UniProt functional annotation for P0C6X7



	UniProt functional annotation for P0C6X7

UniProt codes: P0C6X7, P59641.

Organism: Severe acute respiratory syndrome coronavirus (SARS-CoV).

Taxonomy: Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes; Nidovirales; Cornidovirineae; Coronaviridae; Orthocoronavirinae; Betacoronavirus; Sarbecovirus.

Function: [Isoform Replicase polyprotein 1ab]: Multifunctional protein involved in the transcription and replication of viral RNAs. Contains the proteinases responsible for the cleavages of the polyprotein.

Function: [Host translation inhibitor nsp1]: Inhibits host translation by interacting with the 40S ribosomal subunit. The nsp1-40S ribosome complex further induces an endonucleolytic cleavage near the 5'UTR of host mRNAs, targeting them for degradation. Viral mRNAs are not susceptible to nsp1-mediated endonucleolytic RNA cleavage thanks to the presence of a 5'-end leader sequence and are therefore protected from degradation. By suppressing host gene expression, nsp1 facilitates efficient viral gene expression in infected cells and evasion from host immune response (PubMed:23035226). May disrupt nuclear pore function by binding and displacing host NUP93 (PubMed:30943371). {ECO:0000269|PubMed:23035226, ECO:0000269|PubMed:30943371}.

Function: [Non-structural protein 2]: 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. {ECO:0000269|PubMed:19640993}.

Function: [Non-structural protein 3]: Responsible for the cleavages located at the N-terminus of the replicase polyprotein. In addition, PL-PRO possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates (PubMed:17692280). Plays a role in host membrane rearrangement that leads to creation of cytoplasmic double-membrane vesicles (DMV) necessary for viral replication. Nsp3, nsp4 and nsp6 together are sufficient to form DMV (PubMed:24410069). Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF3 (PubMed:19369340, PubMed:24622840). Prevents also host NF- kappa-B signaling. {ECO:0000269|PubMed:16271890, ECO:0000269|PubMed:17692280, ECO:0000269|PubMed:19369340, ECO:0000269|PubMed:24622840, ECO:0000303|PubMed:24410069}.

Function: [Non-structural protein 4]: Plays a role in host membrane rearrangement that leads to creation of cytoplasmic double-membrane vesicles (DMV) necessary for viral replication. Alone appears incapable to induce membrane curvature, but together with nsp3 is able to induce paired membranes. Nsp3, nsp4 and nsp6 together are sufficient to form DMV. {ECO:0000269|PubMed:23943763, ECO:0000303|PubMed:24410069}.

Function: [3C-like proteinase]: Cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-|-[SGACN]. Also able to bind an ADP-ribose-1''- phosphate (ADRP). May cleave host ATP6V1G1 thereby modifying host vacuoles intracellular pH. {ECO:0000255|PROSITE-ProRule:PRU00772, ECO:0000269|PubMed:16226257}.

Function: [Non-structural protein 6]: Plays a role in host membrane rearrangement that leads to creation of cytoplasmic double-membrane vesicles (DMV) necessary for viral replication. Nsp3, nsp4 and nsp6 together are sufficient to form DMV (PubMed:24410069). Plays a role in the initial induction of autophagosomes from host reticulum endoplasmic. Later, limits the expansion of these phagosomes that are no longer able to deliver viral components to lysosomes (PubMed:24991833). {ECO:0000269|PubMed:24991833, ECO:0000303|PubMed:24410069}.

Function: [Non-structural protein 7]: 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. {ECO:0000269|PubMed:22039154}.

Function: [Non-structural protein 8]: 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. {ECO:0000269|PubMed:22039154}.

Function: [Non-structural protein 9]: May participate in viral replication by acting as a ssRNA-binding protein. {ECO:0000269|PubMed:19153232}.

Function: [Non-structural protein 10]: Plays a pivotal role in viral transcription by stimulating both nsp14 3'-5' exoribonuclease and nsp16 2'-O-methyltransferase activities. Therefore plays an essential role in viral mRNAs cap methylation. {ECO:0000269|PubMed:22635272}.

Function: [RNA-directed RNA polymerase]: Responsible for replication and transcription of the viral RNA genome. {ECO:0000269|PubMed:22791111}.

Function: [Helicase]: 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. {ECO:0000269|PubMed:12917423, ECO:0000269|PubMed:22615777}.

Function: [Proofreading exoribonuclease]: Enzyme possessing two different activities: an exoribonuclease activity acting on both ssRNA and dsRNA in a 3' to 5' direction and a N7-guanine methyltransferase activity (PubMed:16549795, PubMed:20421945, PubMed:22635272). Acts as a proofreading exoribonuclease for RNA replication, thereby lowering The sensitivity of the virus to RNA mutagens (PubMed:23966862, PubMed:29511076, PubMed:21593585). {ECO:0000269|PubMed:16549795, ECO:0000269|PubMed:20421945, ECO:0000269|PubMed:21593585, ECO:0000269|PubMed:22635272, ECO:0000269|PubMed:23966862, ECO:0000269|PubMed:29511076}.

Function: [Uridylate-specific endoribonuclease]: Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond.

Function: [2'-O-methyltransferase]: Methyltransferase that mediates mRNA cap 2'-O-ribose methylation to the 5'-cap structure of viral mRNAs. N7-methyl guanosine cap is a prerequisite for binding of nsp16. Therefore plays an essential role in viral mRNAs cap methylation which is essential to evade immune system. {ECO:0000269|PubMed:18417574, ECO:0000269|PubMed:20421945, ECO:0000305}.

Catalytic activity: [RNA-directed RNA polymerase]: Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:11128, Rhea:RHEA- COMP:11129, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:83400; EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539, ECO:0000269|PubMed:14561748};

Catalytic activity: [Helicase]: Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.12;

Catalytic activity: [Helicase]: Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13;

Catalytic activity: [3C-like proteinase]: Reaction=TSAVLQ-|-SGFRK-NH(2) and SGVTFQ-|-GKFKK the two peptides corresponding to the two self-cleavage sites of the SARS 3C-like proteinase are the two most reactive peptide substrates. The enzyme exhibits a strong preference for substrates containing Gln at P1 position and Leu at P2 position.; EC=3.4.22.69; Evidence={ECO:0000269|PubMed:14561748};

Catalytic activity: [Non-structural protein 3]: Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76- residue protein attached to proteins as an intracellular targeting signal).; EC=3.4.19.12; Evidence={ECO:0000269|PubMed:17692280};

Activity regulation: [Proofreading exoribonuclease]: Inhibited by Remdesivir (GS-5734). {ECO:0000269|PubMed:29511076}.

Biophysicochemical properties: Kinetic parameters: KM=1.15 mM for peptide TSAVLQSGFRK-NH(2) {ECO:0000269|PubMed:14561748}; KM=0.58 mM for peptide SGVTFQGKFKK {ECO:0000269|PubMed:14561748}; KM=1.44 mM for peptide ATVRLQAGNAT {ECO:0000269|PubMed:14561748}; Note=The kinetic parameters are studied for the 3C-like proteinase domain.; pH dependence: Optimum pH is 7.0 for 3C-like proteinase activity. {ECO:0000269|PubMed:14561748};

Subunit: [Non-structural protein 2]: Interacts with host PHB and PHB2. {ECO:0000269|PubMed:19640993}.

Subunit: [Non-structural protein 4]: Interacts with PL-PRO and nsp6. {ECO:0000269|PubMed:21345958}.

Subunit: [3C-like proteinase]: Exists as monomer and homodimer. Only the homodimer shows catalytic activity. {ECO:0000269|PubMed:14561748, ECO:0000269|PubMed:15507456}.

Subunit: [Non-structural protein 7]: Eight copies of nsp7 and eight copies of nsp8 assemble to form a heterohexadecamer dsRNA-encircling ring structure. {ECO:0000269|PubMed:16228002}.

Subunit: [Non-structural protein 8]: Interacts with ORF6 protein. {ECO:0000269|PubMed:17532020}.

Subunit: [Non-structural protein 9]: Homodimerizes. {ECO:0000269|PubMed:19153232}.

Subunit: [Non-structural protein 10]: Forms a dodecamer and interacts with nsp14 and nsp16; these interactions enhance nsp14 and nsp16 enzymatic activities. {ECO:0000269|PubMed:16873247, ECO:0000269|PubMed:18827877, ECO:0000269|PubMed:22635272}.

Subunit: [Proofreading exoribonuclease]: Interacts (via N-terminus) with DDX1. {ECO:0000269|PubMed:20573827}.

Subcellular location: [Non-structural protein 3]: Host membrane; Multi- pass membrane protein. Host cytoplasm {ECO:0000269|PubMed:23943763}.

Subcellular location: [Non-structural protein 4]: Host membrane; Multi- pass membrane protein. Host cytoplasm. Note=Localizes in virally- induced cytoplasmic double-membrane vesicles. {ECO:0000269|PubMed:17855519, ECO:0000269|PubMed:21345958, ECO:0000269|PubMed:23943763}.

Subcellular location: [Non-structural protein 6]: Host membrane {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}.

Subcellular location: [Non-structural protein 7]: Host cytoplasm, host perinuclear region {ECO:0000250}. Note=nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes (By similarity). {ECO:0000250}.

Subcellular location: [Non-structural protein 8]: Host cytoplasm, host perinuclear region {ECO:0000269|PubMed:17532020}. Note=nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes (By similarity). {ECO:0000250}.

Subcellular location: [Non-structural protein 9]: Host cytoplasm, host perinuclear region {ECO:0000250}. Note=nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes (By similarity). {ECO:0000250}.

Subcellular location: [Non-structural protein 10]: Host cytoplasm, host perinuclear region {ECO:0000250}. Note=nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes (By similarity). {ECO:0000250}.

Subcellular location: [Helicase]: Host endoplasmic reticulum-Golgi intermediate compartment {ECO:0000305}. Note=The helicase interacts with the N protein in membranous complexes and colocalizes with sites of synthesis of new viral RNA. {ECO:0000250}.

Subcellular location: [Uridylate-specific endoribonuclease]: Host cytoplasm, host perinuclear region {ECO:0000250}.

Domain: The hydrophobic domains (HD) could mediate the membrane association of the replication complex and thereby alter the architecture of the host cell membrane.

Ptm: Specific enzymatic cleavages in vivo by its own proteases yield mature proteins (PubMed:32083638). 3CL-PRO and PL-PRO proteinases are autocatalytically processed (By similarity). {ECO:0000250, ECO:0000269|PubMed:32083638}.

Mass spectrometry: [Non-structural protein 8]: Mass=21871; Method=Electrospray; Evidence={ECO:0000269|PubMed:32083638};

Mass spectrometry: [Non-structural protein 9]: Mass=12403; Method=Electrospray; Evidence={ECO:0000269|PubMed:32083638};

Mass spectrometry: [Non-structural protein 10]: Mass=14974; Method=Electrospray; Evidence={ECO:0000269|PubMed:32083638};

Miscellaneous: [Isoform Replicase polyprotein 1ab]: Produced by -1 ribosomal frameshifting at the 1a-1b genes boundary.

Similarity: Belongs to the coronaviruses polyprotein 1ab family. {ECO:0000305}.

Sequence caution: Sequence=AAP13440.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=AAP41036.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=AAP82975.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=AAP97881.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=AAQ01596.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=AAQ01608.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Severe acute respiratory syndrome coronavirus (SARS-CoV).
Taxonomy:		Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes; Nidovirales; Cornidovirineae; Coronaviridae; Orthocoronavirinae; Betacoronavirus; Sarbecovirus.



Function:		[Isoform Replicase polyprotein 1ab]: Multifunctional protein involved in the transcription and replication of viral RNAs. Contains the proteinases responsible for the cleavages of the polyprotein.



Function:		[Host translation inhibitor nsp1]: Inhibits host translation by interacting with the 40S ribosomal subunit. The nsp1-40S ribosome complex further induces an endonucleolytic cleavage near the 5'UTR of host mRNAs, targeting them for degradation. Viral mRNAs are not susceptible to nsp1-mediated endonucleolytic RNA cleavage thanks to the presence of a 5'-end leader sequence and are therefore protected from degradation. By suppressing host gene expression, nsp1 facilitates efficient viral gene expression in infected cells and evasion from host immune response (PubMed:23035226). May disrupt nuclear pore function by binding and displacing host NUP93 (PubMed:30943371). {ECO:0000269\|PubMed:23035226, ECO:0000269\|PubMed:30943371}.



Function:		[Non-structural protein 2]: 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. {ECO:0000269\|PubMed:19640993}.



Function:		[Non-structural protein 3]: Responsible for the cleavages located at the N-terminus of the replicase polyprotein. In addition, PL-PRO possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates (PubMed:17692280). Plays a role in host membrane rearrangement that leads to creation of cytoplasmic double-membrane vesicles (DMV) necessary for viral replication. Nsp3, nsp4 and nsp6 together are sufficient to form DMV (PubMed:24410069). Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF3 (PubMed:19369340, PubMed:24622840). Prevents also host NF- kappa-B signaling. {ECO:0000269\|PubMed:16271890, ECO:0000269\|PubMed:17692280, ECO:0000269\|PubMed:19369340, ECO:0000269\|PubMed:24622840, ECO:0000303\|PubMed:24410069}.



Function:		[Non-structural protein 4]: Plays a role in host membrane rearrangement that leads to creation of cytoplasmic double-membrane vesicles (DMV) necessary for viral replication. Alone appears incapable to induce membrane curvature, but together with nsp3 is able to induce paired membranes. Nsp3, nsp4 and nsp6 together are sufficient to form DMV. {ECO:0000269\|PubMed:23943763, ECO:0000303\|PubMed:24410069}.



Function:		[3C-like proteinase]: Cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-\|-[SGACN]. Also able to bind an ADP-ribose-1''- phosphate (ADRP). May cleave host ATP6V1G1 thereby modifying host vacuoles intracellular pH. {ECO:0000255\|PROSITE-ProRule:PRU00772, ECO:0000269\|PubMed:16226257}.



Function:		[Non-structural protein 6]: Plays a role in host membrane rearrangement that leads to creation of cytoplasmic double-membrane vesicles (DMV) necessary for viral replication. Nsp3, nsp4 and nsp6 together are sufficient to form DMV (PubMed:24410069). Plays a role in the initial induction of autophagosomes from host reticulum endoplasmic. Later, limits the expansion of these phagosomes that are no longer able to deliver viral components to lysosomes (PubMed:24991833). {ECO:0000269\|PubMed:24991833, ECO:0000303\|PubMed:24410069}.



Function:		[Non-structural protein 7]: 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. {ECO:0000269\|PubMed:22039154}.



Function:		[Non-structural protein 8]: 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. {ECO:0000269\|PubMed:22039154}.



Function:		[Non-structural protein 9]: May participate in viral replication by acting as a ssRNA-binding protein. {ECO:0000269\|PubMed:19153232}.



Function:		[Non-structural protein 10]: Plays a pivotal role in viral transcription by stimulating both nsp14 3'-5' exoribonuclease and nsp16 2'-O-methyltransferase activities. Therefore plays an essential role in viral mRNAs cap methylation. {ECO:0000269\|PubMed:22635272}.



Function:		[RNA-directed RNA polymerase]: Responsible for replication and transcription of the viral RNA genome. {ECO:0000269\|PubMed:22791111}.



Function:		[Helicase]: 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. {ECO:0000269\|PubMed:12917423, ECO:0000269\|PubMed:22615777}.



Function:		[Proofreading exoribonuclease]: Enzyme possessing two different activities: an exoribonuclease activity acting on both ssRNA and dsRNA in a 3' to 5' direction and a N7-guanine methyltransferase activity (PubMed:16549795, PubMed:20421945, PubMed:22635272). Acts as a proofreading exoribonuclease for RNA replication, thereby lowering The sensitivity of the virus to RNA mutagens (PubMed:23966862, PubMed:29511076, PubMed:21593585). {ECO:0000269\|PubMed:16549795, ECO:0000269\|PubMed:20421945, ECO:0000269\|PubMed:21593585, ECO:0000269\|PubMed:22635272, ECO:0000269\|PubMed:23966862, ECO:0000269\|PubMed:29511076}.



Function:		[Uridylate-specific endoribonuclease]: Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond.



Function:		[2'-O-methyltransferase]: Methyltransferase that mediates mRNA cap 2'-O-ribose methylation to the 5'-cap structure of viral mRNAs. N7-methyl guanosine cap is a prerequisite for binding of nsp16. Therefore plays an essential role in viral mRNAs cap methylation which is essential to evade immune system. {ECO:0000269\|PubMed:18417574, ECO:0000269\|PubMed:20421945, ECO:0000305}.


Catalytic activity:		[RNA-directed RNA polymerase]: Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:11128, Rhea:RHEA- COMP:11129, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:83400; EC=2.7.7.48; Evidence={ECO:0000255\|PROSITE-ProRule:PRU00539, ECO:0000269\|PubMed:14561748};
Catalytic activity:		[Helicase]: Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.12;
Catalytic activity:		[Helicase]: Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13;
Catalytic activity:		[3C-like proteinase]: Reaction=TSAVLQ-\|-SGFRK-NH(2) and SGVTFQ-\|-GKFKK the two peptides corresponding to the two self-cleavage sites of the SARS 3C-like proteinase are the two most reactive peptide substrates. The enzyme exhibits a strong preference for substrates containing Gln at P1 position and Leu at P2 position.; EC=3.4.22.69; Evidence={ECO:0000269\|PubMed:14561748};
Catalytic activity:		[Non-structural protein 3]: Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76- residue protein attached to proteins as an intracellular targeting signal).; EC=3.4.19.12; Evidence={ECO:0000269\|PubMed:17692280};
Activity regulation:		[Proofreading exoribonuclease]: Inhibited by Remdesivir (GS-5734). {ECO:0000269\|PubMed:29511076}.
Biophysicochemical properties:		Kinetic parameters: KM=1.15 mM for peptide TSAVLQSGFRK-NH(2) {ECO:0000269\|PubMed:14561748}; KM=0.58 mM for peptide SGVTFQGKFKK {ECO:0000269\|PubMed:14561748}; KM=1.44 mM for peptide ATVRLQAGNAT {ECO:0000269\|PubMed:14561748}; Note=The kinetic parameters are studied for the 3C-like proteinase domain.; pH dependence: Optimum pH is 7.0 for 3C-like proteinase activity. {ECO:0000269\|PubMed:14561748};
Subunit:		[Non-structural protein 2]: Interacts with host PHB and PHB2. {ECO:0000269\|PubMed:19640993}.
Subunit:		[Non-structural protein 4]: Interacts with PL-PRO and nsp6. {ECO:0000269\|PubMed:21345958}.
Subunit:		[3C-like proteinase]: Exists as monomer and homodimer. Only the homodimer shows catalytic activity. {ECO:0000269\|PubMed:14561748, ECO:0000269\|PubMed:15507456}.
Subunit:		[Non-structural protein 7]: Eight copies of nsp7 and eight copies of nsp8 assemble to form a heterohexadecamer dsRNA-encircling ring structure. {ECO:0000269\|PubMed:16228002}.
Subunit:		[Non-structural protein 8]: Interacts with ORF6 protein. {ECO:0000269\|PubMed:17532020}.
Subunit:		[Non-structural protein 9]: Homodimerizes. {ECO:0000269\|PubMed:19153232}.
Subunit:		[Non-structural protein 10]: Forms a dodecamer and interacts with nsp14 and nsp16; these interactions enhance nsp14 and nsp16 enzymatic activities. {ECO:0000269\|PubMed:16873247, ECO:0000269\|PubMed:18827877, ECO:0000269\|PubMed:22635272}.
Subunit:		[Proofreading exoribonuclease]: Interacts (via N-terminus) with DDX1. {ECO:0000269\|PubMed:20573827}.
Subcellular location:		[Non-structural protein 3]: Host membrane; Multi- pass membrane protein. Host cytoplasm {ECO:0000269\|PubMed:23943763}.
Subcellular location:		[Non-structural protein 4]: Host membrane; Multi- pass membrane protein. Host cytoplasm. Note=Localizes in virally- induced cytoplasmic double-membrane vesicles. {ECO:0000269\|PubMed:17855519, ECO:0000269\|PubMed:21345958, ECO:0000269\|PubMed:23943763}.
Subcellular location:		[Non-structural protein 6]: Host membrane {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}.
Subcellular location:		[Non-structural protein 7]: Host cytoplasm, host perinuclear region {ECO:0000250}. Note=nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes (By similarity). {ECO:0000250}.
Subcellular location:		[Non-structural protein 8]: Host cytoplasm, host perinuclear region {ECO:0000269\|PubMed:17532020}. Note=nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes (By similarity). {ECO:0000250}.
Subcellular location:		[Non-structural protein 9]: Host cytoplasm, host perinuclear region {ECO:0000250}. Note=nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes (By similarity). {ECO:0000250}.
Subcellular location:		[Non-structural protein 10]: Host cytoplasm, host perinuclear region {ECO:0000250}. Note=nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes (By similarity). {ECO:0000250}.
Subcellular location:		[Helicase]: Host endoplasmic reticulum-Golgi intermediate compartment {ECO:0000305}. Note=The helicase interacts with the N protein in membranous complexes and colocalizes with sites of synthesis of new viral RNA. {ECO:0000250}.
Subcellular location:		[Uridylate-specific endoribonuclease]: Host cytoplasm, host perinuclear region {ECO:0000250}.
Domain:		The hydrophobic domains (HD) could mediate the membrane association of the replication complex and thereby alter the architecture of the host cell membrane.
Ptm:		Specific enzymatic cleavages in vivo by its own proteases yield mature proteins (PubMed:32083638). 3CL-PRO and PL-PRO proteinases are autocatalytically processed (By similarity). {ECO:0000250, ECO:0000269\|PubMed:32083638}.
Mass spectrometry:		[Non-structural protein 8]: Mass=21871; Method=Electrospray; Evidence={ECO:0000269\|PubMed:32083638};
Mass spectrometry:		[Non-structural protein 9]: Mass=12403; Method=Electrospray; Evidence={ECO:0000269\|PubMed:32083638};
Mass spectrometry:		[Non-structural protein 10]: Mass=14974; Method=Electrospray; Evidence={ECO:0000269\|PubMed:32083638};
Miscellaneous:		[Isoform Replicase polyprotein 1ab]: Produced by -1 ribosomal frameshifting at the 1a-1b genes boundary.
Similarity:		Belongs to the coronaviruses polyprotein 1ab family. {ECO:0000305}.
Sequence caution:		Sequence=AAP13440.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=AAP41036.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=AAP82975.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=AAP97881.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=AAQ01596.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=AAQ01608.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};