R1A_CVMJH
ID R1A_CVMJH Reviewed; 4474 AA.
AC P0C6V1; P19751;
DT 10-JUN-2008, integrated into UniProtKB/Swiss-Prot.
DT 10-JUN-2008, sequence version 1.
DT 03-AUG-2022, entry version 91.
DE RecName: Full=Replicase polyprotein 1a;
DE Short=pp1a;
DE AltName: Full=ORF1a polyprotein;
DE Contains:
DE RecName: Full=Non-structural protein 1;
DE Short=nsp1;
DE AltName: Full=p28;
DE Contains:
DE RecName: Full=Non-structural protein 2;
DE Short=nsp2;
DE AltName: Full=p65;
DE Contains:
DE RecName: Full=Non-structural protein 3;
DE Short=nsp3;
DE EC=3.4.19.12;
DE EC=3.4.22.69;
DE AltName: Full=PL1-PRO/PL2-PRO;
DE AltName: Full=PL1/PL2;
DE AltName: Full=Papain-like proteinases 1/2;
DE AltName: Full=p210;
DE Contains:
DE RecName: Full=Non-structural protein 4;
DE Short=nsp4;
DE AltName: Full=Peptide HD2;
DE AltName: Full=p44;
DE Contains:
DE RecName: Full=3C-like proteinase;
DE Short=3CL-PRO;
DE Short=3CLp;
DE EC=3.4.22.-;
DE AltName: Full=M-PRO;
DE AltName: Full=nsp5;
DE AltName: Full=p27;
DE Contains:
DE RecName: Full=Non-structural protein 6;
DE Short=nsp6;
DE Contains:
DE RecName: Full=Non-structural protein 7;
DE Short=nsp7;
DE AltName: Full=p10;
DE Contains:
DE RecName: Full=Non-structural protein 8;
DE Short=nsp8;
DE AltName: Full=p22;
DE Contains:
DE RecName: Full=Non-structural protein 9;
DE Short=nsp9;
DE AltName: Full=p12;
DE Contains:
DE RecName: Full=Non-structural protein 10;
DE Short=nsp10;
DE AltName: Full=Growth factor-like peptide;
DE Short=GFL;
DE AltName: Full=p15;
DE Contains:
DE RecName: Full=Non-structural protein 11;
DE Short=nsp11;
GN ORFNames=1a;
OS Murine coronavirus (strain JHM) (MHV-JHM) (Murine hepatitis virus).
OC Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes;
OC Nidovirales; Cornidovirineae; Coronaviridae; Orthocoronavirinae;
OC Betacoronavirus; Embecovirus.
OX NCBI_TaxID=11144;
OH NCBI_TaxID=10090; Mus musculus (Mouse).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=1846489; DOI=10.1016/0042-6822(91)90071-i;
RA Lee H.-J., Shieh C.-K., Gorbalenya A.E., Koonin E.V., la Monica N.,
RA Tuler J., Bagdzhardzhyan A., Lai M.M.C.;
RT "The complete sequence (22 kilobases) of murine coronavirus gene 1 encoding
RT the putative proteases and RNA polymerase.";
RL Virology 180:567-582(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-595.
RX PubMed=2824826; DOI=10.1128/jvi.61.12.3968-3976.1987;
RA Soe L.H., Shieh C.-K., Baker S.C., Chang M.F., Lai M.M.C.;
RT "Sequence and translation of the murine coronavirus 5'-end genomic RNA
RT reveals the N-terminal structure of the putative RNA polymerase.";
RL J. Virol. 61:3968-3976(1987).
RN [3]
RP SEQUENCE REVISION.
RX PubMed=8291254; DOI=10.1006/viro.1994.1088;
RA Bonilla P.J., Gorbalenya A.E., Weiss S.R.;
RT "Mouse hepatitis virus strain A59 RNA polymerase gene ORF 1a: heterogeneity
RT among MHV strains.";
RL Virology 198:736-740(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1021-1326.
RX PubMed=1966414; DOI=10.1007/978-1-4684-5823-7_39;
RA Baker S.C., La Monica N., Shieh C.K., Lai M.M.;
RT "Murine coronavirus gene 1 polyprotein contains an autoproteolytic
RT activity.";
RL Adv. Exp. Med. Biol. 276:283-289(1990).
RN [5]
RP PROTEOLYTIC PROCESSING OF POLYPROTEIN, AND MUTAGENESIS OF PHE-2835;
RP SER-2836; LEU-2837; LYS-2838; GLY-2839; GLY-2840; ALA-2841; VAL-2842 AND
RP VAL-2846.
RX PubMed=12805436; DOI=10.1128/jvi.77.13.7376-7382.2003;
RA Kanjanahaluethai A., Jukneliene D., Baker S.C.;
RT "Identification of the murine coronavirus MP1 cleavage site recognized by
RT papain-like proteinase 2.";
RL J. Virol. 77:7376-7382(2003).
RN [6]
RP PROTEOLYTIC PROCESSING OF POLYPROTEIN, AND SUBCELLULAR LOCATION.
RX PubMed=9514967; DOI=10.1006/viro.1997.9010;
RA Schiller J.J., Kanjanahaluethai A., Baker S.C.;
RT "Processing of the coronavirus MHV-JHM polymerase polyprotein:
RT identification of precursors and proteolytic products spanning 400
RT kilodaltons of ORF1a.";
RL Virology 242:288-302(1998).
RN [7]
RP PROTEOLYTIC PROCESSING OF POLYPROTEIN.
RX PubMed=11842254; DOI=10.1099/0022-1317-83-3-595;
RA Hegyi A., Ziebuhr J.;
RT "Conservation of substrate specificities among coronavirus main
RT proteases.";
RL J. Gen. Virol. 83:595-599(2002).
CC -!- FUNCTION: The papain-like proteinase 1 (PL1-PRO) and papain-like
CC proteinase 2 (PL2-PRO) are responsible for the cleavages located at the
CC N-terminus of the replicase polyprotein. In addition, PLP2 possesses a
CC deubiquitinating/deISGylating activity and processes both 'Lys-48'- and
CC 'Lys-63'-linked polyubiquitin chains from cellular substrates.
CC Antagonizes innate immune induction of type I interferon by blocking
CC the phosphorylation, dimerization and subsequent nuclear translocation
CC of host IRF-3 (By similarity). {ECO:0000250}.
CC -!- FUNCTION: [3C-like proteinase]: Responsible for the majority of
CC cleavages as it cleaves the C-terminus of replicase polyprotein at 11
CC sites. Recognizes substrates containing the core sequence [ILMVF]-Q-|-
CC [SGACN]. Inhibited by the substrate-analog Cbz-Val-Asn-Ser-Thr-Leu-Gln-
CC CMK. Also contains an ADP-ribose-1''-phosphate (ADRP)-binding function
CC (By similarity). {ECO:0000255|PROSITE-ProRule:PRU00772}.
CC -!- FUNCTION: Nsp7-nsp8 hexadecamer may possibly confer processivity to the
CC polymerase, maybe by binding to dsRNA or by producing primers utilized
CC by the latter. {ECO:0000250}.
CC -!- FUNCTION: Nsp9 is a ssRNA-binding protein. {ECO:0000250}.
CC -!- FUNCTION: [Non-structural protein 1]: Binds to the 40S ribosomal
CC subunit and inhibits host translation. The nsp1-40S ribosome complex
CC further induces an endonucleolytic cleavage near the 5'UTR of host
CC mRNAs, targeting them for degradation. By suppressing host gene
CC expression, nsp1 facilitates efficient viral gene expression in
CC infected cells and evasion from host immune response (By similarity).
CC {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=TSAVLQ-|-SGFRK-NH2 and SGVTFQ-|-GKFKK the two peptides
CC corresponding to the two self-cleavage sites of the SARS 3C-like
CC proteinase are the two most reactive peptide substrates. The enzyme
CC exhibits a strong preference for substrates containing Gln at P1
CC position and Leu at P2 position.; EC=3.4.22.69;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide
CC and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-
CC residue protein attached to proteins as an intracellular targeting
CC signal).; EC=3.4.19.12;
CC -!- SUBUNIT: 3CL-PRO exists as monomer and homodimer. Eight copies of nsp7
CC and eight copies of nsp8 assemble to form a heterohexadecamer. Nsp9 is
CC a dimer. Nsp10 forms a dodecamer (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 3]: Host membrane
CC {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 4]: Host membrane
CC {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 6]: Host membrane
CC {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 7]: Host cytoplasm, host
CC perinuclear region {ECO:0000250}. Note=nsp7, nsp8, nsp9 and nsp10 are
CC localized in cytoplasmic foci, largely perinuclear. Late in infection,
CC they merge into confluent complexes (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 8]: Host cytoplasm, host
CC perinuclear region {ECO:0000250}. Note=nsp7, nsp8, nsp9 and nsp10 are
CC localized in cytoplasmic foci, largely perinuclear. Late in infection,
CC they merge into confluent complexes (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 9]: Host cytoplasm, host
CC perinuclear region {ECO:0000250}. Note=nsp7, nsp8, nsp9 and nsp10 are
CC localized in cytoplasmic foci, largely perinuclear. Late in infection,
CC they merge into confluent complexes (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 10]: Host cytoplasm, host
CC perinuclear region {ECO:0000250}. Note=nsp7, nsp8, nsp9 and nsp10 are
CC localized in cytoplasmic foci, largely perinuclear. Late in infection,
CC they merge into confluent complexes (By similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Ribosomal frameshifting; Named isoforms=2;
CC Name=Replicase polyprotein 1a; Synonyms=pp1a, ORF1a polyprotein;
CC IsoId=P0C6V1-1; Sequence=Displayed;
CC Name=Replicase polyprotein 1ab; Synonyms=pp1ab;
CC IsoId=P0C6Y0-1; Sequence=External;
CC -!- DOMAIN: The hydrophobic domains (HD) could mediate the membrane
CC association of the replication complex and thereby alter the
CC architecture of the host cell membrane.
CC -!- PTM: Specific enzymatic cleavages in vivo by its own proteases yield
CC mature proteins. 3CL-PRO and PL-PRO proteinases are autocatalytically
CC processed (By similarity). {ECO:0000250}.
CC -!- MISCELLANEOUS: [Isoform Replicase polyprotein 1a]: Produced by
CC conventional translation.
CC -!- SIMILARITY: Belongs to the coronaviruses polyprotein 1ab family.
CC {ECO:0000305}.
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DR EMBL; M55148; AAA46457.1; -; Genomic_RNA.
DR EMBL; M18040; AAA46466.1; -; Genomic_RNA.
DR EMBL; S51684; AAB19566.1; -; Genomic_RNA.
DR PIR; A36815; RRIHM2.
DR PIR; B36815; VFIHJH.
DR RefSeq; YP_209230.1; AC_000192.1. [P0C6V1-1]
DR SMR; P0C6V1; -.
DR MEROPS; C16.001; -.
DR MEROPS; C16.006; -.
DR MEROPS; C30.001; -.
DR BRENDA; 3.4.22.B14; 3467.
DR Proteomes; UP000007193; Genome.
DR GO; GO:0033644; C:host cell membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0044220; C:host cell perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IEA:UniProtKB-EC.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IMP:CACAO.
DR GO; GO:0008242; F:omega peptidase activity; IEA:InterPro.
DR GO; GO:0003968; F:RNA-directed 5'-3' RNA polymerase activity; IEA:InterPro.
DR GO; GO:0003727; F:single-stranded RNA binding; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0039595; P:induction by virus of catabolism of host mRNA; IEA:UniProtKB-KW.
DR GO; GO:0039520; P:induction by virus of host autophagy; IEA:UniProtKB-KW.
DR GO; GO:0039648; P:modulation by virus of host protein ubiquitination; IEA:UniProtKB-KW.
DR GO; GO:0097264; P:self proteolysis; IDA:CACAO.
DR GO; GO:0039657; P:suppression by virus of host gene expression; IEA:UniProtKB-KW.
DR GO; GO:0039579; P:suppression by virus of host ISG15-protein conjugation; IEA:UniProtKB-KW.
DR GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0039548; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of IRF3 activity; IEA:UniProtKB-KW.
DR GO; GO:0019079; P:viral genome replication; IEA:InterPro.
DR GO; GO:0019082; P:viral protein processing; IEA:InterPro.
DR CDD; cd21560; betaCoV-Nsp6; 1.
DR CDD; cd21666; betaCoV_Nsp5_Mpro; 1.
DR CDD; cd21519; cv_beta_Nsp2_MHV-like; 1.
DR CDD; cd21473; cv_Nsp4_TM; 1.
DR CDD; cd21524; DPUP_MHV_Nsp3; 1.
DR CDD; cd21467; Ubl1_cv_Nsp3_N-like; 1.
DR CDD; cd21466; Ubl2_cv_PLpro_N_Nsp3-like; 1.
DR Gene3D; 1.10.150.420; -; 1.
DR Gene3D; 1.10.1840.10; -; 1.
DR Gene3D; 1.10.8.1190; -; 2.
DR Gene3D; 1.10.8.370; -; 1.
DR Gene3D; 2.40.10.10; -; 2.
DR Gene3D; 2.40.10.250; -; 1.
DR Gene3D; 2.60.120.1680; -; 1.
DR Gene3D; 3.10.20.350; -; 1.
DR Gene3D; 3.10.20.540; -; 1.
DR Gene3D; 3.30.70.3540; -; 1.
DR Gene3D; 3.40.220.10; -; 1.
DR Gene3D; 3.40.50.11020; -; 1.
DR InterPro; IPR022570; B-CoV_A_NSP1.
DR InterPro; IPR043613; CoV_NSP2_C.
DR InterPro; IPR043611; CoV_NSP3_C.
DR InterPro; IPR032505; CoV_NSP4_C.
DR InterPro; IPR043612; CoV_NSP4_N.
DR InterPro; IPR022733; DPUP_SUD_C_bCoV.
DR InterPro; IPR002589; Macro_dom.
DR InterPro; IPR043472; Macro_dom-like.
DR InterPro; IPR036333; NSP10_sf_CoV.
DR InterPro; IPR044384; NSP2_MHV-like.
DR InterPro; IPR044381; NSP3_DPUP_MHV.
DR InterPro; IPR032592; NSP3_NAB_bCoV.
DR InterPro; IPR042570; NSP3_NAB_bCoV_sf.
DR InterPro; IPR044357; NSP3_Ubl1_dom_CoV.
DR InterPro; IPR044353; Nsp3_Ubl2_dom_CoV.
DR InterPro; IPR038083; NSP3A-like.
DR InterPro; IPR038123; NSP4_C_sf_CoV.
DR InterPro; IPR044367; NSP6_betaCoV.
DR InterPro; IPR043610; NSP6_CoV.
DR InterPro; IPR014828; NSP7_CoV.
DR InterPro; IPR037204; NSP7_sf_CoV.
DR InterPro; IPR014829; NSP8_CoV.
DR InterPro; IPR037230; NSP8_sf_CoV.
DR InterPro; IPR014822; NSP9_CoV.
DR InterPro; IPR036499; NSP9_sf_CoV.
DR InterPro; IPR002705; Pept_C30/C16_B_coronavir.
DR InterPro; IPR013016; Peptidase_C16_CoV.
DR InterPro; IPR008740; Peptidase_C30_CoV.
DR InterPro; IPR043477; Peptidase_C30_dom3_CoV.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR043177; PLpro_N_sf_CoV.
DR InterPro; IPR043503; PLpro_palm_finger_dom_CoV.
DR InterPro; IPR043178; PLpro_thumb_sf_CoV.
DR InterPro; IPR018995; RNA_synth_NSP10_CoV.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR Pfam; PF16251; bCoV_NAR; 1.
DR Pfam; PF09401; CoV_NSP10; 1.
DR Pfam; PF19212; CoV_NSP2_C; 1.
DR Pfam; PF19218; CoV_NSP3_C; 1.
DR Pfam; PF16348; CoV_NSP4_C; 1.
DR Pfam; PF19217; CoV_NSP4_N; 1.
DR Pfam; PF19213; CoV_NSP6; 1.
DR Pfam; PF08716; CoV_NSP7; 1.
DR Pfam; PF08717; CoV_NSP8; 1.
DR Pfam; PF08710; CoV_NSP9; 1.
DR Pfam; PF08715; CoV_peptidase; 1.
DR Pfam; PF11963; DUF3477; 2.
DR Pfam; PF01661; Macro; 1.
DR Pfam; PF01831; Peptidase_C16; 1.
DR Pfam; PF05409; Peptidase_C30; 1.
DR SMART; SM00506; A1pp; 1.
DR SUPFAM; SSF101816; SSF101816; 1.
DR SUPFAM; SSF140367; SSF140367; 1.
DR SUPFAM; SSF143076; SSF143076; 1.
DR SUPFAM; SSF144246; SSF144246; 1.
DR SUPFAM; SSF159936; SSF159936; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR SUPFAM; SSF52949; SSF52949; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS51963; BCOV_NSP1_C; 1.
DR PROSITE; PS51942; BCOV_NSP3C_C; 1.
DR PROSITE; PS51994; BCOV_NSP3E_G2M; 1.
DR PROSITE; PS51945; BCOV_NSP3E_NAB; 1.
DR PROSITE; PS51952; COV_EXON_MTASE_COACT; 1.
DR PROSITE; PS51962; COV_NSP1; 1.
DR PROSITE; PS51991; COV_NSP2_C; 1.
DR PROSITE; PS51990; COV_NSP2_M; 1.
DR PROSITE; PS51989; COV_NSP2_N; 1.
DR PROSITE; PS51992; COV_NSP3_Y3; 1.
DR PROSITE; PS51943; COV_NSP3A_UBL; 1.
DR PROSITE; PS51944; COV_NSP3D_UBL; 1.
DR PROSITE; PS51946; COV_NSP4C; 1.
DR PROSITE; PS51949; COV_NSP7; 1.
DR PROSITE; PS51950; COV_NSP8; 1.
DR PROSITE; PS51951; COV_NSP9_SSRNA_BD; 1.
DR PROSITE; PS51442; M_PRO; 1.
DR PROSITE; PS51154; MACRO; 1.
DR PROSITE; PS51124; PEPTIDASE_C16; 2.
PE 1: Evidence at protein level;
KW Activation of host autophagy by virus; Decay of host mRNAs by virus;
KW Eukaryotic host gene expression shutoff by virus;
KW Eukaryotic host translation shutoff by virus; Host cytoplasm;
KW Host gene expression shutoff by virus; Host membrane;
KW Host mRNA suppression by virus; Host-virus interaction; Hydrolase;
KW Inhibition of host innate immune response by virus;
KW Inhibition of host interferon signaling pathway by virus;
KW Inhibition of host IRF3 by virus; Inhibition of host ISG15 by virus;
KW Inhibition of host RLR pathway by virus; Membrane; Metal-binding;
KW Modulation of host ubiquitin pathway by viral deubiquitinase;
KW Modulation of host ubiquitin pathway by virus; Protease; Repeat;
KW Ribosomal frameshifting; RNA-binding; Thiol protease; Transmembrane;
KW Transmembrane helix; Ubl conjugation pathway; Viral immunoevasion; Zinc;
KW Zinc-finger.
FT CHAIN 1..4474
FT /note="Replicase polyprotein 1a"
FT /id="PRO_0000338290"
FT CHAIN 1..247
FT /note="Non-structural protein 1"
FT /evidence="ECO:0000305"
FT /id="PRO_0000338291"
FT CHAIN 248..832
FT /note="Non-structural protein 2"
FT /evidence="ECO:0000305"
FT /id="PRO_0000338292"
FT CHAIN 833..2840
FT /note="Non-structural protein 3"
FT /evidence="ECO:0000305"
FT /id="PRO_0000338293"
FT CHAIN 2841..3336
FT /note="Non-structural protein 4"
FT /evidence="ECO:0000305"
FT /id="PRO_0000338294"
FT CHAIN 3337..3639
FT /note="3C-like proteinase"
FT /evidence="ECO:0000305"
FT /id="PRO_0000338295"
FT CHAIN 3640..3927
FT /note="Non-structural protein 6"
FT /evidence="ECO:0000305"
FT /id="PRO_0000338296"
FT CHAIN 3928..4019
FT /note="Non-structural protein 7"
FT /evidence="ECO:0000305"
FT /id="PRO_0000338297"
FT CHAIN 4020..4213
FT /note="Non-structural protein 8"
FT /id="PRO_0000338298"
FT CHAIN 4214..4323
FT /note="Non-structural protein 9"
FT /evidence="ECO:0000305"
FT /id="PRO_0000338299"
FT CHAIN 4323..4474
FT /note="Non-structural protein 11"
FT /evidence="ECO:0000255"
FT /id="PRO_0000338301"
FT CHAIN 4324..4460
FT /note="Non-structural protein 10"
FT /evidence="ECO:0000305"
FT /id="PRO_0000338300"
FT TRANSMEM 2289..2309
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 2320..2340
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 2403..2423
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 2445..2465
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 2846..2866
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3099..3119
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3121..3141
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3153..3173
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3180..3200
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3205..3225
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3648..3668
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3678..3698
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3705..3725
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3748..3768
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3775..3795
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3802..3822
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3846..3866
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 54..196
FT /note="CoV Nsp1 globular"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01307"
FT DOMAIN 217..247
FT /note="BetaCoV Nsp1 C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01308"
FT DOMAIN 251..513
FT /note="CoV Nsp2 N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT DOMAIN 518..706
FT /note="CoV Nsp2 middle"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01334"
FT DOMAIN 726..832
FT /note="CoV Nsp2 C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01335"
FT DOMAIN 834..946
FT /note="Ubiquitin-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT DOMAIN 1083..1320
FT /note="Peptidase C16 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT DOMAIN 1321..1481
FT /note="Macro"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00490"
FT DOMAIN 1536..1608
FT /note="DPUP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01289"
FT DOMAIN 1607..1662
FT /note="Ubiquitin-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT DOMAIN 1677..1936
FT /note="Peptidase C16 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT DOMAIN 1950..2051
FT /note="Nucleic acid-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01290"
FT DOMAIN 2106..2259
FT /note="G2M"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01338"
FT DOMAIN 2737..2840
FT /note="CoV Nsp3 Y3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT DOMAIN 3239..3336
FT /note="Nsp4C"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01291"
FT DOMAIN 3337..3639
FT /note="Peptidase C30"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00772"
FT DOMAIN 3928..4016
FT /note="RdRp Nsp7 cofactor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01294"
FT DOMAIN 4017..4213
FT /note="RdRp Nsp8 cofactor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01295"
FT DOMAIN 4214..4323
FT /note="Nsp9 ssRNA-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01296"
FT DOMAIN 4324..4461
FT /note="ExoN/MTase coactivator"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT ZN_FING 1197..1225
FT /note="C4-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT ZN_FING 1793..1829
FT /note="C4-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT ZN_FING 4397..4413
FT /evidence="ECO:0000250"
FT ZN_FING 4439..4452
FT /evidence="ECO:0000250"
FT REGION 390..414
FT /note="C4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT REGION 2228..2465
FT /note="HD1"
FT REGION 2846..3225
FT /note="HD2"
FT REGION 3648..3866
FT /note="HD3"
FT ACT_SITE 1120
FT /note="For PL1-PRO activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT ACT_SITE 1271
FT /note="For PL1-PRO activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT ACT_SITE 1715
FT /note="For PL2-PRO activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT ACT_SITE 1872
FT /note="For PL2-PRO activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT ACT_SITE 3377
FT /note="For 3CL-PRO activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00772"
FT ACT_SITE 3481
FT /note="For 3CL-PRO activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00772"
FT BINDING 390
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT BINDING 395
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT BINDING 411
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT BINDING 414
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT BINDING 4397
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT BINDING 4400
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT BINDING 4406
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT BINDING 4413
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT BINDING 4439
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT BINDING 4442
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT BINDING 4450
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT BINDING 4452
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT SITE 247..248
FT /note="Cleavage; by PL1-PRO"
FT /evidence="ECO:0000305"
FT SITE 832..833
FT /note="Cleavage; by PL1-PRO"
FT /evidence="ECO:0000305"
FT SITE 2840..2841
FT /note="Cleavage; by PL2-PRO"
FT /evidence="ECO:0000305"
FT SITE 3336..3337
FT /note="Cleavage; by 3CL-PRO"
FT /evidence="ECO:0000305"
FT SITE 3639..3640
FT /note="Cleavage; by 3CL-PRO"
FT /evidence="ECO:0000305"
FT SITE 3927..3928
FT /note="Cleavage; by 3CL-PRO"
FT /evidence="ECO:0000305"
FT SITE 4019..4020
FT /note="Cleavage; by 3CL-PRO"
FT /evidence="ECO:0000305"
FT SITE 4213..4214
FT /note="Cleavage; by 3CL-PRO"
FT /evidence="ECO:0000305"
FT SITE 4323..4324
FT /note="Cleavage; by 3CL-PRO"
FT /evidence="ECO:0000305"
FT SITE 4460..4461
FT /note="Cleavage; by 3CL-PRO"
FT /evidence="ECO:0000305"
FT MUTAGEN 2835
FT /note="F->A: No processing between p210 and peptide HD2."
FT /evidence="ECO:0000269|PubMed:12805436"
FT MUTAGEN 2836
FT /note="S->A: No effect."
FT /evidence="ECO:0000269|PubMed:12805436"
FT MUTAGEN 2837
FT /note="L->A: No effect."
FT /evidence="ECO:0000269|PubMed:12805436"
FT MUTAGEN 2838
FT /note="K->A: No effect."
FT /evidence="ECO:0000269|PubMed:12805436"
FT MUTAGEN 2838
FT /note="K->N: No effect."
FT /evidence="ECO:0000269|PubMed:12805436"
FT MUTAGEN 2839
FT /note="G->A: Partial processing between p210 and peptide
FT HD2."
FT /evidence="ECO:0000269|PubMed:12805436"
FT MUTAGEN 2839
FT /note="G->N: No processing between p210 and peptide HD2."
FT /evidence="ECO:0000269|PubMed:12805436"
FT MUTAGEN 2839
FT /note="G->V: No processing between p210 and peptide HD2."
FT /evidence="ECO:0000269|PubMed:12805436"
FT MUTAGEN 2840
FT /note="G->A: No processing between p210 and peptide HD2."
FT /evidence="ECO:0000269|PubMed:12805436"
FT MUTAGEN 2840
FT /note="G->N: No processing between p210 and peptide HD2."
FT /evidence="ECO:0000269|PubMed:12805436"
FT MUTAGEN 2840
FT /note="G->V: No processing between p210 and peptide HD2."
FT /evidence="ECO:0000269|PubMed:12805436"
FT MUTAGEN 2841
FT /note="A->N: No effect."
FT /evidence="ECO:0000269|PubMed:12805436"
FT MUTAGEN 2842
FT /note="V->N,M: No effect."
FT /evidence="ECO:0000269|PubMed:12805436"
FT MUTAGEN 2846
FT /note="V->M: No effect."
FT /evidence="ECO:0000269|PubMed:12805436"
SQ SEQUENCE 4474 AA; 497595 MW; 7F09A6BF0E052D83 CRC64;
MAKMGKYGLG FKWAPEFPWM LPNASEKLGN PERSEEDGFC PSAAQEPKVK GKTLVNHVRV
DCSRLPALEC CVQSAIIRDI FVDEDPQKVE ASTMMALQFG SAVLVKPSKR LSVQAWAKLG
VLPKTPAMGL FKRFCLCNTR ECVCDAHVAF QLFTVQPDGV CLGNGRFIGW FVPVTAIPEY
AKQWLQPWSI LLRKGGNKGS VTSGHFRRAV TMPVYDFNVE DACEEVHLNP RGKYSCKAYA
LLRGYRGVKP ILFVDQYGCD YTGCLAKGLE DYGDLTLSEM KELSPVWRDS LDNEVVVAWH
VDRDPRAVMR LQTLATVRSI EYVGQPIEDM VDGDVVMREP AHLLAPNAIV KRLPRLVETM
LYTDSSVTEF CYKTKLCDCG FITQFGYVDC CGDTCGFRGW VPGNMMDGFP CPGCCKSYMP
WELEAQSSGV IPEGGVLFTQ STDTVNRESF KLYGHAVVPF GGAAYWSPYP GMWLPVIWSS
VKSYSYLTYT GVVGCKAIVQ ETDAICRFLY MDYVQHKCGN LEQRAILGLD DVYHRQLLVN
RGDYSLLLEN VDLFVKRRAE FACKFATCGD GLVPLLLDGL VPRSYYLIKS GQAFTSLMVN
FSREVVDMCM DMALLFMHDV KVATKYVKKV TGKVAVRFKA LGIAVVRKIT EWFDLAVDTA
ASAAGWLCYQ LVNGLFAVAN GVITFIQEVP ELVKNFVDKF KTFFKVLIDS MSVSILSGLT
VVKTASNRVC LAGSKVYEVV QKSLPAYIMP VGCSEATCLV GEIEPAVFED DVVDVVKAPL
TYQGCCKPPS SFEKICIVDK LYMAKCGDQF YPVVVDNDTV GVLDQCWRFP CAGKKVVFND
KPKVKEVPST RKIKIIFALD ATFDSVLSKA CSEFEVDKDV TLDELLDVVL DAVESTLSPC
KEHGVIGTKV CALLERLVDD YVYLFDEGGE EVIASRMYCS FSAPDEDCVA TDVVYADENQ
DDDADDPVVL VADTQEEDGV AREQVDSADS EICVAHTGGQ EMTEPDVVGS QTPIASAEET
EVGEACDREG IAEVKATVCA DALDACPDQV EAFDIEKVED SILSELQTEL NAPADKTYED
VLAFDAIYSE TLSAFYAVPS DETHFKVCGF YSPAIERTNC WLRSTLIVMQ SLPLEFKDLG
MQKLWLSYKA GYDQCFVDKL VKSAPKSIIL PQGGYVADFA YFFLSQCSFK VHANWRCLKC
GMELKLQGLD AVFFYGDVVS HMCKCGNSMT LLSADIPYTF DFGVRDDKFC AFYTPRKVFR
AACAVDVNDC HSMAVVDGKQ IDGKVVTKFN GDKFDFMVGH GMTFSMSPFE IAQLYGSCIT
PNVCFVKGDV IKVLRRVGAE VIVNPANGRM AHGAGVAGAI AKAAGKAFIN ETADMVKAQG
VCQVGGCYES TGGKLCKKVL NIVGPDARGH GNECYSLLER AYQHINKCDN VVTTLISAGI
FSVPTDVSLT YLLGVVTKNV ILVSNNQDDF DVIEKCQVTS VAGTKALSFQ LAKNLCRDVK
FVTNACSSLF SESSFVSSYD VLQEVEALRH DIQLDDDARV FVQANMDCLP TDWRLVNKFD
SVDGVRTIKY FECPGEVFVS SQGKKFGYVQ NGSFKEASVS QIRALLANKV DVLCTVDGVN
FRSCCVAEGE VFGKTLGSVF CDGINVTKVR CSAIHKGKVF FQYSGLSAAD LAAVKDAFGF
DEPQLLQYYS MLGMCKWPVV VCGNYFAFKQ SNNNCYINVA CLMLQHLSLK FPKWQWRRPG
NEFRSGKPLR FVSLVLAKGS FKFNEPSDST DFIRVELREA DLSGATCDLE FICKCGVKQE
QRKGVDAVMH FGTLDKSGLV KGYNIACTCG DKLVHCTQFN VPFLICSNTP EGKKLPDDVV
AANIFTGGSV GHYTHVKCKP KYQLYDACNV SKVSEAKGNF TDCLYLKNLK QTFSSVLTTY
YLDDVKCVAY KPDLSQYYCE SGKYYTKPII KAQFRTFEKV EGVYTNFKLV GHDIAEKLNA
KLGFDCNSPF MEYKITEWPT ATGDVVLASD DLYVSRYSGG CVTFGKPVIW RGHEEASLKS
LTYFNRPSVV CENKFNVLPV DVSEPTDRRP VPSAVLVTGA ASGADASAIS TEPGTAKEQK
ACASDSVEDQ IVMEAQKKSS VTTVAVKEVK LNGVKKPVKW NCSVVVNDPT SETKVVKSLS
IVDVYDMFLT GCRYVVWTAN ELSRLINSPT VREYVKWGMS KLIIPANLLL LRDEKQEFVA
PKVVKAKAIA CYGAVKWFLL YCFSWIKFNT DNKVIYTTEV ASKLTFKLCC LAFKNALQTF
NWSVVSRGFF LVATVFLLWF NFLYANVILS DFYLPNIGPL PMFVGQIVAW VKTTFGVLTI
CDFYQVTDLG YRSSFCNGSM VCELCFSGFD MLDNYESINV VQHVVDRRVS FDYISLFKLV
VELVIGYSLY TVCFYPLFVL VGMQLLTTWL PEFFMLGTMH WSARLFVFVA NMLPAFTLLR
FYIVVTAMYK VYCLCRHVMY GCSKPGCLFC YKRNRSVRVK CSTVVGGSLR YYDVMANGGT
GFCTKHQWNC LNCNSWKPGN TFITHEAAAD LSKELKRPVN PTDSAYYSVI EVKQVGCSMR
LFYERDGQRV YDDVSASLFV DMNGLLHSKV KGVPETHVVV VENEADKAGF LNAAVFYAQS
LYRPMLMVEK KLITTANTGL SVSRTMFDLY VYSLLRHLDV DRKSLTSFVN AAHNSLKEGV
QLEQVMDTFV GCARRKCAID SDVETKSITK SVMAAVNAGV EVTDESCNNL VPTYVKSDTI
VAADLGVLIQ NNAKHVQSNV AKAANVACIW SVDAFNQLSA DLQHRLRKAC VKTGLKIKLT
YNKQEANVPI LTTPFSLKGG AVFSRVLQWL FVANLICFIV LWALMPTYAV HKSDMQLPLY
ASFKVIDNGV LRDVSVTDAC FANKFNQFDQ WYESTFGLVY YRNSKACPVV VAVIDQDIGH
TLFNVPTKVL RYGFHVLHFI THAFATDRVQ CYTPHMQIPY DNFYASGCVL SSLCTMLAHA
DGTPHPYCYT EGVMHNASLY SSLVPHVRYN LASSNGYIRF PEVVSEGIVR VVRTRSMTYC
RVGLCEEAEE GICFNFNSSW VLNNPYYRAM PGTFCGRNAF DLIHQVLGGL VQPIDFFALT
ASSVAGAILA IIVVLAFYYL IKLKRAFGDY TSVVVINVIV WCINFLMLFV FQVYPTLSCL
YACFYFYTTL YFPSEISVVM HLQWLVMYGA IMPLWFCITY VAVVVSNHAL WLFSYCRKIG
TDVRSDGTFE EMALTTFMIT KESYCKLKNS VSDVAFNRYL SLYNKYRYFS GKMDTATYRE
AACSQLAKAM ETFNHNNGND VLYQPPTASV TTSFLQSGIV KMVSPTSKVE PCVVSVTYGN
MTLNGLWLDD KVYCPRHVIC SSADMTDPDY PNLLCRVTSS DFCVMSDRMS LTVMSYQMQG
SLLVLTVTLQ NPNTPKYSFG VVKPGETFTV LAAYNGRPQG AFHVVMRSSH TIKGSFLCGS
CGSVGYVLTG DSVRFVYMHQ LELSTGCHTG TDFSGNFYGP YRDAQVVQLP VQDYTQTVNV
VAWLYAAILN RCNWFVQSDS CSLEEFNVWA MTNGFSSIKA DLVLDALASM TGVTVEQVLA
AIKRLHSGFQ GKQILGSCVL EDELTPSDVY QQLAGVKLQS KRTRVIKGTC CWILASTFLF
CSIISAFVKW TMFMYVTTHM LGVTLCALCF VIFAMLLIKH KHLYLTMYIM PVLCTLFYTN
YLVVGYKQSF RGLAYAWLSY FVPAVDYTYM DEVLYGVVLL VAMVFVTMRS INHDVFSTMF
LVGRLVSLVS MWYFGANLEE EVLLFLTSLF GTYTWTTMLS LATAKVIAKW LAVNVLYFTD
IPQIKLVLLS YLCIGYVCCC YWGVLSLLNS IFRMPLGVYN YKISVQELRY MNANGLRPPR
NSFEALMLNF KLLGIGGVPV IEVSQIQSRL TDVKCANVVL LNCLQHLHIA SNSKLWQYCS
TLHNEILATS DLSVAFDKLA QLLVVLFANP AAVDSKCLAS IEEVSDDYVR DNTVLQALQS
EFVNMASFVE YELAKKNLDE AKASGSANQQ QIKQLEKACN IAKSAYERDR AVARKLERMA
DLALTNMYKE ARINDKKSKV VSALQTMLFS MVRKLDNQAL NSILDNAVKG CVPLNAIPPL
TSNTLTIIVP DKQVFDQVVD NVYVTYAPNV WHIQSIQDAD GAVKQLNEID VNSTWPLVIS
ANRHNEVSTV VLQNNELMPQ KLRTQVVNSG SDMNCNIPTQ CYYNTTGTGK IVYAILSDCD
GLKYTKIVKE DGNCVVLELD PPCKFSVQDV KGLKIKYLYF VKGCNTLARG WVVGTLSSTV
RLQAGTATEY ASNSAILSLC AFSVDPKKTY LDYIQQGGVP VTNCVKMLCD HAGTGMAITI
KPEATTNQDS YGGASVCIYC RSRVEHPDVD GLCKLRGKFV QVPLGIKDPV SYVLTHDVCQ
VCGFWRDGSC SCVGTGSQFQ SKDTNFLNGF GVQV
