| Type |
Details |
Score |
| Publication |
| First Author: |
Aricò M |
| Year: |
1992 |
| Journal: |
Clin Exp Dermatol |
| Title: |
Localized crusted scabies in the acquired immunodeficiency syndrome. |
| Volume: |
17 |
| Issue: |
5 |
| Pages: |
339-41 |
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| Publication |
| First Author: |
Faesen AC |
| Year: |
2012 |
| Journal: |
Biochem Soc Trans |
| Title: |
The role of UBL domains in ubiquitin-specific proteases. |
| Volume: |
40 |
| Issue: |
3 |
| Pages: |
539-45 |
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•
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| Publication |
| First Author: |
Willis MS |
| Year: |
2007 |
| Journal: |
Circ Res |
| Title: |
Muscle ring finger 1, but not muscle ring finger 2, regulates cardiac hypertrophy in vivo. |
| Volume: |
100 |
| Issue: |
4 |
| Pages: |
456-9 |
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•
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| Publication |
| First Author: |
Willis MS |
| Year: |
2014 |
| Journal: |
Cell Biochem Funct |
| Title: |
Muscle ring finger 1 and muscle ring finger 2 are necessary but functionally redundant during developmental cardiac growth and regulate E2F1-mediated gene expression in vivo. |
| Volume: |
32 |
| Issue: |
1 |
| Pages: |
39-50 |
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| Publication |
| First Author: |
Lodka D |
| Year: |
2016 |
| Journal: |
J Cachexia Sarcopenia Muscle |
| Title: |
Muscle RING-finger 2 and 3 maintain striated-muscle structure and function. |
| Volume: |
7 |
| Issue: |
2 |
| Pages: |
165-80 |
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| Publication |
| First Author: |
Witt CC |
| Year: |
2008 |
| Journal: |
EMBO J |
| Title: |
Cooperative control of striated muscle mass and metabolism by MuRF1 and MuRF2. |
| Volume: |
27 |
| Issue: |
2 |
| Pages: |
350-60 |
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| Publication |
| First Author: |
Jayaram H |
| Year: |
2006 |
| Journal: |
J Virol |
| Title: |
X-ray structures of the N- and C-terminal domains of a coronavirus nucleocapsid protein: implications for nucleocapsid formation. |
| Volume: |
80 |
| Issue: |
13 |
| Pages: |
6612-20 |
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| Publication |
| First Author: |
Hurst KR |
| Year: |
2009 |
| Journal: |
J Virol |
| Title: |
Identification of in vivo-interacting domains of the murine coronavirus nucleocapsid protein. |
| Volume: |
83 |
| Issue: |
14 |
| Pages: |
7221-34 |
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| Publication |
| First Author: |
Flower TG |
| Year: |
2020 |
| Journal: |
bioRxiv |
| Title: |
Structure of SARS-CoV-2 ORF8, a rapidly evolving coronavirus protein implicated in immune evasion. |
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•
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| Publication |
| First Author: |
Zinzula L |
| Year: |
2021 |
| Journal: |
Biochem Biophys Res Commun |
| Title: |
Lost in deletion: The enigmatic ORF8 protein of SARS-CoV-2. |
| Volume: |
538 |
|
| Pages: |
116-124 |
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•
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| Publication |
| First Author: |
Hussain M |
| Year: |
2021 |
| Journal: |
J Med Virol |
| Title: |
Immunoinformatic analysis of structural and epitope variations in the spike and Orf8 proteins of SARS-CoV-2/B.1.1.7. |
| Volume: |
93 |
| Issue: |
7 |
| Pages: |
4461-4468 |
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| Protein Domain |
| Type: |
Domain |
| Description: |
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 (RDB) of the Spike protein S1 subunit from the porcine hemagglutinating encephalomyelitis virus (HEV), which is related to SARS and MERS betacoronaviruses and is associated with acute outbreaks of wasting and encephalitis in nursing piglets from pig farms. Porcine HEV uses 9-O-acetyl-sialic acid (9-O-Ac-Sia) as a receptor, like the closely related HCoV-OC43 and HCoV-HKU1 viruses []. |
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•
•
•
•
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| Protein Domain |
| Type: |
Homologous_superfamily |
| Description: |
The multi-domain non-structural protein NSP3 is the largest protein encoded by the coronavirus (CoV) genome, with an average molecular mass of about 200 kD. While some of the domains differ between CoV genera, eight domains of NSP3 exist in all known CoVs: the ubiquitin-like domain 1 (Ubl1), the Glu-rich acidic domain (also called "hypervariable region"), a macrodomain (also named "X domain"), the ubiquitin-like domain 2 (Ubl2), the papain-like protease 2 (PL2pro), the NSP3 ectodomain (3Ecto, also called "zinc-finger domain"), as well as the domains Y1 and CoV-Y of unknown functions. There are also two transmembrane regions, TM1 and TM2, which exist in all CoVs [].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 []. |
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•
•
•
•
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| Protein Domain |
| Type: |
Domain |
| Description: |
Coronaviruses (CoVs) have a similar genomic structure and encodes four structural proteins (S, E, M and N) and a variable number of accessory proteins. Accessory proteins play an important role in virus-host interactions, especially in antagonizing or regulating host immunity and virus adaptation to the host. There are large variations in the number of accessory proteins (1-10) among coronaviruses. BetaCoVs have 3-5 accessory proteins, except for SARS-CoV and SARS-CoV-2, which possess the largest number of accessory proteins among all coronaviruses (10 and 9, respectively). ORF8 is the most variable accessory protein among those encoded by SARS related coronaviruses (SARSr-CoVs) and isnot shared by all members of subgenus Sarbecovirus. SARSr ORF8 accessory proteins are characterized by the presence of an N-terminal hydrophobic signal peptide, a conserved N-glycosylation site, and enough cysteine residues with the potential to form disulfide bonds, drawing their picture as structurally stable potential ER-resident proteins. There is functional overlap between these proteins with involvement in immune modulation, which is probably accomplished through involvement in protein quality control. When ORF8 is exogenously overexpressed in cells, it disrupts IFN-I signaling. Unlike ORF8a/b of SARS-CoV, the SARS-CoV-2 ORF8 downregulates MHC-I in cells.This entry represents the immunoglobulin (Ig)-like domain from SARSr ORF8 [, , , , ]. |
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•
•
•
•
•
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| Protein Domain |
| Type: |
Domain |
| Description: |
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 []. |
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•
•
•
•
|
| Protein Domain |
| Type: |
Domain |
| Description: |
The Nucleocapsid (N) protein is a highly immunogenic phosphoprotein also implicated in viral genome replication and in modulating cell signalling pathways. The N protein interacts with genomic and subgenomic RNA molecules. Together with the envelope protein M, it participates in genome condensation and packaging. The N protein is a highly immunogenic and abundantly expressed protein during infection, capable of inducing protective immune responses against SARS-CoV and SARS-CoV-2 [, , , , ].Coronavirus (CoV) nucleocapsid (N) proteins have 3 highly conserved domains. The N-terminal domain (NTD) (N1b), the C-terminal domain (CTD)(N2b) and the N3 region. The N1b and N2b domains from SARS CoV, infectious bronchitis virus (IBV), human CoV 229E and mouse hepatic virus (MHV) display similar topological organisations. N proteins form dimers, which are asymmetrically arranged into octamers via their N2b domains []. Both domains contribute to the binding of viral RNA genome [, ].This entry represents the C-terminal domain of the nucleocapsid proteins from Coronavirus. The C-terminal domain of the N protein (N-CTD) is involved in dimerization, and is thus, also called the dimerization domain [, ]. Structurally, the C-terminal domain forms a tightly intertwined dimer with an intermolecular four-stranded central β-sheet platform flanked by alpha helices, indicating that the basic building block for coronavirus nucleocapsid formation is a dimeric assembly of N protein []. |
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•
•
•
•
•
|
| Protein Domain |
| Type: |
Domain |
| Description: |
The Nucleocapsid (N) protein is a highly immunogenic phosphoprotein also implicated in viral genome replication and in modulating cell signalling pathways. The N protein interacts with genomic and subgenomic RNA molecules. Together with the envelope protein M, it participates in genome condensation and packaging. The N protein is a highly immunogenic and abundantly expressed protein during infection, capable of inducing protective immune responses against SARS-CoV and SARS-CoV-2 [, , , , ].Coronavirus (CoV) nucleocapsid (N) proteins have 3 highly conserved domains. The N-terminal domain (NTD) (N1b), the C-terminal domain (CTD)(N2b) and the N3 region. The N1b and N2b domains from SARS CoV, infectious bronchitis virus (IBV), human CoV 229E and mouse hepatic virus (MHV) display similar topological organisations. N proteins form dimers, which are asymmetrically arranged into octamers via their N2b domains []. Both domains contribute to the binding of viral RNA genome [, ].This entry represents the N-terminal domain of the nucleocapsid (N) protein predominantly from Coronavirus. It exhibits a U-shaped structure, with two arms rich in basic residues, providing a module for specific interaction with RNA [, ]. The overall structure of the N-terminal domain found in SARS-CoV-2 is similar to other reported coronavirus nucleocapsid protein N-terminal domains, but the surface charge distribution patterns are different. This domain also interacts with the viral membrane protein during virion assembly and plays a critical role in enhancing the efficiency of virus transcription and assembly. It has been identified as an important drug target []. |
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•
•
•
•
•
|
| Protein Domain |
| Type: |
Homologous_superfamily |
| Description: |
The Nucleocapsid (N) protein is a highly immunogenic phosphoprotein also implicated in viral genome replication and in modulating cell signalling pathways. The N protein interacts with genomic and subgenomic RNA molecules. Together with the envelope protein M, it participates in genome condensation and packaging. The N protein is a highly immunogenic and abundantly expressed protein during infection, capable of inducing protective immune responses against SARS-CoV and SARS-CoV-2 [, , , , ].Coronavirus (CoV) nucleocapsid (N) proteins have 3 highly conserved domains. The N-terminal domain (NTD) (N1b), the C-terminal domain (CTD)(N2b) and the N3 region. The N1b and N2b domains from SARS CoV, infectious bronchitis virus (IBV), human CoV 229E and mouse hepatic virus (MHV) display similar topological organisations. N proteins form dimers, which are asymmetrically arranged into octamers via their N2b domains []. Both domains contribute to the binding of viral RNA genome [, ].This entry represents the N-terminal domain of the nucleocapsid (N) protein predominantly from Coronavirus. It exhibits a U-shaped structure, with two arms rich in basic residues, providing a module for specific interaction with RNA [, ]. The overall structure of the N-terminal domain found in SARS-CoV-2 is similar to other reported coronavirus nucleocapsid protein N-terminal domains, but the surface charge distribution patterns are different. This domain also interacts with the viral membrane protein during virion assembly and plays a critical role in enhancing the efficiency of virus transcription and assembly. It has been identified as an important drug target []. |
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•
•
•
•
•
|
| Protein Domain |
| Type: |
Homologous_superfamily |
| Description: |
The Nucleocapsid (N) protein is a highly immunogenic phosphoprotein also implicated in viral genome replication and in modulating cell signalling pathways. The N protein interacts with genomic and subgenomic RNA molecules. Together with the envelope protein M, it participates in genome condensation and packaging. The N protein is a highly immunogenic and abundantly expressed protein during infection, capable of inducing protective immune responses against SARS-CoV and SARS-CoV-2 [, , , , ].Coronavirus (CoV) nucleocapsid (N) proteins have 3 highly conserved domains. The N-terminal domain (NTD) (N1b), the C-terminal domain (CTD)(N2b) and the N3 region. The N1b and N2b domains from SARS CoV, infectious bronchitis virus (IBV), human CoV 229E and mouse hepatic virus (MHV) display similar topological organisations. N proteins form dimers, which are asymmetrically arranged into octamers via their N2b domains []. Both domains contribute to the binding of viral RNA genome [, ].This entry represents the C-terminal domain of the nucleocapsid proteins from Coronavirus and Arterivirus. The C-terminal domain of the N protein (N-CTD) is involved in dimerization, and is thus, also called the dimerization domain []. Structurally, the C-terminal domain forms a tightly intertwined dimer with an intermolecular four-stranded central β-sheet platform flanked by alpha helices, indicating that the basic building block for coronavirus nucleocapsid formation is a dimeric assembly of N protein []. |
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•
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| Publication |
| First Author: |
Snijder EJ |
| Year: |
2003 |
| Journal: |
J Mol Biol |
| Title: |
Unique and conserved features of genome and proteome of SARS-coronavirus, an early split-off from the coronavirus group 2 lineage. |
| Volume: |
331 |
| Issue: |
5 |
| Pages: |
991-1004 |
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•
•
•
•
|
| Publication |
| First Author: |
Chatterjee A |
| Year: |
2009 |
| Journal: |
J Virol |
| Title: |
Nuclear magnetic resonance structure shows that the severe acute respiratory syndrome coronavirus-unique domain contains a macrodomain fold. |
| Volume: |
83 |
| Issue: |
4 |
| Pages: |
1823-36 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Oberto G |
| Year: |
2007 |
| Journal: |
Radiat Res |
| Title: |
Carcinogenicity study of 217 Hz pulsed 900 MHz electromagnetic fields in Pim1 transgenic mice. |
| Volume: |
168 |
| Issue: |
3 |
| Pages: |
316-26 |
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•
•
•
•
|
| Publication |
| First Author: |
Roberts A |
| Year: |
2007 |
| Journal: |
PLoS Pathog |
| Title: |
A mouse-adapted SARS-coronavirus causes disease and mortality in BALB/c mice. |
| Volume: |
3 |
| Issue: |
1 |
| Pages: |
e5 |
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•
•
•
•
•
|
| Publication |
| First Author: |
Zhou Y |
| Year: |
2015 |
| Journal: |
Antiviral Res |
| Title: |
Protease inhibitors targeting coronavirus and filovirus entry. |
| Volume: |
116 |
|
| Pages: |
76-84 |
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•
•
•
•
|
| Publication |
| First Author: |
Salah S |
| Year: |
2022 |
| Journal: |
bioRxiv |
| Title: |
Development of a Novel SARS-CoV-2 Immune Complex Vaccine Candidate (CRCx) with Broad Immune Responses: A Preclinical Trial in Animal Model. |
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•
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| Gene |
| Type: |
gene |
| Organism: |
human |
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•
•
•
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| Gene |
| Type: |
gene |
| Organism: |
human |
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•
•
•
|
| Publication |
| First Author: |
He J |
| Year: |
2015 |
| Journal: |
Cardiovasc Diabetol |
| Title: |
MuRF2 regulates PPARÎł1 activity to protect against diabetic cardiomyopathy and enhance weight gain induced by a high fat diet. |
| Volume: |
14 |
|
| Pages: |
97 |
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•
•
•
•
•
|
| Publication |
| First Author: |
Ahmed SF |
| Year: |
2020 |
| Journal: |
Viruses |
| Title: |
Preliminary Identification of Potential Vaccine Targets for the COVID-19 Coronavirus (SARS-CoV-2) Based on SARS-CoV Immunological Studies. |
| Volume: |
12 |
| Issue: |
3 |
|
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•
•
•
•
•
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| Publication |
| First Author: |
Lin Y |
| Year: |
2003 |
| Journal: |
Cell Res |
| Title: |
Identification of an epitope of SARS-coronavirus nucleocapsid protein. |
| Volume: |
13 |
| Issue: |
3 |
| Pages: |
141-5 |
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•
•
•
•
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| Publication |
| First Author: |
Shang B |
| Year: |
2005 |
| Journal: |
Biochem Biophys Res Commun |
| Title: |
Characterization and application of monoclonal antibodies against N protein of SARS-coronavirus. |
| Volume: |
336 |
| Issue: |
1 |
| Pages: |
110-7 |
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•
•
•
•
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| Publication |
| First Author: |
Lin SY |
| Year: |
2014 |
| Journal: |
J Med Chem |
| Title: |
Structural basis for the identification of the N-terminal domain of coronavirus nucleocapsid protein as an antiviral target. |
| Volume: |
57 |
| Issue: |
6 |
| Pages: |
2247-57 |
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•
•
•
•
|
| Publication |
| First Author: |
Schaecher SR |
| Year: |
2007 |
| Journal: |
J Virol |
| Title: |
The ORF7b protein of severe acute respiratory syndrome coronavirus (SARS-CoV) is expressed in virus-infected cells and incorporated into SARS-CoV particles. |
| Volume: |
81 |
| Issue: |
2 |
| Pages: |
718-31 |
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•
•
•
•
|
| Publication |
| First Author: |
Schaecher SR |
| Year: |
2008 |
| Journal: |
J Virol |
| Title: |
The transmembrane domain of the severe acute respiratory syndrome coronavirus ORF7b protein is necessary and sufficient for its retention in the Golgi complex. |
| Volume: |
82 |
| Issue: |
19 |
| Pages: |
9477-91 |
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•
•
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•
•
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| Protein Domain |
| Type: |
Domain |
| Description: |
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 [, ]. |
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•
•
•
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| Protein Domain |
| Type: |
Domain |
| Description: |
This entry represents the N-terminal region of the SUD domain (SUD-N or Mac2) found in non-structural protein NSP3, the product of ORF1a in group 2 (beta) coronaviruses. It is found in human SARS-CoV and SARS-CoV-2 polyprotein 1a and 1ab, and in related coronavirus polyproteins [].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 [].Nsp3c-N and Nsp3c-M each display a typical α/β/α Macro domain fold, in spite of the complete absence of sequence similarities. The central β-sheet with six β-strands in the order β1-β6-β5-β2-β4-β3 is flanked by two (or three) helices on either side. Only the last strand, β3, is antiparallel to the other strands. Currently, most known functions of Nsp3c-N/M are connected with RNA binding. All the residues important for binding ADP-ribose and for de-MARylation/de-PARylation activity are not conserved in Nsp3c-N/M; therefore Nsp3c-N/M cannot bind ADP-ribose. Both Nsp3c-N and Nsp3c-M domains bind unusual nucleic acid structures formed by consecutives guanosine nucleotides, where four strands of nucleic acid are forming a superhelix (so-called G-quadruplexes) [, , , , ]. |
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| Publication |
| First Author: |
Iwata-Yoshikawa N |
| Year: |
2014 |
| Journal: |
J Virol |
| Title: |
Effects of Toll-like receptor stimulation on eosinophilic infiltration in lungs of BALB/c mice immunized with UV-inactivated severe acute respiratory syndrome-related coronavirus vaccine. |
| Volume: |
88 |
| Issue: |
15 |
| Pages: |
8597-614 |
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•
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| Publication |
| First Author: |
Deming D |
| Year: |
2006 |
| Journal: |
PLoS Med |
| Title: |
Vaccine efficacy in senescent mice challenged with recombinant SARS-CoV bearing epidemic and zoonotic spike variants. |
| Volume: |
3 |
| Issue: |
12 |
| Pages: |
e525 |
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•
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| Publication |
| First Author: |
Bleau C |
| Year: |
2015 |
| Journal: |
J Virol |
| Title: |
Brain Invasion by Mouse Hepatitis Virus Depends on Impairment of Tight Junctions and Beta Interferon Production in Brain Microvascular Endothelial Cells. |
| Volume: |
89 |
| Issue: |
19 |
| Pages: |
9896-908 |
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•
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| Publication |
| First Author: |
Kim E |
| Year: |
2020 |
| Journal: |
EBioMedicine |
| Title: |
Microneedle array delivered recombinant coronavirus vaccines: Immunogenicity and rapid translational development. |
| Volume: |
55 |
|
| Pages: |
102743 |
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•
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| Publication |
| First Author: |
Lei J |
| Year: |
2018 |
| Journal: |
Antiviral Res |
| Title: |
Nsp3 of coronaviruses: Structures and functions of a large multi-domain protein. |
| Volume: |
149 |
|
| Pages: |
58-74 |
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•
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| Publication |
| First Author: |
Bian H |
| Year: |
2018 |
| Journal: |
FEBS Open Bio |
| Title: |
The E3 ubiquitin ligase MuRF2 attenuates LPS-induced macrophage activation by inhibiting production of inflammatory cytokines and migration. |
| Volume: |
8 |
| Issue: |
2 |
| Pages: |
234-243 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Shin D |
| Year: |
2020 |
| Journal: |
Nature |
| Title: |
Papain-like protease regulates SARS-CoV-2 viral spread and innate immunity. |
| Volume: |
587 |
| Issue: |
7835 |
| Pages: |
657-662 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Cong Y |
| Year: |
2017 |
| Journal: |
Sci Rep |
| Title: |
Coronavirus nucleocapsid proteins assemble constitutively in high molecular oligomers. |
| Volume: |
7 |
| Issue: |
1 |
| Pages: |
5740 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Wu CH |
| Year: |
2014 |
| Journal: |
Cell Host Microbe |
| Title: |
Nucleocapsid phosphorylation and RNA helicase DDX1 recruitment enables coronavirus transition from discontinuous to continuous transcription. |
| Volume: |
16 |
| Issue: |
4 |
| Pages: |
462-72 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Zinzula L |
| Year: |
2021 |
| Journal: |
Biochem Biophys Res Commun |
| Title: |
High-resolution structure and biophysical characterization of the nucleocapsid phosphoprotein dimerization domain from the Covid-19 severe acute respiratory syndrome coronavirus 2. |
| Volume: |
538 |
|
| Pages: |
54-62 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Osipiuk J |
| Year: |
2021 |
| Journal: |
Nat Commun |
| Title: |
Structure of papain-like protease from SARS-CoV-2 and its complexes with non-covalent inhibitors. |
| Volume: |
12 |
| Issue: |
1 |
| Pages: |
743 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Renzi F |
| Year: |
2006 |
| Journal: |
Proc Natl Acad Sci U S A |
| Title: |
The structure of the endoribonuclease XendoU: From small nucleolar RNA processing to severe acute respiratory syndrome coronavirus replication. |
| Volume: |
103 |
| Issue: |
33 |
| Pages: |
12365-70 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Laneve P |
| Year: |
2008 |
| Journal: |
J Biol Chem |
| Title: |
The tumor marker human placental protein 11 is an endoribonuclease. |
| Volume: |
283 |
| Issue: |
50 |
| Pages: |
34712-9 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Gioia U |
| Year: |
2005 |
| Journal: |
J Biol Chem |
| Title: |
Functional characterization of XendoU, the endoribonuclease involved in small nucleolar RNA biosynthesis. |
| Volume: |
280 |
| Issue: |
19 |
| Pages: |
18996-9002 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Lee HC |
| Year: |
2017 |
| Journal: |
Gene Expr Patterns |
| Title: |
Embryonic expression patterns of Eukaryotic EndoU ribonuclease family gene endouC in zebrafish. |
| Volume: |
25-26 |
|
| Pages: |
66-70 |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Family |
| Description: |
The Nucleocapsid (N) protein is a highly immunogenic phosphoprotein also implicated in viral genome replication and in modulating cell signalling pathways. The N protein interacts with genomic and subgenomic RNA molecules. Together with the envelope protein M, it participates in genome condensation and packaging. The N protein is a highly immunogenic and abundantly expressed protein during infection, capable of inducing protective immune responses against SARS-CoV and SARS-CoV-2 [, , , , ].Coronavirus (CoV) nucleocapsid (N) proteins have 3 highly conserved domains. The N-terminal domain (NTD) (N1b), the C-terminal domain (CTD)(N2b) and the N3 region. The N1b and N2b domains from SARS CoV, infectious bronchitis virus (IBV), human CoV 229E and mouse hepatic virus (MHV) display similar topological organisations. N proteins form dimers, which are asymmetrically arranged into octamers via their N2b domains.Domains N1b and N2b are linked by another domain N2a that contains an SR-rich region (rich in serine and arginine residues). A priming phosphorylation of specific serine residues by an as yet unknown kinase, triggers the subsequent phosphorylation by the host glycogen synthase kinase-3 (GSK-3) of several residues in the SR-rich region. This phosphorylation allows the N protein to associate with the RNA helicase DDX1 permitting template read-through, and enabling the transition from discontinuous transcription of subgenomic mRNAs (sgmRNAs) to continuous synthesis of longer sgmRNAs and genomic RNA (gRNA). Production of gRNA in the presence of N oligomers may promote the formation of ribonucleoprotein complexes, and the newly transcribed sgmRNA would guarantee efficient synthesis of structural proteins [, , ].It has been shown that N proteins interact with nonstructural protein 3 (NSP3) and thus are recruited to the replication-transcription complexes (RTCs). In MHV, the N1b and N2a domains mediate the binding to NSP3 in a gRNA-independent manner. At the RTCs, the N protein is required for the stimulation of gRNA replication and sgmRNA transcription. It remains unclear, however, how and why the N protein orchestrates viral RNA synthesis. The cytoplasmic N-terminal ubiquitin-like domain of NSP3 and the SR-rich region of the N2a domain of the N protein may be important for this interaction. The direct association of N protein with RTCs is a critical step for MHV infection [].This entry represents the nucleocapsid protein from Betacoronavirus. |
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•
•
•
•
•
|
| Protein Domain |
| Type: |
Family |
| Description: |
The Nucleocapsid (N) protein is a highly immunogenic phosphoprotein also implicated in viral genome replication and in modulating cell signalling pathways. The N protein interacts with genomic and subgenomic RNA molecules. Together with the envelope protein M, it participates in genome condensation and packaging. The N protein is a highly immunogenic and abundantly expressed protein during infection, capable of inducing protective immune responses against SARS-CoV and SARS-CoV-2 [, , , , ].Coronavirus (CoV) nucleocapsid (N) proteins have 3 highly conserved domains. The N-terminal domain (NTD) (N1b), the C-terminal domain (CTD)(N2b) and the N3 region. The N1b and N2b domains from SARS CoV, infectious bronchitis virus (IBV), human CoV 229E and mouse hepatic virus (MHV) display similar topological organisations. N proteins form dimers, which are asymmetrically arranged into octamers via their N2b domains.Domains N1b and N2b are linked by another domain N2a that contains an SR-rich region (rich in serine and arginine residues). A priming phosphorylation of specific serine residues by an as yet unknown kinase, triggers the subsequent phosphorylation by the host glycogen synthase kinase-3 (GSK-3) of several residues in the SR-rich region. This phosphorylation allows the N protein to associate with the RNA helicase DDX1 permitting template read-through, and enabling the transition from discontinuous transcription of subgenomic mRNAs (sgmRNAs) to continuous synthesis of longer sgmRNAs and genomic RNA (gRNA). Production of gRNA in the presence of N oligomers may promote the formation of ribonucleoprotein complexes, and the newly transcribed sgmRNA would guarantee efficient synthesis of structural proteins [, , ].It has been shown that N proteins interact with nonstructural protein 3 (NSP3) and thus are recruited to the replication-transcription complexes (RTCs). In MHV, the N1b and N2a domains mediate the binding to NSP3 in a gRNA-independent manner. At the RTCs, the N protein is required for the stimulation of gRNA replication and sgmRNA transcription. It remains unclear, however, how and why the N protein orchestrates viral RNA synthesis. The cytoplasmic N-terminal ubiquitin-like domain of NSP3 and the SR-rich region of the N2a domain of the N protein may be important for this interaction. The direct association of N protein with RTCs is a critical step for MHV infection [].The entry represents the Coronavirus nucleocapsid protein. |
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•
•
•
•
•
|
| Protein Domain |
| Type: |
Domain |
| Description: |
This entry contains coronavirus (CoV) cysteine endopeptidases that belong to MEROPS peptidase family C16 (subfamilies C16A and C16B, clan CA). These peptidases are involved in viral polyprotein processing, releasing NSP1, NSP2 and NSP3 proteins []and they also function as deubiquitinating and deISG15ylating (interferon-induced gene 15) enzymes, disrupting host viral immune response to facilitate viral proliferation and replication. Therefore, this is an important target to develop antiviral treatments [].All coronaviruses encode between one and two accessory cysteine proteinases that recognise and process one or three sites in the amino-terminal half of the replicase polyprotein during assembly of the viral replication complex. MHV, HCoV and TGEV encode two accessory proteinases, called coronavirus papain-like proteinase 1 and 2 (PL1-PRO and PL2-PRO) []. IBV and SARS encodes only one called PL-PRO (PL2-PRO, conserved in all CoVs) [, , ]. The structures of both PL-PROs are similar and they also have restricted specificities. The PL1-PRO of TGEV cleaves the polyprotein between Nsp2-Nsp3 recognising the Lys-Met-Gly-Gly motif, and recognises Leu-Arg-Gly-Gly in ubiquitin (ub) which shows that it is able to accommodate residues as different as Lys and Leu. In contrast, PL-PRO from SARS-CoV recognises Leu-Xaa-Gly-Gly (Xaa could be any amino acid) and cleaves peptide bonds between Nsp1-Nsp2, Nsp2-Nsp3 and between Nsp3-Nsp4 [, , ]. In Ub and ISG15 proteins, it recognises Leu-Arg-Gly-Gly motifs. SARS-CoV and SARS-CoV-2 are closely related but exhibit different host substrate preferences: SARS-CoV-2 PL-PRO preferentially cleaves the ubiquitin-like ISG15, whereas SARS-CoV PL-PRO predominantly targets ubiquitin chains [, ].The peptidase family C16 domain is about 260 amino acids in length and the solved structures determined that it consists of thumb, palm, and fingers subdomains. The thumb is comprised of six α-helices and a small β-hairpin; the fingers subdomain is made of six β-strands and two α-helices and includes a zinc binding site, in which the zinc ion is coordinated by four cysteine residues. Zinc binding is essential for structural integrity and protease activity, with a conformation that varies most between different PL-PRO structures. The palm subdomain is comprised of six β-strands and includes the catalytic residues Cys-His-Asp, located at the interface between the thumb and palm subdomains []. |
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•
•
•
•
•
|
| Protein Domain |
| Type: |
Domain |
| Description: |
This entry represents the macrodomain referred to as SUD-M (middle SUD subdomain) of the SARS-unique domain (SUD) which binds G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides) []. It can be found in non-structural protein 3 (NSP3) of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and related coronaviruses []. NSP3 binds to viral RNA, nucleocapsid protein, as well as other viral proteins, and participates in polyprotein processing. It is a multifunctional protein comprising up to 16 different domains and regions []. In SARS-CoV the SUD-M (527-651) domain has been shown to bind single-stranded poly(A). It has been shown through the contact area with this RNA on the protein surface, and the electrophoretic mobility shift assays, that SUD-M has higher affinity for purine bases than for pyrimidine bases [].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 [].Nsp3c-N and Nsp3c-M each display a typical α/β/α Macro domain fold, in spite of the complete absence of sequence similarities. The central β-sheet with six β-strands in the order β1-β6-β5-β2-β4-β3 is flanked by two (or three) helices on either side. Only the last strand, β3, is antiparallel to the other strands. Currently, most known functions of Nsp3c-N/M are connected with RNA binding. All the residues important for binding ADP-ribose and for de-MARylation/de-PARylation activity are not conserved in Nsp3c-N/M; therefore Nsp3c-N/M cannot bind ADP-ribose. Both Nsp3c-N and Nsp3c-M domains bind unusual nucleic acid structures formed by consecutives guanosine nucleotides, where four strands of nucleic acid are forming a superhelix (so-called G-quadruplexes) [, , , , ]. |
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•
•
•
•
•
|
| Protein Domain |
| Type: |
Family |
| Description: |
The Nucleocapsid (N) protein is a highly immunogenic phosphoprotein also implicated in viral genome replication and in modulating cell signalling pathways. The N protein interacts with genomic and subgenomic RNA molecules. Together with the envelope protein M, it participates in genome condensation and packaging. The N protein is a highly immunogenic and abundantly expressed protein during infection, capable of inducing protective immune responses against SARS-CoV and SARS-CoV-2 [, , , , ].Coronavirus (CoV) nucleocapsid (N) proteins have 3 highly conserved domains. The N-terminal domain (NTD) (N1b), the C-terminal domain (CTD)(N2b) and the N3 region. The N1b and N2b domains from SARS CoV, infectious bronchitis virus (IBV), human CoV 229E and mouse hepatic virus (MHV) display similar topological organisations. N proteins form dimers, which are asymmetrically arranged into octamers via their N2b domains.Domains N1b and N2b are linked by another domain N2a that contains an SR-rich region (rich in serine and arginine residues). A priming phosphorylation of specific serine residues by an as yet unknown kinase, triggers the subsequent phosphorylation by the host glycogen synthase kinase-3 (GSK-3) of several residues in the SR-rich region. This phosphorylation allows the N protein to associate with the RNA helicase DDX1 permitting template read-through, and enabling the transition from discontinuous transcription of subgenomic mRNAs (sgmRNAs) to continuous synthesis of longer sgmRNAs and genomic RNA (gRNA). Production of gRNA in the presence of N oligomers may promote the formation of ribonucleoprotein complexes, and the newly transcribed sgmRNA would guarantee efficient synthesis of structural proteins [, , ].It has been shown that N proteins interact with nonstructural protein 3 (NSP3) and thus are recruited to the replication-transcription complexes (RTCs). In MHV, the N1b and N2a domains mediate the binding to NSP3 in a gRNA-independent manner. At the RTCs, the N protein is required for the stimulation of gRNA replication and sgmRNA transcription. It remains unclear, however, how and why the N protein orchestrates viral RNA synthesis. The cytoplasmic N-terminal ubiquitin-like domain of NSP3 and the SR-rich region of the N2a domain of the N protein may be important for this interaction. The direct association of N protein with RTCs is a critical step for MHV infection [].This entry represents the nucleocapsid protein from gammacoronavirus. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Family |
| Description: |
The Nucleocapsid (N) protein is a highly immunogenic phosphoprotein also implicated in viral genome replication and in modulating cell signalling pathways. The N protein interacts with genomic and subgenomic RNA molecules. Together with the envelope protein M, it participates in genome condensation and packaging. The N protein is a highly immunogenic and abundantly expressed protein during infection, capable of inducing protective immune responses against SARS-CoV and SARS-CoV-2 [, , , , ].Coronavirus (CoV) nucleocapsid (N) proteins have 3 highly conserved domains. The N-terminal domain (NTD) (N1b), the C-terminal domain (CTD)(N2b) and the N3 region. The N1b and N2b domains from SARS CoV, infectious bronchitis virus (IBV), human CoV 229E and mouse hepatic virus (MHV) display similar topological organisations. N proteins form dimers, which are asymmetrically arranged into octamers via their N2b domains.DomainsN1b and N2b are linked by another domain N2a that contains an SR-rich region (rich in serine and arginine residues). A priming phosphorylation of specific serine residues by an as yet unknown kinase, triggers the subsequent phosphorylation by the host glycogen synthase kinase-3 (GSK-3) of several residues in the SR-rich region. This phosphorylation allows the N protein to associate with the RNA helicase DDX1 permitting template read-through, and enabling the transition from discontinuous transcription of subgenomic mRNAs (sgmRNAs) to continuous synthesis of longer sgmRNAs and genomic RNA (gRNA). Production of gRNA in the presence of N oligomers may promote the formation of ribonucleoprotein complexes, and the newly transcribed sgmRNA would guarantee efficient synthesis of structural proteins [, , ].It has been shown that N proteins interact with nonstructural protein 3 (NSP3) and thus are recruited to the replication-transcription complexes (RTCs). In MHV, the N1b and N2a domains mediate the binding to NSP3 in a gRNA-independent manner. At the RTCs, the N protein is required for the stimulation of gRNA replication and sgmRNA transcription. It remains unclear, however, how and why the N protein orchestrates viral RNA synthesis. The cytoplasmic N-terminal ubiquitin-like domain of NSP3 and the SR-rich region of the N2a domain of the N protein may be important for this interaction. The direct association of N protein with RTCs is a critical step for MHV infection [].This entry represents the nucleocapsid protein from alphacoronavirus. |
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•
•
•
•
•
|
| Publication |
| First Author: |
Kusov Y |
| Year: |
2015 |
| Journal: |
Virology |
| Title: |
A G-quadruplex-binding macrodomain within the "SARS-unique domain" is essential for the activity of the SARS-coronavirus replication-transcription complex. |
| Volume: |
484 |
|
| Pages: |
313-22 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Tortorici MA |
| Year: |
2019 |
| Journal: |
Nat Struct Mol Biol |
| Title: |
Structural basis for human coronavirus attachment to sialic acid receptors. |
| Volume: |
26 |
| Issue: |
6 |
| Pages: |
481-489 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Robichaud S |
| Year: |
2021 |
| Journal: |
Autophagy |
| Title: |
Identification of novel lipid droplet factors that regulate lipophagy and cholesterol efflux in macrophage foam cells. |
| Volume: |
17 |
| Issue: |
11 |
| Pages: |
3671-3689 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Cong Y |
| Year: |
2020 |
| Journal: |
J Virol |
| Title: |
Nucleocapsid Protein Recruitment to Replication-Transcription Complexes Plays a Crucial Role in Coronaviral Life Cycle. |
| Volume: |
94 |
| Issue: |
4 |
|
|
•
•
•
•
•
|
| Publication |
| First Author: |
Ou X |
| Year: |
2017 |
| Journal: |
Nat Commun |
| Title: |
Crystal structure of the receptor binding domain of the spike glycoprotein of human betacoronavirus HKU1. |
| Volume: |
8 |
|
| Pages: |
15216 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Hackbart M |
| Year: |
2020 |
| Journal: |
Proc Natl Acad Sci U S A |
| Title: |
Coronavirus endoribonuclease targets viral polyuridine sequences to evade activating host sensors. |
| Volume: |
117 |
| Issue: |
14 |
| Pages: |
8094-8103 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Baker SC |
| Year: |
1993 |
| Journal: |
J Virol |
| Title: |
Identification of the catalytic sites of a papain-like cysteine proteinase of murine coronavirus. |
| Volume: |
67 |
| Issue: |
10 |
| Pages: |
6056-63 |
|
•
•
•
•
•
|
| Gene |
| Type: |
gene |
| Organism: |
human |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Perera S |
| Year: |
2011 |
| Journal: |
Dev Biol |
| Title: |
Developmental regulation of MURF ubiquitin ligases and autophagy proteins nbr1, p62/SQSTM1 and LC3 during cardiac myofibril assembly and turnover. |
| Volume: |
351 |
| Issue: |
1 |
| Pages: |
46-61 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Witt SH |
| Year: |
2005 |
| Journal: |
J Mol Biol |
| Title: |
MURF-1 and MURF-2 target a specific subset of myofibrillar proteins redundantly: towards understanding MURF-dependent muscle ubiquitination. |
| Volume: |
350 |
| Issue: |
4 |
| Pages: |
713-22 |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
412
 |
| Fragment?: |
false |
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•
•
•
•
|
| Publication |
| First Author: |
Kanjanahaluethai A |
| Year: |
2003 |
| Journal: |
J Virol |
| Title: |
Identification of the murine coronavirus MP1 cleavage site recognized by papain-like proteinase 2. |
| Volume: |
77 |
| Issue: |
13 |
| Pages: |
7376-82 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Arya R |
| Year: |
2021 |
| Journal: |
J Mol Biol |
| Title: |
Structural insights into SARS-CoV-2 proteins. |
| Volume: |
433 |
| Issue: |
2 |
| Pages: |
166725 |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Domain |
| Description: |
This entry represents a domainfound in betacoronavirus cysteine endopeptidases that belong to MEROPS peptidase families C30 (clan PA) and C16 (subfamiles C16A and C16B, clan CA). These peptidase are involved in viral polyprotein processing. All coronaviruses encodes between one and two accessory cysteine proteinases that recognise and process one or two sites in the amino-terminal half of the replicase polyprotein during assembly of the viral replication complex. MHV, HCoV and TGEV encode two accesssory proteinases, called coronavirus papain-like proteinase 1 and 2 (PL1-PRO and PL2-PRO). IBV and SARS encodes only one called PL-PRO []. Coronavirus papain-like proteinases 1 and 2 have restricted specificities, cleaving respectively two and one bond(s)in the polyprotein. This restricted activity may be due to extended specificity sites: Arg or Lys at the cleavage site position P5 are required for PL1-PRO [], and Phe at the cleavage site position P6 is required for PL2-PRO []. PL1-PRO releases p28 and p65 from the N terminus of the polyprotein; PL2-PRO cleaves between p210 and p150. A cysteine peptidase is a proteolytic enzyme that hydrolyses a peptide bond using the thiol group of a cysteine residue as a nucleophile. Hydrolysis involves usually a catalytic triad consisting of the thiol group of the cysteine, the imidazolium ring of a histidine, and a third residue, usually asparagine or aspartic acid, to orientate and activate the imidazolium ring. In only one family of cysteine peptidases, is the role of the general base assigned to a residue other than a histidine: in peptidases from family C89 (acid ceramidase) an arginine is the general base. Cysteine peptidases can be grouped into fourteen different clans, with members of each clan possessing a tertiary fold unique to the clan. Four clans of cysteine peptidases share structural similarities with serine and threonine peptidases and asparagine lyases. From sequence similarities, cysteine peptidases can be clustered into over 80 different families []. Clans CF, CM, CN, CO, CP and PD contain only one family.Cysteine peptidases are often active at acidic pH and are therefore confined to acidic environments, such as the animal lysosome or plant vacuole. Cysteine peptidases can be endopeptidases, aminopeptidases, carboxypeptidases, dipeptidyl-peptidases or omega-peptidases. They are inhibited by thiol chelators such as iodoacetate, iodoacetic acid, N-ethylmaleimide or p-chloromercuribenzoate.Clan CA includes proteins with a papain-like fold. There is a catalytic triad which occurs in the order: Cys/His/Asn (or Asp). A fourth residue, usually Gln, is important for stabilising the acyl intermediate that forms during catalysis, and this precedes the active site Cys. The fold consists of two subdomains with the active site between them. One subdomain consists of a bundle of helices, with the catalytic Cys at the end of one of them, and the other subdomain is a β-barrel with the active site His and Asn (or Asp). There are over thirty families in the clan, and tertiary structures have been solved for members of most of these. Peptidases in clan CA are usually sensitive to the small molecule inhibitor E64, which is ineffective against peptidases from other clans of cysteine peptidases [].Clan CD includes proteins with a caspase-like fold. Proteins in the clan have an α/β/α sandwich structure. There is a catalytic dyad which occurs in the order His/Cys. The active site His occurs in a His-Gly motif and the active site Cys occurs in an Ala-Cys motif; both motifs are preceded by a block of hydrophobic residues []. Specificity is predominantly directed towards residues that occupy the S1 binding pocket, so that caspases cleave aspartyl bonds, legumains cleave asparaginyl bonds, and gingipains cleave lysyl or arginyl bonds.Clan CE includes proteins with an adenain-like fold. The fold consists of two subdomains with the active site between them. One domain is a bundle of helices, and the other a β-barrell. The subdomains are in the opposite order to those found in peptidases from clan CA, and this is reflected in the order of active site residues: His/Asn/Gln/Cys. This has prompted speculation that proteins in clans CA and CE are related, and that members of one clan are derived from a circular permutation of the structure of the other.Clan CL includes proteins with a sortase B-like fold. Peptidases in the clan hydrolyse and transfer bacterial cell wall peptides. The fold shows a closed β-barrel decorated with helices with the active site at one end of the barrel []. The active site consists of a His/Cys catalytic dyad.Cysteine peptidases with a chymotrypsin-like fold are included in clan PA, which also includes serine peptidases. Cysteine peptidases that are N-terminal nucleophile hydrolases are included in clan PB. Cysteine peptidases with a tertiary structure similar to that of the serine-type aspartyl dipeptidase are included in clan PC. Cysteine peptidases with an intein-like fold are included in clan PD, which also includes asparagine lyases. |
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•
•
•
•
|
| Publication |
| First Author: |
Weinert S |
| Year: |
2006 |
| Journal: |
J Cell Biol |
| Title: |
M line-deficient titin causes cardiac lethality through impaired maturation of the sarcomere. |
| Volume: |
173 |
| Issue: |
4 |
| Pages: |
559-70 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Lau SK |
| Year: |
2010 |
| Journal: |
J Virol |
| Title: |
Coexistence of different genotypes in the same bat and serological characterization of Rousettus bat coronavirus HKU9 belonging to a novel Betacoronavirus subgroup. |
| Volume: |
84 |
| Issue: |
21 |
| Pages: |
11385-94 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Luo Y |
| Year: |
2018 |
| Journal: |
Virol Sin |
| Title: |
Longitudinal Surveillance of Betacoronaviruses in Fruit Bats in Yunnan Province, China During 2009-2016. |
| Volume: |
33 |
| Issue: |
1 |
| Pages: |
87-95 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Tai W |
| Year: |
2020 |
| Journal: |
Cell Mol Immunol |
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