FEATURES

FAMILY

DESCRIPTION

Also known as R1A_SARS, ORF1a. Multifunctional protein involved in the transcription and replication of viral RNAs. Contains the proteinases responsible for the cleavages of the polyprotein., 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)., 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)., 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:24410069, PubMed:23943763). 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 (PubMed:19369340, PubMed:24622840)., 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)., 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., 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 reticulum endoplasmic. Later, limits the expansion of these phagosomes that are no longer able to deliver viral components to lysosomes (PubMed:24991833)., 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., 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., 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., Plays a pivotal role in viral transcription by stimulating both nsp14 3'-5' exoribonuclease and nsp16 Interacts with host PHB and PHB2.

EXTERNAL LINKS

ORF1a

Replicase polyprotein 1a

ORF1a

Molecular Synopsis