFIGPACSA 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    131 YCEAASLLGNSWDKGIFSWACVNYELDNKISYPTFSRTLP---SPIRVLVTVMKYFQWAHAGVISSDED-IWVHTANRVA 206
Cdd:cd06352   81 AADAVGRLATYWNIPIITWGAVSASFLDKSRYPTLTRTSPnslSLAEALLALLKQFNWKRAAIIYSDDDsKCFSIANDLE 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    207 SALRS-HGLPVGVV-LTTGQDSQSMRKALQRIHQadRIRIIIMCMHSaliggETQMHLLECAHDLKMTDGTYVFVPYDAL 284
Cdd:cd06352  161 DALNQeDNLTISYYeFVEVNSDSDYSSILQEAKK--RARIIVLCFDS-----ETVRQFMLAAHDLGMTNGEYVFIFIELF 233
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    285 L--YSLPYKHTPYQVLRNNPKLREAYDAVLTITVE----SQEKTFYQAFTEAAARGEIPEKLE-FDQVSPLFGTIYNSIY 357
Cdd:cd06352  234 KdgFGGNSTDGWERNDGRDEDAKQAYESLLVISLSrpsnPEYDNFSKEVKARAKEPPFYCYDAsEEEVSPYAAALYDAVY 313
                        330       340       350       360       370       380       390
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 945225    358 FIAQAMNNAMKENGQA-GAASLVQHSRNMQFHGFNQLMRTDSNGNGISEYVILDTNLKEWELHSTYTVDMEMELLRF 433
Cdd:cd06352  314 LYALALNETLAEGGNYrNGTAIAQRMWNRTFQGITGPVTIDSNGDRDPDYALLDLDPSTGKFVVVLTYDGTSNGLVV 390
PK_GC-A_B cd14042
Pseudokinase domain of the membrane Guanylate Cyclase receptors, GC-A and GC-B; The ...
547-815 1.58e-76

Pseudokinase domain of the membrane Guanylate Cyclase receptors, GC-A and GC-B; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding. GC-A binds and is activated by the atrial and B-type natriuretic peptides, ANP and BNP, which are important in blood pressure regulation and cardiac pathophysiology. GC-B binds the C-type natriuretic peptide, CNP, which is a potent vasorelaxant and functions in vascular remodeling and bone growth regulation. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC-A/B subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270944 [Multi-domain]  Cd Length: 279  Bit Score: 253.29  E-value: 1.58e-76
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    547 SFSSGSL-TPATYENS----NIAIYEGDWVWLKKFSLgdfgdlKSIKSRASDVFEM--MKDLRHENINPLLGFFYDSGMF 619
Cdd:cd14042    4 SSSYGSLmTAASFDQSqiftKTGYYKGNLVAIKKVNK------KRIDLTREVLKELkhMRDLQHDNLTRFIGACVDPPNI 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    620 AIVTEFCSRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFV-HGRLKSRNCVVDGRFVLKVTDYGfndiLEML 698
Cdd:cd14042   78 CILTEYCPKGSLQDILENEDIKLDWMFRYSLIHDIVKGMHYLHDSEIKsHGNLKSSNCVVDSRFVLKITDFG----LHSF 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    699 RLSEEESSMEELL-----WTAPELLRAPRGSRLGSFAGDVYSFAIIMQEVMVRGTPF--CMMDLPAQEIINRLKKPPPVY 771
Cdd:cd14042  154 RSGQEPPDDSHAYyakllWTAPELLRDPNPPPPGTQKGDVYSFGIILQEIATRQGPFyeEGPDLSPKEIIKKKVRNGEKP 233
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*.
gi 945225    772 RP--VVPPEHAPPECLQLMKQCWAEAAEQRPTFDEIFNQFKTFNKG 815
Cdd:cd14042  234 PFrpSLDELECPDEVLSLMQRCWAEDPEERPDFSTLRNKLKKLNKG 279
ANF_receptor pfam01094
Receptor family ligand binding region; This family includes extracellular ligand binding ...
71-412 1.02e-74

Receptor family ligand binding region; This family includes extracellular ligand binding domains of a wide range of receptors. This family also includes the bacterial amino acid binding proteins of known structure.


Pssm-ID: 460062 [Multi-domain]  Cd Length: 347  Bit Score: 251.15  E-value: 1.02e-74
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225       71 LPEVAARLAIERINRDPSFDLSYSFEYVILNEDCQTSRALSSFISHHQ-MASGFIGPTNPGYCEAASLLGNSWDKGIFSW 149
Cdd:pfam01094    1 LVLLAVRLAVEDINADPGLLPGTKLEYIILDTCCDPSLALAAALDLLKgEVVAIIGPSCSSVASAVASLANEWKVPLISY 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225      150 ACVNYELDNKISYPTFSRTLPS---PIRVLVTVMKYFQWAHAGVISSDEDIWVHTANRVASALRSHGLPVGVVLTTGQ-- 224
Cdd:pfam01094   81 GSTSPALSDLNRYPTFLRTTPSdtsQADAIVDILKHFGWKRVALIYSDDDYGESGLQALEDALRERGIRVAYKAVIPPaq 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225      225 -DSQSMRKALQRIHQadRIRIIIMCMHSaliggETQMHLLECAHDLKMTDGTYVFVPYDALLYSLPYKHTPYqvlrnnpk 303
Cdd:pfam01094  161 dDDEIARKLLKEVKS--RARVIVVCCSS-----ETARRLLKAARELGMMGEGYVWIATDGLTTSLVILNPST-------- 225
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225      304 lREAYDAVLTITVESQEKTFYQAFTE--AAARGEIPEKLEFDQVSPLFgTIYNSIYFIAQAMNNAMKENGQ--------- 372
Cdd:pfam01094  226 -LEAAGGVLGFRLHPPDSPEFSEFFWekLSDEKELYENLGGLPVSYGA-LAYDAVYLLAHALHNLLRDDKPgracgalgp 303
                          330       340       350       360
                   ....*....|....*....|....*....|....*....|..
gi 945225      373 -AGAASLVQHSRNMQFHGFNQLMRTDSNGNGIS-EYVILDTN 412
Cdd:pfam01094  304 wNGGQKLLRYLKNVNFTGLTGNVQFDENGDRINpDYDILNLN 345
PK_GC cd13992
Pseudokinase domain of membrane Guanylate Cyclase receptors; The pseudokinase domain shows ...
598-805 5.88e-71

Pseudokinase domain of membrane Guanylate Cyclase receptors; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs lack a critical aspartate involved in ATP binding and does not exhibit kinase activity. It functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270894 [Multi-domain]  Cd Length: 268  Bit Score: 237.67  E-value: 5.88e-71
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    598 MKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLH-HREFVHGRLKSRNC 676
Cdd:cd13992   50 LKELVHDNLNKFIGICINPPNIAVVTEYCTRGSLQDVLLNREIKMDWMFKSSFIKDIVKGMNYLHsSSIGYHGRLKSSNC 129
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    677 VVDGRFVLKVTDYGFNDILE--MLRLSEEESSMEELLWTAPELLRAPRGSRLGSFAGDVYSFAIIMQEVMVRGTPFCMMD 754
Cdd:cd13992  130 LVDSRWVVKLTDFGLRNLLEeqTNHQLDEDAQHKKLLWTAPELLRGSLLEVRGTQKGDVYSFAIILYEILFRSDPFALER 209
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 945225    755 -LPAQEIINRLKKPPPVYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEI 805
Cdd:cd13992  210 eVAIVEKVISGGNKPFRPELAVLLDEFPPRLVLLVKQCWAENPEKRPSFKQI 261
CHD cd07302
cyclase homology domain; Catalytic domains of the mononucleotidyl cyclases (MNC's), also ...
883-1060 2.94e-65

cyclase homology domain; Catalytic domains of the mononucleotidyl cyclases (MNC's), also called cyclase homology domains (CHDs), are part of the class III nucleotidyl cyclases. This class includes eukaryotic and prokaryotic adenylate cyclases (AC's) and guanylate cyclases (GC's). They seem to share a common catalytic mechanism in their requirement for two magnesium ions to bind the polyphosphate moiety of the nucleotide.


Pssm-ID: 143636 [Multi-domain]  Cd Length: 177  Bit Score: 217.83  E-value: 2.94e-65
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    883 VTLYFSDIVGFTTISAMSEPIEVVDLLNDLYTLFDAIIGSHDVYKVETIGDAYMVASGLPKRNGsRHAAEIANMSLDILS 962
Cdd:cd07302    2 VTVLFADIVGFTALSERLGPEELVELLNEYFSAFDEIIERHGGTVDKTIGDAVMAVFGLPGAHE-DHAERAVRAALEMQE 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    963 SVGTFKMRHMPEVPVRIRIGLHSGPVVAGVVGLTMPRYCLFGDTVNTASRMESTGLPYRIHVSLSTVTILQNlsEGYEVE 1042
Cdd:cd07302   81 ALAELNAEREGGPPLRLRIGIHTGPVVAGVVGSERPEYTVIGDTVNLAARLESLAKPGQILVSEATYELLGD--AGFEFE 158
                        170
                 ....*....|....*....
gi 945225   1043 LRGRTELKGK-GTEETFWL 1060
Cdd:cd07302  159 ELGEVELKGKsGPVRVYRL 177
AcyC COG2114
Adenylate cyclase, class 3 [Signal transduction mechanisms];
820-1065 5.67e-48

Adenylate cyclase, class 3 [Signal transduction mechanisms];


Pssm-ID: 441717 [Multi-domain]  Cd Length: 407  Bit Score: 176.92  E-value: 5.67e-48
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    820 IIDSMLRMLEQYSSNLEDLIRERTEELEIEKQKTEKLLTQMLPPSVAESLKKGCTVEPEG--FDLVTLYFSDIVGFTTIS 897
Cdd:COG2114  158 VALLLLALLLLLLLLLLLALLLLLLLALRERERLRDLLGRYLPPEVAERLLAGGEELRLGgeRREVTVLFADIVGFTALS 237
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    898 AMSEPIEVVDLLNDLYTLFDAIIGSHDVYKVETIGDAYMVASGLPKRNGSrHAAEIANMSLDILSSVGTF--KMRHMPEV 975
Cdd:COG2114  238 ERLGPEELVELLNRYFSAMVEIIERHGGTVDKFIGDGVMAVFGAPVARED-HAERAVRAALAMQEALAELnaELPAEGGP 316
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    976 PVRIRIGLHSGPVVAGVVGLTMPR-YCLFGDTVNTASRMESTGLPYRIHVSLSTVtilQNLSEGYEVELRGRTELKGKGT 1054
Cdd:COG2114  317 PLRVRIGIHTGEVVVGNIGSEDRLdYTVIGDTVNLAARLESLAKPGEILVSEATY---DLLRDRFEFRELGEVRLKGKAE 393
                        250
                 ....*....|..
gi 945225   1055 E-ETFWLIGKKG 1065
Cdd:COG2114  394 PvEVYELLGAKE 405
STKc_MAP3K-like cd13999
Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-like Serine ...
549-805 2.10e-44

Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed mainly of MAP3Ks and similar proteins, including TGF-beta Activated Kinase-1 (TAK1, also called MAP3K7), MAP3K12, MAP3K13, Mixed lineage kinase (MLK), MLK-Like mitogen-activated protein Triple Kinase (MLTK), and Raf (Rapidly Accelerated Fibrosarcoma) kinases. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Also included in this subfamily is the pseudokinase Kinase Suppressor of Ras (KSR), which is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway.


Pssm-ID: 270901 [Multi-domain]  Cd Length: 245  Bit Score: 161.17  E-value: 2.10e-44
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    549 SSGSLTPATYENSNIAIyegdwvwlKKFSLGDFGDlksiksRASDVF----EMMKDLRHENINPLLGFFYDSGMFAIVTE 624
Cdd:cd13999    5 SFGEVYKGKWRGTDVAI--------KKLKVEDDND------ELLKEFrrevSILSKLRHPNIVQFIGACLSPPPLCIVTE 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    625 FCSRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGF----NDILEMLRl 700
Cdd:cd13999   71 YMPGGSLYDLLHKKKIPLSWSLRLKIALDIARGMNYLHSPPIIHRDLKSLNILLDENFTVKIADFGLsrikNSTTEKMT- 149
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    701 seeeSSMEELLWTAPELLRaprgSRLGSFAGDVYSFAIIMQEVMVRGTPFcmMDLPAQEIInrlKKPPPVYRPVVPPEHA 780
Cdd:cd13999  150 ----GVVGTPRWMAPEVLR----GEPYTEKADVYSFGIVLWELLTGEVPF--KELSPIQIA---AAVVQKGLRPPIPPDC 216
                        250       260
                 ....*....|....*....|....*
gi 945225    781 PPECLQLMKQCWAEAAEQRPTFDEI 805
Cdd:cd13999  217 PPELSKLIKRCWNEDPEKRPSFSEI 241
PK_GC_unk cd14045
Pseudokinase domain of the unknown subfamily of membrane Guanylate Cyclase receptors; The ...
546-805 1.34e-39

Pseudokinase domain of the unknown subfamily of membrane Guanylate Cyclase receptors; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs lack a critical aspartate involved in ATP binding and does not exhibit kinase activity. It functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270947 [Multi-domain]  Cd Length: 269  Bit Score: 148.08  E-value: 1.34e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    546 LSFSSGSLTPATYENSNIAIYEGDWVWLKKFSLGDFGDLKSIKSRASDVfemmKDLRHENINPLLGFFYDSGMFAIVTEF 625
Cdd:cd14045    8 LSSCTTAHNAQKKPFTQTGIYDGRTVAIKKIAKKSFTLSKRIRKEVKQV----RELDHPNLCKFIGGCIEVPNVAIITEY 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    626 CSRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGfndiLEMLRLSEEES 705
Cdd:cd14045   84 CPKGSLNDVLLNEDIPLNWGFRFSFATDIARGMAYLHQHKIYHGRLKSSNCVIDDRWVCKIADYG----LTTYRKEDGSE 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    706 SMEELLWTAPELLRAPRGSRLGSF----AGDVYSFAIIMQEVMVRGTPF--------CMMDLPAQEIInrlkkpppvYRP 773
Cdd:cd14045  160 NASGYQQRLMQVYLPPENHSNTDTeptqATDVYSYAIILLEIATRNDPVpeddysldEAWCPPLPELI---------SGK 230
                        250       260       270
                 ....*....|....*....|....*....|..
gi 945225    774 VVPPEHAPPECLQLMKQCWAEAAEQRPTFDEI 805
Cdd:cd14045  231 TENSCPCPADYVELIRRCRKNNPAQRPTFEQI 262
PTKc cd00192
Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
585-810 2.17e-39

Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. They can be classified into receptor and non-receptor tyr kinases. PTKs play important roles in many cellular processes including, lymphocyte activation, epithelium growth and maintenance, metabolism control, organogenesis regulation, survival, proliferation, differentiation, migration, adhesion, motility, and morphogenesis. Receptor tyr kinases (RTKs) are integral membrane proteins which contain an extracellular ligand-binding region, a transmembrane segment, and an intracellular tyr kinase domain. RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain, leading to intracellular signaling. Some RTKs are orphan receptors with no known ligands. Non-receptor (or cytoplasmic) tyr kinases are distributed in different intracellular compartments and are usually multi-domain proteins containing a catalytic tyr kinase domain as well as various regulatory domains such as SH3 and SH2. PTKs are usually autoinhibited and require a mechanism for activation. In many PTKs, the phosphorylation of tyr residues in the activation loop is essential for optimal activity. Aberrant expression of PTKs is associated with many development abnormalities and cancers.The PTK family is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270623 [Multi-domain]  Cd Length: 262  Bit Score: 147.30  E-value: 2.17e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    585 KSIKSRASDV--------FEMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKLDWMFKSSL-LLDLI 655
Cdd:cd00192   29 KTLKEDASESerkdflkeARVMKKLGHPNVVRLLGVCTEEEPLYLVMEYMEGGDLLDFLRKSRPVFPSPEPSTLsLKDLL 108
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    656 -------KGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGfndileMLRLSEEESSMEELL-------WTAPELLRap 721
Cdd:cd00192  109 sfaiqiaKGMEYLASKKFVHRDLAARNCLVGEDLVVKISDFG------LSRDIYDDDYYRKKTggklpirWMAPESLK-- 180
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    722 rgSRLGSFAGDVYSFAIIMQEVMVRG-TPFCmmDLPAQEII------NRLKKPppvyrpvvppEHAPPECLQLMKQCWAE 794
Cdd:cd00192  181 --DGIFTSKSDVWSFGVLLWEIFTLGaTPYP--GLSNEEVLeylrkgYRLPKP----------ENCPDELYELMLSCWQL 246
                        250
                 ....*....|....*.
gi 945225    795 AAEQRPTFDEIFNQFK 810
Cdd:cd00192  247 DPEDRPTFSELVERLE 262
TyrKc smart00219
Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.
585-809 1.22e-37

Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.


Pssm-ID: 197581 [Multi-domain]  Cd Length: 257  Bit Score: 141.90  E-value: 1.22e-37
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225       585 KSIKSRASDV--------FEMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKLDWMFKSSLLLDLIK 656
Cdd:smart00219   34 KTLKEDASEQqieeflreARIMRKLDHPNVVKLLGVCTEEEPLYIVMEYMEGGDLLSYLRKNRPKLSLSDLLSFALQIAR 113
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225       657 GMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGfndileMLRLSEEESSMEELL------WTAPELLRaprgSRLGSFA 730
Cdd:smart00219  114 GMEYLESKNFIHRDLAARNCLVGENLVVKISDFG------LSRDLYDDDYYRKRGgklpirWMAPESLK----EGKFTSK 183
                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225       731 GDVYSFAIIMQEVMVRG-TPFCmmDLPAQEIINRLKKpppvYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEIFNQF 809
Cdd:smart00219  184 SDVWSFGVLLWEIFTLGeQPYP--GMSNEEVLEYLKN----GYRLPQPPNCPPELYDLMLQCWAEDPEDRPTFSELVEIL 257
PK_Tyr_Ser-Thr pfam07714
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ...
596-809 2.84e-37

Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyze the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyze the reverse process. Protein kinases fall into three broad classes, characterized with respect to substrate specificity; Serine/threonine-protein kinases, tyrosine-protein kinases, and dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins). This entry represents the catalytic domain found in a number of serine/threonine- and tyrosine-protein kinases. It does not include the catalytic domain of dual specificity kinases.


Pssm-ID: 462242 [Multi-domain]  Cd Length: 258  Bit Score: 141.09  E-value: 2.84e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225      596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRN 675
Cdd:pfam07714   53 SIMKKLDHPNIVKLLGVCTQGEPLYIVTEYMPGGDLLDFLRKHKRKLTLKDLLSMALQIAKGMEYLESKNFVHRDLAARN 132
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225      676 CVVDGRFVLKVTDYG-FNDILEMLRLSEEESSMEELLWTAPELLRAprgsRLGSFAGDVYSFAIIMQEVMVRG-TPFCmm 753
Cdd:pfam07714  133 CLVSENLVVKISDFGlSRDIYDDDYYRKRGGGKLPIKWMAPESLKD----GKFTSKSDVWSFGVLLWEIFTLGeQPYP-- 206
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 945225      754 DLPAQEIINRLKKpppvYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEIFNQF 809
Cdd:pfam07714  207 GMSNEEVLEFLED----GYRLPQPENCPDELYDLMKQCWAYDPEDRPTFSELVEDL 258
STYKc smart00221
Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class ...
596-809 3.91e-37

Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class of kinases can not be predicted. Possible dual-specificity Ser/Thr/Tyr kinase.


Pssm-ID: 214568 [Multi-domain]  Cd Length: 258  Bit Score: 140.76  E-value: 3.91e-37
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225       596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDIL-TNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSR 674
Cdd:smart00221   53 RIMRKLDHPNIVKLLGVCTEEEPLMIVMEYMPGGDLLDYLrKNRPKELSLSDLLSFALQIARGMEYLESKNFIHRDLAAR 132
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225       675 NCVVDGRFVLKVTDYGfndileMLRLSEEESSMEELL------WTAPELLRaprgSRLGSFAGDVYSFAIIMQEVMVRG- 747
Cdd:smart00221  133 NCLVGENLVVKISDFG------LSRDLYDDDYYKVKGgklpirWMAPESLK----EGKFTSKSDVWSFGVLLWEIFTLGe 202
                           170       180       190       200       210       220
                    ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 945225       748 TPFCmmDLPAQEIINRLKKPPPVYRPvvppEHAPPECLQLMKQCWAEAAEQRPTFDEIFNQF 809
Cdd:smart00221  203 EPYP--GMSNAEVLEYLKKGYRLPKP----PNCPPELYKLMLQCWAEDPEDRPTFSELVEIL 258
Nucleotidyl_cyc_III cd07556
Class III nucleotidyl cyclases; Class III nucleotidyl cyclases are the largest, most diverse ...
882-1023 3.84e-36

Class III nucleotidyl cyclases; Class III nucleotidyl cyclases are the largest, most diverse group of nucleotidyl cyclases (NC's) containing prokaryotic and eukaryotic proteins. They can be divided into two major groups; the mononucleotidyl cyclases (MNC's) and the diguanylate cyclases (DGC's). The MNC's, which include the adenylate cyclases (AC's) and the guanylate cyclases (GC's), have a conserved cyclase homology domain (CHD), while the DGC's have a conserved GGDEF domain, named after a conserved motif within this subgroup. Their products, cyclic guanylyl and adenylyl nucleotides, are second messengers that play important roles in eukaryotic signal transduction and prokaryotic sensory pathways.


Pssm-ID: 143637 [Multi-domain]  Cd Length: 133  Bit Score: 133.25  E-value: 3.84e-36
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    882 LVTLYFSDIVGFTTISAMSEPIEVVDLLNDLYTLFDAIIGSHDVYKVETIGDAYMVASGLPkrngsrHAAEIANMSLDIL 961
Cdd:cd07556    1 PVTILFADIVGFTSLADALGPDEGDELLNELAGRFDSLIRRSGDLKIKTIGDEFMVVSGLD------HPAAAVAFAEDMR 74
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 945225    962 SSVGtfKMRHMPEVPVRIRIGLHSGPVVAGVVGLtMPRYCLFGDTVNTASRMESTGLPYRIH 1023
Cdd:cd07556   75 EAVS--ALNQSEGNPVRVRIGIHTGPVVVGVIGS-RPQYDVWGALVNLASRMESQAKAGQVL 133
PK_GC-C cd14044
Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-C; The pseudokinase domain ...
597-807 4.41e-36

Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-C; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding. GC-C binds and is activated by the intestinal hormones, guanylin (GN) and uroguanylin (UGN), which are secreted after salty meals to inhibit sodium absorption and induce the secretion of chloride, bicarbonate, and water. GN and UGN are also present in the kidney, where they induce increased salt and water secretion. This prevents the development of hypernatremia and hypervolemia after ingestion of high amounts of salt. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC-C subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270946 [Multi-domain]  Cd Length: 271  Bit Score: 138.09  E-value: 4.41e-36
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHEN----------INPLLGF-------FY-----DSGMFAIVtEFCSRGSLEDILTNQ-----DVKLDWMFKSS 649
Cdd:cd14044   35 ILKDLKNNEgnftekqkieLNKLLQIdyynltkFYgtvklDTMIFGVI-EYCERGSLRDVLNDKisypdGTFMDWEFKIS 113
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    650 LLLDLIKGMKYLHHREF-VHGRLKSRNCVVDGRFVLKVTDYGFNDILEMLRlseeessmeeLLWTAPELLRAPRGSRlgs 728
Cdd:cd14044  114 VMYDIAKGMSYLHSSKTeVHGRLKSTNCVVDSRMVVKITDFGCNSILPPSK----------DLWTAPEHLRQAGTSQ--- 180
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    729 fAGDVYSFAIIMQEVMVRGTPFCMMDLP-AQEIINRLK-----KPPPVYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTF 802
Cdd:cd14044  181 -KGDVYSYGIIAQEIILRKETFYTAACSdRKEKIYRVQnpkgmKPFRPDLNLESAGEREREVYGLVKNCWEEDPEKRPDF 259

                 ....*
gi 945225    803 DEIFN 807
Cdd:cd14044  260 KKIEN 264
PBP1_SAP_GC-like cd06370
Ligand-binding domain of membrane bound guanylyl cyclases; Ligand-binding domain of membrane ...
53-410 1.44e-35

Ligand-binding domain of membrane bound guanylyl cyclases; Ligand-binding domain of membrane bound guanylyl cyclases (GCs), which are known to be activated by sperm-activating peptides (SAPs), such as speract or resact. These ligand peptides are released by a range of invertebrates to stimulate the metabolism and motility of spermatozoa and are also potent chemoattractants. These GCs contain a single transmembrane segment, an extracellular ligand binding domain, and intracellular protein kinase-like and cyclase catalytic domains. GCs of insect and nematodes, which exhibit high sequence similarity to the speract receptor are also included in this model.


Pssm-ID: 380593 [Multi-domain]  Cd Length: 400  Bit Score: 140.07  E-value: 1.44e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225     53 YKIGVVGPWACDS-------LFSKALPevaarLAIERINRDPSFDLSYSFEYVILNEDCQTSRALSSFISHHQM-ASGFI 124
Cdd:cd06370    1 ITIGYLTPYSGAGsydrqgrVISGAIT-----LAVDDVNNDPNLLPGHTLSFVWNDTRCDELLSIRAMTELWKRgVSAFI 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    125 GPTnpGYCEAASLLGNSWDKGIFSWACVNYELDNKISYPTFSRTLPSPIRV---LVTVMKYFQWAHAGVISSDEDIWVHT 201
Cdd:cd06370   76 GPG--CTCATEARLAAAFNLPMISYKCADPEVSDKSLYPTFARTIPPDSQIsksVIALLKHFNWNKVSIVYENETKWSKI 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    202 ANRVASALRSHG--------LPVGVVLTTGQDSQsMRKALQRIHQADRIRIIIMCMHSAliggetqMHLLECAHDLKMTD 273
Cdd:cd06370  154 ADTIKELLELNNieinheeyFPDPYPYTTSHGNP-FDKIVEETKEKTRIYVFLGDYSLL-------REFMYYAEDLGLLD 225
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    274 -GTYVFVPYDALLY--SLPYKHTPYQVLRNN----PKLREAYDAVLTITVESQEKTFYQAFTEAAAR--------GEIPE 338
Cdd:cd06370  226 nGDYVVIGVELDQYdvDDPAKYPNFLSGDYTkndtKEALEAFRSVLIVTPSPPTNPEYEKFTKKVKEynklppfnFPNPE 305
                        330       340       350       360       370       380       390
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 945225    339 KLEFDQVSPLFGT-IYNSIYFIAQAMNNAMKENGQA--GAAsLVQHSRNMQFH---GFNqlMRTDSNGNGISEYVILD 410
Cdd:cd06370  306 GIEKTKEVPIYAAyLYDAVMLYARALNETLAEGGDPrdGTA-IISKIRNRTYEsiqGFD--VYIDENGDAEGNYTLLA 380
PKc cd00180
Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group ...
566-809 2.40e-32

Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. PKs make up a large family of serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins. Majority of protein phosphorylation occurs on serine residues while only 1% occurs on tyrosine residues. Protein phosphorylation is a mechanism by which a wide variety of cellular proteins, such as enzymes and membrane channels, are reversibly regulated in response to certain stimuli. PKs often function as components of signal transduction pathways in which one kinase activates a second kinase, which in turn, may act on other kinases; this sequential action transmits a signal from the cell surface to target proteins, which results in cellular responses. The PK family is one of the largest known protein families with more than 100 homologous yeast enzymes and more than 500 human proteins. A fraction of PK family members are pseudokinases that lack crucial residues for catalytic activity. The mutiplicity of kinases allows for specific regulation according to substrate, tissue distribution, and cellular localization. PKs regulate many cellular processes including proliferation, division, differentiation, motility, survival, metabolism, cell-cycle progression, cytoskeletal rearrangement, immunity, and neuronal functions. Many kinases are implicated in the development of various human diseases including different types of cancer. The PK family is part of a larger superfamily that includes the catalytic domains of RIO kinases, aminoglycoside phosphotransferase, choline kinase, phosphoinositide 3-kinase (PI3K), and actin-fragmin kinase.


Pssm-ID: 270622 [Multi-domain]  Cd Length: 215  Bit Score: 125.46  E-value: 2.40e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    566 YEGDWVWLKKFSLGDFgdlKSIKSRASDVFEMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKLDWM 645
Cdd:cd00180   16 ETGKKVAVKVIPKEKL---KKLLEELLREIEILKKLNHPNIVKLYDVFETENFLYLVMEYCEGGSLKDLLKENKGPLSEE 92
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    646 FKSSLLLDLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGFNDILEMLRLSEEESSMEELLWTAPELLrapRGSR 725
Cdd:cd00180   93 EALSILRQLLSALEYLHSNGIIHRDLKPENILLDSDGTVKLADFGLAKDLDSDDSLLKTTGGTTPPYYAPPEL---LGGR 169
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    726 LGSFAGDVYSFAIIMqevmvrgtpFCMmdlpaqeiinrlkkpppvyrpvvppehapPECLQLMKQCWAEAAEQRPTFDEI 805
Cdd:cd00180  170 YYGPKVDIWSLGVIL---------YEL-----------------------------EELKDLIRRMLQYDPKKRPSAKEL 211

                 ....
gi 945225    806 FNQF 809
Cdd:cd00180  212 LEHL 215
PBP1_GC_G-like cd06372
Ligand-binding domain of membrane guanylyl cyclase G; This group includes the ligand-binding ...
55-410 2.58e-29

Ligand-binding domain of membrane guanylyl cyclase G; This group includes the ligand-binding domain of membrane guanylyl cyclase G (GC-G) which is a sperm surface receptor and might function, similar to its sea urchin counterpart, in the early signaling event that regulates the Ca2+ influx/efflux and subsequent motility response in sperm. GC-G appears to be a pseudogene in human. Furthermore, in contrast to the other orphan receptor GCs, GC-G has a broad tissue distribution in rat, including lung, intestine, kidney, and skeletal muscle.


Pssm-ID: 380595 [Multi-domain]  Cd Length: 390  Bit Score: 121.44  E-value: 2.58e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225     55 IGVVGPWACDSLFSKALPEVAARLAIERINRDPSFDLSYSFEYVILNEDCQTSRALSSFISHHQMA--SGFIGPTNPGYC 132
Cdd:cd06372    2 VGFQAPWNLSHPFSAQRLGSAIQLAVDKVNSEPSLLGNYSLDFVYTDCGCNAKESLGAFIDQVQKEniSALFGPACPEAA 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    133 EAASLLGNSWDKGIFSWACVNYELDNKISYPTFSRTLPSPIR---VLVTVMKYFQWAHAGVI--SSDEDIWVHTAN---R 204
Cdd:cd06372   82 EVTGLLASEWNIPMFGFVGQSPKLDDRDVYDTYVKLVPPLQRigeVLVKTLQFFGWTHVAMFggSSATSTWDKVDElwkS 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    205 VASALRSHGLPVGVVLTTGQDSQSMRKALQRIHQADRIrIIIMCmhsaliGGETQMHLLECAHDLKMTDGTYVFVPYDAL 284
Cdd:cd06372  162 VENQLKFNFNVTAKVKYDTSNPDLLQENLRYISSVARV-IVLIC------SSEDARSILLEAEKLGLMDGEYVFFLLQQF 234
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    285 LYSLpYKHTPYQvlRNNPKLREAYDAVLTITVESQE--------KTFYQAFTEAAARGEIPEKlefDQVSPLFGTIYNSI 356
Cdd:cd06372  235 EDSF-WKEVLND--EKNQVFLKAYEMVFLIAQSSYGtygysdfrKQVHQKLRRAPFYSSISSE---DQVSPYSAYLHDAV 308
                        330       340       350       360       370
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 945225    357 YFIAQAMNNAMKE-----NGQAGAASLvQHSRNMQFHGFNQLMRTDSNGNGISEYVILD 410
Cdd:cd06372  309 LLYAMGLKEMLKDgkdprDGRALLQTL-RGYNQTTFYGITGLVYLDVQGERHMDYSVYD 366
PTKc_Csk_like cd05039
Catalytic domain of C-terminal Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
579-812 8.04e-27

Catalytic domain of C-terminal Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of Csk, Chk, and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. They negatively regulate the activity of Src kinases that are anchored to the plasma membrane. To inhibit Src kinases, Csk and Chk are translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. Csk catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. Chk inhibit Src kinases using a noncatalytic mechanism by simply binding to them. As negative regulators of Src kinases, Csk and Chk play important roles in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. The Csk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270635 [Multi-domain]  Cd Length: 256  Bit Score: 110.90  E-value: 8.04e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    579 GDFGD------------LKSIK--SRASDVF----EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDIL----- 635
Cdd:cd05039   17 GEFGDvmlgdyrgqkvaVKCLKddSTAAQAFlaeaSVMTTLRHPNLVQLLGVVLEGNGLYIVTEYMAKGSLVDYLrsrgr 96
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    636 ---TNQDVKldwMFKssllLDLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGfndiLEMLRLSEEESSMEELLW 712
Cdd:cd05039   97 aviTRKDQL---GFA----LDVCEGMEYLESKKFVHRDLAARNVLVSEDNVAKVSDFG----LAKEASSNQDGGKLPIKW 165
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    713 TAPELLRaprgsrLGSFA--GDVYSFAIIMQEVMVRG-TPFCMMdlPAQEIINRLKKPPPVYRPvvppEHAPPECLQLMK 789
Cdd:cd05039  166 TAPEALR------EKKFStkSDVWSFGILLWEIYSFGrVPYPRI--PLKDVVPHVEKGYRMEAP----EGCPPEVYKVMK 233
                        250       260
                 ....*....|....*....|...
gi 945225    790 QCWAEAAEQRPTFDEIFNQFKTF 812
Cdd:cd05039  234 NCWELDPAKRPTFKQLREKLEHI 256
PTKc_Jak_rpt2 cd05038
Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily ...
596-811 1.19e-25

Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily is composed of Jak1, Jak2, Jak3, TYK2, and similar proteins. They are PTKs, catalyzing the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jaks are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase catalytic domain. Most Jaks are expressed in a wide variety of tissues, except for Jak3, which is expressed only in hematopoietic cells. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). Jaks are also involved in regulating the surface expression of some cytokine receptors. The Jak-STAT pathway is involved in many biological processes including hematopoiesis, immunoregulation, host defense, fertility, lactation, growth, and embryogenesis. The Jak subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270634 [Multi-domain]  Cd Length: 284  Bit Score: 108.24  E-value: 1.19e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFA--IVTEFCSRGSLEDILTNQDVKLDwmfKSSLLL---DLIKGMKYLHHREFVHGR 670
Cdd:cd05038   58 EILRTLDHEYIVKYKGVCESPGRRSlrLIMEYLPSGSLRDYLQRHRDQID---LKRLLLfasQICKGMEYLGSQRYIHRD 134
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    671 LKSRNCVVDGRFVLKVTDYGFNDILEMLRLSEEESSMEEL--LWTAPELLRAPRGSrlgsFAGDVYSFAIIMQEVMVRGT 748
Cdd:cd05038  135 LAARNILVESEDLVKISDFGLAKVLPEDKEYYYVKEPGESpiFWYAPECLRESRFS----SASDVWSFGVTLYELFTYGD 210
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 945225    749 PFC---------MMDLPAQEIINRLKKPPPVYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEIFNQFKT 811
Cdd:cd05038  211 PSQsppalflrmIGIAQGQMIVTRLLELLKSGERLPRPPSCPDEVYDLMKECWEYEPQDRPSFSDLILIIDR 282
STKc_RIP cd13978
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein; STKs catalyze ...
596-802 1.54e-25

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP kinases serve as essential sensors of cellular stress. They are involved in regulating NF-kappaB and MAPK signaling, and are implicated in mediating cellular processes such as apoptosis, necroptosis, differentiation, and survival. RIP kinases contain a homologous N-terminal kinase domain and varying C-terminal domains. Higher vertebrates contain multiple RIP kinases, with mammals harboring at least five members. RIP1 and RIP2 harbor C-terminal domains from the Death domain (DD) superfamily while RIP4 contains ankyrin (ANK) repeats. RIP3 contain a RIP homotypic interaction motif (RHIM) that facilitates binding to RIP1. RIP1 and RIP3 are important in apoptosis and necroptosis, while RIP2 and RIP4 play roles in keratinocyte differentiation and inflammatory immune responses. The RIP subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270880 [Multi-domain]  Cd Length: 263  Bit Score: 107.15  E-value: 1.54e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHRE--FVHGRLKS 673
Cdd:cd13978   44 EKMERARHSYVLPLLGVCVERRSLGLVMEYMENGSLKSLLEREIQDVPWSLRFRIIHEIALGMNFLHNMDppLLHHDLKP 123
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    674 RNCVVDGRFVLKVTDYGFNDI----LEMLRLSEEESSMEELLWTAPELLRAprGSRLGSFAGDVYSFAIIMQEVMVRGTP 749
Cdd:cd13978  124 ENILLDNHFHVKISDFGLSKLgmksISANRRRGTENLGGTPIYMAPEAFDD--FNKKPTSKSDVYSFAIVIWAVLTRKEP 201
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 945225    750 FCMMDLPAQEIINRLK--KPPPVYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTF 802
Cdd:cd13978  202 FENAINPLLIMQIVSKgdRPSLDDIGRLKQIENVQELISLMIRCWDGNPDARPTF 256
PTKc_Fes_like cd05041
Catalytic domain of Fes-like Protein Tyrosine Kinases; Protein Tyrosine Kinase (PTK) family; ...
596-810 1.58e-25

Catalytic domain of Fes-like Protein Tyrosine Kinases; Protein Tyrosine Kinase (PTK) family; Fes subfamily; catalytic (c) domain. Fes subfamily members include Fes (or Fps), Fer, and similar proteins. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fes subfamily proteins are cytoplasmic (or nonreceptor) tyr kinases containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. The genes for Fes (feline sarcoma) and Fps (Fujinami poultry sarcoma) were first isolated from tumor-causing retroviruses. The viral oncogenes encode chimeric Fes proteins consisting of Gag sequences at the N-termini, resulting in unregulated tyr kinase activity. Fes and Fer kinases play roles in haematopoiesis, inflammation and immunity, growth factor signaling, cytoskeletal regulation, cell migration and adhesion, and the regulation of cell-cell interactions. Fes and Fer show redundancy in their biological functions.


Pssm-ID: 270637 [Multi-domain]  Cd Length: 251  Bit Score: 106.76  E-value: 1.58e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRN 675
Cdd:cd05041   45 RILKQYDHPNIVKLIGVCVQKQPIMIVMELVPGGSLLTFLRKKGARLTVKQLLQMCLDAAAGMEYLESKNCIHRDLAARN 124
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    676 CVVDGRFVLKVTDYGfndileMLRLSEEESSMEEL-------LWTAPELLRAPRGSRLgsfaGDVYSFAIIMQEVMVRG- 747
Cdd:cd05041  125 CLVGENNVLKISDFG------MSREEEDGEYTVSDglkqipiKWTAPEALNYGRYTSE----SDVWSFGILLWEIFSLGa 194
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 945225    748 TPFC-MMDLPAQEIINRlkkpppvYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEIFNQFK 810
Cdd:cd05041  195 TPYPgMSNQQTREQIES-------GYRMPAPELCPEAVYRLMLQCWAYDPENRPSFSEIYNELQ 251
PBP1_NPR-like cd06373
Ligand binding domain of natriuretic peptide receptor (NPR) family; Ligand binding domain of ...
54-412 5.51e-25

Ligand binding domain of natriuretic peptide receptor (NPR) family; Ligand binding domain of natriuretic peptide receptor (NPR) family which consists of three different subtypes: type A natriuretic peptide receptor (NPR-A, or GC-A), type B natriuretic peptide receptors (NPR-B, or GC-B), and type C natriuretic peptide receptor (NPR-C). There are three types of natriuretic peptide (NP) ligands specific to the receptors: atrial NP (ANP), brain or B-type NP (BNP), and C-type NP (CNP). The NP family is thought to have arisen through gene duplication during evolution and plays an essential role in cardiovascular and body fluid homeostasis. ANP and BNP bind mainly to NPR-A, while CNP binds specifically to NPR-B. Both NPR-A and NPR-B have guanylyl cyclase catalytic activity and produces intracellular secondary messenger cGMP in response to peptide-ligand binding. Consequently, the NPR-A activation results in vasodilation and inhibition of vascular smooth muscle cell proliferation. NPR-C acts as the receptor for all the three members of NP family, and functions as a clearance receptor. Unlike NPR-A and -B, NPR-C lacks an intracellular guanylyl cyclase domain and is thought to exert biological actions by sequestration of released natriuretic peptides and/or inhibition of adenylyl cyclase.


Pssm-ID: 380596 [Multi-domain]  Cd Length: 394  Bit Score: 108.52  E-value: 5.51e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225     54 KIGVVGPWACDSLFS--KALPevAARLAIERINRDPSFdLSYSFEYVILNEDCQTSRALSSFISHHQMAS--GFIGPTnp 129
Cdd:cd06373    1 TLAVLLPQDDSYPFSlaKVLP--AIELALRRVERRGFL-PGWRFQVHYRDTKCSDTLAPLAAVDLYCAKKvdVFLGPV-- 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    130 gyCE--AASL--LGNSWDKGIFSWACVNYELDNKISYPTFSRTLPSPIR---VLVTVMKYFQWAHAGVISSDED---IWV 199
Cdd:cd06373   76 --CEyaLAPVarYAGHWNVPVLTAGGLAAGFDDKTEYPLLTRMGGSYVKlgeFVLTLLRHFGWRRVALLYHDNLrrkAGN 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    200 HTANRVASALRSHGLPVGVVL-----TTGQDSQSMRKALQRIhqADRIRIIIMCMHSaliggETQMHLLECAHDLKMTDG 274
Cdd:cd06373  154 SNCYFTLEGIFNALTGERDSIhksfdEFDETKDDFEILLKRV--SNSARIVILCASP-----DTVREIMLAAHELGMING 226
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    275 TYVFVPYDALLYSLPYKHTPYQVLR---NNPKLREAYDAVLTITVESQEKTFYQAFTEaaargEIPEK---------LEF 342
Cdd:cd06373  227 EYVFFNIDLFSSSSKGARPWYRENDtdeRNEKARKAYRALLTVTLRRPDSPEYRNFSE-----EVKERakekynyftYGD 301
                        330       340       350       360       370       380       390
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 945225    343 DQVSPLFGTIYNSIYFIAQAMNNAMKENGQA--GAAsLVQHSRNMQFHGFNQLMRTDSNGNGISEYVILDTN 412
Cdd:cd06373  302 EEVNSFVGAFHDAVLLYALALNETLAEGGSPrnGTE-ITERMWNRTFEGITGNVSIDANGDRNADYSLLDMN 372
S_TKc smart00220
Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or ...
584-807 1.36e-24

Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or threonine-specific kinase subfamily.


Pssm-ID: 214567 [Multi-domain]  Cd Length: 254  Bit Score: 104.15  E-value: 1.36e-24
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225       584 LKSIKSRASDVF--------EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDvKLDWMFKSSLLLDLI 655
Cdd:smart00220   29 IKVIKKKKIKKDrerilreiKILKKLKHPNIVRLYDVFEDEDKLYLVMEYCEGGDLFDLLKKRG-RLSEDEARFYLRQIL 107
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225       656 KGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGFNDILEmlRLSEEESSMEELLWTAPELLRaprgsRLG-SFAGDVY 734
Cdd:smart00220  108 SALEYLHSKGIVHRDLKPENILLDEDGHVKLADFGLARQLD--PGEKLTTFVGTPEYMAPEVLL-----GKGyGKAVDIW 180
                           170       180       190       200       210       220       230
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 945225       735 SFAIIMQEVMVRGTPFCMMDLPaQEIINRLKKPPPVYRPVVPPehAPPECLQLMKQCWAEAAEQRPTFDEIFN 807
Cdd:smart00220  181 SLGVILYELLTGKPPFPGDDQL-LELFKKIGKPKPPFPPPEWD--ISPEAKDLIRKLLVKDPEKRLTAEEALQ 250
PTKc_Csk cd05082
Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase; PTKs catalyze the ...
579-810 1.46e-24

Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Csk catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. Csk is expressed in a wide variety of tissues. As a negative regulator of Src, Csk plays a role in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. Csk is a cytoplasmic (or nonreceptor) PTK containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. To inhibit Src kinases, Csk is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. In addition, Csk also shows Src-independent functions. It is a critical component in G-protein signaling, and plays a role in cytoskeletal reorganization and cell migration. The Csk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133213 [Multi-domain]  Cd Length: 256  Bit Score: 104.29  E-value: 1.46e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    579 GDFGDL------------KSIKSRAS-DVF----EMMKDLRHENINPLLGFFY-DSGMFAIVTEFCSRGSLEDILTNQDV 640
Cdd:cd05082   17 GEFGDVmlgdyrgnkvavKCIKNDATaQAFlaeaSVMTQLRHSNLVQLLGVIVeEKGGLYIVTEYMAKGSLVDYLRSRGR 96
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    641 KL---DWMFKSSLllDLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGfndiLEMLRLSEEESSMEELLWTAPEL 717
Cdd:cd05082   97 SVlggDCLLKFSL--DVCEAMEYLEGNNFVHRDLAARNVLVSEDNVAKVSDFG----LTKEASSTQDTGKLPVKWTAPEA 170
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    718 LRaprgSRLGSFAGDVYSFAIIMQEVMVRG-TPFcmMDLPAQEIINRLKKpppvYRPVVPPEHAPPECLQLMKQCWAEAA 796
Cdd:cd05082  171 LR----EKKFSTKSDVWSFGILLWEIYSFGrVPY--PRIPLKDVVPRVEK----GYKMDAPDGCPPAVYDVMKNCWHLDA 240
                        250
                 ....*....|....
gi 945225    797 EQRPTFDEIFNQFK 810
Cdd:cd05082  241 AMRPSFLQLREQLE 254
PTKc_EphR cd05033
Catalytic domain of Ephrin Receptor Protein Tyrosine Kinases; PTKs catalyze the transfer of ...
598-809 9.99e-24

Catalytic domain of Ephrin Receptor Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EphRs comprise the largest subfamily of receptor PTKs (RTKs). They can be classified into two classes (EphA and EphB), according to their extracellular sequences, which largely correspond to binding preferences for either GPI-anchored ephrin-A ligands or transmembrane ephrin-B ligands. Vertebrates have ten EphA and six EphB receptors, which display promiscuous ligand interactions within each class. EphRs contain an ephrin binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. This allows ephrin/EphR dimers to form, leading to the activation of the intracellular tyr kinase domain. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). The main effect of ephrin/EphR interaction is cell-cell repulsion or adhesion. Ephrin/EphR signaling is important in neural development and plasticity, cell morphogenesis and proliferation, cell-fate determination, embryonic development, tissue patterning, and angiogenesis.The EphR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270629 [Multi-domain]  Cd Length: 266  Bit Score: 102.07  E-value: 9.99e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    598 MKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNCV 677
Cdd:cd05033   59 MGQFDHPNVIRLEGVVTKSRPVMIVTEYMENGSLDKFLRENDGKFTVTQLVGMLRGIASGMKYLSEMNYVHRDLAARNIL 138
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    678 VDGRFVLKVTDYGFNDILEMLRLSEEESS-MEELLWTAPELLraprGSRLGSFAGDVYSFAIIMQEVMVRGT-PFcmMDL 755
Cdd:cd05033  139 VNSDLVCKVSDFGLSRRLEDSEATYTTKGgKIPIRWTAPEAI----AYRKFTSASDVWSFGIVMWEVMSYGErPY--WDM 212
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 945225    756 PAQEIINRLKKPPPVYrpvvppehAPPEC----LQLMKQCWAEAAEQRPTFDEIFNQF 809
Cdd:cd05033  213 SNQDVIKAVEDGYRLP--------PPMDCpsalYQLMLDCWQKDRNERPTFSQIVSTL 262
STKc_RIP1 cd14027
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1; STKs catalyze ...
597-812 1.58e-23

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP1 harbors a C-terminal Death domain (DD), which binds death receptors (DRs) including TNF receptor 1, Fas, TNF-related apoptosis-inducing ligand receptor 1 (TRAILR1), and TRAILR2. It also interacts with other DD-containing adaptor proteins such as TRADD and FADD. RIP1 can also recruit other kinases including MEKK1, MEKK3, and RIP3 through an intermediate domain (ID) that bears a RIP homotypic interaction motif (RHIM). RIP1 plays a crucial role in determining a cell's fate, between survival or death, following exposure to stress signals. It is important in the signaling of NF-kappaB and MAPKs, and it links DR-associated signaling to reactive oxygen species (ROS) production. Abnormal RIP1 function may result in ROS accummulation affecting inflammatory responses, innate immunity, stress responses, and cell survival. RIP kinases serve as essential sensors of cellular stress. The RIP1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270929 [Multi-domain]  Cd Length: 267  Bit Score: 101.42  E-value: 1.58e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKLDwmFKSSLLLDLIKGMKYLHHREFVHGRLKSRNC 676
Cdd:cd14027   44 MMNRLRHSRVVKLLGVILEEGKYSLVMEYMEKGNLMHVLKKVSVPLS--VKGRIILEIIEGMAYLHGKGVIHKDLKPENI 121
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    677 VVDGRFVLKVTDYG---FNDILEMLRLSEEESSMEELL---------WTAPELLRAPRGSrlGSFAGDVYSFAIIMQEVM 744
Cdd:cd14027  122 LVDNDFHIKIADLGlasFKMWSKLTKEEHNEQREVDGTakknagtlyYMAPEHLNDVNAK--PTEKSDVYSFAIVLWAIF 199
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 945225    745 VRGTPFcmMDLPAQEIINRLKKPPPVYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEIFNQFKTF 812
Cdd:cd14027  200 ANKEPY--ENAINEDQIIMCIKSGNRPDVDDITEYCPREIIDLMKLCWEANPEARPTFPGIEEKFRPF 265
STKc_MLTK cd14060
Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated ...
596-811 1.55e-22

Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated protein Triple Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLTK, also called zipper sterile-alpha-motif kinase (ZAK), contains a catalytic kinase domain and a leucine zipper. There are two alternatively-spliced variants, MLTK-alpha and MLTK-beta. MLTK-alpha contains a sterile-alpha-motif (SAM) at the C-terminus. MLTK regulates the c-Jun N-terminal kinase, extracellular signal-regulated kinase, p38 MAPK, and NF-kB pathways. ZAK is the MAP3K involved in the signaling cascade that leads to the ribotoxic stress response initiated by cellular damage due to Shiga toxins and ricin. It may also play a role in cell transformation and cancer development. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals.The MLTK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270962 [Multi-domain]  Cd Length: 242  Bit Score: 97.72  E-value: 1.55e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDIL-TNQDVKLDWMFKSSLLLDLIKGMKYLHHR---EFVHGRL 671
Cdd:cd14060   34 EILSVLSHRNIIQFYGAILEAPNYGIVTEYASYGSLFDYLnSNESEEMDMDQIMTWATDIAKGMHYLHMEapvKVIHRDL 113
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    672 KSRNCVVDGRFVLKVTDYGFNdilEMLRLSEEESSMEELLWTAPELLRAPRGSRLgsfaGDVYSFAIIMQEVMVRGTPFC 751
Cdd:cd14060  114 KSRNVVIAADGVLKICDFGAS---RFHSHTTHMSLVGTFPWMAPEVIQSLPVSET----CDTYSYGVVLWEMLTREVPFK 186
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 945225    752 MMD--LPAQEIINRLKKpppvyrpVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEIFNQFKT 811
Cdd:cd14060  187 GLEglQVAWLVVEKNER-------PTIPSSCPRSFAELMRRCWEADVKERPSFKQIIGILES 241
STKc_IRAK cd14066
Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases ...
585-806 8.26e-22

Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases and related STKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. Some IRAKs may also play roles in T- and B-cell signaling, and adaptive immunity. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK-1, -2, and -4 are ubiquitously expressed and are active kinases, while IRAK-M is only induced in monocytes and macrophages and is an inactive kinase. Variations in IRAK genes are linked to diverse diseases including infection, sepsis, cancer, and autoimmune diseases. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain (a pseudokinase domain in the case of IRAK3), and a C-terminal domain; IRAK-4 lacks the C-terminal domain. This subfamily includes plant receptor-like kinases (RLKs) including Arabidopsis thaliana BAK1 and CLAVATA1 (CLV1). BAK1 functions in BR (brassinosteroid)-regulated plant development and in pathways involved in plant resistance to pathogen infection and herbivore attack. CLV1, directly binds small signaling peptides, CLAVATA3 (CLV3) and CLAVATA3/EMBRYO SURROUNDING REGI0N (CLE), to restrict stem cell proliferation: the CLV3-CLV1-WUS (WUSCHEL) module influences stem cell maintenance in the shoot apical meristem, and the CLE40 (CLAVATA3/EMBRYO SURROUNDING REGION40) -ACR4 (CRINKLY4) -CLV1- WOX5 (WUSCHEL-RELATED HOMEOBOX5) module at the root apical meristem. The IRAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270968 [Multi-domain]  Cd Length: 272  Bit Score: 96.57  E-value: 8.26e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    585 KSIKSRASDVFEMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVK--LDWMFKSSLLLDLIKGMKYLH 662
Cdd:cd14066   31 AASKKEFLTELEMLGRLRHPNLVRLLGYCLESDEKLLVYEYMPNGSLEDRLHCHKGSppLPWPQRLKIAKGIARGLEYLH 110
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    663 HREF---VHGRLKSRNCVVDGRFVLKVTDYGFNDIL-EMLRLSEEESSMEELLWTAPELLRaprgSRLGSFAGDVYSFAI 738
Cdd:cd14066  111 EECPppiIHGDIKSSNILLDEDFEPKLTDFGLARLIpPSESVSKTSAVKGTIGYLAPEYIR----TGRVSTKSDVYSFGV 186
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    739 IMQEVMVR-------GTPFCMMDLpAQEIINRLKKPPPV---YRPVVPPEHAPPECLQLMK---QCWAEAAEQRPTFDEI 805
Cdd:cd14066  187 VLLELLTGkpavdenRENASRKDL-VEWVESKGKEELEDildKRLVDDDGVEEEEVEALLRlalLCTRSDPSLRPSMKEV 265

                 .
gi 945225    806 F 806
Cdd:cd14066  266 V 266
PTKc_Src_like cd05034
Catalytic domain of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of ...
596-809 1.03e-21

Catalytic domain of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, and Yes. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, and Lyn show a limited expression pattern. The Src-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270630 [Multi-domain]  Cd Length: 248  Bit Score: 95.81  E-value: 1.03e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKldwMFKSSLLLDLI----KGMKYLHHREFVHGRL 671
Cdd:cd05034   42 QIMKKLRHDKLVQLYAVCSDEEPIYIVTELMSKGSLLDYLRTGEGR---ALRLPQLIDMAaqiaSGMAYLESRNYIHRDL 118
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    672 KSRNCVVDGRFVLKVTDYGFNDILEMLRLSEEESSMEELLWTAPEllrAPRGSRLgSFAGDVYSFAIIMQEVMVRG-TPF 750
Cdd:cd05034  119 AARNILVGENNVCKVADFGLARLIEDDEYTAREGAKFPIKWTAPE---AALYGRF-TIKSDVWSFGILLYEIVTYGrVPY 194
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 945225    751 CMMDLPaqEIINRLKKPPPVYRPvvppEHAPPECLQLMKQCWAEAAEQRPTFDEIFNQF 809
Cdd:cd05034  195 PGMTNR--EVLEQVERGYRMPKP----PGCPDELYDIMLQCWKKEPEERPTFEYLQSFL 247
PTKc_Lyn cd05072
Catalytic domain of the Protein Tyrosine Kinase, Lyn; PTKs catalyze the transfer of the ...
597-816 1.22e-21

Catalytic domain of the Protein Tyrosine Kinase, Lyn; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Lyn is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lyn is expressed in B lymphocytes and myeloid cells. It exhibits both positive and negative regulatory roles in B cell receptor (BCR) signaling. Lyn, as well as Fyn and Blk, promotes B cell activation by phosphorylating ITAMs (immunoreceptor tyr activation motifs) in CD19 and in Ig components of BCR. It negatively regulates signaling by its unique ability to phosphorylate ITIMs (immunoreceptor tyr inhibition motifs) in cell surface receptors like CD22 and CD5. Lyn also plays an important role in G-CSF receptor signaling by phosphorylating a variety of adaptor molecules. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Lyn subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270657 [Multi-domain]  Cd Length: 272  Bit Score: 96.26  E-value: 1.22e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQD---VKLDWMFKSSLllDLIKGMKYLHHREFVHGRLKS 673
Cdd:cd05072   55 LMKTLQHDKLVRLYAVVTKEEPIYIITEYMAKGSLLDFLKSDEggkVLLPKLIDFSA--QIAEGMAYIERKNYIHRDLRA 132
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    674 RNCVVDGRFVLKVTDYGFNDILEMLRLSEEESSMEELLWTAPELLRaprgsrLGSFA--GDVYSFAIIMQEVMVRGT-PF 750
Cdd:cd05072  133 ANVLVSESLMCKIADFGLARVIEDNEYTAREGAKFPIKWTAPEAIN------FGSFTikSDVWSFGILLYEIVTYGKiPY 206
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 945225    751 CMMDlpAQEIINRLKKPPPVYRPvvppEHAPPECLQLMKQCWAEAAEQRPTFD---EIFNQFKTFNKGK 816
Cdd:cd05072  207 PGMS--NSDVMSALQRGYRMPRM----ENCPDELYDIMKTCWKEKAEERPTFDylqSVLDDFYTATEGQ 269
PTKc_Tec_like cd05059
Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
596-808 1.58e-21

Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Tec-like subfamily is composed of Tec, Btk, Bmx (Etk), Itk (Tsk, Emt), Rlk (Txk), and similar proteins. They are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, some members contain the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. Tec kinases form the second largest subfamily of nonreceptor PTKs and are expressed mainly by haematopoietic cells, although Tec and Bmx are also found in endothelial cells. B-cells express Btk and Tec, while T-cells express Itk, Txk, and Tec. Collectively, Tec kinases are expressed in a variety of myeloid cells such as mast cells, platelets, macrophages, and dendritic cells. Each Tec kinase shows a distinct cell-type pattern of expression. Tec kinases play important roles in the development, differentiation, maturation, regulation, survival, and function of B-cells and T-cells. Mutations in Btk cause the severe B-cell immunodeficiency, X-linked agammaglobulinaemia (XLA). The Tec-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173637 [Multi-domain]  Cd Length: 256  Bit Score: 95.21  E-value: 1.58e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKldwmFKSSLLL----DLIKGMKYLHHREFVHGRL 671
Cdd:cd05059   51 KVMMKLSHPKLVQLYGVCTKQRPIFIVTEYMANGCLLNYLRERRGK----FQTEQLLemckDVCEAMEYLESNGFIHRDL 126
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    672 KSRNCVVDGRFVLKVTDYGFNDILEMLRLSEEESSMEELLWTAPELLRAPRGSRlgsfAGDVYSFAIIMQEVMVRGTpfc 751
Cdd:cd05059  127 AARNCLVGEQNVVKVSDFGLARYVLDDEYTSSVGTKFPVKWSPPEVFMYSKFSS----KSDVWSFGVLMWEVFSEGK--- 199
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 945225    752 mmdLPAQEIIN-----------RLKKPPPvyrpvvppehAPPECLQLMKQCWAEAAEQRPTFDEIFNQ 808
Cdd:cd05059  200 ---MPYERFSNsevvehisqgyRLYRPHL----------APTEVYTIMYSCWHEKPEERPTFKILLSQ 254
PTKc_Abl cd05052
Catalytic domain of the Protein Tyrosine Kinase, Abelson kinase; PTKs catalyze the transfer of ...
565-811 3.79e-21

Catalytic domain of the Protein Tyrosine Kinase, Abelson kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Abl (or c-Abl) is a ubiquitously-expressed cytoplasmic (or nonreceptor) PTK that contains SH3, SH2, and tyr kinase domains in its N-terminal region, as well as nuclear localization motifs, a putative DNA-binding domain, and F- and G-actin binding domains in its C-terminal tail. It also contains a short autoinhibitory cap region in its N-terminus. Abl function depends on its subcellular localization. In the cytoplasm, Abl plays a role in cell proliferation and survival. In response to DNA damage or oxidative stress, Abl is transported to the nucleus where it induces apoptosis. In chronic myelogenous leukemia (CML) patients, an aberrant translocation results in the replacement of the first exon of Abl with the BCR (breakpoint cluster region) gene. The resulting BCR-Abl fusion protein is constitutively active and associates into tetramers, resulting in a hyperactive kinase sending a continuous signal. This leads to uncontrolled proliferation, morphological transformation and anti-apoptotic effects. BCR-Abl is the target of selective inhibitors, such as imatinib (Gleevec), used in the treatment of CML. Abl2, also known as ARG (Abelson-related gene), is thought to play a cooperative role with Abl in the proper development of the nervous system. The Tel-ARG fusion protein, resulting from reciprocal translocation between chromosomes 1 and 12, is associated with acute myeloid leukemia (AML). The TEL gene is a frequent fusion partner of other tyr kinase oncogenes, including Tel/Abl, Tel/PDGFRbeta, and Tel/Jak2, found in patients with leukemia and myeloproliferative disorders. The Abl subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270645 [Multi-domain]  Cd Length: 263  Bit Score: 94.41  E-value: 3.79e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    565 IYEGDWvwlKKFSLGDfgDLKSIKSRASDVFE------MMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDIL-TN 637
Cdd:cd05052   22 VYEGVW---KKYNLTV--AVKTLKEDTMEVEEflkeaaVMKEIKHPNLVQLLGVCTREPPFYIITEFMPYGNLLDYLrEC 96
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    638 QDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGFNDILEMLRLSEEESSMEELLWTAPEL 717
Cdd:cd05052   97 NREELNAVVLLYMATQIASAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFPIKWTAPES 176
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    718 LraprGSRLGSFAGDVYSFAIIMQEVMVRG-TPFCMMDLpaQEIINRLKKPPPVYRPvvppEHAPPECLQLMKQCWAEAA 796
Cdd:cd05052  177 L----AYNKFSIKSDVWAFGVLLWEIATYGmSPYPGIDL--SQVYELLEKGYRMERP----EGCPPKVYELMRACWQWNP 246
                        250
                 ....*....|....*
gi 945225    797 EQRPTFDEIFNQFKT 811
Cdd:cd05052  247 SDRPSFAEIHQALET 261
PTKc_EphR_B cd05065
Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors; PTKs catalyze ...
597-807 5.30e-21

Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Class EphB receptors bind to transmembrane ephrin-B ligands. There are six vertebrate EphB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands. One exception is EphB2, which also interacts with ephrin A5. EphB receptors play important roles in synapse formation and plasticity, spine morphogenesis, axon guidance, and angiogenesis. In the intestinal epithelium, EphBs are Wnt signaling target genes that control cell compartmentalization. They function as suppressors of colon cancer progression. EphRs comprise the largest subfamily of receptor PTKs (RTKs). They contain an ephrin-binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion. The EphB subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173638 [Multi-domain]  Cd Length: 269  Bit Score: 94.17  E-value: 5.30e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNC 676
Cdd:cd05065   58 IMGQFDHPNIIHLEGVVTKSRPVMIITEFMENGALDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLSEMNYVHRDLAARNI 137
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    677 VVDGRFVLKVTDYGFNDILEMLRLSEEESSME----ELLWTAPELLraprGSRLGSFAGDVYSFAIIMQEVMVRGT-PFc 751
Cdd:cd05065  138 LVNSNLVCKVSDFGLSRFLEDDTSDPTYTSSLggkiPIRWTAPEAI----AYRKFTSASDVWSYGIVMWEVMSYGErPY- 212
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    752 mMDLPAQEIINRLKKPPPVYrpvvppehAPPEC----LQLMKQCWAEAAEQRPTFDEIFN 807
Cdd:cd05065  213 -WDMSNQDVINAIEQDYRLP--------PPMDCptalHQLMLDCWQKDRNLRPKFGQIVN 263
PTKc_EphR_A2 cd05063
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A2; PTKs catalyze the ...
597-807 5.73e-21

Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The EphA2 receptor is overexpressed in tumor cells and tumor blood vessels in a variety of cancers including breast, prostate, lung, and colon. As a result, it is an attractive target for drug design since its inhibition could affect several aspects of tumor progression. EphRs comprise the largest subfamily of receptor PTKs (RTKs). Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphRs contain an ephrin binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis. The EphA2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 133194 [Multi-domain]  Cd Length: 268  Bit Score: 93.89  E-value: 5.73e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNC 676
Cdd:cd05063   59 IMGQFSHHNIIRLEGVVTKFKPAMIITEYMENGALDKYLRDHDGEFSSYQLVGMLRGIAAGMKYLSDMNYVHRDLAARNI 138
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    677 VVDGRFVLKVTDYGFNDILEMLRLSEEESS--MEELLWTAPELLraprGSRLGSFAGDVYSFAIIMQEVMVRGT-PFcmM 753
Cdd:cd05063  139 LVNSNLECKVSDFGLSRVLEDDPEGTYTTSggKIPIRWTAPEAI----AYRKFTSASDVWSFGIVMWEVMSFGErPY--W 212
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 945225    754 DLPAQEIINRLKKPPPVYrpvvppehAPPEC----LQLMKQCWAEAAEQRPTFDEIFN 807
Cdd:cd05063  213 DMSNHEVMKAINDGFRLP--------APMDCpsavYQLMLQCWQQDRARRPRFVDIVN 262
PTKc_Lck_Blk cd05067
Catalytic domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk; PTKs ...
573-812 6.60e-21

Catalytic domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Lck and Blk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lck is expressed in T-cells and natural killer cells. It plays a critical role in T-cell maturation, activation, and T-cell receptor (TCR) signaling. Lck phosphorylates ITAM (immunoreceptor tyr activation motif) sequences on several subunits of TCRs, leading to the activation of different second messenger cascades. Phosphorylated ITAMs serve as binding sites for other signaling factor such as Syk and ZAP-70, leading to their activation and propagation of downstream events. In addition, Lck regulates drug-induced apoptosis by interfering with the mitochondrial death pathway. The apototic role of Lck is independent of its primary function in T-cell signaling. Blk is expressed specifically in B-cells. It is involved in pre-BCR (B-cell receptor) signaling. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Lck/Blk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270652 [Multi-domain]  Cd Length: 264  Bit Score: 93.80  E-value: 6.60e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    573 LKKFSLGDFGD-------------LKSIK--SRASDVF----EMMKDLRHENINPLLGFFYDSGMFaIVTEFCSRGSLED 633
Cdd:cd05067   12 VERLGAGQFGEvwmgyynghtkvaIKSLKqgSMSPDAFlaeaNLMKQLQHQRLVRLYAVVTQEPIY-IITEYMENGSLVD 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    634 IL-TNQDVKLdwmfKSSLLLDLI----KGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGFNDILEMLRLSEEESSME 708
Cdd:cd05067   91 FLkTPSGIKL----TINKLLDMAaqiaEGMAFIEERNYIHRDLRAANILVSDTLSCKIADFGLARLIEDNEYTAREGAKF 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    709 ELLWTAPELLRaprgsrLGSFA--GDVYSFAIIMQEVMVRG-TPFCMMDLPaqEIINRLKKPPPVYRPvvppEHAPPECL 785
Cdd:cd05067  167 PIKWTAPEAIN------YGTFTikSDVWSFGILLTEIVTHGrIPYPGMTNP--EVIQNLERGYRMPRP----DNCPEELY 234
                        250       260
                 ....*....|....*....|....*..
gi 945225    786 QLMKQCWAEAAEQRPTFDEIFNQFKTF 812
Cdd:cd05067  235 QLMRLCWKERPEDRPTFEYLRSVLEDF 261
PKc_LIMK_like cd14065
Catalytic domain of the LIM domain kinase-like protein kinases; PKs catalyze the transfer of ...
596-805 8.97e-21

Catalytic domain of the LIM domain kinase-like protein kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. Members of this subfamily include LIMK, Testicular or testis-specific protein kinase (TESK), and similar proteins. LIMKs are characterized as serine/threonine kinases (STKs) while TESKs are dual-specificity protein kinases. Both LIMK and TESK phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They are implicated in many cellular functions including cell spreading, motility, morphogenesis, meiosis, mitosis, and spermatogenesis. The LIMK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270967 [Multi-domain]  Cd Length: 252  Bit Score: 92.94  E-value: 8.97e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRN 675
Cdd:cd14065   40 KLMRRLSHPNILRFIGVCVKDNKLNFITEYVNGGTLEELLKSMDEQLPWSQRVSLAKDIASGMAYLHSKNIIHRDLNSKN 119
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    676 CVV---DGRFVLKVTDYGFNDILEMLRLSEEESSMEELL-----WTAPELLRAprgsRLGSFAGDVYSFAIIMQEVMVRg 747
Cdd:cd14065  120 CLVreaNRGRNAVVADFGLAREMPDEKTKKPDRKKRLTVvgspyWMAPEMLRG----ESYDEKVDVFSFGIVLCEIIGR- 194
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 945225    748 tpfcmmdLPAQ-EIINRLKK--PPPVYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEI 805
Cdd:cd14065  195 -------VPADpDYLPRTMDfgLDVRAFRTLYVPDCPPSFLPLAIRCCQLDPEKRPSFVEL 248
PTKc_Jak2_rpt2 cd14205
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 2; PTKs catalyze the ...
596-805 1.16e-20

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak2 is widely expressed in many tissues and is essential for the signaling of hormone-like cytokines such as growth hormone, erythropoietin, thrombopoietin, and prolactin, as well as some IFNs and cytokines that signal through the IL-3 and gp130 receptors. Disruption of Jak2 in mice results in an embryonic lethal phenotype with multiple defects including erythropoietic and cardiac abnormalities. It is the only Jak gene that results in a lethal phenotype when disrupted in mice. A mutation in the pseudokinase domain of Jak2, V617F, is present in many myeloproliferative diseases, including almost all patients with polycythemia vera, and 50% of patients with essential thrombocytosis and myelofibrosis. Jak2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal catalytic tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271107 [Multi-domain]  Cd Length: 284  Bit Score: 93.54  E-value: 1.16e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGM--FAIVTEFCSRGSLEDILTNQDVKLDWmfkSSLLL---DLIKGMKYLHHREFVHGR 670
Cdd:cd14205   57 EILKSLQHDNIVKYKGVCYSAGRrnLRLIMEYLPYGSLRDYLQKHKERIDH---IKLLQytsQICKGMEYLGTKRYIHRD 133
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    671 LKSRNCVVDGRFVLKVTDYGFNDILEMLRLSEEESS--MEELLWTAPELLRAPRgsrlGSFAGDVYSFAIIMQEVMV--- 745
Cdd:cd14205  134 LATRNILVENENRVKIGDFGLTKVLPQDKEYYKVKEpgESPIFWYAPESLTESK----FSVASDVWSFGVVLYELFTyie 209
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 945225    746 --RGTPFCMM-----DLPAQEIINRLKKPPPVYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEI 805
Cdd:cd14205  210 ksKSPPAEFMrmignDKQGQMIVFHLIELLKNNGRLPRPDGCPDEIYMIMTECWNNNVNQRPSFRDL 276
PTKc_Src_Fyn_like cd14203
Catalytic domain of a subset of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
596-803 1.38e-20

Catalytic domain of a subset of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily includes a subset of Src-like PTKs including Src, Fyn, Yrk, and Yes, which are all widely expressed. Yrk has been detected only in chickens. It is primarily found in neuronal and epithelial cells and in macrophages. It may play a role in inflammation and in response to injury. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells and tumor vasculature, contributing to cancer progression and metastasis. They are also implicated in acute inflammatory responses and osteoclast function. The Src/Fyn-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271105 [Multi-domain]  Cd Length: 248  Bit Score: 92.29  E-value: 1.38e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFaIVTEFCSRGSLEDILTNQDVKldwMFKSSLLLDL----IKGMKYLHHREFVHGRL 671
Cdd:cd14203   42 QIMKKLRHDKLVQLYAVVSEEPIY-IVTEFMSKGSLLDFLKDGEGK---YLKLPQLVDMaaqiASGMAYIERMNYIHRDL 117
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    672 KSRNCVVDGRFVLKVTDYGFNDILEMLRLSEEESSMEELLWTAPEllraprGSRLGSFA--GDVYSFAIIMQEVMVRG-T 748
Cdd:cd14203  118 RAANILVGDNLVCKIADFGLARLIEDNEYTARQGAKFPIKWTAPE------AALYGRFTikSDVWSFGILLTELVTKGrV 191
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 945225    749 PFCMMDlpAQEIINRLKKPPPVYrpvvppehAPPEC----LQLMKQCWAEAAEQRPTFD 803
Cdd:cd14203  192 PYPGMN--NREVLEQVERGYRMP--------CPPGCpeslHELMCQCWRKDPEERPTFE 240
PTKc_Met_Ron cd05058
Catalytic domain of the Protein Tyrosine Kinases, Met and Ron; PTKs catalyze the transfer of ...
597-805 2.93e-20

Catalytic domain of the Protein Tyrosine Kinases, Met and Ron; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Met and Ron are receptor PTKs (RTKs) composed of an alpha-beta heterodimer. The extracellular alpha chain is disulfide linked to the beta chain, which contains an extracellular ligand-binding region with a sema domain, a PSI domain and four IPT repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. Met binds to the ligand, hepatocyte growth factor/scatter factor (HGF/SF), and is also called the HGF receptor. HGF/Met signaling plays a role in growth, transformation, cell motility, invasion, metastasis, angiogenesis, wound healing, and tissue regeneration. Aberrant expression of Met through mutations or gene amplification is associated with many human cancers including hereditary papillary renal and gastric carcinomas. The ligand for Ron is macrophage stimulating protein (MSP). Ron signaling is important in regulating cell motility, adhesion, proliferation, and apoptosis. Aberrant Ron expression is implicated in tumorigenesis and metastasis. The Met/Ron subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270649 [Multi-domain]  Cd Length: 262  Bit Score: 91.77  E-value: 2.93e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFFYDS-GMFAIVTEFCSRGSLEDILTNQD----VKlDWMfksSLLLDLIKGMKYLHHREFVHGRL 671
Cdd:cd05058   49 IMKDFSHPNVLSLLGICLPSeGSPLVVLPYMKHGDLRNFIRSEThnptVK-DLI---GFGLQVAKGMEYLASKKFVHRDL 124
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    672 KSRNCVVDGRFVLKVTDYGF-NDIL--EMLRLSEEESSMEELLWTAPELLRAPRGSRlgsfAGDVYSFAIIMQEVMVRGT 748
Cdd:cd05058  125 AARNCMLDESFTVKVADFGLaRDIYdkEYYSVHNHTGAKLPVKWMALESLQTQKFTT----KSDVWSFGVLLWELMTRGA 200
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 945225    749 PfCMMDLPAQEIINRLKKpppvYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEI 805
Cdd:cd05058  201 P-PYPDVDSFDITVYLLQ----GRRLLQPEYCPDPLYEVMLSCWHPKPEMRPTFSEL 252
PBP1_GABAb_receptor cd06366
ligand-binding domain of GABAb receptors, which are metabotropic transmembrane receptors for ...
75-442 3.00e-20

ligand-binding domain of GABAb receptors, which are metabotropic transmembrane receptors for gamma-aminobutyric acid (GABA); Ligand-binding domain of GABAb receptors, which are metabotropic transmembrane receptors for gamma-aminobutyric acid (GABA). GABA is the major inhibitory neurotransmitter in the mammalian CNS and, like glutamate and other transmitters, acts via both ligand gated ion channels (GABAa receptors) and G-protein coupled receptors (GABAb receptor or GABAbR). GABAa receptors are members of the ionotropic receptor superfamily which includes alpha-adrenergic and glycine receptors. The GABAb receptor is a member of a receptor superfamily which includes the mGlu receptors. The GABAb receptor is coupled to G alpha-i proteins, and activation causes a decrease in calcium, an increase in potassium membrane conductance, and inhibition of cAMP formation. The response is thus inhibitory and leads to hyperpolarization and decreased neurotransmitter release, for example.


Pssm-ID: 380589 [Multi-domain]  Cd Length: 404  Bit Score: 94.62  E-value: 3.00e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225     75 AARLAIERINRDPSFDLSYSFEYVILNEDCQTSRALSSFIshHQMAS-----GFIGPTNPGYCEAASLLGNSWDKGIFSW 149
Cdd:cd06366   23 AAEMALEHINNRSDILPGYNLELIWNDTQCDPGLGLKALY--DLLYTpppkvMLLGPGCSSVTEPVAEASKYWNLVQLSY 100
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    150 ACVNYELDNKISYPTFSRTLPSP---IRVLVTVMKYFQWAHAGVISSDEDIWVHTANRVASALRSHGlpVGVVLTTGQDS 226
Cdd:cd06366  101 AATSPALSDRKRYPYFFRTVPSDtafNPARIALLKHFGWKRVATIYQNDEVFSSTAEDLEELLEEAN--ITIVATESFSS 178
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    227 QSMRKALQRIHQADRiRIIImcmhsaLIGGETQMHLLEC-AHDLKMTDGTYV-FVP--YDALLYSLPYKH---TPYQvlr 299
Cdd:cd06366  179 EDPTDQLENLKEKDA-RIII------GLFYEDAARKVFCeAYKLGMYGPKYVwILPgwYDDNWWDVPDNDvncTPEQ--- 248
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    300 nnpkLREAYDAVLTITVE----SQEKT--------FYQAFTEAAArgeiPEKLEFDQVSPLfgtIYNSIYFIAQAMNNAM 367
Cdd:cd06366  249 ----MLEALEGHFSTELLplnpDNTKTisgltaqeFLKEYLERLS----NSNYTGSPYAPF---AYDAVWAIALALNKTI 317
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    368 KENgQAGAASLVQHSRNMQFHG--FNQLMRTdSNGNGISEYV--------ILDTNLKEWELHSTYTV---DMEMELLRF- 433
Cdd:cd06366  318 EKL-AEYNKTLEDFTYNDKEMAdlFLEAMNS-TSFEGVSGPVsfdskgdrLGTVDIEQLQGGSYVKVglyDPNADSLLLl 395

                 ....*....
gi 945225    434 GGTPIHFPG 442
Cdd:cd06366  396 NESSIVWPG 404
PTKc_EphR_A cd05066
Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors; PTKs catalyze ...
597-807 4.94e-20

Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of most class EphA receptors including EphA3, EphA4, EphA5, and EphA7, but excluding EphA1, EphA2 and EphA10. Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. One exception is EphA4, which also binds ephrins-B2/B3. EphA receptors and ephrin-A ligands are expressed in multiple areas of the developing brain, especially in the retina and tectum. They are part of a system controlling retinotectal mapping. EphRs comprise the largest subfamily of receptor PTKs (RTKs). EphRs contain an ephrin-binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis. The EphA subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270651 [Multi-domain]  Cd Length: 267  Bit Score: 91.08  E-value: 4.94e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNC 676
Cdd:cd05066   58 IMGQFDHPNIIHLEGVVTRSKPVMIVTEYMENGSLDAFLRKHDGQFTVIQLVGMLRGIASGMKYLSDMGYVHRDLAARNI 137
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    677 VVDGRFVLKVTDYGFNDILE--MLRLSEEESSMEELLWTAPELLraprGSRLGSFAGDVYSFAIIMQEVMVRGT-PFcmM 753
Cdd:cd05066  138 LVNSNLVCKVSDFGLSRVLEddPEAAYTTRGGKIPIRWTAPEAI----AYRKFTSASDVWSYGIVMWEVMSYGErPY--W 211
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 945225    754 DLPAQEIINRLKKPPPVYrpvvppehAPPEC----LQLMKQCWAEAAEQRPTFDEIFN 807
Cdd:cd05066  212 EMSNQDVIKAIEEGYRLP--------APMDCpaalHQLMLDCWQKDRNERPKFEQIVS 261
PTKc_Chk cd05083
Catalytic domain of the Protein Tyrosine Kinase, Csk homologous kinase; PTKs catalyze the ...
598-805 6.89e-20

Catalytic domain of the Protein Tyrosine Kinase, Csk homologous kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Chk is also referred to as megakaryocyte-associated tyrosine kinase (Matk). Chk inhibits Src kinases using a noncatalytic mechanism by simply binding to them. As a negative regulator of Src kinases, Chk may play important roles in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. Chk is expressed in brain and hematopoietic cells. Like Csk, it is a cytoplasmic (or nonreceptor) tyr kinase containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. To inhibit Src kinases that are anchored to the plasma membrane, Chk is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. Studies in mice reveal that Chk is not functionally redundant with Csk and that it plays an important role as a regulator of immune responses. Chk also plays a role in neural differentiation in a manner independent of Src by enhancing Mapk activation via Ras-mediated signaling. The Chk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270666 [Multi-domain]  Cd Length: 254  Bit Score: 90.32  E-value: 6.89e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    598 MKDLRHENINPLLGFFYDSGMFaIVTEFCSRGSLEDILTNQD---VKLDWMFKSSLllDLIKGMKYLHHREFVHGRLKSR 674
Cdd:cd05083   53 MTKLQHKNLVRLLGVILHNGLY-IVMELMSKGNLVNFLRSRGralVPVIQLLQFSL--DVAEGMEYLESKKLVHRDLAAR 129
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    675 NCVVDGRFVLKVTDYGfndiLEMLRLSEEESSMEELLWTAPELLRAPRGSRlgsfAGDVYSFAIIMQEVMVRG-TPFCMM 753
Cdd:cd05083  130 NILVSEDGVAKISDFG----LAKVGSMGVDNSRLPVKWTAPEALKNKKFSS----KSDVWSYGVLLWEVFSYGrAPYPKM 201
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 945225    754 DLpaQEIINRLKKpppvYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEI 805
Cdd:cd05083  202 SV--KEVKEAVEK----GYRMEPPEGCPPDVYSIMTSCWEAEPGKRPSFKKL 247
PTKc_Yes cd05069
Catalytic domain of the Protein Tyrosine Kinase, Yes; PTKs catalyze the transfer of the ...
596-805 7.48e-20

Catalytic domain of the Protein Tyrosine Kinase, Yes; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Yes (or c-Yes) is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. c-Yes kinase is the cellular homolog of the oncogenic protein (v-Yes) encoded by the Yamaguchi 73 and Esh sarcoma viruses. It displays functional overlap with other Src subfamily members, particularly Src. It also shows some unique functions such as binding to occludins, transmembrane proteins that regulate extracellular interactions in tight junctions. Yes also associates with a number of proteins in different cell types that Src does not interact with, like JAK2 and gp130 in pre-adipocytes, and Pyk2 in treated pulmonary vein endothelial cells. Although the biological function of Yes remains unclear, it appears to have a role in regulating cell-cell interactions and vesicle trafficking in polarized cells. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Yes subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 270654 [Multi-domain]  Cd Length: 279  Bit Score: 90.90  E-value: 7.48e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFaIVTEFCSRGSLEDILTNQDVKldwMFKSSLLLDLIK----GMKYLHHREFVHGRL 671
Cdd:cd05069   59 QIMKKLRHDKLVPLYAVVSEEPIY-IVTEFMGKGSLLDFLKEGDGK---YLKLPQLVDMAAqiadGMAYIERMNYIHRDL 134
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    672 KSRNCVVDGRFVLKVTDYGFNDILEMLRLSEEESSMEELLWTAPEllraprGSRLGSFA--GDVYSFAIIMQEVMVRGTp 749
Cdd:cd05069  135 RAANILVGDNLVCKIADFGLARLIEDNEYTARQGAKFPIKWTAPE------AALYGRFTikSDVWSFGILLTELVTKGR- 207
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 945225    750 fcmmdLPAQEIINRLKKPPPVYRPVVPPEHAPPECL-QLMKQCWAEAAEQRPTFDEI 805
Cdd:cd05069  208 -----VPYPGMVNREVLEQVERGYRMPCPQGCPESLhELMKLCWKKDPDERPTFEYI 259
PTKc_EphR_A10 cd05064
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A10; PTKs catalyze the ...
598-805 8.93e-20

Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A10; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EphA10, which contains an inactive tyr kinase domain, may function to attenuate signals of co-clustered active receptors. EphA10 is mainly expressed in the testis. Ephrin/EphR interaction results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis. EphRs comprise the largest subfamily of receptor tyr kinases (RTKs). In general, class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphRs contain an ephrin binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). The EphA10 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133195 [Multi-domain]  Cd Length: 266  Bit Score: 90.37  E-value: 8.93e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    598 MKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNCV 677
Cdd:cd05064   60 LGQFDHSNIVRLEGVITRGNTMMIVTEYMSNGALDSFLRKHEGQLVAGQLMGMLPGLASGMKYLSEMGYVHKGLAAHKVL 139
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    678 VDGRFVLKVTDYGFNDILEMLRLSEEESSMEELLWTAPELLRAPRGSRlgsfAGDVYSFAIIMQEVMVRGT-PFcmMDLP 756
Cdd:cd05064  140 VNSDLVCKISGFRRLQEDKSEAIYTTMSGKSPVLWAAPEAIQYHHFSS----ASDVWSFGIVMWEVMSYGErPY--WDMS 213
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 945225    757 AQEIInrlkKPPPVYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEI 805
Cdd:cd05064  214 GQDVI----KAVEDGFRLPAPRNCPNLLHQLMLDCWQKERGERPRFSQI 258
PK_KSR cd14063
Pseudokinase domain of Kinase Suppressor of Ras; The pseudokinase domain shows similarity to ...
583-802 1.06e-19

Pseudokinase domain of Kinase Suppressor of Ras; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. KSR is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. KSR proteins regulate the assembly and activation of the Raf/MEK/ERK module upon Ras activation at the membrane by direct association of its components. They are widely regarded as pseudokinases, but there is some debate in this designation as a few groups have reported detecting kinase catalytic activity for KSRs, specifically KSR1. Vertebrates contain two KSR proteins, KSR1 and KSR2. The KSR subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270965 [Multi-domain]  Cd Length: 271  Bit Score: 90.49  E-value: 1.06e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    583 DLKSIKSRASdvfeMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLH 662
Cdd:cd14063   39 QLEAFKEEVA----AYKNTRHDNLVLFMGACMDPPHLAIVTSLCKGRTLYSLIHERKEKFDFNKTVQIAQQICQGMGYLH 114
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    663 HREFVHGRLKSRNCVVD-GRFVlkVTDYGFNDILEMLRLSEEESS-MEELLWT---APELLRA-----PRGSRLG-SFAG 731
Cdd:cd14063  115 AKGIIHKDLKSKNIFLEnGRVV--ITDFGLFSLSGLLQPGRREDTlVIPNGWLcylAPEIIRAlspdlDFEESLPfTKAS 192
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 945225    732 DVYSFAIIMQEVMVRGTPFcmMDLPAQEIINRLKKPPPVYRPVVPPehaPPECLQLMKQCWAEAAEQRPTF 802
Cdd:cd14063  193 DVYAFGTVWYELLAGRWPF--KEQPAESIIWQVGCGKKQSLSQLDI---GREVKDILMQCWAYDPEKRPTF 258
PTKc_Hck cd05073
Catalytic domain of the Protein Tyrosine Kinase, Hematopoietic cell kinase; PTKs catalyze the ...
597-812 1.84e-19

Catalytic domain of the Protein Tyrosine Kinase, Hematopoietic cell kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Hck is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Hck is present in myeloid and lymphoid cells that play a role in the development of cancer. It may be important in the oncogenic signaling of the protein Tel-Abl, which induces a chronic myelogenous leukemia (CML)-like disease. Hck also acts as a negative regulator of G-CSF-induced proliferation of granulocytic precursors, suggesting a possible role in the development of acute myeloid leukemia (AML). In addition, Hck is essential in regulating the degranulation of polymorphonuclear leukocytes. Genetic polymorphisms affect the expression level of Hck, which affects PMN mediator release and influences the development of chronic obstructive pulmonary disease (COPD). Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Hck subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270658 [Multi-domain]  Cd Length: 265  Bit Score: 89.70  E-value: 1.84e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFFYDSGMFaIVTEFCSRGSLEDILTNQD---VKLDWMFKSSLllDLIKGMKYLHHREFVHGRLKS 673
Cdd:cd05073   59 VMKTLQHDKLVKLHAVVTKEPIY-IITEFMAKGSLLDFLKSDEgskQPLPKLIDFSA--QIAEGMAFIEQRNYIHRDLRA 135
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    674 RNCVVDGRFVLKVTDYGFNDILEMLRLSEEESSMEELLWTAPELLraprgsRLGSFA--GDVYSFAIIMQEVMVRG-TPF 750
Cdd:cd05073  136 ANILVSASLVCKIADFGLARVIEDNEYTAREGAKFPIKWTAPEAI------NFGSFTikSDVWSFGILLMEIVTYGrIPY 209
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 945225    751 CMMDLPaqEIINRLKKpppvYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEIFNQFKTF 812
Cdd:cd05073  210 PGMSNP--EVIRALER----GYRMPRPENCPEELYNIMMRCWKNRPEERPTFEYIQSVLDDF 265
PTKc_Tyk2_rpt2 cd05080
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; PTKs catalyze ...
596-812 1.92e-19

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tyk2 is widely expressed in many tissues. It is involved in signaling via the cytokine receptors IFN-alphabeta, IL-6, IL-10, IL-12, IL-13, and IL-23. It mediates cell surface urokinase receptor (uPAR) signaling and plays a role in modulating vascular smooth muscle cell (VSMC) functional behavior in response to injury. Tyk2 is also important in dendritic cell function and T helper (Th)1 cell differentiation. A homozygous mutation of Tyk2 was found in a patient with hyper-IgE syndrome (HIES), a primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and elevated serum IgE. This suggests that Tyk2 may play important roles in multiple cytokine signaling involved in innate and adaptive immunity. Tyk2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase catalytic domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The Tyk2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270664 [Multi-domain]  Cd Length: 283  Bit Score: 89.96  E-value: 1.92e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSG--MFAIVTEFCSRGSLEDILTNQDVKLdwmfkSSLLL---DLIKGMKYLHHREFVHGR 670
Cdd:cd05080   58 DILKTLYHENIVKYKGCCSEQGgkSLQLIMEYVPLGSLRDYLPKHSIGL-----AQLLLfaqQICEGMAYLHSQHYIHRD 132
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    671 LKSRNCVVDGRFVLKVTDYGFNDILEM--LRLSEEESSMEELLWTAPELLRAPRGSrlgsFAGDVYSFAIIMQEVMVRGT 748
Cdd:cd05080  133 LAARNVLLDNDRLVKIGDFGLAKAVPEghEYYRVREDGDSPVFWYAPECLKEYKFY----YASDVWSFGVTLYELLTHCD 208
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 945225    749 P-------FCMMDLPAQEIIN--RLKKPPPVYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEIFNQFKTF 812
Cdd:cd05080  209 SsqspptkFLEMIGIAQGQMTvvRLIELLERGERLPCPDKCPQEVYHLMKNCWETEASFRPTFENLIPILKTV 281
PKc_LIMK_like_unk cd14156
Catalytic domain of an unknown subfamily of LIM domain kinase-like protein kinases; PKs ...
596-810 2.79e-19

Catalytic domain of an unknown subfamily of LIM domain kinase-like protein kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. This group is composed of uncharacterized proteins with similarity to LIMK and Testicular or testis-specific protein kinase (TESK). LIMKs are characterized as serine/threonine kinases (STKs) while TESKs are dual-specificity protein kinases. Both LIMK and TESK phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They are implicated in many cellular functions including cell spreading, motility, morphogenesis, meiosis, mitosis, and spermatogenesis. The LIMK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271058 [Multi-domain]  Cd Length: 256  Bit Score: 88.73  E-value: 2.79e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRN 675
Cdd:cd14156   40 SLLQKLSHPNIVRYLGICVKDEKLHPILEYVSGGCLEELLAREELPLSWREKVELACDISRGMVYLHSKNIYHRDLNSKN 119
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    676 CVV----DGRFVLkVTDYGFNDILEMLRLSEEESSME---ELLWTAPELLRAPRGSRlgsfAGDVYSFAIIMQEVMVRgt 748
Cdd:cd14156  120 CLIrvtpRGREAV-VTDFGLAREVGEMPANDPERKLSlvgSAFWMAPEMLRGEPYDR----KVDVFSFGIVLCEILAR-- 192
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 945225    749 pfcmmdLPAQ-EIINRLKKP-PPVYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEIFNQFK 810
Cdd:cd14156  193 ------IPADpEVLPRTGDFgLDVQAFKEMVPGCPEPFLDLAASCCRMDAFKRPSFAELLDELE 250
PTKc_Src cd05071
Catalytic domain of the Protein Tyrosine Kinase, Src; PTKs catalyze the transfer of the ...
596-803 7.65e-19

Catalytic domain of the Protein Tyrosine Kinase, Src; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Src (or c-Src) is a cytoplasmic (or non-receptor) PTK, containing an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region with a conserved tyr. It is activated by autophosphorylation at the tyr kinase domain, and is negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). c-Src is the vertebrate homolog of the oncogenic protein (v-Src) from Rous sarcoma virus. Together with other Src subfamily proteins, it is involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. Src also play a role in regulating cell adhesion, invasion, and motility in cancer cells and tumor vasculature, contributing to cancer progression and metastasis. Elevated levels of Src kinase activity have been reported in a variety of human cancers. Several inhibitors of Src have been developed as anti-cancer drugs. Src is also implicated in acute inflammatory responses and osteoclast function. The Src subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270656 [Multi-domain]  Cd Length: 277  Bit Score: 88.21  E-value: 7.65e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFaIVTEFCSRGSLEDILTNQDVKldwMFKSSLLLD----LIKGMKYLHHREFVHGRL 671
Cdd:cd05071   56 QVMKKLRHEKLVQLYAVVSEEPIY-IVTEYMSKGSLLDFLKGEMGK---YLRLPQLVDmaaqIASGMAYVERMNYVHRDL 131
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    672 KSRNCVVDGRFVLKVTDYGFNDILEMLRLSEEESSMEELLWTAPEllraprGSRLGSFA--GDVYSFAIIMQEVMVRG-T 748
Cdd:cd05071  132 RAANILVGENLVCKVADFGLARLIEDNEYTARQGAKFPIKWTAPE------AALYGRFTikSDVWSFGILLTELTTKGrV 205
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 945225    749 PFCMMdlPAQEIINRLKKPPPVYrpvvppehAPPEC----LQLMKQCWAEAAEQRPTFD 803
Cdd:cd05071  206 PYPGM--VNREVLDQVERGYRMP--------CPPECpeslHDLMCQCWRKEPEERPTFE 254
PTKc_FGFR cd05053
Catalytic domain of the Protein Tyrosine Kinases, Fibroblast Growth Factor Receptors; PTKs ...
596-805 9.08e-19

Catalytic domain of the Protein Tyrosine Kinases, Fibroblast Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The FGFR subfamily consists of FGFR1, FGFR2, FGFR3, FGFR4, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, and to heparin/heparan sulfate (HS) results in the formation of a ternary complex, which leads to receptor dimerization and activation, and intracellular signaling. There are at least 23 FGFs and four types of FGFRs. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. FGF/FGFR signaling is important in the regulation of embryonic development, homeostasis, and regenerative processes. Depending on the cell type and stage, FGFR signaling produces diverse cellular responses including proliferation, growth arrest, differentiation, and apoptosis. Aberrant signaling leads to many human diseases such as skeletal, olfactory, and metabolic disorders, as well as cancer. The FGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase .


Pssm-ID: 270646 [Multi-domain]  Cd Length: 294  Bit Score: 88.24  E-value: 9.08e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDL-RHENINPLLGFFYDSGMFAIVTEFCSRGSLEDIL-----TNQDVKLDWMFKSSLLL---DLI-------KGMK 659
Cdd:cd05053   68 EMMKMIgKHKNIINLLGACTQDGPLYVVVEYASKGNLREFLrarrpPGEEASPDDPRVPEEQLtqkDLVsfayqvaRGME 147
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    660 YLHHREFVHGRLKSRNCVVDGRFVLKVTDYGF-NDILEMLRLSEEESSMEELLWTAPELLRaprgSRLGSFAGDVYSFAI 738
Cdd:cd05053  148 YLASKKCIHRDLAARNVLVTEDNVMKIADFGLaRDIHHIDYYRKTTNGRLPVKWMAPEALF----DRVYTHQSDVWSFGV 223
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 945225    739 IMQEVM-VRGTPFcmMDLPAQEIINRLKKPPPVYRpvvppehaPPECLQ----LMKQCWAEAAEQRPTFDEI 805
Cdd:cd05053  224 LLWEIFtLGGSPY--PGIPVEELFKLLKEGHRMEK--------PQNCTQelymLMRDCWHEVPSQRPTFKQL 285
PTKc_Itk cd05112
Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase; PTKs ...
597-809 9.72e-19

Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Itk, also known as Tsk or Emt, is a member of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, Itk contains the Tec homology (TH) domain containing one proline-rich region and a zinc-binding region. Itk is expressed in T-cells and mast cells, and is important in their development and differentiation. Of the three Tec kinases expressed in T-cells, Itk plays the predominant role in T-cell receptor (TCR) signaling. It is activated by phosphorylation upon TCR crosslinking and is involved in the pathway resulting in phospholipase C-gamma1 activation and actin polymerization. It also plays a role in the downstream signaling of the T-cell costimulatory receptor CD28, the T-cell surface receptor CD2, and the chemokine receptor CXCR4. In addition, Itk is crucial for the development of T-helper(Th)2 effector responses. The Itk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133243 [Multi-domain]  Cd Length: 256  Bit Score: 87.31  E-value: 9.72e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKdLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKLDwmfKSSLL---LDLIKGMKYLHHREFVHGRLKS 673
Cdd:cd05112   53 MMK-LSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYLRTQRGLFS---AETLLgmcLDVCEGMAYLEEASVIHRDLAA 128
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    674 RNCVVDGRFVLKVTDYGFNDILEMLRLSEEESSMEELLWTAPELLRAPRGSRlgsfAGDVYSFAIIMQEVMVRG-TPF-C 751
Cdd:cd05112  129 RNCLVGENQVVKVSDFGMTRFVLDDQYTSSTGTKFPVKWSSPEVFSFSRYSS----KSDVWSFGVLMWEVFSEGkIPYeN 204
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 945225    752 MMDLPAQEIIN---RLKKPPPvyrpvvppehAPPECLQLMKQCWAEAAEQRPTFDEIFNQF 809
Cdd:cd05112  205 RSNSEVVEDINagfRLYKPRL----------ASTHVYEIMNHCWKERPEDRPSFSLLLRQL 255
PTKc_FGFR4 cd05099
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 4; PTKs ...
584-832 1.35e-18

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 4; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Unlike other FGFRs, there is only one splice form of FGFR4. It binds FGF1, FGF2, FGF6, FGF19, and FGF23. FGF19 is a selective ligand for FGFR4. Although disruption of FGFR4 in mice causes no obvious phenotype, in vivo inhibition of FGFR4 in cultured skeletal muscle cells resulted in an arrest of muscle progenitor differentiation. FGF6 and FGFR4 are uniquely expressed in myofibers and satellite cells. FGF6/FGFR4 signaling appears to play a key role in the regulation of muscle regeneration. A polymorphism in FGFR4 is found in head and neck squamous cell carcinoma. FGFR4 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR4 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133230 [Multi-domain]  Cd Length: 314  Bit Score: 88.10  E-value: 1.35e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    584 LKSIKSRASDV--------FEMMKDL-RHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQ-----DVKLD------ 643
Cdd:cd05099   49 VKMLKDNATDKdladliseMELMKLIgKHKNIINLLGVCTQEGPLYVIVEYAAKGNLREFLRARrppgpDYTFDitkvpe 128
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    644 --WMFKS--SLLLDLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGF-NDILEMLRLSEEESSMEELLWTAPELL 718
Cdd:cd05099  129 eqLSFKDlvSCAYQVARGMEYLESRRCIHRDLAARNVLVTEDNVMKIADFGLaRGVHDIDYYKKTSNGRLPVKWMAPEAL 208
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    719 RaprgSRLGSFAGDVYSFAIIMQEVM-VRGTPFcmMDLPAQEIINRLKKPPPVyrpvvppeHAPPECLQ----LMKQCWA 793
Cdd:cd05099  209 F----DRVYTHQSDVWSFGILMWEIFtLGGSPY--PGIPVEELFKLLREGHRM--------DKPSNCTHelymLMRECWH 274
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|
gi 945225    794 EAAEQRPTFDEIFNQFKTFNKGKKTNIIDsmLRM-LEQYS 832
Cdd:cd05099  275 AVPTQRPTFKQLVEALDKVLAAVSEEYLD--LSMpFEQYS 312
PTKc_Srm_Brk cd05148
Catalytic domain of the Protein Tyrosine Kinases, Src-related kinase lacking C-terminal ...
565-802 1.77e-18

Catalytic domain of the Protein Tyrosine Kinases, Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristylation sites (Srm) and Breast tumor kinase (Brk); PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Srm and Brk (also called protein tyrosine kinase 6) are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Brk has been found to be overexpressed in a majority of breast tumors. Src kinases in general contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr; they are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Srm and Brk however, lack the N-terminal myristylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. The Srm/Brk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133248 [Multi-domain]  Cd Length: 261  Bit Score: 86.72  E-value: 1.77e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    565 IYEGDWVWLKKFSLgdfgdlKSIKSRASDVFEM-------MKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTN 637
Cdd:cd05148   22 VWEGLWKNRVRVAI------KILKSDDLLKQQDfqkevqaLKRLRHKHLISLFAVCSVGEPVYIITELMEKGSLLAFLRS 95
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    638 QDVKldwMFKSSLLLDL----IKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGFNDILEMlRLSEEESSMEELLWT 713
Cdd:cd05148   96 PEGQ---VLPVASLIDMacqvAEGMAYLEEQNSIHRDLAARNILVGEDLVCKVADFGLARLIKE-DVYLSSDKKIPYKWT 171
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    714 APELLraprGSRLGSFAGDVYSFAIIMQEVMVRG-TPFCMMDlpAQEIINRLKKPPPVYRPVVppehAPPECLQLMKQCW 792
Cdd:cd05148  172 APEAA----SHGTFSTKSDVWSFGILLYEMFTYGqVPYPGMN--NHEVYDQITAGYRMPCPAK----CPQEIYKIMLECW 241
                        250
                 ....*....|
gi 945225    793 AEAAEQRPTF 802
Cdd:cd05148  242 AAEPEDRPSF 251
PTKc_EGFR_like cd05057
Catalytic domain of Epidermal Growth Factor Receptor-like Protein Tyrosine Kinases; PTKs ...
597-812 1.99e-18

Catalytic domain of Epidermal Growth Factor Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EGFR (HER, ErbB) subfamily members include EGFR (HER1, ErbB1), HER2 (ErbB2), HER3 (ErbB3), HER4 (ErbB4), and similar proteins. They are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, resulting in the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Collectively, they can recognize a variety of ligands including EGF, TGFalpha, and neuregulins, among others. All four subfamily members can form homo- or heterodimers. HER3 contains an impaired kinase domain and depends on its heterodimerization partner for activation. EGFR subfamily members are involved in signaling pathways leading to a broad range of cellular responses including cell proliferation, differentiation, migration, growth inhibition, and apoptosis. Gain of function alterations, through their overexpression, deletions, or point mutations in their kinase domains, have been implicated in various cancers. These receptors are targets of many small molecule inhibitors and monoclonal antibodies used in cancer therapy. The EGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270648 [Multi-domain]  Cd Length: 279  Bit Score: 86.70  E-value: 1.99e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFFYDSGMfAIVTEFCSRGSLEDILTNQDVKLDwmfkSSLLLD----LIKGMKYLHHREFVHGRLK 672
Cdd:cd05057   62 VMASVDHPHLVRLLGICLSSQV-QLITQLMPLGCLLDYVRNHRDNIG----SQLLLNwcvqIAKGMSYLEEKRLVHRDLA 136
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    673 SRNCVVDGRFVLKVTDYGFNDILEMLRLSEEESSMEE-LLWTAPELLRaprgSRLGSFAGDVYSFAIIMQEVMVRGT-PF 750
Cdd:cd05057  137 ARNVLVKTPNHVKITDFGLAKLLDVDEKEYHAEGGKVpIKWMALESIQ----YRIYTHKSDVWSYGVTVWELMTFGAkPY 212
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 945225    751 cmMDLPAQEIINRLKKPPPVYRpvvppehaPPEC----LQLMKQCWAEAAEQRPTFDEIFNQFKTF 812
Cdd:cd05057  213 --EGIPAVEIPDLLEKGERLPQ--------PPICtidvYMVLVKCWMIDAESRPTFKELANEFSKM 268
PTKc_c-ros cd05044
Catalytic domain of the Protein Tyrosine Kinase, C-ros; PTKs catalyze the transfer of the ...
597-808 3.40e-18

Catalytic domain of the Protein Tyrosine Kinase, C-ros; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily contains c-ros, Sevenless, and similar proteins. The proto-oncogene c-ros encodes an orphan receptor PTK (RTK) with an unknown ligand. RTKs contain an extracellular ligand-binding domain, a transmembrane region, and an intracellular tyr kinase domain. RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. C-ros is expressed in embryonic cells of the kidney, intestine and lung, but disappears soon after birth. It persists only in the adult epididymis. Male mice bearing inactive mutations of c-ros lack the initial segment of the epididymis and are infertile. The Drosophila protein, Sevenless, is required for the specification of the R7 photoreceptor cell during eye development. The c-ros subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270640 [Multi-domain]  Cd Length: 268  Bit Score: 85.93  E-value: 3.40e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDIL------TNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGR 670
Cdd:cd05044   52 LMSNFKHPNILKLLGVCLDNDPQYIILELMEGGDLLSYLraarptAFTPPLLTLKDLLSICVDVAKGCVYLEDMHFVHRD 131
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    671 LKSRNCVV---DGRF-VLKVTDYGF-NDILEMLRLSEEESSMEELLWTAPELLRAprgsrlGSFA--GDVYSFAIIMQEV 743
Cdd:cd05044  132 LAARNCLVsskDYRErVVKIGDFGLaRDIYKNDYYRKEGEGLLPVRWMAPESLVD------GVFTtqSDVWAFGVLMWEI 205
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 945225    744 MVRGT-PFcmmdlPA---QEIIN------RLKKPppvyrpvvppEHAPPECLQLMKQCWAEAAEQRPTFDEIFNQ 808
Cdd:cd05044  206 LTLGQqPY-----PArnnLEVLHfvraggRLDQP----------DNCPDDLYELMLRCWSTDPEERPSFARILEQ 265
PTKc_FAK cd05056
Catalytic domain of the Protein Tyrosine Kinase, Focal Adhesion Kinase; PTKs catalyze the ...
597-805 4.61e-18

Catalytic domain of the Protein Tyrosine Kinase, Focal Adhesion Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. FAK is a cytoplasmic (or nonreceptor) PTK that contains an autophosphorylation site and a FERM domain at the N-terminus, a central tyr kinase domain, proline-rich regions, and a C-terminal FAT (focal adhesion targeting) domain. FAK activity is dependent on integrin-mediated cell adhesion, which facilitates N-terminal autophosphorylation. Full activation is achieved by the phosphorylation of its two adjacent A-loop tyrosines. FAK is important in mediating signaling initiated at sites of cell adhesions and at growth factor receptors. Through diverse molecular interactions, FAK functions as a biosensor or integrator to control cell motility. It is a key regulator of cell survival, proliferation, migration and invasion, and thus plays an important role in the development and progression of cancer. Src binds to autophosphorylated FAK forming the FAK-Src dual kinase complex, which is activated in a wide variety of tumor cells and generates signals promoting growth and metastasis. FAK is being developed as a target for cancer therapy. The FAK subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133187 [Multi-domain]  Cd Length: 270  Bit Score: 85.55  E-value: 4.61e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFFYDSGMFaIVTEFCSRGSLEDILTnqdVKLDWMFKSSLLL---DLIKGMKYLHHREFVHGRLKS 673
Cdd:cd05056   60 IMRQFDHPHIVKLIGVITENPVW-IVMELAPLGELRSYLQ---VNKYSLDLASLILyayQLSTALAYLESKRFVHRDIAA 135
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    674 RNCVVDGRFVLKVTDYGFNDILEMLRLSEEESSMEELLWTAPELLRAPRGSRlgsfAGDVYSFAIIMQEVMVRGT-PFcm 752
Cdd:cd05056  136 RNVLVSSPDCVKLGDFGLSRYMEDESYYKASKGKLPIKWMAPESINFRRFTS----ASDVWMFGVCMWEILMLGVkPF-- 209
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 945225    753 MDLPAQEIINRLKKPPPVYRPvvppEHAPPECLQLMKQCWAEAAEQRPTFDEI 805
Cdd:cd05056  210 QGVKNNDVIGRIENGERLPMP----PNCPPTLYSLMTKCWAYDPSKRPRFTEL 258
STKc_MLK cd14061
Catalytic domain of the Serine/Threonine Kinases, Mixed Lineage Kinases; STKs catalyze the ...
584-811 1.69e-17

Catalytic domain of the Serine/Threonine Kinases, Mixed Lineage Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Mammals have four MLKs (MLK1-4), mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270963 [Multi-domain]  Cd Length: 258  Bit Score: 83.60  E-value: 1.69e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    584 LKSIKSRAsDVFEMmkdLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQ----DVKLDWMfkssllLDLIKGMK 659
Cdd:cd14061   37 LENVRQEA-RLFWM---LRHPNIIALRGVCLQPPNLCLVMEYARGGALNRVLAGRkippHVLVDWA------IQIARGMN 106
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    660 YLHHREFV---HGRLKSRNCVVDGRF--------VLKVTDYGFNDilEMLRLSEEESSMEELlWTAPELLRaprgSRLGS 728
Cdd:cd14061  107 YLHNEAPVpiiHRDLKSSNILILEAIenedlenkTLKITDFGLAR--EWHKTTRMSAAGTYA-WMAPEVIK----SSTFS 179
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    729 FAGDVYSFAIIMQEVMVRGTPFCMMDLPAQEI---INRLkkpppvyrpvvpPEHAPPEC----LQLMKQCWAEAAEQRPT 801
Cdd:cd14061  180 KASDVWSYGVLLWELLTGEVPYKGIDGLAVAYgvaVNKL------------TLPIPSTCpepfAQLMKDCWQPDPHDRPS 247
                        250
                 ....*....|
gi 945225    802 FDEIFNQFKT 811
Cdd:cd14061  248 FADILKQLEN 257
PTKc_Btk_Bmx cd05113
Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow ...
569-805 2.16e-17

Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow kinase on the X chromosome; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Btk and Bmx (also named Etk) are members of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, Btk contains the Tec homology (TH) domain with proline-rich and zinc-binding regions. Btk is expressed in B-cells, and a variety of myeloid cells including mast cells, platelets, neutrophils, and dendrictic cells. It interacts with a variety of partners, from cytosolic proteins to nuclear transcription factors, suggesting a diversity of functions. Stimulation of a diverse array of cell surface receptors, including antigen engagement of the B-cell receptor, leads to PH-mediated membrane translocation of Btk and subsequent phosphorylation by Src kinase and activation. Btk plays an important role in the life cycle of B-cells including their development, differentiation, proliferation, survival, and apoptosis. Mutations in Btk cause the primary immunodeficiency disease, X-linked agammaglobulinaemia (XLA) in humans. Bmx is primarily expressed in bone marrow and the arterial endothelium, and plays an important role in ischemia-induced angiogenesis. It facilitates arterial growth, capillary formation, vessel maturation, and bone marrow-derived endothelial progenitor cell mobilization. The Btk/Bmx subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173657 [Multi-domain]  Cd Length: 256  Bit Score: 83.39  E-value: 2.16e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    569 DWVWLKKFSLGDFG-------------DLKSIK--SRASDVF----EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRG 629
Cdd:cd05113    5 DLTFLKELGTGQFGvvkygkwrgqydvAIKMIKegSMSEDEFieeaKVMMNLSHEKLVQLYGVCTKQRPIFIITEYMANG 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    630 SLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGFNDILEMLRLSEEESSMEE 709
Cdd:cd05113   85 CLLNYLREMRKRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLSRYVLDDEYTSSVGSKFP 164
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    710 LLWTAPELLRAPRGSRlgsfAGDVYSFAIIMQEVMVRGT-PFCMMDlpAQEIINRLKKPPPVYRPVVPPEhappECLQLM 788
Cdd:cd05113  165 VRWSPPEVLMYSKFSS----KSDVWAFGVLMWEVYSLGKmPYERFT--NSETVEHVSQGLRLYRPHLASE----KVYTIM 234
                        250
                 ....*....|....*..
gi 945225    789 KQCWAEAAEQRPTFDEI 805
Cdd:cd05113  235 YSCWHEKADERPTFKIL 251
STKc_RIP2 cd14026
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 2; STKs catalyze ...
596-802 2.79e-17

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP2, also called RICK or CARDIAK, harbors a C-terminal Caspase Activation and Recruitment domain (CARD) belonging to the Death domain (DD) superfamily. It functions as an effector kinase downstream of the pattern recognition receptors from the Nod-like (NLR) family, Nod1 and Nod2, which recognizes bacterial peptidoglycans released upon infection. RIP2 may also be involved in regulating wound healing and keratinocyte proliferation. RIP kinases serve as essential sensors of cellular stress. The RIP2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270928 [Multi-domain]  Cd Length: 284  Bit Score: 83.43  E-value: 2.79e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKLD--WMFKSSLLLDLIKGMKYLHHRE--FVHGRL 671
Cdd:cd14026   49 EILHKARFSYILPILGICNEPEFLGIVTEYMTNGSLNELLHEKDIYPDvaWPLRLRILYEIALGVNYLHNMSppLLHHDL 128
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    672 KSRNCVVDGRFVLKVTDYGFNDILEML----RLSEEESSMEELLWTAPELLRaPRGSRLGSFAGDVYSFAIIMQEVMVRG 747
Cdd:cd14026  129 KTQNILLDGEFHVKIADFGLSKWRQLSisqsRSSKSAPEGGTIIYMPPEEYE-PSQKRRASVKHDIYSYAIIMWEVLSRK 207
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 945225    748 TPFCMMDLPAQEIINRLKKPPPVYRPVVPPEHAPPECL--QLMKQCWAEAAEQRPTF 802
Cdd:cd14026  208 IPFEEVTNPLQIMYSVSQGHRPDTGEDSLPVDIPHRATliNLIESGWAQNPDERPSF 264
PTK_CCK4 cd05046
Pseudokinase domain of the Protein Tyrosine Kinase, Colon Carcinoma Kinase 4; CCK4, also ...
596-805 3.20e-17

Pseudokinase domain of the Protein Tyrosine Kinase, Colon Carcinoma Kinase 4; CCK4, also called protein tyrosine kinase 7 (PTK7), is an orphan receptor PTK (RTK) containing an extracellular region with seven immunoglobulin domains, a transmembrane segment, and an intracellular inactive pseudokinase domain, which shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. Studies in mice reveal that CCK4 is essential for neural development. Mouse embryos containing a truncated CCK4 die perinatally and display craniorachischisis, a severe form of neural tube defect. The mechanism of action of the CCK4 pseudokinase is still unknown. Other pseudokinases such as HER3 rely on the activity of partner RTKs. The CCK4 subfamily is part of a larger superfamily that includes other pseudokinases and the catalytic domains of active kinases including PTKs, protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133178 [Multi-domain]  Cd Length: 275  Bit Score: 83.28  E-value: 3.20e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDIL--------TNQDVKLDWMFKSSLLLDLIKGMKYLHHREFV 667
Cdd:cd05046   60 DMFRKLSHKNVVRLLGLCREAEPHYMILEYTDLGDLKQFLratkskdeKLKPPPLSTKQKVALCTQIALGMDHLSNARFV 139
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    668 HGRLKSRNCVVDGRFVLKVTD------------YGFNDILEMLRlseeessmeellWTAPELLRAPRGSRlgsfAGDVYS 735
Cdd:cd05046  140 HRDLAARNCLVSSQREVKVSLlslskdvynseyYKLRNALIPLR------------WLAPEAVQEDDFST----KSDVWS 203
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 945225    736 FAIIMQEVMVRGT-PFcmMDLPAQEIINRLKkppPVYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEI 805
Cdd:cd05046  204 FGVLMWEVFTQGElPF--YGLSDEEVLNRLQ---AGKLELPVPEGCPSRLYKLMTRCWAVNPKDRPSFSEL 269
PTKc_Ror cd05048
Catalytic Domain of the Protein Tyrosine Kinases, Receptor tyrosine kinase-like Orphan ...
596-811 9.56e-17

Catalytic Domain of the Protein Tyrosine Kinases, Receptor tyrosine kinase-like Orphan Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Ror subfamily consists of Ror1, Ror2, and similar proteins. Ror proteins are orphan receptor PTKs (RTKs) containing an extracellular region with immunoglobulin-like, cysteine-rich, and kringle domains, a transmembrane segment, and an intracellular catalytic domain. Ror RTKs are unrelated to the nuclear receptor subfamily called retinoid-related orphan receptors (RORs). RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. Ror kinases are expressed in many tissues during development. They play important roles in bone and heart formation. Mutations in human Ror2 result in two different bone development genetic disorders, recessive Robinow syndrome and brachydactyly type B. Drosophila Ror is expressed only in the developing nervous system during neurite outgrowth and neuronal differentiation, suggesting a role for Drosophila Ror in neural development. More recently, mouse Ror1 and Ror2 have also been found to play an important role in regulating neurite growth in central neurons. Ror1 and Ror2 are believed to have some overlapping and redundant functions. The Ror subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270642 [Multi-domain]  Cd Length: 283  Bit Score: 82.04  E-value: 9.56e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILT----NQDVKL---DWMFKSSLL-LDLI-------KGMKY 660
Cdd:cd05048   60 ELMSDLQHPNIVCLLGVCTKEQPQCMLFEYMAHGDLHEFLVrhspHSDVGVssdDDGTASSLDqSDFLhiaiqiaAGMEY 139
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    661 LHHREFVHGRLKSRNCVVDGRFVLKVTDYG-FNDILEMLRLSEEESSMEELLWTAPELLraprgsRLGSF--AGDVYSFA 737
Cdd:cd05048  140 LSSHHYVHRDLAARNCLVGDGLTVKISDFGlSRDIYSSDYYRVQSKSLLPVRWMPPEAI------LYGKFttESDVWSFG 213
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 945225    738 IIMQEVMVRGT-PFCmmDLPAQEIINRLKKpppvYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEIFNQFKT 811
Cdd:cd05048  214 VVLWEIFSYGLqPYY--GYSNQEVIEMIRS----RQLLPCPEDCPARVYSLMVECWHEIPSRRPRFKEIHTRLRT 282
PTKc_Jak3_rpt2 cd05081
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 3; PTKs catalyze the ...
596-805 1.16e-16

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak3 is expressed only in hematopoietic cells. It binds the shared receptor subunit common gamma chain and thus, is essential in the signaling of cytokines that use it such as IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Jak3 is important in lymphoid development and myeloid cell differentiation. Inactivating mutations in Jak3 have been reported in humans with severe combined immunodeficiency (SCID). Jak3 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal catalytic tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270665 [Multi-domain]  Cd Length: 283  Bit Score: 81.86  E-value: 1.16e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGM--FAIVTEFCSRGSLEDILTNQDVKLDwmfKSSLLL---DLIKGMKYLHHREFVHGR 670
Cdd:cd05081   57 QILKALHSDFIVKYRGVSYGPGRrsLRLVMEYLPSGCLRDFLQRHRARLD---ASRLLLyssQICKGMEYLGSRRCVHRD 133
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    671 LKSRNCVVDGRFVLKVTDYGFNDILEMLRLSEEESS--MEELLWTAPELLRAPRGSRlgsfAGDVYSFAIIMQEVMVRGT 748
Cdd:cd05081  134 LAARNILVESEAHVKIADFGLAKLLPLDKDYYVVREpgQSPIFWYAPESLSDNIFSR----QSDVWSFGVVLYELFTYCD 209
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 945225    749 PFC--------MMDLP-AQEIINRLKKPPPVYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEI 805
Cdd:cd05081  210 KSCspsaeflrMMGCErDVPALCRLLELLEEGQRLPAPPACPAEVHELMKLCWAPSPQDRPSFSAL 275
PTKc_Ack_like cd05040
Catalytic domain of the Protein Tyrosine Kinase, Activated Cdc42-associated kinase; PTKs ...
584-805 1.28e-16

Catalytic domain of the Protein Tyrosine Kinase, Activated Cdc42-associated kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily includes Ack1, thirty-eight-negative kinase 1 (Tnk1), and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing an N-terminal catalytic domain, an SH3 domain, a Cdc42-binding CRIB domain, and a proline-rich region. They are mainly expressed in brain and skeletal tissues and are involved in the regulation of cell adhesion and growth, receptor degradation, and axonal guidance. Ack1 is also associated with androgen-independent prostate cancer progression. Tnk1 regulates TNFalpha signaling and may play an important role in cell death. The Ack-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270636 [Multi-domain]  Cd Length: 258  Bit Score: 80.85  E-value: 1.28e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    584 LKSIKSRASDVFE-------MMKDLRHENINPLLGFFYDSGMFaIVTEFCSRGSLEDILTNQdvkldwmfKSSLLLDLI- 655
Cdd:cd05040   31 LKSDVLSQPNAMDdflkevnAMHSLDHPNLIRLYGVVLSSPLM-MVTELAPLGSLLDRLRKD--------QGHFLISTLc 101
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    656 -------KGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGFNDILEMLRLSEEESSMEEL--LWTAPELLRaprgSRL 726
Cdd:cd05040  102 dyavqiaNGMAYLESKRFIHRDLAARNILLASKDKVKIGDFGLMRALPQNEDHYVMQEHRKVpfAWCAPESLK----TRK 177
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    727 GSFAGDVYSFAIIMQEVMVRG-TPFcmMDLPAQEIinrLKKPPPVYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEI 805
Cdd:cd05040  178 FSHASDVWMFGVTLWEMFTYGeEPW--LGLNGSQI---LEKIDKEGERLERPDDCPQDIYNVMLQCWAHKPADRPTFVAL 252
PTKc_Jak1_rpt2 cd05079
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 1; PTKs catalyze the ...
596-811 1.33e-16

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak1 is widely expressed in many tissues. Many cytokines are dependent on Jak1 for signaling, including those that use the shared receptor subunits common gamma chain (IL-2, IL-4, IL-7, IL-9, IL-15, IL-21) and gp130 (IL-6, IL-11, oncostatin M, G-CSF, and IFNs, among others). The many varied interactions of Jak1 and its ubiquitous expression suggest many biological roles. Jak1 is important in neurological development, as well as in lymphoid development and function. It also plays a role in the pathophysiology of cardiac hypertrophy and heart failure. A mutation in the ATP-binding site of Jak1 was identified in a human uterine leiomyosarcoma cell line, resulting in defective cytokine induction and antigen presentation, thus allowing the tumor to evade the immune system. Jak1 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The Jak1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173644 [Multi-domain]  Cd Length: 284  Bit Score: 81.51  E-value: 1.33e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAI--VTEFCSRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKS 673
Cdd:cd05079   58 EILRNLYHENIVKYKGICTEDGGNGIklIMEFLPSGSLKEYLPRNKNKINLKQQLKYAVQICKGMDYLGSRQYVHRDLAA 137
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    674 RNCVVDGRFVLKVTDYGFNDILEMLRLSEEES--SMEELLWTAPELLRAPRGSRlgsfAGDVYSFAIIMQEVMVRG---- 747
Cdd:cd05079  138 RNVLVESEHQVKIGDFGLTKAIETDKEYYTVKddLDSPVFWYAPECLIQSKFYI----ASDVWSFGVTLYELLTYCdses 213
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 945225    748 ---TPFCMMDLP--AQEIINRLKKPPPVYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEIFNQFKT 811
Cdd:cd05079  214 spmTLFLKMIGPthGQMTVTRLVRVLEEGKRLPRPPNCPEEVYQLMRKCWEFQPSKRTTFQNLIEGFEA 282
PTKc_PDGFR cd05055
Catalytic domain of the Protein Tyrosine Kinases, Platelet Derived Growth Factor Receptors; ...
584-805 2.87e-16

Catalytic domain of the Protein Tyrosine Kinases, Platelet Derived Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The PDGFR subfamily consists of PDGFR alpha, PDGFR beta, KIT, CSF-1R, the mammalian FLT3, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. PDGFR kinase domains are autoinhibited by their juxtamembrane regions containing tyr residues. The binding to their ligands leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. PDGFR subfamily receptors are important in the development of a variety of cells. PDGFRs are expressed in a many cells including fibroblasts, neurons, endometrial cells, mammary epithelial cells, and vascular smooth muscle cells. PDGFR signaling is critical in normal embryonic development, angiogenesis, and wound healing. Kit is important in the development of melanocytes, germ cells, mast cells, hematopoietic stem cells, the interstitial cells of Cajal, and the pacemaker cells of the GI tract. CSF-1R signaling is critical in the regulation of macrophages and osteoclasts. Mammalian FLT3 plays an important role in the survival, proliferation, and differentiation of stem cells. The PDGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase .


Pssm-ID: 133186 [Multi-domain]  Cd Length: 302  Bit Score: 80.99  E-value: 2.87e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    584 LKSiKSRASDVFEMMKDLR-------HENINPLLGFFYDSGMFAIVTEFCSRGSLEDIL-TNQDVKLDWMFKSSLLLDLI 655
Cdd:cd05055   73 LKP-TAHSSEREALMSELKimshlgnHENIVNLLGACTIGGPILVITEYCCYGDLLNFLrRKRESFLTLEDLLSFSYQVA 151
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    656 KGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGF-NDILEMLRLSEEESSMEELLWTAPELLRaprgSRLGSFAGDVY 734
Cdd:cd05055  152 KGMAFLASKNCIHRDLAARNVLLTHGKIVKICDFGLaRDIMNDSNYVVKGNARLPVKWMAPESIF----NCVYTFESDVW 227
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 945225    735 SFAIIMQEVMVRG-TPFcmmdlPAQEIINRLKKPPPVYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEI 805
Cdd:cd05055  228 SYGILLWEIFSLGsNPY-----PGMPVDSKFYKLIKEGYRMAQPEHAPAEIYDIMKTCWDADPLKRPTFKQI 294
PTKc_Frk_like cd05068
Catalytic domain of Fyn-related kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
573-803 3.09e-16

Catalytic domain of Fyn-related kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Frk and Srk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Frk, also known as Rak, is specifically expressed in liver, lung, kidney, intestine, mammary glands, and the islets of Langerhans. Rodent homologs were previously referred to as GTK (gastrointestinal tyr kinase), BSK (beta-cell Src-like kinase), or IYK (intestinal tyr kinase). Studies in mice reveal that Frk is not essential for viability. It plays a role in the signaling that leads to cytokine-induced beta-cell death in Type I diabetes. It also regulates beta-cell number during embryogenesis and early in life. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Frk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270653 [Multi-domain]  Cd Length: 267  Bit Score: 80.14  E-value: 3.09e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    573 LKKFSLGDFGD-------------LKSIKSRASDVFE------MMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLED 633
Cdd:cd05068   13 LRKLGSGQFGEvweglwnnttpvaVKTLKPGTMDPEDflreaqIMKKLRHPKLIQLYAVCTLEEPIYIITELMKHGSLLE 92
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    634 ILTNQDVKLdwmfKSSLLLDL----IKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGF------NDILEmlrlsEE 703
Cdd:cd05068   93 YLQGKGRSL----QLPQLIDMaaqvASGMAYLESQNYIHRDLAARNVLVGENNICKVADFGLarvikvEDEYE-----AR 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    704 ESSMEELLWTAPEllrAPRGSRLgSFAGDVYSFAIIMQEVMVRG-TPFCMMdlPAQEIINRLKKPPPVYRPVVppehAPP 782
Cdd:cd05068  164 EGAKFPIKWTAPE---AANYNRF-SIKSDVWSFGILLTEIVTYGrIPYPGM--TNAEVLQQVERGYRMPCPPN----CPP 233
                        250       260
                 ....*....|....*....|.
gi 945225    783 ECLQLMKQCWAEAAEQRPTFD 803
Cdd:cd05068  234 QLYDIMLECWKADPMERPTFE 254
STKc_MAP3K12_13 cd14059
Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase ...
598-805 3.33e-16

Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinases 12 and 13; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP3K12 is also called MAPK upstream kinase (MUK), dual leucine zipper-bearing kinase (DLK) or leucine-zipper protein kinase (ZPK). It is involved in the c-Jun N-terminal kinase (JNK) pathway that directly regulates axonal regulation through the phosphorylation of microtubule-associated protein 1B (MAP1B). It also regulates the differentiation of many cell types including adipocytes and may play a role in adipogenesis. MAP3K13, also called leucine zipper-bearing kinase (LZK), directly phosphorylates and activates MKK7, which in turn activates the JNK pathway. It also activates NF-kB through IKK activation and this activity is enhanced by antioxidant protein-1 (AOP-1). MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAP2Ks (MAPKKs or MKKs), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The MAP3K12/13 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270961 [Multi-domain]  Cd Length: 237  Bit Score: 79.46  E-value: 3.33e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    598 MKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVkldwmFKSSLLLDLIK----GMKYLHHREFVHGRLKS 673
Cdd:cd14059   35 LRKLNHPNIIKFKGVCTQAPCYCILMEYCPYGQLYEVLRAGRE-----ITPSLLVDWSKqiasGMNYLHLHKIIHRDLKS 109
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    674 RNCVVDGRFVLKVTDYGFNDilEMLRLSEEESSMEELLWTAPELLRaprgSRLGSFAGDVYSFAIIMQEVMVRGTPFcmM 753
Cdd:cd14059  110 PNVLVTYNDVLKISDFGTSK--ELSEKSTKMSFAGTVAWMAPEVIR----NEPCSEKVDIWSFGVVLWELLTGEIPY--K 181
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 945225    754 DLPAQEII-----NRLkkpppvyrpvvppeHAP-----PECLQ-LMKQCWAEAAEQRPTFDEI 805
Cdd:cd14059  182 DVDSSAIIwgvgsNSL--------------QLPvpstcPDGFKlLMKQCWNSKPRNRPSFRQI 230
PTKc_FGFR2 cd05101
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 2; PTKs ...
596-805 3.72e-16

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. There are many splice variants of FGFR2 which show differential expression and binding to FGF ligands. Disruption of either FGFR2 or FGFR2b is lethal in mice, due to defects in the placenta or severe impairment of tissue development including lung, limb, and thyroid, respectively. Disruption of FGFR2c in mice results in defective bone and skull development. Genetic alterations of FGFR2 are associated with many human skeletal disorders including Apert syndrome, Crouzon syndrome, Jackson-Weiss syndrome, and Pfeiffer syndrome. FGFR2 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270679 [Multi-domain]  Cd Length: 313  Bit Score: 80.83  E-value: 3.72e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDL-RHENINPLLGFFYDSGMFAIVTEFCSRGSLE---------------DILTNQDVKLDWMFKSSLLLDLIKGMK 659
Cdd:cd05101   81 EMMKMIgKHKNIINLLGACTQDGPLYVIVEYASKGNLReylrarrppgmeysyDINRVPEEQMTFKDLVSCTYQLARGME 160
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    660 YLHHREFVHGRLKSRNCVVDGRFVLKVTDYGF-NDILEMLRLSEEESSMEELLWTAPELLRaprgSRLGSFAGDVYSFAI 738
Cdd:cd05101  161 YLASQKCIHRDLAARNVLVTENNVMKIADFGLaRDINNIDYYKKTTNGRLPVKWMAPEALF----DRVYTHQSDVWSFGV 236
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 945225    739 IMQEVM-VRGTPFcmMDLPAQEIINRLKKPPPVyrpvvppeHAPPECLQ----LMKQCWAEAAEQRPTFDEI 805
Cdd:cd05101  237 LMWEIFtLGGSPY--PGIPVEELFKLLKEGHRM--------DKPANCTNelymMMRDCWHAVPSQRPTFKQL 298
PTKc_Fer cd05085
Catalytic domain of the Protein Tyrosine Kinase, Fer; Protein Tyrosine Kinase (PTK) family; ...
596-805 3.86e-16

Catalytic domain of the Protein Tyrosine Kinase, Fer; Protein Tyrosine Kinase (PTK) family; Fer kinase; catalytic (c) domain. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fer kinase is a member of the Fes subfamily of proteins which are cytoplasmic (or nonreceptor) tyr kinases containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. Fer kinase is expressed in a wide variety of tissues, and is found to reside in both the cytoplasm and the nucleus. It plays important roles in neuronal polarization and neurite development, cytoskeletal reorganization, cell migration, growth factor signaling, and the regulation of cell-cell interactions mediated by adherens junctions and focal adhesions. Fer kinase also regulates cell cycle progression in malignant cells.


Pssm-ID: 270668 [Multi-domain]  Cd Length: 251  Bit Score: 79.28  E-value: 3.86e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQ--DVKLDWMFKSSLllDLIKGMKYLHHREFVHGRLKS 673
Cdd:cd05085   45 RILKQYDHPNIVKLIGVCTQRQPIYIVMELVPGGDFLSFLRKKkdELKTKQLVKFSL--DAAAGMAYLESKNCIHRDLAA 122
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    674 RNCVVDGRFVLKVTDYGFNDILEMLRLSEEESSMEELLWTAPELLRAPRGSRlgsfAGDVYSFAIIMQEVMVRGT-PF-C 751
Cdd:cd05085  123 RNCLVGENNALKISDFGMSRQEDDGVYSSSGLKQIPIKWTAPEALNYGRYSS----ESDVWSFGILLWETFSLGVcPYpG 198
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 945225    752 MMDLPAQEIINRLKKpppvyrpVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEI 805
Cdd:cd05085  199 MTNQQAREQVEKGYR-------MSAPQRCPEDIYKIMQRCWDYNPENRPKFSEL 245
PTKc_FGFR3 cd05100
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 3; PTKs ...
578-837 5.03e-16

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Many FGFR3 splice variants have been reported with the IIIb and IIIc isoforms being the predominant forms. FGFR3 IIIc is the isoform expressed in chondrocytes, the cells affected in dwarfism, while IIIb is expressed in epithelial cells. FGFR3 ligands include FGF1, FGF2, FGF4, FGF8, FGF9, and FGF23. It is a negative regulator of long bone growth. In the cochlear duct and in the lens, FGFR3 is involved in differentiation while it appears to have a role in cell proliferation in epithelial cells. Germline mutations in FGFR3 are associated with skeletal disorders including several forms of dwarfism. Some missense mutations are associated with multiple myeloma and carcinomas of the bladder and cervix. Overexpression of FGFR3 is found in thyroid carcinoma. FGFR3 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173652 [Multi-domain]  Cd Length: 334  Bit Score: 80.84  E-value: 5.03e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    578 LGDFGDLKSIKSRASDVfEMMKDL-RHENINPLLGFFYDSGMFAIVTEFCSRGSLEDIL-TNQDVKLDWMFKSSLL---- 651
Cdd:cd05100   52 LKDDATDKDLSDLVSEM-EMMKMIgKHKNIINLLGACTQDGPLYVLVEYASKGNLREYLrARRPPGMDYSFDTCKLpeeq 130
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    652 ---LDLI-------KGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGF-NDILEMLRLSEEESSMEELLWTAPELLRa 720
Cdd:cd05100  131 ltfKDLVscayqvaRGMEYLASQKCIHRDLAARNVLVTEDNVMKIADFGLaRDVHNIDYYKKTTNGRLPVKWMAPEALF- 209
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    721 prgSRLGSFAGDVYSFAIIMQEVMVRG-TPFcmMDLPAQEIINRLKKPPPVyrpvvppeHAPPECLQ----LMKQCWAEA 795
Cdd:cd05100  210 ---DRVYTHQSDVWSFGVLLWEIFTLGgSPY--PGIPVEELFKLLKEGHRM--------DKPANCTHelymIMRECWHAV 276
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|..
gi 945225    796 AEQRPTFDEIFNQFKTFNKGKKTNIIDSMLRMLEQYSSNLED 837
Cdd:cd05100  277 PSQRPTFKQLVEDLDRVLTVTSTDEYLDLSVPFEQYSPGCPD 318
STKc_TAK1 cd14058
Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated ...
603-805 5.43e-16

Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated Kinase-1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAK1 is also known as mitogen-activated protein kinase kinase kinase 7 (MAPKKK7 or MAP3K7), TAK, or MEKK7. As a MAPKKK, it is an important mediator of cellular responses to extracellular signals. It regulates both the c-Jun N-terminal kinase and p38 MAPK cascades by activating the MAPK kinases, MKK4 and MKK3/6. In addition, TAK1 plays diverse roles in immunity and development, in different biological contexts, through many signaling pathways including TGFbeta/BMP, Wnt/Fz, and NF-kB. It is also implicated in the activation of the tumor suppressor kinase, LKB1. The TAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270960 [Multi-domain]  Cd Length: 253  Bit Score: 79.02  E-value: 5.43e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    603 HENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVK--------LDWMFKSSllldliKGMKYLHH---REFVHGRL 671
Cdd:cd14058   45 HPNIIKLYGACSNQKPVCLVMEYAEGGSLYNVLHGKEPKpiytaahaMSWALQCA------KGVAYLHSmkpKALIHRDL 118
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    672 KSRN-CVVDGRFVLKVTDYGF-NDILEMLrlseeESSMEELLWTAPELLRAprgsRLGSFAGDVYSFAIIMQEVMVRGTP 749
Cdd:cd14058  119 KPPNlLLTNGGTVLKICDFGTaCDISTHM-----TNNKGSAAWMAPEVFEG----SKYSEKCDVFSWGIILWEVITRRKP 189
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 945225    750 FCMMDLPAQEIINRLKKpppvyrpvvpPEHAP-----PECL-QLMKQCWAEAAEQRPTFDEI 805
Cdd:cd14058  190 FDHIGGPAFRIMWAVHN----------GERPPlikncPKPIeSLMTRCWSKDPEKRPSMKEI 241
PTKc_FGFR1 cd05098
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 1; PTKs ...
584-805 1.12e-15

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Alternative splicing of FGFR1 transcripts produces a variety of isoforms, which are differentially expressed in cells. FGFR1 binds the ligands, FGF1 and FGF2, with high affinity and has also been reported to bind FGF4, FGF6, and FGF9. FGFR1 signaling is critical in the control of cell migration during embryo development. It promotes cell proliferation in fibroblasts. Nuclear FGFR1 plays a role in the regulation of transcription. Mutations, insertions or deletions of FGFR1 have been identified in patients with Kallman's syndrome (KS), an inherited disorder characterized by hypogonadotropic hypogonadism and loss of olfaction. Aberrant FGFR1 expression has been found in some human cancers including 8P11 myeloproliferative syndrome (EMS), breast cancer, and pancreatic adenocarcinoma. FGFR1 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270678 [Multi-domain]  Cd Length: 302  Bit Score: 79.29  E-value: 1.12e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    584 LKSIKSRASDV--------FEMMKDL-RHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILT---------------NQD 639
Cdd:cd05098   50 VKMLKSDATEKdlsdliseMEMMKMIgKHKNIINLLGACTQDGPLYVIVEYASKGNLREYLQarrppgmeycynpshNPE 129
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    640 VKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGF-NDILEMLRLSEEESSMEELLWTAPELL 718
Cdd:cd05098  130 EQLSSKDLVSCAYQVARGMEYLASKKCIHRDLAARNVLVTEDNVMKIADFGLaRDIHHIDYYKKTTNGRLPVKWMAPEAL 209
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    719 RaprgSRLGSFAGDVYSFAIIMQEVM-VRGTPFcmMDLPAQEIINRLKKPPPVyrpvvppeHAPPECLQ----LMKQCWA 793
Cdd:cd05098  210 F----DRIYTHQSDVWSFGVLLWEIFtLGGSPY--PGVPVEELFKLLKEGHRM--------DKPSNCTNelymMMRDCWH 275
                        250
                 ....*....|..
gi 945225    794 EAAEQRPTFDEI 805
Cdd:cd05098  276 AVPSQRPTFKQL 287
PTKc_Tec_Rlk cd05114
Catalytic domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in hepatocellular ...
597-808 1.34e-15

Catalytic domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in hepatocellular carcinoma and Resting lymphocyte kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tec and Rlk (also named Txk) are members of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. Instead of PH, Rlk contains an N-terminal cysteine-rich region. In addition to PH, Tec also contains the Tec homology (TH) domain with proline-rich and zinc-binding regions. Tec kinases are expressed mainly by haematopoietic cells. Tec is more widely-expressed than other Tec-like subfamily kinases. It is found in endothelial cells, both B- and T-cells, and a variety of myeloid cells including mast cells, erythroid cells, platelets, macrophages and neutrophils. Rlk is expressed in T-cells and mast cell lines. Tec and Rlk are both key components of T-cell receptor (TCR) signaling. They are important in TCR-stimulated proliferation, IL-2 production and phopholipase C-gamma1 activation. The Tec/Rlk subfamily is part of a larger superfamily, that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270685 [Multi-domain]  Cd Length: 260  Bit Score: 77.98  E-value: 1.34e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKdLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNC 676
Cdd:cd05114   53 MMK-LTHPKLVQLYGVCTQQKPIYIVTEFMENGCLLNYLRQRRGKLSRDMLLSMCQDVCEGMEYLERNNFIHRDLAARNC 131
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    677 VVDGRFVLKVTDYGFNDILEMLRLSEEESSMEELLWTAPELLRAPRGSRlgsfAGDVYSFAIIMQEVMVRG-TPF-CMMD 754
Cdd:cd05114  132 LVNDTGVVKVSDFGMTRYVLDDQYTSSSGAKFPVKWSPPEVFNYSKFSS----KSDVWSFGVLMWEVFTEGkMPFeSKSN 207
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 945225    755 LPAQEII---NRLKKPPPvyrpvvppehAPPECLQLMKQCWAEAAEQRPTFDEIFNQ 808
Cdd:cd05114  208 YEVVEMVsrgHRLYRPKL----------ASKSVYEVMYSCWHEKPEGRPTFADLLRT 254
STKc_KSR1 cd14152
Catalytic domain of the Serine/Threonine Kinase, Kinase Suppressor of Ras 1; STKs catalyze the ...
596-814 1.62e-15

Catalytic domain of the Serine/Threonine Kinase, Kinase Suppressor of Ras 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. KSR1 functions as a transducer of TNFalpha-stimulated C-Raf activation of ERK1/2 and NF-kB. Detected activity of KSR1 is cell type specific and context dependent. It is inactive in normal colon epithelial cells and becomes activated at the onset of inflammatory bowel disease (IBD). Similarly, KSR1 activity is undetectable prior to stimulation by EGF or ceramide in COS-7 or YAMC cells, respectively. KSR proteins are widely regarded as pseudokinases, however, this matter is up for debate as catalytic activity has been detected for KSR1 in some systems. The KSR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271054 [Multi-domain]  Cd Length: 279  Bit Score: 78.09  E-value: 1.62e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMM--KDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKS 673
Cdd:cd14152   46 EVMnyRQTRHENVVLFMGACMHPPHLAIITSFCKGRTLYSFVRDPKTSLDINKTRQIAQEIIKGMGYLHAKGIVHKDLKS 125
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    674 RNCVVDGRFVLkVTDYGFNDI----LEMLRLSEEESSMEELLWTAPELLR--AP-RGSRLGSF--AGDVYSFAIIMQEVM 744
Cdd:cd14152  126 KNVFYDNGKVV-ITDFGLFGIsgvvQEGRRENELKLPHDWLCYLAPEIVRemTPgKDEDCLPFskAADVYAFGTIWYELQ 204
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    745 VRGTPFcmMDLPAQEIINRLKKPPPVYRPVVPPEHApPECLQLMKQCWAEAAEQRPTFDEIFNQFKTFNK 814
Cdd:cd14152  205 ARDWPL--KNQPAEALIWQIGSGEGMKQVLTTISLG-KEVTEILSACWAFDLEERPSFTLLMDMLEKLPK 271
PTKc_Fes cd05084
Catalytic domain of the Protein Tyrosine Kinase, Fes; PTKs catalyze the transfer of the ...
597-805 1.83e-15

Catalytic domain of the Protein Tyrosine Kinase, Fes; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fes (or Fps) is a cytoplasmic (or nonreceptor) PTK containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. The genes for Fes (feline sarcoma) and Fps (Fujinami poultry sarcoma) were first isolated from tumor-causing retroviruses. The viral oncogenes encode chimeric Fes proteins consisting of Gag sequences at the N-termini, resulting in unregulated PTK activity. Fes kinase is expressed in myeloid, vascular endothelial, epithelial, and neuronal cells. It plays important roles in cell growth and differentiation, angiogenesis, inflammation and immunity, and cytoskeletal regulation. A recent study implicates Fes kinase as a tumor suppressor in colorectal cancer. The Fes subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270667 [Multi-domain]  Cd Length: 252  Bit Score: 77.66  E-value: 1.83e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKLdwmfKSSLLLDLIK----GMKYLHHREFVHGRLK 672
Cdd:cd05084   47 ILKQYSHPNIVRLIGVCTQKQPIYIVMELVQGGDFLTFLRTEGPRL----KVKELIRMVEnaaaGMEYLESKHCIHRDLA 122
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    673 SRNCVVDGRFVLKVTDYGFN-DILEMLRLSEEESSMEELLWTAPELLRAPRGSRlgsfAGDVYSFAIIMQEVMVRG-TPF 750
Cdd:cd05084  123 ARNCLVTEKNVLKISDFGMSrEEEDGVYAATGGMKQIPVKWTAPEALNYGRYSS----ESDVWSFGILLWETFSLGaVPY 198
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 945225    751 CMM-DLPAQEIINRlkkpppvYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEI 805
Cdd:cd05084  199 ANLsNQQTREAVEQ-------GVRLPCPENCPDEVYRLMEQCWEYDPRKRPSFSTV 247
STKc_A-Raf cd14150
Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) ...
596-806 1.84e-15

Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. A-Raf cooperates with C-Raf in regulating ERK transient phosphorylation that is associated with cyclin D expression and cell cycle progression. Mice deficient in A-Raf are born alive but show neurological and intestinal defects. A-Raf demonstrates low kinase activity to MEK, compared with B- and C-Raf, and may also have alternative functions other than in the ERK signaling cascade. It regulates the M2 type pyruvate kinase, a key glycolytic enzyme. It also plays a role in endocytic membrane trafficking. A-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. It functions in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The A-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271052 [Multi-domain]  Cd Length: 265  Bit Score: 77.75  E-value: 1.84e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGmFAIVTEFCSRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRN 675
Cdd:cd14150   48 QVLRKTRHVNILLFMGFMTRPN-FAIITQWCEGSSLYRHLHVTETRFDTMQLIDVARQTAQGMDYLHAKNIIHRDLKSNN 126
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    676 CVVDGRFVLKVTDYGFNDILEMLR-LSEEESSMEELLWTAPELLRAPRGSRLgSFAGDVYSFAIIMQEVMVRGTPFCMMD 754
Cdd:cd14150  127 IFLHEGLTVKIGDFGLATVKTRWSgSQQVEQPSGSILWMAPEVIRMQDTNPY-SFQSDVYAYGVVLYELMSGTLPYSNIN 205
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 945225    755 LPAQeIINRLKKPPPVYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEIF 806
Cdd:cd14150  206 NRDQ-IIFMVGRGYLSPDLSKLSSNCPKAMKRLLIDCLKFKREERPLFPQIL 256
PTKc_Fyn cd05070
Catalytic domain of the Protein Tyrosine Kinase, Fyn; PTKs catalyze the transfer of the ...
596-803 1.87e-15

Catalytic domain of the Protein Tyrosine Kinase, Fyn; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fyn and Yrk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Fyn, together with Lck, plays a critical role in T-cell signal transduction by phosphorylating ITAM (immunoreceptor tyr activation motif) sequences on T-cell receptors, ultimately leading to the proliferation and differentiation of T-cells. In addition, Fyn is involved in the myelination of neurons, and is implicated in Alzheimer's and Parkinson's diseases. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Fyn/Yrk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase.


Pssm-ID: 270655 [Multi-domain]  Cd Length: 274  Bit Score: 77.80  E-value: 1.87e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFaIVTEFCSRGSLEDILTNQDVKldwMFKSSLLLDLIK----GMKYLHHREFVHGRL 671
Cdd:cd05070   56 QIMKKLKHDKLVQLYAVVSEEPIY-IVTEYMSKGSLLDFLKDGEGR---ALKLPNLVDMAAqvaaGMAYIERMNYIHRDL 131
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    672 KSRNCVVDGRFVLKVTDYGFNDILEMLRLSEEESSMEELLWTAPEllraprGSRLGSFA--GDVYSFAIIMQEVMVRG-T 748
Cdd:cd05070  132 RSANILVGNGLICKIADFGLARLIEDNEYTARQGAKFPIKWTAPE------AALYGRFTikSDVWSFGILLTELVTKGrV 205
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 945225    749 PFCMMDlpAQEIINRLKKpppvYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFD 803
Cdd:cd05070  206 PYPGMN--NREVLEQVER----GYRMPCPQDCPISLHELMIHCWKKDPEERPTFE 254
PKc_STE cd05122
Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the ...
596-749 2.57e-15

Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. This family is composed of STKs, and some dual-specificity PKs that phosphorylate both threonine and tyrosine residues of target proteins. Most members are kinases involved in mitogen-activated protein kinase (MAPK) signaling cascades, acting as MAPK kinases (MAPKKs), MAPKK kinases (MAPKKKs), or MAPKKK kinases (MAP4Ks). The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPKK, which itself is phosphorylated and activated by a MAPKKK. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAPKKK to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Other STE family members include p21-activated kinases (PAKs) and class III myosins, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain, which can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, as well as autophosphorylate the C-terminal motor domain. They play an important role in maintaining the structural integrity of photoreceptor cell microvilli. The STE family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270692 [Multi-domain]  Cd Length: 254  Bit Score: 76.86  E-value: 2.57e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRN 675
Cdd:cd05122   49 AILKKCKHPNIVKYYGSYLKKDELWIVMEFCSGGSLKDLLKNTNKTLTEQQIAYVCKEVLKGLEYLHSHGIIHRDIKAAN 128
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 945225    676 CVVDGRFVLKVTDYGFNDILEmlRLSEEESSMEELLWTAPELLRAPRgsrlGSFAGDVYSFAIIMQEvMVRGTP 749
Cdd:cd05122  129 ILLTSDGEVKLIDFGLSAQLS--DGKTRNTFVGTPYWMAPEVIQGKP----YGFKADIWSLGITAIE-MAEGKP 195
STKc_Raf cd14062
Catalytic domain of the Serine/Threonine Kinases, Raf (Rapidly Accelerated Fibrosarcoma) ...
565-808 4.96e-15

Catalytic domain of the Serine/Threonine Kinases, Raf (Rapidly Accelerated Fibrosarcoma) kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Raf kinases act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. Aberrant expression or activation of components in this pathway are associated with tumor initiation, progression, and metastasis. Raf proteins contain a Ras binding domain, a zinc finger cysteine-rich domain, and a catalytic kinase domain. Vertebrates have three Raf isoforms (A-, B-, and C-Raf) with different expression profiles, modes of regulation, and abilities to function in the ERK cascade, depending on cellular context and stimuli. They have essential and non-overlapping roles during embryo- and organogenesis. Knockout of each isoform results in a lethal phenotype or abnormality in most mouse strains. The Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270964 [Multi-domain]  Cd Length: 253  Bit Score: 76.28  E-value: 4.96e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    565 IYEGDW---VWLKKFSLGDFG--DLKSIKSRASdvfeMMKDLRHENINPLLGFFYDSGmFAIVTEFCSRGSLEDILTNQD 639
Cdd:cd14062    9 VYKGRWhgdVAVKKLNVTDPTpsQLQAFKNEVA----VLRKTRHVNILLFMGYMTKPQ-LAIVTQWCEGSSLYKHLHVLE 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    640 VKldwmFKSSLLLDLIK----GMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGfndiLEMLRLSEEESSMEEL----- 710
Cdd:cd14062   84 TK----FEMLQLIDIARqtaqGMDYLHAKNIIHRDLKSNNIFLHEDLTVKIGDFG----LATVKTRWSGSQQFEQptgsi 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    711 LWTAPELLRAPRGSRLgSFAGDVYSFAIIMQEVMVRGTPFCMMDlPAQEIINRLKKPPPVYRPVVPPEHAPPECLQLMKQ 790
Cdd:cd14062  156 LWMAPEVIRMQDENPY-SFQSDVYAFGIVLYELLTGQLPYSHIN-NRDQILFMVGRGYLRPDLSKVRSDTPKALRRLMED 233
                        250
                 ....*....|....*...
gi 945225    791 CWAEAAEQRPTFDEIFNQ 808
Cdd:cd14062  234 CIKFQRDERPLFPQILAS 251
PKc_TESK cd14155
Catalytic domain of the Dual-specificity protein kinase, Testicular protein kinase; ...
596-805 7.64e-15

Catalytic domain of the Dual-specificity protein kinase, Testicular protein kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TESK proteins phosphorylate cofilin and induce actin cytoskeletal reorganization. In the Drosphila eye, TESK is required for epithelial cell organization. Mammals contain two TESK proteins, TESK1 and TESK2, which are highly expressed in testis and play roles in spermatogenesis. TESK1 is found in testicular germ cells while TESK2 is expressed mainly in nongerminal Sertoli cells. TESK1 is stimulated by integrin-mediated signaling pathways. It regulates cell spreading and focal adhesion formation. The TESK subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271057 [Multi-domain]  Cd Length: 253  Bit Score: 75.59  E-value: 7.64e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNqDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRN 675
Cdd:cd14155   40 QLMNRLSHPNILRFMGVCVHQGQLHALTEYINGGNLEQLLDS-NEPLSWTVRVKLALDIARGLSYLHSKGIFHRDLTSKN 118
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    676 CVV---DGRFVLKVTDYGFND-ILEMLRLSEEESSMEELLWTAPELLR-APRGSRlgsfaGDVYSFAIIMQEVMVRgtpf 750
Cdd:cd14155  119 CLIkrdENGYTAVVGDFGLAEkIPDYSDGKEKLAVVGSPYWMAPEVLRgEPYNEK-----ADVFSYGIILCEIIAR---- 189
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 945225    751 cmmdLPAQEiiNRLKKPPPVYRPVVPPEH----APPECLQLMKQCWAEAAEQRPTFDEI 805
Cdd:cd14155  190 ----IQADP--DYLPRTEDFGLDYDAFQHmvgdCPPDFLQLAFNCCNMDPKSRPSFHDI 242
STKc_MAPKKK cd06606
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase ...
595-804 8.09e-15

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKKKs (MKKKs or MAP3Ks) are also called MAP/ERK kinase kinases (MEKKs) in some cases. They phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. This subfamily is composed of the Apoptosis Signal-regulating Kinases ASK1 (or MAPKKK5) and ASK2 (or MAPKKK6), MEKK1, MEKK2, MEKK3, MEKK4, as well as plant and fungal MAPKKKs. Also included in this subfamily are the cell division control proteins Schizosaccharomyces pombe Cdc7 and Saccharomyces cerevisiae Cdc15. The MAPKKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270783 [Multi-domain]  Cd Length: 258  Bit Score: 75.63  E-value: 8.09e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    595 FEMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTN------QDVKldwmfksSLLLDLIKGMKYLHHREFVH 668
Cdd:cd06606   50 IRILSSLKHPNIVRYLGTERTENTLNIFLEYVPGGSLASLLKKfgklpePVVR-------KYTRQILEGLEYLHSNGIVH 122
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    669 GRLKSRNCVVDGRFVLKVTDYGFN-DILEMLRLSEEESSMEELLWTAPELLrapRGSRLGsFAGDVYSFAIIMQEvMVRG 747
Cdd:cd06606  123 RDIKGANILVDSDGVVKLADFGCAkRLAEIATGEGTKSLRGTPYWMAPEVI---RGEGYG-RAADIWSLGCTVIE-MATG 197
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 945225    748 T-PFCMMDLPAQEiinrLKKPPPVYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDE 804
Cdd:cd06606  198 KpPWSELGNPVAA----LFKIGSSGEPPPIPEHLSEEAKDFLRKCLQRDPKKRPTADE 251
PTKc_Axl cd05075
Catalytic domain of the Protein Tyrosine Kinase, Axl; PTKs catalyze the transfer of the ...
598-814 9.42e-15

Catalytic domain of the Protein Tyrosine Kinase, Axl; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Axl is widely expressed in a variety of organs and cells including epithelial, mesenchymal, hematopoietic, as well as non-transformed cells. It is important in many cellular functions such as survival, anti-apoptosis, proliferation, migration, and adhesion. Axl was originally isolated from patients with chronic myelogenous leukemia and a chronic myeloproliferative disorder. It is overexpressed in many human cancers including colon, squamous cell, thyroid, breast, and lung carcinomas. Axl is a member of the TAM subfamily, composed of receptor PTKs (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to its ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. The Axl subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270660 [Multi-domain]  Cd Length: 277  Bit Score: 75.81  E-value: 9.42e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    598 MKDLRHENINPLLGFFY---DSGMF---AIVTEFCSRGSLEDILT-----NQDVKLDWMFKSSLLLDLIKGMKYLHHREF 666
Cdd:cd05075   55 MKEFDHPNVMRLIGVCLqntESEGYpspVVILPFMKHGDLHSFLLysrlgDCPVYLPTQMLVKFMTDIASGMEYLSSKNF 134
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    667 VHGRLKSRNCVVDGRFVLKVTDYGFN-DILEMLRLSEEESSMEELLWTAPELLraprGSRLGSFAGDVYSFAIIMQEVMV 745
Cdd:cd05075  135 IHRDLAARNCMLNENMNVCVADFGLSkKIYNGDYYRQGRISKMPVKWIAIESL----ADRVYTTKSDVWSFGVTMWEIAT 210
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    746 RG-TPFCMMDlpAQEII------NRLKKpppvyrpvvppehaPPECL----QLMKQCWAEAAEQRPTFDEIFNQFKTFNK 814
Cdd:cd05075  211 RGqTPYPGVE--NSEIYdylrqgNRLKQ--------------PPDCLdglyELMSSCWLLNPKDRPSFETLRCELEKILK 274
PTKc_DDR cd05051
Catalytic domain of the Protein Tyrosine Kinases, Discoidin Domain Receptors; PTKs catalyze ...
598-806 1.47e-14

Catalytic domain of the Protein Tyrosine Kinases, Discoidin Domain Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The DDR subfamily consists of homologs of mammalian DDR1, DDR2, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDRs results in a slow but sustained receptor activation. DDRs regulate cell adhesion, proliferation, and extracellular matrix remodeling. They have been linked to a variety of human cancers including breast, colon, ovarian, brain, and lung. There is no evidence showing that DDRs act as transforming oncogenes. They are more likely to play a role in the regulation of tumor growth and metastasis. The DDR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270644 [Multi-domain]  Cd Length: 297  Bit Score: 75.84  E-value: 1.47e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    598 MKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTN---QDVKLDWMFKSSL----LLDLIK----GMKYLHHREF 666
Cdd:cd05051   73 MSQLKDPNIVRLLGVCTRDEPLCMIVEYMENGDLNQFLQKheaETQGASATNSKTLsygtLLYMATqiasGMKYLESLNF 152
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    667 VHGRLKSRNCVVDGRFVLKVTDYGFNDIL-----------EML--RlseeessmeellWTAPE-LLraprgsrLGSF--A 730
Cdd:cd05051  153 VHRDLATRNCLVGPNYTIKIADFGMSRNLysgdyyriegrAVLpiR------------WMAWEsIL-------LGKFttK 213
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    731 GDVYSFAIIMQEVMV--RGTPFcmMDLPAQEIIN---RLKKPPPVYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEI 805
Cdd:cd05051  214 SDVWAFGVTLWEILTlcKEQPY--EHLTDEQVIEnagEFFRDDGMEVYLSRPPNCPKEIYELMLECWRRDEEDRPTFREI 291

                 .
gi 945225    806 F 806
Cdd:cd05051  292 H 292
PBP1_NPR_B cd06384
ligand-binding domain of type B natriuretic peptide receptor; Ligand-binding domain of type B ...
67-399 1.97e-14

ligand-binding domain of type B natriuretic peptide receptor; Ligand-binding domain of type B natriuretic peptide receptor (NPR-B). NPR-B is one of three known single membrane-spanning natriuretic peptide receptors that have been identified. Natriuretic peptides are family of structurally related but genetically distinct hormones/paracrine factors that regulate blood volume, blood pressure, ventricular hypertrophy, pulmonary hypertension, fat metabolism, and long bone growth. In mammals there are three natriuretic peptides: ANP, BNP, and CNP. Like NPR-A (or GC-A), NPR-B (or GC-B) is a transmembrane guanylyl cyclase, an enzyme that catalyzes the synthesis of cGMP. NPR-B is the predominant natriuretic peptide receptor in the brain. The rank of order activation of NPR-B by natriuretic peptides is CNP>>ANP>BNP. Homozygous inactivating mutations in human NPR-B cause a form of short-limbed dwarfism known as acromesomelic dysplasia type Maroteaux.


Pssm-ID: 380607 [Multi-domain]  Cd Length: 399  Bit Score: 76.82  E-value: 1.97e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225     67 FSKALPEV--AARLAIERINRDPSFDLSYSFEYVILNEDCQTsrALSSFISH--------HQMASGFIGPTnpgyC--EA 134
Cdd:cd06384   13 YAWAWPRVfpALRMAVDALQRKGKLLRGYTVNLLFHSSELQG--ACSEYVAPlmavdlklYHDPDVLFGPG----CvyPA 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    135 ASL--LGNSWDKGIFSWACVNYELDNKIS-YPTFSRTLPSPIRV---LVTVMKYFQW-AHAGVI----SSDEDIWVHTAN 203
Cdd:cd06384   87 ASVgrFASHWRLPLITAGAVAFGFSSKDEhYRTTVRTGPSAPKLgefVSHLHSHFNWtSRAALLyhdlKTDDRPYYFIIE 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    204 RVASALRSHGLPVGVVLTTGQDSQSMRKALQRIHQADRIriIIMCmhsaligG--ETQMHLLECAHDLKMTDGTYVFVPY 281
Cdd:cd06384  167 GVFLALDGENLTVEHVPYDDQENGDPREAIHFIKANGRI--VYIC-------GplEMLHEIMLQAQRENLTNGDYVFFYL 237
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    282 DALLYSL---PYKHTPYQVLRNNPK-LREAYDAVLTITVESQEKTFYQAFTE---AAARGEIPEKLEFDQVSPLFGTIYN 354
Cdd:cd06384  238 DVFGESLrddDTRPAEKPSSDIQWQdLREAFKTVLVITYKEPDNPEYQEFQReliARAKQEFGVQLNPSLMNLIAGCFYD 317
                        330       340       350       360
                 ....*....|....*....|....*....|....*....|....*.
gi 945225    355 SIYFIAQAMNNAMKENG-QAGAASLVQHSRNMQFHGFNQLMRTDSN 399
Cdd:cd06384  318 GVLLYAQALNETLREGGsQKDGLNIVEKMQDRRFWGVTGLVSMDKN 363
STKc_PknB_like cd14014
Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs ...
575-801 2.94e-14

Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes many bacterial eukaryotic-type STKs including Staphylococcus aureus PknB (also called PrkC or Stk1), Bacillus subtilis PrkC, and Mycobacterium tuberculosis Pkn proteins (PknB, PknD, PknE, PknF, PknL, and PknH), among others. S. aureus PknB is the only eukaryotic-type STK present in this species, although many microorganisms encode for several such proteins. It is important for the survival and pathogenesis of S. aureus as it is involved in the regulation of purine and pyrimidine biosynthesis, cell wall metabolism, autolysis, virulence, and antibiotic resistance. M. tuberculosis PknB is essential for growth and it acts on diverse substrates including proteins involved in peptidoglycan synthesis, cell division, transcription, stress responses, and metabolic regulation. B. subtilis PrkC is located at the inner membrane of endospores and functions to trigger spore germination. Bacterial STKs in this subfamily show varied domain architectures. The well-characterized members such as S. aureus and M. tuberculosis PknB, and B. subtilis PrkC, contain an N-terminal cytosolic kinase domain, a transmembrane (TM) segment, and mutliple C-terminal extracellular PASTA domains. The PknB subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270916 [Multi-domain]  Cd Length: 260  Bit Score: 74.16  E-value: 2.94e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    575 KFSLGDFGDLKSIKSRASDVFEMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILtNQDVKLDWMFKSSLLLDL 654
Cdd:cd14014   31 KVLRPELAEDEEFRERFLREARALARLSHPNIVRVYDVGEDDGRPYIVMEYVEGGSLADLL-RERGPLPPREALRILAQI 109
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    655 IKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGFNDILEMLRLSEEESSMEELLWTAPELLrapRGSRLGsFAGDVY 734
Cdd:cd14014  110 ADALAAAHRAGIVHRDIKPANILLTEDGRVKLTDFGIARALGDSGLTQTGSVLGTPAYMAPEQA---RGGPVD-PRSDIY 185
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 945225    735 SFAIIMQEvMVRGTPFCMMDLPAQEIINRLKKPPPVYRPVVPpeHAPPECLQLMKQCWAEAAEQRPT 801
Cdd:cd14014  186 SLGVVLYE-LLTGRPPFDGDSPAAVLAKHLQEAPPPPSPLNP--DVPPALDAIILRALAKDPEERPQ 249
PTKc_InsR_like cd05032
Catalytic domain of Insulin Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer ...
598-805 2.95e-14

Catalytic domain of Insulin Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The InsR subfamily is composed of InsR, Insulin-like Growth Factor-1 Receptor (IGF-1R), and similar proteins. InsR and IGF-1R are receptor PTKs (RTKs) composed of two alphabeta heterodimers. Binding of the ligand (insulin, IGF-1, or IGF-2) to the extracellular alpha subunit activates the intracellular tyr kinase domain of the transmembrane beta subunit. Receptor activation leads to autophosphorylation, stimulating downstream kinase activities, which initiate signaling cascades and biological function. InsR and IGF-1R, which share 84% sequence identity in their kinase domains, display physiologically distinct yet overlapping functions in cell growth, differentiation, and metabolism. InsR activation leads primarily to metabolic effects while IGF-1R activation stimulates mitogenic pathways. In cells expressing both receptors, InsR/IGF-1R hybrids are found together with classical receptors. Both receptors can interact with common adaptor molecules such as IRS-1 and IRS-2. The InsR-like subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173625 [Multi-domain]  Cd Length: 277  Bit Score: 74.30  E-value: 2.95e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    598 MKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKLDWM-FKSSLLLDLI--------KGMKYLHHREFVH 668
Cdd:cd05032   63 MKEFNCHHVVRLLGVVSTGQPTLVVMELMAKGDLKSYLRSRRPEAENNpGLGPPTLQKFiqmaaeiaDGMAYLAAKKFVH 142
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    669 GRLKSRNCVVDGRFVLKVTDYGF-NDILEMLRLSEEESSMEELLWTAPELLRAprgsrlGSF--AGDVYSFAIIMQEVMV 745
Cdd:cd05032  143 RDLAARNCMVAEDLTVKIGDFGMtRDIYETDYYRKGGKGLLPVRWMAPESLKD------GVFttKSDVWSFGVVLWEMAT 216
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 945225    746 RGtpfcmmDLPAQEIIN-RLKKPPPVYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEI 805
Cdd:cd05032  217 LA------EQPYQGLSNeEVLKFVIDGGHLDLPENCPDKLLELMRMCWQYNPKMRPTFLEI 271
PTKc_Tie cd05047
Catalytic domain of Tie Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
602-809 3.06e-14

Catalytic domain of Tie Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tie proteins, consisting of Tie1 and Tie2, are receptor PTKs (RTKs) containing an extracellular region, a transmembrane segment, and an intracellular catalytic domain. The extracellular region contains an immunoglobulin (Ig)-like domain, three epidermal growth factor (EGF)-like domains, a second Ig-like domain, and three fibronectin type III repeats. Tie receptors are specifically expressed in endothelial cells and hematopoietic stem cells. The angiopoietins (Ang-1 to Ang-4) serve as ligands for Tie2, while no specific ligand has been identified for Tie1. The binding of Ang-1 to Tie2 leads to receptor autophosphorylation and activation, promoting cell migration and survival. In contrast, Ang-2 binding to Tie2 does not result in the same response, suggesting that Ang-2 may function as an antagonist. In vivo studies of Tie1 show that it is critical in vascular development. The Tie subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270641 [Multi-domain]  Cd Length: 270  Bit Score: 74.31  E-value: 3.06e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    602 RHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDV-KLDWMF----------KSSLLL----DLIKGMKYLHHREF 666
Cdd:cd05047   54 HHPNIINLLGACEHRGYLYLAIEYAPHGNLLDFLRKSRVlETDPAFaianstastlSSQQLLhfaaDVARGMDYLSQKQF 133
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    667 VHGRLKSRNCVVDGRFVLKVTDYGFNDILEMLrlSEEESSMEELLWTAPELLraprGSRLGSFAGDVYSFAIIMQEVM-V 745
Cdd:cd05047  134 IHRDLAARNILVGENYVAKIADFGLSRGQEVY--VKKTMGRLPVRWMAIESL----NYSVYTTNSDVWSYGVLLWEIVsL 207
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 945225    746 RGTPFCMMDlpAQEIINRLKKPPPVYRPVVPPEhappECLQLMKQCWAEAAEQRPTFDEIFNQF 809
Cdd:cd05047  208 GGTPYCGMT--CAELYEKLPQGYRLEKPLNCDD----EVYDLMRQCWREKPYERPSFAQILVSL 265
PTKc_TAM cd05035
Catalytic Domain of TAM (Tyro3, Axl, Mer) Protein Tyrosine Kinases; PTKs catalyze the transfer ...
598-805 3.22e-14

Catalytic Domain of TAM (Tyro3, Axl, Mer) Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The TAM subfamily consists of Tyro3 (or Sky), Axl, Mer (or Mertk), and similar proteins. TAM subfamily members are receptor tyr kinases (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. TAM proteins are implicated in a variety of cellular effects including survival, proliferation, migration, and phagocytosis. They are also associated with several types of cancer as well as inflammatory, autoimmune, vascular, and kidney diseases. The TAM subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270631 [Multi-domain]  Cd Length: 273  Bit Score: 74.11  E-value: 3.22e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    598 MKDLRHENINPLLGFFY---DSGMFA---IVTEFCSRGSLEDIL-----TNQDVKLDWMFKSSLLLDLIKGMKYLHHREF 666
Cdd:cd05035   55 MKDFDHPNVMRLIGVCFtasDLNKPPspmVILPFMKHGDLHSYLlysrlGGLPEKLPLQTLLKFMVDIAKGMEYLSNRNF 134
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    667 VHGRLKSRNCVVDGRFVLKVTDYGFN-DILEMLRLSEEESSMEELLWTAPELLraprGSRLGSFAGDVYSFAIIMQEVMV 745
Cdd:cd05035  135 IHRDLAARNCMLDENMTVCVADFGLSrKIYSGDYYRQGRISKMPVKWIALESL----ADNVYTSKSDVWSFGVTMWEIAT 210
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 945225    746 RG-TPFC------MMDLPAQEiiNRLKKpppvyrpvvpPEHAPPECLQLMKQCWAEAAEQRPTFDEI 805
Cdd:cd05035  211 RGqTPYPgvenheIYDYLRNG--NRLKQ----------PEDCLDEVYFLMYFCWTVDPKDRPTFTKL 265
STKc_B-Raf cd14151
Catalytic domain of the Serine/Threonine Kinase, B-Raf (Rapidly Accelerated Fibrosarcoma) ...
597-806 3.93e-14

Catalytic domain of the Serine/Threonine Kinase, B-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. B-Raf activates ERK with the strongest magnitude, compared with other Raf kinases. Mice embryos deficient in B-Raf die around midgestation due to vascular hemorrhage caused by apoptotic endothelial cells. Mutations in B-Raf have been implicated in initiating tumorigenesis and tumor progression, and are found in malignant cutaneous melanoma, papillary thyroid cancer, as well as in ovarian and colorectal carcinomas. Most oncogenic B-Raf mutations are located at the activation loop of the kinase and surrounding regions; the V600E mutation accounts for around 90% of oncogenic mutations. The V600E mutant constitutively activates MEK, resulting in sustained activation of ERK. B-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The B-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271053 [Multi-domain]  Cd Length: 274  Bit Score: 73.94  E-value: 3.93e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFfYDSGMFAIVTEFCSRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNC 676
Cdd:cd14151   57 VLRKTRHVNILLFMGY-STKPQLAIVTQWCEGSSLYHHLHIIETKFEMIKLIDIARQTAQGMDYLHAKSIIHRDLKSNNI 135
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    677 VVDGRFVLKVTDYGFNDILEMLR-LSEEESSMEELLWTAPELLRApRGSRLGSFAGDVYSFAIIMQEVMVRGTPFCMMDL 755
Cdd:cd14151  136 FLHEDLTVKIGDFGLATVKSRWSgSHQFEQLSGSILWMAPEVIRM-QDKNPYSFQSDVYAFGIVLYELMTGQLPYSNINN 214
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 945225    756 PAQeIINRLKKPPPVYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEIF 806
Cdd:cd14151  215 RDQ-IIFMVGRGYLSPDLSKVRSNCPKAMKRLMAECLKKKRDERPLFPQIL 264
STKc_Mos cd13979
Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze ...
564-804 4.31e-14

Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mos (or c-Mos) is a germ-cell specific kinase that plays roles in both the release of primary arrest and the induction of secondary arrest in oocytes. It is expressed towards the end of meiosis I and is quickly degraded upon fertilization. It is a component of the cytostatic factor (CSF), which is responsible for metaphase II arrest. In addition, Mos activates a phoshorylation cascade that leads to the activation of the p34 subunit of MPF (mitosis-promoting factor or maturation promoting factor), a cyclin-dependent kinase that is responsible for the release of primary arrest in meiosis I. The Mos subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270881 [Multi-domain]  Cd Length: 265  Bit Score: 73.57  E-value: 4.31e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    564 AIYEGDWVWLKKFSlgdfgdlKSIKSRAS-DVFEMMKD---LRHENINPLLG-----FFYDSGMfaIVTEFCSRGSLEDI 634
Cdd:cd13979   22 ATYKGETVAVKIVR-------RRRKNRASrQSFWAELNaarLRHENIVRVLAaetgtDFASLGL--IIMEYCGNGTLQQL 92
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    635 LTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGFNDILEMLRLSEEESSMEELLWT- 713
Cdd:cd13979   93 IYEGSEPLPLAHRILISLDIARALRFCHSHGIVHLDVKPANILISEQGVCKLCDFGCSVKLGEGNEVGTPRSHIGGTYTy 172
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    714 -APELLRAPRGSRlgsfAGDVYSFAIIMQEVMVRGTPF------------------CMMDLPAQEIINRLKKpppvyrpv 774
Cdd:cd13979  173 rAPELLKGERVTP----KADIYSFGITLWQMLTRELPYaglrqhvlyavvakdlrpDLSGLEDSEFGQRLRS-------- 240
                        250       260       270
                 ....*....|....*....|....*....|
gi 945225    775 vppehappeclqLMKQCWAEAAEQRPTFDE 804
Cdd:cd13979  241 ------------LISRCWSAQPAERPNADE 258
PTK_Ryk cd05043
Pseudokinase domain of Ryk (Receptor related to tyrosine kinase); Ryk is a receptor tyr kinase ...
649-813 6.69e-14

Pseudokinase domain of Ryk (Receptor related to tyrosine kinase); Ryk is a receptor tyr kinase (RTK) containing an extracellular region with two leucine-rich motifs, a transmembrane segment, and an intracellular inactive pseudokinase domain, which shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. The extracellular region of Ryk shows homology to the N-terminal domain of Wnt inhibitory factor-1 (WIF) and serves as the ligand (Wnt) binding domain of Ryk. Ryk is expressed in many different tissues both during development and in adults, suggesting a widespread function. It acts as a chemorepulsive axon guidance receptor of Wnt glycoproteins and is responsible for the establishment of axon tracts during the development of the central nervous system. In addition, studies in mice reveal that Ryk is essential in skeletal, craniofacial, and cardiac development. Thus, it appears Ryk is involved in signal transduction despite its lack of kinase activity. Ryk may function as an accessory protein that modulates the signals coming from catalytically active partner RTKs such as the Eph receptors. The Ryk subfamily is part of a larger superfamily that includes other pseudokinases and the catalytic domains of active kinases including PTKs, protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270639 [Multi-domain]  Cd Length: 279  Bit Score: 73.25  E-value: 6.69e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    649 SLLLDLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGFN-DILEMLRLSEEESSMEELLWTAPELLRaprgSRLG 727
Cdd:cd05043  120 HMALQIACGMSYLHRRGVIHKDIAARNCVIDDELQVKITDNALSrDLFPMDYHCLGDNENRPIKWMSLESLV----NKEY 195
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    728 SFAGDVYSFAIIMQEVMVRG-TPFCMMDlpAQEIINRLKKPPPVYRPVvppeHAPPECLQLMKQCWAEAAEQRPTFDEIF 806
Cdd:cd05043  196 SSASDVWSFGVLLWELMTLGqTPYVEID--PFEMAAYLKDGYRLAQPI----NCPDELFAVMACCWALDPEERPSFQQLV 269

                 ....*..
gi 945225    807 NQFKTFN 813
Cdd:cd05043  270 QCLTDFH 276
STKc_RIP4_like cd14025
Catalytic domain of the Serine/Threonine kinases, Receptor Interacting Protein 4 and similar ...
598-805 6.94e-14

Catalytic domain of the Serine/Threonine kinases, Receptor Interacting Protein 4 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of RIP4, ankyrin (ANK) repeat and kinase domain containing 1 (ANKK1), and similar proteins, all of which harbor C-terminal ANK repeats. RIP4, also called Protein Kinase C-associated kinase (PKK), regulates keratinocyte differentiation and cutaneous inflammation. It activates NF-kappaB and is important in the survival of diffuse large B-cell lymphoma cells. The ANKK1 protein, also called PKK2, has not been studied extensively. The ANKK1 gene, located less than 10kb downstream of the D2 dopamine receptor (DRD2) locus, is altered in the Taq1 A1 polymorphism, which is related to a reduced DRD2 binding affinity and consequently, to mental disorders. The RIP4-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270927 [Multi-domain]  Cd Length: 267  Bit Score: 73.30  E-value: 6.94e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    598 MKDLRHENINPLLGFFYDSgmFAIVTEFCSRGSLEDILTNQdvKLDWMFKSSLLLDLIKGMKYLH--HREFVHGRLKSRN 675
Cdd:cd14025   49 MEMAKFRHILPVYGICSEP--VGLVMEYMETGSLEKLLASE--PLPWELRFRIIHETAVGMNFLHcmKPPLLHLDLKPAN 124
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    676 CVVDGRFVLKVTDYGFNDILEMLRLSEEESSME--ELLWTAPELLRapRGSRLGSFAGDVYSFAIIMQEVMVRGTPFC-- 751
Cdd:cd14025  125 ILLDAHYHVKISDFGLAKWNGLSHSHDLSRDGLrgTIAYLPPERFK--EKNRCPDTKHDVYSFAIVIWGILTQKKPFAge 202
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 945225    752 --MMDL---------PAQEIINRLKkpppvyrpvvppehaPPEC---LQLMKQCWAEAAEQRPTFDEI 805
Cdd:cd14025  203 nnILHImvkvvkghrPSLSPIPRQR---------------PSECqqmICLMKRCWDQDPRKRPTFQDI 255
PTKc_Tie1 cd05089
Catalytic domain of the Protein Tyrosine Kinase, Tie1; Protein Tyrosine Kinase (PTK) family; ...
602-820 1.69e-13

Catalytic domain of the Protein Tyrosine Kinase, Tie1; Protein Tyrosine Kinase (PTK) family; Tie1; catalytic (c) domain. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tie1 is a receptor tyr kinase (RTK) containing an extracellular region, a transmembrane segment, and an intracellular catalytic domain. The extracellular region contains an immunoglobulin (Ig)-like domain, three epidermal growth factor (EGF)-like domains, a second Ig-like domain, and three fibronectin type III repeats. Tie receptors are specifically expressed in endothelial cells and hematopoietic stem cells. No specific ligand has been identified for Tie1, although the angiopoietin, Ang-1, binds to Tie1 through integrins at high concentrations. In vivo studies of Tie1 show that it is critical in vascular development.


Pssm-ID: 270671 [Multi-domain]  Cd Length: 297  Bit Score: 72.34  E-value: 1.69e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    602 RHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDV-KLDWMF----------KSSLLL----DLIKGMKYLHHREF 666
Cdd:cd05089   61 HHPNIINLLGACENRGYLYIAIEYAPYGNLLDFLRKSRVlETDPAFakehgtastlTSQQLLqfasDVAKGMQYLSEKQF 140
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    667 VHGRLKSRNCVVDGRFVLKVTDYGFNDILEMLrlSEEESSMEELLWTAPELLraprGSRLGSFAGDVYSFAIIMQEVM-V 745
Cdd:cd05089  141 IHRDLAARNVLVGENLVSKIADFGLSRGEEVY--VKKTMGRLPVRWMAIESL----NYSVYTTKSDVWSFGVLLWEIVsL 214
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 945225    746 RGTPFCMMDlpAQEIINRLKKpppvYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEIFNQFKTFNKGKKTNI 820
Cdd:cd05089  215 GGTPYCGMT--CAELYEKLPQ----GYRMEKPRNCDDEVYELMRQCWRDRPYERPPFSQISVQLSRMLEARKAYV 283
PTKc_VEGFR cd05054
Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; ...
589-805 1.95e-13

Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The VEGFR subfamily consists of VEGFR1 (Flt1), VEGFR2 (Flk1), VEGFR3 (Flt4), and similar proteins. VEGFR subfamily members are receptor PTKss (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. In VEGFR3, the fifth Ig-like domain is replaced by a disulfide bridge. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. There are five VEGF ligands in mammals, which bind, in an overlapping pattern to the three VEGFRs, which can form homo or heterodimers. VEGFRs regulate the cardiovascular system. They are critical for vascular development during embryogenesis and blood vessel formation in adults. They induce cellular functions common to other growth factor receptors such as cell migration, survival, and proliferation. The VEGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270647 [Multi-domain]  Cd Length: 298  Bit Score: 72.14  E-value: 1.95e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    589 SRASDVFEMMKDLR-------HENINPLLGFFYDS-GMFAIVTEFCSRGSLEDILT--------NQDVKL---------D 643
Cdd:cd05054   49 ATASEHKALMTELKilihighHLNVVNLLGACTKPgGPLMVIVEFCKFGNLSNYLRskreefvpYRDKGArdveeeeddD 128
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    644 WMFKSSLLL-DLI-------KGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGF-NDILEMLRLSEEESSMEELLWTA 714
Cdd:cd05054  129 ELYKEPLTLeDLIcysfqvaRGMEFLASRKCIHRDLAARNILLSENNVVKICDFGLaRDIYKDPDYVRKGDARLPLKWMA 208
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    715 PELLRaprgSRLGSFAGDVYSFAIIMQEVMVRGT---PFCMMDlpaQEIINRLKKPPPVYRPvvppEHAPPECLQLMKQC 791
Cdd:cd05054  209 PESIF----DKVYTTQSDVWSFGVLLWEIFSLGAspyPGVQMD---EEFCRRLKEGTRMRAP----EYTTPEIYQIMLDC 277
                        250
                 ....*....|....
gi 945225    792 WAEAAEQRPTFDEI 805
Cdd:cd05054  278 WHGEPKERPTFSEL 291
PTKc_InsR cd05061
Catalytic domain of the Protein Tyrosine Kinase, Insulin Receptor; PTKs catalyze the transfer ...
653-810 1.95e-13

Catalytic domain of the Protein Tyrosine Kinase, Insulin Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. InsR is a receptor PTK (RTK) that is composed of two alphabeta heterodimers. Binding of the insulin ligand to the extracellular alpha subunit activates the intracellular tyr kinase domain of the transmembrane beta subunit. Receptor activation leads to autophosphorylation, stimulating downstream kinase activities, which initiate signaling cascades and biological function. InsR signaling plays an important role in many cellular processes including glucose homeostasis, glycogen synthesis, lipid and protein metabolism, ion and amino acid transport, cell cycle and proliferation, cell differentiation, gene transcription, and nitric oxide synthesis. Insulin resistance, caused by abnormalities in InsR signaling, has been described in diabetes, hypertension, cardiovascular disease, metabolic syndrome, heart failure, and female infertility. The InsR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133192 [Multi-domain]  Cd Length: 288  Bit Score: 72.31  E-value: 1.95e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    653 DLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGFN-DILEMLRLSEEESSMEELLWTAPELLRAprgsrlGSFA- 730
Cdd:cd05061  127 EIADGMAYLNAKKFVHRDLAARNCMVAHDFTVKIGDFGMTrDIYETDYYRKGGKGLLPVRWMAPESLKD------GVFTt 200
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    731 -GDVYSFAIIMQEVMvrgtpfCMMDLPAQEIIN-RLKKPPPVYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEIFNQ 808
Cdd:cd05061  201 sSDMWSFGVVLWEIT------SLAEQPYQGLSNeQVLKFVMDGGYLDQPDNCPERVTDLMRMCWQFNPKMRPTFLEIVNL 274

                 ..
gi 945225    809 FK 810
Cdd:cd05061  275 LK 276
PKc_TNNI3K cd14064
Catalytic domain of the Dual-specificity protein kinase, TNNI3-interacting kinase; ...
615-805 1.97e-13

Catalytic domain of the Dual-specificity protein kinase, TNNI3-interacting kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TNNI3K, also called cardiac ankyrin repeat kinase (CARK), is a cardiac-specific troponin I-interacting kinase that promotes cardiac myogenesis, improves cardiac performance, and protects the myocardium from ischemic injury. It contains N-terminal ankyrin repeats, a catalytic kinase domain, and a C-terminal serine-rich domain. TNNI3K exerts a disease-accelerating effect on cardiac dysfunction and reduced survival in mouse models of cardiomyopathy. The TNNI3K subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270966 [Multi-domain]  Cd Length: 254  Bit Score: 71.41  E-value: 1.97e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    615 DSGMFAIVTEFCSRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHH--REFVHGRLKSRNCVV--DGRFVlkVTDYG 690
Cdd:cd14064   63 DPSQFAIVTQYVSGGSLFSLLHEQKRVIDLQSKLIIAVDVAKGMEYLHNltQPIIHRDLNSHNILLyeDGHAV--VADFG 140
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    691 FNDILEMLRLSEEESSMEELLWTAPELL-RAPRGSRlgsfAGDVYSFAIIMQEVMVRGTPFCMMDlPAQEIINRLKKPPP 769
Cdd:cd14064  141 ESRFLQSLDEDNMTKQPGNLRWMAPEVFtQCTRYSI----KADVFSYALCLWELLTGEIPFAHLK-PAAAAADMAYHHIR 215
                        170       180       190
                 ....*....|....*....|....*....|....*.
gi 945225    770 VYRPVVPpehaPPECLQLMKQCWAEAAEQRPTFDEI 805
Cdd:cd14064  216 PPIGYSI----PKPISSLLMRGWNAEPESRPSFVEI 247
STKc_MLK1 cd14145
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 1; STKs catalyze the ...
584-811 2.20e-13

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK1 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK) and is also called MAP3K9. MAP3Ks phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Little is known about the specific function of MLK1. It is capable of activating the c-Jun N-terminal kinase pathway. Mice lacking both MLK1 and MLK2 are viable, fertile, and have normal life spans. There could be redundancy in the function of MLKs. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271047 [Multi-domain]  Cd Length: 270  Bit Score: 71.61  E-value: 2.20e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    584 LKSIKSRASdVFEMmkdLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQ----DVKLDWMfkssllLDLIKGMK 659
Cdd:cd14145   49 IENVRQEAK-LFAM---LKHPNIIALRGVCLKEPNLCLVMEFARGGPLNRVLSGKrippDILVNWA------VQIARGMN 118
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    660 YLHHREFV---HGRLKSRNCVVDGRF--------VLKVTDYGfndILEMLRLSEEESSMEELLWTAPELLRAPRGSRlGS 728
Cdd:cd14145  119 YLHCEAIVpviHRDLKSSNILILEKVengdlsnkILKITDFG---LAREWHRTTKMSAAGTYAWMAPEVIRSSMFSK-GS 194
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    729 fagDVYSFAIIMQEVMVRGTPFCMMDLPAQE---IINRLKkpppvyrpVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEI 805
Cdd:cd14145  195 ---DVWSYGVLLWELLTGEVPFRGIDGLAVAygvAMNKLS--------LPIPSTCPEPFARLMEDCWNPDPHSRPPFTNI 263

                 ....*.
gi 945225    806 FNQFKT 811
Cdd:cd14145  264 LDQLTA 269
PTKc_Syk_like cd05060
Catalytic domain of Spleen Tyrosine Kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
596-811 2.32e-13

Catalytic domain of Spleen Tyrosine Kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Syk-like subfamily is composed of Syk, ZAP-70, Shark, and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. They are involved in the signaling downstream of activated receptors (including B-cell, T-cell, and Fc receptors) that contain ITAMs (immunoreceptor tyr activation motifs), leading to processes such as cell proliferation, differentiation, survival, adhesion, migration, and phagocytosis. Syk is important in B-cell receptor signaling, while Zap-70 is primarily expressed in T-cells and NK cells, and is a crucial component in T-cell receptor signaling. Syk also plays a central role in Fc receptor-mediated phagocytosis in the adaptive immune system. Shark is exclusively expressed in ectodermally derived epithelia, and is localized preferentially to the apical surface of the epithelial cells, it may play a role in a signaling pathway for epithelial cell polarity. The Syk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270650 [Multi-domain]  Cd Length: 257  Bit Score: 71.23  E-value: 2.32e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFfYDSGMFAIVTEFCSRGSLEDIL------TNQDVKLdWMFKSSLlldlikGMKYLHHREFVHG 669
Cdd:cd05060   48 SVMAQLDHPCIVRLIGV-CKGEPLMLVMELAPLGPLLKYLkkrreiPVSDLKE-LAHQVAM------GMAYLESKHFVHR 119
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    670 RLKSRNCVVDGRFVLKVTDYGfndileMLRLSEEESSMEELL--------WTAPELLRaprgsrLGSF--AGDVYSFAII 739
Cdd:cd05060  120 DLAARNVLLVNRHQAKISDFG------MSRALGAGSDYYRATtagrwplkWYAPECIN------YGKFssKSDVWSYGVT 187
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 945225    740 MQEVMVRGT-PFcmMDLPAQEIINRLKKPPPVYRPvvppEHAPPECLQLMKQCWAEAAEQRPTFDEIFNQFKT 811
Cdd:cd05060  188 LWEAFSYGAkPY--GEMKGPEVIAMLESGERLPRP----EECPQEIYSIMLSCWKYRPEDRPTFSELESTFRR 254
STKc_C-Raf cd14149
Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) ...
597-810 2.99e-13

Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. C-Raf, also known as Raf-1 or c-Raf-1, is ubiquitously expressed and was the first Raf identified. It was characterized as the acquired oncogene from an acutely transforming murine sarcoma virus (3611-MSV) and the transforming agent from the avian retrovirus MH2. C-Raf-deficient mice embryos die around midgestation with increased apoptosis of embryonic tissues, especially in the fetal liver. One of the main functions of C-Raf is restricting caspase activation to promote survival in response to specific stimuli such as Fas stimulation, macrophage apoptosis, and erythroid differentiation. C-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. It functions in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The C-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271051 [Multi-domain]  Cd Length: 283  Bit Score: 71.60  E-value: 2.99e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFFyDSGMFAIVTEFCSRGSLEDILTNQDVKLDwMFKsslLLDLIK----GMKYLHHREFVHGRLK 672
Cdd:cd14149   61 VLRKTRHVNILLFMGYM-TKDNLAIVTQWCEGSSLYKHLHVQETKFQ-MFQ---LIDIARqtaqGMDYLHAKNIIHRDMK 135
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    673 SRNCVVDGRFVLKVTDYGFNDILEMLR-LSEEESSMEELLWTAPELLRAPRGSRLgSFAGDVYSFAIIMQEVMVRGTPFC 751
Cdd:cd14149  136 SNNIFLHEGLTVKIGDFGLATVKSRWSgSQQVEQPTGSILWMAPEVIRMQDNNPF-SFQSDVYSYGIVLYELMTGELPYS 214
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 945225    752 MMDlPAQEIINRLKKPPPVYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEIFNQFK 810
Cdd:cd14149  215 HIN-NRDQIIFMVGRGYASPDLSKLYKNCPKAMKRLVADCIKKVKEERPLFPQILSSIE 272
PTKc_Tyro3 cd05074
Catalytic domain of the Protein Tyrosine Kinase, Tyro3; PTKs catalyze the transfer of the ...
598-810 3.88e-13

Catalytic domain of the Protein Tyrosine Kinase, Tyro3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tyro3 (or Sky) is predominantly expressed in the central nervous system and the brain, and functions as a neurotrophic factor. It is also expressed in osteoclasts and has a role in bone resorption. Tyro3 is a member of the TAM subfamily, composed of receptor PTKs (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. The Tyro3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270659 [Multi-domain]  Cd Length: 284  Bit Score: 71.10  E-value: 3.88e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    598 MKDLRHENINPLLGFFYDS---GMFAI---VTEFCSRGSLEDILT-----NQDVKLDWMFKSSLLLDLIKGMKYLHHREF 666
Cdd:cd05074   65 MKEFDHPNVIKLIGVSLRSrakGRLPIpmvILPFMKHGDLHTFLLmsrigEEPFTLPLQTLVRFMIDIASGMEYLSSKNF 144
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    667 VHGRLKSRNCVVDGRFVLKVTDYGFN-DILEMLRLSEEESSMEELLWTAPELLraprGSRLGSFAGDVYSFAIIMQEVMV 745
Cdd:cd05074  145 IHRDLAARNCMLNENMTVCVADFGLSkKIYSGDYYRQGCASKLPVKWLALESL----ADNVYTTHSDVWAFGVTMWEIMT 220
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 945225    746 RG-TPFCMMDlpAQEII------NRLKKpppvyrpvvppehaPPECL----QLMKQCWAEAAEQRPTFDEIFNQFK 810
Cdd:cd05074  221 RGqTPYAGVE--NSEIYnylikgNRLKQ--------------PPDCLedvyELMCQCWSPEPKCRPSFQHLRDQLE 280
PTKc_DDR_like cd05097
Catalytic domain of Discoidin Domain Receptor-like Protein Tyrosine Kinases; PTKs catalyze the ...
580-805 4.28e-13

Catalytic domain of Discoidin Domain Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. DDR-like proteins are members of the DDR subfamily, which are receptor PTKs (RTKs) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDRs results in a slow but sustained receptor activation. DDRs regulate cell adhesion, proliferation, and extracellular matrix remodeling. They have been linked to a variety of human cancers including breast, colon, ovarian, brain, and lung. There is no evidence showing that DDRs act as transforming oncogenes. They are more likely to play a role in the regulation of tumor growth and metastasis. The DDR-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133228 [Multi-domain]  Cd Length: 295  Bit Score: 71.16  E-value: 4.28e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    580 DFgdLKSIKsrasdvfeMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVK--------LDWMFKSSLL 651
Cdd:cd05097   63 DF--LKEIK--------IMSRLKNPNIIRLLGVCVSDDPLCMITEYMENGDLNQFLSQREIEstfthannIPSVSIANLL 132
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    652 ---LDLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGFNDIL---EMLRlsEEESSMEELLWTAPELLraprgsR 725
Cdd:cd05097  133 ymaVQIASGMKYLASLNFVHRDLATRNCLVGNHYTIKIADFGMSRNLysgDYYR--IQGRAVLPIRWMAWESI------L 204
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    726 LGSF--AGDVYSFAIIMQEV--MVRGTPFCMmdLPAQEIINRLKKPPPVYRPVVPPEhAPPEC----LQLMKQCWAEAAE 797
Cdd:cd05097  205 LGKFttASDVWAFGVTLWEMftLCKEQPYSL--LSDEQVIENTGEFFRNQGRQIYLS-QTPLCpspvFKLMMRCWSRDIK 281

                 ....*...
gi 945225    798 QRPTFDEI 805
Cdd:cd05097  282 DRPTFNKI 289
PTKc_Ror1 cd05090
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ...
597-812 4.96e-13

Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Ror kinases are expressed in many tissues during development. Avian Ror1 was found to be involved in late limb development. Studies in mice reveal that Ror1 is important in the regulation of neurite growth in central neurons, as well as in respiratory development. Loss of Ror1 also enhances the heart and skeletal abnormalities found in Ror2-deficient mice. Ror proteins are orphan receptor PTKs (RTKs) containing an extracellular region with immunoglobulin-like, cysteine-rich, and kringle domains, a transmembrane segment, and an intracellular catalytic domain. Ror RTKs are unrelated to the nuclear receptor subfamily called retinoid-related orphan receptors (RORs). RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. The Ror1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270672 [Multi-domain]  Cd Length: 283  Bit Score: 70.81  E-value: 4.96e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILT----NQDVKL----DWMFKSSL--------LLDLIKGMKY 660
Cdd:cd05090   60 LMTELHHPNIVCLLGVVTQEQPVCMLFEFMNQGDLHEFLImrspHSDVGCssdeDGTVKSSLdhgdflhiAIQIAAGMEY 139
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    661 LHHREFVHGRLKSRNCVVDGRFVLKVTDYGFN-DILEMLRLSEEESSMEELLWTAPELLRaprgsrLGSFAGD--VYSFA 737
Cdd:cd05090  140 LSSHFFVHKDLAARNILVGEQLHVKISDLGLSrEIYSSDYYRVQNKSLLPIRWMPPEAIM------YGKFSSDsdIWSFG 213
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 945225    738 IIMQEVMVRG-TPFcmMDLPAQEIINRLKKPPPVYRPvvppEHAPPECLQLMKQCWAEAAEQRPTFDEIFNQFKTF 812
Cdd:cd05090  214 VVLWEIFSFGlQPY--YGFSNQEVIEMVRKRQLLPCS----EDCPPRMYSLMTECWQEIPSRRPRFKDIHARLRSW 283
STKc_PAK cd06614
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the ...
597-805 5.53e-13

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs are implicated in the regulation of many cellular processes including growth factor receptor-mediated proliferation, cell polarity, cell motility, cell death and survival, and actin cytoskeleton organization. PAK deregulation is associated with tumor development. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). Group II PAKs contain a PBD and a catalytic domain, but lack other motifs found in group I PAKs. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. Group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX; no such binding has been demonstrated for group II PAKs. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270789 [Multi-domain]  Cd Length: 255  Bit Score: 70.32  E-value: 5.53e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNC 676
Cdd:cd06614   49 IMKECKHPNIVDYYDSYLVGDELWVVMEYMDGGSLTDIITQNPVRMNESQIAYVCREVLQGLEYLHSQNVIHRDIKSDNI 128
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    677 VVDGRFVLKVTDYGFNDILEMlRLSEEESSMEELLWTAPELLRaprgSRLGSFAGDVYSFAIIMQEvMVRGTPFCMMDLP 756
Cdd:cd06614  129 LLSKDGSVKLADFGFAAQLTK-EKSKRNSVVGTPYWMAPEVIK----RKDYGPKVDIWSLGIMCIE-MAEGEPPYLEEPP 202
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 945225    757 AQEI-------INRLKKpppvyrpvvpPEHAPPECLQLMKQCWAEAAEQRPTFDEI 805
Cdd:cd06614  203 LRALflittkgIPPLKN----------PEKWSPEFKDFLNKCLVKDPEKRPSAEEL 248
PK_KSR2 cd14153
Pseudokinase domain of Kinase Suppressor of Ras 2; The pseudokinase domain shows similarity to ...
565-814 6.62e-13

Pseudokinase domain of Kinase Suppressor of Ras 2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. KSR2 interacts with the protein phosphatase calcineurin and functions in calcium-mediated ERK signaling. It also functions in energy metabolism by regulating AMP kinase and AMPK-dependent processes such as glucose uptake and fatty acid oxidation. KSR proteins act as scaffold proteins that function downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. KSR proteins regulate the assembly and activation of the Raf/MEK/ERK module upon Ras activation at the membrane by direct association of its components. They are widely regarded as pseudokinases. The KSR2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271055 [Multi-domain]  Cd Length: 270  Bit Score: 70.42  E-value: 6.62e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    565 IYEGDW-----VWLKKFSLGDFGDLKSIKSrasdvfEMM--KDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTN 637
Cdd:cd14153   16 VYHGRWhgevaIRLIDIERDNEEQLKAFKR------EVMayRQTRHENVVLFMGACMSPPHLAIITSLCKGRTLYSVVRD 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    638 QDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNCVVD-GRFVlkVTDYGFNDILEML----RLSEEESSMEELLW 712
Cdd:cd14153   90 AKVVLDVNKTRQIAQEIVKGMGYLHAKGILHKDLKSKNVFYDnGKVV--ITDFGLFTISGVLqagrREDKLRIQSGWLCH 167
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    713 TAPELLR--APRGSRLG---SFAGDVYSFAIIMQEVMVRGTPFcmMDLPAQEIINRLKKPPPVYRPVVPPEHappECLQL 787
Cdd:cd14153  168 LAPEIIRqlSPETEEDKlpfSKHSDVFAFGTIWYELHAREWPF--KTQPAEAIIWQVGSGMKPNLSQIGMGK---EISDI 242
                        250       260
                 ....*....|....*....|....*..
gi 945225    788 MKQCWAEAAEQRPTFDEIFNQFKTFNK 814
Cdd:cd14153  243 LLFCWAYEQEERPTFSKLMEMLEKLPK 269
PTKc_Zap-70 cd05115
Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa; PTKs ...
596-812 7.62e-13

Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Zap-70 is a cytoplasmic (or nonreceptor) PTK containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. Zap-70 is primarily expressed in T-cells and NK cells, and is a crucial component in T-cell receptor (TCR) signaling. Zap-70 binds the phosphorylated ITAM (immunoreceptor tyr activation motif) sequences of the activated TCR zeta-chain through its SH2 domains, leading to its phosphorylation and activation. It then phosphorylates target proteins, which propagate the signals to downstream pathways. Zap-70 is hardly detected in normal peripheral B-cells, but is present in some B-cell malignancies. It is used as a diagnostic marker for chronic lymphocytic leukemia (CLL) as it is associated with the more aggressive subtype of the disease. The Zap-70 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270686 [Multi-domain]  Cd Length: 269  Bit Score: 69.97  E-value: 7.62e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKD--LRHENINP----LLGFFyDSGMFAIVTEFCSRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHG 669
Cdd:cd05115   50 EMMREaqIMHQLDNPyivrMIGVC-EAEALMLVMEMASGGPLNKFLSGKKDEITVSNVVELMHQVSMGMKYLEEKNFVHR 128
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    670 RLKSRNCVVDGRFVLKVTDYGFNDILEMLRLSEEESSMEE--LLWTAPELLRAprgsRLGSFAGDVYSFAIIMQEVMVRG 747
Cdd:cd05115  129 DLAARNVLLVNQHYAKISDFGLSKALGADDSYYKARSAGKwpLKWYAPECINF----RKFSSRSDVWSYGVTMWEAFSYG 204
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 945225    748 -TPFCMMDLPaqEIINRLKKPPPVYRPVVppehAPPECLQLMKQCWAEAAEQRPTFDEIFNQFKTF 812
Cdd:cd05115  205 qKPYKKMKGP--EVMSFIEQGKRMDCPAE----CPPEMYALMSDCWIYKWEDRPNFLTVEQRMRTY 264
PTKc_Mer cd14204
Catalytic Domain of the Protein Tyrosine Kinase, Mer; PTKs catalyze the transfer of the ...
598-815 8.49e-13

Catalytic Domain of the Protein Tyrosine Kinase, Mer; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Mer (or Mertk) is named after its original reported expression pattern (monocytes, epithelial, and reproductive tissues). It is required for the ingestion of apoptotic cells by phagocytes such as macrophages, retinal pigment epithelial cells, and dendritic cells. Mer is also important in maintaining immune homeostasis. Mer is a member of the TAM subfamily, composed of receptor PTKs (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. The Mer subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271106 [Multi-domain]  Cd Length: 284  Bit Score: 70.35  E-value: 8.49e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    598 MKDLRHENINPLLGFFYDSGMFAI-----VTEFCSRGSLEDILTN-------QDVKLDWMFKssLLLDLIKGMKYLHHRE 665
Cdd:cd14204   63 MKDFNHPNVIRLLGVCLEVGSQRIpkpmvILPFMKYGDLHSFLLRsrlgsgpQHVPLQTLLK--FMIDIALGMEYLSSRN 140
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    666 FVHGRLKSRNCVVDGRFVLKVTDYGFN-DILEMLRLSEEESSMEELLWTAPELLraprGSRLGSFAGDVYSFAIIMQEVM 744
Cdd:cd14204  141 FLHRDLAARNCMLRDDMTVCVADFGLSkKIYSGDYYRQGRIAKMPVKWIAVESL----ADRVYTVKSDVWAFGVTMWEIA 216
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    745 VRG-TPFcmMDLPAQEII------NRLKKpppvyrpvvppehaPPECL----QLMKQCWAEAAEQRPTFDEIFNQFKTFN 813
Cdd:cd14204  217 TRGmTPY--PGVQNHEIYdyllhgHRLKQ--------------PEDCLdelyDIMYSCWRSDPTDRPTFTQLRENLEKLL 280

                 ..
gi 945225    814 KG 815
Cdd:cd14204  281 ES 282
PTKc_RET cd05045
Catalytic domain of the Protein Tyrosine Kinase, REarranged during Transfection protein; PTKs ...
595-810 8.65e-13

Catalytic domain of the Protein Tyrosine Kinase, REarranged during Transfection protein; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. RET is a receptor PTK (RTK) containing an extracellular region with four cadherin-like repeats, a calcium-binding site, and a cysteine-rich domain, a transmembrane segment, and an intracellular catalytic domain. It is part of a multisubunit complex that binds glial-derived neurotropic factor (GDNF) family ligands (GFLs) including GDNF, neurturin, artemin, and persephin. GFLs bind RET along with four GPI-anchored coreceptors, bringing two RET molecules together, leading to autophosphorylation, activation, and intracellular signaling. RET is essential for the development of the sympathetic, parasympathetic and enteric nervous systems, and the kidney. RET disruption by germline mutations causes diseases in humans including congenital aganglionosis of the gastrointestinal tract (Hirschsprung's disease) and three related inherited cancers: multiple endocrine neoplasia type 2A (MEN2A), MEN2B, and familial medullary thyroid carcinoma. The RET subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173631 [Multi-domain]  Cd Length: 290  Bit Score: 70.38  E-value: 8.65e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    595 FEMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQD------VKLDWMFKSSLLL----------DLI--- 655
Cdd:cd05045   54 FNLLKQVNHPHVIKLYGACSQDGPLLLIVEYAKYGSLRSFLRESRkvgpsyLGSDGNRNSSYLDnpderaltmgDLIsfa 133
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    656 ----KGMKYLHHREFVHGRLKSRNCVV-DGRfVLKVTDYGFN-DILEMLRLSEEESSMEELLWTAPELLraprGSRLGSF 729
Cdd:cd05045  134 wqisRGMQYLAEMKLVHRDLAARNVLVaEGR-KMKISDFGLSrDVYEEDSYVKRSKGRIPVKWMAIESL----FDHIYTT 208
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    730 AGDVYSFAIIMQE-VMVRGTPFcmMDLPAQEIINRLKkpppVYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEIFNQ 808
Cdd:cd05045  209 QSDVWSFGVLLWEiVTLGGNPY--PGIAPERLFNLLK----TGYRMERPENCSEEMYNLMLTCWKQEPDKRPTFADISKE 282

                 ..
gi 945225    809 FK 810
Cdd:cd05045  283 LE 284
STKc_AMPK-like cd14003
Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze ...
596-807 1.11e-12

Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The AMPK-like subfamily is composed of AMPK, MARK, BRSK, NUAK, MELK, SNRK, TSSK, and SIK, among others. LKB1 serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. AMPK, also called SNF1 (sucrose non-fermenting1) in yeasts and SnRK1 (SNF1-related kinase1) in plants, is a heterotrimeric enzyme composed of a catalytic alpha subunit and two regulatory subunits, beta and gamma. It is a stress-activated kinase that serves as master regulator of glucose and lipid metabolism by monitoring carbon and energy supplies, via sensing the cell's AMP:ATP ratio. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport. They are involved in embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. BRSKs play important roles in establishing neuronal polarity. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. The AMPK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270905 [Multi-domain]  Cd Length: 252  Bit Score: 69.08  E-value: 1.11e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILtNQDVKLD-----WMFKSsllldLIKGMKYLHHREFVHGR 670
Cdd:cd14003   51 EIMKLLNHPNIIKLYEVIETENKIYLVMEYASGGELFDYI-VNNGRLSedearRFFQQ-----LISAVDYCHSNGIVHRD 124
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    671 LKSRNCVVDGRFVLKVTDYGFNDilEMLRLSEEESSMEELLWTAPELLRapRGSRLGsFAGDVYSFAIIMQeVMVRGTpf 750
Cdd:cd14003  125 LKLENILLDKNGNLKIIDFGLSN--EFRGGSLLKTFCGTPAYAAPEVLL--GRKYDG-PKADVWSLGVILY-AMLTGY-- 196
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 945225    751 cmmdLP--AQEIINRLKKppPVYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEIFN 807
Cdd:cd14003  197 ----LPfdDDNDSKLFRK--ILKGKYPIPSHLSPDARDLIRRMLVVDPSKRITIEEILN 249
PTKc_DDR1 cd05096
Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 1; PTKs catalyze ...
596-805 1.45e-12

Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. DDR1 is a receptor PTK (RTK) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDR1 results in a slow but sustained receptor activation. DDR1 binds to all collagens tested to date (types I-IV). It is widely expressed in many tissues. It is abundant in the brain and is also found in keratinocytes, colonic mucosa epithelium, lung epithelium, thyroid follicles, and the islets of Langerhans. During embryonic development, it is found in the developing neuroectoderm. DDR1 is a key regulator of cell morphogenesis, differentiation and proliferation. It is important in the development of the mammary gland, the vasculator and the kidney. DDR1 is also found in human leukocytes, where it facilitates cell adhesion, migration, maturation, and cytokine production. The DDR1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133227 [Multi-domain]  Cd Length: 304  Bit Score: 69.96  E-value: 1.45e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTN---------------QDVKLDWMFKSSLL---LDLIKG 657
Cdd:cd05096   71 KILSRLKDPNIIRLLGVCVDEDPLCMITEYMENGDLNQFLSShhlddkeengndavpPAHCLPAISYSSLLhvaLQIASG 150
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    658 MKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGFNDIL---EMLRlsEEESSMEELLWTAPELLraprgsRLGSF--AGD 732
Cdd:cd05096  151 MKYLSSLNFVHRDLATRNCLVGENLTIKIADFGMSRNLyagDYYR--IQGRAVLPIRWMAWECI------LMGKFttASD 222
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 945225    733 VYSFAIIMQEVMV--RGTPFCmmDLPAQEIINRLKKPPPVYRPVVPPEHaPPECLQ----LMKQCWAEAAEQRPTFDEI 805
Cdd:cd05096  223 VWAFGVTLWEILMlcKEQPYG--ELTDEQVIENAGEFFRDQGRQVYLFR-PPPCPQglyeLMLQCWSRDCRERPSFSDI 298
PTKc_PDGFR_beta cd05107
Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor beta; ...
596-805 1.50e-12

Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor beta; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. PDGFR beta is a receptor PTK (RTK) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding to its ligands, the PDGFs, leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. PDGFR beta forms homodimers or heterodimers with PDGFR alpha, depending on the nature of the PDGF ligand. PDGF-BB and PDGF-DD induce PDGFR beta homodimerization. PDGFR signaling plays many roles in normal embryonic development and adult physiology. PDGFR beta signaling leads to a variety of cellular effects including the stimulation of cell growth and chemotaxis, as well as the inhibition of apoptosis and GAP junctional communication. It is critical in normal angiogenesis as it is involved in the recruitment of pericytes and smooth muscle cells essential for vessel stability. Aberrant PDGFR beta expression is associated with some human cancers. The continuously-active fusion proteins of PDGFR beta with COL1A1 and TEL are associated with dermatofibrosarcoma protuberans (DFSP) and a subset of chronic myelomonocytic leukemia (CMML), respectively. The PDGFR beta subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133238 [Multi-domain]  Cd Length: 401  Bit Score: 70.81  E-value: 1.50e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPL-LGFFYDSGMFAivtefCSRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSR 674
Cdd:cd05107  194 DMKGTVKYADIESSnYESPYDQYLPS-----APERTRRDTLINESPALSYMDLVGFSYQVANGMEFLASKNCVHRDLAAR 268
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    675 NCVV-DGRFVlKVTDYGF-NDILEMLRLSEEESSMEELLWTAPELLRaprgSRLGSFAGDVYSFAIIMQEVM-VRGTPFc 751
Cdd:cd05107  269 NVLIcEGKLV-KICDFGLaRDIMRDSNYISKGSTFLPLKWMAPESIF----NNLYTTLSDVWSFGILLWEIFtLGGTPY- 342
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 945225    752 mMDLPAQEII-NRLKKPPPVYRPVvppeHAPPECLQLMKQCWAEAAEQRPTFDEI 805
Cdd:cd05107  343 -PELPMNEQFyNAIKRGYRMAKPA----HASDEIYEIMQKCWEEKFEIRPDFSQL 392
PTKc_VEGFR2 cd05103
Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 2; ...
625-805 1.83e-12

Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR2 (or Flk1) binds the ligands VEGFA, VEGFC, VEGFD and VEGFE. VEGFR2 signaling is implicated in all aspects of normal and pathological vascular endothelial cell biology. It induces a variety of cellular effects including migration, survival, and proliferation. It is critical in regulating embryonic vascular development and angiogenesis. VEGFR2 is the major signal transducer in pathological angiogenesis including cancer and diabetic retinopathy, and is a target for inhibition in cancer therapy. The carboxyl terminus of VEGFR2 plays an important role in its autophosphorylation and activation. VEGFR2 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270681 [Multi-domain]  Cd Length: 343  Bit Score: 70.01  E-value: 1.83e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    625 FCSRGSLEDIlTNQDVKLDWMFKSSLLL-DLI-------KGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGF-NDIL 695
Cdd:cd05103  152 FVEEKSLSDV-EEEEAGQEDLYKDFLTLeDLIcysfqvaKGMEFLASRKCIHRDLAARNILLSENNVVKICDFGLaRDIY 230
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    696 EMLRLSEEESSMEELLWTAPELLRaprgSRLGSFAGDVYSFAIIMQEVMVRG-TPFCMMDLPaQEIINRLKKPPPVYRPv 774
Cdd:cd05103  231 KDPDYVRKGDARLPLKWMAPETIF----DRVYTIQSDVWSFGVLLWEIFSLGaSPYPGVKID-EEFCRRLKEGTRMRAP- 304
                        170       180       190
                 ....*....|....*....|....*....|.
gi 945225    775 vppEHAPPECLQLMKQCWAEAAEQRPTFDEI 805
Cdd:cd05103  305 ---DYTTPEMYQTMLDCWHGEPSQRPTFSEL 332
STKc_LRRK cd14000
Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase; STKs catalyze the ...
597-810 3.11e-12

Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. Vertebrates contain two members, LRRK1 and LRRK2, which show complementary expression in the brain. Mutations in LRRK2 are linked to both familial and sporadic forms of Parkinson's disease. The normal roles of LRRKs are not clearly defined. They may be involved in mitogen-activated protein kinase (MAPK) pathways, protein translation control, programmed cell death pathways, and cytoskeletal dynamics. The LRRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270902 [Multi-domain]  Cd Length: 275  Bit Score: 68.41  E-value: 3.11e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFFYDSGMFAIvtEFCSRGSLEDIL---TNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKS 673
Cdd:cd14000   63 VLSHLHHPSIVYLLGIGIHPLMLVL--ELAPLGSLDHLLqqdSRSFASLGRTLQQRIALQVADGLRYLHSAMIIYRDLKS 140
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    674 RNCVV-----DGRFVLKVTDYGfndILEMLRLSEEESSMEELLWTAPELLRaprGSRLGSFAGDVYSFAIIMQEVMVRGT 748
Cdd:cd14000  141 HNVLVwtlypNSAIIIKIADYG---ISRQCCRMGAKGSEGTPGFRAPEIAR---GNVIYNEKVDVFSFGMLLYEILSGGA 214
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 945225    749 PFcmmdLPAQEIINRLKKPPPVYRPVVPPEHAPPECLQ-LMKQCWAEAAEQRPTFDEIFNQFK 810
Cdd:cd14000  215 PM----VGHLKFPNEFDIHGGLRPPLKQYECAPWPEVEvLMKKCWKENPQQRPTAVTVVSILN 273
PTKc_Tie2 cd05088
Catalytic domain of the Protein Tyrosine Kinase, Tie2; PTKs catalyze the transfer of the ...
603-820 3.93e-12

Catalytic domain of the Protein Tyrosine Kinase, Tie2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tie2 is a receptor PTK (RTK) containing an extracellular region, a transmembrane segment, and an intracellular catalytic domain. The extracellular region contains an immunoglobulin (Ig)-like domain, three epidermal growth factor (EGF)-like domains, a second Ig-like domain, and three fibronectin type III repeats. Tie2 is expressed mainly in endothelial cells and hematopoietic stem cells. It is also found in a subset of tumor-associated monocytes and eosinophils. The angiopoietins (Ang-1 to Ang-4) serve as ligands for Tie2. The binding of Ang-1 to Tie2 leads to receptor autophosphorylation and activation, promoting cell migration and survival. In contrast, Ang-2 binding to Tie2 does not result in the same response, suggesting that Ang-2 may function as an antagonist. Tie2 signaling plays key regulatory roles in vascular integrity and quiescence, and in inflammation. The Tie2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133219 [Multi-domain]  Cd Length: 303  Bit Score: 68.49  E-value: 3.93e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    603 HENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDV-KLDWMF----------KSSLLL----DLIKGMKYLHHREFV 667
Cdd:cd05088   67 HPNIINLLGACEHRGYLYLAIEYAPHGNLLDFLRKSRVlETDPAFaianstastlSSQQLLhfaaDVARGMDYLSQKQFI 146
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    668 HGRLKSRNCVVDGRFVLKVTDYGFNDILEMLrlSEEESSMEELLWTAPELLraprGSRLGSFAGDVYSFAIIMQEVM-VR 746
Cdd:cd05088  147 HRDLAARNILVGENYVAKIADFGLSRGQEVY--VKKTMGRLPVRWMAIESL----NYSVYTTNSDVWSYGVLLWEIVsLG 220
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 945225    747 GTPFCMMDlpAQEIINRLKKPPPVYRPVvppeHAPPECLQLMKQCWAEAAEQRPTFDEIFNQFKTFNKGKKTNI 820
Cdd:cd05088  221 GTPYCGMT--CAELYEKLPQGYRLEKPL----NCDDEVYDLMRQCWREKPYERPSFAQILVSLNRMLEERKTYV 288
PTKc_Ror2 cd05091
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ...
597-812 4.06e-12

Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Ror2 plays important roles in skeletal and heart formation. Ror2-deficient mice show widespread bone abnormalities, ventricular defects in the heart, and respiratory dysfunction. Mutations in human Ror2 result in two different bone development genetic disorders, recessive Robinow syndrome and brachydactyly type B. Ror2 is also implicated in neural development. Ror proteins are orphan receptor PTKs (RTKs) containing an extracellular region with immunoglobulin-like, cysteine-rich, and kringle domains, a transmembrane segment, and an intracellular catalytic domain. Ror RTKs are unrelated to the nuclear receptor subfamily called retinoid-related orphan receptors (RORs). RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. The Ror2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270673 [Multi-domain]  Cd Length: 284  Bit Score: 68.12  E-value: 4.06e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKD-LRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILT----NQDVKL---DWMFKSSL--------LLDLIKGMKY 660
Cdd:cd05091   61 MLRSrLQHPNIVCLLGVVTKEQPMSMIFSYCSHGDLHEFLVmrspHSDVGStddDKTVKSTLepadflhiVTQIAAGMEY 140
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    661 LHHREFVHGRLKSRNCVVDGRFVLKVTDYG-FNDILEMLRLSEEESSMEELLWTAPELLRaprgsrLGSFA--GDVYSFA 737
Cdd:cd05091  141 LSSHHVVHKDLATRNVLVFDKLNVKISDLGlFREVYAADYYKLMGNSLLPIRWMSPEAIM------YGKFSidSDIWSYG 214
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    738 IIMQEVMVRG-TPFCmmDLPAQEIINRLKKPPPVYrpvvppehAPPEC----LQLMKQCWAEAAEQRPTFDEIFNQFKTF 812
Cdd:cd05091  215 VVLWEVFSYGlQPYC--GYSNQDVIEMIRNRQVLP--------CPDDCpawvYTLMLECWNEFPSRRPRFKDIHSRLRTW 284
STKc_LIMK1 cd14221
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 1; STKs catalyze the ...
596-746 4.62e-12

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMK1 activation is induced by bone morphogenic protein, vascular endothelial growth factor, and thrombin. It plays roles in microtubule disassembly and cell cycle progression, and is critical in the regulation of neurite outgrowth. LIMK1 knockout mice show abnormalities in dendritic spine morphology and synaptic function. LIMK1 is one of the genes deleted in patients with Williams Syndrome, which is characterized by distinct craniofacial features, cardiovascular problems, as well as behavioral and neurological abnormalities. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. The LIMK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271123 [Multi-domain]  Cd Length: 267  Bit Score: 67.67  E-value: 4.62e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRN 675
Cdd:cd14221   42 KVMRCLEHPNVLKFIGVLYKDKRLNFITEYIKGGTLRGIIKSMDSHYPWSQRVSFAKDIASGMAYLHSMNIIHRDLNSHN 121
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    676 CVVDGRFVLKVTDYGFNDILEMLRLSEEESSMEELL-------------WTAPELLRAprgsRLGSFAGDVYSFAIIMQE 742
Cdd:cd14221  122 CLVRENKSVVVADFGLARLMVDEKTQPEGLRSLKKPdrkkrytvvgnpyWMAPEMING----RSYDEKVDVFSFGIVLCE 197

                 ....
gi 945225    743 VMVR 746
Cdd:cd14221  198 IIGR 201
STKc_LIMK2 cd14222
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 2; STKs catalyze the ...
596-813 6.89e-12

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMK2 activation is induced by transforming growth factor-beta l (TGFb-l) and shares the same subcellular location as the cofilin family member twinfilin, which may be its biological substrate. LIMK2 plays a role in spermatogenesis, and may contribute to tumor progression and metastasis formation in some cancer cells. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. The LIMK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271124 [Multi-domain]  Cd Length: 272  Bit Score: 67.28  E-value: 6.89e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDvKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRN 675
Cdd:cd14222   42 KVMRSLDHPNVLKFIGVLYKDKRLNLLTEFIEGGTLKDFLRADD-PFPWQQKVSFAKGIASGMAYLHSMSIIHRDLNSHN 120
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    676 CVVDGRFVLKVTDYGFNDIL----------------EMLRLSEEESSMEEL---LWTAPELLRAPRGSRlgsfAGDVYSF 736
Cdd:cd14222  121 CLIKLDKTVVVADFGLSRLIveekkkpppdkpttkkRTLRKNDRKKRYTVVgnpYWMAPEMLNGKSYDE----KVDIFSF 196
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    737 AIIMQEVM--VRGTPFCM-----MDLPAQEIINRLkkpppvyrpvvPPEHAPPECLQLMKQCWAEAAEQRPTFDEIFNQF 809
Cdd:cd14222  197 GIVLCEIIgqVYADPDCLprtldFGLNVRLFWEKF-----------VPKDCPPAFFPLAAICCRLEPDSRPAFSKLEDSF 265

                 ....
gi 945225    810 KTFN 813
Cdd:cd14222  266 EALS 269
STKc_Byr2_like cd06628
Catalytic domain of the Serine/Threonine Kinases, fungal Byr2-like Mitogen-Activated Protein ...
596-805 7.32e-12

Catalytic domain of the Serine/Threonine Kinases, fungal Byr2-like Mitogen-Activated Protein Kinase Kinase Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include the MAPKKKs Schizosaccharomyces pombe Byr2, Saccharomyces cerevisiae and Cryptococcus neoformans Ste11, and related proteins. They contain an N-terminal SAM (sterile alpha-motif) domain, which mediates protein-protein interaction, and a C-terminal catalytic domain. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Fission yeast Byr2 is regulated by Ras1. It responds to pheromone signaling and controls mating through the MAPK pathway. Budding yeast Ste11 functions in MAPK cascades that regulate mating, high osmolarity glycerol, and filamentous growth responses. The Byr2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270798 [Multi-domain]  Cd Length: 267  Bit Score: 67.17  E-value: 7.32e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVkldwmFKSSLLLDLI----KGMKYLHHREFVHGRL 671
Cdd:cd06628   58 ALLRELQHENIVQYLGSSSDANHLNIFLEYVPGGSVATLLNNYGA-----FEESLVRNFVrqilKGLNYLHNRGIIHRDI 132
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    672 KSRNCVVDGRFVLKVTDYGFN-----DILEMLRLSEEESSMEELLWTAPELLRAPRGSRlgsfAGDVYSFAIIMQEVMVR 746
Cdd:cd06628  133 KGANILVDNKGGIKISDFGISkkleaNSLSTKNNGARPSLQGSVFWMAPEVVKQTSYTR----KADIWSLGCLVVEMLTG 208
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 945225    747 GTPFcmMDLPAQEIINRLKKpppvYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEI 805
Cdd:cd06628  209 THPF--PDCTQMQAIFKIGE----NASPTIPSNISSEARDFLEKTFEIDHNKRPTADEL 261
STKc_PASK cd14004
Catalytic domain of the Serine/Threonine kinase, Per-ARNT-Sim (PAS) domain Kinase; STKs ...
583-807 7.36e-12

Catalytic domain of the Serine/Threonine kinase, Per-ARNT-Sim (PAS) domain Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PASK (or PASKIN) is a nutrient and energy sensor and thus, plays an important role in maintaining cellular energy homeostasis. It coordinates the utilization of glucose in response to metabolic demand. It contains an N-terminal PAS domain which directly interacts and inhibits a C-terminal catalytic kinase domain. The PAS domain serves as a sensory module for different environmental signals such as light, redox state, and various metabolites. Binding of ligands to the PAS domain causes structural changes which leads to kinase activation and the phosphorylation of substrates to trigger the appropriate cellular response. The PASK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270906 [Multi-domain]  Cd Length: 256  Bit Score: 67.03  E-value: 7.36e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    583 DLKSIKSRASdVFEMMKDLRHENINPLLGFFYDSGMFAIVTEfcSRGSLEDILTNQDVK--LDWMFKSSLLLDLIKGMKY 660
Cdd:cd14004   48 KLGTVPLEIH-ILDTLNKRSHPNIVKLLDFFEDDEFYYLVME--KHGSGMDLFDFIERKpnMDEKEAKYIFRQVADAVKH 124
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    661 LHHREFVHGRLKSRNCVVDGRFVLKVTDYGFNdilEMLRLSEEESSMEELLWTAPELLrapRGSRLGSFAGDVYSFAIIM 740
Cdd:cd14004  125 LHDQGIVHRDIKDENVILDGNGTIKLIDFGSA---AYIKSGPFDTFVGTIDYAAPEVL---RGNPYGGKEQDIWALGVLL 198
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 945225    741 QEVMVRGTPFCMMDlpaqEIINRLKKPPPVYRPvvppehappECLQLMKQCWAEAAEQRPTFDEIFN 807
Cdd:cd14004  199 YTLVFKENPFYNIE----EILEADLRIPYAVSE---------DLIDLISRMLNRDVGDRPTIEELLT 252
PTKc_Trk cd05049
Catalytic domain of the Protein Tyrosine Kinases, Tropomyosin Related Kinases; PTKs catalyze ...
596-805 9.58e-12

Catalytic domain of the Protein Tyrosine Kinases, Tropomyosin Related Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Trk subfamily consists of TrkA, TrkB, TrkC, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, the nerve growth factor (NGF) family of neutrotrophins, leads to Trk receptor oligomerization and activation of the catalytic domain. Trk receptors are mainly expressed in the peripheral and central nervous systems. They play important roles in cell fate determination, neuronal survival and differentiation, as well as in the regulation of synaptic plasticity. Altered expression of Trk receptors is associated with many human diseases. The Trk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270643 [Multi-domain]  Cd Length: 280  Bit Score: 67.11  E-value: 9.58e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLED----------ILTNQDVKLDWMFKSSLL---LDLIKGMKYLH 662
Cdd:cd05049   60 ELLTNLQHENIVKFYGVCTEGDPLLMVFEYMEHGDLNKflrshgpdaaFLASEDSAPGELTLSQLLhiaVQIASGMVYLA 139
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    663 HREFVHGRLKSRNCVVDGRFVLKVTDYGFN-DILEMLRLSEEESSMEELLWTAPELLRaprgSRLGSFAGDVYSFAIIMQ 741
Cdd:cd05049  140 SQHFVHRDLATRNCLVGTNLVVKIGDFGMSrDIYSTDYYRVGGHTMLPIRWMPPESIL----YRKFTTESDVWSFGVVLW 215
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 945225    742 EVMVRG-TPFcmMDLPAQEIINRLKKpppvYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEI 805
Cdd:cd05049  216 EIFTYGkQPW--FQLSNTEVIECITQ----GRLLQRPRTCPSEVYAVMLGCWKREPQQRLNIKDI 274
STK_BAK1_like cd14664
Catalytic domain of the Serine/Threonine Kinase, BRI1 associated kinase 1 and related STKs; ...
596-750 1.16e-11

Catalytic domain of the Serine/Threonine Kinase, BRI1 associated kinase 1 and related STKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes three leucine-rich repeat receptor-like kinases (LRR-RLKs): Arabidopsis thaliana BAK1 and CLAVATA1 (CLV1), and Physcomitrella patens CLL1B clavata1-like receptor S/T protein kinase. BAK1 functions in various signaling pathways. It plays a role in BR (brassinosteroid)-regulated plant development as a co-receptor of BRASSINOSTEROID (BR) INSENSITIVE 1 (BRI1), the receptor for BRs, and is required for full activation of BR signaling. It also modulates pathways involved in plant resistance to pathogen infection (pattern-triggered immunity, PTI) and herbivore attack (wound- or herbivore feeding-induced accumulation of jasmonic acid (JA) and JA-isoleucine. CLV1, directly binds small signaling peptides, CLAVATA3 (CLV3) and CLAVATA3/EMBRYO SURROUNDING REGI0N (CLE), to restrict stem cell proliferation: the CLV3-CLV1-WUS (WUSCHEL) module influences stem cell maintenance in the shoot apical meristem, and the CLE40 (CLAVATA3/EMBRYO SURROUNDING REGION40) -ACR4 (CRINKLY4) -CLV1- WOX5 (WUSCHEL-RELATED HOMEOBOX5) module at the root apical meristem. The STK_BAK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271134 [Multi-domain]  Cd Length: 270  Bit Score: 66.36  E-value: 1.16e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDIL---TNQDVKLDWMFKSSLLLDLIKGMKYLHHR---EFVHG 669
Cdd:cd14664   42 QTLGMIRHRNIVRLRGYCSNPTTNLLVYEYMPNGSLGELLhsrPESQPPLDWETRQRIALGSARGLAYLHHDcspLIIHR 121
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    670 RLKSRNCVVDGRFVLKVTDYGFNDILEMLRLSEEESSMEELLWTAPELLRAPRGSRlgsfAGDVYSFAIIMQEVMVRGTP 749
Cdd:cd14664  122 DVKSNNILLDEEFEAHVADFGLAKLMDDKDSHVMSSVAGSYGYIAPEYAYTGKVSE----KSDVYSYGVVLLELITGKRP 197

                 .
gi 945225    750 F 750
Cdd:cd14664  198 F 198
STKc_LIMK cd14154
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase; STKs catalyze the transfer ...
597-811 1.29e-11

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. Vertebrate have two members, LIMK1 and LIMK2. The LIMK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271056 [Multi-domain]  Cd Length: 272  Bit Score: 66.38  E-value: 1.29e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNC 676
Cdd:cd14154   43 VMRSLDHPNVLKFIGVLYKDKKLNLITEYIPGGTLKDVLKDMARPLPWAQRVRFAKDIASGMAYLHSMNIIHRDLNSHNC 122
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    677 VVDGRFVLKVTDYGFNDILEMLRLSEEESSMEELL-------------------WTAPELLRAprgsRLGSFAGDVYSFA 737
Cdd:cd14154  123 LVREDKTVVVADFGLARLIVEERLPSGNMSPSETLrhlkspdrkkrytvvgnpyWMAPEMLNG----RSYDEKVDIFSFG 198
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 945225    738 IIMQEVM--VRGTPFCM---MDLPAQEIINRLKkpppvyrpvvPPEHAPPECLQLMKQCWAEAAEQRPTFDEIFNQFKT 811
Cdd:cd14154  199 IVLCEIIgrVEADPDYLprtKDFGLNVDSFREK----------FCAGCPPPFFKLAFLCCDLDPEKRPPFETLEEWLEA 267
STKc_MLK4 cd14146
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 4; STKs catalyze the ...
585-809 1.40e-11

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK4 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The specific function of MLK4 is yet to be determined. Mutations in the kinase domain of MLK4 have been detected in colorectal cancers. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation.The MLK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271048 [Multi-domain]  Cd Length: 268  Bit Score: 66.21  E-value: 1.40e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    585 KSIKSRASdVFEMmkdLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQD--------------VKLDWMfkssl 650
Cdd:cd14146   38 ESVRQEAK-LFSM---LRHPNIIKLEGVCLEEPNLCLVMEFARGGTLNRALAAANaapgprrarripphILVNWA----- 108
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    651 lLDLIKGMKYLHHREFV---HGRLKSRNCVV--------DGRFVLKVTDYGfndILEMLRLSEEESSMEELLWTAPELLR 719
Cdd:cd14146  109 -VQIARGMLYLHEEAVVpilHRDLKSSNILLlekiehddICNKTLKITDFG---LAREWHRTTKMSAAGTYAWMAPEVIK 184
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    720 aprgSRLGSFAGDVYSFAIIMQEVMVRGTPFCMMDLPAQE---IINRLkkpppvyrPVVPPEHAPPECLQLMKQCWAEAA 796
Cdd:cd14146  185 ----SSLFSKGSDIWSYGVLLWELLTGEVPYRGIDGLAVAygvAVNKL--------TLPIPSTCPEPFAKLMKECWEQDP 252
                        250
                 ....*....|...
gi 945225    797 EQRPTFDEIFNQF 809
Cdd:cd14146  253 HIRPSFALILEQL 265
STKc_ULK4 cd14010
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the ...
585-750 1.71e-11

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ULK4 is a functionally uncharacterized kinase that shows similarity to ATG1/ULKs. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. The ULK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270912 [Multi-domain]  Cd Length: 269  Bit Score: 66.16  E-value: 1.71e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    585 KSIKSRASDVFEMMKDLRHENInplLGFF--YD-SGMFAIVTEFCSRGSLEDILTnQDVKLDWMFKSSLLLDLIKGMKYL 661
Cdd:cd14010   35 KSKRPEVLNEVRLTHELKHPNV---LKFYewYEtSNHLWLVVEYCTGGDLETLLR-QDGNLPESSVRKFGRDLVRGLHYI 110
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    662 HHREFVHGRLKSRNCVVDGRFVLKVTDYG----FNDILEMLRLSEEESSMEELL-----------WTAPELLRAPrgsrL 726
Cdd:cd14010  111 HSKGIIYCDLKPSNILLDGNGTLKLSDFGlarrEGEILKELFGQFSDEGNVNKVskkqakrgtpyYMAPELFQGG----V 186
                        170       180
                 ....*....|....*....|....
gi 945225    727 GSFAGDVYSFAIIMQEVMVRGTPF 750
Cdd:cd14010  187 HSFASDLWALGCVLYEMFTGKPPF 210
PTKc_EGFR cd05108
Catalytic domain of the Protein Tyrosine Kinase, Epidermal Growth Factor Receptor; PTKs ...
597-809 1.75e-11

Catalytic domain of the Protein Tyrosine Kinase, Epidermal Growth Factor Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EGFR (HER1, ErbB1) is a receptor PTK (RTK) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Ligands for EGFR include EGF, heparin binding EGF-like growth factor (HBEGF), epiregulin, amphiregulin, TGFalpha, and betacellulin. Upon ligand binding, EGFR can form homo- or heterodimers with other EGFR subfamily members. The EGFR signaling pathway is one of the most important pathways regulating cell proliferation, differentiation, survival, and growth. Overexpression and mutation in the kinase domain of EGFR have been implicated in the development and progression of a variety of cancers. A number of monoclonal antibodies and small molecule inhibitors have been developed that target EGFR, including the antibodies Cetuximab and Panitumumab, which are used in combination with other therapies for the treatment of colorectal cancer and non-small cell lung carcinoma (NSCLC). The small molecule inhibitors Gefitinib (Iressa) and Erlotinib (Tarceva), already used for NSCLC, are undergoing clinical trials for other types of cancer including gastrointestinal, breast, head and neck, and bladder. The EGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270683 [Multi-domain]  Cd Length: 313  Bit Score: 66.58  E-value: 1.75e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFFYDSGMfAIVTEFCSRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNC 676
Cdd:cd05108   62 VMASVDNPHVCRLLGICLTSTV-QLITQLMPFGCLLDYVREHKDNIGSQYLLNWCVQIAKGMNYLEDRRLVHRDLAARNV 140
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    677 VVDGRFVLKVTDYGFNDILEM-LRLSEEESSMEELLWTAPELLRaprgSRLGSFAGDVYSFAIIMQEVMVRGT-PFcmMD 754
Cdd:cd05108  141 LVKTPQHVKITDFGLAKLLGAeEKEYHAEGGKVPIKWMALESIL----HRIYTHQSDVWSYGVTVWELMTFGSkPY--DG 214
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 945225    755 LPAQEIINRLKKPPPVYRpvvppehaPPEC----LQLMKQCWAEAAEQRPTFDEIFNQF 809
Cdd:cd05108  215 IPASEISSILEKGERLPQ--------PPICtidvYMIMVKCWMIDADSRPKFRELIIEF 265
PK_eIF2AK_GCN2_rpt1 cd14012
Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or ...
595-738 1.82e-11

Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the overall downregulation of protein synthesis. eIF-2 phosphorylation is induced in response to cellular stresses including virus infection, heat shock, nutrient deficiency, and the accummulation of unfolded proteins, among others. There are four distinct kinases that phosphorylate eIF-2 and control protein synthesis under different stress conditions: GCN2, protein kinase regulated by RNA (PKR), heme-regulated inhibitor kinase (HRI), and PKR-like endoplasmic reticulum kinase (PERK). GCN2 is activated by amino acid or serum starvation and UV irradiation. It induces GCN4, a transcriptional activator of amino acid biosynthetic genes, leading to increased production of amino acids under amino acid-deficient conditions. In serum-starved cells, GCN2 activation induces translation of the stress-responsive transcription factor ATF4, while under UV stress, GCN2 triggers transcriptional rescue via NF-kappaB signaling. GCN2 contains an N-terminal RWD, a degenerate kinase-like (repeat 1), the catalytic kinase (repeat 2), a histidyl-tRNA synthetase (HisRS)-like, and a C-terminal ribosome-binding and dimerization (RB/DD) domains. The degenerate pseudokinase domain of GCN2 may function as a regulatory domain. The GCN2 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270914 [Multi-domain]  Cd Length: 254  Bit Score: 65.84  E-value: 1.82e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    595 FEMMKDLRHENINPLLGFFY------DSGMFAIVTEFCSRGSLEDIL-TNQDVKLD----WMfkssllLDLIKGMKYLHH 663
Cdd:cd14012   49 LESLKKLRHPNLVSYLAFSIerrgrsDGWKVYLLTEYAPGGSLSELLdSVGSVPLDtarrWT------LQLLEALEYLHR 122
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 945225    664 REFVHGRLKSRNCVVD---GRFVLKVTDYGFNDILEMLRLSEEESSMEELLWTAPELLrapRGSRLGSFAGDVYSFAI 738
Cdd:cd14012  123 NGVVHKSLHAGNVLLDrdaGTGIVKLTDYSLGKTLLDMCSRGSLDEFKQTYWLPPELA---QGSKSPTRKTDVWDLGL 197
PBP1_glutamate_receptors-like cd06269
ligand-binding domain of family C G-protein couples receptors (GPCRs), membrane bound guanylyl ...
54-327 2.89e-11

ligand-binding domain of family C G-protein couples receptors (GPCRs), membrane bound guanylyl cyclases such as natriuretic peptide receptors (NPRs), and N-terminal leucine/isoleucine/valine-binding protein (LIVBP)-like domain of ionotropic glutamate rece; This CD represents the ligand-binding domain of the family C G-protein couples receptors (GPCRs), membrane bound guanylyl cyclases such as the family of natriuretic peptide receptors (NPRs), and the N-terminal leucine-isoleucine-valine binding protein (LIVBP)-like domain of the ionotropic glutamate receptors, all of which are structurally similar and related to the periplasmic-binding fold type 1 family. The family C GPCRs consists of metabotropic glutamate receptor (mGluR), a calcium-sensing receptor (CaSR), gamma-aminobutyric acid receptor (GABAbR), the promiscuous L-alpha-amino acid receptor GPR6A, families of taste and pheromone receptors, and orphan receptors. Truncated splicing variants of the orphan receptors are not included in this CD. The family C GPCRs are activated by endogenous agonists such as amino acids, ions, and sugar based molecules. Their amino terminal ligand-binding region is homologous to the bacterial leucine-isoleucine-valine binding protein (LIVBP) and a leucine binding protein (LBP). The ionotropic glutamate receptors (iGluRs) have an integral ion channel and are subdivided into three major groups based on their pharmacology and structural similarities: NMDA receptors, AMPA receptors, and kainate receptors. The family of membrane bound guanylyl cyclases is further divided into three subfamilies: the ANP receptor (GC-A)/C-type natriuretic peptide receptor (GC-B), the heat-stable enterotoxin receptor (GC-C)/sensory organ specific membrane GCs such as retinal receptors (GC-E, GC-F), and olfactory receptors (GC-D and GC-G).


Pssm-ID: 380493 [Multi-domain]  Cd Length: 332  Bit Score: 66.29  E-value: 2.89e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225     54 KIGVVGPwACDSLFSKALPEVAARLAIERINRDPSFDLSYSFEYVILNEDCQTSRALSS---FISHHQMAsGFIGPTNPG 130
Cdd:cd06269    1 TIGALLP-VHDYLESGAKVLPAFELALSDVNSRPDLLPKTTLGLAIRDSECNPTQALLSacdLLAAAKVV-AILGPGCSA 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    131 YCEAASLLGNSWDKGIFSWACVNYELDNKISYPTFSRTLPSPIR---VLVTVMKYFQWAHAGVISSDEDIWVHTANRVAS 207
Cdd:cd06269   79 SAAPVANLARHWDIPVLSYGATAPGLSDKSRYAYFLRTVPPDSKqadAMLALVRRLGWNKVVLIYSDDEYGEFGLEGLEE 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    208 ALRSHGLPVGVVLTTGQDSQSMRKALQRIHQADRIRIIIMCMHSALIGGetqmhLLECAHDLKMTDGTYVFVPYDAllys 287
Cdd:cd06269  159 LFQEKGGLITSRQSFDENKDDDLTKLLRNLRDTEARVIILLASPDTARS-----LMLEAKRLDMTSKDYVWFVIDG---- 229
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|
gi 945225    288 lpYKHTPYQVLRnnpKLREAYDAVLTITVESQEKTFYQAF 327
Cdd:cd06269  230 --EASSSDEHGD---EARQAAEGAITVTLIFPVVKEFLKF 264
STKc_MEKK1_plant cd06632
Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP) ...
568-807 3.06e-11

Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of plant MAPK kinase kinases (MAPKKKs) including Arabidopsis thaliana MEKK1 and MAPKKK3. Arabidopsis thaliana MEKK1 activates MPK4, a MAPK that regulates systemic acquired resistance. MEKK1 also participates in the regulation of temperature-sensitive and tissue-specific cell death. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The plant MEKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270802 [Multi-domain]  Cd Length: 259  Bit Score: 65.12  E-value: 3.06e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    568 GDWVWLKKFSLGDFGDL--KSIKSRASDVfEMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDvKLDWM 645
Cdd:cd06632   25 GDFFAVKEVSLVDDDKKsrESVKQLEQEI-ALLSKLRHPNIVQYYGTEREEDNLYIFLEYVPGGSIHKLLQRYG-AFEEP 102
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    646 FKSSLLLDLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGFNDILEMLRlsEEESSMEELLWTAPELLRaPRGSR 725
Cdd:cd06632  103 VIRLYTRQILSGLAYLHSRNTVHRDIKGANILVDTNGVVKLADFGMAKHVEAFS--FAKSFKGSPYWMAPEVIM-QKNSG 179
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    726 LGsFAGDVYSFAIIMQEvMVRGTPfcmmdlP--AQEIINRLKKPPPVYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFD 803
Cdd:cd06632  180 YG-LAVDIWSLGCTVLE-MATGKP------PwsQYEGVAAIFKIGNSGELPPIPDHLSPDAKDFIRLCLQRDPEDRPTAS 251

                 ....
gi 945225    804 EIFN 807
Cdd:cd06632  252 QLLE 255
PTKc_IGF-1R cd05062
Catalytic domain of the Protein Tyrosine Kinase, Insulin-like Growth Factor-1 Receptor; PTKs ...
597-810 3.34e-11

Catalytic domain of the Protein Tyrosine Kinase, Insulin-like Growth Factor-1 Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. IGF-1R is a receptor PTK (RTK) that is composed of two alphabeta heterodimers. Binding of the ligand (IGF-1 or IGF-2) to the extracellular alpha subunit activates the intracellular tyr kinase domain of the transmembrane beta subunit. Receptor activation leads to autophosphorylation, which stimulates downstream kinase activities and biological function. IGF-1R signaling is important in the differentiation, growth, and survival of normal cells. In cancer cells, where it is frequently overexpressed, IGF-1R is implicated in proliferation, the suppression of apoptosis, invasion, and metastasis. IGF-1R is being developed as a therapeutic target in cancer treatment. The IGF-1R subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133193 [Multi-domain]  Cd Length: 277  Bit Score: 65.44  E-value: 3.34e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILtnQDVKLDWMFKSSLLLDLIK-----------GMKYLHHRE 665
Cdd:cd05062   62 VMKEFNCHHVVRLLGVVSQGQPTLVIMELMTRGDLKSYL--RSLRPEMENNPVQAPPSLKkmiqmageiadGMAYLNANK 139
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    666 FVHGRLKSRNCVVDGRFVLKVTDYGFN-DILEMLRLSEEESSMEELLWTAPELLRAprgsrlGSFA--GDVYSFAIIMQE 742
Cdd:cd05062  140 FVHRDLAARNCMVAEDFTVKIGDFGMTrDIYETDYYRKGGKGLLPVRWMSPESLKD------GVFTtySDVWSFGVVLWE 213
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 945225    743 VMVrgtpfcMMDLPAQEIIN-RLKKPPPVYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEIFNQFK 810
Cdd:cd05062  214 IAT------LAEQPYQGMSNeQVLRFVMEGGLLDKPDNCPDMLFELMRMCWQYNPKMRPSFLEIISSIK 276
STKc_MLK2 cd14148
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 2; STKs catalyze the ...
601-811 3.38e-11

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK2 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK) and is also called MAP3K10. MAP3Ks phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLK2 is abundant in brain, skeletal muscle, and testis. It functions upstream of the MAPK, c-Jun N-terminal kinase. It binds hippocalcin, a calcium-sensor protein that protects neurons against calcium-induced cell death. Both MLK2 and hippocalcin may be associated with the pathogenesis of Parkinson's disease. MLK2 also binds to normal huntingtin (Htt), which is important in neuronal transcription, development, and survival. MLK2 does not bind to the polyglutamine-expanded Htt, which is implicated in the pathogeneis of Huntington's disease, leading to neuronal toxicity. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 271050 [Multi-domain]  Cd Length: 258  Bit Score: 65.01  E-value: 3.38e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    601 LRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVK----LDWMfkssllLDLIKGMKYLHHREFV---HGRLKS 673
Cdd:cd14148   50 LQHPNIIALRGVCLNPPHLCLVMEYARGGALNRALAGKKVPphvlVNWA------VQIARGMNYLHNEAIVpiiHRDLKS 123
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    674 RNCVVDGRF--------VLKVTDYGfndILEMLRLSEEESSMEELLWTAPELLRAprgsRLGSFAGDVYSFAIIMQEVMV 745
Cdd:cd14148  124 SNILILEPIenddlsgkTLKITDFG---LAREWHKTTKMSAAGTYAWMAPEVIRL----SLFSKSSDVWSFGVLLWELLT 196
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 945225    746 RGTPFCMMDLPAQEI---INRLkkpppvyrPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEIFNQFKT 811
Cdd:cd14148  197 GEVPYREIDALAVAYgvaMNKL--------TLPIPSTCPEPFARLLEECWDPDPHGRPDFGSILKRLED 257
STKc_MLK3 cd14147
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3; STKs catalyze the ...
585-812 6.03e-11

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK3 is a mitogen-activated protein kinase kinase kinases (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLK3 activates multiple MAPK pathways and plays a role in apoptosis, proliferation, migration, and differentiation, depending on the cellular context. It is highly expressed in breast cancer cells and its signaling through c-Jun N-terminal kinase has been implicated in the migration, invasion, and malignancy of cancer cells. MLK3 also functions as a negative regulator of Inhibitor of Nuclear Factor-KappaB Kinase (IKK) and consequently, it also impacts inflammation and immunity. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation.The MLK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271049 [Multi-domain]  Cd Length: 267  Bit Score: 64.28  E-value: 6.03e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    585 KSIKSRASdVFEMmkdLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVK----LDWMfkssllLDLIKGMKY 660
Cdd:cd14147   47 ESVRQEAR-LFAM---LAHPNIIALKAVCLEEPNLCLVMEYAAGGPLSRALAGRRVPphvlVNWA------VQIARGMHY 116
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    661 LHHREFV---HGRLKSRN----------CVVDgrFVLKVTDYGfndILEMLRLSEEESSMEELLWTAPELLRAprgSRLG 727
Cdd:cd14147  117 LHCEALVpviHRDLKSNNilllqpiendDMEH--KTLKITDFG---LAREWHKTTQMSAAGTYAWMAPEVIKA---STFS 188
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    728 SFAgDVYSFAIIMQEVMVRGTPFCMMDLPAQEI---INRLkkpppvyrPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDE 804
Cdd:cd14147  189 KGS-DVWSFGVLLWELLTGEVPYRGIDCLAVAYgvaVNKL--------TLPIPSTCPEPFAQLMADCWAQDPHRRPDFAS 259

                 ....*...
gi 945225    805 IFNQFKTF 812
Cdd:cd14147  260 ILQQLEAL 267
PK_ILK cd14057
Pseudokinase domain of Integrin Linked Kinase; The pseudokinase domain shows similarity to ...
582-805 6.08e-11

Pseudokinase domain of Integrin Linked Kinase; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. ILK contains N-terminal ankyrin repeats, a Pleckstrin Homology (PH) domain, and a C-terminal pseudokinase domain. It is a component of the IPP (ILK/PINCH/Parvin) complex that couples beta integrins to the actin cytoskeleton, and plays important roles in cell adhesion, spreading, invasion, and migration. ILK was initially thought to be an active kinase despite the lack of key conserved residues because of in vitro studies showing that it can phosphorylate certain protein substrates. However, in vivo experiments in Caenorhabditis elegans, Drosophila melanogaster, and mice (ILK-null and knock-in) proved that ILK is not an active kinase. In addition to actin cytoskeleton regulation, ILK also influences the microtubule network and mitotic spindle orientation. The pseudokinase domain of ILK binds several adaptor proteins including the parvins and paxillin. The ILK subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270959 [Multi-domain]  Cd Length: 251  Bit Score: 64.05  E-value: 6.08e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    582 GDLKSIKSRasDVFEMMKDLR---HENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQ-DVKLDWMFKSSLLLDLIKG 657
Cdd:cd14057   29 RDVTTRISR--DFNEEYPRLRifsHPNVLPVLGACNSPPNLVVISQYMPYGSLYNVLHEGtGVVVDQSQAVKFALDIARG 106
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    658 MKYLHHREFVHGR--LKSRNCVVDGRFVLKV----TDYGFNDILEMlrlseeessmEELLWTAPELL-RAPrgSRLGSFA 730
Cdd:cd14057  107 MAFLHTLEPLIPRhhLNSKHVMIDEDMTARInmadVKFSFQEPGKM----------YNPAWMAPEALqKKP--EDINRRS 174
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 945225    731 GDVYSFAIIMQEVMVRGTPFCmmDLPAQEIinrLKKPPPVYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEI 805
Cdd:cd14057  175 ADMWSFAILLWELVTREVPFA--DLSNMEI---GMKIALEGLRVTIPPGISPHMCKLMKICMNEDPGKRPKFDMI 244
STKc_IRAK1 cd14159
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 1; ...
596-744 7.33e-11

Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain, and a C-terminal domain; IRAK-4 lacks the C-terminal domain. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK1 plays a role in the activation of IRF3/7, STAT, and NFkB. It mediates IL-6 and IFN-gamma responses following IL-1 and IL-18 stimulation, respectively. It also plays an essential role in IFN-alpha induction downstream of TLR7 and TLR9. The IRAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271061 [Multi-domain]  Cd Length: 296  Bit Score: 64.46  E-value: 7.33e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQD--VKLDWMFKSSLLLDLIKGMKYLHHRE--FVHGRL 671
Cdd:cd14159   44 EKLSRFRHPNIVDLAGYSAQQGNYCLIYVYLPNGSLEDRLHCQVscPCLSWSQRLHVLLGTARAIQYLHSDSpsLIHGDV 123
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    672 KSRNCVVDGRFVLKVTDYGfndILEMLRLSEEESSMEELLWTA----------PELLRAprgSRLGsFAGDVYSFAIIMQ 741
Cdd:cd14159  124 KSSNILLDAALNPKLGDFG---LARFSRRPKQPGMSSTLARTQtvrgtlaylpEEYVKT---GTLS-VEIDVYSFGVVLL 196

                 ...
gi 945225    742 EVM 744
Cdd:cd14159  197 ELL 199
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
596-750 9.27e-11

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 65.42  E-value: 9.27e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILtNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRN 675
Cdd:COG0515   59 RALARLNHPNIVRVYDVGEEDGRPYLVMEYVEGESLADLL-RRRGPLPPAEALRILAQLAEALAAAHAAGIVHRDIKPAN 137
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 945225    676 CVVDGRFVLKVTDYGFNDILEMLRLSEEESSMEELLWTAPELLrapRGSRLGsFAGDVYSFAIIMQEVMVRGTPF 750
Cdd:COG0515  138 ILLTPDGRVKLIDFGIARALGGATLTQTGTVVGTPGYMAPEQA---RGEPVD-PRSDVYSLGVTLYELLTGRPPF 208
PTKc_Aatyk2 cd05086
Catalytic domain of the Protein Tyrosine Kinase, Apoptosis-associated tyrosine kinase 2; PTKs ...
601-805 1.11e-10

Catalytic domain of the Protein Tyrosine Kinase, Apoptosis-associated tyrosine kinase 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Aatyk2 is a member of the Aatyk subfamily of proteins, which are receptor kinases containing a transmembrane segment and a long C-terminal cytoplasmic tail with a catalytic domain. Aatyk2 is also called lemur tyrosine kinase 2 (Lmtk2) or brain-enriched kinase (Brek). It is expressed at high levels in early postnatal brain, and has been shown to play a role in nerve growth factor (NGF) signaling. Studies with knockout mice reveal that Aatyk2 is essential for late stage spermatogenesis. Although it is classified as a PTK based on sequence similarity and the phylogenetic tree, Aatyk2 has been functionally characterized as a serine/threonine kinase. The Aatyk2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270669 [Multi-domain]  Cd Length: 271  Bit Score: 63.73  E-value: 1.11e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    601 LRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKL----DWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNC 676
Cdd:cd05086   54 LQHPNILQCVGQCVEAIPYLLVFEFCDLGDLKTYLANQQEKLrgdsQIMLLQRMACEIAAGLAHMHKHNFLHSDLALRNC 133
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    677 VVDGRFVLKVTDYGF------NDILEmlrlsEEESSMEELLWTAPELLRAPRGSRLG---SFAGDVYSFAIIMQEVMVR- 746
Cdd:cd05086  134 YLTSDLTVKVGDYGIgfsrykEDYIE-----TDDKKYAPLRWTAPELVTSFQDGLLAaeqTKYSNIWSLGVTLWELFENa 208
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    747 GTPFcmMDLPAQEIINRLKKPPPVYRPVVPPEHAPPE-CLQLMKQCWAeAAEQRPTFDEI 805
Cdd:cd05086  209 AQPY--SDLSDREVLNHVIKERQVKLFKPHLEQPYSDrWYEVLQFCWL-SPEKRPTAEEV 265
STKc_CDK7 cd07841
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7; STKs ...
571-766 1.39e-10

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK7 plays essential roles in the cell cycle and in transcription. It associates with cyclin H and MAT1 and acts as a CDK-Activating Kinase (CAK) by phosphorylating and activating cell cycle CDKs (CDK1/2/4/6). In the brain, it activates CDK5. CDK7 is also a component of the general transcription factor TFIIH, which phosphorylates the C-terminal domain (CTD) of RNA polymerase II when it is bound with unphosphorylated DNA, as present in the pre-initiation complex. Following phosphorylation, the CTD dissociates from the DNA which allows transcription initiation. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270833 [Multi-domain]  Cd Length: 298  Bit Score: 63.74  E-value: 1.39e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    571 VWLKKFSLGDFGD---------LKSIKsrasdvfeMMKDLRHENINPLLGFFYDSGMFAIVTEFCSrGSLEDI------- 634
Cdd:cd07841   28 VAIKKIKLGERKEakdginftaLREIK--------LLQELKHPNIIGLLDVFGHKSNINLVFEFME-TDLEKVikdksiv 98
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    635 LTNQDVKldwmfksSLLLDLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGF-----NDILEMlrlseeeSSMEE 709
Cdd:cd07841   99 LTPADIK-------SYMLMTLRGLEYLHSNWILHRDLKPNNLLIASDGVLKLADFGLarsfgSPNRKM-------THQVV 164
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 945225    710 LLW-TAPELLrapRGSRLGSFAGDVYSFAIIMQEVMVRgTPFcmmdLPAQEIINRLKK 766
Cdd:cd07841  165 TRWyRAPELL---FGARHYGVGVDMWSVGCIFAELLLR-VPF----LPGDSDIDQLGK 214
STKc_HAL4_like cd13994
Catalytic domain of Fungal Halotolerance protein 4-like Serine/Threonine kinases; STKs ...
595-807 1.64e-10

Catalytic domain of Fungal Halotolerance protein 4-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of HAL4, Saccharomyces cerevisiae Ptk2/Stk2, and similar fungal proteins. Proteins in this subfamily are involved in regulating ion transporters. In budding and fission yeast, HAL4 promotes potassium ion uptake, which increases cellular resistance to other cations such as sodium, lithium, and calcium ions. HAL4 stabilizes the major high-affinity K+ transporter Trk1 at the plasma membrane under low K+ conditions, which prevents endocytosis and vacuolar degradation. Budding yeast Ptk2 phosphorylates and regulates the plasma membrane H+ ATPase, Pma1. The HAL4-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270896 [Multi-domain]  Cd Length: 265  Bit Score: 63.09  E-value: 1.64e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    595 FEMMKDLRHENINPLLGFFYD-SGMFAIVTEFCSRGSLEDILTNQDvKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKS 673
Cdd:cd13994   48 YIISSKLHHPNIVKVLDLCQDlHGKWCLVMEYCPGGDLFTLIEKAD-SLSLEEKDCFFKQILRGVAYLHSHGIAHRDLKP 126
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    674 RNCVVDGRFVLKVTDYGFNDILEM---LRLSEEESSMEELLWTAPELLrapRGSRLGSFAGDVYSFAIIMQEVMVRGTPF 750
Cdd:cd13994  127 ENILLDEDGVLKLTDFGTAEVFGMpaeKESPMSAGLCGSEPYMAPEVF---TSGSYDGRAVDVWSCGIVLFALFTGRFPW 203
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    751 ---CMMDLPAQEIINRLKKPPPVYRPVVPPEhaPPECLQLMKQCWAEAAEQRPTFDEIFN 807
Cdd:cd13994  204 rsaKKSDSAYKAYEKSGDFTNGPYEPIENLL--PSECRRLIYRMLHPDPEKRITIDEALN 261
PTKc_ALK_LTK cd05036
Catalytic domain of the Protein Tyrosine Kinases, Anaplastic Lymphoma Kinase and Leukocyte ...
595-805 2.11e-10

Catalytic domain of the Protein Tyrosine Kinases, Anaplastic Lymphoma Kinase and Leukocyte Tyrosine Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyr residues in protein substrates. ALK and LTK are orphan receptor PTKs (RTKs) whose ligands are not yet well-defined. ALK appears to play an important role in mammalian neural development as well as visceral muscle differentiation in Drosophila. ALK is aberrantly expressed as fusion proteins, due to chromosomal translocations, in about 60% of anaplastic large cell lymphomas (ALCLs). ALK fusion proteins are also found in rare cases of diffuse large B cell lymphomas (DLBCLs). LTK is mainly expressed in B lymphocytes and neuronal tissues. It is important in cell proliferation and survival. Transgenic mice expressing TLK display retarded growth and high mortality rate. In addition, a polymorphism in mouse and human LTK is implicated in the pathogenesis of systemic lupus erythematosus. RTKs contain an extracellular ligand-binding domain, a transmembrane region, and an intracellular tyr kinase domain. They are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. The ALK/LTK subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270632 [Multi-domain]  Cd Length: 277  Bit Score: 62.79  E-value: 2.11e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    595 FEM----MKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDIL------TNQDVKLDWMFKSSLLLDLIKGMKYLHHR 664
Cdd:cd05036   56 FLMealiMSKFNHPNIVRCIGVCFQRLPRFILLELMAGGDLKSFLrenrprPEQPSSLTMLDLLQLAQDVAKGCRYLEEN 135
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    665 EFVHGRLKSRNCVVD----GRfVLKVTDYGF-NDILEMLRLSEEESSMEELLWTAPELLRAprgsrlGSFAG--DVYSFA 737
Cdd:cd05036  136 HFIHRDIAARNCLLTckgpGR-VAKIGDFGMaRDIYRADYYRKGGKAMLPVKWMPPEAFLD------GIFTSktDVWSFG 208
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    738 IIMQEVMVRGtpfcMMDLPA---QEIIN------RLKkpppvyrpvvppehAPPEC----LQLMKQCWAEAAEQRPTFDE 804
Cdd:cd05036  209 VLLWEIFSLG----YMPYPGksnQEVMEfvtsggRMD--------------PPKNCpgpvYRIMTQCWQHIPEDRPNFST 270

                 .
gi 945225    805 I 805
Cdd:cd05036  271 I 271
PTKc_PDGFR_alpha cd05105
Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor alpha; ...
643-802 2.92e-10

Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor alpha; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. PDGFR alpha is a receptor PTK (RTK) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding to its ligands, the PDGFs, leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. PDGFR alpha forms homodimers or heterodimers with PDGFR beta, depending on the nature of the PDGF ligand. PDGF-AA, PDGF-AB, and PDGF-CC induce PDGFR alpha homodimerization. PDGFR signaling plays many roles in normal embryonic development and adult physiology. PDGFR alpha signaling is important in the formation of lung alveoli, intestinal villi, mesenchymal dermis, and hair follicles, as well as in the development of oligodendrocytes, retinal astrocytes, neural crest cells, and testicular cells. Aberrant PDGFR alpha expression is associated with some human cancers. Mutations in PDGFR alpha have been found within a subset of gastrointestinal stromal tumors (GISTs). An active fusion protein FIP1L1-PDGFR alpha, derived from interstitial deletion, is associated with idiopathic hypereosinophilic syndrome and chronic eosinophilic leukemia. The PDGFR alpha subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173653 [Multi-domain]  Cd Length: 400  Bit Score: 63.50  E-value: 2.92e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    643 DWMFKSSLLLDLI-------KGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGF-NDILEMLRLSEEESSMEELLWTA 714
Cdd:cd05105  228 DDGSEGLTTLDLLsftyqvaRGMEFLASKNCVHRDLAARNVLLAQGKIVKICDFGLaRDIMHDSNYVSKGSTFLPVKWMA 307
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    715 PELLRaprgSRLGSFAGDVYSFAIIMQEVM-VRGTPFCMMDLPAQeIINRLKKPPPVYRPvvppEHAPPECLQLMKQCWA 793
Cdd:cd05105  308 PESIF----DNLYTTLSDVWSYGILLWEIFsLGGTPYPGMIVDST-FYNKIKSGYRMAKP----DHATQEVYDIMVKCWN 378

                 ....*....
gi 945225    794 EAAEQRPTF 802
Cdd:cd05105  379 SEPEKRPSF 387
PTKc_DDR2 cd05095
Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 2; PTKs catalyze ...
580-805 3.05e-10

Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. DDR2 is a receptor PTK (RTK) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDR2 results in a slow but sustained receptor activation. DDR2 binds mostly to fibrillar collagens as well as collagen X. DDR2 is widely expressed in many tissues with the highest levels found in skeletal muscle, skin, kidney and lung. It is important in cell proliferation and development. Mice, with a deletion of DDR2, suffer from dwarfism and delayed healing of epidermal wounds. DDR2 also contributes to collagen (type I) regulation by inhibiting fibrillogenesis and altering the morphology of collagen fibers. It is also expressed in immature dendritic cells (DCs), where it plays a role in DC activation and function. The DDR2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 270677 [Multi-domain]  Cd Length: 297  Bit Score: 62.70  E-value: 3.05e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    580 DFgdLKSIKsrasdvfeMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKLDWMFKSSLLL------- 652
Cdd:cd05095   65 DF--LKEIK--------IMSRLKDPNIIRLLAVCITDDPLCMITEYMENGDLNQFLSRQQPEGQLALPSNALTvsysdlr 134
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    653 ----DLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGFNDIL---EMLRlsEEESSMEELLWTAPELLraprgsR 725
Cdd:cd05095  135 fmaaQIASGMKYLSSLNFVHRDLATRNCLVGKNYTIKIADFGMSRNLysgDYYR--IQGRAVLPIRWMSWESI------L 206
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    726 LGSF--AGDVYSFAIIMQEVMV--RGTPFCMM-DLPAQEIINRLKKPPPVYRPVVPPEHAPPECLQLMKQCWAEAAEQRP 800
Cdd:cd05095  207 LGKFttASDVWAFGVTLWETLTfcREQPYSQLsDEQVIENTGEFFRDQGRQTYLPQPALCPDSVYKLMLSCWRRDTKDRP 286

                 ....*
gi 945225    801 TFDEI 805
Cdd:cd05095  287 SFQEI 291
Pkinase pfam00069
Protein kinase domain;
596-807 3.54e-10

Protein kinase domain;


Pssm-ID: 459660 [Multi-domain]  Cd Length: 217  Bit Score: 61.11  E-value: 3.54e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225      596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTnqdvkldwmfkssllldlikgmkylhhrefVHGRLKSRn 675
Cdd:pfam00069   50 KILKKLNHPNIVRLYDAFEDKDNLYLVLEYVEGGSLFDLLS------------------------------EKGAFSER- 98
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225      676 cvvDGRFVLKvtdygfnDILEMLRLSEEESSMEE-LLWTAPELLRAPRGSRlgsfAGDVYSFAIIMQEVMVRGTPFCMMD 754
Cdd:pfam00069   99 ---EAKFIMK-------QILEGLESGSSLTTFVGtPWYMAPEVLGGNPYGP----KVDVWSLGCILYELLTGKPPFPGIN 164
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|...
gi 945225      755 LPAQEIINRLKKpppvYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEIFN 807
Cdd:pfam00069  165 GNEIYELIIDQP----YAFPELPSNLSEEAKDLLKKLLKKDPSKRLTATQALQ 213
PTKc_VEGFR1 cd14207
Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; ...
630-805 3.69e-10

Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR1 (or Flt1) binds VEGFA, VEGFB, and placenta growth factor (PLGF). It regulates monocyte and macrophage migration, vascular permeability, haematopoiesis, and the recruitment of haematopietic progenitor cells from the bone marrow. VEGFR1 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271109 [Multi-domain]  Cd Length: 340  Bit Score: 62.71  E-value: 3.69e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    630 SLEDILTNQDVKLDWMFKSSLLLDLI-------KGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGF-NDILEMLRLS 701
Cdd:cd14207  158 SLSDVEEEEEDSGDFYKRPLTMEDLIsysfqvaRGMEFLSSRKCIHRDLAARNILLSENNVVKICDFGLaRDIYKNPDYV 237
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    702 EEESSMEELLWTAPELLRaprgSRLGSFAGDVYSFAIIMQEVMVRGT---PFCMMDlpaQEIINRLKKPPPVYRPvvppE 778
Cdd:cd14207  238 RKGDARLPLKWMAPESIF----DKIYSTKSDVWSYGVLLWEIFSLGAspyPGVQID---EDFCSKLKEGIRMRAP----E 306
                        170       180
                 ....*....|....*....|....*..
gi 945225    779 HAPPECLQLMKQCWAEAAEQRPTFDEI 805
Cdd:cd14207  307 FATSEIYQIMLDCWQGDPNERPRFSEL 333
PTKc_Syk cd05116
Catalytic domain of the Protein Tyrosine Kinase, Spleen tyrosine kinase; PTKs catalyze the ...
584-802 3.95e-10

Catalytic domain of the Protein Tyrosine Kinase, Spleen tyrosine kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Syk is a cytoplasmic (or nonreceptor) PTK containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. Syk was first cloned from the spleen, and its function in hematopoietic cells is well-established. It is involved in the signaling downstream of activated receptors (including B-cell and Fc receptors) that contain ITAMs (immunoreceptor tyr activation motifs), leading to processes such as cell proliferation, differentiation, survival, adhesion, migration, and phagocytosis. More recently, Syk expression has been detected in other cell types (including epithelial cells, vascular endothelial cells, neurons, hepatocytes, and melanocytes), suggesting a variety of biological functions in non-immune cells. Syk plays a critical role in maintaining vascular integrity and in wound healing during embryogenesis. It also regulates Vav3, which is important in osteoclast function including bone development. In breast epithelial cells, where Syk acts as a negative regulator for EGFR signaling, loss of Syk expression is associated with abnormal proliferation during cancer development suggesting a potential role as a tumor suppressor. In mice, Syk has been shown to inhibit malignant transformation of mammary epithelial cells induced with murine mammary tumor virus (MMTV). The Syk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133247 [Multi-domain]  Cd Length: 257  Bit Score: 61.90  E-value: 3.95e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    584 LKSIKSRASDvfEMMKD--LRHENINPLLGFFYDSGMFAI--------VTEFCSRGSLEDILT-NQDVKLDWMfkSSLLL 652
Cdd:cd05116   27 VKILKNEAND--PALKDelLREANVMQQLDNPYIVRMIGIceaeswmlVMEMAELGPLNKFLQkNRHVTEKNI--TELVH 102
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    653 DLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGFNDILEMLRLSEEESSMEE--LLWTAPELLRAPRGSRlgsfA 730
Cdd:cd05116  103 QVSMGMKYLEESNFVHRDLAARNVLLVTQHYAKISDFGLSKALRADENYYKAQTHGKwpVKWYAPECMNYYKFSS----K 178
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 945225    731 GDVYSFAIIMQEVMVRG-TPFCMMDlpAQEIINRLKKPPPVYRPvvppEHAPPECLQLMKQCWAEAAEQRPTF 802
Cdd:cd05116  179 SDVWSFGVLMWEAFSYGqKPYKGMK--GNEVTQMIEKGERMECP----AGCPPEMYDLMKLCWTYDVDERPGF 245
STKc_IRAK4 cd14158
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 4; ...
596-744 4.10e-10

Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain, and a C-terminal domain; IRAK-4 lacks the C-terminal domain. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK4 plays a critical role in NFkB activation by its interaction with MyD88, which acts as a scaffold that enables IRAK4 to phosphorylate and activate IRAK1 and/or IRAK2. It also plays an important role in type I IFN production induced by TLR7/8/9. The IRAK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271060 [Multi-domain]  Cd Length: 288  Bit Score: 62.13  E-value: 4.10e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILT--NQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKS 673
Cdd:cd14158   66 QVMAKCQHENLVELLGYSCDGPQLCLVYTYMPNGSLLDRLAclNDTPPLSWHMRCKIAQGTANGINYLHENNHIHRDIKS 145
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 945225    674 RNCVVDGRFVLKVTDYGFNDILEM-LRLSEEESSMEELLWTAPELLRAPRGSRLgsfagDVYSFAIIMQEVM 744
Cdd:cd14158  146 ANILLDETFVPKISDFGLARASEKfSQTIMTERIVGTTAYMAPEALRGEITPKS-----DIFSFGVVLLEII 212
STKc_CDKL cd07833
Catalytic domain of Cyclin-Dependent protein Kinase Like Serine/Threonine Kinases; STKs ...
568-749 5.48e-10

Catalytic domain of Cyclin-Dependent protein Kinase Like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDKL1-5 and similar proteins. Some CDKLs, like CDKL1 and CDKL3, may be implicated in transformation and others, like CDKL3 and CDKL5, are associated with mental retardation when impaired. CDKL2 plays a role in learning and memory. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270827 [Multi-domain]  Cd Length: 288  Bit Score: 61.56  E-value: 5.48e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    568 GDWVWLKKFSLGDfgDLKSIKSRASDVFEMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDI------LTNQDVK 641
Cdd:cd07833   26 GEIVAIKKFKESE--DDEDVKKTALREVKVLRQLRHENIVNLKEAFRRKGRLYLVFEYVERTLLELLeaspggLPPDAVR 103
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    642 ldwmfksSLLLDLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGFNDILEMlRLSEEESSMEELLW-TAPELLra 720
Cdd:cd07833  104 -------SYIWQLLQAIAYCHSHNIIHRDIKPENILVSESGVLKLCDFGFARALTA-RPASPLTDYVATRWyRAPELL-- 173
                        170       180       190
                 ....*....|....*....|....*....|...
gi 945225    721 prgsrLGS----FAGDVYSFAIIMQEvMVRGTP 749
Cdd:cd07833  174 -----VGDtnygKPVDVWAIGCIMAE-LLDGEP 200
STKc_ULK3 cd14121
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 3; STKs catalyze the ...
596-807 5.76e-10

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK3 mRNA is up-regulated in fibroblasts after Ras-induced senescence, and its overexpression induces both autophagy and senescence in a fibroblast cell line. ULK3, through its kinase activity, positively regulates Gli proteins, mediators of the Sonic hedgehog (Shh) signaling pathway that is implicated in tissue homeostasis maintenance and neurogenesis. It is inhibited by binding to Suppressor of Fused (Sufu). The ULK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271023 [Multi-domain]  Cd Length: 252  Bit Score: 61.15  E-value: 5.76e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDvKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRN 675
Cdd:cd14121   47 ELLKKLKHPHIVELKDFQWDEEHIYLIMEYCSGGDLSRFIRSRR-TLPESTVRRFLQQLASALQFLREHNISHMDLKPQN 125
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    676 CVVDGRF--VLKVTDYGF------NDILEMLRlseeessmEELLWTAPE-LLRAPRGSRLgsfagDVYSFAIIMQEVMVR 746
Cdd:cd14121  126 LLLSSRYnpVLKLADFGFaqhlkpNDEAHSLR--------GSPLYMAPEmILKKKYDARV-----DLWSVGVILYECLFG 192
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 945225    747 GTPFCMMDLpaQEIINRLKKPPPVYRPVVPpeHAPPECLQLMKQCWAEAAEQRPTFDEIFN 807
Cdd:cd14121  193 RAPFASRSF--EELEEKIRSSKPIEIPTRP--ELSADCRDLLLRLLQRDPDRRISFEEFFA 249
PTKc_TrkA cd05092
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase A; PTKs catalyze ...
596-810 6.12e-10

Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase A; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. TrkA is a receptor PTK (RTK) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding of TrkA to its ligand, nerve growth factor (NGF), results in receptor oligomerization and activation of the catalytic domain. TrkA is expressed mainly in neural-crest-derived sensory and sympathetic neurons of the peripheral nervous system, and in basal forebrain cholinergic neurons of the central nervous system. It is critical for neuronal growth, differentiation and survival. Alternative TrkA splicing has been implicated as a pivotal regulator of neuroblastoma (NB) behavior. Normal TrkA expression is associated with better NB prognosis, while the hypoxia-regulated TrkAIII splice variant promotes NB pathogenesis and progression. Aberrant TrkA expression has also been demonstrated in non-neural tumors including prostate, breast, lung, and pancreatic cancers. The TrkA subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270674 [Multi-domain]  Cd Length: 280  Bit Score: 61.52  E-value: 6.12e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDIL-----------TNQDVKLDWMFKSSLL---LDLIKGMKYL 661
Cdd:cd05092   59 ELLTVLQHQHIVRFYGVCTEGEPLIMVFEYMRHGDLNRFLrshgpdakildGGEGQAPGQLTLGQMLqiaSQIASGMVYL 138
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    662 HHREFVHGRLKSRNCVVDGRFVLKVTDYGFN-DILEMLRLSEEESSMEELLWTAPELLRaprgSRLGSFAGDVYSFAIIM 740
Cdd:cd05092  139 ASLHFVHRDLATRNCLVGQGLVVKIGDFGMSrDIYSTDYYRVGGRTMLPIRWMPPESIL----YRKFTTESDIWSFGVVL 214
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 945225    741 QEVMVRGTP--FCMMDLPAQEIINRLKKPPPVYRpvvppehAPPECLQLMKQCWAEAAEQRPTFDEIFNQFK 810
Cdd:cd05092  215 WEIFTYGKQpwYQLSNTEAIECITQGRELERPRT-------CPPEVYAIMQGCWQREPQQRHSIKDIHSRLQ 279
STKc_Nek cd08215
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; ...
596-808 6.61e-10

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Nek family is composed of 11 different mammalian members (Nek1-11) with similarity to the catalytic domain of Aspergillus nidulans NIMA kinase, the founding member of the Nek family, which was identified in a screen for cell cycle mutants that were prevented from entering mitosis. Neks contain a conserved N-terminal catalytic domain and a more divergent C-terminal regulatory region of various sizes and structures. They are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270855 [Multi-domain]  Cd Length: 258  Bit Score: 60.94  E-value: 6.61e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVK---------LDWMFKSSLlldlikGMKYLHHREF 666
Cdd:cd08215   51 KLLSKLKHPNIVKYYESFEENGKLCIVMEYADGGDLAQKIKKQKKKgqpfpeeqiLDWFVQICL------ALKYLHSRKI 124
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    667 VHGRLKSRNCVVDGRFVLKVTDYGFNDILE----MLRlseeessmeellwT--------APELLRaprgSRLGSFAGDVY 734
Cdd:cd08215  125 LHRDLKTQNIFLTKDGVVKLGDFGISKVLEsttdLAK-------------TvvgtpyylSPELCE----NKPYNYKSDIW 187
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    735 SFAIIMQEVMVRGTPFCMMDLPA--QEIINRlkkpppvyrpvvppEHAP-PECL-----QLMKQCWAEAAEQRPTFDEIF 806
Cdd:cd08215  188 ALGCVLYELCTLKHPFEANNLPAlvYKIVKG--------------QYPPiPSQYsselrDLVNSMLQKDPEKRPSANEIL 253

                 ..
gi 945225    807 NQ 808
Cdd:cd08215  254 SS 255
PKc_Myt1 cd14050
Catalytic domain of the Dual-specificity protein kinase, Myt1; Dual-specificity PKs catalyze ...
575-807 7.55e-10

Catalytic domain of the Dual-specificity protein kinase, Myt1; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. Myt1 is a cytoplasmic cell cycle checkpoint kinase that can keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of N-terminal thr (T14) and tyr (Y15) residues, leading to the delay of meiosis I entry. Meiotic progression is ensured by a two-step inhibition and downregulation of Myt1 by CDK1/XRINGO and p90Rsk during oocyte maturation. In addition, Myt1 targets cyclin B1/B2 and is essential for Golgi and ER assembly during telophase. In Drosophila, Myt1 may be a downstream target of Notch during eye development. The Myt1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270952 [Multi-domain]  Cd Length: 249  Bit Score: 60.79  E-value: 7.55e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    575 KFSLGDFGDLKSIKSRASDVFEMMKDLRHENINPLLGFFYDSGMFAIVTEFCsRGSLEDILTNQDvKLDWMFKSSLLLDL 654
Cdd:cd14050   32 KRSRSRFRGEKDRKRKLEEVERHEKLGEHPNCVRFIKAWEEKGILYIQTELC-DTSLQQYCEETH-SLPESEVWNILLDL 109
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    655 IKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGFndILEMLRLSEEESSMEELLWTAPELLRaprgsrlGSF--AGD 732
Cdd:cd14050  110 LKGLKHLHDHGLIHLDIKPANIFLSKDGVCKLGDFGL--VVELDKEDIHDAQEGDPRYMAPELLQ-------GSFtkAAD 180
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    733 VYSFAIIMQEVMvrgtpfCMMDLPA--------------QEIINRLkkpppvyrpvvppehaPPECLQLMKQCWAEAAEQ 798
Cdd:cd14050  181 IFSLGITILELA------CNLELPSggdgwhqlrqgylpEEFTAGL----------------SPELRSIIKLMMDPDPER 238

                 ....*....
gi 945225    799 RPTFDEIFN 807
Cdd:cd14050  239 RPTAEDLLA 247
PTKc_Kit cd05104
Catalytic domain of the Protein Tyrosine Kinase, Kit; PTKs catalyze the transfer of the ...
627-805 7.71e-10

Catalytic domain of the Protein Tyrosine Kinase, Kit; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Kit is important in the development of melanocytes, germ cells, mast cells, hematopoietic stem cells, the interstitial cells of Cajal, and the pacemaker cells of the GI tract. Kit signaling is involved in major cellular functions including cell survival, proliferation, differentiation, adhesion, and chemotaxis. Mutations in Kit, which result in constitutive ligand-independent activation, are found in human cancers such as gastrointestinal stromal tumor (GIST) and testicular germ cell tumor (TGCT). The aberrant expression of Kit and/or SCF is associated with other tumor types such as systemic mastocytosis and cancers of the breast, neurons, lung, prostate, colon, and rectum. Although the structure of the human Kit catalytic domain is known, it is excluded from this specific alignment model because it contains a deletion in its sequence. Kit is a member of the Platelet Derived Growth Factor Receptor (PDGFR) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of Kit to its ligand, the stem-cell factor (SCF), leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. The Kit subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270682 [Multi-domain]  Cd Length: 375  Bit Score: 62.23  E-value: 7.71e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    627 SRGSLEDILTNQDVKLDWMFKSSLLLDL----------IKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGF-NDIL 695
Cdd:cd05104  186 RRGVRSGSYVDQDVTSEILEEDELALDTedllsfsyqvAKGMEFLASKNCIHRDLAARNILLTHGRITKICDFGLaRDIR 265
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    696 EMLRLSEEESSMEELLWTAPELLRaprgSRLGSFAGDVYSFAIIMQEVMVRG-TPFcmmdlPAQEIINRLKKPPPVYRPV 774
Cdd:cd05104  266 NDSNYVVKGNARLPVKWMAPESIF----ECVYTFESDVWSYGILLWEIFSLGsSPY-----PGMPVDSKFYKMIKEGYRM 336
                        170       180       190
                 ....*....|....*....|....*....|.
gi 945225    775 VPPEHAPPECLQLMKQCWAEAAEQRPTFDEI 805
Cdd:cd05104  337 DSPEFAPSEMYDIMRSCWDADPLKRPTFKQI 367
STKc_PLK3 cd14189
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 3; STKs catalyze the ...
596-806 8.36e-10

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK3, also called Prk or Fnk (FGF-inducible kinase), regulates angiogenesis and responses to DNA damage. Activated PLK3 mediates Chk2 phosphorylation by ATM and the resulting checkpoint activation. PLK3 phosphorylates DNA polymerase delta and may be involved in DNA repair. It also inhibits Cdc25c, thereby regulating the onset of mitosis. The PLK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271091 [Multi-domain]  Cd Length: 255  Bit Score: 60.71  E-value: 8.36e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKLDWMFKSsLLLDLIKGMKYLHHREFVHGRLKSRN 675
Cdd:cd14189   53 ELHRDLHHKHVVKFSHHFEDAENIYIFLELCSRKSLAHIWKARHTLLEPEVRY-YLKQIISGLKYLHLKGILHRDLKLGN 131
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    676 CVVDGRFVLKVTDYGFNDILEMLRlSEEESSMEELLWTAPE-LLRAPRGSRlgsfaGDVYSFAIIMQEVMVRGTPFCMMD 754
Cdd:cd14189  132 FFINENMELKVGDFGLAARLEPPE-QRKKTICGTPNYLAPEvLLRQGHGPE-----SDVWSLGCVMYTLLCGNPPFETLD 205
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 945225    755 LpaQEIINRLKKpppvyrpvvpPEHAPPECL-----QLMKQCWAEAAEQRPTFDEIF 806
Cdd:cd14189  206 L--KETYRCIKQ----------VKYTLPASLslparHLLAGILKRNPGDRLTLDQIL 250
PK_IRAK3 cd14160
Pseudokinase domain of Interleukin-1 Receptor Associated Kinase 3; The pseudokinase domain ...
565-807 8.87e-10

Pseudokinase domain of Interleukin-1 Receptor Associated Kinase 3; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain (a pseudokinase in the case of IRAK3), and a C-terminal domain; IRAK-4 lacks the C-terminal domain. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK3 (or IRAK-M) is the only IRAK that does not show kinase activity. It is found only in monocytes and macrophages in humans, and functions as a negative regulator of TLR signaling including TLR-2 induced p38 activation. It also negatively regulates the alternative NFkB pathway in a TLR-2 specific manner. IRAK3 is downregulated in the monocytes of obese people, and is associated with high SOD2, a marker of mitochondrial oxidative stress. It is an important inhibitor of inflammation in association with obesity and metabolic syndrome. The IRAK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271062 [Multi-domain]  Cd Length: 276  Bit Score: 61.05  E-value: 8.87e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    565 IYEGDW----VWLKKFSLGDFGDLKSIKSRASDVFEMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDIL--TNQ 638
Cdd:cd14160    9 VYRVRIgnrsYAVKLFKQEKKMQWKKHWKRFLSELEVLLLFQHPNILELAAYFTETEKFCLVYPYMQNGTLFDRLqcHGV 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    639 DVKLDWMFKSSLLLDLIKGMKYLHHRE---FVHGRLKSRNCVVDGRFVLKVTDYGFNDILEMLRLSE----EESSMEELL 711
Cdd:cd14160   89 TKPLSWHERINILIGIAKAIHYLHNSQpctVICGNISSANILLDDQMQPKLTDFALAHFRPHLEDQSctinMTTALHKHL 168
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    712 WTAPEllRAPRGSRLgSFAGDVYSFAIIMQEVM-----VRGTP--FCMMDLpAQEIINRLKKPPPVYRPVVPPEHAPP-- 782
Cdd:cd14160  169 WYMPE--EYIRQGKL-SVKTDVYSFGIVIMEVLtgckvVLDDPkhLQLRDL-LHELMEKRGLDSCLSFLDLKFPPCPRnf 244
                        250       260
                 ....*....|....*....|....*..
gi 945225    783 --ECLQLMKQCWAEAAEQRPTFDEIFN 807
Cdd:cd14160  245 saKLFRLAGRCTATKAKLRPDMDEVLQ 271
STKc_LRRK2 cd14068
Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 2; STKs catalyze ...
564-807 1.06e-09

Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRK2 is one of two vertebrate LRRKs which show complementary expression in the brain. Mutations in LRRK2, found in the kinase, ROC-COR, and WD40 domains, are linked to both familial and sporadic forms of Parkinson's disease. The most prevalent mutation, G2019S located in the activation loop of the kinase domain, increases kinase activity. The R1441C/G mutations in the GTPase domain have also been reported to influence kinase activity. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. The LRRK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270970 [Multi-domain]  Cd Length: 252  Bit Score: 60.35  E-value: 1.06e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    564 AIYEGDWVWLKKFSlgdfgdlKSIKSRA-SDVFEMMKDLRHENINPLLGFFYDSGMfaIVTEFCSRGSLEDILTNQDVKL 642
Cdd:cd14068   13 AVYRGEDVAVKIFN-------KHTSFRLlRQELVVLSHLHHPSLVALLAAGTAPRM--LVMELAPKGSLDALLQQDNASL 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    643 DWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNCVV-----DGRFVLKVTDYGfndILEMLRLSEEESSMEELLWTAPEL 717
Cdd:cd14068   84 TRTLQHRIALHVADGLRYLHSAMIIYRDLKPHNVLLftlypNCAIIAKIADYG---IAQYCCRMGIKTSEGTPGFRAPEV 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    718 lraPRGSRLGSFAGDVYSFAIIMQEVMVRGTPFCM-MDLPAQ----EIINRLKKPPPVYRPvvppehAP-PECLQLMKQC 791
Cdd:cd14068  161 ---ARGNVIYNQQADVYSFGLLLYDILTCGERIVEgLKFPNEfdelAIQGKLPDPVKEYGC------APwPGVEALIKDC 231
                        250
                 ....*....|....*.
gi 945225    792 WAEAAEQRPTFDEIFN 807
Cdd:cd14068  232 LKENPQCRPTSAQVFD 247
STKc_PLK cd14099
Catalytic domain of the Serine/Threonine Kinases, Polo-like kinases; STKs catalyze the ...
599-805 1.09e-09

Catalytic domain of the Serine/Threonine Kinases, Polo-like kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. PLKs derive their names from homology to polo, a kinase first identified in Drosophila. There are five mammalian PLKs (PLK1-5) from distinct genes. There is good evidence that PLK1 may function as an oncogene while PLK2-5 have tumor suppressive properties. PLK1 functions as a positive regulator of mitosis, meiosis, and cytokinesis. PLK2 functions in G1 progression, S-phase arrest, and centriole duplication. PLK3 regulates angiogenesis and responses to DNA damage. PLK4 is required for late mitotic progression, cell survival, and embryonic development. PLK5 was first identified as a pseudogene containing a stop codon within the kinase domain, however, both murine and human genes encode expressed proteins. PLK5 functions in cell cycle arrest.


Pssm-ID: 271001 [Multi-domain]  Cd Length: 258  Bit Score: 60.26  E-value: 1.09e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    599 KDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDI------LTNQDVKLdwmfkssLLLDLIKGMKYLHHREFVHGRLK 672
Cdd:cd14099   56 RSLKHPNIVKFHDCFEDEENVYILLELCSNGSLMELlkrrkaLTEPEVRY-------FMRQILSGVKYLHSNRIIHRDLK 128
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    673 SRNCVVDGRFVLKVTDYGFNDILEML--RLSeeessmeellwT--------APELLRAPRGSrlgSFAGDVYSFAIIMQE 742
Cdd:cd14099  129 LGNLFLDENMNVKIGDFGLAARLEYDgeRKK-----------TlcgtpnyiAPEVLEKKKGH---SFEVDIWSLGVILYT 194
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 945225    743 VMVRGTPFCMMDLpaQEIINRLKKPPPVYRPVVppeHAPPECLQLMKQCWAEAAEQRPTFDEI 805
Cdd:cd14099  195 LLVGKPPFETSDV--KETYKRIKKNEYSFPSHL---SISDEAKDLIRSMLQPDPTKRPSLDEI 252
PTKc_Musk cd05050
Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase; PTKs catalyze the ...
584-805 1.10e-09

Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Musk is a receptor PTK (RTK) containing an extracellular region with four immunoglobulin-like domains and a cysteine-rich cluster, a transmembrane segment, and an intracellular catalytic domain. Musk is expressed and concentrated in the postsynaptic membrane in skeletal muscle. It is essential for the establishment of the neuromuscular junction (NMJ), a peripheral synapse that conveys signals from motor neurons to muscle cells. Agrin, a large proteoglycan released from motor neurons, stimulates Musk autophosphorylation and activation, leading to the clustering of acetylcholine receptors (AChRs). To date, there is no evidence to suggest that agrin binds directly to Musk. Mutations in AChR, Musk and other partners are responsible for diseases of the NMJ, such as the autoimmune syndrome myasthenia gravis. The Musk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133181 [Multi-domain]  Cd Length: 288  Bit Score: 61.00  E-value: 1.10e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    584 LKSIKSRASDvfEMMKDLRHE----------NINPLLGFFYDSGMFAIVTEFCSRGSLEDIL-------TNQDVKLDWMF 646
Cdd:cd05050   40 VKMLKEEASA--DMQADFQREaalmaefdhpNIVKLLGVCAVGKPMCLLFEYMAYGDLNEFLrhrspraQCSLSHSTSSA 117
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    647 KSSLL--------------LDLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGFN-DILEMLRLSEEESSMEELL 711
Cdd:cd05050  118 RKCGLnplplscteqlciaKQVAAGMAYLSERKFVHRDLATRNCLVGENMVVKIADFGLSrNIYSADYYKASENDAIPIR 197
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    712 WTAPELLRAPRGSRlgsfAGDVYSFAIIMQEVMVRG-TPFCMMdlPAQEIINRLKKpppvYRPVVPPEHAPPECLQLMKQ 790
Cdd:cd05050  198 WMPPESIFYNRYTT----ESDVWAYGVVLWEIFSYGmQPYYGM--AHEEVIYYVRD----GNVLSCPDNCPLELYNLMRL 267
                        250
                 ....*....|....*
gi 945225    791 CWAEAAEQRPTFDEI 805
Cdd:cd05050  268 CWSKLPSDRPSFASI 282
STKc_IRAK2 cd14157
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 2; ...
603-686 1.58e-09

Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain, and a C-terminal domain; IRAK-4 lacks the C-terminal domain. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK2 plays a role in mediating NFkB activation by TLR3, TLR4, and TLR8. It is specifically targeted by the viral protein A52, which is important for virulence, to inhibit all IL-1/TLR pathways, indicating that IRAK2 has a predominant role in NFkB activation. It is redundant with IRAK1 in early signaling but is critical for late and sustained activation. The IRAK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271059 [Multi-domain]  Cd Length: 289  Bit Score: 60.24  E-value: 1.58e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    603 HENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVK--LDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNCVVDG 680
Cdd:cd14157   51 HPNILPLLGFCVESDCHCLIYPYMPNGSLQDRLQQQGGShpLPWEQRLSISLGLLKAVQHLHNFGILHGNIKSSNVLLDG 130

                 ....*.
gi 945225    681 RFVLKV 686
Cdd:cd14157  131 NLLPKL 136
PTKc_HER4 cd05110
Catalytic domain of the Protein Tyrosine Kinase, HER4; PTKs catalyze the transfer of the ...
597-809 1.62e-09

Catalytic domain of the Protein Tyrosine Kinase, HER4; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. HER4 (ErbB4) is a member of the EGFR (HER, ErbB) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Ligands that bind HER4 fall into two groups, the neuregulins (or heregulins) and some EGFR (HER1) ligands including betacellulin, HBEGF, and epiregulin. All four neuregulins (NRG1-4) interact with HER4. Upon ligand binding, HER4 forms homo- or heterodimers with other HER proteins. HER4 is essential in embryonic development. It is implicated in mammary gland, cardiac, and neural development. As a postsynaptic receptor of NRG1, HER4 plays an important role in synaptic plasticity and maturation. The impairment of NRG1/HER4 signaling may contribute to schizophrenia. The HER4 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173655 [Multi-domain]  Cd Length: 303  Bit Score: 60.47  E-value: 1.62e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFFYdSGMFAIVTEFCSRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNC 676
Cdd:cd05110   62 IMASMDHPHLVRLLGVCL-SPTIQLVTQLMPHGCLLDYVHEHKDNIGSQLLLNWCVQIAKGMMYLEERRLVHRDLAARNV 140
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    677 VVDGRFVLKVTDYGFNDILEM-LRLSEEESSMEELLWTAPELLRaprgSRLGSFAGDVYSFAIIMQEVMV-RGTPFcmMD 754
Cdd:cd05110  141 LVKSPNHVKITDFGLARLLEGdEKEYNADGGKMPIKWMALECIH----YRKFTHQSDVWSYGVTIWELMTfGGKPY--DG 214
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 945225    755 LPAQEIINRLKKPPPVYRpvvppehaPPEC----LQLMKQCWAEAAEQRPTFDEIFNQF 809
Cdd:cd05110  215 IPTREIPDLLEKGERLPQ--------PPICtidvYMVMVKCWMIDADSRPKFKELAAEF 265
STKc_Nek11 cd08222
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
567-695 1.69e-09

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 11; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek11 is involved, through direct phosphorylation, in regulating the degradation of Cdc25A (Cell Division Cycle 25 homolog A), which plays a role in cell cycle progression and in activating cyclin dependent kinases. Nek11 is activated by CHK1 (CHeckpoint Kinase 1) and may be involved in the G2/M checkpoint. Nek11 may also play a role in the S-phase checkpoint as well as in DNA replication and genotoxic stress responses. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270861 [Multi-domain]  Cd Length: 260  Bit Score: 59.74  E-value: 1.69e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    567 EGDWVWLKKFSLGDFGDLKSIKsrASDVFEMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILtNQDVKLDWMF 646
Cdd:cd08222   27 DEELKVLKEISVGELQPDETVD--ANREAKLLSKLDHPAIVKFHDSFVEKESFCIVTEYCEGGDLDDKI-SEYKKSGTTI 103
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 945225    647 KSSLLLD----LIKGMKYLHHREFVHGRLKSRNcVVDGRFVLKVTDYGFNDIL 695
Cdd:cd08222  104 DENQILDwfiqLLLAVQYMHERRILHRDLKAKN-IFLKNNVIKVGDFGISRIL 155
STKc_Cdc7_like cd06627
Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs ...
568-690 2.29e-09

Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily include Schizosaccharomyces pombe Cdc7, Saccharomyces cerevisiae Cdc15, Arabidopsis thaliana mitogen-activated protein kinase kinase kinase (MAPKKK) epsilon, and related proteins. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Fission yeast Cdc7 is essential for cell division by playing a key role in the initiation of septum formation and cytokinesis. Budding yeast Cdc15 functions to coordinate mitotic exit with cytokinesis. Arabidopsis MAPKKK epsilon is required for pollen development in the plasma membrane. The Cdc7-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270797 [Multi-domain]  Cd Length: 254  Bit Score: 59.55  E-value: 2.29e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    568 GDWVWLKKFSLGDF--GDLKSIKSRAsdvfEMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDV---KL 642
Cdd:cd06627   25 GEFVAIKQISLEKIpkSDLKSVMGEI----DLLKKLNHPNIVKYIGSVKTKDSLYIILEYVENGSLASIIKKFGKfpeSL 100
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 945225    643 DWMFKSSLLldliKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYG 690
Cdd:cd06627  101 VAVYIYQVL----EGLAYLHEQGVIHRDIKGANILTTKDGLVKLADFG 144
PTKc_HER2 cd05109
Catalytic domain of the Protein Tyrosine Kinase, HER2; PTKs catalyze the transfer of the ...
609-814 2.56e-09

Catalytic domain of the Protein Tyrosine Kinase, HER2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. HER2 (ErbB2, HER2/neu) is a member of the EGFR (HER, ErbB) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. HER2 does not bind to any known EGFR subfamily ligands, but contributes to the kinase activity of all possible heterodimers. It acts as the preferred partner of other ligand-bound EGFR proteins and functions as a signal amplifier, with the HER2-HER3 heterodimer being the most potent pair in mitogenic signaling. HER2 plays an important role in cell development, proliferation, survival and motility. Overexpression of HER2 results in its activation and downstream signaling, even in the absence of ligand. HER2 overexpression, mainly due to gene amplification, has been shown in a variety of human cancers. Its role in breast cancer is especially well-documented. HER2 is up-regulated in about 25% of breast tumors and is associated with increases in tumor aggressiveness, recurrence and mortality. HER2 is a target for monoclonal antibodies and small molecule inhibitors, which are being developed as treatments for cancer. The first humanized antibody approved for clinical use is Trastuzumab (Herceptin), which is being used in combination with other therapies to improve the survival rates of patients with HER2-overexpressing breast cancer. The HER2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270684 [Multi-domain]  Cd Length: 279  Bit Score: 59.65  E-value: 2.56e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    609 LLGFFYDSGMfAIVTEFCSRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTD 688
Cdd:cd05109   74 LLGICLTSTV-QLVTQLMPYGCLLDYVRENKDRIGSQDLLNWCVQIAKGMSYLEEVRLVHRDLAARNVLVKSPNHVKITD 152
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    689 YGFNDILEM-LRLSEEESSMEELLWTAPE-LLRaprgsRLGSFAGDVYSFAIIMQEVMVRGT-PFcmMDLPAQEIINRLK 765
Cdd:cd05109  153 FGLARLLDIdETEYHADGGKVPIKWMALEsILH-----RRFTHQSDVWSYGVTVWELMTFGAkPY--DGIPAREIPDLLE 225
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 945225    766 KPPPVYRpvvppehaPPEC----LQLMKQCWAEAAEQRPTFDEIFNQFKTFNK 814
Cdd:cd05109  226 KGERLPQ--------PPICtidvYMIMVKCWMIDSECRPRFRELVDEFSRMAR 270
PTKc_Aatyk3 cd14206
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 3; PTKs ...
599-808 2.73e-09

Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Aatyk3, also called lemur tyrosine kinase 3 (Lmtk3) is a receptor kinase containing a transmembrane segment and a long C-terminal cytoplasmic tail with a catalytic domain. The function of Aatyk3 is still unknown. The Aatyk3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 271108 [Multi-domain]  Cd Length: 276  Bit Score: 59.58  E-value: 2.73e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    599 KDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDvKLDWMFKSSLLLDLI----------KGMKYLHHREFVH 668
Cdd:cd14206   52 RSLQHPNILQCLGLCTETIPFLLIMEFCQLGDLKRYLRAQR-KADGMTPDLPTRDLRtlqrmayeitLGLLHLHKNNYIH 130
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    669 GRLKSRNCVVDGRFVLKVTDYGF--NDILEMLrLSEEESSMEELLWTAPELLRAPRGSRL---GSFAGDVYSFAIIMQEV 743
Cdd:cd14206  131 SDLALRNCLLTSDLTVRIGDYGLshNNYKEDY-YLTPDRLWIPLRWVAPELLDELHGNLIvvdQSKESNVWSLGVTIWEL 209
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 945225    744 MVRGT-PFcmMDLPAQEIINRLKKPPPVYRpvvppehAPPEC--------LQLMKQCWAeAAEQRPTFDEIFNQ 808
Cdd:cd14206  210 FEFGAqPY--RHLSDEEVLTFVVREQQMKL-------AKPRLklpyadywYEIMQSCWL-PPSQRPSVEELHLQ 273
STKc_PLK2 cd14188
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 2; STKs catalyze the ...
596-805 3.96e-09

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK2, also called Snk (serum-inducible kinase), functions in G1 progression, S-phase arrest, and centriole duplication. Its gene is responsive to both growth factors and cellular stress, is a transcriptional target of p53, and activates a G2-M checkpoint. The PLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271090 [Multi-domain]  Cd Length: 255  Bit Score: 58.87  E-value: 3.96e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKLDWMFKSsLLLDLIKGMKYLHHREFVHGRLKSRN 675
Cdd:cd14188   53 ELHRILHHKHVVQFYHYFEDKENIYILLEYCSRRSMAHILKARKVLTEPEVRY-YLRQIVSGLKYLHEQEILHRDLKLGN 131
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    676 CVVDGRFVLKVTDYGFNDILEMLRlSEEESSMEELLWTAPELLRApRGSRLGSfagDVYSFAIIMQEVMVRGTPFCMMDL 755
Cdd:cd14188  132 FFINENMELKVGDFGLAARLEPLE-HRRRTICGTPNYLSPEVLNK-QGHGCES---DIWALGCVMYTMLLGRPPFETTNL 206
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|
gi 945225    756 PAQEIINRLKKPPPVYRPVVPPEHappeclqLMKQCWAEAAEQRPTFDEI 805
Cdd:cd14188  207 KETYRCIREARYSLPSSLLAPAKH-------LIASMLSKNPEDRPSLDEI 249
STKc_CDK_like cd07829
Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs ...
598-766 4.43e-09

Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. CDKs are partly regulated by their subcellular localization, which defines substrate phosphorylation and the resulting specific function. CDK1, CDK2, CDK4, and CDK6 have well-defined functions in the cell cycle, such as the regulation of the early G1 phase by CDK4 or CDK6, the G1/S phase transition by CDK2, or the entry of mitosis by CDK1. They also exhibit overlapping cyclin specificity and functions in certain conditions. Knockout mice with a single CDK deleted remain viable with specific phenotypes, showing that some CDKs can compensate for each other. For example, CDK4 can compensate for the loss of CDK6, however, double knockout mice with both CDK4 and CDK6 deleted die in utero. CDK8 and CDK9 are mainly involved in transcription while CDK5 is implicated in neuronal function. CDK7 plays essential roles in both the cell cycle as a CDK-Activating Kinase (CAK) and in transcription as a component of the general transcription factor TFIIH. The CDK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270823 [Multi-domain]  Cd Length: 282  Bit Score: 59.03  E-value: 4.43e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    598 MKDLRHENINPLLGFFYDSGMFAIVTEFCSRgSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNCV 677
Cdd:cd07829   52 LKELKHPNIVKLLDVIHTENKLYLVFEYCDQ-DLKKYLDKRPGPLPPNLIKSIMYQLLRGLAYCHSHRILHRDLKPQNLL 130
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    678 VDGRFVLKVTDYGF------------NDILEMlrlseeessmeellW-TAPELLrapRGSRLGSFAGDVYSFAIIMQEvM 744
Cdd:cd07829  131 INRDGVLKLADFGLarafgiplrtytHEVVTL--------------WyRAPEIL---LGSKHYSTAVDIWSVGCIFAE-L 192
                        170       180
                 ....*....|....*....|..
gi 945225    745 VRGTPFcmmdLPAQEIINRLKK 766
Cdd:cd07829  193 ITGKPL----FPGDSEIDQLFK 210
PTK_HER3 cd05111
Pseudokinase domain of the Protein Tyrosine Kinase, HER3; HER3 (ErbB3) is a member of the EGFR ...
598-809 5.32e-09

Pseudokinase domain of the Protein Tyrosine Kinase, HER3; HER3 (ErbB3) is a member of the EGFR (HER, ErbB) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. HER3 contains an impaired tyr kinase domain, which lacks crucial residues for catalytic activity against exogenous substrates but is still able to bind ATP and autophosphorylate. HER3 binds the neuregulin ligands, NRG1 and NRG2, and it relies on its heterodimerization partners for activity following ligand binding. The HER2-HER3 heterodimer constitutes a high affinity co-receptor capable of potent mitogenic signaling. HER3 participates in a signaling pathway involved in the proliferation, survival, adhesion, and motility of tumor cells. The HER3 subfamily is part of a larger superfamily that includes other pseudokinases and the the catalytic domains of active kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173656 [Multi-domain]  Cd Length: 279  Bit Score: 58.81  E-value: 5.32e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    598 MKDLRHENINPLLGFFYDSGMfAIVTEFCSRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNCV 677
Cdd:cd05111   63 IGSLDHAYIVRLLGICPGASL-QLVTQLLPLGSLLDHVRQHRGSLGPQLLLNWCVQIAKGMYYLEEHRMVHRNLAARNVL 141
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    678 VDGRFVLKVTDYGFNDIL-EMLRLSEEESSMEELLWTAPELLRAPRGSRlgsfAGDVYSFAIIMQEVMVRGT-PFCMMDL 755
Cdd:cd05111  142 LKSPSQVQVADFGVADLLyPDDKKYFYSEAKTPIKWMALESIHFGKYTH----QSDVWSYGVTVWEMMTFGAePYAGMRL 217
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 945225    756 PaqEIINRLKKPPPVYRpvvppehaPPEC----LQLMKQCWAEAAEQRPTFDEIFNQF 809
Cdd:cd05111  218 A--EVPDLLEKGERLAQ--------PQICtidvYMVMVKCWMIDENIRPTFKELANEF 265
STKc_TSSK-like cd14080
Catalytic domain of testis-specific serine/threonine kinases and similar proteins; STKs ...
588-807 5.93e-09

Catalytic domain of testis-specific serine/threonine kinases and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK1 and TSSK2 are expressed specifically in meiotic and postmeiotic spermatogenic cells, respectively. TSSK3 has been reported to be expressed in the interstitial Leydig cells of adult testis. TSSK4, also called TSSK5, is expressed in testis from haploid round spermatids to mature spermatozoa. TSSK6, also called SSTK, is expressed at the head of elongated sperm. TSSK1/TSSK2 double knock-out and TSSK6 null mice are sterile without manifesting other defects, making these kinases viable targets for male contraception. The TSSK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270982 [Multi-domain]  Cd Length: 262  Bit Score: 58.35  E-value: 5.93e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    588 KSRASDVF---------EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGS-LEDILTNQDVKLD----WMFKssllld 653
Cdd:cd14080   37 KKKAPKDFlekflprelEILRKLRHPNIIQVYSIFERGSKVFIFMEYAEHGDlLEYIQKRGALSESqariWFRQ------ 110
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    654 LIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGFNdilemlRLSEEESSMEE-------LLWTAPELLrapRGSRL 726
Cdd:cd14080  111 LALAVQYLHSLDIAHRDLKCENILLDSNNNVKLSDFGFA------RLCPDDDGDVLsktfcgsAAYAAPEIL---QGIPY 181
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    727 GSFAGDVYSFAIIMQeVMVRGT-PFCMMDLPA--QEIINRlkkpppVYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFD 803
Cdd:cd14080  182 DPKKYDIWSLGVILY-IMLCGSmPFDDSNIKKmlKDQQNR------KVRFPSSVKKLSPECKDLIDQLLEPDPTKRATIE 254

                 ....
gi 945225    804 EIFN 807
Cdd:cd14080  255 EILN 258
STKc_TSSK3-like cd14163
Catalytic domain of testis-specific serine/threonine kinase 3 and similar proteins; STKs ...
595-756 5.94e-09

Catalytic domain of testis-specific serine/threonine kinase 3 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK3 has been reported to be expressed in the interstitial Leydig cells of adult testis. Its mRNA levels is low at birth, increases at puberty, and remains high throughout adulthood. The TSSK3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271065 [Multi-domain]  Cd Length: 257  Bit Score: 58.08  E-value: 5.94e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    595 FEMMKDLRHENINPLLGFFYDS-GMFAIVTEFCSRGSLEDILTNQDvKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKS 673
Cdd:cd14163   51 LQIVERLDHKNIIHVYEMLESAdGKIYLVMELAEDGDVFDCVLHGG-PLPEHRAKALFRQLVEAIRYCHGCGVAHRDLKC 129
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    674 RNCVVDGrFVLKVTDYGFNDILEMLRLSEEESSMEELLWTAPELLRA-PRGSRlgsfAGDVYSFAIIMQEVMVRGTPFCM 752
Cdd:cd14163  130 ENALLQG-FTLKLTDFGFAKQLPKGGRELSQTFCGSTAYAAPEVLQGvPHDSR----KGDIWSMGVVLYVMLCAQLPFDD 204

                 ....
gi 945225    753 MDLP 756
Cdd:cd14163  205 TDIP 208
STKc_TGFbR_I cd14056
Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta family Type ...
566-801 6.03e-09

Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta family Type I Receptors; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of type I receptors for the TGFbeta family of secreted signaling molecules including TGFbeta, bone morphogenetic proteins, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation through trans-phosphorylation by type II receptors, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. They are inhibited by the immunophilin FKBP12, which is thought to control leaky signaling caused by receptor oligomerization in the absence of ligand. The TGFbR-I subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270958 [Multi-domain]  Cd Length: 287  Bit Score: 58.44  E-value: 6.03e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    566 YEGDWVWLKKFSLGDFGDLKsiksRASDVFEM-MkdLRHENInplLGFF----YDSGMFA---IVTEFCSRGSLEDILTN 637
Cdd:cd14056   16 YRGEKVAVKIFSSRDEDSWF----RETEIYQTvM--LRHENI---LGFIaadiKSTGSWTqlwLITEYHEHGSLYDYLQR 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    638 QDVKLDWMFKssLLLDLIKGMKYLH-------------HREfvhgrLKSRNCVVDGRFVLKVTDYGFNdILEMLRLSEEE 704
Cdd:cd14056   87 NTLDTEEALR--LAYSAASGLAHLHteivgtqgkpaiaHRD-----LKSKNILVKRDGTCCIADLGLA-VRYDSDTNTID 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    705 SSMEELLWT----APELLRAPRGSRlgSFA----GDVYSFAIIMQEVMVR----GTPFCMMdLPAQEIINRLKKPPPVYR 772
Cdd:cd14056  159 IPPNPRVGTkrymAPEVLDDSINPK--SFEsfkmADIYSFGLVLWEIARRceigGIAEEYQ-LPYFGMVPSDPSFEEMRK 235
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|.
gi 945225    773 PVVPPEHAPP--------ECL----QLMKQCWAEAAEQRPT 801
Cdd:cd14056  236 VVCVEKLRPPipnrwksdPVLrsmvKLMQECWSENPHARLT 276
STKc_Aurora cd14007
Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of ...
596-691 6.93e-09

Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Yeast contains only one Aurora kinase while most higher eukaryotes have two. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). Aurora-A regulates cell cycle events from the late S-phase through the M-phase including centrosome maturation, mitotic entry, centrosome separation, spindle assembly, chromosome alignment, cytokinesis, and mitotic exit. Aurora-A activation depends on its autophosphorylation and binding to the microtubule-associated protein TPX2. Aurora-B is most active at the transition during metaphase to the end of mitosis. It is critical for accurate chromosomal segregation, cytokinesis, protein localization to the centrosome and kinetochore, correct microtubule-kinetochore attachments, and regulation of the mitotic checkpoint. Aurora-C is mainly expressed in meiotically dividing cells; it was originally discovered in mice as a testis-specific STK called Aie1. Both Aurora-B and -C are chromosomal passenger proteins that can form complexes with INCENP and survivin, and they may have redundant cellular functions. The Aurora subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270909 [Multi-domain]  Cd Length: 253  Bit Score: 57.87  E-value: 6.93e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDvKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRN 675
Cdd:cd14007   52 EIQSHLRHPNILRLYGYFEDKKRIYLILEYAPNGELYKELKKQK-RFDEKEAAKYIYQLALALDYLHSKNIIHRDIKPEN 130
                         90
                 ....*....|....*.
gi 945225    676 CVVDGRFVLKVTDYGF 691
Cdd:cd14007  131 ILLGSNGELKLADFGW 146
STKc_PLK1 cd14187
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 1; STKs catalyze the ...
588-807 8.34e-09

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK1 functions as a positive regulator of mitosis, meiosis, and cytokinesis. Its localization changes during mitotic progression; associating first with centrosomes in prophase, with kinetochores in prometaphase and metaphase, at the central spindle in anaphase, and in the midbody during telophase. It carries multiple functions throughout the cell cycle through interactions with differrent substrates at these specific subcellular locations. PLK1 is overexpressed in many human cancers and is associated with poor prognosis. The PLK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271089 [Multi-domain]  Cd Length: 265  Bit Score: 58.02  E-value: 8.34e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    588 KSRASDVFEMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDI------LTNQDVKLdwmfkssLLLDLIKGMKYL 661
Cdd:cd14187   51 KEKMSMEIAIHRSLAHQHVVGFHGFFEDNDFVYVVLELCRRRSLLELhkrrkaLTEPEARY-------YLRQIILGCQYL 123
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    662 HHREFVHGRLKSRNCVVDGRFVLKVTDYGFNDILEmLRLSEEESSMEELLWTAPELLraprGSRLGSFAGDVYSFAIIMQ 741
Cdd:cd14187  124 HRNRVIHRDLKLGNLFLNDDMEVKIGDFGLATKVE-YDGERKKTLCGTPNYIAPEVL----SKKGHSFEVDIWSIGCIMY 198
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 945225    742 EVMVRGTPF---CMmdlpaQEIINRLKKpppvyRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEIFN 807
Cdd:cd14187  199 TLLVGKPPFetsCL-----KETYLRIKK-----NEYSIPKHINPVAASLIQKMLQTDPTARPTINELLN 257
PBP1_GPCR_family_C-like cd06350
ligand-binding domain of membrane-bound glutamate receptors that mediate excitatory ...
75-196 1.16e-08

ligand-binding domain of membrane-bound glutamate receptors that mediate excitatory transmission on the cellular surface through initial binding of glutamate; categorized into ionotropic glutamate receptors (iGluRs) and metabotropic glutamate receptors (m; Ligand-binding domain of membrane-bound glutamate receptors that mediate excitatory transmission on the cellular surface through initial binding of glutamate and are categorized into ionotropic glutamate receptors (iGluRs) and metabotropic glutamate receptors (mGluRs). The metabotropic glutamate receptors (mGluR) are key receptors in the modulation of excitatory synaptic transmission in the central nervous system. The mGluRs are coupled to G proteins and are thus distinct from the iGluRs which internally contain ligand-gated ion channels. The mGluR structure is divided into three regions: the extracellular region, the seven-spanning transmembrane region and the cytoplasmic region. The extracellular region is further divided into the ligand-binding domain (LBD) and the cysteine-rich domain. The LBD has sequence similarity to the LIVBP, which is a bacterial periplasmic protein (PBP), as well as to the extracellular region of both iGluR and the gamma-aminobutyric acid (GABA)b receptor. iGluRs are divided into three main subtypes based on pharmacological profile: NMDA, AMPA, and kainate receptors. All family C GPCRs have a large extracellular N terminus that contain a domain with homology to bacterial periplasmic amino acid-binding proteins.


Pssm-ID: 380573  Cd Length: 350  Bit Score: 58.46  E-value: 1.16e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225     75 AARLAIERINRDPS-----------FD--------LSYSFEYVILNEDCQTSRALSSFISHHQMAsGFIGPTNPGYCEA- 134
Cdd:cd06350   32 AMIYAIEEINNDSSllpnvtlgydiRDtcssssvaLESSLEFLLDNGIKLLANSNGQNIGPPNIV-AVIGAASSSVSIAv 110
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 945225    135 ASLLGNSWDKGIfSWACVNYELDNKISYPTFSRTLPSP---IRVLVTVMKYFQWAHAGVISSDED 196
Cdd:cd06350  111 ANLLGLFKIPQI-SYASTSPELSDKIRYPYFLRTVPSDtlqAKAIADLLKHFNWNYVSTVYSDDD 174
PTKc_VEGFR3 cd05102
Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3; ...
636-805 1.21e-08

Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR3 (or Flt4) preferentially binds the ligands VEGFC and VEGFD. VEGFR3 is essential for lymphatic endothelial cell (EC) development and function. It has been shown to regulate adaptive immunity during corneal transplantation. VEGFR3 is upregulated on blood vascular ECs in pathological conditions such as vascular tumors and the periphery of solid tumors. It plays a role in cancer progression and lymph node metastasis. Missense mutations in the VEGFR3 gene are associated with primary human lymphedema. VEGFR3 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. In VEGFR3, the fifth Ig-like domain is replaced by a disulfide bridge. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270680 [Multi-domain]  Cd Length: 336  Bit Score: 58.07  E-value: 1.21e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    636 TNQ-DVKLDWMFKSSLLL-DLI-------KGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGF-NDILEMLRLSEEES 705
Cdd:cd05102  154 TNQpRQEVDDLWQSPLTMeDLIcysfqvaRGMEFLASRKCIHRDLAARNILLSENNVVKICDFGLaRDIYKDPDYVRKGS 233
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    706 SMEELLWTAPELLRaprgSRLGSFAGDVYSFAIIMQEVMVRG-TPFcmmdlPAQEIINRLKKPPPVYRPVVPPEHAPPEC 784
Cdd:cd05102  234 ARLPLKWMAPESIF----DKVYTTQSDVWSFGVLLWEIFSLGaSPY-----PGVQINEEFCQRLKDGTRMRAPEYATPEI 304
                        170       180
                 ....*....|....*....|.
gi 945225    785 LQLMKQCWAEAAEQRPTFDEI 805
Cdd:cd05102  305 YRIMLSCWHGDPKERPTFSDL 325
STKc_PhKG cd14093
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma subunit; STKs ...
602-750 1.53e-08

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). Each subunit has tissue-specific isoforms or splice variants. Vertebrates contain two isoforms of the gamma subunit (gamma 1 and gamma 2). The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270995 [Multi-domain]  Cd Length: 272  Bit Score: 56.98  E-value: 1.53e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    602 RHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTnQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNCVVDGR 681
Cdd:cd14093   67 GHPNIIELHDVFESPTFIFLVFELCRKGELFDYLT-EVVTLSEKKTRRIMRQLFEAVEFLHSLNIVHRDLKPENILLDDN 145
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 945225    682 FVLKVTDYGFNDIL---EMLRlseeeSSMEELLWTAPELLRAPRGSRLGSFAG--DVYSFAIIMQEVMVRGTPF 750
Cdd:cd14093  146 LNVKISDFGFATRLdegEKLR-----ELCGTPGYLAPEVLKCSMYDNAPGYGKevDMWACGVIMYTLLAGCPPF 214
PHA02988 PHA02988
hypothetical protein; Provisional
558-812 1.69e-08

hypothetical protein; Provisional


Pssm-ID: 165291 [Multi-domain]  Cd Length: 283  Bit Score: 57.06  E-value: 1.69e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225     558 YENSNIAIYEGDW----VWLKKFSlGDFGDLKSIKSRASDVFEMMKDLRHENINPLLGFFYDSG----MFAIVTEFCSRG 629
Cdd:PHA02988   29 KENDQNSIYKGIFnnkeVIIRTFK-KFHKGHKVLIDITENEIKNLRRIDSNNILKIYGFIIDIVddlpRLSLILEYCTRG 107
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225     630 SLEDILTNQDvKLDWMFKSSLLLDLIKGMKYLH-HREFVHGRLKSRNCVVDGRFVLKVTDYGfndiLEMLRLSEEESSME 708
Cdd:PHA02988  108 YLREVLDKEK-DLSFKTKLDMAIDCCKGLYNLYkYTNKPYKNLTSVSFLVTENYKLKIICHG----LEKILSSPPFKNVN 182
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225     709 ELLWTAPELLRAPRGSRLgsFAGDVYSFAIIMQEVMVRGTPFCMMDlpAQEIINRLKKpppvyrpVVPPEHAPPECLQLM 788
Cdd:PHA02988  183 FMVYFSYKMLNDIFSEYT--IKDDIYSLGVVLWEIFTGKIPFENLT--TKEIYDLIIN-------KNNSLKLPLDCPLEI 251
                         250       260
                  ....*....|....*....|....*...
gi 945225     789 K----QCWAEAAEQRPTFDEIFNQFKTF 812
Cdd:PHA02988  252 KciveACTSHDSIKRPNIKEILYNLSLY 279
STKc_MST1_2 cd06612
Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2; ...
549-696 1.76e-08

Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MST1, MST2, and related proteins including Drosophila Hippo and Dictyostelium discoideum Krs1 (kinase responsive to stress 1). MST1/2 and Hippo are involved in a conserved pathway that governs cell contact inhibition, organ size control, and tumor development. MST1 activates the mitogen-activated protein kinases (MAPKs) p38 and c-Jun N-terminal kinase (JNK) through MKK7 and MEKK1 by acting as a MAPK kinase kinase kinase. Activation of JNK by MST1 leads to caspase activation and apoptosis. MST1 has also been implicated in cell proliferation and differentiation. Krs1 may regulate cell growth arrest and apoptosis in response to cellular stress. The MST1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132943 [Multi-domain]  Cd Length: 256  Bit Score: 56.89  E-value: 1.76e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    549 SSGSLTPATYENSN--IAIyegdwvwlKKFSLgdFGDLKSIKSRASdvfeMMKDLRHENINPLLGFFYDSGMFAIVTEFC 626
Cdd:cd06612   15 SYGSVYKAIHKETGqvVAI--------KVVPV--EEDLQEIIKEIS----ILKQCDSPYIVKYYGSYFKNTDLWIVMEYC 80
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    627 SRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGFNDILE 696
Cdd:cd06612   81 GAGSVSDIMKITNKTLTEEEIAAILYQTLKGLEYLHSNKKIHRDIKAGNILLNEEGQAKLADFGVSGQLT 150
STKc_ATG1_ULK_like cd14009
Catalytic domain of the Serine/Threonine kinases, Autophagy-related protein 1 and Unc-51-like ...
596-807 2.26e-08

Catalytic domain of the Serine/Threonine kinases, Autophagy-related protein 1 and Unc-51-like kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes yeast ATG1 and metazoan homologs including vertebrate ULK1-3. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. It is involved in nutrient sensing and signaling, the assembly of autophagy factors and the execution of autophagy. In metazoans, ATG1 homologs display additional functions. Unc-51 and ULKs have been implicated in neuronal and axonal development. The ATG1/ULK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270911 [Multi-domain]  Cd Length: 251  Bit Score: 56.46  E-value: 2.26e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDvKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRN 675
Cdd:cd14009   44 AILKSIKHPNIVRLYDVQKTEDFIYLVLEYCAGGDLSQYIRKRG-RLPEAVARHFMQQLASGLKFLRSKNIIHRDLKPQN 122
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    676 CVVDGRF---VLKVTDYGF------NDILEMLRlseeessmEELLWTAPELLrapRGSRLGSFAgDVYSFAIIMQEvMVR 746
Cdd:cd14009  123 LLLSTSGddpVLKIADFGFarslqpASMAETLC--------GSPLYMAPEIL---QFQKYDAKA-DLWSVGAILFE-MLV 189
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 945225    747 GTPfcmmdlP-----AQEIINRLKKpPPVYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEIFN 807
Cdd:cd14009  190 GKP------PfrgsnHVQLLRNIER-SDAVIPFPIAAQLSPDCKDLLRRLLRRDPAERISFEEFFA 248
PTKc_Aatyk cd05042
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinases; PTKs ...
601-805 2.31e-08

Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Aatyk subfamily is also referred to as the lemur tyrosine kinase (Lmtk) subfamily. It consists of Aatyk1 (Lmtk1), Aatyk2 (Lmtk2, Brek), Aatyk3 (Lmtk3), and similar proteins. Aatyk proteins are mostly receptor PTKs (RTKs) containing a transmembrane segment and a long C-terminal cytoplasmic tail with a catalytic domain. Aatyk1 does not contain a transmembrane segment and is a cytoplasmic (or nonreceptor) kinase. Aatyk proteins are classified as PTKs based on overall sequence similarity and the phylogenetic tree. However, analysis of catalytic residues suggests that Aatyk proteins may be multispecific kinases, functioning also as serine/threonine kinases. They are involved in neural differentiation, nerve growth factor (NGF) signaling, apoptosis, and spermatogenesis. The Aatyk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270638 [Multi-domain]  Cd Length: 269  Bit Score: 56.44  E-value: 2.31e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    601 LRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKL----DWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNC 676
Cdd:cd05042   52 LQHPNILQCLGQCVEAIPYLLVMEFCDLGDLKAYLRSEREHErgdsDTRTLQRMACEVAAGLAHLHKLNFVHSDLALRNC 131
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    677 VVDGRFVLKVTDYGF------NDILEmlrlsEEESSMEELLWTAPELLRAPRGSRL---GSFAGDVYSFAIIMQEVMVRG 747
Cdd:cd05042  132 LLTSDLTVKIGDYGLahsrykEDYIE-----TDDKLWFPLRWTAPELVTEFHDRLLvvdQTKYSNIWSLGVTLWELFENG 206
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    748 T-PFcmMDLPAQEIINRLKKPPPVYRPVVPPEHAPPE-CLQLMKQCWAEaAEQRPTFDEI 805
Cdd:cd05042  207 AqPY--SNLSDLDVLAQVVREQDTKLPKPQLELPYSDrWYEVLQFCWLS-PEQRPAAEDV 263
HNOBA pfam07701
Heme NO binding associated; The HNOBA domain is found associated with the HNOB domain and ...
824-869 2.33e-08

Heme NO binding associated; The HNOBA domain is found associated with the HNOB domain and pfam00211 in soluble cyclases and signalling proteins. The HNOB domain is predicted to function as a heme-dependent sensor for gaseous ligands, and transduce diverse downstream signals, in both bacteria and animals.


Pssm-ID: 462234  Cd Length: 214  Bit Score: 55.66  E-value: 2.33e-08
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 945225      824 MLRMLEQYSSNLEDLirerTEELEIEKQKTEKLLTQMLPPSVAESL 869
Cdd:pfam07701  173 ALDQLEQKSAELEES----MRELEEEKKKTDELLYSMLPKSVADRL 214
STKc_PAK_II cd06648
Catalytic domain of the Serine/Threonine Kinase, Group II p21-activated kinase; STKs catalyze ...
597-758 3.93e-08

Catalytic domain of the Serine/Threonine Kinase, Group II p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Group II PAKs, also called non-conventional PAKs, include PAK4, PAK5, and PAK6. Group II PAKs contain PBD (p21-binding domain) and catalytic domains, but lack other motifs found in group I PAKs, such as an AID (autoinhibitory domain) and SH3 binding sites. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. While group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX, no such binding has been demonstrated for group II PAKs. Some known substrates of group II PAKs are also substrates of group I PAKs such as Raf, BAD, LIMK and GEFH1. Unique group II substrates include MARK/Par-1 and PDZ-RhoGEF. Group II PAKs play important roles in filopodia formation, neuron extension, cytoskeletal organization, and cell survival. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270815 [Multi-domain]  Cd Length: 261  Bit Score: 55.91  E-value: 3.93e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNqdVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNC 676
Cdd:cd06648   57 IMRDYQHPNIVEMYSSYLVGDELWVVMEFLEGGALTDIVTH--TRMNEEQIATVCRAVLKALSFLHSQGVIHRDIKSDSI 134
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    677 VV--DGRfvLKVTDYGFNDIL--EMLRlseEESSMEELLWTAPELL-RAPRGSRLgsfagDVYSFAIIMQEvMVRGTPFC 751
Cdd:cd06648  135 LLtsDGR--VKLSDFGFCAQVskEVPR---RKSLVGTPYWMAPEVIsRLPYGTEV-----DIWSLGIMVIE-MVDGEPPY 203

                 ....*..
gi 945225    752 MMDLPAQ 758
Cdd:cd06648  204 FNEPPLQ 210
PTKc_TrkC cd05094
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase C; PTKs catalyze ...
596-818 4.28e-08

Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase C; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. TrkC is a receptor PTK (RTK) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding of TrkC to its ligand, neurotrophin 3 (NT3), results in receptor oligomerization and activation of the catalytic domain. TrkC is broadly expressed in the nervous system and in some non-neural tissues including the developing heart. NT3/TrkC signaling plays an important role in the innervation of the cardiac conducting system and the development of smooth muscle cells. Mice deficient with NT3 and TrkC have multiple heart defects. NT3/TrkC signaling is also critical for the development and maintenance of enteric neurons that are important for the control of gut peristalsis. The TrkC subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270676 [Multi-domain]  Cd Length: 287  Bit Score: 56.17  E-value: 4.28e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDIL-----------------TNQDVKLDWMFKssLLLDLIKGM 658
Cdd:cd05094   59 ELLTNLQHDHIVKFYGVCGDGDPLIMVFEYMKHGDLNKFLrahgpdamilvdgqprqAKGELGLSQMLH--IATQIASGM 136
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    659 KYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGFN-DILEMLRLSEEESSMEELLWTAPELLRaprgSRLGSFAGDVYSFA 737
Cdd:cd05094  137 VYLASQHFVHRDLATRNCLVGANLLVKIGDFGMSrDVYSTDYYRVGGHTMLPIRWMPPESIM----YRKFTTESDVWSFG 212
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    738 IIMQEVMVRGT-PFcmMDLPAQEIINRLKKPPPVYRPVVppehAPPECLQLMKQCWAEAAEQRPTFDEIFNQFktFNKGK 816
Cdd:cd05094  213 VILWEIFTYGKqPW--FQLSNTEVIECITQGRVLERPRV----CPKEVYDIMLGCWQREPQQRLNIKEIYKIL--HALGK 284

                 ..
gi 945225    817 KT 818
Cdd:cd05094  285 AT 286
STKc_PAK5 cd06658
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 5; STKs catalyze the ...
597-760 5.19e-08

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK5 is mainly expressed in the brain. It is not required for viability, but together with PAK6, it is required for normal levels of locomotion and activity, and for learning and memory. PAK5 cooperates with Inca (induced in neural crest by AP2) in the regulation of cell adhesion and cytoskeletal organization in the embryo and in neural crest cells during craniofacial development. PAK5 may also play a role in controlling the signaling of Raf-1, an effector of Ras, at the mitochondria. PAK5 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132989 [Multi-domain]  Cd Length: 292  Bit Score: 55.81  E-value: 5.19e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKLDWMfkSSLLLDLIKGMKYLHHREFVHGRLKSRNC 676
Cdd:cd06658   72 IMRDYHHENVVDMYNSYLVGDELWVVMEFLEGGALTDIVTHTRMNEEQI--ATVCLSVLRALSYLHNQGVIHRDIKSDSI 149
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    677 VV--DGRfvLKVTDYGFNDILEMlRLSEEESSMEELLWTAPELL-RAPRGSRLgsfagDVYSFAIIMQEvMVRGTPFCMM 753
Cdd:cd06658  150 LLtsDGR--IKLSDFGFCAQVSK-EVPKRKSLVGTPYWMAPEVIsRLPYGTEV-----DIWSLGIMVIE-MIDGEPPYFN 220

                 ....*..
gi 945225    754 DLPAQEI 760
Cdd:cd06658  221 EPPLQAM 227
PTKc_Aatyk1 cd05087
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 1; PTKs ...
572-805 8.11e-08

Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Aatyk1 (or simply Aatyk) is also called lemur tyrosine kinase 1 (Lmtk1). It is a cytoplasmic (or nonreceptor) kinase containing a long C-terminal region. The expression of Aatyk1 is upregulated during growth arrest and apoptosis in myeloid cells. Aatyk1 has been implicated in neural differentiation, and is a regulator of the Na-K-2Cl cotransporter, a membrane protein involved in cell proliferation and survival, epithelial transport, and blood pressure control. The Aatyk1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270670 [Multi-domain]  Cd Length: 271  Bit Score: 54.99  E-value: 8.11e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    572 WLKKFSLGDFGD--------LKSIKSRASdVFEMM---------KDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDI 634
Cdd:cd05087    9 WFGKVFLGEVNSglsstqvvVKELKASAS-VQDQMqfleeaqpyRALQHTNLLQCLAQCAEVTPYLLVMEFCPLGDLKGY 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    635 LTN----QDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGFNDI-LEMLRLSEEESSMEE 709
Cdd:cd05087   88 LRScraaESMAPDPLTLQRMACEVACGLLHLHRNNFVHSDLALRNCLLTADLTVKIGDYGLSHCkYKEDYFVTADQLWVP 167
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    710 LLWTAPELLRAPRGSRL---GSFAGDVYSFAIIMQEVMVRGT-PFCMMDlPAQEIINRLKKPPPVYRPVVPPEHAPPECL 785
Cdd:cd05087  168 LRWIAPELVDEVHGNLLvvdQTKQSNVWSLGVTIWELFELGNqPYRHYS-DRQVLTYTVREQQLKLPKPQLKLSLAERWY 246
                        250       260
                 ....*....|....*....|
gi 945225    786 QLMKQCWAEaAEQRPTFDEI 805
Cdd:cd05087  247 EVMQFCWLQ-PEQRPTAEEV 265
PTKc_TrkB cd05093
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase B; PTKs catalyze ...
596-815 8.55e-08

Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase B; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. TrkB is a receptor PTK (RTK) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding of TrkB to its ligands, brain-derived neurotrophic factor (BDNF) or neurotrophin 4 (NT4), results in receptor oligomerization and activation of the catalytic domain. TrkB is broadly expressed in the nervous system and in some non-neural tissues. It plays important roles in cell proliferation, differentiation, and survival. BDNF/Trk signaling plays a key role in regulating activity-dependent synaptic plasticity. TrkB also contributes to protection against gp120-induced neuronal cell death. TrkB overexpression is associated with poor prognosis in neuroblastoma (NB) and other human cancers. It acts as a suppressor of anoikis (detachment-induced apoptosis) and contributes to tumor metastasis. The TrkB subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270675 [Multi-domain]  Cd Length: 288  Bit Score: 55.05  E-value: 8.55e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKLDWMFKSSLLLDLIK------------GMKYLHH 663
Cdd:cd05093   59 ELLTNLQHEHIVKFYGVCVEGDPLIMVFEYMKHGDLNKFLRAHGPDAVLMAEGNRPAELTQsqmlhiaqqiaaGMVYLAS 138
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    664 REFVHGRLKSRNCVVDGRFVLKVTDYGFN-DILEMLRLSEEESSMEELLWTAPELLRaprgSRLGSFAGDVYSFAIIMQE 742
Cdd:cd05093  139 QHFVHRDLATRNCLVGENLLVKIGDFGMSrDVYSTDYYRVGGHTMLPIRWMPPESIM----YRKFTTESDVWSLGVVLWE 214
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 945225    743 VMVRG-TPFcmMDLPAQEIINRLKKPPPVYRPVVppehAPPECLQLMKQCWAEAAEQRPTFDEIFNQFKTFNKG 815
Cdd:cd05093  215 IFTYGkQPW--YQLSNNEVIECITQGRVLQRPRT----CPKEVYDLMLGCWQREPHMRLNIKEIHSLLQNLAKA 282
STKc_LKB1_CaMKK cd14008
Catalytic domain of the Serine/Threonine kinases, Liver Kinase B1, Calmodulin Dependent ...
596-807 8.65e-08

Catalytic domain of the Serine/Threonine kinases, Liver Kinase B1, Calmodulin Dependent Protein Kinase Kinase, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Both LKB1 and CaMKKs can phosphorylate and activate AMP-activated protein kinase (AMPK). LKB1, also called STK11, serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. LKB1 and AMPK are part of an energy-sensing pathway that links cell energy to metabolism and cell growth. They play critical roles in the establishment and maintenance of cell polarity, cell proliferation, cytoskeletal organization, as well as T-cell metabolism, including T-cell development, homeostasis, and effector function. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMPK. Vertebrates contain two CaMKKs, CaMKK1 (or alpha) and CaMKK2 (or beta). CaMKK1 is involved in the regulation of glucose uptake in skeletal muscles. CaMKK2 is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. The LKB1/CaMKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270910 [Multi-domain]  Cd Length: 267  Bit Score: 54.87  E-value: 8.65e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSG---MFaIVTEFCSRGSLEDILTNQDVK-LD-----WMFKsslllDLIKGMKYLHHREF 666
Cdd:cd14008   56 AIMKKLDHPNIVRLYEVIDDPEsdkLY-LVLEYCEGGPVMELDSGDRVPpLPeetarKYFR-----DLVLGLEYLHENGI 129
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    667 VHGRLKSRNCVVDGRFVLKVTDYG----FNDILEMLRLSEEessmeellwT----APELLRAPRGSRLGsFAGDVYSFAI 738
Cdd:cd14008  130 VHRDIKPENLLLTADGTVKISDFGvsemFEDGNDTLQKTAG---------TpaflAPELCDGDSKTYSG-KAADIWALGV 199
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 945225    739 imqevmvrgTPFCMM--DLP--AQEIINRLKKPPPVYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEIFN 807
Cdd:cd14008  200 ---------TLYCLVfgRLPfnGDNILELYEAIQNQNDEFPIPPELSPELKDLLRRMLEKDPEKRITLKEIKE 263
STKc_MELK cd14078
Catalytic domain of the Serine/Threonine Kinase, Maternal Embryonic Leucine zipper Kinase; ...
575-750 9.30e-08

Catalytic domain of the Serine/Threonine Kinase, Maternal Embryonic Leucine zipper Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MELK is a cell cycle dependent protein which functions in cytokinesis, cell cycle, apoptosis, cell proliferation, and mRNA processing. It is found upregulated in many types of cancer cells, playing an indispensable role in cancer cell survival. It makes an attractive target in the design of inhibitors for use in the treatment of a wide range of human cancer. The MELK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270980 [Multi-domain]  Cd Length: 257  Bit Score: 54.70  E-value: 9.30e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    575 KFSLGDfgDLKSIKSRasdvFEMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDvKLDWMFKSSLLLDL 654
Cdd:cd14078   38 KKALGD--DLPRVKTE----IEALKNLSHQHICRLYHVIETDNKIFMVLEYCPGGELFDYIVAKD-RLSEDEARVFFRQI 110
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    655 IKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGFNDILEMLRLSEEESSMEELLWTAPELLRAprGSRLGSFAgDVY 734
Cdd:cd14078  111 VSAVAYVHSQGYAHRDLKPENLLLDEDQNLKLIDFGLCAKPKGGMDHHLETCCGSPAYAAPELIQG--KPYIGSEA-DVW 187
                        170
                 ....*....|....*.
gi 945225    735 SFAIIMQEVMVRGTPF 750
Cdd:cd14078  188 SMGVLLYALLCGFLPF 203
PTKc_CSF-1R cd05106
Catalytic domain of the Protein Tyrosine Kinase, Colony-Stimulating Factor-1 Receptor; PTKs ...
627-805 9.50e-08

Catalytic domain of the Protein Tyrosine Kinase, Colony-Stimulating Factor-1 Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. CSF-1R, also called c-Fms, is a member of the Platelet Derived Growth Factor Receptor (PDGFR) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of CSF-1R to its ligand, CSF-1, leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. CSF-1R signaling is critical in the regulation of macrophages and osteoclasts. It leads to increases in gene transcription and protein translation, and induces cytoskeletal remodeling. CSF-1R signaling leads to a variety of cellular responses including survival, proliferation, and differentiation of target cells. It plays an important role in innate immunity, tissue development and function, and the pathogenesis of some diseases including atherosclerosis and cancer. CSF-1R signaling is also implicated in mammary gland development during pregnancy and lactation. Aberrant CSF-1/CSF-1R expression correlates with tumor cell invasiveness, poor clinical prognosis, and bone metastasis in breast cancer. Although the structure of the human CSF-1R catalytic domain is known, it is excluded from this specific alignment model because it contains a deletion in its sequence. The CSF-1R subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133237 [Multi-domain]  Cd Length: 374  Bit Score: 55.62  E-value: 9.50e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    627 SRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGF-NDILEMLRLSEEES 705
Cdd:cd05106  194 SSDSKDEEDTEDSWPLDLDDLLRFSSQVAQGMDFLASKNCIHRDVAARNVLLTDGRVAKICDFGLaRDIMNDSNYVVKGN 273
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    706 SMEELLWTAPELLRaprgSRLGSFAGDVYSFAIIMQEVMVRG-TPFcmmdlPAQEIINRLKKPPPVYRPVVPPEHAPPEC 784
Cdd:cd05106  274 ARLPVKWMAPESIF----DCVYTVQSDVWSYGILLWEIFSLGkSPY-----PGILVNSKFYKMVKRGYQMSRPDFAPPEI 344
                        170       180
                 ....*....|....*....|.
gi 945225    785 LQLMKQCWAEAAEQRPTFDEI 805
Cdd:cd05106  345 YSIMKMCWNLEPTERPTFSQI 365
STKc_TSSK4-like cd14162
Catalytic domain of testis-specific serine/threonine kinase 4 and similar proteins; STKs ...
596-750 1.13e-07

Catalytic domain of testis-specific serine/threonine kinase 4 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK4, also called TSSK5, is expressed in testis from haploid round spermatids to mature spermatozoa. It phosphorylates Cre-Responsive Element Binding protein (CREB), facilitating the binding of CREB to the specific cis cAMP responsive element (CRE), which is important in activating genes related to germ cell differentiation. Mutations in the human TSSK4 gene is associated with infertile Chinese men with impaired spermatogenesis. The TSSK4-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271064 [Multi-domain]  Cd Length: 259  Bit Score: 54.23  E-value: 1.13e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLediltnqdvkLDWMFKSSLLLD---------LIKGMKYLHHREF 666
Cdd:cd14162   52 EVIKGLKHPNLICFYEAIETTSRVYIIMELAENGDL----------LDYIRKNGALPEpqarrwfrqLVAGVEYCHSKGV 121
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    667 VHGRLKSRNCVVDGRFVLKVTDYGF---NDILEMLRLSEEESSMEELLWTAPELLrapRGSRLGSFAGDVYSFAIIMQEV 743
Cdd:cd14162  122 VHRDLKCENLLLDKNNNLKITDFGFargVMKTKDGKPKLSETYCGSYAYASPEIL---RGIPYDPFLSDIWSMGVVLYTM 198

                 ....*..
gi 945225    744 MVRGTPF 750
Cdd:cd14162  199 VYGRLPF 205
PKc_Dusty cd13975
Catalytic domain of the Dual-specificity Protein Kinase, Dusty; Dual-specificity PKs catalyze ...
595-805 1.88e-07

Catalytic domain of the Dual-specificity Protein Kinase, Dusty; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. Dusty protein kinase is also called Receptor-interacting protein kinase 5 (RIPK5 or RIP5) or RIP-homologous kinase. It is widely distributed in the central nervous system, and may be involved in inducing both caspase-dependent and caspase-independent cell death. The Dusty subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270877 [Multi-domain]  Cd Length: 262  Bit Score: 53.65  E-value: 1.88e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    595 FEMMKDL-RHENINPLLGFFYD---SGMFAI----VTEFCSRgsleDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREF 666
Cdd:cd13975   48 FHYTRSLpKHERIVSLHGSVIDysyGGGSSIavllIMERLHR----DLYTGIKAGLSLEERLQIALDVVEGIRFLHSQGL 123
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    667 VHGRLKSRNCVVDGRFVLKVTDYGFNDILEMLRLSEEESSMEEllwtAPELLRAPRGSRLgsfagDVYSFAIIMQEV--- 743
Cdd:cd13975  124 VHRDIKLKNVLLDKKNRAKITDLGFCKPEAMMSGSIVGTPIHM----APELFSGKYDNSV-----DVYAFGILFWYLcag 194
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 945225    744 MVRgTPFCMMDLPAQEII-NRLKKPPPVYRPVVPPEhappECLQLMKQCWAEAAEQRPTFDEI 805
Cdd:cd13975  195 HVK-LPEAFEQCASKDHLwNNVRKGVRPERLPVFDE----ECWNLMEACWSGDPSQRPLLGIV 252
STKc_STK36 cd14002
Catalytic domain of Serine/Threonine Kinase 36; STKs catalyze the transfer of the ...
583-691 2.21e-07

Catalytic domain of Serine/Threonine Kinase 36; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK36, also called Fused (or Fu) kinase, is involved in the Hedgehog signaling pathway. It is activated by the Smoothened (SMO) signal transducer, resulting in the stabilization of GLI transcription factors and the phosphorylation of SUFU to facilitate the nuclear accumulation of GLI. In Drosophila, Fused kinase is maternally required for proper segmentation during embryonic development and for the development of legs and wings during the larval stage. In mice, STK36 is not necessary for embryonic development, although mice deficient in STK36 display growth retardation postnatally. The STK36 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270904 [Multi-domain]  Cd Length: 253  Bit Score: 53.41  E-value: 2.21e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    583 DLKSIKSRasdvFEMMKDLRHENINPLLGFFYDSGMFAIVTEFcSRGSLEDILTNqDVKLDWMFKSSLLLDLIKGMKYLH 662
Cdd:cd14002   43 ELRNLRQE----IEILRKLNHPNIIEMLDSFETKKEFVVVTEY-AQGELFQILED-DGTLPEEEVRSIAKQLVSALHYLH 116
                         90       100
                 ....*....|....*....|....*....
gi 945225    663 HREFVHGRLKSRNCVVDGRFVLKVTDYGF 691
Cdd:cd14002  117 SNRIIHRDMKPQNILIGKGGVVKLCDFGF 145
STKc_CAMK cd05117
The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of ...
595-696 2.35e-07

The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. CaMKII is a signaling molecule that translates upstream calcium and reactive oxygen species (ROS) signals into downstream responses that play important roles in synaptic function and cardiovascular physiology. CAMKIV is implicated in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors, as well as in T-cell development and signaling. The CAMK family also consists of other related kinases including the Phosphorylase kinase Gamma subunit (PhKG), the C-terminal kinase domains of Ribosomal S6 kinase (RSK) and Mitogen and stress-activated kinase (MSK), Doublecortin-like kinase (DCKL), and the MAPK-activated protein kinases MK2, MK3, and MK5, among others. The CAMK family is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270687 [Multi-domain]  Cd Length: 258  Bit Score: 53.25  E-value: 2.35e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    595 FEMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSL-EDILTN-----QDVKldWMFKsslllDLIKGMKYLHHREFVH 668
Cdd:cd05117   50 IEILKRLDHPNIVKLYEVFEDDKNLYLVMELCTGGELfDRIVKKgsfseREAA--KIMK-----QILSAVAYLHSQGIVH 122
                         90       100       110
                 ....*....|....*....|....*....|.
gi 945225    669 GRLKSRNCVVDGR---FVLKVTDYGFNDILE 696
Cdd:cd05117  123 RDLKPENILLASKdpdSPIKIIDFGLAKIFE 153
PBP1_NPR_A cd06385
Ligand-binding domain of type A natriuretic peptide receptor; Ligand-binding domain of type A ...
60-401 2.36e-07

Ligand-binding domain of type A natriuretic peptide receptor; Ligand-binding domain of type A natriuretic peptide receptor (NPR-A). NPR-A is one of three known single membrane-spanning natriuretic peptide receptors that regulate blood volume, blood pressure, ventricular hypertrophy, pulmonary hypertension, fat metabolism, and long bone growth. In mammals there are three natriuretic peptides: ANP, BNP, and CNP. NPR-A is highly expressed in kidney, adrenal, terminal ileum, adipose, aortic, and lung tissues. The rank order of NPR-A activation by natriuretic peptides is ANP>BNP>>CNP. Single allele-inactivating mutations in the promoter of human NPR-A are associated with hypertension and heart failure.


Pssm-ID: 380608 [Multi-domain]  Cd Length: 408  Bit Score: 54.44  E-value: 2.36e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225     60 PWAcdslfskaLPEV--AARLAIERINRDPSFDLSYSFEYVILN-ED----CQTSRALSSFI----SHHQMAsgFIGPtn 128
Cdd:cd06385   14 PWA--------WPRVgpAVELALERVNARPDLLPGWHVRTVLGSsENkegvCSDSTAPLVAVdlkfEHHPAV--FLGP-- 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    129 pGYCEAASLLGNS---WDKGIFSWACVNYELDNKISYPTFSRTLPSPIRV--LVTVM-KYFQWAHAGVI-----SSDEDI 197
Cdd:cd06385   82 -GCVYTAAPVARFtahWRVPLLTAGAPALGFGVKDEYALTTRTGPSHKKLgeFVARLhRRYGWERRALLvyadrKGDDRP 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    198 WVHTANRVASALRSH-GLPVGVVLTTGQDSQSMRKALQRIHQadRIRIIIMCMHSaliggETQMHLLECAHDLKMTDGTY 276
Cdd:cd06385  161 CFFAVEGLYMQLRRRlNITVDDLVFNEDEPLNYTELLRDIRQ--KGRVIYVCCSP-----DTFRKLMLQAWREGLCGEDY 233
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    277 VFVPYDALLYSL-----PYKHTP-YQVLRNNPKLREAYDAVLTITVESQEKTFYQAFTEAAARgEIPEKLEFDQVSPLFG 350
Cdd:cd06385  234 AFFYIDIFGASLqsgqfPDPQRPwERGDADDNSAREAFQAVKIITYKEPDNPEYKEFLKQLKT-EAMEMFNFTVEDGLMN 312
                        330       340       350       360       370
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 945225    351 TI----YNSIYFIAQAMNNAMKENGQAGAASLV-QHSRNMQFHGFNQLMRTDSNGN 401
Cdd:cd06385  313 LIaasfHDGVLLYAHAVNETLAHGGTVTNGSAItQRMWNRSFYGVTGYVKIDENGD 368
STKc_NLK cd07853
Catalytic domain of the Serine/Threonine Kinase, Nemo-Like Kinase; STKs catalyze the transfer ...
567-746 2.68e-07

Catalytic domain of the Serine/Threonine Kinase, Nemo-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NLK is an atypical mitogen-activated protein kinase (MAPK) that is not regulated by a MAPK kinase. It functions downstream of the MAPK kinase kinase Tak1, which also plays a role in activating the JNK and p38 MAPKs. The Tak1/NLK pathways are regulated by Wnts, a family of secreted proteins that is critical in the control of asymmetric division and cell polarity. NLK can phosphorylate transcription factors from the TCF/LEF family, inhibiting their ability to activate the transcription of target genes. In prostate cancer cells, NLK is involved in regulating androgen receptor-mediated transcription and its expression is altered during cancer progression. MAPKs are important mediators of cellular responses to extracellular signals. The NLK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173748 [Multi-domain]  Cd Length: 372  Bit Score: 53.98  E-value: 2.68e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    567 EGDWVWLKKFSlGDFGDLKSIKsRASDVFEMMKDLRHENI--------NPLLGFFYDsgMFaIVTEFCSRGSLEDILTNQ 638
Cdd:cd07853   24 DGKRVALKKMP-NVFQNLVSCK-RVFRELKMLCFFKHDNVlsaldilqPPHIDPFEE--IY-VVTELMQSDLHKIIVSPQ 98
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    639 DVKLDWMfkSSLLLDLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGFNDILEMLRLSEEESSMEELLWTAPELL 718
Cdd:cd07853   99 PLSSDHV--KVFLYQILRGLKYLHSAGILHRDIKPGNLLVNSNCVLKICDFGLARVEEPDESKHMTQEVVTQYYRAPEIL 176
                        170       180
                 ....*....|....*....|....*...
gi 945225    719 rapRGSRLGSFAGDVYSFAIIMQEVMVR 746
Cdd:cd07853  177 ---MGSRHYTSAVDIWSVGCIFAELLGR 201
STKc_PAK4 cd06657
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 4; STKs catalyze the ...
597-749 3.12e-07

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK4 regulates cell morphology and cytoskeletal organization. It is essential for embryonic viability and proper neural development. Mice lacking PAK4 die due to defects in the fetal heart. In addition, their spinal cord motor neurons showed failure to differentiate and migrate. PAK4 also plays a role in cell survival and tumorigenesis. It is overexpressed in many primary tumors including colon, esophageal, and mammary tumors. PAK4 has also been implicated in viral and bacterial infection pathways. PAK4 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132988 [Multi-domain]  Cd Length: 292  Bit Score: 53.49  E-value: 3.12e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKLDWMfkSSLLLDLIKGMKYLHHREFVHGRLKSRNC 676
Cdd:cd06657   70 IMRDYQHENVVEMYNSYLVGDELWVVMEFLEGGALTDIVTHTRMNEEQI--AAVCLAVLKALSVLHAQGVIHRDIKSDSI 147
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 945225    677 VV--DGRfvLKVTDYGFNDILEMlRLSEEESSMEELLWTAPELL-RAPRGSRLgsfagDVYSFAIIMQEvMVRGTP 749
Cdd:cd06657  148 LLthDGR--VKLSDFGFCAQVSK-EVPRRKSLVGTPYWMAPELIsRLPYGPEV-----DIWSLGIMVIE-MVDGEP 214
STKc_CDKL2_3 cd07846
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 2 and 3; ...
568-691 3.40e-07

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 2 and 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKL2, also called p56 KKIAMRE, is expressed in testis, kidney, lung, and brain. It functions mainly in mature neurons and plays an important role in learning and memory. Inactivation of CDKL3, also called NKIAMRE (NKIATRE in rat), by translocation is associated with mild mental retardation. It has been reported that CDKL3 is lost in leukemic cells having a chromosome arm 5q deletion, and may contribute to the transformed phenotype. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL2/3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270836 [Multi-domain]  Cd Length: 286  Bit Score: 53.20  E-value: 3.40e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    568 GDWVWLKKFSLGDfgDLKSIKSRASDVFEMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDiLTNQDVKLDWMFK 647
Cdd:cd07846   26 GQIVAIKKFLESE--DDKMVKKIAMREIKMLKQLRHENLVNLIEVFRRKKRWYLVFEFVDHTVLDD-LEKYPNGLDESRV 102
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 945225    648 SSLLLDLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGF 691
Cdd:cd07846  103 RKYLFQILRGIDFCHSHNIIHRDIKPENILVSQSGVVKLCDFGF 146
STKc_SPEG_rpt2 cd14111
Catalytic kinase domain, second repeat, of Giant Serine/Threonine Kinase Striated muscle ...
588-764 4.31e-07

Catalytic kinase domain, second repeat, of Giant Serine/Threonine Kinase Striated muscle preferentially expressed protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Striated muscle preferentially expressed gene (SPEG) generates 4 different isoforms through alternative promoter use and splicing in a tissue-specific manner: SPEGalpha and SPEGbeta are expressed in cardiac and skeletal striated muscle; Aortic Preferentially Expressed Protein-1 (APEG-1) is expressed in vascular smooth muscle; and Brain preferentially expressed gene (BPEG) is found in the brain and aorta. SPEG proteins have mutliple immunoglobulin (Ig), 2 fibronectin type III (FN3), and two kinase domains. They are necessary for cardiac development and survival. The SPEG subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271013 [Multi-domain]  Cd Length: 257  Bit Score: 52.52  E-value: 4.31e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    588 KSRASDVFEMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQ------DVkldwmfkSSLLLDLIKGMKYL 661
Cdd:cd14111   43 KQGVLQEYEILKSLHHERIMALHEAYITPRYLVLIAEFCSGKELLHSLIDRfrysedDV-------VGYLVQILQGLEYL 115
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    662 HHREFVHGRLKSRNCVVDGRFVLKVTDYGFNDILEMLRLSEEESSMEELLWTAPELLrapRGSRLGSfAGDVYSFAIIMQ 741
Cdd:cd14111  116 HGRRVLHLDIKPDNIMVTNLNAIKIVDFGSAQSFNPLSLRQLGRRTGTLEYMAPEMV---KGEPVGP-PADIWSIGVLTY 191
                        170       180
                 ....*....|....*....|....
gi 945225    742 eVMVRG-TPFcmMDLPAQEIINRL 764
Cdd:cd14111  192 -IMLSGrSPF--EDQDPQETEAKI 212
STKc_PhKG2 cd14181
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 2 subunit; STKs ...
584-696 5.37e-07

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 2 subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). The gamma 2 subunit (PhKG2) is also referred to as the testis/liver gamma isoform. Mutations in its gene cause autosomal-recessive glycogenosis of the liver. The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271083 [Multi-domain]  Cd Length: 279  Bit Score: 52.67  E-value: 5.37e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    584 LKSIKSRASDVFEMMKDLR-HENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTnQDVKLDWMFKSSLLLDLIKGMKYLH 662
Cdd:cd14181   55 LEEVRSSTLKEIHILRQVSgHPSIITLIDSYESSTFIFLVFDLMRRGELFDYLT-EKVTLSEKETRSIMRSLLEAVSYLH 133
                         90       100       110
                 ....*....|....*....|....*....|....
gi 945225    663 HREFVHGRLKSRNCVVDGRFVLKVTDYGFNDILE 696
Cdd:cd14181  134 ANNIVHRDLKPENILLDDQLHIKLSDFGFSCHLE 167
PLN00034 PLN00034
mitogen-activated protein kinase kinase; Provisional
596-695 5.78e-07

mitogen-activated protein kinase kinase; Provisional


Pssm-ID: 215036 [Multi-domain]  Cd Length: 353  Bit Score: 52.90  E-value: 5.78e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225     596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKLdwmfkSSLLLDLIKGMKYLHHREFVHGRLKSRN 675
Cdd:PLN00034  124 EILRDVNHPNVVKCHDMFDHNGEIQVLLEFMDGGSLEGTHIADEQFL-----ADVARQILSGIAYLHRRHIVHRDIKPSN 198
                          90       100
                  ....*....|....*....|
gi 945225     676 CVVDGRFVLKVTDYGFNDIL 695
Cdd:PLN00034  199 LLINSAKNVKIADFGVSRIL 218
STKc_Pat1_like cd13993
Catalytic domain of Fungal Pat1-like Serine/Threonine kinases; STKs catalyze the transfer of ...
602-740 5.79e-07

Catalytic domain of Fungal Pat1-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Schizosaccharomyces pombe Pat1 (also called Ran1), Saccharomyces cerevisiae VHS1 and KSP1, and similar fungal STKs. Pat1 blocks Mei2, an RNA-binding protein which is indispensable in the initiation of meiosis. Pat1 is inactivated and Mei2 activated, which initiates meiosis, under nutrient-deprived conditions through a signaling cascade involving Ste11. Meiosis induced by Pat1 inactivation may show different characteristics than normal meiosis including aberrant positioning of centromeres. VHS1 was identified in a screen for suppressors of cell cycle arrest at the G1/S transition, while KSP1 may be involved in regulating PRP20, which is required for mRNA export and maintenance of nuclear structure. The Pat1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270895 [Multi-domain]  Cd Length: 267  Bit Score: 52.35  E-value: 5.79e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    602 RHENINPLLGFFYDSGMFAIVTEFCSRGSL-EDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNCVVDG 680
Cdd:cd13993   63 RHPNIITLHDVFETEVAIYIVLEYCPNGDLfEAITENRIYVGKTELIKNVFLQLIDAVKHCHSLGIYHRDIKPENILLSQ 142
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 945225    681 RF-VLKVTDYGfndiLEMLRLSEEESSMEELLWTAPELLR--APRGSRLGSFAGDVYSFAIIM 740
Cdd:cd13993  143 DEgTVKLCDFG----LATTEKISMDFGVGSEFYMAPECFDevGRSLKGYPCAAGDIWSLGIIL 201
STKc_MEKK4 cd06626
Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP) ...
582-749 6.68e-07

Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK4 is a MAPK kinase kinase that phosphorylates and activates the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. JNK and p38 are collectively known as stress-activated MAPKs, as they are activated in response to a variety of environmental stresses and pro-inflammatory cytokines. MEKK4 also plays roles in the re-polarization of the actin cytoskeleton in response to osmotic stress, in the proper closure of the neural tube, in cardiovascular development, and in immune responses. The MEKK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270796 [Multi-domain]  Cd Length: 265  Bit Score: 51.92  E-value: 6.68e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    582 GDLKSIKSRA--SDVFEMmkdLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVkLDWMFKSSLLLDLIKGMK 659
Cdd:cd06626   38 NDPKTIKEIAdeMKVLEG---LDHPNLVRYYGVEVHREEVYIFMEYCQEGTLEELLRHGRI-LDEAVIRVYTLQLLEGLA 113
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    660 YLHHREFVHGRLKSRNCVVDGRFVLKVTDYGFNDIL----EMLRLSEEESSMEELLWTAPELLRAPRGS-RLGsfAGDVY 734
Cdd:cd06626  114 YLHENGIVHRDIKPANIFLDSNGLIKLGDFGSAVKLknntTTMAPGEVNSLVGTPAYMAPEVITGNKGEgHGR--AADIW 191
                        170
                 ....*....|....*
gi 945225    735 SFAIIMQEvMVRGTP 749
Cdd:cd06626  192 SLGCVVLE-MATGKR 205
STKc_PAK2 cd06655
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 2; STKs catalyze the ...
597-749 6.89e-07

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK2 plays a role in pro-apoptotic signaling. It is cleaved and activated by caspases leading to morphological changes during apoptosis. PAK2 is also activated in response to a variety of stresses including DNA damage, hyperosmolarity, serum starvation, and contact inhibition, and may play a role in coordinating the stress response. PAK2 also contributes to cancer cell invasion through a mechanism distinct from that of PAK1. It belongs to the group I PAKs, which contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132986 [Multi-domain]  Cd Length: 296  Bit Score: 52.42  E-value: 6.89e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTnqDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNC 676
Cdd:cd06655   69 VMKELKNPNIVNFLDSFLVGDELFVVMEYLAGGSLTDVVT--ETCMDEAQIAAVCRECLQALEFLHANQVIHRDIKSDNV 146
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 945225    677 VVDGRFVLKVTDYGFNDILEMlRLSEEESSMEELLWTAPELL-RAPRGSRLgsfagDVYSFAIIMQEvMVRGTP 749
Cdd:cd06655  147 LLGMDGSVKLTDFGFCAQITP-EQSKRSTMVGTPYWMAPEVVtRKAYGPKV-----DIWSLGIMAIE-MVEGEP 213
PTK_Jak_rpt1 cd05037
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak ...
584-806 8.75e-07

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily is composed of Jak1, Jak2, Jak3, TYK2, and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal catalytic tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. In the case of Jak2, the presumed pseudokinase (repeat 1) domain exhibits dual-specificity kinase activity, phosphorylating two negative regulatory sites in Jak2: Ser523 and Tyr570. Most Jaks are expressed in a wide variety of tissues, except for Jak3, which is expressed only in hematopoietic cells. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). Jaks are also involved in regulating the surface expression of some cytokine receptors. The Jak-STAT pathway is involved in many biological processes including hematopoiesis, immunoregulation, host defense, fertility, lactation, growth, and embryogenesis. The Jak subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270633 [Multi-domain]  Cd Length: 259  Bit Score: 51.71  E-value: 8.75e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    584 LKSIKSRASDVFE-------MMKDLRHENINPLLGFFYDSGmFAIVTEFCSRGSLEDILTNQ--DVKLDWMFKssLLLDL 654
Cdd:cd05037   35 LKVLDSDHRDISEsffetasLMSQISHKHLVKLYGVCVADE-NIMVQEYVRYGPLDKYLRRMgnNVPLSWKLQ--VAKQL 111
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    655 IKGMKYLHHREFVHGRLKSRNCVV-------DGRFVlKVTDYGFNdilemLRLSEEESSMEELLWTAPELLRAPRGSRlg 727
Cdd:cd05037  112 ASALHYLEDKKLIHGNVRGRNILLaregldgYPPFI-KLSDPGVP-----ITVLSREERVDRIPWIAPECLRNLQANL-- 183
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    728 SFAGDVYSFAIIMQEVMVRGT-PFcmMDLPAQEIINRLKKPPPVyrpvvppehAPPECLQL---MKQCWAEAAEQRPTFD 803
Cdd:cd05037  184 TIAADKWSFGTTLWEICSGGEePL--SALSSQEKLQFYEDQHQL---------PAPDCAELaelIMQCWTYEPTKRPSFR 252

                 ...
gi 945225    804 EIF 806
Cdd:cd05037  253 AIL 255
STKc_CDKL5 cd07848
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase Like 5; STKs ...
571-764 9.35e-07

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase Like 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mutations in the gene encoding CDKL5, previously called STK9, are associated with early onset epilepsy and severe mental retardation [X-linked infantile spasm syndrome (ISSX) or West syndrome]. In addition, CDKL5 mutations also sometimes cause a phenotype similar to Rett syndrome (RTT), a progressive neurodevelopmental disorder. These pathogenic mutations are located in the N-terminal portion of the protein within the kinase domain. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270838 [Multi-domain]  Cd Length: 287  Bit Score: 51.92  E-value: 9.35e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    571 VWLKKFSlgDFGDLKSIKSRASDVFEMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKLDWMFKSsL 650
Cdd:cd07848   29 VAIKKFK--DSEENEEVKETTLRELKMLRTLKQENIVELKEAFRRRGKLYLVFEYVEKNMLELLEEMPNGVPPEKVRS-Y 105
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    651 LLDLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGFNDILEMLRLSEEESSMEELLWTAPELLR-APRGSrlgsf 729
Cdd:cd07848  106 IYQLIKAIHWCHKNDIVHRDIKPENLLISHNDVLKLCDFGFARNLSEGSNANYTEYVATRWYRSPELLLgAPYGK----- 180
                        170       180       190
                 ....*....|....*....|....*....|....*
gi 945225    730 AGDVYSFAIIMQEvMVRGTPFcmmdLPAQEIINRL 764
Cdd:cd07848  181 AVDMWSVGCILGE-LSDGQPL----FPGESEIDQL 210
STKc_Kin4 cd14076
Catalytic domain of the yeast Serine/Threonine Kinase, Kin4; STKs catalyze the transfer of the ...
597-750 9.41e-07

Catalytic domain of the yeast Serine/Threonine Kinase, Kin4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Kin4 is a central component of the spindle position checkpoint (SPOC), which monitors spindle position and regulates the mitotic exit network (MEN). Kin4 associates with spindle pole bodies in mother cells to inhibit MEN signaling and delay mitosis until the anaphase nucleus is properly positioned along the mother-bud axis. Kin4 activity is regulated by both the bud neck-associated kinase Elm1 and protein phosphatase 2A. The Kin4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270978 [Multi-domain]  Cd Length: 270  Bit Score: 51.72  E-value: 9.41e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLED-ILTNQdvKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRN 675
Cdd:cd14076   59 ILKGLTHPNIVRLLDVLKTKKYIGIVLEFVSGGELFDyILARR--RLKDSVACRLFAQLISGVAYLHKKGVVHRDLKLEN 136
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 945225    676 CVVDGRFVLKVTDYGFNDILEMLRLSEEESSMEELLWTAPEL--LRAPRGSRlgsfAGDVYSFAIIMQEVMVRGTPF 750
Cdd:cd14076  137 LLLDKNRNLVITDFGFANTFDHFNGDLMSTSCGSPCYAAPELvvSDSMYAGR----KADIWSCGVILYAMLAGYLPF 209
STKc_TBK1 cd13988
Catalytic domain of the Serine/Threonine kinase, TANK Binding Kinase 1; STKs catalyze the ...
582-690 9.87e-07

Catalytic domain of the Serine/Threonine kinase, TANK Binding Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TBK1 is also called T2K and NF-kB-activating kinase. It is widely expressed in most cell types and acts as an IkappaB kinase (IKK)-activating kinase responsible for NF-kB activation in response to growth factors. It plays a role in modulating inflammatory responses through the NF-kB pathway. TKB1 is also a major player in innate immune responses since it functions as a virus-activated kinase necessary for establishing an antiviral state. It phosphorylates IRF-3 and IRF-7, which are important transcription factors for inducing type I interferon during viral infection. In addition, TBK1 may also play roles in cell transformation and oncogenesis. The TBK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270890 [Multi-domain]  Cd Length: 316  Bit Score: 52.11  E-value: 9.87e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    582 GDLKSIKS-------RASDV----FEMMKDLRHENINPLLGFFYD--SGMFAIVTEFCSRGSLEDILTNQDvKLDWMFKS 648
Cdd:cd13988   18 GDLYAVKVfnnlsfmRPLDVqmreFEVLKKLNHKNIVKLFAIEEEltTRHKVLVMELCPCGSLYTVLEEPS-NAYGLPES 96
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 945225    649 SLLL---DLIKGMKYLHHREFVHGRLKSRNCVV----DGRFVLKVTDYG 690
Cdd:cd13988   97 EFLIvlrDVVAGMNHLRENGIVHRDIKPGNIMRvigeDGQSVYKLTDFG 145
STKc_TNIK cd06637
Catalytic domain of the Serine/Threonine Kinase, Traf2- and Nck-Interacting Kinase; STKs ...
603-753 1.07e-06

Catalytic domain of the Serine/Threonine Kinase, Traf2- and Nck-Interacting Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TNIK is an effector of Rap2, a small GTP-binding protein from the Ras family. TNIK specifically activates the c-Jun N-terminal kinase (JNK) pathway and plays a role in regulating the actin cytoskeleton. The TNIK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270807 [Multi-domain]  Cd Length: 296  Bit Score: 51.64  E-value: 1.07e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    603 HENINPLLGFFYDS---GM---FAIVTEFCSRGSLEDILTN---QDVKLDWMfkSSLLLDLIKGMKYLHHREFVHGRLKS 673
Cdd:cd06637   62 HRNIATYYGAFIKKnppGMddqLWLVMEFCGAGSVTDLIKNtkgNTLKEEWI--AYICREILRGLSHLHQHKVIHRDIKG 139
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    674 RNCVVDGRFVLKVTDYGFNDILEMlRLSEEESSMEELLWTAPELLRAPRGSRLG-SFAGDVYSFAIIMQEVMVRGTPFCM 752
Cdd:cd06637  140 QNVLLTENAEVKLVDFGVSAQLDR-TVGRRNTFIGTPYWMAPEVIACDENPDATyDFKSDLWSLGITAIEMAEGAPPLCD 218

                 .
gi 945225    753 M 753
Cdd:cd06637  219 M 219
STKc_PAK_I cd06647
Catalytic domain of the Serine/Threonine Kinase, Group I p21-activated kinase; STKs catalyze ...
597-749 1.09e-06

Catalytic domain of the Serine/Threonine Kinase, Group I p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Group I PAKs, also called conventional PAKs, include PAK1, PAK2, and PAK3. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). They interact with the SH3 domain containing proteins Nck, Grb2 and PIX. Binding of group I PAKs to activated GTPases leads to conformational changes that destabilize the AID, allowing autophosphorylation and full activation of the kinase domain. Known group I PAK substrates include MLCK, Bad, Raf, MEK1, LIMK, Merlin, Vimentin, Myc, Stat5a, and Aurora A, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs are implicated in the regulation of many cellular processes including growth factor receptor-mediated proliferation, cell polarity, cell motility, cell death and survival, and actin cytoskeleton organization. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270814 [Multi-domain]  Cd Length: 261  Bit Score: 51.47  E-value: 1.09e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTnqDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNC 676
Cdd:cd06647   57 VMRENKNPNIVNYLDSYLVGDELWVVMEYLAGGSLTDVVT--ETCMDEGQIAAVCRECLQALEFLHSNQVIHRDIKSDNI 134
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 945225    677 VVDGRFVLKVTDYGFNDILEMlRLSEEESSMEELLWTAPELL-RAPRGSRLgsfagDVYSFAIIMQEvMVRGTP 749
Cdd:cd06647  135 LLGMDGSVKLTDFGFCAQITP-EQSKRSTMVGTPYWMAPEVVtRKAYGPKV-----DIWSLGIMAIE-MVEGEP 201
STKc_Pho85 cd07836
Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase Pho85; ...
597-749 1.32e-06

Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase Pho85; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Pho85 is a multifunctional CDK in yeast. It is regulated by 10 different cyclins (Pcls) and plays a role in G1 progression, cell polarity, phosphate and glycogen metabolism, gene expression, and in signaling changes in the environment. It is not essential for yeast viability and is the functional homolog of mammalian CDK5, which plays a role in central nervous system development. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The Pho85 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143341 [Multi-domain]  Cd Length: 284  Bit Score: 51.33  E-value: 1.32e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFFYDSGMFAIVTEFCSrGSLE---DILTNQDVkLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKS 673
Cdd:cd07836   51 LMKELKHENIVRLHDVIHTENKLMLVFEYMD-KDLKkymDTHGVRGA-LDPNTVKSFTYQLLKGIAFCHENRVLHRDLKP 128
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    674 RNCVVDGRFVLKVTDYGF------------NDILEMLrlseeessmeellWTAPELLrapRGSRLGSFAGDVYSFAIIMQ 741
Cdd:cd07836  129 QNLLINKRGELKLADFGLarafgipvntfsNEVVTLW-------------YRAPDVL---LGSRTYSTSIDIWSVGCIMA 192

                 ....*...
gi 945225    742 EvMVRGTP 749
Cdd:cd07836  193 E-MITGRP 199
STKc_EIF2AK cd13996
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
597-808 1.43e-06

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. eIF-2 phosphorylation is induced in response to cellular stresses including virus infection, heat shock, nutrient deficiency, and the accummulation of unfolded proteins, among others. There are four distinct kinases that phosphorylate eIF-2 and control protein synthesis under different stress conditions: General Control Non-derepressible-2 (GCN2) which is activated during amino acid or serum starvation; protein kinase regulated by RNA (PKR) which is activated by double stranded RNA; heme-regulated inhibitor kinase (HRI) which is activated under heme-deficient conditions; and PKR-like endoplasmic reticulum kinase (PERK) which is activated when misfolded proteins accumulate in the ER. The EIF2AK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270898 [Multi-domain]  Cd Length: 273  Bit Score: 51.14  E-value: 1.43e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENInplLGFFY----DSGMFaIVTEFCSRGSLEDIL------TNQDVKLDWmfksSLLLDLIKGMKYLHHREF 666
Cdd:cd13996   57 ALAKLNHPNI---VRYYTawveEPPLY-IQMELCEGGTLRDWIdrrnssSKNDRKLAL----ELFKQILKGVSYIHSKGI 128
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    667 VHGRLKSRNCVVDGRF-VLKVTDYG-------------FNDILEMLRLSEEESSMEELLWTAPELLRaprgSRLGSFAGD 732
Cdd:cd13996  129 VHRDLKPSNIFLDNDDlQVKIGDFGlatsignqkrelnNLNNNNNGNTSNNSVGIGTPLYASPEQLD----GENYNEKAD 204
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 945225    733 VYSFAIIMQEVMV-RGTPFcmmdlpaqEIINRLKKPPPVYRPVVPPEHAPPEcLQLMKQCWAEAAEQRPTFDEIFNQ 808
Cdd:cd13996  205 IYSLGIILFEMLHpFKTAM--------ERSTILTDLRNGILPESFKAKHPKE-ADLIQSLLSKNPEERPSAEQLLRS 272
PTZ00024 PTZ00024
cyclin-dependent protein kinase; Provisional
597-766 1.50e-06

cyclin-dependent protein kinase; Provisional


Pssm-ID: 240233 [Multi-domain]  Cd Length: 335  Bit Score: 51.69  E-value: 1.50e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225     597 MMKDLRHENINPLLGFFYDSGMFAIVTEFCSrGSLEDILtNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNC 676
Cdd:PTZ00024   73 IMNEIKHENIMGLVDVYVEGDFINLVMDIMA-SDLKKVV-DRKIRLTESQVKCILLQILNGLNVLHKWYFMHRDLSPANI 150
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225     677 VVDGRFVLKVTDYG-------------FNDILEMLRLSEEESSMEELLWTAPELLrapRGSRLGSFAGDVYSFAIIMQEV 743
Cdd:PTZ00024  151 FINSKGICKIADFGlarrygyppysdtLSKDETMQRREEMTSKVVTLWYRAPELL---MGAEKYHFAVDMWSVGCIFAEL 227
                         170       180
                  ....*....|....*....|...
gi 945225     744 MVrGTPFcmmdLPAQEIINRLKK 766
Cdd:PTZ00024  228 LT-GKPL----FPGENEIDQLGR 245
STKc_ASK cd06624
Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase; STKs ...
599-750 1.73e-06

Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily are mitogen-activated protein kinase (MAPK) kinase kinases (MAPKKKs or MKKKs) and include ASK1, ASK2, and MAPKKK15. ASK1 (also called MAPKKK5) functions in the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. It plays important roles in cytokine and stress responses, as well as in reactive oxygen species-mediated cellular responses. ASK1 is implicated in various diseases mediated by oxidative stress including inschemic heart disease, hypertension, vessel injury, brain ischemia, Fanconi anemia, asthma, and pulmonary edema, among others. ASK2 (also called MAPKKK6) functions only in a heteromeric complex with ASK1, and can activate ASK1 by direct phosphorylation. The function of MAPKKK15 is still unknown. The ASK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270794 [Multi-domain]  Cd Length: 268  Bit Score: 50.87  E-value: 1.73e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    599 KDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILtnqdvkldwMFKSSLLLD-----------LIKGMKYLHHREFV 667
Cdd:cd06624   60 SRLSHKNIVQYLGSVSEDGFFKIFMEQVPGGSLSALL---------RSKWGPLKDnentigyytkqILEGLKYLHDNKIV 130
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    668 HGRLKSRNCVVD---GrfVLKVTDYGFNDILEMLRlSEEESSMEELLWTAPELL-RAPRGsrLGSFAgDVYSFAIIMQEV 743
Cdd:cd06624  131 HRDIKGDNVLVNtysG--VVKISDFGTSKRLAGIN-PCTETFTGTLQYMAPEVIdKGQRG--YGPPA-DIWSLGCTIIEM 204

                 ....*..
gi 945225    744 MVRGTPF 750
Cdd:cd06624  205 ATGKPPF 211
STKc_Bck1_like cd06629
Catalytic domain of the Serine/Threonine Kinases, fungal Bck1-like Mitogen-Activated Protein ...
584-690 1.74e-06

Catalytic domain of the Serine/Threonine Kinases, fungal Bck1-like Mitogen-Activated Protein Kinase Kinase Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include the MAPKKKs Saccharomyces cerevisiae Bck1 and Schizosaccharomyces pombe Mkh1, and related proteins. Budding yeast Bck1 is part of the cell integrity MAPK pathway, which is activated by stresses and aggressions to the cell wall. The MAPKKK Bck1, MAPKKs Mkk1 and Mkk2, and the MAPK Slt2 make up the cascade that is important in the maintenance of cell wall homeostasis. Fission yeast Mkh1 is involved in MAPK cascades regulating cell morphology, cell wall integrity, salt resistance, and filamentous growth in response to stress. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The Bck1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270799 [Multi-domain]  Cd Length: 270  Bit Score: 50.84  E-value: 1.74e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    584 LKSIKSRAsdvfEMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDvKLDWMFKSSLLLDLIKGMKYLHH 663
Cdd:cd06629   52 VDALKSEI----DTLKDLDHPNIVQYLGFEETEDYFSIFLEYVPGGSIGSCLRKYG-KFEEDLVRFFTRQILDGLAYLHS 126
                         90       100
                 ....*....|....*....|....*..
gi 945225    664 REFVHGRLKSRNCVVDGRFVLKVTDYG 690
Cdd:cd06629  127 KGILHRDLKADNILVDLEGICKISDFG 153
STKc_ULK1 cd14202
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 1; STKs catalyze the ...
596-750 1.81e-06

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK1 is required for efficient amino acid starvation-induced autophagy and mitochondrial clearance. It associates with three autophagy-related proteins (Atg13, FIP200 amd Atg101) to form the ULK1 complex. All fours proteins are essential for autophagosome formation. ULK1 is regulated by both mammalian target-of rapamycin complex 1 (mTORC1) and AMP-activated protein kinase (AMPK). mTORC1 negatively regulates the ULK1 complex in a nutrient-dependent manner while AMPK stimulates autophagy by inhibiting mTORC1. ULK1 also plays neuron-specific roles and is involved in non-clathrin-coated endocytosis in growth cones, filopodia extension, neurite extension, and axon branching. The ULK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271104 [Multi-domain]  Cd Length: 267  Bit Score: 50.78  E-value: 1.81e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDIL-TNQDVKLDWMfksSLLLDLIKG-MKYLHHREFVHGRLKS 673
Cdd:cd14202   53 KILKELKHENIVALYDFQEIANSVYLVMEYCNGGDLADYLhTMRTLSEDTI---RLFLQQIAGaMKMLHSKGIIHRDLKP 129
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    674 RNCVVD---GR------FVLKVTDYGFNDILEmlRLSEEESSMEELLWTAPELLRaprgSRLGSFAGDVYSFAIIMQEVM 744
Cdd:cd14202  130 QNILLSysgGRksnpnnIRIKIADFGFARYLQ--NNMMAATLCGSPMYMAPEVIM----SQHYDAKADLWSIGTIIYQCL 203

                 ....*.
gi 945225    745 VRGTPF 750
Cdd:cd14202  204 TGKAPF 209
STKc_CDK5 cd07839
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 5; STKs ...
568-690 1.86e-06

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK5 is unusual in that it is regulated by non-cyclin proteins, p35 and p39. It is highly expressed in the nervous system and is critical in normal neural development and function. It plays a role in neuronal migration and differentiation, and is also important in synaptic plasticity and learning. CDK5 also participates in protecting against cell death and promoting angiogenesis. Impaired CDK5 activity is implicated in Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease and acute neuronal injury. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143344 [Multi-domain]  Cd Length: 284  Bit Score: 50.89  E-value: 1.86e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    568 GDWVWLKKFSLGDfgDLKSIKSRASDVFEMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRgSLEDILTNQDVKLDWMFK 647
Cdd:cd07839   25 HEIVALKRVRLDD--DDEGVPSSALREICLLKELKHKNIVRLYDVLHSDKKLTLVFEYCDQ-DLKKYFDSCNGDIDPEIV 101
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 945225    648 SSLLLDLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYG 690
Cdd:cd07839  102 KSFMFQLLKGLAFCHSHNVLHRDLKPQNLLINKNGELKLADFG 144
PBP1_mGluR cd06362
ligand binding domain of metabotropic glutamate receptors (mGluR); Ligand binding domain of ...
79-409 2.27e-06

ligand binding domain of metabotropic glutamate receptors (mGluR); Ligand binding domain of the metabotropic glutamate receptors (mGluR), which are members of the family C of G-protein-coupled receptors that transduce extracellular signals into G-protein activation and ultimately into cellular responses. mGluRs bind to glutamate and function as an excitatory neurotransmitter; they are involved in learning, memory, anxiety, and the perception of pain. Eight subtypes of mGluRs have been cloned so far, and are classified into three groups according to their sequence similarities, transduction mechanisms, and pharmacological profiles. Group I is composed of mGlu1R and mGlu5R that both stimulate PLC hydrolysis. Group II includes mGlu2R and mGlu3R, which inhibit adenylyl cyclase, as do mGlu4R, mGlu6R, mGlu7R, and mGlu8R, which form group III.


Pssm-ID: 380585 [Multi-domain]  Cd Length: 460  Bit Score: 51.53  E-value: 2.27e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225     79 AIERINRDPSFDLSYSFEYVILnEDCQTS-----RALSsFISHHQMASGfiGPTNPGYCEAASLLGNSWDK--------- 144
Cdd:cd06362   39 AIDEINSRPDLLPNITLGFVIL-DDCSSDttaleQALH-FIRDSLLSQE--SAGFCQCSDDPPNLDESFQFydvvgviga 114
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    145 -------------GIFSWACVNY-----ELDNKISYPTFSRTLPS---PIRVLVTVMKYFQWAHAGVISSDEDIWVHTAN 203
Cdd:cd06362  115 esssvsiqvanllRLFKIPQISYastsdELSDKERYPYFLRTVPSdsfQAKAIVDILLHFNWTYVSVVYSEGSYGEEGYK 194
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    204 RVASALRSHGLPVGV--VLTTGQDSQSMRKALQRIHQADRIRIIIMcmhsaLIGGETQMHLLEcAHDLKMTDGTYVFVPY 281
Cdd:cd06362  195 AFKKLARKAGICIAEseRISQDSDEKDYDDVIQKLLQKKNARVVVL-----FADQEDIRGLLR-AAKRLGASGRFIWLGS 268
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    282 DAL---------------------LYSLP-------YKH-TPYQVlRNNPKLREAYDAVLTIT-VESQEKTFYQAFteaa 331
Cdd:cd06362  269 DGWgtniddlkgnedvalgaltvqPYSEEvprfddyFKSlTPSNN-TRNPWFREFWQELFQCSfRPSRENSCNDDK---- 343
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    332 arGEIPEKLEFDQVSPLfGTIYNSIYFIAQAMNNAMKEN--GQAGAA----------SLVQHSRNMQFHG-FNQLMRTDS 398
Cdd:cd06362  344 --LLINKSEGYKQESKV-SFVIDAVYAFAHALHKMHKDLcpGDTGLCqdlmkcidgsELLEYLLNVSFTGeAGGEIRFDE 420
                        410
                 ....*....|.
gi 945225    399 NGNGISEYVIL 409
Cdd:cd06362  421 NGDGPGRYDIM 431
STKc_BUR1 cd07866
Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase (CDK), ...
571-690 2.33e-06

Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase (CDK), Bypass UAS Requirement 1, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BUR1, also called SGV1, is a yeast CDK that is functionally equivalent to mammalian CDK9. It associates with the cyclin BUR2. BUR genes were orginally identified in a genetic screen as factors involved in general transcription. The BUR1/BUR2 complex phosphorylates the C-terminal domain of RNA polymerase II. In addition, this complex regulates histone modification by phosporylating Rad6 and mediating the association of the Paf1 complex with chromatin. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The BUR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270849 [Multi-domain]  Cd Length: 311  Bit Score: 50.78  E-value: 2.33e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    571 VWLKKFSLGDFGD------LKSIKsrasdvfeMMKDLRHENINPLLGFFYDS--------GMFAIVTEFCSRgSLEDILT 636
Cdd:cd07866   36 VALKKILMHNEKDgfpitaLREIK--------ILKKLKHPNVVPLIDMAVERpdkskrkrGSVYMVTPYMDH-DLSGLLE 106
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 945225    637 NQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYG 690
Cdd:cd07866  107 NPSVKLTESQIKCYMLQLLEGINYLHENHILHRDIKAANILIDNQGILKIADFG 160
STKc_SIK cd14071
Catalytic domain of the Serine/Threonine Kinases, Salt-Inducible kinases; STKs catalyze the ...
596-696 2.42e-06

Catalytic domain of the Serine/Threonine Kinases, Salt-Inducible kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SIKs are part of a complex network that regulates Na,K-ATPase to maintain sodium homeostasis and blood pressure. Vertebrates contain three forms of SIKs (SIK1-3) from three distinct genes, which display tissue-specific effects. SIK1, also called SNF1LK, controls steroidogenic enzyme production in adrenocortical cells. In the brain, both SIK1 and SIK2 regulate energy metabolism. SIK2, also called QIK or SNF1LK2, is involved in the regulation of gluconeogenesis in the liver and lipogenesis in adipose tissues, where it phosphorylates the insulin receptor substrate-1. In the liver, SIK3 (also called QSK) regulates cholesterol and bile acid metabolism. In addition, SIK2 plays an important role in the initiation of mitosis and regulates the localization of C-Nap1, a centrosome linker protein. The SIK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270973 [Multi-domain]  Cd Length: 253  Bit Score: 50.08  E-value: 2.42e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQ----DVKLDWMFKSsllldLIKGMKYLHHREFVHGRL 671
Cdd:cd14071   51 QIMKMLNHPHIIKLYQVMETKDMLYLVTEYASNGEIFDYLAQHgrmsEKEARKKFWQ-----ILSAVEYCHKRHIVHRDL 125
                         90       100
                 ....*....|....*....|....*
gi 945225    672 KSRNCVVDGRFVLKVTDYGFNDILE 696
Cdd:cd14071  126 KAENLLLDANMNIKIADFGFSNFFK 150
STKc_TSSK1_2-like cd14165
Catalytic domain of testis-specific serine/threonine kinase 1, TSSK2, and similar proteins; ...
596-805 2.86e-06

Catalytic domain of testis-specific serine/threonine kinase 1, TSSK2, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK1 and TSSK2 are expressed specifically in meiotic and postmeiotic spermatogenic cells, respectively. TSSK2 is localized in the sperm neck, equatorial segment, and mid-piece of the sperm tail. Both TSSK1 and TSSK2 phosphorylate their common substrate TSKS (testis-specific-kinase-substrate). TSSK1/TSSK2 double knock-out mice are sterile without manifesting other defects, making these kinases viable targets for male contraception. The TSSK1/2-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271067 [Multi-domain]  Cd Length: 263  Bit Score: 50.16  E-value: 2.86e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDS-GMFAIVTEFCSRGSLEDILTNQDvKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSR 674
Cdd:cd14165   53 EILARLNHKSIIKTYEIFETSdGKVYIVMELGVQGDLLEFIKLRG-ALPEDVARKMFHQLSSAIKYCHELDIVHRDLKCE 131
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    675 NCVVDGRFVLKVTDYGFNDIL---EMLRLSEEESSMEELLWTAPELLRA----PRGSrlgsfagDVYSFAIIMQeVMVRG 747
Cdd:cd14165  132 NLLLDKDFNIKLTDFGFSKRClrdENGRIVLSKTFCGSAAYAAPEVLQGipydPRIY-------DIWSLGVILY-IMVCG 203
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 945225    748 TpfcmMDLPAQEIINRLKKPPPVYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEI 805
Cdd:cd14165  204 S----MPYDDSNVKKMLKIQKEHRVRFPRSKNLTSECKDLIYRLLQPDVSQRLCIDEV 257
STKc_Chk1 cd14069
Catalytic domain of the Serine/Threonine kinase, Checkpoint kinase 1; STKs catalyze the ...
599-756 3.82e-06

Catalytic domain of the Serine/Threonine kinase, Checkpoint kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chk1 is implicated in many major checkpoints of the cell cycle, providing a link between upstream sensors and the cell cycle engine. It plays an important role in DNA damage response and maintaining genomic stability. Chk1 acts as an effector of the sensor kinase, ATR (ATM and Rad3-related), a member of the PI3K family, which is activated upon DNA replication stress. Chk1 delays mitotic entry in response to replication blocks by inhibiting cyclin dependent kinase (Cdk) activity. In addition, Chk1 contributes to the function of centrosome and spindle-based checkpoints, inhibits firing of origins of DNA replication (Ori), and represses transcription of cell cycle proteins including cyclin B and Cdk1. The Chk1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270971 [Multi-domain]  Cd Length: 261  Bit Score: 49.64  E-value: 3.82e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    599 KDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILtNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNCVV 678
Cdd:cd14069   55 KMLSHKNVVRFYGHRREGEFQYLFLEYASGGELFDKI-EPDVGMPEDVAQFYFQQLMAGLKYLHSCGITHRDIKPENLLL 133
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    679 DGRFVLKVTDYGF------NDILEMLrlseeESSMEELLWTAPELLRAP--RGSRLgsfagDVYSFAIIMQEVMVRGTPF 750
Cdd:cd14069  134 DENDNLKISDFGLatvfryKGKERLL-----NKMCGTLPYVAPELLAKKkyRAEPV-----DVWSCGIVLFAMLAGELPW 203

                 ....*.
gi 945225    751 cmmDLP 756
Cdd:cd14069  204 ---DQP 206
PK_STRAD cd08216
Pseudokinase domain of STE20-related kinase adapter protein; The pseudokinase domain shows ...
597-765 4.54e-06

Pseudokinase domain of STE20-related kinase adapter protein; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. STRAD forms a complex with the scaffolding protein MO25, and the serine/threonine kinase (STK), LKB1, resulting in the activation of the kinase. In the complex, LKB1 phosphorylates and activates adenosine monophosphate-activated protein kinases (AMPKs), which regulate cell energy metabolism and cell polarity. LKB1 is a tumor suppressor linked to the rare inherited disease, Peutz-Jeghers syndrome, which is characterized by a predisposition to benign polyps and hyperpigmentation of the buccal mucosa. There are two forms of STRAD, alpha and beta, that complex with LKB1 and MO25. The structure of STRAD-alpha is available and shows that this protein binds ATP, has an ordered activation loop, and adopts a closed conformation typical of fully active protein kinases. It does not possess activity due to nonconservative substitutions of essential catalytic residues. ATP binding enhances the affinity of STRAD for MO25. The conformation of STRAD-alpha stabilized through ATP and MO25 may be needed to activate LKB1. The STRAD subfamily is part of a larger superfamily that includes the catalytic domains of STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270856 [Multi-domain]  Cd Length: 315  Bit Score: 49.99  E-value: 4.54e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQdvkldwmFKSSL--------LLDLIKGMKYLHHREFVH 668
Cdd:cd08216   52 TSRQLQHPNILPYVTSFVVDNDLYVVTPLMAYGSCRDLLKTH-------FPEGLpelaiafiLRDVLNALEYIHSKGYIH 124
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    669 GRLKSRNCVV--DGRFVLKvtdyGFNDILEMLRL--------SEEESSMEELLWTAPELLRAprgsrlgSFAG-----DV 733
Cdd:cd08216  125 RSVKASHILIsgDGKVVLS----GLRYAYSMVKHgkrqrvvhDFPKSSEKNLPWLSPEVLQQ-------NLLGyneksDI 193
                        170       180       190
                 ....*....|....*....|....*....|..
gi 945225    734 YSFAIIMQEVMVRGTPFCMMDlPAQEIINRLK 765
Cdd:cd08216  194 YSVGITACELANGVVPFSDMP-ATQMLLEKVR 224
PTKc_Wee1_fungi cd14052
Catalytic domain of the Protein Tyrosine Kinases, Fungal Wee1 proteins; PTKs catalyze the ...
593-743 4.66e-06

Catalytic domain of the Protein Tyrosine Kinases, Fungal Wee1 proteins; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of fungal Wee1 proteins, also called Swe1 in budding yeast and Mik1 in fission yeast. Yeast Wee1 is required to control cell size. Wee1 is a cell cycle checkpoint kinase that helps keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of an N-terminal tyr (Y15) residue. During the late G2 phase, CDK1 is activated and mitotic entry is promoted by the removal of this inhibitory phosphorylation by the phosphatase Cdc25. Although Wee1 is functionally a tyr kinase, it is more closely related to serine/threonine kinases (STKs). It contains a catalytic kinase domain sandwiched in between N- and C-terminal regulatory domains. It is regulated by phosphorylation and degradation, and its expression levels are also controlled by circadian clock proteins. The fungal Wee1 subfamily is part of a larger superfamily that includes the catalytic domains of STKs, other PTKs, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270954 [Multi-domain]  Cd Length: 278  Bit Score: 49.73  E-value: 4.66e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    593 DVFEMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVK--LD----WmfksSLLLDLIKGMKYLHHREF 666
Cdd:cd14052   52 SILRELTLDGHDNIVQLIDSWEYHGHLYIQTELCENGSLDVFLSELGLLgrLDefrvW----KILVELSLGLRFIHDHHF 127
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 945225    667 VHGRLKSRNCVVDGRFVLKVTDYGFNDILEMLRlseEESSMEELLWTAPELLraprGSRLGSFAGDVYSFAIIMQEV 743
Cdd:cd14052  128 VHLDLKPANVLITFEGTLKIGDFGMATVWPLIR---GIEREGDREYIAPEIL----SEHMYDKPADIFSLGLILLEA 197
PKc_Wee1_like cd13997
Catalytic domain of the Wee1-like Protein Kinases; PKs catalyze the transfer of the ...
603-750 5.33e-06

Catalytic domain of the Wee1-like Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. This subfamily is composed of the dual-specificity kinase Myt1, the protein tyrosine kinase Wee1, and similar proteins. These proteins are cell cycle checkpoint kinases that are involved in the regulation of cyclin-dependent kinase CDK1, the master engine for mitosis. CDK1 is kept inactivated through phosphorylation of N-terminal thr (T14 by Myt1) and tyr (Y15 by Myt1 and Wee1) residues. Mitosis progression is ensured through activation of CDK1 by dephoshorylation and inactivation of Myt1/Wee1. The Wee1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270899 [Multi-domain]  Cd Length: 252  Bit Score: 49.30  E-value: 5.33e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    603 HENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTN--QDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNCVVDG 680
Cdd:cd13997   59 HPNIVRYYSSWEEGGHLYIQMELCENGSLQDALEElsPISKLSEAEVWDLLLQVALGLAFIHSKGIVHLDIKPDNIFISN 138
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    681 RFVLKVTDYGFNDILEmlrlSEEESSMEELLWTAPELLrapRGSRLGSFAGDVYSFAIIMQEvMVRGTPF 750
Cdd:cd13997  139 KGTCKIGDFGLATRLE----TSGDVEEGDSRYLAPELL---NENYTHLPKADIFSLGVTVYE-AATGEPL 200
STKc_MEKK2 cd06652
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular ...
596-806 5.71e-06

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK2 is a MAPK kinase kinase (MAPKKK or MKKK), that phosphorylates and activates the MAPK kinase MEK5 (or MKK5), which in turn phosphorylates and activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK2 also activates ERK1/2, c-Jun N-terminal kinase (JNK) and p38 through their respective MAPKKs MEK1/2, JNK-activating kinase 2 (JNKK2), and MKK3/6. MEKK2 plays roles in T cell receptor signaling, immune synapse formation, cytokine gene expression, as well as in EGF and FGF receptor signaling. The MEKK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270818 [Multi-domain]  Cd Length: 264  Bit Score: 49.27  E-value: 5.71e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDS--GMFAIVTEFCSRGSLEDILTNQDVKLDWMFKSsLLLDLIKGMKYLHHREFVHGRLKS 673
Cdd:cd06652   56 QLLKNLLHERIVQYYGCLRDPqeRTLSIFMEYMPGGSIKDQLKSYGALTENVTRK-YTRQILEGVHYLHSNMIVHRDIKG 134
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    674 RNCVVDGRFVLKVTDYGFNDILEM--LRLSEEESSMEELLWTAPELLrapRGSRLGSFAgDVYSFAIIMQEVMVRGTPFC 751
Cdd:cd06652  135 ANILRDSVGNVKLGDFGASKRLQTicLSGTGMKSVTGTPYWMSPEVI---SGEGYGRKA-DIWSVGCTVVEMLTEKPPWA 210
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 945225    752 MMdlpaqEIINRLKKPPPVYRPVVPPEHAPPECLQLMKQCWAEaAEQRPTFDEIF 806
Cdd:cd06652  211 EF-----EAMAAIFKIATQPTNPQLPAHVSDHCRDFLKRIFVE-AKLRPSADELL 259
STKc_PAK6 cd06659
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 6; STKs catalyze the ...
597-765 5.74e-06

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK6 may play a role in stress responses through its activation by the mitogen-activated protein kinase (MAPK) p38 and MAPK kinase 6 (MKK6) pathway. PAK6 is highly expressed in the brain. It is not required for viability, but together with PAK5, it is required for normal levels of locomotion and activity, and for learning and memory. Increased expression of PAK6 is found in primary and metastatic prostate cancer. PAK6 may play a role in the regulation of motility. PAK6 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270821 [Multi-domain]  Cd Length: 297  Bit Score: 49.60  E-value: 5.74e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTnqDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNC 676
Cdd:cd06659   71 IMRDYQHPNVVEMYKSYLVGEELWVLMEYLQGGALTDIVS--QTRLNEEQIATVCEAVLQALAYLHSQGVIHRDIKSDSI 148
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    677 V--VDGRfvLKVTDYGF-----NDILEmlrlseEESSMEELLWTAPE-LLRAPRGSRLgsfagDVYSFAIIMQEvMVRGT 748
Cdd:cd06659  149 LltLDGR--VKLSDFGFcaqisKDVPK------RKSLVGTPYWMAPEvISRCPYGTEV-----DIWSLGIMVIE-MVDGE 214
                        170
                 ....*....|....*..
gi 945225    749 PFCMMDLPAQEiINRLK 765
Cdd:cd06659  215 PPYFSDSPVQA-MKRLR 230
STKc_CDK9 cd07865
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 9; STKs ...
597-690 6.10e-06

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 9; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK9, together with a cyclin partner (cyclin T1, T2a, T2b, or K), is the main component of distinct positive transcription elongation factors (P-TEFb), which function as Ser2 C-terminal domain kinases of RNA polymerase II. P-TEFb participates in multiple steps of gene expression including transcription elongation, mRNA synthesis, processing, export, and translation. It also plays a role in mediating cytokine induced transcription networks such as IL6-induced STAT3 signaling. In addition, the CDK9/cyclin T2a complex promotes muscle differentiation and enhances the function of some myogenic regulatory factors. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK9 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270848 [Multi-domain]  Cd Length: 310  Bit Score: 49.67  E-value: 6.10e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLL--------GFFYDSGMFAIVTEFCSRgSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVH 668
Cdd:cd07865   64 ILQLLKHENVVNLIeicrtkatPYNRYKGSIYLVFEFCEH-DLAGLLSNKNVKFTLSEIKKVMKMLLNGLYYIHRNKILH 142
                         90       100
                 ....*....|....*....|..
gi 945225    669 GRLKSRNCVVDGRFVLKVTDYG 690
Cdd:cd07865  143 RDMKAANILITKDGVLKLADFG 164
STKc_MAP4K5 cd06646
Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase ...
568-690 6.17e-06

Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase kinase kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP4K5, also called germinal center kinase-related enzyme (GCKR), has been shown to activate the MAPK c-Jun N-terminal kinase (JNK). MAP4K5 also facilitates Wnt signaling in B cells, and may therefore be implicated in the control of cell fate, proliferation, and polarity. MAP4Ks are involved in some MAPK signaling pathways by activating a MAPK kinase kinase. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. The MAP4K5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270813 [Multi-domain]  Cd Length: 268  Bit Score: 49.26  E-value: 6.17e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    568 GDWVWLKKFSLGDFGDLKSIKSRASDVFE-------MMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDI--LTN- 637
Cdd:cd06646   23 GDVYKARNLHTGELAAVKIIKLEPGDDFSliqqeifMVKECKHCNIVAYFGSYLSREKLWICMEYCGGGSLQDIyhVTGp 102
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 945225    638 -QDVKLDWMFKSSLlldliKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYG 690
Cdd:cd06646  103 lSELQIAYVCRETL-----QGLAYLHSKGKMHRDIKGANILLTDNGDVKLADFG 151
STKc_MAP4K3 cd06645
Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase ...
568-690 6.22e-06

Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase kinase kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP4K3 plays a role in the nutrient-responsive pathway of mTOR (mammalian target of rapamycin) signaling. MAP4K3 is required in the activation of S6 kinase by amino acids and for the phosphorylation of the mTOR-regulated inhibitor of eukaryotic initiation factor 4E. mTOR regulates ribosome biogenesis and protein translation, and is frequently deregulated in cancer. MAP4Ks are involved in MAPK signaling pathways by activating a MAPK kinase kinase. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. The MAP4K3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270812 [Multi-domain]  Cd Length: 272  Bit Score: 49.27  E-value: 6.22e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    568 GDWVWLKKFSLGDFGDLKSIKSRASDVFE-------MMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDI--LTNQ 638
Cdd:cd06645   25 GDVYKARNVNTGELAAIKVIKLEPGEDFAvvqqeiiMMKDCKHSNIVAYFGSYLRRDKLWICMEFCGGGSLQDIyhVTGP 104
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 945225    639 DVKLDWMFKSSlllDLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYG 690
Cdd:cd06645  105 LSESQIAYVSR---ETLQGLYYLHSKGKMHRDIKGANILLTDNGHVKLADFG 153
STKc_Nek5 cd08225
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
597-699 6.70e-06

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Neks are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. The specific function of Nek5 is unknown. Nek5 is one in a family of 11 different Neks (Nek1-11). The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173765 [Multi-domain]  Cd Length: 257  Bit Score: 48.80  E-value: 6.70e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSL-------EDILTNQDVKLDWMFKSSLlldlikGMKYLHHREFVHG 669
Cdd:cd08225   52 LLAKMKHPNIVTFFASFQENGRLFIVMEYCDGGDLmkrinrqRGVLFSEDQILSWFVQISL------GLKHIHDRKILHR 125
                         90       100       110
                 ....*....|....*....|....*....|....*
gi 945225    670 RLKSRNCVVDGR-FVLKVTDYG----FNDILEMLR 699
Cdd:cd08225  126 DIKSQNIFLSKNgMVAKLGDFGiarqLNDSMELAY 160
STKc_CDK10 cd07845
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 10; STKs ...
597-764 7.32e-06

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 10; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK10, also called PISSLRE, is essential for cell growth and proliferation, and acts through the G2/M phase of the cell cycle. CDK10 has also been identified as an important factor in endocrine therapy resistance in breast cancer. CDK10 silencing increases the transcription of c-RAF and the activation of the p42/p44 MAPK pathway, which leads to antiestrogen resistance. Patients who express low levels of CDK10 relapse early on tamoxifen. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK10 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173742 [Multi-domain]  Cd Length: 309  Bit Score: 49.29  E-value: 7.32e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLL----GFFYDSgMFaIVTEFCSR--GSLED----ILTNQDVKldwmfksSLLLDLIKGMKYLHHREF 666
Cdd:cd07845   59 LLLNLRHPNIVELKevvvGKHLDS-IF-LVMEYCEQdlASLLDnmptPFSESQVK-------CLMLQLLRGLQYLHENFI 129
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    667 VHGRLKSRNCVVDGRFVLKVTDYGFNDILEMlrLSEEESSMEELLW-TAPELLrapRGSRLGSFAGDVYSFAIIMQEVMV 745
Cdd:cd07845  130 IHRDLKVSNLLLTDKGCLKIADFGLARTYGL--PAKPMTPKVVTLWyRAPELL---LGCTTYTTAIDMWAVGCILAELLA 204
                        170
                 ....*....|....*....
gi 945225    746 rGTPFcmmdLPAQEIINRL 764
Cdd:cd07845  205 -HKPL----LPGKSEIEQL 218
STKc_Aurora-A cd14116
Catalytic domain of the Serine/Threonine kinase, Aurora-A kinase; STKs catalyze the transfer ...
596-692 7.74e-06

Catalytic domain of the Serine/Threonine kinase, Aurora-A kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). Aurora-A regulates cell cycle events from the late S-phase through the M-phase including centrosome maturation, mitotic entry, centrosome separation, spindle assembly, chromosome alignment, cytokinesis, and mitotic exit. Aurora-A activation depends on its autophosphorylation and binding to the microtubule-associated protein TPX2, which also localizes the kinase to spindle microtubules. Aurora-A is overexpressed in many cancer types such as prostate, ovarian, breast, bladder, gastric, and pancreatic. The Aurora subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271018 [Multi-domain]  Cd Length: 258  Bit Score: 48.80  E-value: 7.74e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILtNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRN 675
Cdd:cd14116   57 EIQSHLRHPNILRLYGYFHDATRVYLILEYAPLGTVYREL-QKLSKFDEQRTATYITELANALSYCHSKRVIHRDIKPEN 135
                         90
                 ....*....|....*..
gi 945225    676 CVVDGRFVLKVTDYGFN 692
Cdd:cd14116  136 LLLGSAGELKIADFGWS 152
STKc_STK33 cd14097
Catalytic domain of Serine/Threonine Kinase 33; STKs catalyze the transfer of the ...
597-749 8.13e-06

Catalytic domain of Serine/Threonine Kinase 33; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK33 is highly expressed in the testis and is present in low levels in most tissues. It may be involved in spermatogenesis and organ ontogenesis. It interacts with and phosphorylates vimentin and may be involved in regulating intermediate filament cytoskeletal dynamics. Its role in promoting the cell viability of KRAS-dependent cancer cells is under debate; some studies have found STK33 to promote cancer cell viability, while other studies have found it to be non-essential. KRAS is the most commonly mutated human oncogene, thus, studies on the role of STK33 in KRAS mutant cancer cells are important. The STK33 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270999 [Multi-domain]  Cd Length: 266  Bit Score: 48.70  E-value: 8.13e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDV----KLDWMFKSsllldLIKGMKYLHHREFVHGRLK 672
Cdd:cd14097   53 ILKHVNHAHIIHLEEVFETPKRMYLVMELCEDGELKELLLRKGFfsenETRHIIQS-----LASAVAYLHKNDIVHRDLK 127
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    673 SRNCVVDG-------RFVLKVTDYGFNDILEMLRLSEEESSMEELLWTAPELLRAprgsRLGSFAGDVYSFAIIMQeVMV 745
Cdd:cd14097  128 LENILVKSsiidnndKLNIKVTDFGLSVQKYGLGEDMLQETCGTPIYMAPEVISA----HGYSQQCDIWSIGVIMY-MLL 202

                 ....
gi 945225    746 RGTP 749
Cdd:cd14097  203 CGEP 206
PKc_TOPK cd14001
Catalytic domain of the Dual-specificity protein kinase, Lymphokine-activated killer ...
570-744 8.69e-06

Catalytic domain of the Dual-specificity protein kinase, Lymphokine-activated killer T-cell-originated protein kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TOPK, also called PDZ-binding kinase (PBK), is activated at the early stage of mitosis and plays a critical role in cytokinesis. It partly functions as a mitogen-activated protein kinase (MAPK) kinase and is capable of phosphorylating p38, JNK1, and ERK2. TOPK also plays a role in DNA damage sensing and repair through its phosphorylation of histone H2AX. It contributes to cancer development and progression by downregulating the function of tumor suppressor p53 and reducing cell-cycle regulatory proteins. TOPK is found highly expressed in breast and skin cancer cells. The TOPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270903 [Multi-domain]  Cd Length: 292  Bit Score: 48.93  E-value: 8.69e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    570 WVWLKKFSLGDFGDLKSIKSRASDVFEMMKDLRHENInplLGF--FYDS--GMFAIVTEFCSRgSLEDILTNQDVKLDWM 645
Cdd:cd14001   31 WAVKKINSKCDKGQRSLYQERLKEEAKILKSLNHPNI---VGFraFTKSedGSLCLAMEYGGK-SLNDLIEERYEAGLGP 106
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    646 FKSS----LLLDLIKGMKYLHH-REFVHGRLKSRNCVVDGRF-VLKVTDYG----FNDILEMLrLSEEESSMEELLWTAP 715
Cdd:cd14001  107 FPAAtilkVALSIARALEYLHNeKKILHGDIKSGNVLIKGDFeSVKLCDFGvslpLTENLEVD-SDPKAQYVGTEPWKAK 185
                        170       180
                 ....*....|....*....|....*....
gi 945225    716 ELLRapRGSRLGSFAgDVYSFAIIMQEVM 744
Cdd:cd14001  186 EALE--EGGVITDKA-DIFAYGLVLWEMM 211
PBP1_CaSR cd06364
ligand-binding domain of the CaSR calcium-sensing receptor, a member of the family C receptors ...
79-196 8.83e-06

ligand-binding domain of the CaSR calcium-sensing receptor, a member of the family C receptors within the G-protein coupled receptor superfamily; Ligand-binding domain of the CaSR calcium-sensing receptor, which is a member of the family C receptors within the G-protein coupled receptor superfamily. CaSR provides feedback control of extracellular calcium homeostasis by responding sensitively to acute fluctuations in extracellular ionized Ca2+ concentration. This ligand-binding domain has homology to the bacterial leucine-isoleucine-valine binding protein (LIVBP) and a leucine binding protein (LBP). CaSR is widely expressed in mammalian tissues and is active in tissues that are not directly involved in extracellular calcium homeostasis. Moreover, CaSR responds to aromatic, aliphatic, and polar amino acids, but not to positively charged or branched chain amino acids, which suggests that changes in plasma amino acid levels are likely to modulate whole body calcium metabolism. Additionally, the family C GPCRs includes at least two receptors with broad-spectrum amino acid-sensing properties: GPRC6A which recognizes basic and various aliphatic amino acids, its gold-fish homolog the 5.24 chemoreceptor, and a specific taste receptor (T1R) which responds to aliphatic, polar, charged, and branched amino acids, but not to aromatic amino acids.


Pssm-ID: 380587 [Multi-domain]  Cd Length: 473  Bit Score: 49.56  E-value: 8.83e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225     79 AIERINRDPSFDLSYSFEYVILNEDCQTSRALSSFIShhqMASGfIGPTNPGY-CEA----ASLLGNSWDK--------- 144
Cdd:cd06364   45 AIEEINNSPDLLPNITLGYRIYDSCATISKALRAALA---LVNG-QEETNLDErCSGgppvAAVIGESGSTlsiavartl 120
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    145 GIFSWACVNYE-----LDNKISYPTFSRTLPSPI---RVLVTVMKYFQWAHAGVISSDED 196
Cdd:cd06364  121 GLFYIPQVSYFascacLSDKKQFPSFLRTIPSDYyqsRALAQLVKHFGWTWVGAIASDDD 180
STKc_WNK3 cd14031
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3; STKs catalyze ...
565-808 1.03e-05

Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK3 shows a restricted expression pattern; it is found at high levels in the pituary glands and is also expressed in the kidney and brain. It has been shown to regulate many ion transporters including members of the SLC12A family of cation-chloride cotransporters such as NCC and NKCC2, the renal potassium channel ROMK, and the epithelial calcium channels TRPV5 and TRPV6. WNK3 appears to sense low-chloride hypotonic stress and under these conditions, it activates SPAK, which directly interacts and phosphorylates cation-chloride cotransporters. WNK3 has also been shown to promote cell survival, possibly through interaction with procaspase-3 and HSP70. WNKs comprise a subfamily of STKs with an unusual placement of the catalytic lysine relative to all other protein kinases. The WNK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270933 [Multi-domain]  Cd Length: 275  Bit Score: 48.56  E-value: 1.03e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    565 IYEG----DWVWLKKFSLGDFGDLKSIKSRASDVFEMMKDLRHENINPllgfFYDS--------GMFAIVTEFCSRGSLE 632
Cdd:cd14031   26 VYKGldteTWVEVAWCELQDRKLTKAEQQRFKEEAEMLKGLQHPNIVR----FYDSwesvlkgkKCIVLVTELMTSGTLK 101
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    633 DILTNQDVKLDWMFKsSLLLDLIKGMKYLHHRE--FVHGRLKSRNCVVDG-RFVLKVTDYGfndILEMLRLSEEESSMEE 709
Cdd:cd14031  102 TYLKRFKVMKPKVLR-SWCRQILKGLQFLHTRTppIIHRDLKCDNIFITGpTGSVKIGDLG---LATLMRTSFAKSVIGT 177
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    710 LLWTAPELLRAPRGSRLgsfagDVYSFAIIMQEVMVRGTPFCMMDLPAQeiinRLKKPPPVYRPVVPPEHAPPECLQLMK 789
Cdd:cd14031  178 PEFMAPEMYEEHYDESV-----DVYAFGMCMLEMATSEYPYSECQNAAQ----IYRKVTSGIKPASFNKVTDPEVKEIIE 248
                        250
                 ....*....|....*....
gi 945225    790 QCWAEAAEQRPTFDEIFNQ 808
Cdd:cd14031  249 GCIRQNKSERLSIKDLLNH 267
STKc_NUAK2 cd14161
Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK 2; STKs ...
573-694 1.11e-05

Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NUAK proteins are classified as AMP-activated protein kinase (AMPK)-related kinases, which like AMPK are activated by the major tumor suppressor LKB1. Vertebrates contain two NUAK proteins, called NUAK1 and NUAK2. NUAK2, also called SNARK (Sucrose, non-fermenting 1/AMP-activated protein kinase-related kinase), is involved in energy metabolism. It is activated by hyperosmotic stress, DNA damage, and nutrients such as glucose and glutamine. NUAK2-knockout mice develop obesity, altered serum lipid profiles, hyperinsulinaemia, hyperglycaemia, and impaired glucose tolerance. NUAK2 is implicated in regulating actin stress fiber assembly through its association with myosin phosphatase Rho-interacting protein (MRIP), which leads to an increase in myosin regulatory light chain (MLC) phosphorylation. It is also associated with tumor growth, migration, and oncogenicity of melanoma cells. The NUAK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271063 [Multi-domain]  Cd Length: 255  Bit Score: 48.41  E-value: 1.11e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    573 LKKFSLGDFGDLKSIKSRasdvFEMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDvKLDWMFKSSLLL 652
Cdd:cd14161   35 IRKDRIKDEQDLLHIRRE----IEIMSSLNHPHIISVYEVFENSSKIVIVMEYASRGDLYDYISERQ-RLSELEARHFFR 109
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 945225    653 DLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGFNDI 694
Cdd:cd14161  110 QIVSAVHYCHANGIVHRDLKLENILLDANGNIKIADFGLSNL 151
STKc_OSR1_SPAK cd06610
Catalytic domain of the Serine/Threonine Kinases, Oxidative stress response kinase and ...
597-749 1.19e-05

Catalytic domain of the Serine/Threonine Kinases, Oxidative stress response kinase and Ste20-related proline alanine-rich kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SPAK is also referred to as STK39 or PASK (proline-alanine-rich STE20-related kinase). OSR1 and SPAK regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. They are also implicated in cytoskeletal rearrangement, cell differentiation, transformation and proliferation. OSR1 and SPAK contain a conserved C-terminal (CCT) domain, which recognizes a unique motif ([RK]FX[VI]) present in their activating kinases (WNK1/WNK4) and their substrates. The OSR1 and SPAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270787 [Multi-domain]  Cd Length: 267  Bit Score: 48.12  E-value: 1.19e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILT---NQDVkLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKS 673
Cdd:cd06610   52 AMSQCNHPNVVSYYTSFVVGDELWLVMPLLSGGSLLDIMKssyPRGG-LDEAIIATVLKEVLKGLEYLHSNGQIHRDVKA 130
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 945225    674 RNCVVDGRFVLKVTDYGFNDILE---MLRLSEEESSMEELLWTAPELLRAPRGSrlgSFAGDVYSFAIIMQEvMVRGTP 749
Cdd:cd06610  131 GNILLGEDGSVKIADFGVSASLAtggDRTRKVRKTFVGTPCWMAPEVMEQVRGY---DFKADIWSFGITAIE-LATGAA 205
STKc_STK10 cd06644
Catalytic domain of the Serine/Threonine Kinase, STK10 (also called Lymphocyte-Oriented Kinase ...
596-690 1.43e-05

Catalytic domain of the Serine/Threonine Kinase, STK10 (also called Lymphocyte-Oriented Kinase or LOK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK10/LOK is also called polo-like kinase kinase 1 in Xenopus (xPlkk1). It is highly expressed in lymphocytes and is responsible in regulating leukocyte function associated antigen (LFA-1)-mediated lymphocyte adhesion. It plays a role in regulating the CD28 responsive element in T cells, and may also function as a regulator of polo-like kinase 1 (Plk1), a protein which is overexpressed in multiple tumor types. The STK10 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132975 [Multi-domain]  Cd Length: 292  Bit Score: 48.10  E-value: 1.43e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRN 675
Cdd:cd06644   61 EILATCNHPYIVKLLGAFYWDGKLWIMIEFCPGGAVDAIMLELDRGLTEPQIQVICRQMLEALQYLHSMKIIHRDLKAGN 140
                         90
                 ....*....|....*
gi 945225    676 CVVDGRFVLKVTDYG 690
Cdd:cd06644  141 VLLTLDGDIKLADFG 155
STKc_PCTAIRE1 cd07873
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-1 kinase; STKs catalyze the transfer ...
597-691 1.45e-05

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-1 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-1 is expressed ubiquitously and is localized in the cytoplasm. Its kinase activity is cell cycle dependent and peaks at the S and G2 phases. PCTAIRE-1 is highly expressed in the brain and may play a role in regulating neurite outgrowth. It can also associate with Trap (Tudor repeat associator with PCTAIRE-2), a physiological partner of PCTAIRE-2; with p11, a small dimeric protein with similarity to S100; and with 14-3-3 proteins, mediators of phosphorylation-dependent interactions in many different proteins. PCTAIRE-1 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270854 [Multi-domain]  Cd Length: 297  Bit Score: 48.08  E-value: 1.45e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFFYDSGMFAIVTEFCSRG---SLED---ILTNQDVKLdwmfkssLLLDLIKGMKYLHHREFVHGR 670
Cdd:cd07873   53 LLKDLKHANIVTLHDIIHTEKSLTLVFEYLDKDlkqYLDDcgnSINMHNVKL-------FLFQLLRGLAYCHRRKVLHRD 125
                         90       100
                 ....*....|....*....|.
gi 945225    671 LKSRNCVVDGRFVLKVTDYGF 691
Cdd:cd07873  126 LKPQNLLINERGELKLADFGL 146
STKc_BMPR2_AMHR2 cd14054
Catalytic domain of the Serine/Threonine Kinases, Bone Morphogenetic Protein and ...
600-746 1.55e-05

Catalytic domain of the Serine/Threonine Kinases, Bone Morphogenetic Protein and Anti-Muellerian Hormone Type II Receptors; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BMPR2 and AMHR2 belong to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, BMPs, activins, growth and differentiation factors (GDFs), and AMH, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. Type II receptors are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. BMPR2 and AMHR2 act primarily as a receptor for BMPs and AMH, respectively. BMPs induce bone and cartilage formation, as well as regulate tooth, kidney, skin, hair, haematopoietic, and neuronal development. Mutations in BMPR2A is associated with familial pulmonary arterial hypertension. AMH is mainly responsible for the regression of Mullerian ducts during male sex differentiation. It is expressed exclusively by somatic cells of the gonads. Mutations in either AMH or AMHR2 cause persistent Mullerian duct syndrome (PMDS), a rare form of male pseudohermaphroditism characterized by the presence of Mullerian derivatives (ovary and tubes) in otherwise normally masculine males. The BMPR2/AMHR2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270956 [Multi-domain]  Cd Length: 300  Bit Score: 48.13  E-value: 1.55e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    600 DLRHENINPLLGffYDSGMFA-------IVTEFCSRGSLEDILTNQdvKLDWMFKSSLLLDLIKGMKYLH---HRE---- 665
Cdd:cd14054   45 LMEHSNILRFIG--ADERPTAdgrmeylLVLEYAPKGSLCSYLREN--TLDWMSSCRMALSLTRGLAYLHtdlRRGdqyk 120
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    666 --FVHGRLKSRNCVV--DGRFVLkvTDYGFNDILEMLRLSEEESSMEELL---------WTAPELLRAP---RGSRLGSF 729
Cdd:cd14054  121 paIAHRDLNSRNVLVkaDGSCVI--CDFGLAMVLRGSSLVRGRPGAAENAsisevgtlrYMAPEVLEGAvnlRDCESALK 198
                        170
                 ....*....|....*..
gi 945225    730 AGDVYSFAIIMQEVMVR 746
Cdd:cd14054  199 QVDVYALGLVLWEIAMR 215
LivK COG0683
ABC-type branched-chain amino acid transport system, periplasmic component [Amino acid ...
52-409 1.58e-05

ABC-type branched-chain amino acid transport system, periplasmic component [Amino acid transport and metabolism];


Pssm-ID: 440447 [Multi-domain]  Cd Length: 314  Bit Score: 48.39  E-value: 1.58e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225     52 PYKIGVV----GPWAcdsLFSKALpEVAARLAIERINRDPSFdLSYSFEYVILNEDCQTSRALS---SFISHHQmASGFI 124
Cdd:COG0683    3 PIKIGVLlpltGPYA---ALGQPI-KNGAELAVEEINAAGGV-LGRKIELVVEDDASDPDTAVAaarKLIDQDK-VDAIV 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    125 GPTNPGYCEAASLLGNswDKGI--FSWACVNYELDNKISYPTFSRTLPSP---IRVLVTVMKY-FQWAHAGVISSDEDIW 198
Cdd:COG0683   77 GPLSSGVALAVAPVAE--EAGVplISPSATAPALTGPECSPYVFRTAPSDaqqAEALADYLAKkLGAKKVALLYDDYAYG 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    199 VHTANRVASALRSHGLPVGVVLTTGQDSQSMRKALQRIHQADririiimcmhsaliggetqmhllecahdlkmtdgtyvf 278
Cdd:COG0683  155 QGLAAAFKAALKAAGGEVVGEEYYPPGTTDFSAQLTKIKAAG-------------------------------------- 196
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    279 vPyDALLYSLPYKHTPyQVLRNnpkLREA-YDAVLTitvesqeKTFYQAFTEAAARgeipeklefdQVSPLFGTIYNSIY 357
Cdd:COG0683  197 -P-DAVFLAGYGGDAA-LFIKQ---AREAgLKGPLN-------KAFVKAYKAKYGR----------EPSSYAAAGYDAAL 253
                        330       340       350       360       370
                 ....*....|....*....|....*....|....*....|....*....|..
gi 945225    358 FIAQAMNNAMKENGQAGAASLvqhsRNMQFHGFNQLMRTDSNGNGISEYVIL 409
Cdd:COG0683  254 LLAEAIEKAGSTDREAVRDAL----EGLKFDGVTGPITFDPDGQGVQPVYIV 301
STKc_PhKG1 cd14182
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 1 subunit; STKs ...
603-750 1.70e-05

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 1 subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). The gamma 1 subunit (PhKG1) is also referred to as the muscle gamma isoform. The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271084 [Multi-domain]  Cd Length: 276  Bit Score: 47.99  E-value: 1.70e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    603 HENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQdVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNCVVDGRF 682
Cdd:cd14182   69 HPNIIQLKDTYETNTFFFLVFDLMKKGELFDYLTEK-VTLSEKETRKIMRALLEVICALHKLNIVHRDLKPENILLDDDM 147
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    683 VLKVTDYGFNdiLEMLRLSEEESSMEELLWTAPELLRAPRGSRLGSFAG--DVYSFAIIMQEVMVRGTPF 750
Cdd:cd14182  148 NIKLTDFGFS--CQLDPGEKLREVCGTPGYLAPEIIECSMDDNHPGYGKevDMWSTGVIMYTLLAGSPPF 215
STKc_DCKL3 cd14185
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 3 (also called ...
597-691 1.71e-05

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 3 (also called Doublecortin-like and CAM kinase-like 3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL3 (or DCAMKL3) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. DCKL3 contains a single DCX domain (instead of a tandem) and a C-terminal kinase domain with similarity to CAMKs. It has been shown to interact with tubulin and JIP1/2. The DCKL3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271087 [Multi-domain]  Cd Length: 258  Bit Score: 47.64  E-value: 1.71e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTnQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNC 676
Cdd:cd14185   51 IIKSLSHPNIVKLFEVYETEKEIYLILEYVRGGDLFDAII-ESVKFTEHDAALMIIDLCEALVYIHSKHIVHRDLKPENL 129
                         90
                 ....*....|....*....
gi 945225    677 VV----DGRFVLKVTDYGF 691
Cdd:cd14185  130 LVqhnpDKSTTLKLADFGL 148
STKc_LKB1 cd14119
Catalytic domain of the Serine/Threonine kinase, Liver Kinase B1; STKs catalyze the transfer ...
597-697 2.12e-05

Catalytic domain of the Serine/Threonine kinase, Liver Kinase B1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LKB1, also called STK11, was first identified as a tumor suppressor responsible for Peutz-Jeghers syndrome, a disorder that leads to an increased risk of spontaneous epithelial cancer. It serves as a master upstream kinase that activates AMP-activated protein kinase (AMPK) and most AMPK-like kinases. LKB1 and AMPK are part of an energy-sensing pathway that links cell energy to metabolism and cell growth. They play critical roles in the establishment and maintenance of cell polarity, cell proliferation, cytoskeletal organization, as well as T-cell metabolism, including T-cell development, homeostasis, and effector function. To be activated, LKB1 requires the adaptor proteins STe20-Related ADaptor (STRAD) and mouse protein 25 (MO25). The LKB1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271021 [Multi-domain]  Cd Length: 255  Bit Score: 47.25  E-value: 2.12e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFFYD--SGMFAIVTEFCSRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSR 674
Cdd:cd14119   47 ILRRLNHRNVIKLVDVLYNeeKQKLYMVMEYCVGGLQEMLDSAPDKRLPIWQAHGYFVQLIDGLEYLHSQGIIHKDIKPG 126
                         90       100
                 ....*....|....*....|...
gi 945225    675 NCVVDGRFVLKVTDYGFNDILEM 697
Cdd:cd14119  127 NLLLTTDGTLKISDFGVAEALDL 149
STKc_PAK1 cd06654
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 1; STKs catalyze the ...
604-749 2.28e-05

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK1 is important in the regulation of many cellular processes including cytoskeletal dynamics, cell motility, growth, and proliferation. Although PAK1 has been regarded mainly as a cytosolic protein, recent reports indicate that PAK1 also exists in significant amounts in the nucleus, where it is involved in transcription modulation and in cell cycle regulatory events. PAK1 is also involved in transformation and tumorigenesis. Its overexpression, hyperactivation and increased nuclear accumulation is correlated to breast cancer invasiveness and progression. Nuclear accumulation is also linked to tamoxifen resistance in breast cancer cells. PAK1 belongs to the group I PAKs, which contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270820 [Multi-domain]  Cd Length: 296  Bit Score: 47.80  E-value: 2.28e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    604 ENINPLLGFFYDSGMFA----IVTEFCSRGSLEDILTnqDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNCVVD 679
Cdd:cd06654   73 ENKNPNIVNYLDSYLVGdelwVVMEYLAGGSLTDVVT--ETCMDEGQIAAVCRECLQALEFLHSNQVIHRDIKSDNILLG 150
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 945225    680 GRFVLKVTDYGFNDILEMlRLSEEESSMEELLWTAPELL-RAPRGSRLgsfagDVYSFAIIMQEvMVRGTP 749
Cdd:cd06654  151 MDGSVKLTDFGFCAQITP-EQSKRSTMVGTPYWMAPEVVtRKAYGPKV-----DIWSLGIMAIE-MIEGEP 214
STKc_MAP4K4_6_N cd06636
N-terminal Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase ...
603-753 2.28e-05

N-terminal Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 and 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. MAP4K4 is also called Nck Interacting kinase (NIK). It facilitates the activation of the MAPKs, extracellular signal-regulated kinase (ERK) 1, ERK2, and c-Jun N-terminal kinase (JNK), by phosphorylating and activating MEKK1. MAP4K4 plays a role in tumor necrosis factor (TNF) alpha-induced insulin resistance. MAP4K4 silencing in skeletal muscle cells from type II diabetic patients restores insulin-mediated glucose uptake. MAP4K4, through JNK, also plays a broad role in cell motility, which impacts inflammation, homeostasis, as well as the invasion and spread of cancer. MAP4K4 is found to be highly expressed in most tumor cell lines relative to normal tissue. MAP4K6 (also called MINK for Misshapen/NIKs-related kinase) is activated after Ras induction and mediates activation of p38 MAPK. MAP4K6 plays a role in cell cycle arrest, cytoskeleton organization, cell adhesion, and cell motility. The MAP4K4/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270806 [Multi-domain]  Cd Length: 282  Bit Score: 47.69  E-value: 2.28e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    603 HENINPLLGFF-------YDSGMFaIVTEFCSRGSLEDILTNQD---VKLDWMfkSSLLLDLIKGMKYLHHREFVHGRLK 672
Cdd:cd06636   72 HRNIATYYGAFikksppgHDDQLW-LVMEFCGAGSVTDLVKNTKgnaLKEDWI--AYICREILRGLAHLHAHKVIHRDIK 148
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    673 SRNCVVDGRFVLKVTDYGFNDILEMlRLSEEESSMEELLWTAPELLRAPRG-SRLGSFAGDVYSFAIIMQEVMVRGTPFC 751
Cdd:cd06636  149 GQNVLLTENAEVKLVDFGVSAQLDR-TVGRRNTFIGTPYWMAPEVIACDENpDATYDYRSDIWSLGITAIEMAEGAPPLC 227

                 ..
gi 945225    752 MM 753
Cdd:cd06636  228 DM 229
STKc_PAK3 cd06656
Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3; Serine ...
604-749 2.55e-05

Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3; Serine/threonine kinases (STKs), p21-activated kinase (PAK) 3, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. PAK3 belongs to group I. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAK3 is highly expressed in the brain. It is implicated in neuronal plasticity, synapse formation, dendritic spine morphogenesis, cell cycle progression, neuronal migration, and apoptosis. Inactivating mutations in the PAK3 gene cause X-linked non-syndromic mental retardation, the severity of which depends on the site of the mutation.


Pssm-ID: 132987 [Multi-domain]  Cd Length: 297  Bit Score: 47.41  E-value: 2.55e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    604 ENINPLLGFFYDSGMFA----IVTEFCSRGSLEDILTnqDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNCVVD 679
Cdd:cd06656   72 ENKNPNIVNYLDSYLVGdelwVVMEYLAGGSLTDVVT--ETCMDEGQIAAVCRECLQALDFLHSNQVIHRDIKSDNILLG 149
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 945225    680 GRFVLKVTDYGFNDILEMlRLSEEESSMEELLWTAPELL-RAPRGSRLgsfagDVYSFAIIMQEvMVRGTP 749
Cdd:cd06656  150 MDGSVKLTDFGFCAQITP-EQSKRSTMVGTPYWMAPEVVtRKAYGPKV-----DIWSLGIMAIE-MVEGEP 213
STKc_SnRK2-3 cd14665
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
599-808 2.65e-05

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 2, group 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK2 is represented in this cd. SnRK2s are involved in plant response to abiotic stresses and abscisic acid (ABA)-dependent plant development. The SnRK2s subfamily is in turn classed into three subgroups, all 3 of which are represented in this CD. Group 1 comprises kinases not activated by ABA, group 2 - kinases not activated or activated very weakly by ABA (depending on plant species), and group 3 - kinases strongly activated by ABA. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271135 [Multi-domain]  Cd Length: 257  Bit Score: 47.29  E-value: 2.65e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    599 KDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTN----QDVKLDWMFKSsllldLIKGMKYLHHREFVHGRLKSR 674
Cdd:cd14665   51 RSLRHPNIVRFKEVILTPTHLAIVMEYAAGGELFERICNagrfSEDEARFFFQQ-----LISGVSYCHSMQICHRDLKLE 125
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    675 NCVVDGRFV--LKVTDYGFNDilEMLRLSEEESSMEELLWTAPELLRapRGSRLGSFAgDVYSFAIIMQEVMVRGTPFCM 752
Cdd:cd14665  126 NTLLDGSPAprLKICDFGYSK--SSVLHSQPKSTVGTPAYIAPEVLL--KKEYDGKIA-DVWSCGVTLYVMLVGAYPFED 200
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 945225    753 MDLPaQEIINRLKKPPPVYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEIFNQ 808
Cdd:cd14665  201 PEEP-RNFRKTIQRILSVQYSIPDYVHISPECRHLISRIFVADPATRITIPEIRNH 255
STKc_PCTAIRE3 cd07871
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-3 kinase; STKs catalyze the transfer ...
597-691 2.70e-05

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-3 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-3 shows a restricted pattern of expression and is present in brain, kidney, and intestine. It is elevated in Alzheimer's disease (AD) and has been shown to associate with paired helical filaments (PHFs) and stimulate Tau phosphorylation. As AD progresses, phosphorylated Tau aggregates and forms PHFs, which leads to the formation of neurofibrillary tangles. In human glioma cells, PCTAIRE-3 induces cell cycle arrest and cell death. PCTAIRE-3 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270853 [Multi-domain]  Cd Length: 288  Bit Score: 47.31  E-value: 2.70e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFFYDSGMFAIVTEFCSrGSLEDILTN-------QDVKLdWMFKssllldLIKGMKYLHHREFVHG 669
Cdd:cd07871   56 LLKNLKHANIVTLHDIIHTERCLTLVFEYLD-SDLKQYLDNcgnlmsmHNVKI-FMFQ------LLRGLSYCHKRKILHR 127
                         90       100
                 ....*....|....*....|..
gi 945225    670 RLKSRNCVVDGRFVLKVTDYGF 691
Cdd:cd07871  128 DLKPQNLLINEKGELKLADFGL 149
STKc_Nek1 cd08218
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
596-695 2.71e-05

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek1 is associated with centrosomes throughout the cell cycle. It is involved in the formation of primary cilium and in the maintenance of centrosomes. It cycles through the nucleus and may be capable of relaying signals between the cilium and the nucleus. Nek1 is implicated in the development of polycystic kidney disease, which is characterized by benign polycystic tumors formed by abnormal overgrowth of renal epithelial cells. It appears also to be involved in DNA damage response, and may be important for both correct DNA damage checkpoint activation and DNA repair. Nek1 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270858 [Multi-domain]  Cd Length: 256  Bit Score: 47.11  E-value: 2.71e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSL-------EDILTNQDVKLDWMFKSSLlldlikGMKYLHHREFVH 668
Cdd:cd08218   51 AVLSKMKHPNIVQYQESFEENGNLYIVMDYCDGGDLykrinaqRGVLFPEDQILDWFVQLCL------ALKHVHDRKILH 124
                         90       100
                 ....*....|....*....|....*..
gi 945225    669 GRLKSRNCVVDGRFVLKVTDYGFNDIL 695
Cdd:cd08218  125 RDIKSQNIFLTKDGIIKLGDFGIARVL 151
STKc_16 cd13986
Catalytic domain of Serine/Threonine Kinase 16; STKs catalyze the transfer of the ...
596-810 3.58e-05

Catalytic domain of Serine/Threonine Kinase 16; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK16 is associated with many names including Myristylated and Palmitylated Serine/threonine Kinase 1 (MPSK1), Kinase related to cerevisiae and thaliana (Krct), and Protein Kinase expressed in day 12 fetal liver (PKL12). It is widely expressed in mammals with highest levels found in liver, testis, and kidney. It is localized in the Golgi but is translocated to the nucleus upon disorganization of the Golgi. STK16 is constitutively active and is capable of phosphorylating itself and other substrates. It may be involved in regulating stromal-epithelial interactions during mammary gland ductal morphogenesis. It may also function as a transcriptional co-activator of type-C natriuretic peptide and VEGF. The STK16 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270888 [Multi-domain]  Cd Length: 282  Bit Score: 46.91  E-value: 3.58e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLgffyDSGMFA---------IVTEFCSRGSLEDILTNQDVKLDWMFKSSLL---LDLIKGMKYLH- 662
Cdd:cd13986   49 ENYRLFNHPNILRLL----DSQIVKeaggkkevyLLLPYYKRGSLQDEIERRLVKGTFFPEDRILhifLGICRGLKAMHe 124
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    663 --HREFVHGRLKSRNCVVDGRFVLKVTDYG--------FNDILEMLRLSEEESSMEELLWTAPELLRAPRGSRLGSFAgD 732
Cdd:cd13986  125 peLVPYAHRDIKPGNVLLSEDDEPILMDLGsmnparieIEGRREALALQDWAAEHCTMPYRAPELFDVKSHCTIDEKT-D 203
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    733 VYSFAIIMQEVMVRGTPFCMM----DLPAQEIINRLKKPPPVYRPvvppehaPPECLQLMKQCWAEAAEQRPTFDEIFNQ 808
Cdd:cd13986  204 IWSLGCTLYALMYGESPFERIfqkgDSLALAVLSGNYSFPDNSRY-------SEELHQLVKSMLVVNPAERPSIDDLLSR 276

                 ..
gi 945225    809 FK 810
Cdd:cd13986  277 VH 278
STKc_CCRK cd07832
Catalytic domain of the Serine/Threonine Kinase, Cell Cycle-Related Kinase; STKs catalyze the ...
603-749 3.70e-05

Catalytic domain of the Serine/Threonine Kinase, Cell Cycle-Related Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CCRK was previously called p42. It is a Cyclin-Dependent Kinase (CDK)-Activating Kinase (CAK) which is essential for the activation of CDK2. It is indispensable for cell growth and has been implicated in the progression of glioblastoma multiforme. In the heart, a splice variant of CCRK with a different C-terminal half is expressed; this variant promotes cardiac cell growth and survival and is significantly down-regulated during the development of heart failure. The CCRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270826 [Multi-domain]  Cd Length: 287  Bit Score: 46.94  E-value: 3.70e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    603 HENINPLLGFFYDSGMFAIVTEFCSRgSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNCVVDGRF 682
Cdd:cd07832   59 HPYVVKLRDVFPHGTGFVLVFEYMLS-SLSEVLRDEERPLTEAQVKRYMRMLLKGVAYMHANRIMHRDLKPANLLISSTG 137
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 945225    683 VLKVTDYGFNDILEMLRLSEEESSMEELLWTAPELLrapRGSRLGSFAGDVYSFAIIMQEvMVRGTP 749
Cdd:cd07832  138 VLKIADFGLARLFSEEDPRLYSHQVATRWYRAPELL---YGSRKYDEGVDLWAVGCIFAE-LLNGSP 200
STKc_CaMKI_gamma cd14166
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
573-750 3.80e-05

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I gamma; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-gamma subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271068 [Multi-domain]  Cd Length: 285  Bit Score: 46.91  E-value: 3.80e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    573 LKKFSLGDFGDLKSIK----SRASDV---FEMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLED------ILTNQD 639
Cdd:cd14166   22 VKQRSTGKLYALKCIKksplSRDSSLeneIAVLKRIKHENIVTLEDIYESTTHYYLVMQLVSGGELFDrilergVYTEKD 101
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    640 VkldwmfkSSLLLDLIKGMKYLHHREFVHGRLKSRNCVV---DGRFVLKVTDYGFNdilEMLRLSEEESSMEELLWTAPE 716
Cdd:cd14166  102 A-------SRVINQVLSAVKYLHENGIVHRDLKPENLLYltpDENSKIMITDFGLS---KMEQNGIMSTACGTPGYVAPE 171
                        170       180       190
                 ....*....|....*....|....*....|....
gi 945225    717 LLRAPRGSRlgsfAGDVYSFAIIMQEVMVRGTPF 750
Cdd:cd14166  172 VLAQKPYSK----AVDCWSIGVITYILLCGYPPF 201
STKc_FA2-like cd08529
Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii FA2 and similar ...
588-695 3.89e-05

Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii FA2 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chlamydomonas reinhardtii FA2 was discovered in a genetic screen for deflagellation-defective mutants. It is essential for basal-body/centriole-associated microtubule severing, and plays a role in cell cycle progression. No cellular function has yet been ascribed to CNK4. The Chlamydomonas reinhardtii FA2-like subfamily belongs to the (NIMA)-related kinase (Nek) family, which includes seven different Chlamydomonas Neks (CNKs 1-6 and Fa2). This subfamily contains FA2 and CNK4. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270868 [Multi-domain]  Cd Length: 256  Bit Score: 46.64  E-value: 3.89e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    588 KSRASDVFEMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVK-----LDWMFKSSLLLdlikGMKYLH 662
Cdd:cd08529   43 REEAIDEARVLSKLNSPYVIKYYDSFVDKGKLNIVMEYAENGDLHSLIKSQRGRplpedQIWKFFIQTLL----GLSHLH 118
                         90       100       110
                 ....*....|....*....|....*....|...
gi 945225    663 HREFVHGRLKSRNCVVDGRFVLKVTDYGFNDIL 695
Cdd:cd08529  119 SKKILHRDIKSMNIFLDKGDNVKIGDLGVAKIL 151
PKc_Pek1_like cd06621
Catalytic domain of fungal Pek1-like dual-specificity Mitogen-Activated Protein Kinase Kinases; ...
596-690 3.93e-05

Catalytic domain of fungal Pek1-like dual-specificity Mitogen-Activated Protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Pek1/Skh1 from Schizosaccharomyces pombe and MKK2 from Saccharomyces cerevisiae, and related proteins. Both fission yeast Pek1 and baker's yeast MKK2 are components of the cell integrity MAPK pathway. In fission yeast, Pek1 phosphorylates and activates Pmk1/Spm1 and is regulated by the MAPKK kinase Mkh1. In baker's yeast, the pathway involves the MAPK Slt2, the MAPKKs MKK1 and MKK2, and the MAPKK kinase Bck1. The cell integrity MAPK cascade is activated by multiple stress conditions, and is essential in cell wall construction, morphogenesis, cytokinesis, and ion homeostasis. MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270793 [Multi-domain]  Cd Length: 287  Bit Score: 46.65  E-value: 3.93e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYD--SGMFAIVTEFCSRGSLEDILTNqdVKLDWMFKSSLLLDLI-----KGMKYLHHREFVH 668
Cdd:cd06621   51 EINKSCASPYIVKYYGAFLDeqDSSIGIAMEYCEGGSLDSIYKK--VKKKGGRIGEKVLGKIaesvlKGLSYLHSRKIIH 128
                         90       100
                 ....*....|....*....|..
gi 945225    669 GRLKSRNCVVDGRFVLKVTDYG 690
Cdd:cd06621  129 RDIKPSNILLTRKGQVKLCDFG 150
STKc_MARK cd14072
Catalytic domain of the Serine/Threonine Kinases, MAP/microtubule affinity-regulating kinases; ...
597-750 4.15e-05

Catalytic domain of the Serine/Threonine Kinases, MAP/microtubule affinity-regulating kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MARKs, also called Partitioning-defective 1 (Par1) proteins, function as regulators of diverse cellular processes in nematodes, Drosophila, yeast, and vertebrates. They are involved in embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport. Vertebrates contain four isoforms, namely MARK1 (or Par1c), MARK2 (or Par1b), MARK3 (Par1a), and MARK4 (or MARKL1). Known substrates of MARKs include the cell cycle-regulating phosphatase Cdc25, tyrosine phosphatase PTPH1, MAPK scaffolding protein KSR1, class IIa histone deacetylases, and plakophilin 2. The MARK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270974 [Multi-domain]  Cd Length: 253  Bit Score: 46.36  E-value: 4.15e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDvKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNC 676
Cdd:cd14072   52 IMKILNHPNIVKLFEVIETEKTLYLVMEYASGGEVFDYLVAHG-RMKEKEARAKFRQIVSAVQYCHQKRIVHRDLKAENL 130
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 945225    677 VVDGRFVLKVTDYGFNDilEMLRLSEEESSMEELLWTAPELLrapRGSRLGSFAGDVYSFAIIMQEVMVRGTPF 750
Cdd:cd14072  131 LLDADMNIKIADFGFSN--EFTPGNKLDTFCGSPPYAAPELF---QGKKYDGPEVDVWSLGVILYTLVSGSLPF 199
STKc_myosinIIIB_N cd06639
N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIB myosin; STKs catalyze ...
603-718 4.21e-05

N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIB myosin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class IIIB myosin is expressed highly in retina. It is also present in the brain and testis. The human class IIIB myosin gene maps to a region that overlaps the locus for Bardet-Biedl syndrome, which is characterized by dysmorphic extremities, retinal dystrophy, obesity, male hypogenitalism, and renal abnormalities. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain. They may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. They may also function as cargo carriers during light-dependent translocation, in photoreceptor cells, of proteins such as transducin and arrestin. The class III myosin subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270808 [Multi-domain]  Cd Length: 291  Bit Score: 46.91  E-value: 4.21e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    603 HENINPLLGFFYDS-----GMFAIVTEFCSRGSLEDI---LTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSR 674
Cdd:cd06639   78 HPNVVKFYGMFYKAdqyvgGQLWLVLELCNGGSVTELvkgLLKCGQRLDEAMISYILYGALLGLQHLHNNRIIHRDVKGN 157
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 945225    675 NCVVDGRFVLKVTDYGFNDILEMLRlSEEESSMEELLWTAPELL 718
Cdd:cd06639  158 NILLTTEGGVKLVDFGVSAQLTSAR-LRRNTSVGTPFWMAPEVI 200
STKc_TGFbR-like cd13998
Catalytic domain of Transforming Growth Factor beta Receptor-like Serine/Threonine Kinases; ...
564-746 4.73e-05

Catalytic domain of Transforming Growth Factor beta Receptor-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of receptors for the TGFbeta family of secreted signaling molecules including TGFbeta, bone morphogenetic proteins (BMPs), activins, growth and differentiation factors (GDFs), and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. There are two types of TGFbeta receptors included in this subfamily, I and II, that play different roles in signaling. For signaling to occur, the ligand first binds to the high-affinity type II receptor, which is followed by the recruitment of the low-affinity type I receptor to the complex and its activation through trans-phosphorylation by the type II receptor. The active type I receptor kinase starts intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. Different ligands interact with various combinations of types I and II receptors to elicit a specific signaling pathway. Activins primarily signal through combinations of ACVR1b/ALK7 and ACVR2a/b; myostatin and GDF11 through TGFbR1/ALK4 and ACVR2a/b; BMPs through ACVR1/ALK1 and BMPR2; and TGFbeta through TGFbR1 and TGFbR2. The TGFbR-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270900 [Multi-domain]  Cd Length: 289  Bit Score: 46.66  E-value: 4.73e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    564 AIYEGDW----VWLKKFSLGDFGDLKSIKSRASDVFemmkdLRHENInplLGFF------YDSGM-FAIVTEFCSRGSLE 632
Cdd:cd13998   10 EVWKASLknepVAVKIFSSRDKQSWFREKEIYRTPM-----LKHENI---LQFIaaderdTALRTeLWLVTAFHPNGSL* 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    633 DILTNQdvKLDWMFKSSLLLDLIKGMKYLHHREF---------VHGRLKSRNCVV--DGRFVLkvTDYGFNDILEMLRLS 701
Cdd:cd13998   82 DYLSLH--TIDWVSLCRLALSVARGLAHLHSEIPgctqgkpaiAHRDLKSKNILVknDGTCCI--ADFGLAVRLSPSTGE 157
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|
gi 945225    702 EEESSME---ELLWTAPELLR-APRGSRLGSFAG-DVYSFAIIMQEVMVR 746
Cdd:cd13998  158 EDNANNGqvgTKRYMAPEVLEgAINLRDFESFKRvDIYAMGLVLWEMASR 207
STKc_CDK1_euk cd07861
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 1 from higher ...
568-690 4.73e-05

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 1 from higher eukaryotes; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK1 is also called Cell division control protein 2 (Cdc2) or p34 protein kinase, and is regulated by cyclins A, B, and E. The CDK1/cyclin A complex controls G2 phase entry and progression. CDK1/cyclin A2 has also been implicated as an important regulator of S phase events. The CDK1/cyclin B complex is critical for G2 to M phase transition. It induces mitosis by activating nuclear enzymes that regulate chromatin condensation, nuclear membrane degradation, mitosis-specific microtubule and cytoskeletal reorganization. CDK1 also associates with cyclin E and plays a role in the entry into S phase. CDK1 transcription is stable throughout the cell cycle but is modulated in some pathological conditions. It may play a role in regulating apoptosis under these conditions. In breast cancer cells, HER2 can mediate apoptosis by inactivating CDK1. Activation of CDK1 may contribute to HIV-1 induced apoptosis as well as neuronal apoptosis in neurodegenerative diseases. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270845 [Multi-domain]  Cd Length: 285  Bit Score: 46.64  E-value: 4.73e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    568 GDWVWLKKFSLGDfgDLKSIKSRASDVFEMMKDLRHENINPLLGFFYDSGMFAIVTEFCS---RGSLEDILTNQdvKLDW 644
Cdd:cd07861   25 GQIVAMKKIRLES--EEEGVPSTAIREISLLKELQHPNIVCLEDVLMQENRLYLVFEFLSmdlKKYLDSLPKGK--YMDA 100
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 945225    645 MFKSSLLLDLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYG 690
Cdd:cd07861  101 ELVKSYLYQILQGILFCHSRRVLHRDLKPQNLLIDNKGVIKLADFG 146
PBP1_taste_receptor cd06363
ligand-binding domain of the T1R taste receptor; Ligand-binding domain of the T1R taste ...
148-417 4.77e-05

ligand-binding domain of the T1R taste receptor; Ligand-binding domain of the T1R taste receptor. The T1R is a member of the family C receptors within the G-protein coupled receptor superfamily, which also includes the metabotropic glutamate receptors, GABAb receptors, the calcium-sensing receptor (CaSR), the V2R pheromone receptors, and a small group of uncharacterized orphan receptors.


Pssm-ID: 380586 [Multi-domain]  Cd Length: 418  Bit Score: 47.30  E-value: 4.77e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    148 SWACVNYELDNKISYPTFSRTLPSP---IRVLVTVMKYFQWAHAGVISSDEDIWVHTANRVASALRSHGLPV---GVVLT 221
Cdd:cd06363  137 SYGASSEELSNKLLYPSFLRTVPSDkyqVEAMVQLLQEFGWNWVAFLGSDDEYGQDGLQLFSEKAANTGICVayqGLIPT 216
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    222 TGQDSQSMRKALQRIHQAdRIRIIIMCMHSaliggETQMHLLECAHDLKMTDGtyVFVPYDALLYSlpykhtpyQVLRNN 301
Cdd:cd06363  217 DTDPKPKYQDILKKINQT-KVNVVVVFAPK-----QAAKAFFEEVIRQNLTGK--VWIASEAWSLN--------DTVTSL 280
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    302 PKLrEAYDAVLTITVESQEKTFYQAFTEAAArgeipekleFdqvsplfgTIYNSIYFIAQAMNNAMkengQAGAAS---- 377
Cdd:cd06363  281 PGI-QSIGTVLGFAIQTGTLPGFQEFIYAFA---------F--------SVYAAVYAVAHALHNLL----GCNSGAcpkg 338
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*..
gi 945225    378 -------LVQHSRNMQFHGFNQLMRTDSNGNGISEYvildtNLKEWE 417
Cdd:cd06363  339 rvvypwqLLEELKKVNFTLLNQTIRFDENGDPNFGY-----DIVQWI 380
STKc_DCKL cd14095
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase (also called ...
596-690 4.80e-05

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase (also called Doublecortin-like and CAM kinase-like); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL (or DCAMKL) proteins belong to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL proteins contain a C-terminal kinase domain with similarity to CAMKs. They are involved in the regulation of cAMP signaling. Vertebrates contain three DCKL proteins (DCKL1-3); DCKL1 and 2 also contain a serine, threonine, and proline rich domain (SP), while DCKL3 contains only a single DCX domain instead of tandem domains. The DCKL subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270997 [Multi-domain]  Cd Length: 258  Bit Score: 46.16  E-value: 4.80e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTnQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRN 675
Cdd:cd14095   50 AILRRVKHPNIVQLIEEYDTDTELYLVMELVKGGDLFDAIT-SSTKFTERDASRMVTDLAQALKYLHSLSIVHRDIKPEN 128
                         90
                 ....*....|....*....
gi 945225    676 CVV----DGRFVLKVTDYG 690
Cdd:cd14095  129 LLVveheDGSKSLKLADFG 147
STKc_Aurora-B_like cd14117
Catalytic domain of the Serine/Threonine kinase, Aurora-B kinase and similar proteins; STKs ...
596-799 4.80e-05

Catalytic domain of the Serine/Threonine kinase, Aurora-B kinase and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). This subfamily includes Aurora-B and Aurora-C. Aurora-B is most active at the transition during metaphase to the end of mitosis. It associates with centromeres, relocates to the midzone of the central spindle, and concentrates at the midbody during cell division. It is critical for accurate chromosomal segregation, cytokinesis, protein localization to the centrosome and kinetochore, correct microtubule-kinetochore attachments, and regulation of the mitotic checkpoint. Aurora-C is mainly expressed in meiotically dividing cells; it was originally discovered in mice as a testis-specific STK called Aie1. Both Aurora-B and -C are chromosomal passenger proteins that can form complexes with INCENP and survivin, and they may have redundant cellular functions. INCENP participates in the activation of Aurora-B in a two-step process: first by binding to form an intermediate state of activation and the phosphorylation of its C-terminal TSS motif to generate the fully active kinase. The Aurora-B subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271019 [Multi-domain]  Cd Length: 270  Bit Score: 46.40  E-value: 4.80e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDvKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRN 675
Cdd:cd14117   58 EIQSHLRHPNILRLYNYFHDRKRIYLILEYAPRGELYKELQKHG-RFDEQRTATFMEELADALHYCHEKKVIHRDIKPEN 136
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    676 CVVDGRFVLKVTDYGFNDILEMLRlseEESSMEELLWTAPELLRAprgsRLGSFAGDVYSFAIIMQEVMVRGTPF----- 750
Cdd:cd14117  137 LLMGYKGELKIADFGWSVHAPSLR---RRTMCGTLDYLPPEMIEG----RTHDEKVDLWCIGVLCYELLVGMPPFesash 209
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 945225    751 ---------------CMMDLPAQEIINRLKKpppvyrpvvppeHAPPECL---QLMKQCWAEAAEQR 799
Cdd:cd14117  210 tetyrrivkvdlkfpPFLSDGSRDLISKLLR------------YHPSERLplkGVMEHPWVKANSRR 264
STKc_GSK3 cd14137
The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3; STKs catalyze ...
585-690 5.82e-05

The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GSK3 is a mutifunctional kinase involved in many cellular processes including cell division, proliferation, differentiation, adhesion, and apoptosis. In plants, GSK3 plays a role in the response to osmotic stress. In Caenorhabditis elegans, it plays a role in regulating normal oocyte-to-embryo transition and response to oxidative stress. In Chlamydomonas reinhardtii, GSK3 regulates flagellar length and assembly. In mammals, there are two isoforms, GSK3alpha and GSK3beta, which show both distinct and redundant functions. The two isoforms differ mainly in their N-termini. They are both involved in axon formation and in Wnt signaling.They play distinct roles in cardiogenesis, with GSKalpha being essential in cardiomyocyte survival, and GSKbeta regulating heart positioning and left-right symmetry. GSK3beta was first identified as a regulator of glycogen synthesis, but has since been determined to play other roles. It regulates the degradation of beta-catenin and IkB. Beta-catenin is the main effector of Wnt, which is involved in normal haematopoiesis and stem cell function. IkB is a central inhibitor of NF-kB, which is critical in maintaining leukemic cell growth. GSK3beta is enriched in the brain and is involved in regulating neuronal signaling pathways. It is implicated in the pathogenesis of many diseases including Type II diabetes, obesity, mood disorders, Alzheimer's disease, osteoporosis, and some types of cancer, among others. The GSK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271039 [Multi-domain]  Cd Length: 293  Bit Score: 46.34  E-value: 5.82e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    585 KSIKSRAsdvFEMMKDLRHENINPLLGFFYDSG------MFAIVTEFCSrGSLEDI----------LTNQDVKLdWMFKs 648
Cdd:cd14137   41 KRYKNRE---LQIMRRLKHPNIVKLKYFFYSSGekkdevYLNLVMEYMP-ETLYRVirhysknkqtIPIIYVKL-YSYQ- 114
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 945225    649 sllldLIKGMKYLHHREFVHGRLKSRNCVVDGRF-VLKVTDYG 690
Cdd:cd14137  115 -----LFRGLAYLHSLGICHRDIKPQNLLVDPETgVLKLCDFG 152
STKc_ACVR2 cd14053
Catalytic domain of the Serine/Threonine Kinase, Activin Type II Receptor; STKs catalyze the ...
621-746 6.65e-05

Catalytic domain of the Serine/Threonine Kinase, Activin Type II Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ACVR2 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins (BMPs), activins, growth and differentiation factors (GDFs), and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. Type II receptors, such as ACVR2, are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. ACVR2 acts primarily as the receptors for activins, nodal, myostatin, GDF11, and a subset of BMPs. ACVR2 signaling impacts many cellular and physiological processes including reproductive and gonadal functions, myogenesis, bone remodeling and tooth development, kidney organogenesis, apoptosis, fibrosis, inflammation, and neurogenesis. Vertebrates contain two ACVR2 proteins, ACVR2a (or ActRIIA) and ACVR2b (or ActRIIB). The ACVR2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270955 [Multi-domain]  Cd Length: 290  Bit Score: 46.17  E-value: 6.65e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    621 IVTEFCSRGSLEDILTNQDVKLDWMFKssLLLDLIKGMKYLH---------------HREFvhgrlKSRNCVVDGRFVLK 685
Cdd:cd14053   70 LITEFHERGSLCDYLKGNVISWNELCK--IAESMARGLAYLHedipatngghkpsiaHRDF-----KSKNVLLKSDLTAC 142
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 945225    686 VTDYGFNDILEMLRLSEEESSME-ELLWTAPELLRAPRGSRLGSF-AGDVYSFAIIMQEVMVR 746
Cdd:cd14053  143 IADFGLALKFEPGKSCGDTHGQVgTRRYMAPEVLEGAINFTRDAFlRIDMYAMGLVLWELLSR 205
STKc_MAP4K3_like cd06613
Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 3-like ...
568-690 6.65e-05

Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes MAP4K3, MAP4K1, MAP4K2, MAP4K5, and related proteins. Vertebrate members contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. MAP4K1, also called haematopoietic progenitor kinase 1 (HPK1), is a hematopoietic-specific STK involved in many cellular signaling cascades including MAPK, antigen receptor, apoptosis, growth factor, and cytokine signaling. It participates in the regulation of T cell receptor signaling and T cell-mediated immune responses. MAP4K2 was referred to as germinal center (GC) kinase because of its preferred location in GC B cells. MAP4K3 plays a role in the nutrient-responsive pathway of mTOR (mammalian target of rapamycin) signaling. It is required in the activation of S6 kinase by amino acids and for the phosphorylation of the mTOR-regulated inhibitor of eukaryotic initiation factor 4E. MAP4K5, also called germinal center kinase-related enzyme (GCKR), has been shown to activate the MAPK c-Jun N-terminal kinase (JNK). The MAP4K3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270788 [Multi-domain]  Cd Length: 259  Bit Score: 45.76  E-value: 6.65e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    568 GDWVWLKKFSLGDFGDLKSIKSRasdvFEMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDI--LTN--QDVKLD 643
Cdd:cd06613   25 GELAAVKVIKLEPGDDFEIIQQE----ISMLKECRHPNIVAYFGSYLRRDKLWIVMEYCGGGSLQDIyqVTGplSELQIA 100
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 945225    644 WMFKSSLlldliKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYG 690
Cdd:cd06613  101 YVCRETL-----KGLAYLHSTGKIHRDIKGANILLTEDGDVKLADFG 142
STKc_Kin1_2 cd14077
Catalytic domain of Kin1, Kin2, and simlar Serine/Threonine Kinases; STKs catalyze the ...
601-757 7.02e-05

Catalytic domain of Kin1, Kin2, and simlar Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of yeast Kin1, Kin2, and similar proteins. Fission yeast Kin1 is a membrane-associated kinase that is involved in regulating cell surface cohesiveness during interphase. It also plays a role during mitosis, linking actomyosin ring assembly with septum synthesis and membrane closure to ensure separation of daughter cells. Budding yeast Kin1 and Kin2 act downstream of the Rab-GTPase Sec4 and are associated with the exocytic apparatus; they play roles in the secretory pathway. The Kin1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270979 [Multi-domain]  Cd Length: 267  Bit Score: 45.90  E-value: 7.02e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    601 LRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTnQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNCVVDG 680
Cdd:cd14077   70 LNHPHICRLRDFLRTPNHYYMLFEYVDGGQLLDYII-SHGKLKEKQARKFARQIASALDYLHRNSIVHRDLKIENILISK 148
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    681 RFVLKVTDYGFNDILEmlRLSEEESSMEELLWTAPELLRAPRgsrlgsFAG---DVYSFAIIMQeVMVRG-TPFCMMDLP 756
Cdd:cd14077  149 SGNIKIIDFGLSNLYD--PRRLLRTFCGSLYFAAPELLQAQP------YTGpevDVWSFGVVLY-VLVCGkVPFDDENMP 219

                 .
gi 945225    757 A 757
Cdd:cd14077  220 A 220
STKc_TAO2 cd06634
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 2; STKs catalyze ...
596-859 7.94e-05

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Human TAO2 is also known as prostate-derived Ste20-like kinase (PSK) and was identified in a screen for overexpressed RNAs in prostate cancer. TAO2 possesses mitogen-activated protein kinase (MAPK) kinase kinase activity and activates both p38 and c-Jun N-terminal kinase (JNK), by phosphorylating and activating their respective MAP/ERK kinases, MEK3/MEK6 and MKK4/MKK7. It contains a long C-terminal extension with autoinhibitory segments, and is activated by the release of this inhibition and the phosphorylation of its activation loop serine. TAO2 functions as a regulator of actin cytoskeletal and microtubule organization. In addition, it regulates the transforming growth factor-activated kinase 1 (TAK1), which is a MAPKKK that plays an essential role in the signaling pathways of tumor necrosis factor, interleukin 1, and Toll-like receptor. The TAO2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270804 [Multi-domain]  Cd Length: 308  Bit Score: 46.17  E-value: 7.94e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCsRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRN 675
Cdd:cd06634   67 KFLQKLRHPNTIEYRGCYLREHTAWLVMEYC-LGSASDLLEVHKKPLQEVEIAAITHGALQGLAYLHSHNMIHRDVKAGN 145
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    676 CVVDGRFVLKVTDYGFNDILemlrlSEEESSMEELLWTAPELLRAprgSRLGSFAG--DVYSFAIIMQEVMVRGTPFCMM 753
Cdd:cd06634  146 ILLTEPGLVKLGDFGSASIM-----APANSFVGTPYWMAPEVILA---MDEGQYDGkvDVWSLGITCIELAERKPPLFNM 217
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    754 DlpaqeIINRLKKPPPVYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEIFNQFKTFNKGKKTNIIDSMLRMleqyss 833
Cdd:cd06634  218 N-----AMSALYHIAQNESPALQSGHWSEYFRNFVDSCLQKIPQDRPTSDVLLKHRFLLRERPPTVIMDLIQRT------ 286
                        250       260
                 ....*....|....*....|....*.
gi 945225    834 nlEDLIRERTeelEIEKQKTEKLLTQ 859
Cdd:cd06634  287 --KDAVRELD---NLQYRKMKKILFQ 307
STKc_Trio_C cd14113
C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide ...
595-750 8.72e-05

C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide Exchange Factor, Triple functional domain protein; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Triple functional domain protein (Trio), also called PTPRF-interacting protein, is a large multidomain protein containing a series of spectrin-like repeats, two each of RhoGEF and SH3 domains, an immunoglobulin-like (Ig) domain and a C-terminal kinase. Trio plays important roles in neuronal cell migration and axon guidance. It was originally identified as an interacting partner of the of the receptor-like tyrosine phosphatase (RPTP) LAR (leukocyte-antigen-related protein), a family of receptors that function in the signaling to the actin cytoskeleton during development. Trio functions as a GEF for Rac1, RhoG, and RhoA, and is involved in the regulation of lamellipodia formation, mediating Rac1-dependent cell spreading and migration. The Trio subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271015 [Multi-domain]  Cd Length: 263  Bit Score: 45.74  E-value: 8.72e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    595 FEMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDI------LTNQDVKldwmfksSLLLDLIKGMKYLHHREFVH 668
Cdd:cd14113   54 LGVLQSLQHPQLVGLLDTFETPTSYILVLEMADQGRLLDYvvrwgnLTEEKIR-------FYLREILEALQYLHNCRIAH 126
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    669 GRLKSRNCVVD---GRFVLKVTDYGfnDILEMLRLSEEESSMEELLWTAPELLraprgsrLG---SFAGDVYSFAIIMQE 742
Cdd:cd14113  127 LDLKPENILVDqslSKPTIKLADFG--DAVQLNTTYYIHQLLGSPEFAAPEII-------LGnpvSLTSDLWSIGVLTYV 197

                 ....*...
gi 945225    743 VMVRGTPF 750
Cdd:cd14113  198 LLSGVSPF 205
STKc_SnRK3 cd14663
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
596-750 8.80e-05

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK3 is represented in this cd. The SnRK3 group contains members also known as CBL-interacting protein kinase, salt overly sensitive 2, SOS3-interacting proteins and protein kinase S. These kinases interact with calcium-binding proteins such as SOS3, SCaBPs, and CBL proteins, and are involved in responses to salt stress and in sugar and ABA signaling. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271133 [Multi-domain]  Cd Length: 256  Bit Score: 45.47  E-value: 8.80e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLED-ILTNQDVKLD---WMFKSsllldLIKGMKYLHHREFVHGRL 671
Cdd:cd14663   52 AIMKLLRHPNIVELHEVMATKTKIFFVMELVTGGELFSkIAKNGRLKEDkarKYFQQ-----LIDAVDYCHSRGVFHRDL 126
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    672 KSRNCVVDGRFVLKVTDYGFNDILEMLRLSEEESSM-EELLWTAPELLrAPRGsrLGSFAGDVYSFAIIMQEVMVRGTPF 750
Cdd:cd14663  127 KPENLLLDEDGNLKISDFGLSALSEQFRQDGLLHTTcGTPNYVAPEVL-ARRG--YDGAKADIWSCGVILFVLLAGYLPF 203
STKc_MAK_like cd07830
Catalytic domain of Male germ cell-Associated Kinase-like Serine/Threonine Kinases; STKs ...
574-690 1.02e-04

Catalytic domain of Male germ cell-Associated Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of human MAK and MAK-related kinase (MRK), Saccharomyces cerevisiae Ime2p, Schizosaccharomyces pombe Mei4-dependent protein 3 (Mde3) and Pit1, Caenorhabditis elegans dyf-5, Arabidopsis thaliana MHK, and similar proteins. These proteins play important roles during meiosis. MAK is highly expressed in testicular cells specifically in the meiotic phase, but is not essential for spermatogenesis and fertility. It functions as a coactivator of the androgen receptor in prostate cells. MRK, also called Intestinal Cell Kinase (ICK), is expressed ubiquitously, with highest expression in the ovary and uterus. A missense mutation in MRK causes endocrine-cerebro-osteodysplasia, suggesting that this protein plays an important role in the development of many organs. MAK and MRK may be involved in regulating cell cycle and cell fate. Ime2p is a meiosis-specific kinase that is important during meiotic initiation and during the later stages of meiosis. Mde3 functions downstream of the transcription factor Mei-4 which is essential for meiotic prophase I. The MAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270824 [Multi-domain]  Cd Length: 283  Bit Score: 45.60  E-value: 1.02e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    574 KKF-SLGDFGDLKSIKSrasdvfeMMKDLRHENINPLLGFFYDSGMFAIVTEFCSrGSLEDILTNQDVKL-------DWM 645
Cdd:cd07830   34 KKFySWEECMNLREVKS-------LRKLNEHPNIVKLKEVFRENDELYFVFEYME-GNLYQLMKDRKGKPfsesvirSII 105
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 945225    646 FKssllldLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYG 690
Cdd:cd07830  106 YQ------ILQGLAHIHKHGFFHRDLKPENLLVSGPEVVKIADFG 144
STKc_ULK1_2-like cd14120
Catalytic domain of the Serine/Threonine kinases, Unc-51-like kinases 1 and 2, and similar ...
596-691 1.13e-04

Catalytic domain of the Serine/Threonine kinases, Unc-51-like kinases 1 and 2, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK1 is required for efficient amino acid starvation-induced autophagy and mitochondrial clearance. ULK2 is ubiquitously expressed and is essential in autophagy induction. ULK1 and ULK2 have unique and cell-type specific roles, but also display partially redundant roles in starvation-induced autophagy. They both display neuron-specific functions: ULK1 is involved in non-clathrin-coated endocytosis in growth cones, filopodia extension, and axon branching; ULK2 plays a role in axon development. The ULK1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271022 [Multi-domain]  Cd Length: 256  Bit Score: 45.05  E-value: 1.13e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNqdvkldwmfKSSLLLDLIK--------GMKYLHHREFV 667
Cdd:cd14120   44 KILKELSHENVVALLDCQETSSSVYLVMEYCNGGDLADYLQA---------KGTLSEDTIRvflqqiaaAMKALHSKGIV 114
                         90       100       110
                 ....*....|....*....|....*....|...
gi 945225    668 HGRLKSRNCVVD---------GRFVLKVTDYGF 691
Cdd:cd14120  115 HRDLKPQNILLShnsgrkpspNDIRLKIADFGF 147
STKc_obscurin_rpt2 cd14110
Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs ...
595-690 1.30e-04

Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Obscurin, approximately 800 kDa in size, is one of three giant proteins expressed in vetebrate striated muscle, together with titin and nebulin. It is a multidomain protein composed of tandem adhesion and signaling domains, including 49 immunoglobulin (Ig) and 2 fibronectin type III (FN3) domains at the N-terminus followed by a more complex region containing more Ig domains, a conserved SH3 domain near a RhoGEF and PH domains, non-modular regions, as well as IQ and phosphorylation motifs. The obscurin gene also encode two kinase domains, which are not expressed as part of the 800 kDa protein, but as a smaller, alternatively spliced product present mainly in the heart muscle, also called obscurin-MLCK. Obscurin is localized at the peripheries of Z-disks and M-lines, where it is able to communicate with the surrounding myoplasm. It interacts with diverse proteins including sAnk1, myosin, titin, and MyBP-C. It may act as a scaffold for the assembly of elements of the contractile apparatus. The obscurin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271012 [Multi-domain]  Cd Length: 257  Bit Score: 44.91  E-value: 1.30e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    595 FEMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKLDWMFKSsLLLDLIKGMKYLHHREFVHGRLKSR 674
Cdd:cd14110   50 YQVLRRLSHPRIAQLHSAYLSPRHLVLIEELCSGPELLYNLAERNSYSEAEVTD-YLWQILSAVDYLHSRRILHLDLRSE 128
                         90
                 ....*....|....*.
gi 945225    675 NCVVDGRFVLKVTDYG 690
Cdd:cd14110  129 NMIITEKNLLKIVDLG 144
STKc_cGK cd05572
Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG); ...
596-750 1.37e-04

Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mammals have two cGK isoforms from different genes, cGKI and cGKII. cGKI exists as two splice variants, cGKI-alpha and cGKI-beta. cGK consists of an N-terminal regulatory domain containing a dimerization and an autoinhibitory pseudosubstrate region, two cGMP-binding domains, and a C-terminal catalytic domain. Binding of cGMP to both binding sites releases the inhibition of the catalytic center by the pseudosubstrate region, allowing autophosphorylation and activation of the kinase. cGKI is a soluble protein expressed in all smooth muscles, platelets, cerebellum, and kidney. It is also expressed at lower concentrations in other tissues. cGKII is a membrane-bound protein that is most abundantly expressed in the intestine. It is also present in the brain nuclei, adrenal cortex, kidney, lung, and prostate. cGKI is involved in the regulation of smooth muscle tone, smooth cell proliferation, and platelet activation. cGKII plays a role in the regulation of secretion, such as renin secretion by the kidney and aldosterone secretion by the adrenal. It also regulates bone growth and the circadian rhythm. The cGK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270724 [Multi-domain]  Cd Length: 262  Bit Score: 44.91  E-value: 1.37e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDvkldwmfksslLLD----------LIKGMKYLHHRE 665
Cdd:cd05572   45 EILEECNSPFIVKLYRTFKDKKYLYMLMEYCLGGELWTILRDRG-----------LFDeytarfytacVVLAFEYLHSRG 113
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    666 FVHGRLKSRNCVVDGRFVLKVTDYGFNDILEmlrlseeessMEELLWT--------APELLRApRGSrlgSFAGDVYSFA 737
Cdd:cd05572  114 IIYRDLKPENLLLDSNGYVKLVDFGFAKKLG----------SGRKTWTfcgtpeyvAPEIILN-KGY---DFSVDYWSLG 179
                        170
                 ....*....|...
gi 945225    738 IIMQEVMVRGTPF 750
Cdd:cd05572  180 ILLYELLTGRPPF 192
STKc_PCTAIRE2 cd07872
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-2 kinase; STKs catalyze the transfer ...
597-691 1.42e-04

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-2 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-2 is specifically expressed in neurons in the central nervous system, mainly in terminally differentiated neurons. It associates with Trap (Tudor repeat associator with PCTAIRE-2) and could play a role in regulating mitochondrial function in neurons. PCTAIRE-2 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143377 [Multi-domain]  Cd Length: 309  Bit Score: 45.37  E-value: 1.42e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLE------DILTNQDVKLdwmfkssLLLDLIKGMKYLHHREFVHGR 670
Cdd:cd07872   57 LLKDLKHANIVTLHDIVHTDKSLTLVFEYLDKDLKQymddcgNIMSMHNVKI-------FLYQILRGLAYCHRRKVLHRD 129
                         90       100
                 ....*....|....*....|.
gi 945225    671 LKSRNCVVDGRFVLKVTDYGF 691
Cdd:cd07872  130 LKPQNLLINERGELKLADFGL 150
PK_STRAD_alpha cd08227
Pseudokinase domain of STE20-related kinase adapter protein alpha; The pseudokinase domain ...
599-761 1.49e-04

Pseudokinase domain of STE20-related kinase adapter protein alpha; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. The structure of STRAD-alpha is available and shows that this protein binds ATP, has an ordered activation loop, and adopts a closed conformation typical of fully active protein kinases. It does not possess activity due to nonconservative substitutions of essential catalytic residues. ATP binding enhances the affinity of STRAD for MO25. The conformation of STRAD-alpha, stabilized through ATP and MO25, may be needed to activate LKB1. A mutation which results in a truncation of a C-terminal part of the human STRAD-alpha pseudokinase domain and disrupts its association with LKB1, leads to PMSE (polyhydramnios, megalencephaly, symptomatic epilepsy) syndrome. Several splice variants of STRAD-alpha exist which exhibit different effects on the localization and activation of LKB1. STRAD forms a complex with the scaffolding protein MO25, and the serine/threonine kinase (STK), LKB1, resulting in the activation of the kinase. In the complex, LKB1 phosphorylates and activates adenosine monophosphate-activated protein kinases (AMPKs), which regulate cell energy metabolism and cell polarity. The STRAD alpha subfamily is part of a larger superfamily that includes the catalytic domains of STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173767 [Multi-domain]  Cd Length: 327  Bit Score: 45.32  E-value: 1.49e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    599 KDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLED-ILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNCV 677
Cdd:cd08227   54 KLFNHPNIVPYRATFIADNELWVVTSFMAYGSAKDlICTHFMDGMSELAIAYILQGVLKALDYIHHMGYVHRSVKASHIL 133
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    678 --VDGRFVLKvtdyGFNDILEMLRLSEEES--------SMEELLWTAPELLRAP-RGSRLGSfagDVYSFAIIMQEVMVR 746
Cdd:cd08227  134 isVDGKVYLS----GLRSNLSMINHGQRLRvvhdfpkySVKVLPWLSPEVLQQNlQGYDAKS---DIYSVGITACELANG 206
                        170
                 ....*....|....*
gi 945225    747 GTPFcmMDLPAQEII 761
Cdd:cd08227  207 HVPF--KDMPATQML 219
PBP1_NPR_C cd06386
ligand-binding domain of type C natriuretic peptide receptor; Ligand-binding domain of type C ...
66-401 1.54e-04

ligand-binding domain of type C natriuretic peptide receptor; Ligand-binding domain of type C natriuretic peptide receptor (NPR-C). NPR-C is found in atrial, mesentery, placenta, lung, kidney, venous tissue, aortic smooth muscle, and aortic endothelial cells. The affinity of NPR-C for natriuretic peptides is ANP>CNP>BNP. The extracellular domain of NPR-C is about 30% identical to NPR-A and NPR-B. However, unlike the cyclase-linked receptors, it contains only 37 intracellular amino acids and no guanylyl cyclase activity. Major function of NPR-C is to clear natriuretic peptides from the circulation or extracellular surroundings through constitutive receptor-mediated internalization and degradation.


Pssm-ID: 380609 [Multi-domain]  Cd Length: 391  Bit Score: 45.62  E-value: 1.54e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225     66 LFSKALPEVAARLAIERINRDPSFDLSYSFEYVILNEDCqTSRALSSFI----SHHQMASGFIGPTnpgyCEAASL---- 137
Cdd:cd06386   16 LFSLTRVRPAIEYALRSVEGNGLLPPGTRFNVAYEDSDC-GNRALFSLVdrvaQKRAKPDLILGPV----CEYAAApvar 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    138 LGNSWDKGIFSWACVNYELDNKIS-YPTFSRTLPSPIRV---LVTVMKYFQWAHAGVISSDEDIWVH---TANRVASALR 210
Cdd:cd06386   91 LASHWNLPMLSAGALAAGFSHKDSeYSHLTRVAPAYAKMgemFLALFRHHHWSRAFLVYSDDKLERNcyfTLEGVHEVFQ 170
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    211 SHGLPVGVV---LTTGQDSQSMRKALQrihqaDRIRIIIMCMHSaliggETQMHLLECAHDLKMTDGTYVFVPYDaLLYS 287
Cdd:cd06386  171 EEGLHTSIYsfdETKDLDLEEIVRNIQ-----ASERVVIMCASS-----DTIRSIMLVAHRHGMTNGDYAFFNIE-LFNS 239
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    288 LPYKHTPYQV-LRNNPKLREAYDAVLTITVESQEKTFYQAFT-EAAARGEIPEKLEFDQVSPLFGTIYNSIYFIAQAMNN 365
Cdd:cd06386  240 SSYGNGSWKRgDKHDFEAKQAYSSLQTVTLLRTVKPEFEKFSmEVKSSVQKQGLNDEDYVNMFVEGFHDAILLYALALHE 319
                        330       340       350
                 ....*....|....*....|....*....|....*...
gi 945225    366 AMKeNG--QAGAASLVQHSRNMQFHGFNQLMRTDSNGN 401
Cdd:cd06386  320 VLR-NGysKKDGGKIIQQTWNRTFEGIAGQVSIDANGD 356
STKc_Rim15_like cd05611
Catalytic domain of fungal Rim15-like Protein Serine/Threonine Kinases; STKs catalyze the ...
571-750 1.55e-04

Catalytic domain of fungal Rim15-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include Saccharomyces cerevisiae Rim15, Schizosaccharomyces pombe cek1, and similar fungal proteins. They contain a central catalytic domain, which contains an insert relative to MAST kinases. In addition, Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. Rim15 (or Rim15p) functions as a regulator of meiosis. It acts as a downstream effector of PKA and regulates entry into stationary phase (G0). Thus, it plays a crucial role in regulating yeast proliferation, differentiation, and aging. Cek1 may facilitate progression of mitotic anaphase. The Rim15-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270762 [Multi-domain]  Cd Length: 263  Bit Score: 44.78  E-value: 1.55e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    571 VWL-KKFSLGDFGDLKSIKSRASDVFEMMKDLRHENINPL----------LGFFYDSGMF-AIVTEFCSRGSLEDIL-TN 637
Cdd:cd05611   12 VYLaKKRSTGDYFAIKVLKKSDMIAKNQVTNVKAERAIMMiqgespyvakLYYSFQSKDYlYLVMEYLNGGDCASLIkTL 91
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    638 QDVKLDWMFKssLLLDLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGFNDILEMLRlsEEESSMEELLWTAPEL 717
Cdd:cd05611   92 GGLPEDWAKQ--YIAEVVLGVEDLHQRGIIHRDIKPENLLIDQTGHLKLTDFGLSRNGLEKR--HNKKFVGTPDYLAPET 167
                        170       180       190
                 ....*....|....*....|....*....|...
gi 945225    718 LRAPRGSRlgsfAGDVYSFAIIMQEVMVRGTPF 750
Cdd:cd05611  168 ILGVGDDK----MSDWWSLGCVIFEFLFGYPPF 196
STKc_Sty1_Hog1 cd07856
Catalytic domain of the Serine/Threonine Kinases, Fungal Mitogen-Activated Protein Kinases ...
596-696 1.65e-04

Catalytic domain of the Serine/Threonine Kinases, Fungal Mitogen-Activated Protein Kinases Sty1 and Hog1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPKs Sty1 from Schizosaccharomyces pombe, Hog1 from Saccharomyces cerevisiae, and similar proteins. Sty1 and Hog1 are stress-activated MAPKs that partipate in transcriptional regulation in response to stress. Sty1 is activated in response to oxidative stress, osmotic stress, and UV radiation. It is regulated by the MAP2K Wis1, which is activated by the MAP3Ks Wis4 and Win1, which receive signals of the stress condition from membrane-spanning histidine kinases Mak1-3. Activated Sty1 stabilizes the Atf1 transcription factor and induces transcription of Atf1-dependent genes of the core environmetal stress response. Hog1 is the key element in the high osmolarity glycerol (HOG) pathway and is activated upon hyperosmotic stress. Activated Hog1 accumulates in the nucleus and regulates stress-induced transcription. The HOG pathway is mediated by two transmembrane osmosensors, Sln1 and Sho1. MAPKs are important mediators of cellular responses to extracellular signals. The Sty1/Hog1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270843 [Multi-domain]  Cd Length: 328  Bit Score: 45.26  E-value: 1.65e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYD-SGMFAIVTEFCSRgSLEDILTNQdvKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSR 674
Cdd:cd07856   61 KLLKHLRHENIISLSDIFISpLEDIYFVTELLGT-DLHRLLTSR--PLEKQFIQYFLYQILRGLKYVHSAGVIHRDLKPS 137
                         90       100
                 ....*....|....*....|..
gi 945225    675 NCVVDGRFVLKVTDYGFNDILE 696
Cdd:cd07856  138 NILVNENCDLKICDFGLARIQD 159
STKc_WNK cd13983
Catalytic domain of the Serine/Threonine kinase, With No Lysine (WNK) kinase; STKs catalyze ...
588-758 1.80e-04

Catalytic domain of the Serine/Threonine kinase, With No Lysine (WNK) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNKs comprise a subfamily of STKs with an unusual placement of a catalytic lysine relative to all other protein kinases. They are critical in regulating ion balance and are thus, important components in the control of blood pressure. They are also involved in cell signaling, survival, proliferation, and organ development. WNKs are activated by hyperosmotic or low-chloride hypotonic stress and they function upstream of SPAK and OSR1 kinases, which regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. There are four vertebrate WNKs which show varying expression patterns. WNK1 and WNK2 are widely expressed while WNK3 and WNK4 show a more restricted expression pattern. Because mutations in human WNK1 and WNK4 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension (due to increased sodium reabsorption) and hyperkalemia (due to impaired renal potassium secretion), there are more studies conducted on these two proteins, compared to WNK2 and WNK3. The WNK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270885 [Multi-domain]  Cd Length: 258  Bit Score: 44.52  E-value: 1.80e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    588 KSRASDVFEMMKDLRHENINPllgfFYDS------GMFAIVTEFCSRGSLEDILTN-QDVKLdWMFKSsLLLDLIKGMKY 660
Cdd:cd13983   44 RQRFKQEIEILKSLKHPNIIK----FYDSweskskKEVIFITELMTSGTLKQYLKRfKRLKL-KVIKS-WCRQILEGLNY 117
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    661 LHHRE--FVHGRLKSRNCVVDG-RFVLKVTDYGfndILEMLRLSEEESSMEELLWTAPELLRAPRGSRLgsfagDVYSFA 737
Cdd:cd13983  118 LHTRDppIIHRDLKCDNIFINGnTGEVKIGDLG---LATLLRQSFAKSVIGTPEFMAPEMYEEHYDEKV-----DIYAFG 189
                        170       180
                 ....*....|....*....|.
gi 945225    738 IIMQEVMVRGTPFCMMDLPAQ 758
Cdd:cd13983  190 MCLLEMATGEYPYSECTNAAQ 210
STKc_p38alpha cd07877
Catalytic domain of the Serine/Threonine Kinase, p38alpha Mitogen-Activated Protein Kinase ...
595-765 1.93e-04

Catalytic domain of the Serine/Threonine Kinase, p38alpha Mitogen-Activated Protein Kinase (also called MAPK14); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38alpha/MAPK14 is expressed in most tissues and is the major isoform involved in the immune and inflammatory response. It is the central p38 MAPK involved in myogenesis. It plays a role in regulating cell cycle check-point transition and promoting cell differentiation. p38alpha also regulates cell proliferation and death through crosstalk with the JNK pathway. Its substrates include MAPK activated protein kinase 2 (MK2), MK5, and the transcription factors ATF2 and Mitf. p38 kinases MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38alpha subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143382 [Multi-domain]  Cd Length: 345  Bit Score: 45.03  E-value: 1.93e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    595 FEMMKDLRHENINPLLGFFYDSGMFA------IVTEFCSrGSLEDILTNQDVKLDWMfkSSLLLDLIKGMKYLHHREFVH 668
Cdd:cd07877   67 LRLLKHMKHENVIGLLDVFTPARSLEefndvyLVTHLMG-ADLNNIVKCQKLTDDHV--QFLIYQILRGLKYIHSADIIH 143
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    669 GRLKSRNCVVDGRFVLKVTDYGFndilemlrlsEEESSMEELLWTAPELLRAPR---GSRLGSFAGDVYSFAIIMQEVMV 745
Cdd:cd07877  144 RDLKPSNLAVNEDCELKILDFGL----------ARHTDDEMTGYVATRWYRAPEimlNWMHYNQTVDIWSVGCIMAELLT 213
                        170       180
                 ....*....|....*....|
gi 945225    746 RGTPFcmmdlPAQEIINRLK 765
Cdd:cd07877  214 GRTLF-----PGTDHIDQLK 228
STKc_WNK4 cd14033
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 4; STKs catalyze ...
585-758 1.96e-04

Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK4 shows a restricted expression pattern and is usually found in epithelial cells. It is expressed in nephrons and in extrarenal tissues including intestine, eye, mammary glands, and prostate. WNK4 regulates a variety of ion transport proteins including apical or basolateral ion transporters, ion channels in the transcellular pathway, and claudins in the paracellular pathway. Mutations in WNK4 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension and hyperkalemia. WNK4 inhibits the activity of the thiazide-sensitive Na-Cl cotransporter (NCC), which is responsible for about 15% of NaCl reabsorption in the kidney. It also inhibits the renal outer medullary potassium channel (ROMK) and decreases its surface expression. Hypertension and hyperkalemia in PHAII patients with WNK4 mutations may be partly due to increased NaCl reabsorption through NCC and impaired renal potassium secretion by ROMK, respectively. The WNK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270935 [Multi-domain]  Cd Length: 261  Bit Score: 44.61  E-value: 1.96e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    585 KSIKSRASDVFEMMKDLRHENINPllgfFYDS------GMFAI--VTEFCSRGSLEDILTN-QDVKLDWMFKSSllLDLI 655
Cdd:cd14033   41 KGERQRFSEEVEMLKGLQHPNIVR----FYDSwkstvrGHKCIilVTELMTSGTLKTYLKRfREMKLKLLQRWS--RQIL 114
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    656 KGMKYLHHR--EFVHGRLKSRNCVVDG-RFVLKVTDYGfndILEMLRLSEEESSMEELLWTAPELLRAPRGSrlgsfAGD 732
Cdd:cd14033  115 KGLHFLHSRcpPILHRDLKCDNIFITGpTGSVKIGDLG---LATLKRASFAKSVIGTPEFMAPEMYEEKYDE-----AVD 186
                        170       180
                 ....*....|....*....|....*.
gi 945225    733 VYSFAIIMQEVMVRGTPFCMMDLPAQ 758
Cdd:cd14033  187 VYAFGMCILEMATSEYPYSECQNAAQ 212
PBP1_pheromone_receptor cd06365
Ligand-binding domain of the V2R pheromone receptor, a member of the family C receptors within ...
75-254 2.02e-04

Ligand-binding domain of the V2R pheromone receptor, a member of the family C receptors within the G-protein coupled receptor superfamily; Ligand-binding domain of the V2R pheromone receptor, a member of the family C receptors within the G-protein coupled receptor superfamily, which also includes the metabotropic glutamate receptor, the GABAb receptor, the calcium-sensing receptor (CaSR), the T1R taste receptor, and a small group of uncharacterized orphan receptors.


Pssm-ID: 380588 [Multi-domain]  Cd Length: 464  Bit Score: 45.33  E-value: 2.02e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225     75 AARLAIERINRDPS-----------FDLSYSFE--------------YVILNEDCQTSRALSSFISH------HQMA--- 120
Cdd:cd06365   41 AFLFAIEEINKNPDllpnitlgfhiYDSCSSERlalesslsilsgnsEPIPNYSCREQRKLVAFIGDlssstsVAMAril 120
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    121 --SGFI----GPTNPgyceaasllgnswdkgifswacvnyELDNKISYPTFSRTLPSP---IRVLVTVMKYFQWAHAGVI 191
Cdd:cd06365  121 glYKYPqisyGAFDP-------------------------LLSDKVQFPSFYRTVPSDtsqSLAIVQLLKHFGWTWVGLI 175
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 945225    192 SSDEDIWVHTANRVASALRSHGLPVGVVLTTGQDSQSMR--KALQRIHQADRIRIIIMCMHSALI 254
Cdd:cd06365  176 ISDDDYGEQFSQDLKKEMEKNGICVAFVEKIPTNSSLKRiiKYINQIIKSSANVIIIYGDTDSLL 240
STKc_SLK_like cd06611
Catalytic domain of Ste20-Like Kinase-like Serine/Threonine Kinases; STKs catalyze the ...
596-690 2.11e-04

Catalytic domain of Ste20-Like Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of the subfamily include SLK, STK10 (also called LOK for Lymphocyte-Oriented Kinase), SmSLK (Schistosoma mansoni SLK), and related proteins. SLK promotes apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and the mitogen-activated protein kinase (MAPK) p38. It also plays a role in mediating actin reorganization. STK10 is responsible in regulating the CD28 responsive element in T cells, as well as leukocyte function associated antigen (LFA-1)-mediated lymphocyte adhesion. SmSLK is capable of activating the MAPK Jun N-terminal kinase (JNK) pathway in human embryonic kidney cells as well as in Xenopus oocytes. It may participate in regulating MAPK cascades during host-parasite interactions. The SLK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132942 [Multi-domain]  Cd Length: 280  Bit Score: 44.35  E-value: 2.11e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRN 675
Cdd:cd06611   54 DILSECKHPNIVGLYEAYFYENKLWILIEFCDGGALDSIMLELERGLTEPQIRYVCRQMLEALNFLHSHKVIHRDLKAGN 133
                         90
                 ....*....|....*
gi 945225    676 CVVDGRFVLKVTDYG 690
Cdd:cd06611  134 ILLTLDGDVKLADFG 148
PKc_MAPKK cd06605
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein Kinase ...
611-690 2.47e-04

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein Kinase Kinase; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MAPKKs are dual-specificity PKs that phosphorylate their downstream targets, MAPKs, at specific threonine and tyrosine residues. The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising the MAPK, which is phosphorylated and activated by a MAPK kinase (MAPKK or MKK or MAP2K), which itself is phosphorylated and activated by a MAPKK kinase (MAPKKK or MKKK or MAP3K). There are three MAPK subfamilies: extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. In mammalian cells, there are seven MAPKKs (named MKK1-7) and 20 MAPKKKs. Each MAPK subfamily can be activated by at least two cognate MAPKKs and by multiple MAPKKKs. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270782 [Multi-domain]  Cd Length: 265  Bit Score: 44.26  E-value: 2.47e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    611 GFFYDSGMFAIVTEFCSRGSLEDILTNQDVkLDWMFKSSLLLDLIKGMKYLHH-REFVHGRLKSRNCVVDGRFVLKVTDY 689
Cdd:cd06605   66 GAFYSEGDISICMEYMDGGSLDKILKEVGR-IPERILGKIAVAVVKGLIYLHEkHKIIHRDVKPSNILVNSRGQVKLCDF 144

                 .
gi 945225    690 G 690
Cdd:cd06605  145 G 145
STKc_Chk2 cd14084
Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze ...
596-807 2.55e-04

Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Checkpoint Kinase 2 (Chk2) plays an important role in cellular responses to DNA double-strand breaks and related lesions. It is phosphorylated and activated by ATM kinase, resulting in its dissociation from sites of damage to phosphorylate downstream targets such as BRCA1, p53, cell cycle transcription factor E2F1, the promyelocytic leukemia protein (PML) involved in apoptosis, and CDC25 phosphatases, among others. Mutations in Chk2 is linked to a variety of cancers including familial breast cancer, myelodysplastic syndromes, prostate cancer, lung cancer, and osteosarcomas. Chk2 contains an N-terminal SQ/TQ cluster domain (SCD), a central forkhead-associated (FHA) domain, and a C-terminal catalytic kinase domain. The Chk2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270986 [Multi-domain]  Cd Length: 275  Bit Score: 44.31  E-value: 2.55e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQdVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRN 675
Cdd:cd14084   63 EILKKLSHPCIIKIEDFFDAEDDYYIVLELMEGGELFDRVVSN-KRLKEAICKLYFYQMLLAVKYLHSNGIIHRDLKPEN 141
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    676 CVV---DGRFVLKVTDYGFNDILEmlRLSEEESSMEELLWTAPELLRAprGSRLG-SFAGDVYSFAIIMQEVMVRGTPFC 751
Cdd:cd14084  142 VLLssqEEECLIKITDFGLSKILG--ETSLMKTLCGTPTYLAPEVLRS--FGTEGyTRAVDCWSLGVILFICLSGYPPFS 217
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 945225    752 --MMDLPAQEIINRLKKPPPVYRPVVPPEHAppecLQLMKQCWAEAAEQRPTFDEIFN 807
Cdd:cd14084  218 eeYTQMSLKEQILSGKYTFIPKAWKNVSEEA----KDLVKKMLVVDPSRRPSIEEALE 271
STKc_ROCK1 cd05622
Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein ...
569-750 2.60e-04

Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ROCK1 is preferentially expressed in the liver, lung, spleen, testes, and kidney. It mediates signaling from Rho to the actin cytoskeleton. It is implicated in the development of cardiac fibrosis, cardiomyocyte apoptosis, and hyperglycemia. Mice deficient with ROCK1 display eyelids open at birth (EOB) and omphalocele phenotypes due to the disorganization of actin filaments in the eyelids and the umbilical ring. ROCK contains an N-terminal extension, a catalytic kinase domain, and a C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain, and is activated via interaction with Rho GTPases. The ROCK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270772 [Multi-domain]  Cd Length: 405  Bit Score: 44.61  E-value: 2.60e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    569 DWVWLKKFSLGDFGDLKSIKSRAS---------DVFEMMKD------------LRHENINPLLGFFY---DSGMFAIVTE 624
Cdd:cd05622   74 DYEVVKVIGRGAFGEVQLVRHKSTrkvyamkllSKFEMIKRsdsaffweerdiMAFANSPWVVQLFYafqDDRYLYMVME 153
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    625 FCSRGSLEDILTNQDVKLDWM-FKSSlllDLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGFNDILEMLRLSEE 703
Cdd:cd05622  154 YMPGGDLVNLMSNYDVPEKWArFYTA---EVVLALDAIHSMGFIHRDVKPDNMLLDKSGHLKLADFGTCMKMNKEGMVRC 230
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 945225    704 ESSMEELLWTAPELLRAPRGSRLGSFAGDVYSFAIIMQEVMVRGTPF 750
Cdd:cd05622  231 DTAVGTPDYISPEVLKSQGGDGYYGRECDWWSVGVFLYEMLVGDTPF 277
PTK_Tyk2_rpt1 cd05076
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; Tyk2 is ...
621-806 2.66e-04

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; Tyk2 is widely expressed in many tissues. It is involved in signaling via the cytokine receptors IFN-alphabeta, IL-6, IL-10, IL-12, IL-13, and IL-23. It mediates cell surface urokinase receptor (uPAR) signaling and plays a role in modulating vascular smooth muscle cell (VSMC) functional behavior in response to injury. Tyk2 is also important in dendritic cell function and T helper (Th)1 cell differentiation. A homozygous mutation of Tyk2 was found in a patient with hyper-IgE syndrome (HIES), a primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and elevated serum IgE. This suggests that Tyk2 may play important roles in multiple cytokine signaling involved in innate and adaptive immunity. Tyk2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. The Tyk2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270661 [Multi-domain]  Cd Length: 273  Bit Score: 44.13  E-value: 2.66e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    621 IVTEFCSRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNCVVDGR--------FVlKVTDYGFN 692
Cdd:cd05076   92 MVEEFVEHGPLDVWLRKEKGHVPMAWKFVVARQLASALSYLENKNLVHGNVCAKNILLARLgleegtspFI-KLSDPGVG 170
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    693 dilemLRLSEEESSMEELLWTAPELLraPRGSRLGSfAGDVYSFAIIMQEVMVRGtpfcmmDLPAQEiINRLKKPPPVYR 772
Cdd:cd05076  171 -----LGVLSREERVERIPWIAPECV--PGGNSLST-AADKWGFGATLLEICFNG------EAPLQS-RTPSEKERFYQR 235
                        170       180       190
                 ....*....|....*....|....*....|....
gi 945225    773 PVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEIF 806
Cdd:cd05076  236 QHRLPEPSCPELATLISQCLTYEPTQRPSFRTIL 269
STKc_SnRK2 cd14662
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
599-807 2.77e-04

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK2 is represented in this cd. SnRK2s are involved in plant response to abiotic stresses and abscisic acid (ABA)-dependent plant development. The SnRK2s subfamily is in turn classed into three subgroups, all 3 of which are represented in this CD. Group 1 comprises kinases not activated by ABA, group 2 - kinases not activated or activated very weakly by ABA (depending on plant species), and group 3 - kinases strongly activated by ABA. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271132 [Multi-domain]  Cd Length: 257  Bit Score: 43.99  E-value: 2.77e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    599 KDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTN----QDVKLDWMFKSsllldLIKGMKYLHHREFVHGRLKSR 674
Cdd:cd14662   51 RSLRHPNIIRFKEVVLTPTHLAIVMEYAAGGELFERICNagrfSEDEARYFFQQ-----LISGVSYCHSMQICHRDLKLE 125
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    675 NCVVDGRFV--LKVTDYGFNDilEMLRLSEEESSMEELLWTAPELLraPRGSRLGSFAgDVYSFAIIMQEVMVRGTPFCM 752
Cdd:cd14662  126 NTLLDGSPAprLKICDFGYSK--SSVLHSQPKSTVGTPAYIAPEVL--SRKEYDGKVA-DVWSCGVTLYVMLVGAYPFED 200
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 945225    753 MDLPaQEIINRLKKPPPVYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEIFN 807
Cdd:cd14662  201 PDDP-KNFRKTIQRIMSVQYKIPDYVRVSQDCRHLLSRIFVANPAKRITIPEIKN 254
STKc_MEKK3 cd06651
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular ...
596-808 2.94e-04

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK3 is a MAPK kinase kinase (MAPKKK or MKKK), that phosphorylates and activates the MAPK kinase MEK5 (or MKK5), which in turn phosphorylates and activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. In addition, MEKK3 is involved in interleukin-1 receptor and Toll-like receptor 4 signaling. It is also a specific regulator of the proinflammatory cytokines IL-6 and GM-CSF in some immune cells. MEKK3 also regulates calcineurin, which plays a critical role in T cell activation, apoptosis, skeletal myocyte differentiation, and cardiac hypertrophy. The MEKK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270817 [Multi-domain]  Cd Length: 271  Bit Score: 43.92  E-value: 2.94e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSG--MFAIVTEFCSRGSLEDILTNQDVkLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKS 673
Cdd:cd06651   61 QLLKNLQHERIVQYYGCLRDRAekTLTIFMEYMPGGSVKDQLKAYGA-LTESVTRKYTRQILEGMSYLHSNMIVHRDIKG 139
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    674 RNCVVDGRFVLKVTDYGFNDILEM--LRLSEEESSMEELLWTAPELLRAPRGSRlgsfAGDVYSFAIIMQEVMVRGTPFC 751
Cdd:cd06651  140 ANILRDSAGNVKLGDFGASKRLQTicMSGTGIRSVTGTPYWMSPEVISGEGYGR----KADVWSLGCTVVEMLTEKPPWA 215
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 945225    752 mmdlpAQEIINRLKKPPPVYRPVVPPEHAPPECLQLMKQCWAEaAEQRPTFDEIFNQ 808
Cdd:cd06651  216 -----EYEAMAAIFKIATQPTNPQLPSHISEHARDFLGCIFVE-ARHRPSAEELLRH 266
STKc_PLK4 cd14186
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 4; STKs catalyze the ...
590-697 3.06e-04

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK4, also called SAK or STK18, is structurally different from other PLKs in that it contains only one polo box that can form two adjacent polo boxes and a functional PDB by homodimerization. It is required for late mitotic progression, cell survival, and embryonic development. It localizes to centrosomes and is required for centriole duplication and chromosomal stability. Overexpression of PLK4 may be associated with colon tumors. The PLK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271088 [Multi-domain]  Cd Length: 256  Bit Score: 43.70  E-value: 3.06e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    590 RASDVFEMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHG 669
Cdd:cd14186   47 RVRNEVEIHCQLKHPSILELYNYFEDSNYVYLVLEMCHNGEMSRYLKNRKKPFTEDEARHFMHQIVTGMLYLHSHGILHR 126
                         90       100
                 ....*....|....*....|....*...
gi 945225    670 RLKSRNCVVDGRFVLKVTDYGFNDILEM 697
Cdd:cd14186  127 DLTLSNLLLTRNMNIKIADFGLATQLKM 154
STKc_Unc-89_rpt2 cd14112
Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Uncoordinated ...
595-690 3.56e-04

Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Uncoordinated protein 89; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The nematode Unc-89 gene, through alternative promoter use and splicing, encodes at least six major isoforms (Unc-89A to Unc-89F) of giant muscle proteins that are homologs for the vetebrate obscurin. In flies, five isoforms of Unc-89 have been detected: four in the muscles of adult flies (two in the indirect flight muscle and two in other muscles) and another isoform in the larva. Unc-89 in nematodes is required for normal muscle cell architecture. In flies, it is necessary for the development of a symmetrical sarcomere in the flight muscles. Unc-89 proteins contain several adhesion and signaling domains including multiple copies of the immunoglobulin (Ig) domain, as well as fibronectin type III (FN3), SH3, RhoGEF, and PH domains. The nematode Unc-89 isoforms D, C, D, and F contain two kinase domain with B and F having two complete kinase domains while the first repeat of C and D are partial domains. Homology modeling suggests that the first kinase repeat of Unc-89 may be catalytically inactive, a pseudokinase, while the second kinase repeat may be active. The Unc-89 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271014 [Multi-domain]  Cd Length: 259  Bit Score: 43.67  E-value: 3.56e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    595 FEMMKDLRHENINPLLGFFYDSGMFAIVTE-----FCSRGSLEDILTNQDVkldwmfkSSLLLDLIKGMKYLHHREFVHG 669
Cdd:cd14112   51 FESLRTLQHENVQRLIAAFKPSNFAYLVMEklqedVFTRFSSNDYYSEEQV-------ATTVRQILDALHYLHFKGIAHL 123
                         90       100
                 ....*....|....*....|...
gi 945225    670 RLKSRNCVVDGR--FVLKVTDYG 690
Cdd:cd14112  124 DVQPDNIMFQSVrsWQVKLVDFG 146
PKc_like cd13968
Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large ...
592-690 3.64e-04

Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large family of typical PKs that includes serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins, as well as pseudokinases that lack crucial residues for catalytic activity and/or ATP binding. It also includes phosphoinositide 3-kinases (PI3Ks), aminoglycoside 3'-phosphotransferases (APHs), choline kinase (ChoK), Actin-Fragmin Kinase (AFK), and the atypical RIO and Abc1p-like protein kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to their target substrates; these include serine/threonine/tyrosine residues in proteins for typical or atypical PKs, the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives for PI3Ks, the 4-hydroxyl of PtdIns for PI4Ks, and other small molecule substrates for APH/ChoK and similar proteins such as aminoglycosides, macrolides, choline, ethanolamine, and homoserine.


Pssm-ID: 270870 [Multi-domain]  Cd Length: 136  Bit Score: 41.66  E-value: 3.64e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    592 SDVFEMMKDLRHE-NINPLLGFFYDSGMFAIVTEFCSRGSLEDILtnQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGR 670
Cdd:cd13968   39 SEMDILRRLKGLElNIPKVLVTEDVDGPNILLMELVKGGTLIAYT--QEEELDEKDVESIMYQLAECMRLLHSFHLIHRD 116
                         90       100
                 ....*....|....*....|
gi 945225    671 LKSRNCVVDGRFVLKVTDYG 690
Cdd:cd13968  117 LNNDNILLSEDGNVKLIDFG 136
PBP1_GPC6A-like cd06361
ligand-binding domain of the promiscuous L-alpha-amino acid receptor GPRC6A which is a ...
155-196 4.34e-04

ligand-binding domain of the promiscuous L-alpha-amino acid receptor GPRC6A which is a broad-spectrum amino acid-sensing receptor; This family includes the ligand-binding domain of the promiscuous L-alpha-amino acid receptor GPRC6A which is a broad-spectrum amino acid-sensing receptor, and its fish homolog, the 5.24 chemoreceptor. GPRC6A is a member of the family C of G-protein-coupled receptors that transduce extracellular signals into G-protein activation and ultimately into cellular responses.


Pssm-ID: 380584 [Multi-domain]  Cd Length: 401  Bit Score: 43.90  E-value: 4.34e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 945225    155 ELDNKISYPTFSRTLPS---PIRVLVTVMKYFQWAHAGVISSDED 196
Cdd:cd06361  137 ILSDKLRFPSFLRTVPSdfhQTKAMAKLISHFGWNWVGIIYTDDD 181
STKc_STK25 cd06642
Catalytic domain of Serine/Threonine Kinase 25 (also called Yeast Sps1/Ste20-related kinase 1); ...
573-749 4.53e-04

Catalytic domain of Serine/Threonine Kinase 25 (also called Yeast Sps1/Ste20-related kinase 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK25 is also called Ste20/oxidant stress response kinase 1 (SOK1) or yeast Sps1/Ste20-related kinase 1 (YSK1). It is localized in the Golgi apparatus through its interaction with the Golgi matrix protein GM130. It may be involved in the regulation of cell migration and polarization. STK25 binds and phosphorylates CCM3 (cerebral cavernous malformation 3), also called PCD10 (programmed cell death 10), and may play a role in apoptosis. Human STK25 is a candidate gene responsible for pseudopseudohypoparathyroidism (PPHP), a disease that shares features with the Albright hereditary osteodystrophy (AHO) phenotype. The STK25 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270810 [Multi-domain]  Cd Length: 277  Bit Score: 43.51  E-value: 4.53e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    573 LKKFSLGDFGDL-KSIKSRASDVFEM-----------MKDLRHE----------NINPLLGFFYDSGMFAIVTEFCSRGS 630
Cdd:cd06642    9 LERIGKGSFGEVyKGIDNRTKEVVAIkiidleeaedeIEDIQQEitvlsqcdspYITRYYGSYLKGTKLWIIMEYLGGGS 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    631 LEDILtnQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGFNDILEMLRlSEEESSMEEL 710
Cdd:cd06642   89 ALDLL--KPGPLEETYIATILREILKGLDYLHSERKIHRDIKAANVLLSEQGDVKLADFGVAGQLTDTQ-IKRNTFVGTP 165
                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 945225    711 LWTAPELLRaprgSRLGSFAGDVYSFAIIMQEvMVRGTP 749
Cdd:cd06642  166 FWMAPEVIK----QSAYDFKADIWSLGITAIE-LAKGEP 199
PTK_Jak1_rpt1 cd05077
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 1; Jak1 is widely ...
541-805 5.04e-04

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 1; Jak1 is widely expressed in many tissues. Many cytokines are dependent on Jak1 for signaling, including those that use the shared receptor subunits, common gamma chain (IL-2, IL-4, IL-7, IL-9, IL-15, IL-21) and gp130 (IL-6, IL-11, oncostatin M, G-CSF, and IFNs, among others). The many varied interactions of Jak1 and its ubiquitous expression suggest many biological roles. Jak1 is important in neurological development, as well as in lymphoid development and function. It also plays a role in the pathophysiology of cardiac hypertrophy and heart failure. A mutation in the ATP-binding site of Jak1 was identified in a human uterine leiomyosarcoma cell line, resulting in defective cytokine induction and antigen presentation, thus allowing the tumor to evade the immune system. Jak1 is a cytoplasmic (or nonreceptor) PTK containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. The Jak1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270662 [Multi-domain]  Cd Length: 266  Bit Score: 43.39  E-value: 5.04e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    541 GRSPRLSFSSGSLTPATYENSNIAIYEgdwvwlKKFSLgdfgDLKSIKSRASDV----FE---MMKDLRHENINPLLGFF 613
Cdd:cd05077    8 GRGTRTQIYAGILNYKDDDEDEGYSYE------KEIKV----ILKVLDPSHRDIslafFEtasMMRQVSHKHIVLLYGVC 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    614 YDSGMFAIVTEFCSRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNCVV-------DGRFVLKV 686
Cdd:cd05077   78 VRDVENIMVEEFVEFGPLDLFMHRKSDVLTTPWKFKVAKQLASALSYLEDKDLVHGNVCTKNILLaregidgECGPFIKL 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    687 TDYGFnDILEMLRlseeESSMEELLWTAPELLrapRGSRLGSFAGDVYSFAIIMQEVMVRG-TPFCMMDLPAQEiinRLK 765
Cdd:cd05077  158 SDPGI-PITVLSR----QECVERIPWIAPECV---EDSKNLSIAADKWSFGTTLWEICYNGeIPLKDKTLAEKE---RFY 226
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|...
gi 945225    766 KPPPVYrpvvppehAPPECLQ---LMKQCWAEAAEQRPTFDEI 805
Cdd:cd05077  227 EGQCML--------VTPSCKEladLMTHCMNYDPNQRPFFRAI 261
PKc_MAPKK_plant_like cd06623
Catalytic domain of Plant dual-specificity Mitogen-Activated Protein Kinase Kinases and ...
584-750 5.16e-04

Catalytic domain of Plant dual-specificity Mitogen-Activated Protein Kinase Kinases and similar proteins; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include MAPKKs from plants, kinetoplastids, alveolates, and mycetozoa. The MAPKK, LmxPK4, from Leishmania mexicana, is important in differentiation and virulence. Dictyostelium discoideum MEK1 is required for proper chemotaxis; MEK1 null mutants display severe defects in cell polarization and directional movement. Plants contain multiple MAPKKs like other eukaryotes. The Arabidopsis genome encodes for 10 MAPKKs while poplar and rice contain 13 MAPKKs each. The functions of these proteins have not been fully elucidated. There is evidence to suggest that MAPK cascades are involved in plant stress responses. In Arabidopsis, MKK3 plays a role in pathogen signaling; MKK2 is involved in cold and salt stress signaling; MKK4/MKK5 participates in innate immunity; and MKK7 regulates basal and systemic acquired resistance. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132954 [Multi-domain]  Cd Length: 264  Bit Score: 43.35  E-value: 5.16e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    584 LKSIKSRASDVF--EMMKDLR--HENINPLL----GFFYDSGMFAIVTEFCSRGSLEDILtnqdvKLDWMFKSSLLLD-- 653
Cdd:cd06623   31 LKKIHVDGDEEFrkQLLRELKtlRSCESPYVvkcyGAFYKEGEISIVLEYMDGGSLADLL-----KKVGKIPEPVLAYia 105
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    654 --LIKGMKYLHH-REFVHGRLKSRNCVVDGRFVLKVTDYGFNDILEmlrlseeESSMEELLW--TA----PELLRaprgS 724
Cdd:cd06623  106 rqILKGLDYLHTkRHIIHRDIKPSNLLINSKGEVKIADFGISKVLE-------NTLDQCNTFvgTVtymsPERIQ----G 174
                        170       180
                 ....*....|....*....|....*.
gi 945225    725 RLGSFAGDVYSFAIIMQEVMVRGTPF 750
Cdd:cd06623  175 ESYSYAADIWSLGLTLLECALGKFPF 200
STKc_PDK1 cd05581
Catalytic domain of the Serine/Threonine Kinase, Phosphoinositide-dependent kinase 1; STKs ...
596-763 5.72e-04

Catalytic domain of the Serine/Threonine Kinase, Phosphoinositide-dependent kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PDK1 carries an N-terminal catalytic domain and a C-terminal pleckstrin homology (PH) domain that binds phosphoinositides. It phosphorylates the activation loop of AGC kinases that are regulated by PI3K such as PKB, SGK, and PKC, among others, and is crucial for their activation. Thus, it contributes in regulating many processes including metabolism, growth, proliferation, and survival. PDK1 also has the ability to autophosphorylate and is constitutively active in mammalian cells. It is essential for normal embryo development and is important in regulating cell volume. The PDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270733 [Multi-domain]  Cd Length: 278  Bit Score: 42.97  E-value: 5.72e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILT---NQDVKlDWMFKSSLLLDlikGMKYLHHREFVHGRLK 672
Cdd:cd05581   53 EVLSRLAHPGIVKLYYTFQDESKLYFVLEYAPNGDLLEYIRkygSLDEK-CTRFYTAEIVL---ALEYLHSKGIIHRDLK 128
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    673 SRNCVVDGRFVLKVTDYGFNDIL------EMLRLSEEESSMEELLWTA----------PELLraprGSRLGSFAGDVYSF 736
Cdd:cd05581  129 PENILLDEDMHIKITDFGTAKVLgpdsspESTKGDADSQIAYNQARAAsfvgtaeyvsPELL----NEKPAGKSSDLWAL 204
                        170       180       190
                 ....*....|....*....|....*....|.
gi 945225    737 -AIIMQevMVRG-TPFCMM--DLPAQEIINR 763
Cdd:cd05581  205 gCIIYQ--MLTGkPPFRGSneYLTFQKIVKL 233
STKc_MEKK3_like cd06625
Catalytic domain of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) ...
596-809 5.79e-04

Catalytic domain of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MEKK3, MEKK2, and related proteins; all contain an N-terminal PB1 domain, which mediates oligomerization, and a C-terminal catalytic domain. MEKK2 and MEKK3 are MAPK kinase kinases (MAPKKKs or MKKK) that activate MEK5 (also called MKK5), which activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. MEKK2 and MEKK3 can also activate the MAPKs, c-Jun N-terminal kinase (JNK) and p38, through their respective MAPKKs. The MEKK3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270795 [Multi-domain]  Cd Length: 260  Bit Score: 43.11  E-value: 5.79e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVkLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRN 675
Cdd:cd06625   54 QLLKNLQHERIVQYYGCLQDEKSLSIFMEYMPGGSVKDEIKAYGA-LTENVTRKYTRQILEGLAYLHSNMIVHRDIKGAN 132
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    676 CVVDGRFVLKVTDYGFNDILEMLRLSEEESSMEEL-LWTAPELLrapRGSRLGSFAgDVYSFAIIMQEVMVRGTPFcmMD 754
Cdd:cd06625  133 ILRDSNGNVKLGDFGASKRLQTICSSTGMKSVTGTpYWMSPEVI---NGEGYGRKA-DIWSVGCTVVEMLTTKPPW--AE 206
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 945225    755 LPAQEIINrlkKPPPVYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEIFNQF 809
Cdd:cd06625  207 FEPMAAIF---KIATQPTNPQLPPHVSEDARDFLSLIFVRNKKQRPSAEELLSHS 258
STKc_CaMKK2 cd14199
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 2; ...
597-696 6.12e-04

Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMP-activated protein kinase (AMPK). CaMKK2, also called CaMKK beta, is one of the most versatile CaMKs. It is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. CaMKK2 contains unique N- and C-terminal domains and a central catalytic kinase domain that is followed by a regulatory domain that bears overlapping autoinhibitory and CaM-binding regions. It can be activated by signaling through G-coupled receptors, IP3 receptors, plasma membrane ion channels, and Toll-like receptors. Thus, CaMKK2 acts as a molecular hub that is capable of receiving and decoding signals from diverse pathways. The CaMKK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271101 [Multi-domain]  Cd Length: 286  Bit Score: 43.03  E-value: 6.12e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFFYDSG--MFAIVTEFCSRGSLEDILTNQDVKLD---WMFKsslllDLIKGMKYLHHREFVHGRL 671
Cdd:cd14199   78 ILKKLDHPNVVKLVEVLDDPSedHLYMVFELVKQGPVMEVPTLKPLSEDqarFYFQ-----DLIKGIEYLHYQKIIHRDV 152
                         90       100
                 ....*....|....*....|....*..
gi 945225    672 KSRNCVV--DGRfvLKVTDYGFNDILE 696
Cdd:cd14199  153 KPSNLLVgeDGH--IKIADFGVSNEFE 177
STKc_MEKK3_like_u1 cd06653
Catalytic domain of an Uncharacterized subfamily of Mitogen-Activated Protein (MAP) ...
596-805 6.24e-04

Catalytic domain of an Uncharacterized subfamily of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of uncharacterized proteins with similarity to MEKK3, MEKK2, and related proteins; they contain an N-terminal PB1 domain, which mediates oligomerization, and a C-terminal catalytic domain. MEKK2 and MEKK3 are MAPK kinase kinases (MAPKKKs or MKKKs), proteins that phosphorylate and activate MAPK kinases (MAPKKs or MKKs), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MEKK2 and MEKK3 activate MEK5 (also called MKK5), which activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. MEKK2 and MEKK3 can also activate the MAPKs, c-Jun N-terminal kinase (JNK) and p38, through their respective MAPKKs. The MEKK3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270819 [Multi-domain]  Cd Length: 264  Bit Score: 43.09  E-value: 6.24e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYD--SGMFAIVTEFCSRGSLEDILTNQDVkLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKS 673
Cdd:cd06653   56 QLLKNLRHDRIVQYYGCLRDpeEKKLSIFVEYMPGGSVKDQLKAYGA-LTENVTRRYTRQILQGVSYLHSNMIVHRDIKG 134
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    674 RNCVVDGRFVLKVTDYGFNDILEML--RLSEEESSMEELLWTAPELLrapRGSRLGSFAgDVYSFAIIMQEVMVRGTPFC 751
Cdd:cd06653  135 ANILRDSAGNVKLGDFGASKRIQTIcmSGTGIKSVTGTPYWMSPEVI---SGEGYGRKA-DVWSVACTVVEMLTEKPPWA 210
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 945225    752 MMdlpaqEIINRLKKPPPVYRPVVPPEHAPPECLQLMKQCWAEaAEQRPTFDEI 805
Cdd:cd06653  211 EY-----EAMAAIFKIATQPTKPQLPDGVSDACRDFLRQIFVE-EKRRPTAEFL 258
STKc_WNK2_like cd14032
Catalytic domain of With No Lysine (WNK) 2-like Serine/Threonine kinases; STKs catalyze the ...
565-799 6.31e-04

Catalytic domain of With No Lysine (WNK) 2-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK2 is widely expressed and has been shown to be epigenetically silenced in gliomas. It inhibits cell growth by acting as a negative regulator of MEK1-ERK1/2 signaling. WNK2 modulates growth factor-induced cancer cell proliferation, suggesting that it may be a tumor suppressor gene. WNKs comprise a subfamily of STKs with an unusual placement of the catalytic lysine relative to all other protein kinases. They are critical in regulating ion balance and are thus, important components in the control of blood pressure. The WNK2-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270934 [Multi-domain]  Cd Length: 266  Bit Score: 42.76  E-value: 6.31e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    565 IYEG----DWVWLKKFSLGDFGDLKSIKSRASDVFEMMKDLRHENINPLLGFFYDSGM----FAIVTEFCSRGSLEDILT 636
Cdd:cd14032   17 VYKGldteTWVEVAWCELQDRKLTKVERQRFKEEAEMLKGLQHPNIVRFYDFWESCAKgkrcIVLVTELMTSGTLKTYLK 96
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    637 NQDVKLDWMFKsSLLLDLIKGMKYLHHRE--FVHGRLKSRNCVVDGRF-VLKVTDYGfndILEMLRLSEEESSMEELLWT 713
Cdd:cd14032   97 RFKVMKPKVLR-SWCRQILKGLLFLHTRTppIIHRDLKCDNIFITGPTgSVKIGDLG---LATLKRASFAKSVIGTPEFM 172
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    714 APELLRAPRGSRLgsfagDVYSFAIIMQEVMVRGTPFCMMDLPAQeiinRLKKPPPVYRPVVPPEHAPPECLQLMKQCWA 793
Cdd:cd14032  173 APEMYEEHYDESV-----DVYAFGMCMLEMATSEYPYSECQNAAQ----IYRKVTCGIKPASFEKVTDPEIKEIIGECIC 243

                 ....*.
gi 945225    794 EAAEQR 799
Cdd:cd14032  244 KNKEER 249
STKc_ROCK2 cd05621
Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein ...
569-750 6.73e-04

Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ROCK2 was the first identified target of activated RhoA, and was found to play a role in stress fiber and focal adhesion formation. It is prominently expressed in the brain, heart, and skeletal muscles. It is implicated in vascular and neurological disorders, such as hypertension and vasospasm of the coronary and cerebral arteries. ROCK2 is also activated by caspase-2 cleavage, resulting in thrombin-induced microparticle generation in response to cell activation. Mice deficient in ROCK2 show intrauterine growth retardation and embryonic lethality because of placental dysfunction. ROCK contains an N-terminal extension, a catalytic kinase domain, and a C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain, and is activated via interaction with Rho GTPases. The ROCK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270771 [Multi-domain]  Cd Length: 379  Bit Score: 43.45  E-value: 6.73e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    569 DWVWLKKFSLGDFGDLKSIKSRAS---------DVFEMMK-----------DLRHENINP----LLGFFYDSGMFAIVTE 624
Cdd:cd05621   53 DYDVVKVIGRGAFGEVQLVRHKASqkvyamkllSKFEMIKrsdsaffweerDIMAFANSPwvvqLFCAFQDDKYLYMVME 132
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    625 FCSRGSLEDILTNQDVKLDWM-FKSSlllDLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGFNDILEMLRLSEE 703
Cdd:cd05621  133 YMPGGDLVNLMSNYDVPEKWAkFYTA---EVVLALDAIHSMGLIHRDVKPDNMLLDKYGHLKLADFGTCMKMDETGMVHC 209
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 945225    704 ESSMEELLWTAPELLRAPRGSRLGSFAGDVYSFAIIMQEVMVRGTPF 750
Cdd:cd05621  210 DTAVGTPDYISPEVLKSQGGDGYYGRECDWWSVGVFLFEMLVGDTPF 256
STKc_PCTAIRE_like cd07844
Catalytic domain of PCTAIRE-like Serine/Threonine Kinases; STKs catalyze the transfer of the ...
597-690 6.85e-04

Catalytic domain of PCTAIRE-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-like proteins show unusual expression patterns with high levels in post-mitotic tissues, suggesting that they may be involved in regulating post-mitotic cellular events. They share sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The association of PCTAIRE-like proteins with cyclins has not been widely studied, although PFTAIRE-1 has been shown to function as a CDK which is regulated by cyclin D3 as well as the membrane-associated cyclin Y. The PCTAIRE-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270835 [Multi-domain]  Cd Length: 286  Bit Score: 42.75  E-value: 6.85e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFFYDSGMFAIVTEFCSRG---SLED---ILTNQDVKLdwmfkssLLLDLIKGMKYLHHREFVHGR 670
Cdd:cd07844   51 LLKDLKHANIVTLHDIIHTKKTLTLVFEYLDTDlkqYMDDcggGLSMHNVRL-------FLFQLLRGLAYCHQRRVLHRD 123
                         90       100
                 ....*....|....*....|
gi 945225    671 LKSRNCVVDGRFVLKVTDYG 690
Cdd:cd07844  124 LKPQNLLISERGELKLADFG 143
STKc_DCKL2 cd14184
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 2 (also called ...
597-696 7.62e-04

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 2 (also called Doublecortin-like and CAM kinase-like 2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL2 (or DCAMKL2) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL2 contains a serine, threonine, and proline rich domain (SP) and a C-terminal kinase domain with similarity to CAMKs. DCKL2 has been shown to interact with tubulin, JIP1/2, JNK, neurabin 2, and actin. It is associated with the terminal segments of axons and dendrites, and may function as a phosphorylation-dependent switch to control microtubule dynamics in neuronal growth cones. The DCKL2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271086 [Multi-domain]  Cd Length: 259  Bit Score: 42.71  E-value: 7.62e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQdVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNC 676
Cdd:cd14184   52 ILRRVKHPNIIMLIEEMDTPAELYLVMELVKGGDLFDAITSS-TKYTERDASAMVYNLASALKYLHGLCIVHRDIKPENL 130
                         90       100
                 ....*....|....*....|....
gi 945225    677 VV----DGRFVLKVTDYGFNDILE 696
Cdd:cd14184  131 LVceypDGTKSLKLGDFGLATVVE 154
STKc_MLCK1 cd14191
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 1; STKs catalyze ...
574-750 7.70e-04

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK1 (or MYLK1) phosphorylates myosin regulatory light chain and controls the contraction of smooth muscles. The MLCK1 gene expresses three transcripts in a cell-specific manner: a short MLCK1 which contains three immunoglobulin (Ig)-like and one fibronectin type III (FN3) domains, PEVK and actin-binding regions, and a kinase domain near the C-terminus followed by a regulatory segment containing an autoinhibitory Ca2+/calmodulin binding site; a long MLCK1 containing six additional Ig-like domains at the N-terminus compared to the short MLCK1; and the C-terminal Ig module which results in the expression of telokin in phasic smooth muscles, leading to Ca2+ desensitization by cyclic nucleotides of smooth muscle force. MLCK1 is also responsible for myosin regulatory light chain phosphorylation in nonmuscle cells and may play a role in regulating myosin II ATPase activity. The MLCK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271093 [Multi-domain]  Cd Length: 259  Bit Score: 42.68  E-value: 7.70e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    574 KKFSLGDFGDLKSIKSRAS--DVFEMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKLDWMFKSSLL 651
Cdd:cd14191   27 KKVWAGKFFKAYSAKEKENirQEISIMNCLHHPKLVQCVDAFEEKANIVMVLEMVSGGELFERIIDEDFELTERECIKYM 106
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    652 LDLIKGMKYLHHREFVHGRLKSRN--CVVDGRFVLKVTDYGFNDILEmlRLSEEESSMEELLWTAPELLraprGSRLGSF 729
Cdd:cd14191  107 RQISEGVEYIHKQGIVHLDLKPENimCVNKTGTKIKLIDFGLARRLE--NAGSLKVLFGTPEFVAPEVI----NYEPIGY 180
                        170       180
                 ....*....|....*....|..
gi 945225    730 AGDVYSFAIIMQeVMVRG-TPF 750
Cdd:cd14191  181 ATDMWSIGVICY-ILVSGlSPF 201
STKc_PIM1 cd14100
Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) ...
618-808 8.38e-04

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are two PIM1 isoforms resulting from alternative translation initiation sites. PIM1 is the founding member of the PIM subfamily. It is involved in regulating cell growth, differentiation, and apoptosis. It promotes cancer development when overexpressed by inhibiting apoptosis, promoting cell proliferation, and promoting genomic instability. The PIM1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271002 [Multi-domain]  Cd Length: 254  Bit Score: 42.65  E-value: 8.38e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    618 MFAIVTEfcsRGSLEDILTNqdvkldwmfksSLLLDLIKGMKYLHHREFVHGRLKSRNCVVD-GRFVLKVTDYGFNdilE 696
Cdd:cd14100   93 LFDFITE---RGALPEELAR-----------SFFRQVLEAVRHCHNCGVLHRDIKDENILIDlNTGELKLIDFGSG---A 155
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    697 MLRLSEEESSMEELLWTAPELLRAprgSRLGSFAGDVYSFAIIMQEVMVRGTPFcmmdLPAQEIINrlkkpppvyRPVVP 776
Cdd:cd14100  156 LLKDTVYTDFDGTRVYSPPEWIRF---HRYHGRSAAVWSLGILLYDMVCGDIPF----EHDEEIIR---------GQVFF 219
                        170       180       190
                 ....*....|....*....|....*....|..
gi 945225    777 PEHAPPECLQLMKQCWAEAAEQRPTFDEIFNQ 808
Cdd:cd14100  220 RQRVSSECQHLIKWCLALRPSDRPSFEDIQNH 251
PK_STRAD_beta cd08226
Pseudokinase domain of STE20-related kinase adapter protein beta; The pseudokinase domain ...
602-765 8.38e-04

Pseudokinase domain of STE20-related kinase adapter protein beta; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity.STRAD-beta is also referred to as ALS2CR2 (Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 2 protein), since the human gene encoding it is located within the juvenile ALS2 critical region on chromosome 2q33-q34. It is not linked to the development of ALS2. STRAD forms a complex with the scaffolding protein MO25, and the serine/threonine kinase (STK), LKB1, resulting in the activation of the kinase. In the complex, LKB1 phosphorylates and activates adenosine monophosphate-activated protein kinases (AMPKs), which regulate cell energy metabolism and cell polarity. LKB1 is a tumor suppressor linked to the rare inherited disease, Peutz-Jeghers syndrome, which is characterized by a predisposition to benign polyps and hyperpigmentation of the buccal mucosa. The STRAD-beta subfamily is part of a larger superfamily that includes the catalytic domains of STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270864 [Multi-domain]  Cd Length: 328  Bit Score: 42.93  E-value: 8.38e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    602 RHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVK-LDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNCVVDG 680
Cdd:cd08226   57 RHPNIMTHWTVFTEGSWLWVISPFMAYGSARGLLKTYFPEgMNEALIGNILYGAIKALNYLHQNGCIHRSVKASHILISG 136
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    681 RFVlkVTDYGFNDILEMLRLSEEES--------SMEELLWTAPELLRAP-RGSRLGSfagDVYSFAIIMQEVMVRGTPFc 751
Cdd:cd08226  137 DGL--VSLSGLSHLYSMVTNGQRSKvvydfpqfSTSVLPWLSPELLRQDlHGYNVKS---DIYSVGITACELARGQVPF- 210
                        170
                 ....*....|....*
gi 945225    752 mMDLP-AQEIINRLK 765
Cdd:cd08226  211 -QDMRrTQMLLQKLK 224
STKc_MEKK1 cd06630
Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP) ...
596-690 1.03e-03

Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK1 is a MAPK kinase kinase (MAPKKK or MKKK) that phosphorylates and activates activates the ERK1/2 and c-Jun N-terminal kinase (JNK) pathways by activating their respective MAPKKs, MEK1/2 and MKK4/MKK7, respectively. MEKK1 is important in regulating cell survival and apoptosis. MEKK1 also plays a role in cell migration, tissue maintenance and homeostasis, and wound healing. The MEKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270800 [Multi-domain]  Cd Length: 268  Bit Score: 42.42  E-value: 1.03e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVkldwmFKSSLL----LDLIKGMKYLHHREFVHGRL 671
Cdd:cd06630   55 RMMARLNHPNIVRMLGATQHKSHFNIFVEWMAGGSVASLLSKYGA-----FSENVIinytLQILRGLAYLHDNQIIHRDL 129
                         90       100
                 ....*....|....*....|.
gi 945225    672 KSRNCVVD--GRfVLKVTDYG 690
Cdd:cd06630  130 KGANLLVDstGQ-RLRIADFG 149
STKc_WNK1 cd14030
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 1; STKs catalyze ...
585-808 1.23e-03

Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK1 is widely expressed and is most abundant in the testis. In hyperosmotic or hypotonic low-chloride stress conditions, WNK1 is activated and it phosphorylates its substrates including SPAK and OSR1 kinases, which regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. Mutations in WNK1 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension and hyperkalemia. WNK1 negates WNK4-mediated inhibition of the sodium-chloride cotransporter NCC and activates the epithelial sodium channel ENaC by activating SGK1. WNK1 also decreases the surface expression of renal outer medullary potassium channel (ROMK) by stimulating their endocytosis. Hypertension and hyperkalemia in PHAII patients with WNK1 mutations may be due partly to increased activity of NCC and ENaC, and impaired renal potassium secretion by ROMK, respectively. In addition, WNK1 interacts with MEKK2/3 and acts as an activator of extracellular signal-regulated kinase (ERK) 5. It also negatively regulates TGFbeta signaling. WNKs comprise a subfamily of STKs with an unusual placement of the catalytic lysine relative to all other protein kinases. The WNK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270932 [Multi-domain]  Cd Length: 289  Bit Score: 42.34  E-value: 1.23e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    585 KSIKSRASDVFEMMKDLRHENINPllgfFYDS--------GMFAIVTEFCSRGSLEDILTNQDVKLDWMFKSsLLLDLIK 656
Cdd:cd14030   65 KSERQRFKEEAGMLKGLQHPNIVR----FYDSwestvkgkKCIVLVTELMTSGTLKTYLKRFKVMKIKVLRS-WCRQILK 139
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    657 GMKYLHHRE--FVHGRLKSRNCVVDGRF-VLKVTDYGfndILEMLRLSEEESSMEELLWTAPELLRAPRGSRLgsfagDV 733
Cdd:cd14030  140 GLQFLHTRTppIIHRDLKCDNIFITGPTgSVKIGDLG---LATLKRASFAKSVIGTPEFMAPEMYEEKYDESV-----DV 211
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 945225    734 YSFAIIMQEVMVRGTPFCMMDLPAQeIINRLKKPPPVYRPVVPpehAPPECLQLMKQCWAEAAEQRPTFDEIFNQ 808
Cdd:cd14030  212 YAFGMCMLEMATSEYPYSECQNAAQ-IYRRVTSGVKPASFDKV---AIPEVKEIIEGCIRQNKDERYAIKDLLNH 282
STKc_SLK cd06643
Catalytic domain of the Serine/Threonine Kinase, Ste20-Like Kinase; STKs catalyze the transfer ...
603-743 1.26e-03

Catalytic domain of the Serine/Threonine Kinase, Ste20-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SLK promotes apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and the mitogen-activated protein kinase (MAPK) p38. It acts as a MAPK kinase kinase by phosphorylating ASK1, resulting in the phosphorylation of p38. SLK also plays a role in mediating actin reorganization. It is part of a microtubule-associated complex that is targeted at adhesion sites, and is required in focal adhesion turnover and in regulating cell migration. The SLK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270811 [Multi-domain]  Cd Length: 283  Bit Score: 41.94  E-value: 1.26e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    603 HENINPLLGFFYDSGMFAIVTEFCSRGS-------LEDILTNQDVKLdwMFKSSLlldliKGMKYLHHREFVHGRLKSRN 675
Cdd:cd06643   61 HPNIVKLLDAFYYENNLWILIEFCAGGAvdavmleLERPLTEPQIRV--VCKQTL-----EALVYLHENKIIHRDLKAGN 133
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 945225    676 CV--VDGRfvLKVTDYGFN--DILEMLRlseEESSMEELLWTAPELLRAPRGS-RLGSFAGDVYSFAIIMQEV 743
Cdd:cd06643  134 ILftLDGD--IKLADFGVSakNTRTLQR---RDSFIGTPYWMAPEVVMCETSKdRPYDYKADVWSLGVTLIEM 201
STKc_MST3_like cd06609
Catalytic domain of Mammalian Ste20-like protein kinase 3-like Serine/Threonine Kinases; STKs ...
597-690 1.33e-03

Catalytic domain of Mammalian Ste20-like protein kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MST3, MST4, STK25, Schizosaccharomyces pombe Nak1 and Sid1, Saccharomyces cerevisiae sporulation-specific protein 1 (SPS1), and related proteins. Nak1 is required by fission yeast for polarizing the tips of actin cytoskeleton and is involved in cell growth, cell separation, cell morphology and cell-cycle progression. Sid1 is a component in the septation initiation network (SIN) signaling pathway, and plays a role in cytokinesis. SPS1 plays a role in regulating proteins required for spore wall formation. MST4 plays a role in mitogen-activated protein kinase (MAPK) signaling during cytoskeletal rearrangement, morphogenesis, and apoptosis. MST3 phosphorylates the STK NDR and may play a role in cell cycle progression and cell morphology. STK25 may play a role in the regulation of cell migration and polarization. The MST3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270786 [Multi-domain]  Cd Length: 274  Bit Score: 41.85  E-value: 1.33e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQdvKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNC 676
Cdd:cd06609   52 FLSQCDSPYITKYYGSFLKGSKLWIIMEYCGGGSVLDLLKPG--PLDETYIAFILREVLLGLEYLHSEGKIHRDIKAANI 129
                         90
                 ....*....|....
gi 945225    677 VVDGRFVLKVTDYG 690
Cdd:cd06609  130 LLSEEGDVKLADFG 143
STKc_YSK4 cd06631
Catalytic domain of the Serine/Threonine Kinase, Yeast Sps1/Ste20-related Kinase 4; STKs ...
596-690 1.34e-03

Catalytic domain of the Serine/Threonine Kinase, Yeast Sps1/Ste20-related Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. YSK4 is a putative MAPKKK, whose mammalian gene has been isolated. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The YSK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270801 [Multi-domain]  Cd Length: 266  Bit Score: 42.04  E-value: 1.34e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILtNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRN 675
Cdd:cd06631   55 DLLKTLKHVNIVGYLGTCLEDNVVSIFMEFVPGGSIASIL-ARFGALEEPVFCRYTKQILEGVAYLHNNNVIHRDIKGNN 133
                         90
                 ....*....|....*
gi 945225    676 CVVDGRFVLKVTDYG 690
Cdd:cd06631  134 IMLMPNGVIKLIDFG 148
STKc_MLCK cd14103
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase; STKs catalyze the ...
596-690 1.66e-03

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. In vertebrates, different MLCKs function in smooth (MLCK1), skeletal (MLCK2), and cardiac (MLCK3) muscles. A fourth protein, MLCK4, has also been identified through comprehensive genome analysis although it has not been biochemically characterized. The MLCK1 gene expresses three transcripts in a cell-specific manner: a short MLCK1 which contains three immunoglobulin (Ig)-like and one fibronectin type III (FN3) domains, PEVK and actin-binding regions, and a kinase domain near the C-terminus; a long MLCK1 containing six additional Ig-like domains at the N-terminus compared to the short MLCK1; and the C-terminal Ig module. MLCK2, MLCK3, and MLCK4 share a simpler domain architecture of a single kinase domain near the C-terminus and the absence of Ig-like or FN3 domains. The MLCK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271005 [Multi-domain]  Cd Length: 250  Bit Score: 41.44  E-value: 1.66e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSL------ED-ILTNQDVKLdwmfkssLLLDLIKGMKYLHHREFVH 668
Cdd:cd14103   42 EIMNQLRHPRLLQLYDAFETPREMVLVMEYVAGGELfervvdDDfELTERDCIL-------FMRQICEGVQYMHKQGILH 114
                         90       100
                 ....*....|....*....|....
gi 945225    669 GRLKSRN--CVVDGRFVLKVTDYG 690
Cdd:cd14103  115 LDLKPENilCVSRTGNQIKIIDFG 138
STKc_TAO1 cd06635
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 1; STKs catalyze ...
596-859 1.75e-03

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO1 is sometimes referred to as prostate-derived sterile 20-like kinase 2 (PSK2). TAO1 activates the p38 MAPK through direct interaction with and activation of MEK3. TAO1 is highly expressed in the brain and may play a role in neuronal apoptosis. TAO1 interacts with the checkpoint proteins BubR1 and Mad2, and plays an important role in regulating mitotic progression, which is required for both chromosome congression and checkpoint-induced anaphase delay. TAO1 may play a role in protecting genomic stability. TAO proteins possess MAPK kinase kinase activity. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The TAO1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270805 [Multi-domain]  Cd Length: 317  Bit Score: 41.96  E-value: 1.75e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCsRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRN 675
Cdd:cd06635   77 KFLQRIKHPNSIEYKGCYLREHTAWLVMEYC-LGSASDLLEVHKKPLQEIEIAAITHGALQGLAYLHSHNMIHRDIKAGN 155
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    676 CVVDGRFVLKVTDYGFNDILEmlrlsEEESSMEELLWTAPELLRAprgSRLGSFAG--DVYSFAIIMQEVMVRGTPFCMM 753
Cdd:cd06635  156 ILLTEPGQVKLADFGSASIAS-----PANSFVGTPYWMAPEVILA---MDEGQYDGkvDVWSLGITCIELAERKPPLFNM 227
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    754 DlpaqeIINRLKKPPPVYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEIFNQFKTFNKGKKTNIIDSMLRMleqyss 833
Cdd:cd06635  228 N-----AMSALYHIAQNESPTLQSNEWSDYFRNFVDSCLQKIPQDRPTSEELLKHMFVLRERPETVLIDLIQRT------ 296
                        250       260
                 ....*....|....*....|....*.
gi 945225    834 nlEDLIRERTeelEIEKQKTEKLLTQ 859
Cdd:cd06635  297 --KDAVRELD---NLQYRKMKKLLFQ 317
STKc_TAO3 cd06633
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 3; STKs catalyze ...
596-754 1.94e-03

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO3 is also known as JIK (c-Jun N-terminal kinase inhibitory kinase) or KFC (kinase from chicken). It specifically activates JNK, presumably by phosphorylating and activating MKK4/MKK7. In Saccharomyces cerevisiae, TAO3 is a component of the RAM (regulation of Ace2p activity and cellular morphogenesis) signaling pathway. TAO3 is upregulated in retinal ganglion cells after axotomy, and may play a role in apoptosis. TAO proteins possess mitogen-activated protein kinase (MAPK) kinase kinase activity. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The TAO3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270803 [Multi-domain]  Cd Length: 313  Bit Score: 41.56  E-value: 1.94e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCsRGSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRN 675
Cdd:cd06633   73 KFLQQLKHPNTIEYKGCYLKDHTAWLVMEYC-LGSASDLLEVHKKPLQEVEIAAITHGALQGLAYLHSHNMIHRDIKAGN 151
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    676 CVVDGRFVLKVTDYGFNDIlemlrLSEEESSMEELLWTAPELLRAprgSRLGSFAG--DVYSFAIIMQEVMVRGTPFCMM 753
Cdd:cd06633  152 ILLTEPGQVKLADFGSASI-----ASPANSFVGTPYWMAPEVILA---MDEGQYDGkvDIWSLGITCIELAERKPPLFNM 223

                 .
gi 945225    754 D 754
Cdd:cd06633  224 N 224
STKc_RSK2_C cd14176
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called ...
585-764 2.07e-03

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called 90kDa ribosomal protein S6 kinase 3 or Ribosomal protein S6 kinase alpha-3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK2 is also called p90RSK3, RPS6KA3, S6K-alpha-3, or MAPK-activated protein kinase 1b (MAPKAPK-1b). RSK2 is expressed highly in the regions of the brain with high synaptic activity. It plays a role in the maintenance and consolidation of excitatory synapses. It is a specific modulator of phospholipase D in calcium-regulated exocytosis. Mutations in the RSK2 gene, RPS6KA3, cause Coffin-Lowry syndrome (CLS), a rare syndromic form of X-linked mental retardation characterized by growth and psychomotor retardation and skeletal abnormalities. RSK2 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271078 [Multi-domain]  Cd Length: 339  Bit Score: 41.54  E-value: 2.07e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    585 KSIKSRASDVFEMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVkLDWMFKSSLLLDLIKGMKYLHHR 664
Cdd:cd14176   54 KSKRDPTEEIEILLRYGQHPNIITLKDVYDDGKYVYVVTELMKGGELLDKILRQKF-FSEREASAVLFTITKTVEYLHAQ 132
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    665 EFVHGRLKSRNCV-VD---GRFVLKVTDYGFNDILEMlRLSEEESSMEELLWTAPELLRaprgsRLG-SFAGDVYSFAII 739
Cdd:cd14176  133 GVVHRDLKPSNILyVDesgNPESIRICDFGFAKQLRA-ENGLLMTPCYTANFVAPEVLE-----RQGyDAACDIWSLGVL 206
                        170       180
                 ....*....|....*....|....*..
gi 945225    740 MQEVMVRGTPFCM--MDLPaQEIINRL 764
Cdd:cd14176  207 LYTMLTGYTPFANgpDDTP-EEILARI 232
STKc_NUAK cd14073
Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK; STKs catalyze ...
573-690 2.91e-03

Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NUAK proteins are classified as AMP-activated protein kinase (AMPK)-related kinases, which like AMPK are activated by the major tumor suppressor LKB1. Vertebrates contain two NUAK proteins, called NUAK1 and NUAK2. NUAK1, also called ARK5 (AMPK-related protein kinase 5), regulates cell proliferation and displays tumor suppression through direct interaction and phosphorylation of p53. It is also involved in cell senescence and motility. High NUAK1 expression is associated with invasiveness of nonsmall cell lung cancer (NSCLC) and breast cancer cells. NUAK2, also called SNARK (Sucrose, non-fermenting 1/AMP-activated protein kinase-related kinase), is involved in energy metabolism. It is activated by hyperosmotic stress, DNA damage, and nutrients such as glucose and glutamine. NUAK2-knockout mice develop obesity, altered serum lipid profiles, hyperinsulinaemia, hyperglycaemia, and impaired glucose tolerance. The NUAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270975 [Multi-domain]  Cd Length: 254  Bit Score: 40.83  E-value: 2.91e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    573 LKKFSLGDFGDLKSIKSRasdvFEMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDvKLDWMFKSSLLL 652
Cdd:cd14073   34 IKKDKIEDEQDMVRIRRE----IEIMSSLNHPHIIRIYEVFENKDKIVIVMEYASGGELYDYISERR-RLPEREARRIFR 108
                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 945225    653 DLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYG 690
Cdd:cd14073  109 QIVSAVHYCHKNGVVHRDLKLENILLDQNGNAKIADFG 146
STKc_JNK cd07850
Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase; STKs catalyze the ...
590-690 3.07e-03

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. They are also essential regulators of physiological and pathological processes and are involved in the pathogenesis of several diseases such as diabetes, atherosclerosis, stroke, Parkinson's and Alzheimer's. Vetebrates harbor three different JNK genes (Jnk1, Jnk2, and Jnk3) that are alternatively spliced to produce at least 10 isoforms. JNKs are specifically activated by the MAPK kinases MKK4 and MKK7, which are in turn activated by upstream MAPK kinase kinases as a result of different stimuli including stresses such as ultraviolet (UV) irradiation, hyperosmolarity, heat shock, or cytokines. JNKs activate a large number of different substrates based on specific stimulus, cell type, and cellular condition, and may be implicated in seemingly contradictory functions. The JNK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270840 [Multi-domain]  Cd Length: 337  Bit Score: 41.25  E-value: 3.07e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    590 RASDVFEMMKDLRHENINPLLGFFydsgmfaivtefCSRGSLEDIltnQDV-----------------KLDWMFKSSLLL 652
Cdd:cd07850   45 RAYRELVLMKLVNHKNIIGLLNVF------------TPQKSLEEF---QDVylvmelmdanlcqviqmDLDHERMSYLLY 109
                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 945225    653 DLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYG 690
Cdd:cd07850  110 QMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFG 147
STKc_MST3 cd06641
Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 3; STKs ...
573-749 3.33e-03

Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MST3 phosphorylates the STK NDR and may play a role in cell cycle progression and cell morphology. It may also regulate paxillin and consequently, cell migration. MST3 is present in human placenta, where it plays an essential role in the oxidative stress-induced apoptosis of trophoblasts in normal spontaneous delivery. Dysregulation of trophoblast apoptosis may result in pregnancy complications such as preeclampsia and intrauterine growth retardation. The MST3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270809 [Multi-domain]  Cd Length: 277  Bit Score: 40.83  E-value: 3.33e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    573 LKKFSLGDFGDL-KSIKSRASDVFEM-----------MKDLRHENI------NPLLGFFYDSGM----FAIVTEFCSRGS 630
Cdd:cd06641    9 LEKIGKGSFGEVfKGIDNRTQKVVAIkiidleeaedeIEDIQQEITvlsqcdSPYVTKYYGSYLkdtkLWIIMEYLGGGS 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    631 LEDILtnQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGFNDILEMLRlSEEESSMEEL 710
Cdd:cd06641   89 ALDLL--EPGPLDETQIATILREILKGLDYLHSEKKIHRDIKAANVLLSEHGEVKLADFGVAGQLTDTQ-IKRN*FVGTP 165
                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 945225    711 LWTAPELLRAprgSRLGSFAgDVYSFAIIMQEvMVRGTP 749
Cdd:cd06641  166 FWMAPEVIKQ---SAYDSKA-DIWSLGITAIE-LARGEP 199
STKc_CDC2L1 cd07843
Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 2-like 1; STKs catalyze ...
595-690 3.89e-03

Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 2-like 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDC2L1, also called PITSLRE, exists in different isoforms which are named using the alias CDK11(p). The CDC2L1 gene produces two protein products, CDK11(p110) and CDK11(p58). CDC2L1 is also represented by the caspase-processed CDK11(p46). CDK11(p110), the major isoform, associates with cyclin L and is expressed throughout the cell cycle. It is involved in RNA processing and the regulation of transcription. CDK11(p58) associates with cyclin D3 and is expressed during the G2/M phase of the cell cycle. It plays roles in spindle morphogenesis, centrosome maturation, sister chromatid cohesion, and the completion of mitosis. CDK11(p46) is formed from the larger isoforms by caspases during TNFalpha- and Fas-induced apoptosis. It functions as a downstream effector kinase in apoptotic signaling pathways and interacts with eukaryotic initiation factor 3f (eIF3f), p21-activated kinase (PAK1), and Ran-binding protein (RanBPM). CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDC2L1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173741 [Multi-domain]  Cd Length: 293  Bit Score: 40.67  E-value: 3.89e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    595 FEMMKDLRHENINPLLGFFYDSGM--FAIVTEFCS---RGSLEDI---LTNQDVKldwmfksSLLLDLIKGMKYLHHREF 666
Cdd:cd07843   55 INILLKLQHPNIVTVKEVVVGSNLdkIYMVMEYVEhdlKSLMETMkqpFLQSEVK-------CLMLQLLSGVAHLHDNWI 127
                         90       100
                 ....*....|....*....|....
gi 945225    667 VHGRLKSRNCVVDGRFVLKVTDYG 690
Cdd:cd07843  128 LHRDLKTSNLLLNNRGILKICDFG 151
STKc_Nek9 cd08221
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
601-808 3.98e-03

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 9; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek9, also called Nercc1, is primarily a cytoplasmic protein but can also localize in the nucleus. It is involved in modulating chromosome alignment and splitting during mitosis. It interacts with the gamma-tubulin ring complex and the Ran GTPase, and is implicated in microtubule organization. Nek9 associates with FACT (FAcilitates Chromatin Transcription) and modulates interphase progression. It also interacts with Nek6, and Nek7, during mitosis, resulting in their activation. Nek9 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270860 [Multi-domain]  Cd Length: 256  Bit Score: 40.49  E-value: 3.98e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    601 LRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKLdwmFKSSLLL----DLIKGMKYLHHREFVHGRLKSRNC 676
Cdd:cd08221   56 LNHDNIITYYNHFLDGESLFIEMEYCNGGNLHDKIAQQKNQL---FPEEVVLwylyQIVSAVSHIHKAGILHRDIKTLNI 132
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    677 VVDGRFVLKVTDYGFNDILEMlRLSEEESSMEELLWTAPELLRAPRgsrlGSFAGDVYSFAIIMQEVMVRGTPFcmmdlp 756
Cdd:cd08221  133 FLTKADLVKLGDFGISKVLDS-ESSMAESIVGTPYYMSPELVQGVK----YNFKSDIWAVGCVLYELLTLKRTF------ 201
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 945225    757 aqEIIN--RLKKPPPVYRPVVPPEHAPPECLQLMKQCWAEAAEQRPTFDEIFNQ 808
Cdd:cd08221  202 --DATNplRLAVKIVQGEYEDIDEQYSEEIIQLVHDCLHQDPEDRPTAEELLER 253
STKc_CDK12 cd07864
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 12; STKs ...
596-764 4.14e-03

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 12; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK12 is also called Cdc2-related protein kinase 7 (CRK7) or Cdc2-related kinase arginine/serine-rich (CrkRS). It is a unique CDK that contains an RS domain, which is predominantly found in splicing factors. CDK12 is widely expressed in tissues. It interacts with cyclins L1 and L2, and plays roles in regulating transcription and alternative splicing. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK12 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270847 [Multi-domain]  Cd Length: 302  Bit Score: 40.56  E-value: 4.14e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPL----------LGFFYDSGMFAIVTEFCSRgSLEDILTNQDVKLDWMFKSSLLLDLIKGMKYLHHRE 665
Cdd:cd07864   58 KILRQLNHRSVVNLkeivtdkqdaLDFKKDKGAFYLVFEYMDH-DLMGLLESGLVHFSEDHIKSFMKQLLEGLNYCHKKN 136
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    666 FVHGRLKSRNCVVDGRFVLKVTDYGFNDILEMLRLSEEESSMEELLWTAPELLrapRGSRLGSFAGDVYSFAIIMQEVMV 745
Cdd:cd07864  137 FLHRDIKCSNILLNNKGQIKLADFGLARLYNSEESRPYTNKVITLWYRPPELL---LGEERYGPAIDVWSCGCILGELFT 213
                        170       180
                 ....*....|....*....|
gi 945225    746 RGTPFCMMDLPAQ-EIINRL 764
Cdd:cd07864  214 KKPIFQANQELAQlELISRL 233
STKc_TSSK6-like cd14164
Catalytic domain of testis-specific serine/threonine kinase 6 and similar proteins; STKs ...
597-750 4.65e-03

Catalytic domain of testis-specific serine/threonine kinase 6 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK6, also called SSTK, is expressed at the head of elongated sperm. It can phosphorylate histones and associate with heat shock protens HSP90 and HSC70. Male mice deficient in TSSK6 are infertile, showing spermatogenic impairment including reduced sperm counts, impaired DNA condensation, abnormal morphology and decreased motility rates. The TSSK6-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271066 [Multi-domain]  Cd Length: 256  Bit Score: 40.23  E-value: 4.65e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFF-YDSGMFAIVTEFCSRGSLEDILTNQDVKLDwmFKSSLLLDLIKGMKYLHHREFVHGRLKSRN 675
Cdd:cd14164   53 ILRRVNHPNIVQMFECIeVANGRLYIVMEAAATDLLQKIQEVHHIPKD--LARDMFAQMVGAVNYLHDMNIVHRDLKCEN 130
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 945225    676 CVV--DGRFVlKVTDYGFNDILEMLrLSEEESSMEELLWTAPE-LLRAPRGSRlgsfAGDVYSFAIIMQeVMVRGT-PF 750
Cdd:cd14164  131 ILLsaDDRKI-KIADFGFARFVEDY-PELSTTFCGSRAYTPPEvILGTPYDPK----KYDVWSLGVVLY-VMVTGTmPF 202
STKc_CDKL1_4 cd07847
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 1 and 4; ...
568-695 5.36e-03

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 1 and 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKL1, also called p42 KKIALRE, is a glial protein that is upregulated in gliosis. It is present in neuroblastoma and A431 human carcinoma cells, and may be implicated in neoplastic transformation. The function of CDKL4 is unknown. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL1/4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270837 [Multi-domain]  Cd Length: 286  Bit Score: 40.05  E-value: 5.36e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    568 GDWVWLKKFSlgDFGDLKSIKSRASDVFEMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDvKLDWMFK 647
Cdd:cd07847   26 GQIVAIKKFV--ESEDDPVIKKIALREIRMLKQLKHPNLVNLIEVFRRKRKLHLVFEYCDHTVLNELEKNPR-GVPEHLI 102
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 945225    648 SSLLLDLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYGFNDIL 695
Cdd:cd07847  103 KKIIWQTLQAVNFCHKHNCIHRDVKPENILITKQGQIKLCDFGFARIL 150
STKc_ULK2 cd14201
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 2; STKs catalyze the ...
596-750 5.47e-03

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK2 is ubiquitously expressed and is essential in autophagy induction. It displays partially redundant functions with ULK1 and is able to compensate for the loss of ULK1 in non-selective autophagy. It also displays neuron-specific functions and is important in axon development. The ULK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271103 [Multi-domain]  Cd Length: 271  Bit Score: 39.99  E-value: 5.47e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDVKLDWMFKsSLLLDLIKGMKYLHHREFVHGRLKSRN 675
Cdd:cd14201   57 KILKELQHENIVALYDVQEMPNSVFLVMEYCNGGDLADYLQAKGTLSEDTIR-VFLQQIAAAMRILHSKGIIHRDLKPQN 135
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    676 CVVD--GR-------FVLKVTDYGFNDILEmlRLSEEESSMEELLWTAPELLRaprgSRLGSFAGDVYSFAIIMQEVMVR 746
Cdd:cd14201  136 ILLSyaSRkkssvsgIRIKIADFGFARYLQ--SNMMAATLCGSPMYMAPEVIM----SQHYDAKADLWSIGTVIYQCLVG 209

                 ....
gi 945225    747 GTPF 750
Cdd:cd14201  210 KPPF 213
STKc_HUNK cd14070
Catalytic domain of the Serine/Threonine Kinase, Hormonally up-regulated Neu-associated kinase ...
596-750 5.74e-03

Catalytic domain of the Serine/Threonine Kinase, Hormonally up-regulated Neu-associated kinase (also called MAK-V); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HUNK/MAK-V was identified from a mammary tumor in an MMTV-neu transgenic mouse. It is required for the metastasis of c-myc-induced mammary tumors, but is not necessary for c-myc-induced primary tumor formation or normal development. It is required for HER2/neu-induced tumor formation and maintenance of the cells' tumorigenic phenotype. It is over-expressed in aggressive subsets of ovary, colon, and breast carcinomas. HUNK interacts with synaptopodin, and may also play a role in synaptic plasticity. The HUNK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270972 [Multi-domain]  Cd Length: 262  Bit Score: 39.80  E-value: 5.74e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQDvKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRN 675
Cdd:cd14070   55 RIQQMIRHPNITQLLDILETENSYYLVMELCPGGNLMHRIYDKK-RLEEREARRYIRQLVSAVEHLHRAGVVHRDLKIEN 133
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 945225    676 CVVDGRFVLKVTDYGFNDILEMLRLSEEESSM-EELLWTAPELL-RAPRGSRLgsfagDVYSFAIIMQEVMVRGTPF 750
Cdd:cd14070  134 LLLDENDNIKLIDFGLSNCAGILGYSDPFSTQcGSPAYAAPELLaRKKYGPKV-----DVWSIGVNMYAMLTGTLPF 205
STKc_CAMKK cd14118
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase; ...
597-696 5.96e-03

Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMP-activated protein kinase (AMPK). Vertebrates contain two CaMKKs, CaMKK1 (or alpha) and CaMKK2 (or beta). CaMKK1 is involved in the regulation of glucose uptake in skeletal muscles. CaMKK2 is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. The CaMKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271020 [Multi-domain]  Cd Length: 275  Bit Score: 40.04  E-value: 5.96e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENI--------NPLLGFFYdsgmfaIVTEFCSRGS-LEDILTNqdvKLDWMFKSSLLLDLIKGMKYLHHREFV 667
Cdd:cd14118   67 ILKKLDHPNVvklvevldDPNEDNLY------MVFELVDKGAvMEVPTDN---PLSEETARSYFRDIVLGIEYLHYQKII 137
                         90       100       110
                 ....*....|....*....|....*....|.
gi 945225    668 HGRLKSRNCVV--DGRfvLKVTDYGFNDILE 696
Cdd:cd14118  138 HRDIKPSNLLLgdDGH--VKIADFGVSNEFE 166
STKc_IRE1 cd13982
Catalytic domain of the Serine/Threonine kinase, Inositol-requiring protein 1; STKs catalyze ...
614-807 6.99e-03

Catalytic domain of the Serine/Threonine kinase, Inositol-requiring protein 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRE1, also called Endoplasmic reticulum (ER)-to-nucleus signaling protein (or ERN), is an ER-localized type I transmembrane protein with kinase and endoribonuclease domains in the cytoplasmic side. It acts as an ER stress sensor and is the oldest and most conserved component of the unfolded protein response (UPR) in eukaryotes. The UPR is activated when protein misfolding is detected in the ER in order to decrease the synthesis of new proteins and increase the capacity of the ER to cope with the stress. During ER stress, IRE1 dimerizes and forms oligomers, allowing the kinase domain to undergo trans-autophosphorylation. This leads to a conformational change that stimulates its endoribonuclease activity and results in the cleavage of its mRNA substrate, HAC1 in yeast and XBP1 in metazoans, promoting a splicing event that enables translation into a transcription factor which activates the UPR. Mammals contain two IRE1 proteins, IRE1alpha (or ERN1) and IRE1beta (or ERN2). The Ire1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270884 [Multi-domain]  Cd Length: 269  Bit Score: 39.56  E-value: 6.99e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    614 YDSGMFAIVTEFCSrGSLEDILTNQDVKLDWMFKS----SLLLDLIKGMKYLHHREFVHGRLKSRNCVVD-----GRFVL 684
Cdd:cd13982   65 KDRQFLYIALELCA-ASLQDLVESPRESKLFLRPGlepvRLLRQIASGLAHLHSLNIVHRDLKPQNILIStpnahGNVRA 143
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    685 KVTDYGFNDILEMLRLSEEESSMEE--LLWTAPELLRAPRGSRLgSFAGDVYSFAIIMQEVMVRGT-PFcmmDLPAQEII 761
Cdd:cd13982  144 MISDFGLCKKLDVGRSSFSRRSGVAgtSGWIAPEMLSGSTKRRQ-TRAVDIFSLGCVFYYVLSGGShPF---GDKLEREA 219
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 945225    762 NRLKKPPPVYRPVVPPEHaPPECLQLMKQCWAEAAEQRPTFDEIFN 807
Cdd:cd13982  220 NILKGKYSLDKLLSLGEH-GPEAQDLIERMIDFDPEKRPSAEEVLN 264
STKc_PKA_like cd05580
Catalytic subunit of the Serine/Threonine Kinases, cAMP-dependent protein kinases; STKs ...
596-750 7.15e-03

Catalytic subunit of the Serine/Threonine Kinases, cAMP-dependent protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the cAMP-dependent protein kinases, PKA and PRKX, and similar proteins. The inactive PKA holoenzyme is a heterotetramer composed of two phosphorylated and active catalytic subunits with a dimer of regulatory (R) subunits. Activation is achieved through the binding of the important second messenger cAMP to the R subunits, which leads to the dissociation of PKA into the R dimer and two active subunits. PKA is present ubiquitously in cells and interacts with many different downstream targets. It plays a role in the regulation of diverse processes such as growth, development, memory, metabolism, gene expression, immunity, and lipolysis. PRKX is also reulated by the R subunit and is is present in many tissues including fetal and adult brain, kidney, and lung. It is implicated in granulocyte/macrophage lineage differentiation, renal cell epithelial migration, and tubular morphogenesis in the developing kidney. The PKA-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270732 [Multi-domain]  Cd Length: 290  Bit Score: 39.87  E-value: 7.15e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    596 EMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDIL------TNQDVKLdwmFKSSLLLDLikgmKYLHHREFVHG 669
Cdd:cd05580   53 RILSEVRHPFIVNLLGSFQDDRNLYMVMEYVPGGELFSLLrrsgrfPNDVAKF---YAAEVVLAL----EYLHSLDIVYR 125
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    670 RLKSRNCVVDGRFVLKVTDYGFNDILEmlrlseeessmeELLWT--------APELLraprgSRLG-SFAGDVYSFAIIM 740
Cdd:cd05580  126 DLKPENLLLDSDGHIKITDFGFAKRVK------------DRTYTlcgtpeylAPEII-----LSKGhGKAVDWWALGILI 188
                        170
                 ....*....|
gi 945225    741 QEVMVRGTPF 750
Cdd:cd05580  189 YEMLAGYPPF 198
STKc_p38beta cd07878
Catalytic domain of the Serine/Threonine Kinase, p38beta Mitogen-Activated Protein Kinase ...
597-691 8.04e-03

Catalytic domain of the Serine/Threonine Kinase, p38beta Mitogen-Activated Protein Kinase (also called MAPK11); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38beta/MAPK11 is widely expressed in tissues and shows more similarity with p38alpha than with the other isoforms. Both are sensitive to pyridinylimidazoles and share some common substrates such as MAPK activated protein kinase 2 (MK2) and the transcription factors ATF2, c-Fos and, ELK-1. p38beta is involved in regulating the activation of the cyclooxygenase-2 promoter and the expression of TGFbeta-induced alpha-smooth muscle cell actin. p38 kinases are mitogen-activated protein kinases (MAPKs), serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38beta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143383 [Multi-domain]  Cd Length: 343  Bit Score: 39.65  E-value: 8.04e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    597 MMKDLRHENINPLLGFFYDSGMFA------IVTEFCSrGSLEDILTNQDVKLDWMfkSSLLLDLIKGMKYLHHREFVHGR 670
Cdd:cd07878   67 LLKHMKHENVIGLLDVFTPATSIEnfnevyLVTNLMG-ADLNNIVKCQKLSDEHV--QFLIYQLLRGLKYIHSAGIIHRD 143
                         90       100
                 ....*....|....*....|.
gi 945225    671 LKSRNCVVDGRFVLKVTDYGF 691
Cdd:cd07878  144 LKPSNVAVNEDCELRILDFGL 164
STKc_JNK3 cd07874
Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 3; STKs catalyze the ...
590-691 8.52e-03

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNK3 is expressed primarily in the brain, and to a lesser extent in the heart and testis. Mice deficient in JNK3 are protected against kainic acid-induced seizures, stroke, sciatic axotomy neural death, and neuronal death due to NGF deprivation, oxidative stress, or exposure to beta-amyloid peptide. This suggests that JNK3 may play roles in the pathogenesis of these diseases. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. The JNK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143379 [Multi-domain]  Cd Length: 355  Bit Score: 39.69  E-value: 8.52e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 945225    590 RASDVFEMMKDLRHENINPLLGFFYDSGMFAIVTEFCSRGSLEDILTNQ--DVKLDWMFKSSLLLDLIKGMKYLHHREFV 667
Cdd:cd07874   62 RAYRELVLMKCVNHKNIISLLNVFTPQKSLEEFQDVYLVMELMDANLCQviQMELDHERMSYLLYQMLCGIKHLHSAGII 141
                         90       100
                 ....*....|....*....|....
gi 945225    668 HGRLKSRNCVVDGRFVLKVTDYGF 691
Cdd:cd07874  142 HRDLKPSNIVVKSDCTLKILDFGL 165
STKc_EIF2AK2_PKR cd14047
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
621-690 8.72e-03

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 2 or Protein Kinase regulated by RNA; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKR (or EIF2AK2) contains an N-terminal double-stranded RNA (dsRNA) binding domain and a C-terminal catalytic kinase domain. It is activated by dsRNA, which is produced as a replication intermediate in virally infected cells. It plays a key role in mediating innate immune responses to viral infection. PKR is also directly activated by PACT (protein activator of PKR) and heparin, and is inhibited by viral proteins and RNAs. PKR also regulates transcription and signal transduction in diseased cells, playing roles in tumorigenesis and neurodegenerative diseases. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The PKR subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270949 [Multi-domain]  Cd Length: 267  Bit Score: 39.40  E-value: 8.72e-03
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 945225    621 IVTEFCSRGSLED-ILTNQDVKLDWMFKSSLLLDLIKGMKYLHHREFVHGRLKSRNCVVDGRFVLKVTDYG 690
Cdd:cd14047   92 IQMEFCEKGTLESwIEKRNGEKLDKVLALEIFEQITKGVEYIHSKKLIHRDLKPSNIFLVDTGKVKIGDFG 162
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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