R1A_CVMA5
ID R1A_CVMA5 Reviewed; 4468 AA.
AC P0C6V0; P16342;
DT 10-JUN-2008, integrated into UniProtKB/Swiss-Prot.
DT 10-JUN-2008, sequence version 1.
DT 03-AUG-2022, entry version 88.
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 A59) (MHV-A59) (Murine hepatitis virus).
OC Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes;
OC Nidovirales; Cornidovirineae; Coronaviridae; Orthocoronavirinae;
OC Betacoronavirus; Embecovirus.
OX NCBI_TaxID=11142;
OH NCBI_TaxID=10090; Mus musculus (Mouse).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
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 [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=Isolate C12 mutant;
RX PubMed=9426441; DOI=10.1006/viro.1997.8877;
RA Leparc-Goffart I., Hingley S.T., Chua M.M., Jiang X., Lavi E., Weiss S.R.;
RT "Altered pathogenesis of a mutant of the murine coronavirus MHV-A59 is
RT associated with a Q159L amino acid substitution in the spike protein.";
RL Virology 239:1-10(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-597.
RX PubMed=2545027; DOI=10.1016/0042-6822(89)90520-5;
RA Pachuk C.J., Bredenbeek P.J., Zoltick P.W., Spaan W.J.M., Weiss S.R.;
RT "Molecular cloning of the gene encoding the putative polymerase of mouse
RT hepatitis coronavirus, strain A59.";
RL Virology 171:141-148(1989).
RN [4]
RP PROTEOLYTIC PROCESSING OF POLYPROTEIN, AND CHARACTERIZATION OF NSP8.
RX PubMed=9499085; DOI=10.1128/jvi.72.3.2265-2271.1998;
RA Lu X.T., Sims A.C., Denison M.R.;
RT "Mouse hepatitis virus 3C-like protease cleaves a 22-kilodalton protein
RT from the open reading frame 1a polyprotein in virus-infected cells and in
RT vitro.";
RL J. Virol. 72:2265-2271(1998).
RN [5]
RP PROTEOLYTIC PROCESSING OF POLYPROTEIN, AND MUTAGENESIS OF PHE-3331;
RP LEU-3332; GLN-3333; SER-3334; GLY-3335; ILE-3336 AND CYS-3478.
RX PubMed=10544119; DOI=10.1006/viro.1999.9954;
RA Pinon J.D., Teng H., Weiss S.R.;
RT "Further requirements for cleavage by the murine coronavirus 3C-like
RT proteinase: identification of a cleavage site within ORF1b.";
RL Virology 263:471-484(1999).
RN [6]
RP PROTEOLYTIC PROCESSING OF POLYPROTEIN, AND CHARACTERIZATION OF NSP7; NSP9
RP AND NSP10.
RX PubMed=10708455; DOI=10.1128/jvi.74.7.3379-3387.2000;
RA Bost A.G., Carnahan R.H., Lu X.T., Denison M.R.;
RT "Four proteins processed from the replicase gene polyprotein of mouse
RT hepatitis virus colocalize in the cell periphery and adjacent to sites of
RT virion assembly.";
RL J. Virol. 74:3379-3387(2000).
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.
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.
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.
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.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Ribosomal frameshifting; Named isoforms=2;
CC Name=Replicase polyprotein 1a; Synonyms=pp1a, ORF1a polyprotein;
CC IsoId=P0C6V0-1; Sequence=Displayed;
CC Name=Replicase polyprotein 1ab; Synonyms=pp1ab;
CC IsoId=P0C6X9-1; 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; X73559; -; NOT_ANNOTATED_CDS; Genomic_RNA.
DR EMBL; AF029248; AAB86820.1; -; Genomic_RNA.
DR EMBL; M27198; AAA74011.1; -; Genomic_RNA.
DR PIR; A32440; A32440.
DR PIR; S15760; S15760.
DR RefSeq; NP_045298.1; NC_001846.1.
DR PDB; 2M0A; NMR; -; A=833-946.
DR PDBsum; 2M0A; -.
DR BMRB; P0C6V0; -.
DR SMR; P0C6V0; -.
DR IntAct; P0C6V0; 5.
DR MEROPS; C30.001; -.
DR GeneID; 1489749; -.
DR BRENDA; 3.4.22.B14; 3442.
DR SABIO-RK; P0C6V0; -.
DR Proteomes; UP000007192; Genome.
DR GO; GO:0039714; C:cytoplasmic viral factory; IDA:UniProtKB.
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; IEA:InterPro.
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; IMP: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; cd21557; Macro_X_Nsp3-like; 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; IPR044371; Macro_X_NSP3-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 3D-structure; Activation of host autophagy by virus;
KW 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;
KW Reference proteome; Repeat; Ribosomal frameshifting; RNA-binding;
KW Thiol protease; Transmembrane; Transmembrane helix;
KW Ubl conjugation pathway; Viral immunoevasion; Zinc; Zinc-finger.
FT CHAIN 1..4468
FT /note="Replicase polyprotein 1a"
FT /id="PRO_0000338278"
FT CHAIN 1..247
FT /note="Non-structural protein 1"
FT /evidence="ECO:0000305"
FT /id="PRO_0000338279"
FT CHAIN 248..832
FT /note="Non-structural protein 2"
FT /evidence="ECO:0000305"
FT /id="PRO_0000338280"
FT CHAIN 833..2837
FT /note="Non-structural protein 3"
FT /evidence="ECO:0000305"
FT /id="PRO_0000338281"
FT CHAIN 2838..3333
FT /note="Non-structural protein 4"
FT /id="PRO_0000338282"
FT CHAIN 3334..3635
FT /note="3C-like proteinase"
FT /id="PRO_0000338283"
FT CHAIN 3636..3921
FT /note="Non-structural protein 6"
FT /evidence="ECO:0000305"
FT /id="PRO_0000338284"
FT CHAIN 3922..4013
FT /note="Non-structural protein 7"
FT /id="PRO_0000338285"
FT CHAIN 4014..4207
FT /note="Non-structural protein 8"
FT /id="PRO_0000338286"
FT CHAIN 4208..4317
FT /note="Non-structural protein 9"
FT /id="PRO_0000338287"
FT CHAIN 4318..4454
FT /note="Non-structural protein 10"
FT /id="PRO_0000338288"
FT CHAIN 4455..4468
FT /note="Non-structural protein 11"
FT /evidence="ECO:0000255"
FT /id="PRO_0000338289"
FT TRANSMEM 2286..2306
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 2314..2334
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 2400..2420
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 2442..2462
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 2625..2645
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 2847..2867
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3096..3116
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3118..3138
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3150..3170
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3177..3197
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3202..3222
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3644..3664
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3674..3694
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3699..3719
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3742..3762
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3769..3789
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3796..3816
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3840..3860
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..511
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 1084..1333
FT /note="Peptidase C16 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT DOMAIN 1323..1482
FT /note="Macro"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00490"
FT DOMAIN 1537..1609
FT /note="DPUP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01289"
FT DOMAIN 1608..1663
FT /note="Ubiquitin-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT DOMAIN 1678..1937
FT /note="Peptidase C16 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT DOMAIN 1951..2052
FT /note="Nucleic acid-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01290"
FT DOMAIN 2107..2256
FT /note="G2M"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01338"
FT DOMAIN 2734..2837
FT /note="CoV Nsp3 Y3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT DOMAIN 3236..3333
FT /note="Nsp4C"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01291"
FT DOMAIN 3334..3635
FT /note="Peptidase C30"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00772"
FT DOMAIN 3922..4010
FT /note="RdRp Nsp7 cofactor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01294"
FT DOMAIN 4011..4207
FT /note="RdRp Nsp8 cofactor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01295"
FT DOMAIN 4208..4317
FT /note="Nsp9 ssRNA-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01296"
FT DOMAIN 4318..4455
FT /note="ExoN/MTase coactivator"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT ZN_FING 1198..1226
FT /note="C4-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT ZN_FING 1794..1830
FT /note="C4-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT ZN_FING 4391..4407
FT /evidence="ECO:0000250"
FT ZN_FING 4433..4446
FT /evidence="ECO:0000250"
FT REGION 390..414
FT /note="C4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT REGION 999..1027
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2225..2645
FT /note="HD1"
FT REGION 2847..3222
FT /note="HD2"
FT REGION 3526..3860
FT /note="HD3"
FT ACT_SITE 1121
FT /note="For PL1-PRO activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT ACT_SITE 1272
FT /note="For PL1-PRO activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT ACT_SITE 1716
FT /note="For PL2-PRO activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT ACT_SITE 1873
FT /note="For PL2-PRO activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT ACT_SITE 3374
FT /note="For 3CL-PRO activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00772"
FT ACT_SITE 3478
FT /note="For 3CL-PRO activity"
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 4391
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT BINDING 4394
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 4407
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT BINDING 4433
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT BINDING 4436
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT BINDING 4444
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT BINDING 4446
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 2837..2838
FT /note="Cleavage; by PL2-PRO"
FT SITE 3333..3334
FT /note="Cleavage; by 3CL-PRO"
FT SITE 3635..3636
FT /note="Cleavage; by 3CL-PRO"
FT SITE 3921..3922
FT /note="Cleavage; by 3CL-PRO"
FT SITE 4013..4014
FT /note="Cleavage; by 3CL-PRO"
FT SITE 4207..4208
FT /note="Cleavage; by 3CL-PRO"
FT SITE 4317..4318
FT /note="Cleavage; by 3CL-PRO"
FT SITE 4454..4455
FT /note="Cleavage; by 3CL-PRO"
FT VARIANT 1699
FT /note="P -> S (in strain: Isolate C12 mutant)"
FT VARIANT 2196
FT /note="M -> K (in strain: Isolate C12 mutant)"
FT MUTAGEN 3331
FT /note="F->A,H,W: No effect."
FT /evidence="ECO:0000269|PubMed:10544119"
FT MUTAGEN 3332
FT /note="L->I,S: No processing between peptide HD2 and 3CL-
FT PRO."
FT /evidence="ECO:0000269|PubMed:10544119"
FT MUTAGEN 3333
FT /note="Q->A,K,R: No processing between peptide HD2 and 3CL-
FT PRO."
FT /evidence="ECO:0000269|PubMed:10544119"
FT MUTAGEN 3334
FT /note="S->A: No effect."
FT /evidence="ECO:0000269|PubMed:10544119"
FT MUTAGEN 3334
FT /note="S->C: No processing between peptide HD2 and 3CL-
FT PRO."
FT /evidence="ECO:0000269|PubMed:10544119"
FT MUTAGEN 3335
FT /note="G->A: No effect."
FT /evidence="ECO:0000269|PubMed:10544119"
FT MUTAGEN 3335
FT /note="G->P: No processing between peptide HD2 and 3CL-
FT PRO."
FT /evidence="ECO:0000269|PubMed:10544119"
FT MUTAGEN 3336
FT /note="I->L: No effect."
FT /evidence="ECO:0000269|PubMed:10544119"
FT MUTAGEN 3478
FT /note="C->A: Complete loss of 3CL-PRO activity."
FT /evidence="ECO:0000269|PubMed:10544119"
FT CONFLICT 287..288
FT /note="WR -> CA (in Ref. 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 311
FT /note="L -> V (in Ref. 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 570
FT /note="D -> G (in Ref. 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 3620
FT /note="E -> EL (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 3711
FT /note="T -> TL (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 3968
FT /note="M -> V (in Ref. 2)"
FT /evidence="ECO:0000305"
FT STRAND 840..842
FT /evidence="ECO:0007829|PDB:2M0A"
FT STRAND 849..853
FT /evidence="ECO:0007829|PDB:2M0A"
FT STRAND 859..861
FT /evidence="ECO:0007829|PDB:2M0A"
FT HELIX 862..870
FT /evidence="ECO:0007829|PDB:2M0A"
FT STRAND 874..877
FT /evidence="ECO:0007829|PDB:2M0A"
FT HELIX 882..896
FT /evidence="ECO:0007829|PDB:2M0A"
FT HELIX 904..907
FT /evidence="ECO:0007829|PDB:2M0A"
FT HELIX 909..918
FT /evidence="ECO:0007829|PDB:2M0A"
FT STRAND 923..930
FT /evidence="ECO:0007829|PDB:2M0A"
FT STRAND 935..942
FT /evidence="ECO:0007829|PDB:2M0A"
SQ SEQUENCE 4468 AA; 496341 MW; 53FB55E845B646A5 CRC64;
MAKMGKYGLG FKWAPEFPWM LPNASEKLGN PERSEEDGFC PSAAQEPKVK GKTLVNHVRV
NCSRLPALEC CVQSAIIRDI FVDEDPQKVE ASTMMALQFG SAVLVKPSKR LSIQAWTNLG
VLPKTAAMGL FKRVCLCNTR ECSCDAHVAF HLFTVQPDGV CLGNGRFIGW FVPVTAIPEY
AKQWLQPWSI LLRKGGNKGS VTSGHFRRAV TMPVYDFNVE DACEEVHLNP KGKYSCKAYA
LLKGYRGVKP ILFVDQYGCD YTGCLAKGLE DYGDLTLSEM KELFPVWRDS LDSEVLVAWH
VDRDPRAAMR LQTLATVRCI DYVGQPTEDV VDGDVVVREP AHLLAANAIV KRLPRLVETM
LYTDSSVTEF CYKTKLCECG FITQFGYVDC CGDTCDFRGW VAGNMMDGFP CPGCTKNYMP
WELEAQSSGV IPEGGVLFTQ STDTVNRESF KLYGHAVVPF GSAVYWSPCP GMWLPVIWSS
VKSYSGLTYT GVVGCKAIVQ ETDAICRSLY MDYVQHKCGN LEQRAILGLD DVYHRQLLVN
RGDYSLLLEN VDLFVKRRAE FACKFATCGD GLVPLLLDGL VPRSYYLIKS GQAFTSMMVN
FSHEVTDMCM DMALLFMHDV KVATKYVKKV TGKLAVRFKA LGVAVVRKIT EWFDLAVDIA
ASAAGWLCYQ LVNGLFAVAN GVITFVQEVP ELVKNFVDKF KAFFKVLIDS MSVSILSGLT
VVKTASNRVC LAGSKVYEVV QKSLSAYVMP VGCSEATCLV GEIEPAVFED DVVDVVKAPL
TYQGCCKPPT SFEKICIVDK LYMAKCGDQF YPVVVDNDTV GVLDQCWRFP CAGKKVEFND
KPKVRKIPST RKIKITFALD ATFDSVLSKA CSEFEVDKDV TLDELLDVVL DAVESTLSPC
KEHDVIGTKV CALLDRLAGD YVYLFDEGGD EVIAPRMYCS FSAPDDEDCV AADVVDADEN
QDDDAEDSAV LVADTQEEDG VAKGQVEADS EICVAHTGSQ EELAEPDAVG SQTPIASAEE
TEVGEASDRE GIAEAKATVC ADAVDACPDQ VEAFEIEKVE DSILDELQTE LNAPADKTYE
DVLAFDAVCS EALSAFYAVP SDETHFKVCG FYSPAIERTN CWLRSTLIVM QSLPLEFKDL
EMQKLWLSYK AGYDQCFVDK LVKSVPKSII LPQGGYVADF AYFFLSQCSF KAYANWRCLE
CDMELKLQGL DAMFFYGDVV SHMCKCGNSM TLLSADIPYT LHFGVRDDKF CAFYTPRKVF
RAACAVDVND CHSMAVVEGK QIDGKVVTKF IGDKFDFMVG YGMTFSMSPF ELAQLYGSCI
TPNVCFVKGD VIKVVRLVNA EVIVNPANGR MAHGAGVAGA IAEKAGSAFI KETSDMVKAQ
GVCQVGECYE SAGGKLCKKV LNIVGPDARG HGKQCYSLLE RAYQHINKCD NVVTTLISAG
IFSVPTDVSL TYLLGVVTKN VILVSNNQDD FDVIEKCQVT SVAGTKALSL QLAKNLCRDV
KFVTNACSSL FSESCFVSSY DVLQEVEALR HDIQLDDDAR VFVQANMDCL PTDWRLVNKF
DSVDGVRTIK YFECPGGIFV SSQGKKFGYV QNGSFKEASV SQIRALLANK VDVLCTVDGV
NFRSCCVAEG EVFGKTLGSV FCDGINVTKV RCSAIYKGKV FFQYSDLSEA DLVAVKDAFG
FDEPQLLKYY TMLGMCKWPV VVCGNYFAFK QSNNNCYINV ACLMLQHLSL KFPKWQWQEA
WNEFRSGKPL RFVSLVLAKG SFKFNEPSDS IDFMRVVLRE ADLSGATCNL EFVCKCGVKQ
EQRKGVDAVM HFGTLDKGDL VRGYNIACTC GSKLVHCTQF NVPFLICSNT PEGRKLPDDV
VAANIFTGGS VGHYTHVKCK PKYQLYDACN VNKVSEAKGN FTDCLYLKNL KQTFSSVLTT
FYLDDVKCVE YKPDLSQYYC ESGKYYTKPI IKAQFRTFEK VDGVYTNFKL VGHSIAEKLN
AKLGFDCNSP FVEYKITEWP TATGDVVLAS DDLYVSRYSS GCITFGKPVV WLGHEEASLK
SLTYFNRPSV VCENKFNVLP VDVSEPTDKG PVPAAVLVTG VPGADASAGA GIAKEQKACA
SASVEDQVVT EVRQEPSVSA ADVKEVKLNG VKKPVKVEGS VVVNDPTSET KVVKSLSIVD
VYDMFLTGCK YVVWTANELS RLVNSPTVRE YVKWGMGKIV TPAKLLLLRD EKQEFVAPKV
VKAKAIACYC AVKWFLLYCF SWIKFNTDNK VIYTTEVASK LTFKLCCLAF KNALQTFNWS
VVSRGFFLVA TVFLLWFNFL YANVILSDFY LPNIGPLPTF VGQIVAWFKT TFGVSTICDF
YQVTDLGYRS SFCNGSMVCE LCFSGFDMLD NYDAINVVQH VVDRRLSFDY ISLFKLVVEL
VIGYSLYTVC FYPLFVLIGM QLLTTWLPEF FMLETMHWSA RLFVFVANML PAFTLLRFYI
VVTAMYKVYC LCRHVMYGCS KPGCLFCYKR NRSVRVKCST VVGGSLRYYD VMANGGTGFC
TKHQWNCLNC NSWKPGNTFI THEAAADLSK ELKRPVNPTD SAYYSVTEVK QVGCSMRLFY
ERDGQRVYDD VNASLFVDMN GLLHSKVKGV PETHVVVVEN EADKAGFLGA AVFYAQSLYR
PMLMVEKKLI TTANTGLSVS RTMFDLYVDS LLNVLDVDRK SLTSFVNAAH NSLKEGVQLE
QVMDTFIGCA RRKCAIDSDV ETKSITKSVM SAVNAGVDFT DESCNNLVPT YVKSDTIVAA
DLGVLIQNNA KHVQANVAKA ANVACIWSVD AFNQLSADLQ HRLRKACSKT GLKIKLTYNK
QEANVPILTT PFSLKGGAVF SRMLQWLFVA NLICFIVLWA LMPTYAVHKS DMQLPLYASF
KVIDNGVLRD VSVTDACFAN KFNQFDQWYE STFGLAYYRN SKACPVVVAV IDQDIGHTLF
NVPTTVLRYG FHVLHFITHA FATDSVQCYT PHMQIPYDNF YASGCVLSSL CTMLAHADGT
PHPYCYTGGV MHNASLYSSL APHVRYNLAS SNGYIRFPEV VSEGIVRVVR TRSMTYCRVG
LCEEAEEGIC FNFNRSWVLN NPYYRAMPGT FCGRNAFDLI HQVLGGLVRP IDFFALTASS
VAGAILAIIV VLAFYYLIKL KRAFGDYTSV VVINVIVWCI NFLMLFVFQV YPTLSCLYAC
FYFYTTLYFP SEISVVMHLQ WLVMYGAIMP LWFCIIYVAV VVSNHALWLF SYCRKIGTEV
RSDGTFEEMA LTTFMITKES YCKLKNSVSD VAFNRYLSLY NKYRYFSGKM DTAAYREAAC
SQLAKAMETF NHNNGNDVLY QPPTASVTTS FLQSGIVKMV SPTSKVEPCI VSVTYGNMTL
NGLWLDDKVY CPRHVICSSA DMTDPDYPNL LCRVTSSDFC VMSGRMSLTV MSYQMQGCQL
VLTVTLQNPN TPKYSFGVVK PGETFTVLAA YNGRPQGAFH VTLRSSHTIK GSFLCGSCGS
VGYVLTGDSV RFVYMHQLEL STGCHTGTDF SGNFYGPYRD AQVVQLPVQD YTQTVNVVAW
LYAAIFNRCN WFVQSDSCSL EEFNVWAMTN GFSSIKADLV LDALASMTGV TVEQVLAAIK
RLHSGFQGKQ ILGSCVLEDE TPSDVYQQLA GVKLQSKRTR VIKGTCCWIL ASTFLFCSII
SAFVKWTMFM YVTTHMLGVT LCALCFVSFA MLLIKHKHLY LTMYIMPVLC TFYTNYLVVY
KQSFRGLAYA WLSHFVPAVD YTYMDEVLYG VVLLVAMVFV TMRSINHDVF SIMFLVGRLV
SLVSMWYFGA NLEEEVLLFL TSLFGTYTWT TMLSLATAKV IAKWLAVNVL YFTDVPQIKL
VLLSYLCIGY VCCCYWGILS LLNSIFRMPL GVYNYKISVQ ELRYMNANGL RPPRNSFEAL
MLNFKLLGIG GVPVIEVSQI QSRLTDVKCA NVVLLNCLQH LHIASNSKLW QYCSTLHNEI
LATSDLSMAF DKLAQLLVVL FANPAAVDSK CLASIEEVSD DYVRDNTVLQ ALQSEFVNMA
SFVEYELAKK NLDEAKASGS ANQQQIKQLE KACNIAKSAY ERDRAVARKL ERMADLALTN
MYKEARINDK KSKVVSALQT MLFSMVRKLD NQALNSILDN AVKGCVPLNA IPSLTSNTLT
IIVPDKQVFD QVVDNVYVTY AGNVWHIQFI QDADGAVKQL NEIDVNSTWP LVIAANRHNE
VSTVVLQNNE LMPQKLRTQV VNSGSDMNCN TPTQCYYNTT GTGKIVYAIL SDCDGLKYTK
IVKEDGNCVV LELDPPCKFS VQDVKGLKIK YLYFVKGCNT LARGWVVGTL SSTVRLQAGT
ATEYASNSAI LSLCAFSVDP KKTYLDYIKQ GGVPVTNCVK MLCDHAGTGM AITIKPEATT
NQDSYGGASV CIYCRSRVEH PDVDGLCKLR GKFVQVPLGI KDPVSYVLTH DVCQVCGFWR
DGSCSCVGTG SQFQSKDTNF LNGFGVQV
