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   27-MAR-2024, entry version 99.
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=Papain-like protease nsp3;
DE              Short=PL-PRO;
DE              EC=3.4.19.12;
DE              EC=3.4.22.-;
DE     AltName: Full=Non-structural protein 3;
DE              Short=nsp3;
DE     AltName: Full=PL1-PRO/PL2-PRO;
DE     AltName: Full=PL1/PL2;
DE     AltName: Full=PL2-PRO;
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 nsp5;
DE              Short=3CL-PRO;
DE              Short=3CLp;
DE              EC=3.4.22.69;
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=RNA-capping enzyme subunit nsp9;
DE     AltName: Full=Non-structural protein 9;
DE              Short=nsp9;
DE              EC=2.7.7.50;
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; Murine coronavirus.
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 nsp5]: 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: [RNA-capping enzyme subunit nsp9]: Catalytic subunit of viral
CC       RNA capping enzyme which catalyzes the RNA guanylyltransferase reaction
CC       for genomic and sub-genomic RNAs. The kinase-like NiRAN domain of NSP12
CC       transfers RNA to the amino terminus of NSP9, forming a covalent RNA-
CC       protein intermediate. Subsequently, the NiRAN domain transfers RNA to
CC       GDP, forming the core cap structure GpppA-RNA. The NSP14 and NSP16
CC       methyltransferases then add methyl groups to form functional cap
CC       structures. {ECO:0000250|UniProtKB:P0DTC1}.
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: [Papain-like protease nsp3]:
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; Evidence={ECO:0000250|UniProtKB:P0DTC1};
CC   -!- CATALYTIC ACTIVITY: [3C-like proteinase nsp5]:
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         Evidence={ECO:0000250|UniProtKB:P0DTC1};
CC   -!- CATALYTIC ACTIVITY: [RNA-capping enzyme subunit nsp9]:
CC       Reaction=a 5'-end diphospho-ribonucleoside in mRNA + GTP + H(+) = a 5'-
CC         end (5'-triphosphoguanosine)-(ribonucleoside) in mRNA + diphosphate;
CC         Xref=Rhea:RHEA:67012, Rhea:RHEA-COMP:17165, Rhea:RHEA-COMP:17166,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:37565,
CC         ChEBI:CHEBI:167616, ChEBI:CHEBI:167617; EC=2.7.7.50;
CC         Evidence={ECO:0000250|UniProtKB:P0DTC1};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:67014;
CC         Evidence={ECO:0000250|UniProtKB:P0DTC1};
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: [Papain-like protease nsp3]: 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: [RNA-capping enzyme subunit nsp9]: Host
CC       cytoplasm, host perinuclear region {ECO:0000250}. Note=nsp7, nsp8, nsp9
CC       and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late
CC       in infection, they merge into confluent complexes (By similarity).
CC       {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:0016020; C: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:0004519; F:endonuclease activity; IEA:UniProtKB-KW.
DR   GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR   GO; GO:0008242; F:omega peptidase activity; IEA:InterPro.
DR   GO; GO:0003968; F:RNA-dependent 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:0032259; P:methylation; IEA:UniProtKB-KW.
DR   GO; GO:0039648; P:modulation by symbiont 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; cd21901; alpha_betaCoV_Nsp10; 1.
DR   CDD; cd21560; betaCoV-Nsp6; 1.
DR   CDD; cd21519; betaCoV_Nsp2_MHV-like; 1.
DR   CDD; cd21666; betaCoV_Nsp5_Mpro; 1.
DR   CDD; cd21827; betaCoV_Nsp7; 1.
DR   CDD; cd21831; betaCoV_Nsp8; 1.
DR   CDD; cd21898; betaCoV_Nsp9; 1.
DR   CDD; cd21732; betaCoV_PLPro; 1.
DR   CDD; cd21473; cv_Nsp4_TM; 1.
DR   CDD; cd21524; DPUP_MHV_Nsp3; 1.
DR   CDD; cd21879; MHV-like_Nsp1; 1.
DR   CDD; cd21812; MHV-like_Nsp3_betaSM; 1.
DR   CDD; cd21824; MHV-like_Nsp3_NAB; 1.
DR   CDD; cd21714; TM_Y_MHV-like_Nsp3_C; 1.
DR   CDD; cd21467; Ubl1_cv_Nsp3_N-like; 1.
DR   Gene3D; 1.10.8.1190; -; 2.
DR   Gene3D; 2.60.120.1680; -; 1.
DR   Gene3D; 3.10.20.350; -; 1.
DR   Gene3D; 3.10.20.540; -; 1.
DR   Gene3D; 6.10.140.2090; -; 1.
DR   Gene3D; 1.10.150.420; Coronavirus nonstructural protein 4 C-terminus; 1.
DR   Gene3D; 3.40.220.10; Leucine Aminopeptidase, subunit E, domain 1; 1.
DR   Gene3D; 1.10.1840.10; main proteinase (3clpro) structure, domain 3; 1.
DR   Gene3D; 1.10.8.370; nsp7 replicase; 1.
DR   Gene3D; 3.30.70.3540; Nsp8 replicase, head domain; 1.
DR   Gene3D; 2.40.10.250; Replicase NSP9; 1.
DR   Gene3D; 3.40.50.11020; Replicase polyprotein, nucleic acid-binding domain; 1.
DR   Gene3D; 2.40.10.10; Trypsin-like serine proteases; 2.
DR   InterPro; IPR046443; a/bCoV_NSP1_glob.
DR   InterPro; IPR022570; B-CoV_A_NSP1.
DR   InterPro; IPR046442; bCoV_NSP1_C.
DR   InterPro; IPR043613; CoV_NSP2_C.
DR   InterPro; IPR047573; CoV_NSP2_M.
DR   InterPro; IPR043611; CoV_NSP3_C.
DR   InterPro; IPR047566; CoV_NSP3_Y3.
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; IPR043615; NSP2_N_CoV.
DR   InterPro; IPR044381; NSP3_DPUP_MHV.
DR   InterPro; IPR047567; NSP3_G2M_bCoV.
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   PANTHER; PTHR11106; GANGLIOSIDE INDUCED DIFFERENTIATION ASSOCIATED PROTEIN 2-RELATED; 1.
DR   PANTHER; PTHR11106:SF111; MACRO DOMAIN-CONTAINING PROTEIN; 1.
DR   Pfam; PF11963; B-CoV_A_NSP1; 2.
DR   Pfam; PF16251; bCoV_NAB; 1.
DR   Pfam; PF09401; CoV_NSP10; 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; PF01661; Macro; 1.
DR   Pfam; PF01831; Peptidase_C16; 1.
DR   Pfam; PF05409; Peptidase_C30; 1.
DR   SMART; SM00506; A1pp; 1.
DR   SUPFAM; SSF144246; Coronavirus NSP10-like; 1.
DR   SUPFAM; SSF140367; Coronavirus NSP7-like; 1.
DR   SUPFAM; SSF143076; Coronavirus NSP8-like; 1.
DR   SUPFAM; SSF52949; Macro domain-like; 1.
DR   SUPFAM; SSF159936; NSP3A-like; 1.
DR   SUPFAM; SSF101816; Replicase NSP9; 1.
DR   SUPFAM; SSF53335; S-adenosyl-L-methionine-dependent methyltransferases; 1.
DR   SUPFAM; SSF50494; Trypsin-like serine proteases; 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; PS51993; COV_3ECTO; 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_Y; 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   Disulfide bond; Endonuclease;
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;
KW   Interferon antiviral system evasion; Membrane; Metal-binding;
KW   Methyltransferase;
KW   Modulation of host ubiquitin pathway by viral deubiquitinase;
KW   Modulation of host ubiquitin pathway by virus; Nuclease; Protease; Repeat;
KW   Ribosomal frameshifting; RNA-binding; Thiol protease; Transferase;
KW   Transmembrane; Transmembrane helix; Ubl conjugation pathway;
KW   Viral immunoevasion; Zinc; 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="Papain-like protease nsp3"
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 nsp5"
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="RNA-capping enzyme subunit nsp9"
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          2325..2386
FT                   /note="3Ecto"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01337"
FT   DOMAIN          2473..2840
FT                   /note="CoV Nsp3 Y"
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          2473..2563
FT                   /note="Y1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   REGION          2477..2490
FT                   /note="ZF1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   REGION          2523..2533
FT                   /note="ZF2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   REGION          2564..2840
FT                   /note="CoV-Y"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   REGION          2564..2656
FT                   /note="Y2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   REGION          2657..2739
FT                   /note="Y3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   REGION          2740..2840
FT                   /note="Y4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
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        1282
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        1886
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                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT   BINDING         395
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT   BINDING         411
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT   BINDING         414
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT   BINDING         1197
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   BINDING         1200
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   BINDING         1223
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   BINDING         1225
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   BINDING         1793
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   BINDING         1795
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   BINDING         1827
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   BINDING         1829
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   BINDING         2477
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   BINDING         2482
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   BINDING         2487
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   BINDING         2490
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   BINDING         2523
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   BINDING         2526
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   BINDING         2530
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   BINDING         2533
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   BINDING         4397
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="6"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT   BINDING         4400
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="6"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT   BINDING         4406
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="6"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT   BINDING         4413
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="6"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT   BINDING         4439
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="7"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT   BINDING         4442
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="7"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT   BINDING         4450
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="7"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT   BINDING         4452
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="7"
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   DISULFID        2341..2365
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01337"
FT   DISULFID        2356..2362
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01337"
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
//