Replicase polyprotein 1a

Function

Multifunctional protein involved in the transcription and replication of viral RNAs. Contains the proteinases responsible for the cleavages of the polyprotein.

Classification

Family (Pfam)

PF16251 bCoV_NAB, PF11501 bCoV_NSP1, PF12379 bCoV_NSP3_N, PF12124 bCoV_SUD_C, PF11633 bCoV_SUD_M, PF09401 CoV_NSP10, PF19211 CoV_NSP2_N, PF19218 CoV_NSP3_C, PF16348 CoV_NSP4_C, PF19217 CoV_NSP4_N, PF19213 CoV_NSP6, PF08716 CoV_NSP7, PF08717 CoV_NSP8, PF08710 CoV_NSP9, PF08715 CoV_peptidase, PF01661 Macro, PF05409 Peptidase_C30

InterPro

a/bCoV_NSP1_glob, bCoV_NSP1_C, CoV_NSP2_C, CoV_NSP2_M, COV_NSP3_3ECTO, CoV_NSP3_C, CoV_NSP3_Y, CoV_NSP4_C, CoV_NSP4_N, DPUP_SUD_C_bCoV, Macro_dom, Macro_dom-like, Macro_X_NSP3-like, NSP10_sf_CoV, NSP1_glob_bCoV, NSP1_glob_sf_bCoV, NSP2_N_CoV, NSP2_SARS-CoV-like, NSP3_bCoV, NSP3_G2M_bCoV, NSP3_N_bCoV, NSP3_NAB_bCoV, NSP3_NAB_bCoV_sf, NSP3_PL2pro_sf_bCoV, NSP3_SUD-M_sf_bCoV, NSP3_SUD-N_bCoV, NSP3_SUD-N_SARS-CoV, NSP3_SUD-N_sf_bCoV, NSP3_Ubl1_dom_CoV, Nsp3_Ubl2_dom_CoV, NSP3A-like, NSP4_C_sf_CoV, NSP6_betaCoV, NSP6_CoV, NSP7_CoV, NSP7_sf_CoV, NSP8_CoV, NSP8_sf_CoV, NSP9_CoV, NSP9_sf_CoV, Peptidase_C16_CoV, Peptidase_C30_CoV, Peptidase_C30_dom3_CoV, Peptidase_S1_PA, Peptidase_S1_PA_chymotrypsin, PLpro_N_sf_CoV, PLpro_palm_finger_dom_CoV, PLpro_thumb_sf_CoV, RNA_synth_NSP10_CoV

Functional cluster

Viral Structural & Replication Proteins

Experimental structures · PDB · 139

• 1Q2W X-ray 1.86A
• 1QZ8 X-ray 2.70A
• 1UJ1 X-ray 1.90A
• 1UK2 X-ray 2.20A
• 1UK3 X-ray 2.40A
• 1UK4 X-ray 2.50A
• 1UW7 X-ray 2.80A
• 1WOF X-ray 2.00A
• 1YSY NMR
• 1Z1I X-ray 2.80A
• 1Z1J X-ray 2.80A
• 2A5A X-ray 2.08A
• … and 127 more

A predicted model is available from AlphaFold.

Gene Ontology · 31

• GO:0062243 double membrane vesicle viral factory outer membrane
• GO:0044165 host cell endoplasmic reticulum
• GO:0044174 host cell endosome
• GO:0044177 host cell Golgi apparatus
• GO:0044220 host cell perinuclear region of cytoplasm
• GO:0004843 cysteine-type deubiquitinase activity
• GO:0004197 cysteine-type endopeptidase activity
• GO:0004519 endonuclease activity
• GO:0002151 G-quadruplex RNA binding
• GO:0042802 identical protein binding
• GO:1990380 K48-linked deubiquitinase activity
• GO:0061578 K63-linked deubiquitinase activity
• GO:0016829 lyase activity
• GO:0008168 methyltransferase activity
• GO:0004484 mRNA guanylyltransferase activity
• GO:0008242 omega peptidase activity
• GO:0003968 RNA-directed RNA polymerase activity
• GO:0003727 single-stranded RNA binding
• GO:0008270 zinc ion binding
• GO:0032259 methylation
• GO:0006508 proteolysis
• GO:0039520 symbiont-mediated activation of host autophagy
• GO:0039595 symbiont-mediated degradation of host mRNA
• GO:0039648 symbiont-mediated perturbation of host ubiquitin-like protein modification
• GO:0039548 symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of IRF3 activity
• GO:0039657 symbiont-mediated suppression of host gene expression
• GO:0039579 symbiont-mediated suppression of host ISG15-protein conjugation
• GO:0039502 symbiont-mediated suppression of host type I interferon-mediated signaling pathway
• GO:0019079 viral genome replication
• GO:0019082 viral protein processing
• GO:0075523 viral translational frameshifting

Drugs targeting this protein · 1

• NIRMATRELVIR inhibitor

Related proteins · sequence + function similarity

• Replicase polyprotein 1a 0.96
• Replicase polyprotein 1ab 0.96
• Replicase polyprotein 1a 0.94
• Replicase polyprotein 1ab 0.94
• Replicase polyprotein 1ab 0.94
• Replicase polyprotein 1a 0.94
• Replicase polyprotein 1ab 0.92
• Replicase polyprotein 1a 0.92
• Replicase polyprotein 1ab 0.86
• Replicase polyprotein 1a 0.86
• Replicase polyprotein 1ab 0.85
• Replicase polyprotein 1a 0.85

Co-cited proteins · studied together in the literature

• Replicase polyprotein 1ab 43 shared papers
• Envelope small membrane protein 8 shared papers
• ORF6 protein 5 shared papers
• Membrane protein 7 shared papers
• Nucleoprotein 8 shared papers
• ORF9b protein 6 shared papers
• Spike glycoprotein 7 shared papers
• Nuclear pore complex protein Nup93 1 shared papers
• ORF3b protein 4 shared papers
• ORF8b protein 4 shared papers
• ORF8a protein 3 shared papers
• Protein non-structural 7b 3 shared papers

Literature · 43 cited papers

• Processing of the SARS-CoV pp1a/ab nsp7-10 region. Biochem. J. · 2020
• SARS coronavirus protein nsp1 disrupts localization of Nup93 from the nuclear pore complex. Biochem. Cell Biol. · 2019
• Coronavirus NSP6 restricts autophagosome expansion. Autophagy · 2014
• SARS coronavirus papain-like protease inhibits the type I interferon signaling pathway through interaction with the STING-TRAF3-TBK1 complex. Protein Cell · 2014
• Untangling membrane rearrangement in the nidovirales. DNA Cell Biol. · 2014
• Severe acute respiratory syndrome coronavirus nonstructural proteins 3, 4, and 6 induce double-membrane vesicles. MBio · 2013
• Severe acute respiratory syndrome coronavirus protein nsp1 is a novel eukaryotic translation inhibitor that represses multiple steps of translation initiation. J. Virol. · 2012
• RNA 3'-end mismatch excision by the severe acute respiratory syndrome coronavirus nonstructural protein nsp10/nsp14 exoribonuclease complex. Proc. Natl. Acad. Sci. U.S.A. · 2012
• SARS coronavirus nsp1 protein induces template-dependent endonucleolytic cleavage of mRNAs: viral mRNAs are resistant to nsp1-induced RNA cleavage. PLoS Pathog. · 2011
• The SARS-coronavirus nsp7+nsp8 complex is a unique multimeric RNA polymerase capable of both de novo initiation and primer extension. Nucleic Acids Res. · 2012
• Mobility and interactions of coronavirus nonstructural protein 4. J. Virol. · 2011
• Severe acute respiratory syndrome coronavirus nonstructural protein 2 interacts with a host protein complex involved in mitochondrial biogenesis and intracellular signaling. J. Virol. · 2009
• … and 31 more in the literature graph