Replicase polyprotein 1ab
Also known as: rep
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)
- PF13087 AAA_12, PF16251 bCoV_NAB, PF11501 bCoV_NSP1, PF12379 bCoV_NSP3_N, PF12124 bCoV_SUD_C, PF11633 bCoV_SUD_M, PF06471 CoV_ExoN, PF06460 CoV_Methyltr_2, PF09401 CoV_NSP10, PF20631 CoV_NSP13_1B, PF20633 CoV_NSP13_stalk, PF20632 CoV_NSP13_ZBD, PF19215 CoV_NSP15_C, PF19216 CoV_NSP15_M, PF19219 CoV_NSP15_N, 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, PF06478 CoV_RPol_N, PF01661 Macro, PF05409 Peptidase_C30, PF00680 RdRP_1
- InterPro
- (+)RNA_virus_helicase_core_dom, a/bCoV_NSP1_glob, AV_NSP11N_COV_NSP15M, bCoV_NSP1_C, Coronavir_polyprotein_1ab, CoV_NSP15_M, CoV_NSP15_N, CoV_NSP2_C, CoV_NSP2_M, COV_NSP3_3ECTO, CoV_NSP3_C, CoV_NSP3_Y, CoV_NSP4_C, CoV_NSP4_N, DNA/RNA_pol_sf, DNA2/NAM7-like_C, DPUP_SUD_C_bCoV, EndoU-like, Macro_dom, Macro_dom-like, Macro_X_NSP3-like, N7_MTase_CoV, NendoU_nidovirus, NIRAN, NIV_2_O_MTASE, NIV_EXON, NSP10_sf_CoV, NSP12_IF_CoV, NSP13_1B_dom_CoV, NSP13_stalk_CoV, NSP13_ZBD_CoV, NSP13_ZBD_CoV-like, NSP14_betaCoV, NSP14_CoV, NSP15_alpha_betaCoV_N, NSP15_M_alpha_beta_CoV, NSP15_middle_sf, NSP15_N_CoV, NSP15_NendoU_CoV, NSP16_CoV-like, 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_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, P-loop_NTPase, 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, RdRp_CoV, RdRp_N_CoV, RdRp_SARS-CoV-like, RNA-dir_pol_C, RNA-dir_pol_PSvirus, RNA_synth_NSP10_CoV, SAM-dependent_MTases_sf
- Functional cluster
- Viral Structural & Replication Proteins
Experimental structures · PDB · 2779
- 5R7Y X-ray 1.65A
- 5R7Z X-ray 1.59A
- 5R80 X-ray 1.93A
- 5R81 X-ray 1.95A
- 5R82 X-ray 1.31A
- 5R83 X-ray 1.58A
- 5R84 X-ray 1.83A
- 5R8T X-ray 1.27A
- 5RE4 X-ray 1.88A
- 5RE5 X-ray 2.07A
- 5RE6 X-ray 1.87A
- 5RE7 X-ray 1.79A
- … and 2767 more
A predicted model is available from AlphaFold.
Gene Ontology · 44
- GO:0062243 double membrane vesicle viral factory outer membrane
- GO:0044167 host cell endoplasmic reticulum membrane
- GO:0044172 host cell endoplasmic reticulum-Golgi intermediate compartment
- GO:0044174 host cell endosome
- GO:0044177 host cell Golgi apparatus
- GO:0042025 host cell nucleus
- GO:0044220 host cell perinuclear region of cytoplasm
- GO:0000175 3'-5'-RNA exonuclease activity
- GO:0043139 5'-3' DNA helicase activity
- GO:0032574 5'-3' RNA helicase activity
- GO:0005524 ATP binding
- GO:0016887 ATP hydrolysis activity
- GO:0005507 copper ion binding
- GO:0004843 cysteine-type deubiquitinase activity
- GO:0004197 cysteine-type endopeptidase activity
- GO:0002151 G-quadruplex RNA binding
- GO:0019785 ISG15-specific peptidase activity
- GO:0008289 lipid binding
- GO:0016829 lyase activity
- GO:0004483 methyltransferase cap1 activity
- GO:0004482 mRNA 5'-cap (guanine-N7-)-methyltransferase activity
- GO:0004484 mRNA guanylyltransferase activity
- GO:0008242 omega peptidase activity
- GO:0044600 protein guanylyltransferase activity
- GO:0003723 RNA binding
- GO:0016892 RNA endonuclease activity producing 3'-phosphomonoesters, hydrolytic mechanism
- GO:0003968 RNA-directed RNA polymerase activity
- GO:0003727 single-stranded RNA binding
- GO:0008270 zinc ion binding
- GO:0006351 DNA-templated transcription
- 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:0039723 symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of TBK1 activity
- GO:0039657 symbiont-mediated suppression of host gene expression
- GO:0039579 symbiont-mediated suppression of host ISG15-protein conjugation
- GO:0085034 symbiont-mediated suppression of host NF-kappaB cascade
- GO:0039722 symbiont-mediated suppression of host toll-like receptor signaling pathway
- GO:0039502 symbiont-mediated suppression of host type I interferon-mediated signaling pathway
- GO:0019082 viral protein processing
- GO:0039694 viral RNA genome replication
- GO:0075523 viral translational frameshifting
Drugs targeting this protein · 3
- GALIDESIVIR inhibitor
- REMDESIVIR inhibitor
- RO-0622 inhibitor
Related proteins · sequence + function similarity
- Replicase polyprotein 1a 1.00
- Replicase polyprotein 1ab 0.96
- Replicase polyprotein 1a 0.96
- Replicase polyprotein 1a 0.95
- Replicase polyprotein 1ab 0.95
- Replicase polyprotein 1a 0.94
- Replicase polyprotein 1ab 0.94
- Replicase polyprotein 1ab 0.92
- Replicase polyprotein 1a 0.92
- Replicase polyprotein 1ab 0.82
- Replicase polyprotein 1a 0.82
- Replicase polyprotein 1ab 0.82
Co-cited proteins · studied together in the literature
- Replicase polyprotein 1a 35 shared papers
- tRNA (guanine(26)-N(2))-dimethyltransferase 3 shared papers
- Staphylococcal nuclease domain-containing protein 1 1 shared papers
- Nucleoprotein 5 shared papers
- ORF7a protein 3 shared papers
- Antiviral innate immune response effector IFIT1 1 shared papers
- Zinc finger FYVE domain-containing protein 1 1 shared papers
- F-box only protein 22 1 shared papers
- ORF3a protein 3 shared papers
- Envelope small membrane protein 2 shared papers
- ORF6 protein 3 shared papers
- ORF8 protein 3 shared papers
Literature · 44 cited papers
- Human coronavirus 3CL protease manipulates host protein STIM1 to facilitate immune evasion. Proc. Natl. Acad. Sci. U.S.A. · 2025
- The SARS-CoV-2 3CL protease inhibits pyroptosis through the cleavage of gasdermin D. Virol. Sin. · 2025
- Recognition and cleavage of human tRNA methyltransferase TRMT1 by the SARS-CoV-2 main protease. Elife · 2025
- E3 ubiquitin ligase FBXO22 inhibits SARS-CoV-2 replication via promoting proteasome-dependent degradation of NSP5. J. Med. Virol. · 2024
- Proteolytic cleavage and inactivation of the TRMT1 tRNA modification enzyme by SARS-CoV-2 main protease. Elife · 2024
- SND1 binds SARS-CoV-2 negative-sense RNA and promotes viral RNA synthesis through NSP9. Cell · 2023
- Recurrent Loss of Macrodomain Activity in Host Immunity and Viral Proteins. Pathogens · 2023
- SARS-CoV-2 main protease Nsp5 cleaves and inactivates human tRNA methyltransferase TRMT1. J. Mol. Cell Biol. · 2023
- SARS-CoV-2 Uses Nonstructural Protein 16 To Evade Restriction by IFIT1 and IFIT3. J. Virol. · 2023
- Crystal structures and fragment screening of SARS-CoV-2 NSP14 reveal details of exoribonuclease activation and mRNA capping and provide starting points for antiviral drug development. Nucleic Acids Res. · 2023
- Nsp1 proteins of human coronaviruses HCoV-OC43 and SARS-CoV2 inhibit stress granule formation. PLoS Pathog. · 2022
- Nsp16 shields SARS-CoV-2 from efficient MDA5 sensing and IFIT1-mediated restriction. EMBO Rep. · 2022
- … and 32 more in the literature graph
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