| comment |
-
FUNCTION Multifunctional protein involved in the transcription and replication of viral RNAs. Contains the proteinases responsible for the cleavages of the polyprotein.FUNCTION 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).FUNCTION May play a role in the modulation of host cell survival signaling pathway by interacting with host PHB and PHB2 (PubMed:19640993). Indeed, these two proteins play a role in maintaining the functional integrity of the mitochondria and protecting cells from various stresses (PubMed:19640993).FUNCTION 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 (PubMed:23943763). Nsp3, nsp4 and nsp6 together are sufficient to form DMV (PubMed:23943763, 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). Also prevents host NF-kappa-B signaling (PubMed:19369340, PubMed:24622840).FUNCTION Plays a role in host membrane rearrangement that leads to creation of cytoplasmic double-membrane vesicles (DMV) necessary for viral replication (PubMed:23943763, PubMed:24410069). Alone appears incapable to induce membrane curvature, but together with nsp3 is able to induce paired membranes (PubMed:23943763). Nsp3, nsp4 and nsp6 together are sufficient to form DMV (PubMed:23943763, PubMed:24410069).FUNCTION 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.FUNCTION Plays a role in host membrane rearrangement that leads to creation of cytoplasmic double-membrane vesicles (DMV) necessary for viral replication (PubMed:23943763). Nsp3, nsp4 and nsp6 together are sufficient to form DMV (PubMed:23943763, PubMed:24410069). Plays a role in the initial induction of autophagosomes from host endoplasmic reticulum. Later, limits the expansion of these phagosomes that are no longer able to deliver viral components to lysosomes (PubMed:24991833).FUNCTION 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.FUNCTION 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.FUNCTION Catalytic subunit of viral RNA capping enzyme which catalyzes the RNA guanylyltransferase reaction for genomic and sub-genomic RNAs. The kinase-like NiRAN domain of NSP12 transfers RNA to the amino terminus of NSP9, forming a covalent RNA-protein intermediate. Subsequently, the NiRAN domain transfers RNA to GDP, forming the core cap structure GpppA-RNA. The NSP14 and NSP16 methyltransferases then add methyl groups to form functional cap structures.FUNCTION 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.CATALYTIC ACTIVITY TSAVLQ-|-SGFRK-NH2 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.CATALYTIC ACTIVITY 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).CATALYTIC ACTIVITY a 5'-end diphospho-ribonucleoside in mRNA + GTP + H(+) = a 5'-end (5'-triphosphoguanosine)-ribonucleoside in mRNA + diphosphateCOFACTOR The kinetic parameters are studied for the 3C-like proteinase domain.SUBUNIT Interacts with host PHB and PHB2.SUBUNIT Interacts with papain-like protease and non-structural protein 6.SUBUNIT Exists as monomer and homodimer. Only the homodimer shows catalytic activity.SUBUNIT Eight copies of nsp7 and eight copies of nsp8 assemble to form a heterohexadecamer dsRNA-encircling ring structure.SUBUNIT Eight copies of nsp7 and eight copies of nsp8 assemble to form a heterohexadecamer dsRNA-encircling ring structure (PubMed:16228002). Interacts with ORF6 protein (PubMed:17532020).SUBUNIT Homodimer.SUBUNIT Homododecamer.INTERACTION Localizes in virally-induced cytoplasmic double-membrane vesicles.SUBCELLULAR LOCATION nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes.SUBCELLULAR LOCATION nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes.SUBCELLULAR LOCATION nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes.SUBCELLULAR LOCATION nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes.ALTERNATIVE PRODUCTS Isoform replicase polyprotein 1ab is produced by -1 ribosomal frameshifting at the 1a-1b genes boundary. Isoform replicase polyprotein 1a is produced by conventional translation.DOMAIN The hydrophobic region HD1 probably mediates the membrane association of the replication complex.DOMAIN The hydrophobic region HD2 probably mediates the membrane association of the replication complex.DOMAIN The hydrophobic region HD3 probably mediates the membrane association of the replication complex.PTM Specific enzymatic cleavages in vivo by its own proteases yield mature proteins (PubMed:12917450, PubMed:15331731, PubMed:15564471, PubMed:16306590, PubMed:32083638). 3C-like proteinase nsp5 liberates nsps 6-11 from the polyprotein (PubMed:32083638). Papain-like and 3C-like proteinases are autocatalytically processed.MASS SPECTROMETRY Belongs to the coronaviruses polyprotein 1ab family.CAUTION Isolates SZ3 and SZ16 have been isolated from Paguma larvata and are described as SARS-like in literature.
|
