Molecular Target Synopsis
Overview
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(P0C6U8) - Overview - Molecular Target Synopsis

Protein


, Replicase polyprotein 1a
Enzyme Classification 3.4.19.12
UniProt P0C6U8

Also Known as R1A_CVHSA

The papain-like proteinase (PL-PRO) is responsible for the cleavages located at the N-terminus of 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. Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF-3., The main proteinase 3CL-PRO is 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 (By similarity). Also contains an ADP-ribose-1''-phosphate (ADRP)-binding function., Nsp7-nsp8 hexadecamer may possibly confer processivity to the polymerase, maybe by binding to dsRNA or by producing primers utilized by the latter., Nsp9 is a ssRNA-binding protein., 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. 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. Eight copies of nsp7 and eight copies of nsp8 assemble to form a heterohexadecamer. Nsp9 is a dimer. Nsp10 forms a dodecamer.

5Y3Q
CRYSTAL STRUCTURE OF SARS CORONAVIRUS PAPAIN-LIKE PROTEASE CONJUGATED WITH BETA-MERCAPTOETHANOL
RCSB/PDB
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Isoforms / Transcripts (Protein Coding)


Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
4382P0C6U8-1

Sub-cellular localization


UniProt: is active in the following subcellular-locations: host cytoplasm, host membrane, host perinuclear region.
GO terms: is active in the following subcellular-locations: cytoplasmic viral factory, host cell membrane, host cell perinuclear region of cytoplasm, integral component of membrane.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project has gain in 0 cell-lines, loss in 0 cell-lines and no signal in 0 cell-lines. (see details)

3D Structures


For there are:
66 structures (136 chains) solved
17 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


has been screened with 204 compounds (334 bioactivities), 12 compounds have bioactivities that show binding affinity of <= 500nM (14 bioactivities). (see details)