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Conserved domains on  [gi|1796318599|ref|YP_009724391|]
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ORF3a protein [Severe acute respiratory syndrome coronavirus 2]

Protein Classification

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
SARS-CoV-like_ORF3a cd21648
accessory protein ORF3a of severe acute respiratory syndrome-associated coronavirus and ...
5-274 0e+00

accessory protein ORF3a of severe acute respiratory syndrome-associated coronavirus and similar proteins from related betacoronavirus; This model represents the accessory protein ORF3a of Severe Acute Respiratory Syndrome-associated coronavirus (SARS-CoV), SARS-COV-2 (also called 2019 novel coronavirus or 2019-nCoV), and related betacoronaviruses in the Sarbecovirus subgenus (B lineage). There are five essential genes in CoVs that result in the following gene products: Spike (S) protein, Membrane (M) glycoprotein, Nucleocapsid (N), Envelope (E) protein, and replicase/protease polyproteins (ORF1ab); all are required to produce a structurally complete viral particle. In addition, CoV genomes also contain ORFs coding for accessory proteins that are specific for certain CoV lineages or for a particular CoV. In general, CoV accessory proteins are considered to be dispensable for viral replication; however, several accessory proteins have been shown to exhibit functions in virus-host interactions during CoV infection. SARS-CoV mRNA 3 encodes the distinct proteins ORF3a and ORF3b, which are translated in different reading frames. Accessory protein ORF3a, also called protein 3a and protein X1, is the largest ORF protein in SARS-CoV. It is also called accessory protein 3 or protein 3 in some bat coronaviruses. SARS-CoV ORF3a promotes membrane rearrangement and cell death; it induces vesicle formation and is necessary for SARS-CoV-induced Golgi fragmentation. It has also been found to activate NF-kappaB and the NLRP3 inflammasome by promoting TNF receptor-associated factor 3 (TRAF3)-dependent ubiquitination of p105 and ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain). The cytoplasmic domain of SARS-CoV ORF3a, composed of amino acids at the C-terminal region, has sequence similarity to a calcium pump present in Plasmodium falciparum and has been shown to bind calcium in vitro. SARS-CoV-2 3a is able to form ion channels; it is a Class IIIA viroporin, having 3 transmembrane helices per protomer and a lumenal amino terminus and cytosolic carboxyl terminus. It can form dimers, tetramers, and potentially higher order oligomers. It has been shown to form cation channels with modest selectivity for Ca2+ and K+ over Na+.


:

Pssm-ID: 439223  Cd Length: 269  Bit Score: 529.42  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1796318599   5 MRIFTIGTVTLKQGEIKDATPSDFVRATATIPIQASLPFGWLIVGVALLAVFQSASKIITLKKRWQLALSKGVHFVCNLL 84
Cdd:cd21648     1 MSIFTLGSITRQPSKIENASPASTVHATATIPLQASLPFGWLVVGVALLAVFQSASKVIALHKRWQLALYKGIQLVCNLL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1796318599  85 LLFVTVYSHLLLVAAGLEAPFLYLYALVYFLQSINFVRIIMRLWLCWKCRSKNPLLYDANYFLCWHTNCYDYCIPYNSVT 164
Cdd:cd21648    81 LLFVTIYSHLLLLAAGMEAQFLYIYALIYILQIVSFCRFIMRCWLCWKCKSKNPLLYDANYFVCWHTHNYDYCIPYNSVT 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1796318599 165 SSIVITSGDGTTSPISEHDYQIGGYTEKWESGVKDCVVLHSYFTSDYYQLYSTQLSTDTGVEHVTFFIYNKIVDEPeEHV 244
Cdd:cd21648   161 DTIVVTAGDGISTPKLKEDYQIGGYSEDWHSGVKDYVVVHGYFTEVYYQLESTQISTDTGIENATFFIFNKLVKDP-PNV 239
                         250       260       270
                  ....*....|....*....|....*....|
gi 1796318599 245 QIHTIDGSSGVVNPVMEPIYDEPTTTTSVP 274
Cdd:cd21648   240 QIHTIDGSSGVVNPAMDPIYDEPTTTTSVP 269
 
Name Accession Description Interval E-value
SARS-CoV-like_ORF3a cd21648
accessory protein ORF3a of severe acute respiratory syndrome-associated coronavirus and ...
5-274 0e+00

accessory protein ORF3a of severe acute respiratory syndrome-associated coronavirus and similar proteins from related betacoronavirus; This model represents the accessory protein ORF3a of Severe Acute Respiratory Syndrome-associated coronavirus (SARS-CoV), SARS-COV-2 (also called 2019 novel coronavirus or 2019-nCoV), and related betacoronaviruses in the Sarbecovirus subgenus (B lineage). There are five essential genes in CoVs that result in the following gene products: Spike (S) protein, Membrane (M) glycoprotein, Nucleocapsid (N), Envelope (E) protein, and replicase/protease polyproteins (ORF1ab); all are required to produce a structurally complete viral particle. In addition, CoV genomes also contain ORFs coding for accessory proteins that are specific for certain CoV lineages or for a particular CoV. In general, CoV accessory proteins are considered to be dispensable for viral replication; however, several accessory proteins have been shown to exhibit functions in virus-host interactions during CoV infection. SARS-CoV mRNA 3 encodes the distinct proteins ORF3a and ORF3b, which are translated in different reading frames. Accessory protein ORF3a, also called protein 3a and protein X1, is the largest ORF protein in SARS-CoV. It is also called accessory protein 3 or protein 3 in some bat coronaviruses. SARS-CoV ORF3a promotes membrane rearrangement and cell death; it induces vesicle formation and is necessary for SARS-CoV-induced Golgi fragmentation. It has also been found to activate NF-kappaB and the NLRP3 inflammasome by promoting TNF receptor-associated factor 3 (TRAF3)-dependent ubiquitination of p105 and ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain). The cytoplasmic domain of SARS-CoV ORF3a, composed of amino acids at the C-terminal region, has sequence similarity to a calcium pump present in Plasmodium falciparum and has been shown to bind calcium in vitro. SARS-CoV-2 3a is able to form ion channels; it is a Class IIIA viroporin, having 3 transmembrane helices per protomer and a lumenal amino terminus and cytosolic carboxyl terminus. It can form dimers, tetramers, and potentially higher order oligomers. It has been shown to form cation channels with modest selectivity for Ca2+ and K+ over Na+.


Pssm-ID: 439223  Cd Length: 269  Bit Score: 529.42  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1796318599   5 MRIFTIGTVTLKQGEIKDATPSDFVRATATIPIQASLPFGWLIVGVALLAVFQSASKIITLKKRWQLALSKGVHFVCNLL 84
Cdd:cd21648     1 MSIFTLGSITRQPSKIENASPASTVHATATIPLQASLPFGWLVVGVALLAVFQSASKVIALHKRWQLALYKGIQLVCNLL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1796318599  85 LLFVTVYSHLLLVAAGLEAPFLYLYALVYFLQSINFVRIIMRLWLCWKCRSKNPLLYDANYFLCWHTNCYDYCIPYNSVT 164
Cdd:cd21648    81 LLFVTIYSHLLLLAAGMEAQFLYIYALIYILQIVSFCRFIMRCWLCWKCKSKNPLLYDANYFVCWHTHNYDYCIPYNSVT 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1796318599 165 SSIVITSGDGTTSPISEHDYQIGGYTEKWESGVKDCVVLHSYFTSDYYQLYSTQLSTDTGVEHVTFFIYNKIVDEPeEHV 244
Cdd:cd21648   161 DTIVVTAGDGISTPKLKEDYQIGGYSEDWHSGVKDYVVVHGYFTEVYYQLESTQISTDTGIENATFFIFNKLVKDP-PNV 239
                         250       260       270
                  ....*....|....*....|....*....|
gi 1796318599 245 QIHTIDGSSGVVNPVMEPIYDEPTTTTSVP 274
Cdd:cd21648   240 QIHTIDGSSGVVNPAMDPIYDEPTTTTSVP 269
bCoV_viroporin pfam11289
Betacoronavirus viroporin; This entry represents protein 3a encoded by Orf3/3a, also known as ...
1-274 9.85e-159

Betacoronavirus viroporin; This entry represents protein 3a encoded by Orf3/3a, also known as X1, which forms homotetrameric potassium, sodium or calcium sensitive ion channels (viroporin) that causes ER-stress in host cells and may modulate virus release. This is a pro-apoptosis-inducing protein that localizes to the endoplasmic reticulum (ER)-Golgi compartment. SARS-CoV causes apoptosis of infected cells through NLRP3 inflammasome activation. Protein 3a also promotes the ubiquitination of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) mediated by its interaction with TNF receptor-associated factor 3 (TRAF3). This protein induces NF-kappa B activation and upregulates fibrinogen secretion with high cytokine production. Through the activation of the PERK pathway of unfolded protein response (UPR), this protein causes phosphorylation of eIF2-alpha leading to reduced translation of cellular proteins and as the activation of pro-apoptotic downstream effectors (i.e ATF4, CHOP).


Pssm-ID: 463255  Cd Length: 273  Bit Score: 442.17  E-value: 9.85e-159
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1796318599   1 MDLFMRIFTIGTVTLKQGEIKDATPSDFVRATATIPIQASLPFGWLIVGVALLAVFQSASKIITLKKRWQLALSKGVHFV 80
Cdd:pfam11289   1 MDLFMRFFTLGAITAQPAKIDNASPASTVHATATIPLQASLPFGWLVIGVAFLAVFQSASKIIALHKRWQLALYKGFQFI 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1796318599  81 CNLLLLFVTVYSHLLLVAAGLEAPFLYLYALVYFLQSINFVRIIMRLWLCWKCRSKNPLLYDANYFLCWHTNCYDYCIPY 160
Cdd:pfam11289  81 CNLLLLFVTIYSHLLLLAAGMEAQFLYIYALIYFLQCINACRFIMRCWLCWKCKSKNPLLYDANYFVCWHTHCFDYCIPY 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1796318599 161 NSVTSSIVITSGDGTTSPISEHDYQIGGYTEKWESGVKDCVVLHSYFTSDYYQLYSTQLSTDTGVEHVTFFIYNKIVDEP 240
Cdd:pfam11289 161 NSITDTIVLTEGDGINQPKLKEDYQIGGYSEDRHSGIKDYVVIHGYFTEVYYQLESTQISPDTGIENATFFIFNKLVKAP 240
                         250       260       270
                  ....*....|....*....|....*....|....
gi 1796318599 241 eEHVQIHTIDGSSGVVNPVMEPIYDEPTTTTSVP 274
Cdd:pfam11289 241 -DHVQIHTIDGSSGVANPAMDPIYDEPTTTTSVP 273
 
Name Accession Description Interval E-value
SARS-CoV-like_ORF3a cd21648
accessory protein ORF3a of severe acute respiratory syndrome-associated coronavirus and ...
5-274 0e+00

accessory protein ORF3a of severe acute respiratory syndrome-associated coronavirus and similar proteins from related betacoronavirus; This model represents the accessory protein ORF3a of Severe Acute Respiratory Syndrome-associated coronavirus (SARS-CoV), SARS-COV-2 (also called 2019 novel coronavirus or 2019-nCoV), and related betacoronaviruses in the Sarbecovirus subgenus (B lineage). There are five essential genes in CoVs that result in the following gene products: Spike (S) protein, Membrane (M) glycoprotein, Nucleocapsid (N), Envelope (E) protein, and replicase/protease polyproteins (ORF1ab); all are required to produce a structurally complete viral particle. In addition, CoV genomes also contain ORFs coding for accessory proteins that are specific for certain CoV lineages or for a particular CoV. In general, CoV accessory proteins are considered to be dispensable for viral replication; however, several accessory proteins have been shown to exhibit functions in virus-host interactions during CoV infection. SARS-CoV mRNA 3 encodes the distinct proteins ORF3a and ORF3b, which are translated in different reading frames. Accessory protein ORF3a, also called protein 3a and protein X1, is the largest ORF protein in SARS-CoV. It is also called accessory protein 3 or protein 3 in some bat coronaviruses. SARS-CoV ORF3a promotes membrane rearrangement and cell death; it induces vesicle formation and is necessary for SARS-CoV-induced Golgi fragmentation. It has also been found to activate NF-kappaB and the NLRP3 inflammasome by promoting TNF receptor-associated factor 3 (TRAF3)-dependent ubiquitination of p105 and ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain). The cytoplasmic domain of SARS-CoV ORF3a, composed of amino acids at the C-terminal region, has sequence similarity to a calcium pump present in Plasmodium falciparum and has been shown to bind calcium in vitro. SARS-CoV-2 3a is able to form ion channels; it is a Class IIIA viroporin, having 3 transmembrane helices per protomer and a lumenal amino terminus and cytosolic carboxyl terminus. It can form dimers, tetramers, and potentially higher order oligomers. It has been shown to form cation channels with modest selectivity for Ca2+ and K+ over Na+.


Pssm-ID: 439223  Cd Length: 269  Bit Score: 529.42  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1796318599   5 MRIFTIGTVTLKQGEIKDATPSDFVRATATIPIQASLPFGWLIVGVALLAVFQSASKIITLKKRWQLALSKGVHFVCNLL 84
Cdd:cd21648     1 MSIFTLGSITRQPSKIENASPASTVHATATIPLQASLPFGWLVVGVALLAVFQSASKVIALHKRWQLALYKGIQLVCNLL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1796318599  85 LLFVTVYSHLLLVAAGLEAPFLYLYALVYFLQSINFVRIIMRLWLCWKCRSKNPLLYDANYFLCWHTNCYDYCIPYNSVT 164
Cdd:cd21648    81 LLFVTIYSHLLLLAAGMEAQFLYIYALIYILQIVSFCRFIMRCWLCWKCKSKNPLLYDANYFVCWHTHNYDYCIPYNSVT 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1796318599 165 SSIVITSGDGTTSPISEHDYQIGGYTEKWESGVKDCVVLHSYFTSDYYQLYSTQLSTDTGVEHVTFFIYNKIVDEPeEHV 244
Cdd:cd21648   161 DTIVVTAGDGISTPKLKEDYQIGGYSEDWHSGVKDYVVVHGYFTEVYYQLESTQISTDTGIENATFFIFNKLVKDP-PNV 239
                         250       260       270
                  ....*....|....*....|....*....|
gi 1796318599 245 QIHTIDGSSGVVNPVMEPIYDEPTTTTSVP 274
Cdd:cd21648   240 QIHTIDGSSGVVNPAMDPIYDEPTTTTSVP 269
bCoV_viroporin pfam11289
Betacoronavirus viroporin; This entry represents protein 3a encoded by Orf3/3a, also known as ...
1-274 9.85e-159

Betacoronavirus viroporin; This entry represents protein 3a encoded by Orf3/3a, also known as X1, which forms homotetrameric potassium, sodium or calcium sensitive ion channels (viroporin) that causes ER-stress in host cells and may modulate virus release. This is a pro-apoptosis-inducing protein that localizes to the endoplasmic reticulum (ER)-Golgi compartment. SARS-CoV causes apoptosis of infected cells through NLRP3 inflammasome activation. Protein 3a also promotes the ubiquitination of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) mediated by its interaction with TNF receptor-associated factor 3 (TRAF3). This protein induces NF-kappa B activation and upregulates fibrinogen secretion with high cytokine production. Through the activation of the PERK pathway of unfolded protein response (UPR), this protein causes phosphorylation of eIF2-alpha leading to reduced translation of cellular proteins and as the activation of pro-apoptotic downstream effectors (i.e ATF4, CHOP).


Pssm-ID: 463255  Cd Length: 273  Bit Score: 442.17  E-value: 9.85e-159
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1796318599   1 MDLFMRIFTIGTVTLKQGEIKDATPSDFVRATATIPIQASLPFGWLIVGVALLAVFQSASKIITLKKRWQLALSKGVHFV 80
Cdd:pfam11289   1 MDLFMRFFTLGAITAQPAKIDNASPASTVHATATIPLQASLPFGWLVIGVAFLAVFQSASKIIALHKRWQLALYKGFQFI 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1796318599  81 CNLLLLFVTVYSHLLLVAAGLEAPFLYLYALVYFLQSINFVRIIMRLWLCWKCRSKNPLLYDANYFLCWHTNCYDYCIPY 160
Cdd:pfam11289  81 CNLLLLFVTIYSHLLLLAAGMEAQFLYIYALIYFLQCINACRFIMRCWLCWKCKSKNPLLYDANYFVCWHTHCFDYCIPY 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1796318599 161 NSVTSSIVITSGDGTTSPISEHDYQIGGYTEKWESGVKDCVVLHSYFTSDYYQLYSTQLSTDTGVEHVTFFIYNKIVDEP 240
Cdd:pfam11289 161 NSITDTIVLTEGDGINQPKLKEDYQIGGYSEDRHSGIKDYVVIHGYFTEVYYQLESTQISPDTGIENATFFIFNKLVKAP 240
                         250       260       270
                  ....*....|....*....|....*....|....
gi 1796318599 241 eEHVQIHTIDGSSGVVNPVMEPIYDEPTTTTSVP 274
Cdd:pfam11289 241 -DHVQIHTIDGSSGVANPAMDPIYDEPTTTTSVP 273
 
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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