P0C6Y0 (R1AB_CVMJH) Reviewed, UniProtKB/Swiss-Prot
Last modified
May 1, 2013.
Version 43.
History...
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: Replicase polyprotein 1ab Short name=pp1ab Alternative name(s): ORF1ab polyprotein Cleaved into the following 15 chains:
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| Gene names |
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| Organism | Murine coronavirus (strain JHM) (MHV-JHM) (Murine hepatitis virus) [Complete proteome] | ||||
| Taxonomic identifier | 11144 [NCBI] | ||||
| Taxonomic lineage | Viruses › ssRNA positive-strand viruses, no DNA stage › Nidovirales › Coronaviridae › Coronavirinae › Betacoronavirus › ![]() | ||||
| Virus host | Mus musculus (Mouse) [TaxID: 10090] |
Protein attributes
| Sequence length | 7180 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny virion RNA as well as proteinases responsible for the cleavage of the polyprotein into functional products. The papain-like proteinase 1 (PL1-PRO) and papain-like proteinase 2 (PL2-PRO) are responsible for the cleavages located at the N-terminus of the replicase polyprotein. In addition, PLP2 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 By similarity. 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. Also contains an ADP-ribose-1''-phosphate (ADRP)-binding function By similarity. The helicase which contains a zinc finger structure displays RNA and DNA duplex-unwinding activities with 5' to 3' polarity. ATPase activity is strongly stimulated by poly(U), poly(dT), poly(C), poly(dA), but not by poly(G) By similarity. The exoribonuclease acts on both ssRNA and dsRNA in a 3' to 5' direction By similarity. Nsp7-nsp8 hexadecamer may possibly confer processivity to the polymerase, maybe by binding to dsRNA or by producing primers utilized by the latter By similarity. Nsp9 is a ssRNA-binding protein By similarity. NendoU is a Mn2+-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond By similarity. |
| Catalytic activity | Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1). ATP + H2O = ADP + phosphate. TSAVLQ-|-SGFRK-NH2 and SGVTFQ-|-GKFKK the two peptides corresponding to the two self-cleavage sites of the SARS 3C-like proteinase are the two most reactive peptide substrates. The enzyme exhibits a strong preference for substrates containing Gln at P1 position and Leu at P2 position. Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal). |
| Subunit structure | 3CL-PRO exists as monomer and homodimer. Eight copies of nsp7 and eight copies of nsp8 assemble to form a heterohexadecamer. Nsp9 is a dimer. Nsp10 forms a dodecamer By similarity. |
| Subcellular location | Non-structural protein 3: Host membrane; Multi-pass membrane protein Potential Ref.6. Non-structural protein 4: Host membrane; Multi-pass membrane protein Potential Ref.6. Non-structural protein 6: Host membrane; Multi-pass membrane protein Potential Ref.6. Non-structural protein 7: Host cytoplasm › host perinuclear region By similarity Ref.6. Note: nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes By similarity. Ref.6 Non-structural protein 8: Host cytoplasm › host perinuclear region By similarity Ref.6. Note: nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes By similarity. Ref.6 Non-structural protein 9: Host cytoplasm › host perinuclear region By similarity Ref.6. Note: nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes By similarity. Ref.6 Non-structural protein 10: Host cytoplasm › host perinuclear region By similarity Ref.6. Note: nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes By similarity. Ref.6 Helicase: Host endoplasmic reticulum-Golgi intermediate compartment Potential. Note: The helicase interacts with the N protein in membranous complexes and colocalizes with sites of synthesis of new viral RNA By similarity. Ref.6 Uridylate-specific endoribonuclease: Host cytoplasm › host perinuclear region By similarity Ref.6. |
| Domain | The hydrophobic domains (HD) could mediate the membrane association of the replication complex and thereby alter the architecture of the host cell membrane. |
| Post-translational modification | Specific enzymatic cleavages in vivo by its own proteases yield mature proteins. 3CL-PRO and PL-PRO proteinases are autocatalytically processed By similarity. |
| Sequence similarities | Belongs to the coronaviruses polyprotein 1ab family. Contains 1 (+)RNA virus helicase ATP-binding domain. Contains 1 (+)RNA virus helicase C-terminal domain. Contains 1 CV MBD (coronavirus metal-binding) domain. Contains 1 Macro domain. Contains 2 peptidase C16 domains. Contains 1 peptidase C30 domain. Contains 1 RdRp catalytic domain. |
| Sequence caution | The sequence AAA46457.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence AAA46457.1 differs from that shown. Reason: Frameshift at positions 690, 915, 1529, 2069 and 3316. The sequence AAA46458.2 differs from that shown. Reason: Erroneous gene model prediction. |
Ontologies
Alternative products
| This entry describes 2 isoforms produced by ribosomal frameshifting. [Align] [Select] | ||||||
| Isoform Replicase polyprotein 1ab (identifier: P0C6Y0-1) Also known as: pp1ab; This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Note: Produced by -1 ribosomal frameshifting at the 1a-1b genes boundary. | ||||||
| Isoform Replicase polyprotein 1a (identifier: P0C6V1-1) Also known as: pp1a; ORF1a polyprotein; The sequence of this isoform can be found in the external entry P0C6V1. Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly. | ||||||
| Note: Produced by conventional translation. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 247 | 247 | Non-structural protein 1 Probable | PRO_0000037354 | |||||
| Chain | 248 – 832 | 585 | Non-structural protein 2 Probable | PRO_0000037355 | |||||
| Chain | 833 – 2840 | 2008 | Non-structural protein 3 Probable | PRO_0000037356 | |||||
| Chain | 2841 – 3336 | 496 | Non-structural protein 4 Probable | PRO_0000037357 | |||||
| Chain | 3337 – 3639 | 303 | 3C-like proteinase Probable | PRO_0000037358 | |||||
| Chain | 3640 – 3927 | 288 | Non-structural protein 6 Probable | PRO_0000037359 | |||||
| Chain | 3928 – 4019 | 92 | Non-structural protein 7 Probable | PRO_0000037360 | |||||
| Chain | 4020 – 4213 | 194 | Non-structural protein 8 | PRO_0000037361 | |||||
| Chain | 4214 – 4323 | 110 | Non-structural protein 9 Probable | PRO_0000037362 | |||||
| Chain | 4324 – 4460 | 137 | Non-structural protein 10 Probable | PRO_0000037363 | |||||
| Chain | 4461 – 5388 | 928 | RNA-directed RNA polymerase Probable | PRO_0000037364 | |||||
| Chain | 5389 – 5988 | 600 | Helicase Probable | PRO_0000037365 | |||||
| Chain | 5989 – 6507 | 519 | Exoribonuclease By similarity | PRO_0000037366 | |||||
| Chain | 6508 – 6881 | 374 | Uridylate-specific endoribonuclease By similarity | PRO_0000037367 | |||||
| Chain | 6882 – 7180 | 299 | Putative 2'-O-methyl transferase By similarity | PRO_0000037368 | |||||
Regions | |||||||||
| Transmembrane | 2228 – 2248 | 21 | Helical; Potential | ||||||
| Transmembrane | 2289 – 2309 | 21 | Helical; Potential | ||||||
| Transmembrane | 2320 – 2340 | 21 | Helical; Potential | ||||||
| Transmembrane | 2403 – 2423 | 21 | Helical; Potential | ||||||
| Transmembrane | 2445 – 2465 | 21 | Helical; Potential | ||||||
| Transmembrane | 2846 – 2866 | 21 | Helical; Potential | ||||||
| Transmembrane | 3099 – 3119 | 21 | Helical; Potential | ||||||
| Transmembrane | 3121 – 3141 | 21 | Helical; Potential | ||||||
| Transmembrane | 3153 – 3173 | 21 | Helical; Potential | ||||||
| Transmembrane | 3180 – 3200 | 21 | Helical; Potential | ||||||
| Transmembrane | 3205 – 3225 | 21 | Helical; Potential | ||||||
| Transmembrane | 3648 – 3668 | 21 | Helical; Potential | ||||||
| Transmembrane | 3678 – 3698 | 21 | Helical; Potential | ||||||
| Transmembrane | 3705 – 3725 | 21 | Helical; Potential | ||||||
| Transmembrane | 3748 – 3768 | 21 | Helical; Potential | ||||||
| Transmembrane | 3775 – 3795 | 21 | Helical; Potential | ||||||
| Transmembrane | 3802 – 3822 | 21 | Helical; Potential | ||||||
| Transmembrane | 3846 – 3866 | 21 | Helical; Potential | ||||||
| Domain | 1083 – 1320 | 238 | Peptidase C16 1 | ||||||
| Domain | 1321 – 1481 | 161 | Macro | ||||||
| Domain | 1677 – 1936 | 260 | Peptidase C16 2 | ||||||
| Domain | 3337 – 3639 | 303 | Peptidase C30 | ||||||
| Domain | 5068 – 5230 | 163 | RdRp catalytic | ||||||
| Domain | 5389 – 5472 | 84 | CV MBD | ||||||
| Domain | 5644 – 5825 | 182 | (+)RNA virus helicase ATP-binding | ||||||
| Domain | 5826 – 6003 | 178 | (+)RNA virus helicase C-terminal | ||||||
| Zinc finger | 1197 – 1225 | 29 | C4-type 1 | ||||||
| Zinc finger | 1793 – 1829 | 37 | C4-type 2 | ||||||
| Zinc finger | 4397 – 4413 | 17 | By similarity | ||||||
| Zinc finger | 4439 – 4452 | 14 | By similarity | ||||||
| Nucleotide binding | 5669 – 5676 | 8 | ATP By similarity | ||||||
| Region | 2228 – 2465 | 238 | HD1 | ||||||
| Region | 2846 – 3225 | 380 | HD2 | ||||||
| Region | 3648 – 3866 | 219 | HD3 | ||||||
Sites | |||||||||
| Active site | 1120 | 1 | For PL1-PRO activity By similarity | ||||||
| Active site | 1271 | 1 | For PL1-PRO activity By similarity | ||||||
| Active site | 1715 | 1 | For PL2-PRO activity By similarity | ||||||
| Active site | 1872 | 1 | For PL2-PRO activity By similarity | ||||||
| Active site | 3377 | 1 | For 3CL-PRO activity By similarity | ||||||
| Active site | 3481 | 1 | For 3CL-PRO activity By similarity | ||||||
| Site | 247 – 248 | 2 | Cleavage; by PL1-PRO Probable | ||||||
| Site | 832 – 833 | 2 | Cleavage; by PL1-PRO Probable | ||||||
| Site | 2840 – 2841 | 2 | Cleavage; by PL2-PRO Probable | ||||||
| Site | 3336 – 3337 | 2 | Cleavage; by 3CL-PRO Probable | ||||||
| Site | 3639 – 3640 | 2 | Cleavage; by 3CL-PRO Probable | ||||||
| Site | 3927 – 3928 | 2 | Cleavage; by 3CL-PRO Probable | ||||||
| Site | 4019 – 4020 | 2 | Cleavage; by 3CL-PRO Probable | ||||||
| Site | 4213 – 4214 | 2 | Cleavage; by 3CL-PRO Probable | ||||||
| Site | 4323 – 4324 | 2 | Cleavage; by 3CL-PRO Probable | ||||||
| Site | 4460 – 4461 | 2 | Cleavage; by 3CL-PRO Probable | ||||||
| Site | 5388 – 5389 | 2 | Cleavage; by 3CL-PRO Probable | ||||||
| Site | 5988 – 5989 | 2 | Cleavage; by 3CL-PRO Probable | ||||||
| Site | 6507 – 6508 | 2 | Cleavage; by 3CL-PRO Probable | ||||||
| Site | 6881 – 6882 | 2 | Cleavage; by 3CL-PRO Probable | ||||||
Experimental info | |||||||||
| Mutagenesis | 2835 | 1 | F → A: No processing between p210 and peptide HD2. Ref.5 | ||||||
| Mutagenesis | 2836 | 1 | S → A: No effect. Ref.5 | ||||||
| Mutagenesis | 2837 | 1 | L → A: No effect. Ref.5 | ||||||
| Mutagenesis | 2838 | 1 | K → A: No effect. Ref.5 | ||||||
| Mutagenesis | 2838 | 1 | K → N: No effect. Ref.5 | ||||||
| Mutagenesis | 2839 | 1 | G → A: Partial processing between p210 and peptide HD2. Ref.5 | ||||||
| Mutagenesis | 2839 | 1 | G → N: No processing between p210 and peptide HD2. Ref.5 | ||||||
| Mutagenesis | 2839 | 1 | G → V: No processing between p210 and peptide HD2. Ref.5 | ||||||
| Mutagenesis | 2840 | 1 | G → A: No processing between p210 and peptide HD2. Ref.5 | ||||||
| Mutagenesis | 2840 | 1 | G → N: No processing between p210 and peptide HD2. Ref.5 | ||||||
| Mutagenesis | 2840 | 1 | G → V: No processing between p210 and peptide HD2. Ref.5 | ||||||
| Mutagenesis | 2841 | 1 | A → N: No effect. Ref.5 | ||||||
| Mutagenesis | 2842 | 1 | V → N or M: No effect. Ref.5 | ||||||
| Mutagenesis | 2846 | 1 | V → M: No effect. Ref.5 | ||||||
Sequences
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References
| [1] | "The complete sequence (22 kilobases) of murine coronavirus gene 1 encoding the putative proteases and RNA polymerase." Lee H.-J., Shieh C.-K., Gorbalenya A.E., Koonin E.V., la Monica N., Tuler J., Bagdzhardzhyan A., Lai M.M.C. Virology 180:567-582(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. |
| [2] | "Sequence and translation of the murine coronavirus 5'-end genomic RNA reveals the N-terminal structure of the putative RNA polymerase." Soe L.H., Shieh C.-K., Baker S.C., Chang M.F., Lai M.M.C. J. Virol. 61:3968-3976(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-595. |
| [3] | "Mouse hepatitis virus strain A59 RNA polymerase gene ORF 1a: heterogeneity among MHV strains." Bonilla P.J., Gorbalenya A.E., Weiss S.R. Virology 198:736-740(1994) [PubMed] [Europe PMC] [Abstract] Cited for: SEQUENCE REVISION. |
| [4] | "Murine coronavirus gene 1 polyprotein contains an autoproteolytic activity." Baker S.C., La Monica N., Shieh C.K., Lai M.M. Adv. Exp. Med. Biol. 276:283-289(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1021-1326. |
| [5] | "Identification of the murine coronavirus MP1 cleavage site recognized by papain-like proteinase 2." Kanjanahaluethai A., Jukneliene D., Baker S.C. J. Virol. 77:7376-7382(2003) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN, MUTAGENESIS OF PHE-2835; SER-2836; LEU-2837; LYS-2838; GLY-2839; GLY-2840; ALA-2841; VAL-2842 AND VAL-2846. |
| [6] | "Processing of the coronavirus MHV-JHM polymerase polyprotein: identification of precursors and proteolytic products spanning 400 kilodaltons of ORF1a." Schiller J.J., Kanjanahaluethai A., Baker S.C. Virology 242:288-302(1998) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN, SUBCELLULAR LOCATION. |
| [7] | "Conservation of substrate specificities among coronavirus main proteases." Hegyi A., Ziebuhr J. J. Gen. Virol. 83:595-599(2002) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | M55148 Genomic RNA. Translation: AAA46457.1. Sequence problems. M55148 Genomic RNA. Translation: AAA46458.2. Sequence problems. M18040 Genomic RNA. Translation: AAA46466.1. S51684 Genomic RNA. Translation: AAB19566.1. |
| PIR | RRIHM2. A36815. VFIHJH. B36815. |
3D structure databases | |
| ProteinModelPortal | P0C6Y0. |
| SMR | P0C6Y0. Positions 4055-4205, 4329-4453, 6508-6876. |
| ModBase | Search... |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
Family and domain databases | |
| InterPro | IPR027351. (+)RNA_virus_helicase_core_dom. IPR002589. A1pp. IPR022570. Coronavirus_NSP1. IPR009461. Coronavirus_NSP13. IPR027352. CV_MBD_dom. IPR009466. NSP11. IPR014828. NSP7. IPR014829. NSP8. IPR014822. NSP9. IPR002705. Pept_C30/C16_sub. IPR008740. Peptidase_C30. IPR013016. Peptidase_C30/C16. IPR001205. RNA-dir_pol_C. IPR007094. RNA-dir_pol_PSvirus. IPR009469. RNA_pol_N_coronovir. IPR018995. RNA_synth_NSP10_coronavirus. IPR009003. Trypsin-like_Pept_dom. IPR014827. Viral_protease. [Graphical view] |
| Pfam | PF06478. Corona_RPol_N. 1 hit. PF11963. DUF3477. 2 hits. PF01661. Macro. 1 hit. PF09401. NSP10. 1 hit. PF06471. NSP11. 1 hit. PF06460. NSP13. 1 hit. PF08716. nsp7. 1 hit. PF08717. nsp8. 1 hit. PF08710. nsp9. 1 hit. PF01831. Peptidase_C16. 1 hit. PF05409. Peptidase_C30. 1 hit. PF00680. RdRP_1. 1 hit. PF08715. Viral_protease. 1 hit. [Graphical view] |
| SMART | SM00506. A1pp. 1 hit. [Graphical view] |
| SUPFAM | SSF101816. Nsp9. 1 hit. SSF50494. Pept_Ser_Cys. 1 hit. SSF144246. SSF144246. 1 hit. |
| PROSITE | PS51653. CV_MBD. 1 hit. PS51442. M_PRO. 1 hit. PS51154. MACRO. 1 hit. PS51124. PEPTIDASE_C16. 2 hits. PS51657. PSRV_HELICASE. 1 hit. PS50507. RDRP_SSRNA_POS. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Entry information
| Entry name | R1AB_CVMJH | ||||||||
| Accession | Primary (citable) accession number: P0C6Y0 Secondary accession number(s): P19751 Q90045 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Viral Protein Annotation Program | ||||||||
Relevant documents
| Peptidase families Classification of peptidase families and list of entries |
| SIMILARITY comments Index of protein domains and families |

Clusters with
