UniProt functional annotation for P0C6U3



	UniProt functional annotation for P0C6U3

UniProt code: P0C6U3.

Organism: Human coronavirus HKU1 (isolate N1) (HCoV-HKU1).

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

Function: The papain-like proteinase 1 (PL1-PRO) and papain-like proteinase 2 (PL2-PRO) are responsible for the cleavages located at the N-terminus of the replicase polyprotein. In addition, PLP2 possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF-3 (By similarity). {ECO:0000250}.

Function: [3C-like proteinase]: Responsible for the majority of cleavages as it cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-|- [SGACN]. Inhibited by the substrate-analog Cbz-Val-Asn-Ser-Thr-Leu-Gln- CMK. Also contains an ADP-ribose-1''-phosphate (ADRP)-binding function (By similarity). {ECO:0000255|PROSITE-ProRule:PRU00772}.

Function: Nsp7-nsp8 hexadecamer may possibly confer processivity to the polymerase, maybe by binding to dsRNA or by producing primers utilized by the latter. {ECO:0000250}.

Function: Nsp9 is a ssRNA-binding protein. {ECO:0000250}.

Function: [Non-structural protein 1]: binds to the 40S ribosomal subunit and inhibits host translation. The nsp1-40S ribosome complex further induces an endonucleolytic cleavage near the 5'UTR of host mRNAs, targeting them for degradation. By suppressing host gene expression, nsp1 facilitates efficient viral gene expression in infected cells and evasion from host immune response (By similarity). {ECO:0000250}.

Catalytic activity: 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;

Catalytic activity: 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;

Subunit: 3CL-PRO exists as monomer and homodimer. Eight copies of nsp7 and eight copies of nsp8 assemble to form a heterohexadecamer. Nsp9 is a dimer. Nsp10 forms a dodecamer (By similarity). {ECO:0000250}.

Subcellular location: [Non-structural protein 3]: Host membrane {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}.

Subcellular location: [Non-structural protein 4]: Host membrane {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}.

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.

Subcellular location: [Non-structural protein 8]: 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.

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.

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.

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. 3CL-PRO and PL-PRO proteinases are autocatalytically processed (By similarity). {ECO:0000250}.

Miscellaneous: Isolate N1 belongs to genotype A.

Miscellaneous: [Isoform Replicase polyprotein 1a]: Produced by conventional translation.

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

Annotations taken from UniProtKB at the EBI.


Organism:		Human coronavirus HKU1 (isolate N1) (HCoV-HKU1).
Taxonomy:		Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes; Nidovirales; Cornidovirineae; Coronaviridae; Orthocoronavirinae; Betacoronavirus; Embecovirus.



Function:		The papain-like proteinase 1 (PL1-PRO) and papain-like proteinase 2 (PL2-PRO) are responsible for the cleavages located at the N-terminus of the replicase polyprotein. In addition, PLP2 possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF-3 (By similarity). {ECO:0000250}.



Function:		[3C-like proteinase]: Responsible for the majority of cleavages as it cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-\|- [SGACN]. Inhibited by the substrate-analog Cbz-Val-Asn-Ser-Thr-Leu-Gln- CMK. Also contains an ADP-ribose-1''-phosphate (ADRP)-binding function (By similarity). {ECO:0000255\|PROSITE-ProRule:PRU00772}.



Function:		Nsp7-nsp8 hexadecamer may possibly confer processivity to the polymerase, maybe by binding to dsRNA or by producing primers utilized by the latter. {ECO:0000250}.



Function:		Nsp9 is a ssRNA-binding protein. {ECO:0000250}.



Function:		[Non-structural protein 1]: binds to the 40S ribosomal subunit and inhibits host translation. The nsp1-40S ribosome complex further induces an endonucleolytic cleavage near the 5'UTR of host mRNAs, targeting them for degradation. By suppressing host gene expression, nsp1 facilitates efficient viral gene expression in infected cells and evasion from host immune response (By similarity). {ECO:0000250}.


Catalytic activity:		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;
Catalytic activity:		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;
Subunit:		3CL-PRO exists as monomer and homodimer. Eight copies of nsp7 and eight copies of nsp8 assemble to form a heterohexadecamer. Nsp9 is a dimer. Nsp10 forms a dodecamer (By similarity). {ECO:0000250}.
Subcellular location:		[Non-structural protein 3]: Host membrane {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}.
Subcellular location:		[Non-structural protein 4]: Host membrane {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}.
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.
Subcellular location:		[Non-structural protein 8]: 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.
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.
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.
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. 3CL-PRO and PL-PRO proteinases are autocatalytically processed (By similarity). {ECO:0000250}.
Miscellaneous:		Isolate N1 belongs to genotype A.
Miscellaneous:		[Isoform Replicase polyprotein 1a]: Produced by conventional translation.
Similarity:		Belongs to the coronaviruses polyprotein 1ab family. {ECO:0000305}.