2697049:GU280 gp02
gene id: 2697049:GU280_gp02
uniprot id: P0DTC2
names: Biotechnology
names: Caution
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Asn-17, Asn-603, Asn-1134, Asn-1158, and Asn-1173 are not glycosylated when S1 or S2 are expressed individually in HEK293 cells.
messages: Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection. The major receptor is host ACE2 (PubMed:32142651, PubMed:33607086, PubMed:32155444). When S2/S2' has been cleaved, binding to the receptor triggers direct fusion at the cell membrane (PubMed:34561887). When S2/S2' has not been cleaved, binding to the receptor results in internalization of the virus by endocytosis leading to fusion of the virion membrane with the host endosomal membrane (PubMed:32221306, PubMed:32075877). Alternatively, may use NRP1/NRP2 (PubMed:33082294, PubMed:33082293) and integrin as entry receptors (PubMed:35150743). The use of NRP1/NRP2 receptors may explain the tropism of the virus in human olfactory epithelial cells, which express these molecules at high levels but ACE2 at low levels (PubMed:33082293). The stalk domain of S contains three hinges, giving the head unexpected orientational freedom (PubMed:32817270).
messages: Belongs to the betacoronaviruses spike protein family.
messages: Binds to host ACE2 (PubMed:32221306, PubMed:33607086, PubMed:32075877, PubMed:32132184, PubMed:32155444, PubMed:32225175, PubMed:32225176). RBD also interacts with the N-linked glycan on 'Asn-90' of ACE2 (PubMed:33607086). Cleavage of S generates a polybasic C-terminal sequence on S1 that binds to host Neuropilin-1 (NRP1) and Neuropilin-2 (NRP2) receptors (PubMed:33082294, PubMed:33082293). Interacts with host integrin alpha-5/beta-1 (ITGA5:ITGB1) and with ACE2 in complex with integrin alpha-5/beta-1 (ITGA5:ITGB1) (PubMed:33102950). May interact via cytoplasmic c-terminus with M protein (PubMed:33229438). May interact (via N-terminus) with host bilirubin and biliverdin, thereby preventing antibody binding to the SARS-CoV-2 spike NTD via an allosteric mechanism (PubMed:33888467).
messages: Contains sequence and structural motifs very similar to those of a bacterial superantigen and can directly bind and activate T-cell receptors. Activation of a broad T-cell repertoire may be involved in the hyperinflammatory syndrome in acute COVID disease.
messages: Fusion peptide 1 (FP1) and fusion peptide 2 (FP2) function cooperatively and have a membrane-ordering effect on lipid headgroups and shallow hydrophobic regions of target bilayers. They are considered as two domains of an extended, bipartite FP. The membrane-ordering activity is calcium-dependent and also dependent on correct folding, which is maintained by an internal disulfide bond in FP2.
messages: Highly decorated by heterogeneous N-linked glycans protruding from the trimer surface (PubMed:32075877, PubMed:32155444, PubMed:32929138). Highly glycosylated by host both on S1 and S2 subunits, occluding many regions across the surface of the protein (PubMed:32366695, PubMed:32363391, PubMed:32929138). Approximately 40% of the protein surface is shielded from antibody recognition by glycans, with the notable exception of the ACE2 receptor binding domain (PubMed:32929138).
messages: Homotrimer; each monomer consists of a S1 and a S2 subunit (PubMed:32075877, PubMed:32155444, PubMed:32245784). The resulting peplomers protrude from the virus surface as spikes (PubMed:32979942). Interacts with ORF3a protein and ORF7a protein (By similarity) (PubMed:32075877, PubMed:32155444, PubMed:32245784, PubMed:32979942). There are an average of 26 +/-15 spike trimers at the surface of virion particles (PubMed:32979942). Binds to host MBL2 (PubMed:35102342). This binding occurs via glycans and inhibits viral infectivity. Inhibition is effective against alpha, beta, gamma, and delta variants (PubMed:35102342).
messages: Host cell membrane
messages: Host endoplasmic reticulum-Golgi intermediate compartment membrane
messages: Main component of the anti-COVID vaccine Chadox1/AZD1222/AstraZeneca; in which the human tPA leader sequence is added in N-terminus to enhance protein secretion.
messages: Main component of the anti-COVID19 vaccine Ad26.COV2.S/Janssen Pharmaceutical; in which the mutations Arg-682 (R682S), Arg-685 (R685G), Lys-986 (K986P) and Val-987 (V987P) have been added to stabilize the protein in the prefusion state.
messages: Main component of the anti-COVID19 vaccines BNT162b2/Pfizer-Biontech and mRNA-1273/Moderna; in which the mutations of Lys-986 (K986P) and Val-987 (V987P) have been added to stabilize the protein in the prefusion state.
messages: O-glycosylated by host GALNT1 at the end of S1. This could reduce the efficiency of S1/S2 cleavage.
messages: Precursor of the fusion protein processed in the biosynthesis of the S protein and the formation of virus particle. Mediates fusion of the virion and cellular membranes by functioning as a class I viral fusion protein. Contains two viral fusion peptides that are unmasked after cleavage. The S2/S2' cleavage occurs during virus entry at the cell membrane by host TMPRSS2 (PubMed:32142651) or during endocytosis by host CSTL (PubMed:32703818, PubMed:34159616). In either case, this triggers an extensive and irreversible conformational change leading to fusion of the viral envelope with the cellular cytoplasmic membrane, releasing viral genomic RNA into the host cell cytoplasm (PubMed:34561887). Under the current model, the protein has at least three conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During fusion of the viral and target cell membranes, the coiled coil regions (heptad repeats) adopt a trimer-of-hairpins structure and position the fusion peptide in close proximity to the C-terminal region of the ectodomain. Formation of this structure appears to promote apposition and subsequent fusion of viral and target cell membranes.
messages: Specific enzymatic cleavages in vivo yield mature proteins. The precursor is processed into S1 and S2 by host furin or unknown proteases to yield the mature S1 and S2 proteins (PubMed:32362314, PubMed:32703818, PubMed:34159616, PubMed:34561887, PubMed:32155444). Processing between S2 and S2' occurs either by host CTSL in endosomes (PubMed:32221306, PubMed:33465165, PubMed:34159616), or by host TMPRSS2 at the cell surface (PubMed:32142651). Both cleavages are necessary for the protein to be fusion competent (PubMed:32703818, PubMed:34159616, PubMed:34561887). Cell surface activation allows the virus to enter the cell despite inhibition of the endosomal pathway by hydroxychloroquine (PubMed:33465165). The polybasic furin cleavage site is absent in SARS-CoV S (PubMed:32155444, PubMed:32362314, PubMed:33465165). It increases the dependence on TMPRSS2 expression by SARS-CoV-2 (PubMed:33465165). D614G substitution would enhance furin cleavage at the S1/S2 junction (PubMed:33417835).
messages: Subunit of the fusion protein that is processed upon entry into the host cell. Mediates fusion of the virion and cellular membranes by functioning as a class I viral fusion protein. Contains a viral fusion peptide that is unmasked after S2 cleavage. This cleavage can occur at the cell membrane by host TMPRSS2 or during endocytosis by host CSTL (PubMed:32703818, PubMed:34159616). In either case, this triggers an extensive and irreversible conformational change that leads to fusion of the viral envelope with the cellular cytoplasmic membrane, releasing viral genomic RNA into the host cell cytoplasm (PubMed:34561887). Under the current model, the protein has at least three conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During fusion of the viral and target cell membranes, the coiled coil regions (heptad repeats) adopt a trimer-of-hairpins structure and position the fusion peptide in close proximity to the C-terminal region of the ectodomain. Formation of this structure appears to promote apposition and subsequent fusion of viral and target cell membranes.
messages: The KxHxx motif seems to function as an ER retrieval and binds COPI in vitro.
messages: The cytoplasmic Cys-rich domain is palmitoylated. Palmitoylated spike proteins drive the formation of localized ordered cholesterol and sphingo-lipid-rich lipid nanodomains in the early Golgi, where viral budding occurs.
messages: Variant Alpha/B.1.1.7 belongs to a lineage isolated first in United Kingdom (December 2020). It is also called Variant of Concern (VOC) 202012/01, Variant Under Investigation (VUI) 202012/01, 501Y.V1 or 20B/501Y.V1 (PubMed:33413740). It has an estimated 25% increase of transmissibility (PubMed:34142653).
messages: Variant Beta/B.1.351 belongs to a lineage first isolated in South Africa (December 2020) and is also called 501Y.V2. It has an estimated 25% increase of transmissibility.
messages: Variant D614G has become the most prevalent circulating sequence in the global pandemic since April 2020 (PubMed:32697968). The mutation is associated with higher viral loads produced in cell culture and animal models (PubMed:32697968, PubMed:33106671, PubMed:33184236). It would not change pathogenicity nor neutralization properties vs vaccination (PubMed:33184236). May be prevalent because the mutation increases virus transmission in human population (PubMed:33106671).
messages: Variant Delta/B.1.617.2 belongs to a lineage first isolated in India (October 2020) and is also called G/478K.V1. It has an estimated 97% increase of transmissibility.
messages: Variant Epsilon/B.1.427/B.1.429 belong to lineages first isolated in USA (Sept 2020). Variant S13I shifts the signal peptide cleavage site from S13-Q14 to C15-V16, thus removing Cys-15 which can no longer establish disulfide bonds with Cys-136. The latter would make a disulfid bond with Cys-152 (W152C variant), thereby changing the N-terminus structure of the protein and its antigenicity.
messages: Variant Gamma/P.1 belongs to a lineage first isolated in Brazil (November 2020) and is also called 20J (V3) and GR/501Y.V3. It has an estimated 38% increase of transmissibility.
messages: Variant Omicron/BA.1 belongs to a lineage first isolated in South Africa (November 2021).
messages: Virion membrane

2697049:GU280 gp03
gene id: 2697049:GU280_gp03
uniprot id: P0DTC3
names: Domain
names: Function
names: PTM
names: Polymorphism
names: Subcellular Location Annotation
names: Subunit
messages: Exists in both O-glycosylated and non-glycosylated forms. The glycosylated form is associated with the virion.
messages: Homodimer (PubMed:34158638), a subset forms homotetramer of two homodimers linked non covalently (PubMed:34158638, PubMed:34158638). Interacts with M, S and E proteins. Also interacts with the accessory protein 7a (By similarity). Interacts with host VPS39, sequestering it on late endosomes (PubMed:33422265). Interacts with host HMGB1; the interaction enhances the association between HMGB1 and host BECN1, promoting reticulophagy (PubMed:35239449). Interacts with HMOX1; the interaction promotes ORF3A-induced autophagy but is unlikely to be involved in ORF3A-mediated induction of reticulophagy (PubMed:35239449).
messages: Host cell membrane
messages: Host cytoplasm
messages: Host endoplasmic reticulum membrane
messages: Host endosome
messages: Host lysosome
messages: Plays a role in viral egress via lysosomal trafficking (PubMed:33157038, PubMed:33422265). Forms homotetrameric ion channels (viroporins) localized at endosomes and lysosomes, that may induce deacidification of lysosomes, allowing safe egress of virions via lysosomal trafficking (PubMed:33157038, PubMed:33422265, PubMed:34158638). Also blocks autolysosome formation by binding and sequestering the host component VPS39 for homotypic fusion and protein sorting (HOPS) on late endosomes (PubMed:33422265). This prevents fusion of autophagosomes with lysosomes, disrupting autophagy and facilitating virus egress (PubMed:33422265). Induces host RETREG1/FAM134B-dependent reticulophagy by interacting with host HMGB1 and enhancing the association between HMGB1 and host BECN1 (PubMed:35239449). This induces endoplasmic reticulum stress and inflammatory responses and facilitates viral infection (PubMed:35239449).
messages: Secreted
messages: The second or the third transmembrane region are responsible for Golgi localization.
messages: Variant Omicron/BA.1 and BA.2 belong to a lineage first isolated in South Africa (November 2021).
messages: Virion

2697049:GU280 gp11
gene id: 2697049:GU280_gp11
uniprot id: A0A663DJA2
names: Caution
names: Subunit
messages: Could be the product of a pseudogene. Probably does not encode a functional protein. No subgenomic RNA was detected that could encode the protein (PubMed:33722935). It has been shown to be non-essential in vivo and in vitro (PubMed:33301543). There are no similar proteins in other betacoronavirus (PubMed:33301543).
messages: May bind host ZYG11B. This would not play any role in SARS-CoV-2 infection.

2697049:GU280 gp01
gene id: 2697049:GU280_gp01
uniprot id: P0DTC1
uniprot id: P0DTD1
names: Activity Regulation
names: Cofactor
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: 3CL-PRO exists as monomer and homodimer. Only the homodimer shows catalytic activity.
messages: Belongs to the coronaviruses polyprotein 1ab family.
messages: Catalytic subunit of viral RNA capping enzyme which catalyzes the RNA guanylyltransferase reaction for genomic and sub-genomic RNAs (PubMed:35944563). The kinase-like NiRAN domain of NSP12 transfers RNA to the amino terminus of NSP9, forming a covalent RNA-protein intermediate (PubMed:35944563). Subsequently, the NiRAN domain transfers RNA to GDP, forming the core cap structure GpppA-RNA (PubMed:35944563). The NSP14 and NSP16 methyltransferases then add methyl groups to form functional cap structures (PubMed:35944563). Interacts with ribosome signal recognition particle RNA (SRP) (PubMed:33080218). Together with NSP8, suppress protein integration into the cell membrane, thereby disrupting host immune defenses (PubMed:33080218).
messages: Cleaves the C-terminus of replicase polyprotein at 11 sites (PubMed:32321856). Recognizes substrates containing the core sequence [ILMVF]-Q-|-[SGACN] (PubMed:32198291, PubMed:32272481). May cleave human NLRP1 in lung epithelial cells, thereby activating the NLRP1 inflammasome pathway (PubMed:35594856). May cleave human GSDMD, triggering alternative GSDME-mediated epithelial cell death upon activation of the NLRP1 inflammasome, which may enhance the release interleukins 1B, 6, 16 and 18 (PubMed:35594856). Also able to bind an ADP-ribose-1''-phosphate (ADRP) (PubMed:32198291, PubMed:32272481).
messages: Forms a dodecamer and interacts with nsp14 and nsp16; these interactions enhance nsp14 and nsp16 enzymatic activities.
messages: Homohexamer.
messages: Host Golgi apparatus
messages: Host cytoplasm
messages: Host endoplasmic reticulum
messages: Host endoplasmic reticulum-Golgi intermediate compartment
messages: Host endosome
messages: Host membrane
messages: Host nucleus
messages: Inhibited by Remdesivir antiviral drug (GS-5734) through non-obligate RNA chain termination.
messages: Inhibited by Remdesivir antiviral drug (GS-5734).
messages: Inhibited by pyridone-containing alpha-ketoamides compounds 13a and 13b. In turn, alpha-ketoamide 13b (tert-butyl (1-((S)-1-(((S)-4-(benzylamino)-3,4-dioxo-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclopropyl-1-oxopropan-2-yl)-2-oxo-1,2-dihydropyridin-3-yl)carbamate) inhibits SARS-CoV-2 replication in human lung cells (PubMed:32198291). Inhibited ex vivo by michael acceptor inhibitor N3 (PubMed:32272481). Inhibited ex vivo by compound 11a and 11b (PubMed:32321856).
messages: Inhibited in vitro by GRL-0617.
messages: Inhibits host translation by associating with the open head conformation of the 40S subunit (PubMed:33479166, PubMed:33080218, PubMed:32680882, PubMed:32908316). The C-terminus binds to and obstructs ribosomal mRNA entry tunnel (PubMed:33479166, PubMed:33080218, PubMed:32680882, PubMed:32908316). Thereby inhibits antiviral response triggered by innate immunity or interferons (PubMed:33080218, PubMed:32680882, PubMed:32979938). The nsp1-40S ribosome complex further induces an endonucleolytic cleavage near the 5'UTR of host mRNAs, targeting them for degradation (By similarity). Viral mRNAs less susceptible to nsp1-mediated inhibition of translation, because of their 5'-end leader sequence (PubMed:32908316, PubMed:33080218).
messages: Interacts (via N-terminus) with DDX1. Interacts with nsp10.
messages: Interacts with PL-PRO and nsp6.
messages: Interacts with host PHB and PHB2.
messages: Interacts with host TBK1; this interaction decreases IRF3 phosphorylation by 57%, which leads to reduced IFN-beta production.
messages: Interacts with host TBK1; this interaction decreases by 57% IRF3 phosphorylation, which leads to reduced IFN-beta production.
messages: Interacts with nsp10.
messages: Interacts with nsp7 and nsp8 to form the replication-transcription complex (RTC): nsp12, nsp7, two subunits of nsp8, and up to two subunits of nsp13 (PubMed:32277040, PubMed:32358203, PubMed:32438371, PubMed:32526208, PubMed:34562452). Interacts with nsp9 (PubMed:35944563).
messages: Interacts with nsp7, nsp13 and nsp12 (PubMed:33232691) to form the replication-transcription complex (RTC): nsp12, nsp7, two subunits of nsp8, and up to two subunits of nsp13 (PubMed:32277040, PubMed:32358203, PubMed:32438371, PubMed:32526208, PubMed:34562452). Eight copies of nsp7 and eight copies of nsp8 assemble to form a heterohexadecamer dsRNA-encircling ring structure (By similarity).
messages: Interacts with nsp8 and nsp12 to form the replication-transcription complex (RTC): nsp12, nsp7, two subunits of nsp8, and up to two subunits of nsp13 (PubMed:32277040, PubMed:32358203, PubMed:32438371, PubMed:32526208, PubMed:34562452). Eight copies of nsp7 and eight copies of nsp8 assemble to form a heterohexadecamer dsRNA-encircling ring structure (By similarity).
messages: Interacts with nsp8 to form the replication-transcription complex (RTC): nsp12, nsp7, two subunits of nsp8, and up to two subunits of nsp13 (PubMed:33232691, PubMed:34562452). Interacts with host TBK1; this interaction inhibits TBK1 phosphorylation and decreases by 75% IRF3 phosphorylation, which leads to reduced IFN-beta production (PubMed:32979938).
messages: Is a dimer (By similarity). Interacts with NSP12 (PubMed:35944563).
messages: Likely affects Nsp15 binding to RNA.
messages: May form homohexamers.
messages: May play a role in the modulation of host cell survival signaling pathway by interacting with host PHB and PHB2. Indeed, these two proteins play a role in maintaining the functional integrity of the mitochondria and protecting cells from various stresses.
messages: Methyltransferase that mediates mRNA cap 2'-O-ribose methylation to the 5'-cap structure of viral mRNAs (PubMed:35944563). N7-methyl guanosine cap is a prerequisite for binding of nsp16 (PubMed:35944563). Therefore plays an essential role in viral mRNAs cap methylation which is essential to evade immune system (PubMed:35944563). May disrupt host mRNA splicing in nucleus by interacting with pre-mRNA Recognition Domains ofthe U1 and U2 snRNAs (PubMed:33080218).
messages: Multifunctional protein involved in the transcription and replication of viral RNAs. Contains the proteinases responsible for the cleavages of the polyprotein.
messages: Participates in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication.
messages: Plays a pivotal role in viral transcription by stimulating both nsp14 3'-5' exoribonuclease (By similarity) and nsp16 2'-O-methyltransferase activities (PubMed:35944563). Therefore plays an essential role in viral mRNAs cap methylation.
messages: Plays a role in the initial induction of autophagosomes from host reticulum endoplasmic (By similarity). Later, limits the expansion of these phagosomes that are no longer able to deliver viral components to lysosomes (By similarity). Binds to host TBK1 without affecting TBK1 phosphorylation; the interaction with TBK1 decreases IRF3 phosphorylation, which leads to reduced IFN-beta production (PubMed:32979938).
messages: Plays a role in viral RNA synthesis (PubMed:32358203, PubMed:32277040, PubMed:32438371, PubMed:32526208). Forms a hexadecamer with nsp7 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers (By similarity). Interacts with ribosome signal recognition particle RNA (SRP) (PubMed:33080218). Together with NSP9, suppress protein integration into the cell membrane, thereby disrupting host immune defenses (PubMed:33080218).
messages: Plays a role in viral RNA synthesis (PubMed:32358203, PubMed:32277040, PubMed:32438371, PubMed:32526208). Forms a hexadecamer with nsp8 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers (By similarity).
messages: Plays a role in viral RNA synthesis (PubMed:33232691). Multi-functional protein with a zinc-binding domain in N-terminus displaying RNA and DNA duplex-unwinding activities with 5' to 3' polarity. Activity of helicase is dependent on magnesium (By similarity). Binds to host TBK1 and inhibits TBK1 phosphorylation; the interaction with TBK1 decreases IRF3 phosphorylation, which leads to reduced IFN-beta production (PubMed:32979938).
messages: Plays a role in viral RNA synthesis through two distinct activities. The N7-guanine methyltransferase activity plays a role in the formation of the cap structure GpppA-RNA (PubMed:35944563). The proofreading exoribonuclease reduces the sensitivity of the virus to RNA mutagens during replication (By similarity). This activity acts on both ssRNA and dsRNA in a 3'-5' direction (By similarity).
messages: Plays a role in viral transcription/replication and prevents the simultaneous activation of host cell dsRNA sensors, such as MDA5/IFIH1, OAS, and PKR (By similarity). Acts by degrading the 5'-polyuridines generated during replication of the poly(A) region of viral genomic and subgenomic RNAs (PubMed:33504779, PubMed:33564093). Catalyzes a two-step reaction in which a 2'3'-cyclic phosphate (2'3'-cP) is first generated by 2'-O transesterification, which is then hydrolyzed to a 3'-phosphate (3'-P) (PubMed:33504779, PubMed:33564093). If not degraded, poly(U) RNA would hybridize with poly(A) RNA tails and activate host dsRNA sensors (By similarity). May bind genomic dsRNA in association with the replication-transcription complex (RTC), and play a role in nsp12 discontinous transcription (PubMed:34562452, PubMed:35706445).
messages: Produced by -1 ribosomal frameshifting at the 1a-1b genes boundary.
messages: Produced by conventional translation.
messages: RNA-directed RNA polymerase that catalyzes the transcription of viral genomic and subgenomic RNAs. Acts in complex with nsp7 and nsp8 to transcribe both the minus and positive strands of genomic RNA (PubMed:32277040, PubMed:32358203, PubMed:32438371, PubMed:32526208). Subgenomic RNAs (sgRNAs) are formed by discontinuous transcription: The polymerase has the ability to pause at transcription-regulating sequences (TRS) and jump to the leader TRS, resulting in a major deletion (PubMed:35706445). This creates a series of subgenomic RNAs that are replicated, transcribed and translated (PubMed:35706445). In addition, Nsp12 is a subunit of the viral RNA capping enzyme that catalyzes the RNA guanylyltransferase reaction for genomic and sub-genomic RNAs (PubMed:35944563). The kinase-like NiRAN domain of NSP12 transfers RNA to the amino terminus of NSP9, forming a covalent RNA-protein intermediate (PubMed:35944563). Subsequently, the NiRAN domain transfers RNA to GDP, and forms the core cap structure GpppA-RNA (PubMed:35944563).
messages: Responsible for the cleavages located at the N-terminus of the replicase polyprotein. Participates together with nsp4 in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication (By similarity). Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF3 (PubMed:32733001). Prevents also host NF-kappa-B signaling (By similarity). In addition, PL-PRO possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates (PubMed:32726803). Cleaves preferentially ISG15 from antiviral protein IFIH1 (MDA5), but not RIGI (PubMed:33727702). Can play a role in host ADP-ribosylation by ADP-ribose (PubMed:32578982).
messages: Responsible for the cleavages located at the N-terminus of the replicase polyprotein. Participates together with nsp4 in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication (By similarity). Forms a molecular pore spanning the double membrane of the coronavirus replication organelle (PubMed:32763915). Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF3 (PubMed:32733001). Prevents also host NF-kappa-B signaling (By similarity). In addition, PL-PRO possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates (PubMed:32726803). Cleaves preferentially ISG15 from antiviral protein IFIH1 (MDA5), but not RIGI (PubMed:33727702). Can play a role in host ADP-ribosylation by binding ADP-ribose (PubMed:32578982).
messages: Specific enzymatic cleavages in vivo by its own proteases yield mature proteins. 3CL-PRO and PL-PRO proteinases are autocatalytically processed.
messages: The hydrophobic domains (HD) could mediate the membrane association of the replication complex and thereby alter the architecture of the host cell membrane.
messages: Variant B.1.1.7 is also called Variant Of Concern (VOC) 202012/01, Variant Under Investigation (VUI) 202012/01, or 20B/501Y.V1.
messages: Variant Omicron/BA.1 and BA.2 belong to a lineage first isolated in South Africa (November 2021).
messages: host perinuclear region

2697049:GU280 gp10
gene id: 2697049:GU280_gp10
uniprot id: P0DTC9
names: Function
names: PTM
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: ADP-ribosylated. The ADP-ribosylation is retained in the virion during infection.
messages: Belongs to the betacoronavirus nucleocapsid protein family.
messages: Homooligomer. Both monomeric and oligomeric forms interact with RNA. Interacts with protein M. Interacts with protein E. Interacts with NSP3; this interaction serves to tether the genome to the newly translated replicase-transcriptase complex at a very early stage of infection (By similarity). May interact with host NLRP3 (PubMed:34341353).
messages: Host cytoplasm
messages: Host extracellular space
messages: May block host chemokine function in vivo, facilitating viral replication and transmission (PubMed:35921414). Acts by being secreted into the extracellular space where it competes to host chemokines for binding to host glycosaminoglycans (GAG) (PubMed:35921414).
messages: May induce inflammasome responses in cultured cells and mice. Acts by interacting with host NLRP3 to facilitate inflammasome assembly, which induces cytokine release that may play a role in COVID lung injury.
messages: Packages the positive strand viral genome RNA into a helical ribonucleocapsid (RNP) and plays a fundamental role during virion assembly through its interactions with the viral genome and membrane protein M (PubMed:33264373). Plays an important role in enhancing the efficiency of subgenomic viral RNA transcription as well as viral replication (By similarity).
messages: Phosphorylated on serine residues by host GSK3A and GSK3B.
messages: Proteolytically cleaved by host CASP6. The cleavage leads to two fragments and facilitates viral replication by inhibiting host IFN signaling. The two fragments may interact with IRF3 inhibiting its nuclear translocation after activation and reduce the expression of IFNB and IFN-stimulated genes.
messages: Secreted
messages: Variant Alpha/B.1.1.7 belongs to a lineage isolated first in United Kingdom (December 2020). It is also called Variant of Concern (VOC) 202012/01, Variant Under Investigation (VUI) 202012/01, 501Y.V1 or 20B/501Y.V1.
messages: Variant Omicron/BA.1 and BA.2 belong to a lineage first isolated in South Africa (November 2021).
messages: Virion

2697049:GU280 gp05
gene id: 2697049:GU280_gp05
uniprot id: P0DTC5
names: Function
names: PTM
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the betacoronaviruses M protein family.
messages: Component of the viral envelope that plays a central role in virus morphogenesis and assembly via its interactions with other viral proteins (By similarity). Regulates the localization of S protein at cis-Golgi, the place of virus budding (PubMed:33229438). May act by binding cytoplasmic c-terminus of S (PubMed:33229438).
messages: Glycosylated at N-terminus.
messages: Homomultimer. Interacts with envelope E protein in the budding compartment of the host cell, which is located between endoplasmic reticulum and the Golgi complex (By similarity). Forms a complex with S proteins (PubMed:33229438). Interacts with nucleocapsid N protein. This interaction probably participates in RNA packaging into the virus (By similarity). Interacts with the accessory proteins 3a and 7a (By similarity).
messages: Host Golgi apparatus membrane
messages: Host membrane
messages: Variant Delta/B.1.617.2 belongs to a lineage first isolated in India (October 2020) and is also called G/478K.V1. It has an estimated 97% increase of transmissibility.
messages: Variant Omicron/BA.1 and BA.2 belong to a lineage first isolated in South Africa (November 2021).
messages: Virion membrane

2697049:GU280 gp06
gene id: 2697049:GU280_gp06
uniprot id: P0DTC6
names: Function
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the coronaviruses accessory protein 6 family.
messages: Disrupts bidirectional nucleocytoplasmic transport by interacting with the host RAE1-NUP98 complex (PubMed:33360543, PubMed:33849972). Disrupts cell nuclear import complex formation by tethering karyopherin alpha 2 and karyopherin beta 1 to the membrane (PubMed:32979938). Retention of import factors at the ER/Golgi membrane leads to a loss of transport into the nucleus (By similarity). Prevents STAT1 nuclear translocation in response to interferon signaling, thus blocking the expression of interferon stimulated genes (ISGs) that display multiple antiviral activities (PubMed:33097660). Suppresses IFN-beta production possibly by blocking IRF3 nuclear translocation (PubMed:32979938). Might induce accumulation of host HNRNPA1 (PubMed:33360543).
messages: Host Golgi apparatus membrane
messages: Host endoplasmic reticulum membrane
messages: May interact with nsp8 (By similarity). Interacts with protein ORF9b (By similarity). Interacts (via C-terminus) with host RAE1 in the NUP98-RAE1 complex (PubMed:35096974); this interaction disrupts the host nuclear import (PubMed:33097660, PubMed:33360543, PubMed:33849972, PubMed:35096974). Interacts with host KPNA2; this interaction may inhibit IFN-beta production by blocking IRF3 nuclear translocation (PubMed:32979938).
messages: May play a role in viral double membrane vesicles networks to enhance viral replication.
messages: Variant Omicron/BA.1 and BA.2 belong to a lineage first isolated in South Africa (November 2021).

2697049:GU280 gp04
gene id: 2697049:GU280_gp04
uniprot id: P0DTC4
names: Function
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the betacoronaviruses E protein family.
messages: Homopentamer (PubMed:33177698). Interacts with membrane protein M in the budding compartment of the host cell, which is located between endoplasmic reticulum and the Golgi complex. Interacts with Nucleoprotein (By similarity). Interacts with the accessory proteins 3a and 7a (By similarity). Interacts (via C-terminus) with human MPP5 (via PDZ domain); this inhibits the interaction between human MPP5 and human CRB3, and causes disruption of epithelial cells tight junctions (PubMed:32891874).
messages: Host Golgi apparatus membrane
messages: Plays a central role in virus morphogenesis and assembly. Acts as a viroporin and self-assembles in host membranes forming pentameric protein-lipid pores that allow ion transport. Also plays a role in the induction of apoptosis (By similarity). Regulates the localization of S protein at cis-Golgi, the place of virus budding (PubMed:33229438). May act by slowing down the cell secretory pathway (PubMed:33229438). May interfere with tight-junction stability by interacting with host MPP5. This would result in disruption of epithelial barriers, thereby amplifying inflammatory processes (PubMed:32891874).
messages: Variant Omicron/BA.1 and BA.2 belong to a lineage first isolated in South Africa (November 2021).

2697049:GU280 gp09
gene id: 2697049:GU280_gp09
uniprot id: P0DTC8
names: Function
names: Miscellaneous
names: Polymorphism
names: Subcellular Location Annotation
names: Subunit
messages: Homodimer (PubMed:33361333, PubMed:35157849). Interacts with host IL17RA (PubMed:33060197, PubMed:35343786). Interacts with host IL17RC (PubMed:35343786). Interacts with host MHC-I (PubMed:34021074).
messages: Plays a role in modulating the host immune response (PubMed:31986261, PubMed:35343786). May act as a secreted virokine by mimicking interleukin-17A (IL17A), and thereby binding to the IL17RA receptor, leading to activation of the IL17 pathway and increased secretion of pro-inflammatory factors (PubMed:35343786). Contributes to the cytokine storm during SARS-CoV-2 infection (PubMed:33723527). May act by down-regulating major histocompability complex class I (MHC-I) at cell surface (PubMed:34021074, PubMed:35157849). May inhibit expression of some members of the IFN-stimulated gene (ISG) family including hosts IGF2BP1/ZBP1, MX1 and MX2, and DHX58 (PubMed:34177923).
messages: Secreted
messages: Similar to some Bat coronavirus ns8 genes, but is entirely different from SARS ns8a or Ns8b (Probable). Elicits strong specific antibody response (PubMed:32807944).
messages: Variant B.1.1.7 is also called Variant Of Concern (VOC) 202012/01, Variant Under Investigation (VUI) 202012/01, or 20B/501Y.V1.
messages: Variant Omicron/BA.1 and BA.2 belong to a lineage first isolated in South Africa (November 2021).

2697049:GU280 gp08
gene id: 2697049:GU280_gp08
uniprot id: P0DTD8
names: Subcellular Location Annotation
messages: Host Golgi apparatus membrane
messages: Host endosome membrane

2697049:GU280 gp07
gene id: 2697049:GU280_gp07
uniprot id: P0DTC7
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Host Golgi apparatus membrane
messages: Host endoplasmic reticulum membrane
messages: Host endoplasmic reticulum-Golgi intermediate compartment membrane
messages: Interacts with host BST2 (PubMed:33930332). Interacts with the spike glycoprotein (By similarity). Interacts with M protein (By similarity). Interacts with E protein (By similarity). Interacts with the ORF3a protein (By similarity).
messages: Plays a role as antagonist of host tetherin (BST2), disrupting its antiviral effect. Acts by binding to BST2 and sequestering it to perinuclear region, thereby preventing its antiviral function at cell membrane.
messages: Poly-ubiquitinated by host with K63-linked polyubiquitin chains.
messages: The di-lysine motif confers endoplasmic reticulum localization for type I membrane proteins.
messages: Variant B.1.1.7 is also called Variant Of Concern (VOC) 202012/01, Variant Under Investigation (VUI) 202012/01, or 20B/501Y.V1.
messages: Virion
messages: host perinuclear region