SII-SWORD/CoKE huggingface dataset:
M matrix/glycoprotein, bat coronavirus HKU9-like (M_batCoV_HKU9-like)
Type: Family

This group contains the Membrane (M) protein of Rousettus bat coronavirus HKU9, and similar proteins from betacoronaviruses in the nobecovirus subgenera (D lineage).

The membrane (M) protein is the most abundant structural protein and defines the shape of the viral envelope. It is also regarded as the central organiser of coronavirus assembly, interacting with all other major coronaviral structural proteins. M proteins play a critical role in protein-protein interactions (as well as protein-RNA interactions) since virus-like particle (VLP) formation in many CoVs requires only the M and envelope (E) proteins for efficient virion assembly . Interaction of spike (S) with M is necessary for retention of S in the ER-Golgi intermediate compartment (ERGIC)/Golgi complex and its incorporation into new virions, but dispensable for the assembly process. Binding of M to nucleocapsid (N) proteins stabilises the nucleocapsid (N protein-RNA complex), as well as the internal core of virions, and, ultimately, promotes completion of viral assembly. Together, M and E protein make up the viral envelope and their interaction is sufficient for the production and release of virus-like particles (VLPs) .
M matrix/glycoprotein, SARS-CoV-like (M_SARS-like-CoV)
Type: Family

The membrane (M) protein is the most abundant structural protein and defines the shape of the viral envelope. It is also regarded as the central organiser of coronavirus assembly, interacting with all other major coronaviral structural proteins. M proteins play a critical role in protein-protein interactions (as well as protein-RNA interactions) since virus-like particle (VLP) formation in many CoVs requires only the M and envelope (E) proteins for efficient virion assembly . Interaction of spike (S) with M is necessary for retention of S in the ER-Golgi intermediate compartment (ERGIC)/Golgi complex and its incorporation into new virions, but dispensable for the assembly process. Binding of M to nucleocapsid (N) proteins stabilises the nucleocapsid (N protein-RNA complex), as well as the internal core of virions, and, ultimately, promotes completion of viral assembly. Together, M and E protein make up the viral envelope and their interaction is sufficient for the production and release of virus-like particles (VLPs) .

This entry contains the Membrane (M) protein of Severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2 (also known as 2019 novel CoV (2019-nCoV) or COVID-19 virus), and related proteins from betacoronaviruses in the sarbecovirus subgenera (B lineage). M protein from SARS-CoV-2 has high sequence identity to its SARS-CoV homologue and is predicted to have a small glycosylated amino-terminal ectodomain, a triple-membrane spanning domain, and a carboxyl-terminal endodomain. The C-terminal portion of coronaviral M proteins binds to the N protein within the cell membrane of the ER or Golgi complex, stabilizing the nucleocapsid and the core of the virion .
M matrix/glycoprotein, HCoV-like (M_HCoV-like)
Type: Family

The membrane (M) protein is the most abundant structural protein and defines the shape of the viral envelope. It is also regarded as the central organiser of coronavirus assembly, interacting with all other major coronaviral structural proteins. M proteins play a critical role in protein-protein interactions (as well as protein-RNA interactions) since virus-like particle (VLP) formation in many CoVs requires only the M and envelope (E) proteins for efficient virion assembly . Interaction of spike (S) with M is necessary for retention of S in the ER-Golgi intermediate compartment (ERGIC)/Golgi complex and its incorporation into new virions, but dispensable for the assembly process. Binding of M to nucleocapsid (N) proteins stabilises the nucleocapsid (N protein-RNA complex), as well as the internal core of virions, and, ultimately, promotes completion of viral assembly. Together, M and E protein make up the viral envelope and their interaction is sufficient for the production and release of virus-like particles (VLPs) .

This entry contains the Membrane (M) protein of human coronaviruses (HCoVs), HCoV-OC43 and HCoV-HKU1, and similar proteins from betacoronaviruses in the embecovirus subgenera (A lineage).
M matrix/glycoprotein, MERS-like-CoV (M_MERS-like-CoV)
Type: Family

This entry contains the Membrane (M) protein of Middle East respiratory syndrome (MERS)-related CoV, bat-CoV HKU5, and similar proteins from betacoronaviruses in the merbecovirus subgenera (C lineage).

The membrane (M) protein is the most abundant structural protein and defines the shape of the viral envelope. It is also regarded as the central organiser of coronavirus assembly, interacting with all other major coronaviral structural proteins. M proteins play a critical role in protein-protein interactions (as well as protein-RNA interactions) since virus-like particle (VLP) formation in many CoVs requires only the M and envelope (E) proteins for efficient virion assembly . Interaction of spike (S) with M is necessary for retention of S in the ER-Golgi intermediate compartment (ERGIC)/Golgi complex and its incorporation into new virions, but dispensable for the assembly process. Binding of M to nucleocapsid (N) proteins stabilises the nucleocapsid (N protein-RNA complex), as well as the internal core of virions, and, ultimately, promotes completion of viral assembly. Together, M and E protein make up the viral envelope and their interaction is sufficient for the production and release of virus-like particles (VLPs) .
Spike (S) protein S1 subunit, receptor-binding domain, HKU5-like (Spike_S1_RBD_HKU5-like)
Type: Domain

This entry represents the receptor-binding domain (RBD) of the S1 subunit of the Spike (S) proteins from betacoronaviruses in the merbecovirus subgenera (C lineage), including Bat coronavirus HKU5, Middle East respiratory syndrome (MERS) CoV and related bat CoVs.

The CoV Spike (S) protein is an envelope glycoprotein that plays the most important role in viral attachment, fusion, and entry into host cells, and serves as a major target for the development of neutralizing antibodies, inhibitors of viral entry, and vaccines. It is synthesised as a precursor protein that is cleaved into an N-terminal S1 subunit (~700 amino acids) and a C-terminal S2 subunit (~600 amino acids) that mediates attachment and membrane fusion, respectively. Three S1/S2 heterodimers assemble to form a trimer spike protruding from the viral envelope. The S1 subunit contains a receptor-binding domain (RBD), while the S2 subunit contains a hydrophobic fusion peptide and two heptad repeat regions. S1 contains two structurally independent domains, the N-terminal domain (NTD) and the C-terminal domain (C-domain). Depending on the virus, either the NTD or the C-domain can serve as the receptor-binding domain (RBD). Most CoVs, including SARS-CoV-2, SARS-CoV, and MERS-CoV use the C-domain to bind their receptors. However, CoV such as mouse hepatitis virus (MHV) uses the NTD to bind its receptor, mouse carcinoembryonic antigen related cell adhesion molecule 1a (mCEACAM1a). The S1 NTD contributes to the Spike trimer interface .
Non-structural protein 6, deltacoronavirus (NSP6_deltaCoV)
Type: Domain

Coronaviruses encode large replicase polyproteins which are proteolytically processed by viral proteases to generate mature Nonstructural Proteins (NSPs) . NSP6 is a membrane protein containing 6 transmembrane domains with a large C-terminal tail . NSP6 from the avian coronavirus, infectious bronchitis virus (IBV) and the mouse hepatitis virus (MHV) have been shown to localise to the ER and to generate autophagosomes . Coronavirus NSP6 proteins have also been shown to limit autophagosome expansion. This may favour coronavirus infection by reducing the ability of autophagosomes to deliver viral components to lysosomes for degradation . NSP6 from IBV, MHV and severe acute respiratory syndrome coronavirus (SARS-CoV) have also been found to activate autophagy .

This entry represents Non-structural protein 6 (NSP6) from deltacoronavirus.
Non-structural protein 6, betacoronavirus (NSP6_betaCoV)
Type: Domain

This entry represents the non-structural protein 6 (NSP6) from betacoronavirus. Recently, it was reported that SARS-CoV-2 NSP6 binds TANK binding kinase 1 (TBK1) to suppress interferon regulatory factor 3 (IRF3) phosphorylation which suppresses IFN-I signalling and production more efficiently than SARS-CoV and MERS-CoV .

Coronaviruses (CoV) redirect and rearrange host cell membranes as part of the viral genome replication and transcription machinery; they induce the formation of double-membrane vesicles in infected cells. CoV non-structural protein 6 (NSP6), a transmembrane-containing protein, together with NSP3 and NSP4, have the ability to induce double-membrane vesicles that are similar to those observed in severe acute respiratory syndrome (SARS) coronavirus-infected cells . By itself, NSP6 can generate autophagosomes from the endoplasmic reticulum. Autophagosomes are normally generated as a cellular response to starvation to carry cellular organelles and long-lived proteins to lysosomes for degradation. Degradation through autophagy may provide an innate defense against virus infection, or conversely, autophagosomes can promote infection by facilitating the assembly of replicase proteins . In addition to initiating autophagosome formation, NSP6 also limits autophagosome expansion regardless of how they were induced, i.e. whether they were induced directly by NSP6, or indirectly by starvation or chemical inhibition of MTOR signalling. This may favour coronavirus infection by compromising the ability of autophagosomes to deliver viral components to lysosomes for degradation .
Non-structural protein 6, gammacoronavirus (NSP6_gammaCoV)
Type: Domain

This entry represents the non-structural protein 6 (NSP6) from gammacoronavirus.

Coronaviruses (CoV) redirect and rearrange host cell membranes as part of the viral genome replication and transcription machinery; they induce the formation of double-membrane vesicles in infected cells. CoV non-structural protein 6 (NSP6), a transmembrane-containing protein, together with NSP3 and NSP4, have the ability to induce double-membrane vesicles that are similar to those observed in severe acute respiratory syndrome (SARS) coronavirus-infected cells . By itself, NSP6 can generate autophagosomes from the endoplasmic reticulum. Autophagosomes are normally generated as a cellular response to starvation to carry cellular organelles and long-lived proteins to lysosomes for degradation. Degradation through autophagy may provide an innate defense against virus infection, or conversely, autophagosomes can promote infection by facilitating the assembly of replicase proteins . In addition to initiating autophagosome formation, NSP6 also limits autophagosome expansion regardless of how they were induced, i.e. whether they were induced directly by NSP6, or indirectly by starvation or chemical inhibition of MTOR signalling. This may favour coronavirus infection by compromising the ability of autophagosomes to deliver viral components to lysosomes for degradation .
Non-structural protein 6, alphacoronavirus (NSP6_alphaCoV)
Type: Domain

This entry represents the non-structural protein 6 (NSP6) from alphacoronavirus.

Coronaviruses (CoV) redirect and rearrange host cell membranes as part of the viral genome replication and transcription machinery; they induce the formation of double-membrane vesicles in infected cells. CoV non-structural protein 6 (NSP6), a transmembrane-containing protein, together with NSP3 and NSP4, have the ability to induce double-membrane vesicles that are similar to those observed in severe acute respiratory syndrome (SARS) coronavirus-infected cells . By itself, NSP6 can generate autophagosomes from the endoplasmic reticulum. Autophagosomes are normally generated as a cellular response to starvation to carry cellular organelles and long-lived proteins to lysosomes for degradation. Degradation through autophagy may provide an innate defense against virus infection, or conversely, autophagosomes can promote infection by facilitating the assembly of replicase proteins . In addition to initiating autophagosome formation, NSP6 also limits autophagosome expansion regardless of how they were induced, i.e. whether they were induced directly by NSP6, or indirectly by starvation or chemical inhibition of MTOR signalling. This may favour coronavirus infection by compromising the ability of autophagosomes to deliver viral components to lysosomes for degradation .
Spike (S) protein S1 subunit, receptor-binding domain, SARS-CoV (Spike_S1_RBD_SARS-CoV)
Type: Domain

The CoV Spike (S) protein is an envelope glycoprotein that plays the most important role in viral attachment, fusion, and entry into host cells, and serves as a major target for the development of neutralizing antibodies, inhibitors of viral entry, and vaccines. It is synthesised as a precursor protein that is cleaved into an N-terminal S1 subunit (~700 amino acids) and a C-terminal S2 subunit (~600 amino acids) that mediates attachment and membrane fusion, respectively. Three S1/S2 heterodimers assemble to form a trimer spike protruding from the viral envelope. The S1 subunit contains a receptor-binding domain (RBD), while the S2 subunit contains a hydrophobic fusion peptide and two heptad repeat regions. S1 contains two structurally independent domains, the N-terminal domain (NTD) and the C-terminal domain (C-domain). Depending on the virus, either the NTD or the C-domain can serve as the receptor-binding domain (RBD). Most CoVs, including SARS-CoV-2, SARS-CoV, and MERS-CoV use the C-domain to bind their receptors. However, CoV such as mouse hepatitis virus (MHV) uses the NTD to bind its receptor, mouse carcinoembryonic antigen related cell adhesion molecule 1a (mCEACAM1a). The S1 NTD contributes to the Spike trimer interface .

This is the receptor-binding domain (RBD) of Spike protein S1 subunit from SARS-CoV which binds the extracellular peptidase domain of angiotensin-converting enzyme 2 (ACE2). It has been shown that the receptor binding induces the dissociation of the S1 with ACE2, prompting the S2 to transit from a metastable pre-fusion to a more-stable post-fusion state that is essential for membrane fusion .
Non-structural protein 3, X-domain-like (Macro_X_NSP3-like)
Type: Domain

The X-domain, a macrodomain, is found in riboviral non-structural protein 3 (NSP3), including the NSP3 of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and other coronaviruses (alpha-, beta-, gamma-, and deltacoronavirus), among others. The SARS-CoV X-domain may function as a module binding poly(ADP-ribose), a metabolic product of NAD+ synthesized by poly(ADP-ribose) polymerase (PARP) . The X-domain of Avian infectious bronchitis virus (IBV) strain Beaudette coronavirus does not bind ADP-ribose; the triple glycine sequence found in the X-domains of SARS-CoV and human coronavirus 229E (HCoV229E), which are involved in ADP-ribose binding, is not conserved in the IBV X-domain. SARS-CoV has two other macrodomains referred to as the SUD-N (N-terminal subdomain) and SUD-M (middle SUD subdomain) of the SARS-unique domain (SUD), which also do not bind ADP-ribose; these bind G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides) .
Spike (S) protein S1 subunit, receptor-binding domain, HCoV-OC43-like (Spike_S1_RBD_HCoV-OC43-like)
Type: Domain

The CoV Spike (S) protein is an envelope glycoprotein that plays the most important role in viral attachment, fusion, and entry into host cells, and serves as a major target for the development of neutralizing antibodies, inhibitors of viral entry, and vaccines. It is synthesised as a precursor protein that is cleaved into an N-terminal S1 subunit (~700 amino acids) and a C-terminal S2 subunit (~600 amino acids) that mediates attachment and membrane fusion, respectively. Three S1/S2 heterodimers assemble to form a trimer spike protruding from the viral envelope. The S1 subunit contains a receptor-binding domain (RBD), while the S2 subunit contains a hydrophobic fusion peptide and two heptad repeat regions. S1 contains two structurally independent domains, the N-terminal domain (NTD) and the C-terminal domain (C-domain). Depending on the virus, either the NTD or the C-domain can serve as the receptor-binding domain (RBD). Most CoVs, including SARS-CoV-2, SARS-CoV, and MERS-CoV use the C-domain to bind their receptors. However, CoV such as mouse hepatitis virus (MHV) uses the NTD to bind its receptor, mouse carcinoembryonic antigen related cell adhesion molecule 1a (mCEACAM1a). The S1 NTD contributes to the Spike trimer interface .

This entry represents the receptor-binding domain (RBD) of the S1 subunit of the Spike (S) protein from several lineage A betacoronaviruses in the embecovirus genera, including human coronavirus OC43 (HCoV-OC43) and bovine respiratory coronavirus (BCoV), among others. HCoV-OC43 is of zoonotic origin and is endemic in the human population, causing mild respiratory tract infections and possible severe complications or fatalities in young children, the elderly, and immunocompromised individuals. HCoV-OC43 uses 9-O-acetyl-sialic acid (9-O-Ac-Sia) as a receptor, which is terminally linked to oligosaccharides decorating glycoproteins and gangliosides at the host cell surface. HCoV-OC43 appears to bind 9-O-Ac-Sia at the NTD .
Non-structural protein 3, SUD-N macrodomain, SARS-CoV (NSP3_SUD-N_SARS-CoV)
Type: Domain

This entry represents a macrodomain referred to as SUD-N (N-terminal subdomain) of the SARS-unique domain (SUD) which binds G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides). It is found in the non-structural protein 3 (NSP3) of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and highly related coronaviruses .

SUD consists of three globular domains separated by short linker peptide segments: SUD-N, SUD-M, and SUD-C . Among these, SUD-N and SUD-M are macrodomains. The SUD-N domain is a related macrodomain which also binds G-quadruplexes . While SUD-N is specific to the NSP3 of SARS and betacoronaviruses of the sarbecovirus subgenera (B lineage), SUD-M is present in most NSP3 proteins except the NSP3 from betacoronaviruses of the embecovirus subgenera (A lineage). SUD-M, despite its name, is not specific to SARS. SUD-C adopts a frataxin-like fold, has structural similarity to DNA-binding domains of DNA-modifying enzymes, binds single-stranded RNA, and regulates the RNA binding behavior of the SUD-M macrodomain. SARS-CoV Nsp3 contains a third macrodomain (the X-domain). The X-domain may function as a module binding poly(ADP-ribose); however, SUD-N and SUD-M do not bind ADP-ribose, as the triple glycine sequence involved in its binding is not conserved in these .
Spike (S) protein S1 subunit, receptor-binding domain, HKU1-like (Spike_S1_RBD_CoV_HKU1-like)
Type: Domain

The CoV Spike (S) protein is an envelope glycoprotein that plays the most important role in viral attachment, fusion, and entry into host cells, and serves as a major target for the development of neutralizing antibodies, inhibitors of viral entry, and vaccines. It is synthesised as a precursor protein that is cleaved into an N-terminal S1 subunit (~700 amino acids) and a C-terminal S2 subunit (~600 amino acids) that mediates attachment and membrane fusion, respectively. Three S1/S2 heterodimers assemble to form a trimer spike protruding from the viral envelope. The S1 subunit contains a receptor-binding domain (RBD), while the S2 subunit contains a hydrophobic fusion peptide and two heptad repeat regions. S1 contains two structurally independent domains, the N-terminal domain (NTD) and the C-terminal domain (C-domain). Depending on the virus, either the NTD or the C-domain can serve as the receptor-binding domain (RBD). Most CoVs, including SARS-CoV-2, SARS-CoV, and MERS-CoV use the C-domain to bind their receptors. However, CoV such as mouse hepatitis virus (MHV) uses the NTD to bind its receptor, mouse carcinoembryonic antigen related cell adhesion molecule 1a (mCEACAM1a). The S1 NTD contributes to the Spike trimer interface .

This domain corresponds to the receptor binding domain (RBD) of the Spike S1 subunit from human coronavirus (CoV) HKU1, isolates N5 and N2. HKU1 is a human lineage A betacoronavirus that causes mild yet prevalent respiratory disease, and is related to the zoonotic SARS and MERS betacoronaviruses. These viruses use 9-O-acetyl-sialic acid (9-O-Ac-Sia) as a receptor which is terminally linked to oligosaccharides decorating glycoproteins and gangliosides at the host cell surface .
Spike (S) protein S1 subunit, receptor-binding domain, MERS-CoV (Spike_S1_RBD_MERS-CoV)
Type: Domain

The CoV Spike (S) protein is an envelope glycoprotein that plays the most important role in viral attachment, fusion, and entry into host cells, and serves as a major target for the development of neutralizing antibodies, inhibitors of viral entry, and vaccines. It is synthesised as a precursor protein that is cleaved into an N-terminal S1 subunit (~700 amino acids) and a C-terminal S2 subunit (~600 amino acids) that mediates attachment and membrane fusion, respectively. Three S1/S2 heterodimers assemble to form a trimer spike protruding from the viral envelope. The S1 subunit contains a receptor-binding domain (RBD), while the S2 subunit contains a hydrophobic fusion peptide and two heptad repeat regions. S1 contains two structurally independent domains, the N-terminal domain (NTD) and the C-terminal domain (C-domain). Depending on the virus, either the NTD or the C-domain can serve as the receptor-binding domain (RBD). Most CoVs, including SARS-CoV-2, SARS-CoV, and MERS-CoV use the C-domain to bind their receptors. However, CoV such as mouse hepatitis virus (MHV) uses the NTD to bind its receptor, mouse carcinoembryonic antigen related cell adhesion molecule 1a (mCEACAM1a). The S1 NTD contributes to the Spike trimer interface .

This entry represents the RDB domain of Spike protein S1 subunit from MERS-CoV. MERS-CoV causes severe pulmonary disease in humans. It binds to its receptor, human dipeptidyl peptidase 4 (DPP4), also called CD26, through the RBD of its S1 subunit and then fuses viral and host membranes through its S2 subunit . The RBD consists of a core subdomain and a unique strand-dominated external receptor binding motif (RBM) that recognises blades IV and V of the CD26 β-propeller .