Molecular Target Synopsis
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rep (P0C6X7) - Overview - Molecular Target Synopsis

Protein


rep, Replicase polyprotein 1ab
Enzyme Classification 3.4.19.12
UniProt P0C6X7

Also Known as R1AB_CVHSA, rep

Replicase polyprotein 1ab: Multifunctional protein involved in the transcription and replication of viral RNAs. Contains the proteinases responsible for the cleavages of the polyprotein., 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., 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., Papain-like proteinase: 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. Participates together with nsp4 in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication. Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF3. Prevents also host NF-kappa-B signaling., Non-structural protein 4: Participates in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication., Proteinase 3CL-PRO: Ccleaves 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)., Non-structural protein 6: 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., 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., 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., Non-structural protein 9: May participate in viral replication by acting as a ssRNA-binding protein., 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., RNA-directed RNA polymerase: Responsible for replication and transcription of the viral RNA genome., 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., Guanine-N7 methyltransferase: 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., Uridylate-specific endoribonuclease: Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond., 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. Nsp2 interacts with host PHB and PHB2. 3CL-PRO exists as monomer and homodimer. Nsp4 interacts with PL-PRO and nsp6. Only the homodimer shows catalytic activity. Eight copies of nsp7 and eight copies of nsp8 assemble to form a heterohexadecamer dsRNA-encircling ring structure. Nsp9 is a dimer. Nsp10 forms a dodecamer and interacts with nsp14 and nsp16; these interactions enhance nsp14 and nsp16 enzymatic activities. Nsp14 interacts (via N-terminus) with DDX1.

5N5O
STRUCTURE OF SARS CORONAVIRUS MAIN PROTEASE IN COMPLEX WITH THE ALPHA- KETOAMIDE (S)-N-BENZYL-3-((S)-2-CINNAMAMIDO-3- CYCLOPROPYLPROPANAMIDO)-2-OXO-4-((S)-2-OXOPYRROLIDIN-3-YL)BUTANAMIDE (CINNAMOYL-CYCLOPROPYLALANINE-GLNLACTAM-CO-CO-NH-BENZYL)
RCSB/PDB
Inspect Structure
See all 3D Structures for rep

Isoforms / Transcripts (Protein Coding)


Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
7073P0C6X7-1

Sub-cellular localization


UniProt: rep is active in the following subcellular-locations: host cytoplasm, host endoplasmic reticulum-golgi intermediate compartment, host membrane, host perinuclear region.
GO terms: rep is active in the following subcellular-locations: cytoplasmic viral factory, host cell endoplasmic reticulum-Golgi intermediate compartment, 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 rep has gain in 0 cell-lines, loss in 0 cell-lines and no signal in 0 cell-lines. (see details)

3D Structures


For rep there are:
69 structures (125 chains) solved
23 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


rep has been screened with 174 compounds (220 bioactivities), 14 compounds have bioactivities that show binding affinity of <= 500nM (17 bioactivities). (see details)