R1AB_CVMA5
ID R1AB_CVMA5 Reviewed; 7176 AA.
AC P0C6X9; O39225; O39226; P16342; P19750;
DT 10-JUN-2008, integrated into UniProtKB/Swiss-Prot.
DT 10-JUN-2008, sequence version 1.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=Replicase polyprotein 1ab;
DE Short=pp1ab;
DE AltName: Full=ORF1ab polyprotein;
DE Contains:
DE RecName: Full=Host translation inhibitor nsp1;
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 proteinase;
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=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=RNA-directed RNA polymerase;
DE Short=Pol;
DE Short=RdRp;
DE EC=2.7.7.48;
DE AltName: Full=nsp12;
DE AltName: Full=p100;
DE Contains:
DE RecName: Full=Helicase;
DE Short=Hel;
DE EC=3.6.4.12;
DE EC=3.6.4.13;
DE AltName: Full=nsp13;
DE AltName: Full=p67;
DE Contains:
DE RecName: Full=Guanine-N7 methyltransferase;
DE Short=ExoN;
DE EC=2.1.1.-;
DE EC=3.1.13.-;
DE AltName: Full=nsp14;
DE Contains:
DE RecName: Full=Uridylate-specific endoribonuclease nsp15;
DE EC=4.6.1.-;
DE AltName: Full=NendoU;
DE AltName: Full=nsp15;
DE AltName: Full=p35;
DE Contains:
DE RecName: Full=2'-O-methyltransferase;
DE EC=2.1.1.57;
DE AltName: Full=nsp16;
GN Name=rep; ORFNames=1a-1b;
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] (ORF1B).
RX PubMed=2159623; DOI=10.1093/nar/18.7.1825;
RA Bredenbeek P.J., Pachuk C.J., Noten A.F.H., Charite J., Luytjes W.,
RA Weiss S.R., Spaan W.J.M.;
RT "The primary structure and expression of the second open reading frame of
RT the polymerase gene of the coronavirus MHV-A59; a highly conserved
RT polymerase is expressed by an efficient ribosomal frameshifting
RT mechanism.";
RL Nucleic Acids Res. 18:1825-1832(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] (ORF1A).
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 [3]
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 [4]
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 [5]
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 [6]
RP SUBCELLULAR LOCATION OF HELICASE.
RX PubMed=10400784; DOI=10.1128/jvi.73.8.6862-6871.1999;
RA Denison M.R., Spaan W.J.M., van der Meer Y., Gibson C.A., Sims A.C.,
RA Prentice E., Lu X.T.;
RT "The putative helicase of the coronavirus mouse hepatitis virus is
RT processed from the replicase gene polyprotein and localizes in complexes
RT that are active in viral RNA synthesis.";
RL J. Virol. 73:6862-6871(1999).
RN [7]
RP PROTEOLYTIC PROCESSING OF POLYPROTEIN, AND MUTAGENESIS OF PHE-3331;
RP LEU-3332; GLN-3333; SER-3334; GLY-3335; ILE-3336; CYS-3478; LEU-5381;
RP GLN-5382 AND SER-5383.
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 [8]
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).
RN [9]
RP FUNCTION (URIDYLATE-SPECIFIC ENDORIBONUCLEASE NSP15).
RX PubMed=32198201; DOI=10.1073/pnas.1921485117;
RA Hackbart M., Deng X., Baker S.C.;
RT "Coronavirus endoribonuclease targets viral polyuridine sequences to evade
RT activating host sensors.";
RL Proc. Natl. Acad. Sci. U.S.A. 117:8094-8103(2020).
CC -!- FUNCTION: The replicase polyprotein of coronaviruses is a
CC multifunctional protein: it contains the activities necessary for the
CC transcription of negative stranded RNA, leader RNA, subgenomic mRNAs
CC and progeny virion RNA as well as proteinases responsible for the
CC cleavage of the polyprotein into functional products.
CC {ECO:0000250|UniProtKB:P0C6X7}.
CC -!- FUNCTION: [Host translation inhibitor nsp1]: Inhibits host translation
CC by interacting with the 40S ribosomal subunit. The nsp1-40S ribosome
CC complex further induces an endonucleolytic cleavage near the 5'UTR of
CC host mRNAs, targeting them for degradation. Viral mRNAs are not
CC susceptible to nsp1-mediated endonucleolytic RNA cleavage thanks to the
CC presence of a 5'-end leader sequence and are therefore protected from
CC degradation. By suppressing host gene expression, nsp1 facilitates
CC efficient viral gene expression in infected cells and evasion from host
CC immune response. {ECO:0000250|UniProtKB:P0C6X7}.
CC -!- FUNCTION: [Non-structural protein 2]: May play a role in the modulation
CC of host cell survival signaling pathway by interacting with host PHB
CC and PHB2. Indeed, these two proteins play a role in maintaining the
CC functional integrity of the mitochondria and protecting cells from
CC various stresses. {ECO:0000250|UniProtKB:P0C6X7}.
CC -!- FUNCTION: [Papain-like proteinase]: Responsible for the cleavages
CC located at the N-terminus of the replicase polyprotein. In addition,
CC PL-PRO possesses a deubiquitinating/deISGylating activity and processes
CC both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular
CC substrates. Participates together with nsp4 in the assembly of virally-
CC induced cytoplasmic double-membrane vesicles necessary for viral
CC replication. Antagonizes innate immune induction of type I interferon
CC by blocking the phosphorylation, dimerization and subsequent nuclear
CC translocation of host IRF3. Prevents also host NF-kappa-B signaling.
CC {ECO:0000250|UniProtKB:P0C6X7}.
CC -!- FUNCTION: [Non-structural protein 4]: Participates in the assembly of
CC virally-induced cytoplasmic double-membrane vesicles necessary for
CC viral replication. {ECO:0000250|UniProtKB:P0C6X7}.
CC -!- FUNCTION: [3C-like proteinase]: Cleaves the C-terminus of replicase
CC polyprotein at 11 sites. Recognizes substrates containing the core
CC sequence [ILMVF]-Q-|-[SGACN]. Also able to bind an ADP-ribose-1''-
CC phosphate (ADRP). {ECO:0000250|UniProtKB:P0C6X7, ECO:0000255|PROSITE-
CC ProRule:PRU00772}.
CC -!- FUNCTION: [Non-structural protein 6]: Plays a role in the initial
CC induction of autophagosomes from host reticulum endoplasmic. Later,
CC limits the expansion of these phagosomes that are no longer able to
CC deliver viral components to lysosomes. {ECO:0000250|UniProtKB:P0C6X7}.
CC -!- FUNCTION: [Non-structural protein 7]: Forms a hexadecamer with nsp8 (8
CC subunits of each) that may participate in viral replication by acting
CC as a primase. Alternatively, may synthesize substantially longer
CC products than oligonucleotide primers. {ECO:0000250|UniProtKB:P0C6X7}.
CC -!- FUNCTION: [Non-structural protein 8]: Forms a hexadecamer with nsp7 (8
CC subunits of each) that may participate in viral replication by acting
CC as a primase. Alternatively, may synthesize substantially longer
CC products than oligonucleotide primers. {ECO:0000250|UniProtKB:P0C6X7}.
CC -!- FUNCTION: [Non-structural protein 9]: May participate in viral
CC replication by acting as a ssRNA-binding protein.
CC {ECO:0000250|UniProtKB:P0C6X7}.
CC -!- FUNCTION: [Non-structural protein 10]: Plays a pivotal role in viral
CC transcription by stimulating both nsp14 3'-5' exoribonuclease and nsp16
CC 2'-O-methyltransferase activities. Therefore plays an essential role in
CC viral mRNAs cap methylation. {ECO:0000250|UniProtKB:P0C6X7}.
CC -!- FUNCTION: [RNA-directed RNA polymerase]: Responsible for replication
CC and transcription of the viral RNA genome.
CC {ECO:0000250|UniProtKB:P0C6X7}.
CC -!- FUNCTION: [Helicase]: Multi-functional protein with a zinc-binding
CC domain in N-terminus displaying RNA and DNA duplex-unwinding activities
CC with 5' to 3' polarity. Activity of helicase is dependent on magnesium.
CC {ECO:0000250|UniProtKB:P0C6X7}.
CC -!- FUNCTION: [Guanine-N7 methyltransferase]: Enzyme possessing two
CC different activities: an exoribonuclease activity acting on both ssRNA
CC and dsRNA in a 3' to 5' direction and a N7-guanine methyltransferase
CC activity. {ECO:0000250|UniProtKB:P0C6X7}.
CC -!- FUNCTION: [Uridylate-specific endoribonuclease nsp15]: Plays a role in
CC viral transcription/replication and prevents the simultaneous
CC activation of host cell dsRNA sensors, such as MDA5/IFIH1, OAS, and PKR
CC (By similarity). Acts by degrading the 5'-polyuridines generated during
CC replication of the poly(A) region of viral genomic and subgenomic RNAs.
CC Catalyzes a two-step reaction in which a 2'3'-cyclic phosphate (2'3'-
CC cP) is first generated by 2'-O transesterification, which is then
CC hydrolyzed to a 3'-phosphate (3'-P) (By similarity). If not degraded,
CC poly(U) RNA would hybridize with poly(A) RNA tails and activate host
CC dsRNA sensors (PubMed:32198201). {ECO:0000250|UniProtKB:P0C6X7,
CC ECO:0000269|PubMed:32198201}.
CC -!- FUNCTION: [2'-O-methyltransferase]: Methyltransferase that mediates
CC mRNA cap 2'-O-ribose methylation to the 5'-cap structure of viral
CC mRNAs. N7-methyl guanosine cap is a prerequisite for binding of nsp16.
CC Therefore plays an essential role in viral mRNAs cap methylation which
CC is essential to evade immune system. {ECO:0000250|UniProtKB:P0C6X7}.
CC -!- CATALYTIC ACTIVITY: [RNA-directed RNA polymerase]:
CC Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate +
CC RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA-
CC COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395;
CC EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539};
CC -!- CATALYTIC ACTIVITY: [Helicase]:
CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.12;
CC -!- CATALYTIC ACTIVITY: [Helicase]:
CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13;
CC -!- CATALYTIC ACTIVITY: [Papain-like proteinase]:
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 -!- CATALYTIC ACTIVITY: [2'-O-methyltransferase]:
CC Reaction=a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-ribonucleoside
CC in mRNA + S-adenosyl-L-methionine = a 5'-end (N(7)-methyl 5'-
CC triphosphoguanosine)-(2'-O-methyl-ribonucleoside) in mRNA + H(+) + S-
CC adenosyl-L-homocysteine; Xref=Rhea:RHEA:67020, Rhea:RHEA-COMP:17167,
CC Rhea:RHEA-COMP:17168, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:156461, ChEBI:CHEBI:167609;
CC EC=2.1.1.57; Evidence={ECO:0000250|UniProtKB:P0C6X7};
CC -!- CATALYTIC ACTIVITY: [Uridylate-specific endoribonuclease nsp15]:
CC Reaction=uridylyl-uridylyl-ribonucleotide-RNA = a 3'-end uridylyl-
CC 2',3'-cyclophospho-uridine-RNA + a 5'-end dephospho-ribonucleoside-
CC RNA; Xref=Rhea:RHEA:67732, Rhea:RHEA-COMP:13936, Rhea:RHEA-
CC COMP:17334, Rhea:RHEA-COMP:17335, ChEBI:CHEBI:138284,
CC ChEBI:CHEBI:173079, ChEBI:CHEBI:173080;
CC Evidence={ECO:0000250|UniProtKB:P0C6X7};
CC -!- COFACTOR: [Uridylate-specific endoribonuclease nsp15]:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:P0C6X7};
CC Note=Likely affects Nsp15 binding to RNA.
CC {ECO:0000250|UniProtKB:P0C6X7};
CC -!- SUBUNIT: Nsp2 interacts with host PHB and PHB2. 3CL-PRO exists as
CC monomer and homodimer. Nsp4 interacts with PL-PRO and nsp6. Only the
CC homodimer shows catalytic activity. Eight copies of nsp7 and eight
CC copies of nsp8 assemble to form a heterohexadecamer dsRNA-encircling
CC ring structure. Nsp9 is a dimer. Nsp10 forms a dodecamer and interacts
CC with nsp14 and nsp16; these interactions enhance nsp14 and nsp16
CC enzymatic activities. Nsp14 interacts (via N-terminus) with DDX1.
CC {ECO:0000250|UniProtKB:P0C6X7}.
CC -!- SUBCELLULAR LOCATION: [Papain-like proteinase]: 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 -!- SUBCELLULAR LOCATION: [Helicase]: Host endoplasmic reticulum-Golgi
CC intermediate compartment {ECO:0000305}. Note=The helicase interacts
CC with the N protein in membranous complexes and colocalizes with sites
CC of synthesis of new viral RNA. {ECO:0000269|PubMed:10400784}.
CC -!- SUBCELLULAR LOCATION: [Uridylate-specific endoribonuclease nsp15]: Host
CC cytoplasm, host perinuclear region {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Ribosomal frameshifting; Named isoforms=2;
CC Name=Replicase polyprotein 1ab; Synonyms=pp1ab;
CC IsoId=P0C6X9-1; Sequence=Displayed;
CC Name=Replicase polyprotein 1a; Synonyms=pp1a, ORF1a polyprotein;
CC IsoId=P0C6V0-1; 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 1ab]: Produced by -1
CC ribosomal frameshifting at the 1a-1b genes boundary.
CC -!- SIMILARITY: Belongs to the coronaviruses polyprotein 1ab family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB86818.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=AAB86820.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=CAA36202.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X51939; CAA36202.1; ALT_SEQ; Genomic_RNA.
DR EMBL; X73559; -; NOT_ANNOTATED_CDS; Genomic_RNA.
DR EMBL; AF029248; AAB86818.1; ALT_SEQ; Genomic_RNA.
DR EMBL; AF029248; AAB86820.1; ALT_SEQ; Genomic_RNA.
DR EMBL; M27198; AAA74011.1; -; Genomic_RNA.
DR PIR; A32440; A32440.
DR PIR; S15760; S15760.
DR RefSeq; NP_045299.1; NC_001846.1.
DR PDB; 2GTH; X-ray; 2.70 A; A=6504-6872.
DR PDB; 2GTI; X-ray; 2.15 A; A=6504-6872.
DR PDB; 3VC8; X-ray; 2.00 A; A/B=3245-3333.
DR PDB; 3VCB; X-ray; 2.40 A; A/B=3245-3333.
DR PDB; 4YPT; X-ray; 2.60 A; A=1525-1911.
DR PDB; 5WFI; X-ray; 1.85 A; A/B=1609-1911.
DR PDB; 6JIJ; X-ray; 2.65 A; A/B/C=3334-3635.
DR PDBsum; 2GTH; -.
DR PDBsum; 2GTI; -.
DR PDBsum; 3VC8; -.
DR PDBsum; 3VCB; -.
DR PDBsum; 4YPT; -.
DR PDBsum; 5WFI; -.
DR PDBsum; 6JIJ; -.
DR BMRB; P0C6X9; -.
DR SMR; P0C6X9; -.
DR ELM; P0C6X9; -.
DR IntAct; P0C6X9; 42.
DR BindingDB; P0C6X9; -.
DR PRIDE; P0C6X9; -.
DR GeneID; 1489749; -.
DR KEGG; vg:1489749; -.
DR BRENDA; 3.4.22.B79; 3467.
DR SABIO-RK; P0C6X9; -.
DR EvolutionaryTrace; P0C6X9; -.
DR Proteomes; UP000007192; Genome.
DR GO; GO:0039714; C:cytoplasmic viral factory; IDA:UniProtKB.
DR GO; GO:0044172; C:host cell endoplasmic reticulum-Golgi intermediate compartment; IEA:UniProtKB-SubCell.
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:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
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:0003678; F:DNA helicase activity; IEA:UniProtKB-EC.
DR GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW.
DR GO; GO:0004532; F:exoribonuclease activity; IEA:InterPro.
DR GO; GO:0016829; F:lyase 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:0003724; F:RNA helicase activity; IEA:UniProtKB-EC.
DR GO; GO:0003968; F:RNA-directed 5'-3' RNA polymerase activity; IEA:UniProtKB-KW.
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 virus of host protein ubiquitination; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
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:0039644; P:suppression by virus of host NF-kappaB cascade; 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:0006351; P:transcription, DNA-templated; IEA:InterPro.
DR GO; GO:0019082; P:viral protein processing; IEA:InterPro.
DR GO; GO:0039694; P:viral RNA genome replication; IEA:InterPro.
DR CDD; cd21409; 1B_cv_Nsp13-like; 1.
DR CDD; cd21560; betaCoV-Nsp6; 1.
DR CDD; cd21659; betaCoV_Nsp14; 1.
DR CDD; cd21666; betaCoV_Nsp5_Mpro; 1.
DR CDD; cd20762; capping_2-OMTase_Nidovirales; 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; cd21593; HCoV_HKU1-like_RdRp; 1.
DR CDD; cd21167; M_alpha_beta_cv_Nsp15-like; 1.
DR CDD; cd21557; Macro_X_Nsp3-like; 1.
DR CDD; cd21161; NendoU_cv_Nsp15-like; 1.
DR CDD; cd21171; NTD_alpha_beta_cv_Nsp15-like; 1.
DR CDD; cd21467; Ubl1_cv_Nsp3_N-like; 1.
DR CDD; cd21466; Ubl2_cv_PLpro_N_Nsp3-like; 1.
DR CDD; cd21401; ZBD_cv_Nsp13-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; 3.30.160.820; -; 1.
DR Gene3D; 3.30.70.3540; -; 1.
DR Gene3D; 3.40.220.10; -; 1.
DR Gene3D; 3.40.50.11020; -; 1.
DR Gene3D; 3.40.50.11580; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR027351; (+)RNA_virus_helicase_core_dom.
DR InterPro; IPR022570; B-CoV_A_NSP1.
DR InterPro; IPR043608; CoV_NSP15_M.
DR InterPro; IPR043606; CoV_NSP15_N.
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; IPR043502; DNA/RNA_pol_sf.
DR InterPro; IPR041679; DNA2/NAM7-like_C.
DR InterPro; IPR022733; DPUP_SUD_C_bCoV.
DR InterPro; IPR037227; EndoU-like.
DR InterPro; IPR002589; Macro_dom.
DR InterPro; IPR043472; Macro_dom-like.
DR InterPro; IPR044371; Macro_X_NSP3-like.
DR InterPro; IPR043609; NendoU_nidovirus.
DR InterPro; IPR044863; NIRAN.
DR InterPro; IPR036333; NSP10_sf_CoV.
DR InterPro; IPR044343; NSP13_1B_dom_CoV.
DR InterPro; IPR027352; NSP13_ZBD_CoV-like.
DR InterPro; IPR044315; NSP14_betaCoV.
DR InterPro; IPR009466; NSP14_CoV.
DR InterPro; IPR044330; NSP15_alpha_betaCoV_N.
DR InterPro; IPR044322; NSP15_M_alpha_beta_CoV.
DR InterPro; IPR043174; NSP15_middle_sf.
DR InterPro; IPR042515; NSP15_N_CoV.
DR InterPro; IPR044401; NSP15_NendoU_CoV.
DR InterPro; IPR009461; NSP16_CoV-like.
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; IPR027417; P-loop_NTPase.
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; IPR044347; RdRp_HCoV_HKU1-like.
DR InterPro; IPR001205; RNA-dir_pol_C.
DR InterPro; IPR007094; RNA-dir_pol_PSvirus.
DR InterPro; IPR009469; RNA_pol_N_CoV.
DR InterPro; IPR018995; RNA_synth_NSP10_CoV.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR Pfam; PF13087; AAA_12; 1.
DR Pfam; PF16251; bCoV_NAR; 1.
DR Pfam; PF06471; CoV_ExoN; 1.
DR Pfam; PF06460; CoV_Methyltr_2; 1.
DR Pfam; PF09401; CoV_NSP10; 1.
DR Pfam; PF19215; CoV_NSP15_C; 1.
DR Pfam; PF19216; CoV_NSP15_M; 1.
DR Pfam; PF19219; CoV_NSP15_N; 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; PF06478; CoV_RPol_N; 1.
DR Pfam; PF11963; DUF3477; 2.
DR Pfam; PF01661; Macro; 1.
DR Pfam; PF01831; Peptidase_C16; 1.
DR Pfam; PF05409; Peptidase_C30; 1.
DR Pfam; PF00680; RdRP_1; 1.
DR SMART; SM00506; A1pp; 1.
DR SUPFAM; SSF101816; SSF101816; 1.
DR SUPFAM; SSF140367; SSF140367; 1.
DR SUPFAM; SSF142877; SSF142877; 1.
DR SUPFAM; SSF143076; SSF143076; 1.
DR SUPFAM; SSF144246; SSF144246; 1.
DR SUPFAM; SSF159936; SSF159936; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF52949; SSF52949; 1.
DR SUPFAM; SSF53335; SSF53335; 2.
DR SUPFAM; SSF56672; SSF56672; 1.
DR PROSITE; PS51961; AV_NSP11N_COV_NSP15M; 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; PS51954; COV_N7_MTASE; 1.
DR PROSITE; PS51962; COV_NSP1; 1.
DR PROSITE; PS51948; COV_NSP12_RDRP; 1.
DR PROSITE; PS51960; COV_NSP15_NTD; 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; PS51653; CV_ZBD; 1.
DR PROSITE; PS51442; M_PRO; 1.
DR PROSITE; PS51154; MACRO; 1.
DR PROSITE; PS51958; NENDOU; 1.
DR PROSITE; PS51947; NIRAN; 1.
DR PROSITE; PS51955; NIV_2_O_MTASE; 1.
DR PROSITE; PS51953; NIV_EXON; 1.
DR PROSITE; PS51124; PEPTIDASE_C16; 2.
DR PROSITE; PS51657; PSRV_HELICASE; 1.
DR PROSITE; PS50507; RDRP_SSRNA_POS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activation of host autophagy by virus; ATP-binding;
KW Decay of host mRNAs by virus; Endonuclease;
KW Eukaryotic host gene expression shutoff by virus;
KW Eukaryotic host translation shutoff by virus; Exonuclease; Helicase;
KW Host cytoplasm; 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 ISG15 by virus; Inhibition of host NF-kappa-B by virus;
KW Lyase; Membrane; Metal-binding; Methyltransferase;
KW Modulation of host ubiquitin pathway by viral deubiquitinase;
KW Modulation of host ubiquitin pathway by virus; Nuclease;
KW Nucleotide-binding; Nucleotidyltransferase; Protease; Reference proteome;
KW Repeat; Ribosomal frameshifting; RNA-binding; RNA-directed RNA polymerase;
KW Thiol protease; Transferase; Transmembrane; Transmembrane helix;
KW Ubl conjugation pathway; Viral immunoevasion; Viral RNA replication; Zinc;
KW Zinc-finger.
FT CHAIN 1..247
FT /note="Host translation inhibitor nsp1"
FT /evidence="ECO:0000250|UniProtKB:P0C6X7"
FT /id="PRO_0000037338"
FT CHAIN 248..832
FT /note="Non-structural protein 2"
FT /evidence="ECO:0000250|UniProtKB:P0C6X7"
FT /id="PRO_0000037339"
FT CHAIN 833..2837
FT /note="Papain-like proteinase"
FT /evidence="ECO:0000250|UniProtKB:P0C6X7"
FT /id="PRO_0000037340"
FT CHAIN 2838..3333
FT /note="Non-structural protein 4"
FT /evidence="ECO:0000250|UniProtKB:P0C6X7"
FT /id="PRO_0000037341"
FT CHAIN 3334..3635
FT /note="3C-like proteinase"
FT /evidence="ECO:0000250|UniProtKB:P0C6X7"
FT /id="PRO_0000037342"
FT CHAIN 3636..3921
FT /note="Non-structural protein 6"
FT /evidence="ECO:0000250|UniProtKB:P0C6X7"
FT /id="PRO_0000037343"
FT CHAIN 3922..4013
FT /note="Non-structural protein 7"
FT /evidence="ECO:0000250|UniProtKB:P0C6X7"
FT /id="PRO_0000037344"
FT CHAIN 4014..4207
FT /note="Non-structural protein 8"
FT /evidence="ECO:0000250|UniProtKB:P0C6X7"
FT /id="PRO_0000037345"
FT CHAIN 4208..4317
FT /note="Non-structural protein 9"
FT /evidence="ECO:0000250|UniProtKB:P0C6X7"
FT /id="PRO_0000037346"
FT CHAIN 4318..4454
FT /note="Non-structural protein 10"
FT /evidence="ECO:0000250|UniProtKB:P0C6X7"
FT /id="PRO_0000037347"
FT CHAIN 4455..5382
FT /note="RNA-directed RNA polymerase"
FT /evidence="ECO:0000250|UniProtKB:P0C6X7"
FT /id="PRO_0000037348"
FT CHAIN 5383..5982
FT /note="Helicase"
FT /evidence="ECO:0000250|UniProtKB:P0C6X7"
FT /id="PRO_0000037349"
FT CHAIN 5983..6503
FT /note="Guanine-N7 methyltransferase"
FT /evidence="ECO:0000250|UniProtKB:P0C6X7"
FT /id="PRO_0000037350"
FT CHAIN 6504..6877
FT /note="Uridylate-specific endoribonuclease nsp15"
FT /evidence="ECO:0000250|UniProtKB:P0C6X7"
FT /id="PRO_0000037351"
FT CHAIN 6878..7176
FT /note="2'-O-methyltransferase"
FT /evidence="ECO:0000250|UniProtKB:P0C6X7"
FT /id="PRO_0000037352"
FT TRANSMEM 2225..2245
FT /note="Helical"
FT /evidence="ECO:0000255"
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 DOMAIN 4460..4715
FT /note="NiRAN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01292"
FT DOMAIN 4815..5382
FT /note="Nsp12 RNA-dependent RNA polymerase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01293"
FT DOMAIN 5062..5224
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT DOMAIN 5383..5466
FT /note="CV ZBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT DOMAIN 5638..5819
FT /note="(+)RNA virus helicase ATP-binding"
FT DOMAIN 5820..5989
FT /note="(+)RNA virus helicase C-terminal"
FT DOMAIN 6053..6268
FT /note="ExoN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"
FT DOMAIN 6277..6503
FT /note="N7-MTase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01299"
FT DOMAIN 6504..6564
FT /note="Nsp15 N-terminal oligomerization"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01305"
FT DOMAIN 6565..6685
FT /note="AV-Nsp11N/CoV-Nsp15M"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01306"
FT DOMAIN 6735..6874
FT /note="NendoU"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01303"
FT DOMAIN 6879..7173
FT /note="Nidovirus-type SAM-dependent 2'-O-MTase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01300"
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 REGION 6390..6404
FT /note="GpppA-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01299"
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 ACT_SITE 5209
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01293"
FT ACT_SITE 5210
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01293"
FT ACT_SITE 5211
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01293"
FT ACT_SITE 6071
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"
FT ACT_SITE 6073
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"
FT ACT_SITE 6172
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"
FT ACT_SITE 6249
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"
FT ACT_SITE 6254
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"
FT ACT_SITE 6765
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01303"
FT ACT_SITE 6780
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01303"
FT ACT_SITE 6820
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01303"
FT ACT_SITE 6923
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01300"
FT ACT_SITE 7007
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01300"
FT ACT_SITE 7047
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01300"
FT ACT_SITE 7080
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01300"
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 BINDING 5387
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT BINDING 5390
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT BINDING 5398
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT BINDING 5401
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT BINDING 5408
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT BINDING 5411
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT BINDING 5415
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT BINDING 5421
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT BINDING 5432
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT BINDING 5437
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT BINDING 5454
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT BINDING 5457
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT BINDING 5663..5670
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 6188
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"
FT BINDING 6191
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"
FT BINDING 6207
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"
FT BINDING 6210
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"
FT BINDING 6238
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"
FT BINDING 6242
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"
FT BINDING 6245
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"
FT BINDING 6260
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"
FT BINDING 6312..6318
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01299"
FT BINDING 6428
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01299"
FT BINDING 6449
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01299"
FT BINDING 6460
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01299"
FT BINDING 6463
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01299"
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 SITE 5382..5383
FT /note="Cleavage; by 3CL-PRO"
FT SITE 5982..5983
FT /note="Cleavage; by 3CL-PRO"
FT /evidence="ECO:0000305"
FT SITE 6503..6504
FT /note="Cleavage; by 3CL-PRO"
FT /evidence="ECO:0000305"
FT SITE 6877..6878
FT /note="Cleavage; by 3CL-PRO"
FT /evidence="ECO:0000305"
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 VARIANT 5773
FT /note="R -> S (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 MUTAGEN 5381
FT /note="L->I: No processing between RDRP and helicase."
FT /evidence="ECO:0000269|PubMed:10544119"
FT MUTAGEN 5381
FT /note="L->M: No effect."
FT /evidence="ECO:0000269|PubMed:10544119"
FT MUTAGEN 5382
FT /note="Q->K,R: No processing between RDRP and helicase."
FT /evidence="ECO:0000269|PubMed:10544119"
FT MUTAGEN 5383
FT /note="S->A: No effect."
FT /evidence="ECO:0000269|PubMed:10544119"
FT MUTAGEN 5383
FT /note="S->N: No processing between RDRP and helicase."
FT /evidence="ECO:0000269|PubMed:10544119"
FT CONFLICT 287..288
FT /note="WR -> CA (in Ref. 4)"
FT /evidence="ECO:0000305"
FT CONFLICT 311
FT /note="L -> V (in Ref. 4)"
FT /evidence="ECO:0000305"
FT CONFLICT 570
FT /note="D -> G (in Ref. 4)"
FT /evidence="ECO:0000305"
FT CONFLICT 3620
FT /note="E -> EL (in Ref. 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 3711
FT /note="T -> TL (in Ref. 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 3968
FT /note="M -> V (in Ref. 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 4464
FT /note="I -> V (in Ref. 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 6156
FT /note="V -> A (in Ref. 3)"
FT /evidence="ECO:0000305"
FT HELIX 1537..1545
FT /evidence="ECO:0007829|PDB:4YPT"
FT STRAND 1556..1563
FT /evidence="ECO:0007829|PDB:4YPT"
FT STRAND 1566..1574
FT /evidence="ECO:0007829|PDB:4YPT"
FT TURN 1575..1577
FT /evidence="ECO:0007829|PDB:4YPT"
FT STRAND 1578..1583
FT /evidence="ECO:0007829|PDB:4YPT"
FT STRAND 1586..1591
FT /evidence="ECO:0007829|PDB:4YPT"
FT STRAND 1594..1597
FT /evidence="ECO:0007829|PDB:4YPT"
FT HELIX 1600..1607
FT /evidence="ECO:0007829|PDB:4YPT"
FT STRAND 1610..1621
FT /evidence="ECO:0007829|PDB:5WFI"
FT STRAND 1623..1628
FT /evidence="ECO:0007829|PDB:5WFI"
FT HELIX 1633..1637
FT /evidence="ECO:0007829|PDB:5WFI"
FT STRAND 1639..1642
FT /evidence="ECO:0007829|PDB:5WFI"
FT HELIX 1654..1656
FT /evidence="ECO:0007829|PDB:5WFI"
FT STRAND 1660..1663
FT /evidence="ECO:0007829|PDB:5WFI"
FT HELIX 1669..1679
FT /evidence="ECO:0007829|PDB:5WFI"
FT HELIX 1683..1695
FT /evidence="ECO:0007829|PDB:5WFI"
FT STRAND 1700..1703
FT /evidence="ECO:0007829|PDB:5WFI"
FT STRAND 1706..1709
FT /evidence="ECO:0007829|PDB:5WFI"
FT HELIX 1716..1725
FT /evidence="ECO:0007829|PDB:5WFI"
FT HELIX 1735..1745
FT /evidence="ECO:0007829|PDB:5WFI"
FT HELIX 1750..1759
FT /evidence="ECO:0007829|PDB:5WFI"
FT HELIX 1770..1780
FT /evidence="ECO:0007829|PDB:5WFI"
FT STRAND 1787..1794
FT /evidence="ECO:0007829|PDB:5WFI"
FT STRAND 1797..1804
FT /evidence="ECO:0007829|PDB:5WFI"
FT HELIX 1806..1809
FT /evidence="ECO:0007829|PDB:5WFI"
FT STRAND 1810..1813
FT /evidence="ECO:0007829|PDB:5WFI"
FT HELIX 1817..1822
FT /evidence="ECO:0007829|PDB:5WFI"
FT STRAND 1824..1828
FT /evidence="ECO:0007829|PDB:5WFI"
FT STRAND 1831..1841
FT /evidence="ECO:0007829|PDB:5WFI"
FT STRAND 1843..1852
FT /evidence="ECO:0007829|PDB:5WFI"
FT STRAND 1861..1878
FT /evidence="ECO:0007829|PDB:5WFI"
FT TURN 1879..1882
FT /evidence="ECO:0007829|PDB:5WFI"
FT STRAND 1884..1887
FT /evidence="ECO:0007829|PDB:5WFI"
FT STRAND 1890..1893
FT /evidence="ECO:0007829|PDB:5WFI"
FT STRAND 1901..1907
FT /evidence="ECO:0007829|PDB:5WFI"
FT HELIX 3246..3249
FT /evidence="ECO:0007829|PDB:3VC8"
FT STRAND 3254..3256
FT /evidence="ECO:0007829|PDB:3VC8"
FT HELIX 3258..3267
FT /evidence="ECO:0007829|PDB:3VC8"
FT HELIX 3270..3278
FT /evidence="ECO:0007829|PDB:3VC8"
FT HELIX 3280..3284
FT /evidence="ECO:0007829|PDB:3VC8"
FT STRAND 3287..3290
FT /evidence="ECO:0007829|PDB:3VCB"
FT HELIX 3292..3313
FT /evidence="ECO:0007829|PDB:3VC8"
FT STRAND 3318..3320
FT /evidence="ECO:0007829|PDB:3VC8"
FT STRAND 3326..3330
FT /evidence="ECO:0007829|PDB:3VCB"
FT TURN 3344..3346
FT /evidence="ECO:0007829|PDB:6JIJ"
FT HELIX 3347..3349
FT /evidence="ECO:0007829|PDB:6JIJ"
FT STRAND 3350..3355
FT /evidence="ECO:0007829|PDB:6JIJ"
FT STRAND 3358..3365
FT /evidence="ECO:0007829|PDB:6JIJ"
FT STRAND 3368..3372
FT /evidence="ECO:0007829|PDB:6JIJ"
FT HELIX 3373..3376
FT /evidence="ECO:0007829|PDB:6JIJ"
FT HELIX 3387..3393
FT /evidence="ECO:0007829|PDB:6JIJ"
FT HELIX 3396..3398
FT /evidence="ECO:0007829|PDB:6JIJ"
FT STRAND 3400..3403
FT /evidence="ECO:0007829|PDB:6JIJ"
FT STRAND 3406..3408
FT /evidence="ECO:0007829|PDB:6JIJ"
FT STRAND 3410..3416
FT /evidence="ECO:0007829|PDB:6JIJ"
FT STRAND 3419..3426
FT /evidence="ECO:0007829|PDB:6JIJ"
FT STRAND 3433..3436
FT /evidence="ECO:0007829|PDB:6JIJ"
FT STRAND 3444..3451
FT /evidence="ECO:0007829|PDB:6JIJ"
FT STRAND 3454..3462
FT /evidence="ECO:0007829|PDB:6JIJ"
FT STRAND 3481..3486
FT /evidence="ECO:0007829|PDB:6JIJ"
FT STRAND 3489..3501
FT /evidence="ECO:0007829|PDB:6JIJ"
FT STRAND 3504..3508
FT /evidence="ECO:0007829|PDB:6JIJ"
FT STRAND 3514..3517
FT /evidence="ECO:0007829|PDB:6JIJ"
FT STRAND 3520..3523
FT /evidence="ECO:0007829|PDB:6JIJ"
FT HELIX 3534..3546
FT /evidence="ECO:0007829|PDB:6JIJ"
FT HELIX 3560..3567
FT /evidence="ECO:0007829|PDB:6JIJ"
FT TURN 3568..3571
FT /evidence="ECO:0007829|PDB:6JIJ"
FT HELIX 3579..3588
FT /evidence="ECO:0007829|PDB:6JIJ"
FT HELIX 3592..3602
FT /evidence="ECO:0007829|PDB:6JIJ"
FT STRAND 3614..3616
FT /evidence="ECO:0007829|PDB:6JIJ"
FT HELIX 3622..3629
FT /evidence="ECO:0007829|PDB:6JIJ"
SQ SEQUENCE 7176 AA; 802596 MW; AE90461FA631BED3 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 LNRIRGTSVN ARLVPCASGL DTDVQLRAFD ICNANRAGIG
LYYKVNCCRF QRVDEDGNKL DKFFVVKRTN LEVYNKEKEC YELTKECGVV AEHEFFTFDV
EGSRVPHIVR KDLSKFTMLD LCYALRHFDR NDCSTLKEIL LTYAECEESY FQKKDWYDFV
ENPDIINVYK KLGPIFNRAL LNTAKFADAL VEAGLVGVLT LDNQDLYGQW YDFGDFVKTV
PGCGVAVADS YYSYMMPMLT MCHALDSELF VNGTYREFDL VQYDFTDFKL ELFTKYFKHW
SMTYHPNTCE CEDDRCIIHC ANFNILFSMV LPKTCFGPLV RQIFVDGVPF VVSIGYHYKE
LGVVMNMDVD THRYRLSLKD LLLYAADPAL HVASASALLD LRTCCFSVAA ITSGVKFQTV
KPGNFNQDFY EFILSKGLLK EGSSVDLKHF FFTQDGNAAI TDYNYYKYNL PTMVDIKQLL
FVLEVVNKYF EIYEGGCIPA TQVIVNNYDK SAGYPFNKFG KARLYYEALS FEEQDEIYAY
TKRNVLPTLT QMNLKYAISA KNRARTVAGV SILSTMTGRM FHQKCLKSIA ATRGVPVVIG
TTKFYGGWDD MLRRLIKDVD SPVLMGWDYP KCDRAMPNIL RIVSSLVLAR KHDSCCSHTD
RFYRLANECA QVLSEIVMCG GCYYVKPGGT SSGDATTAFA NSVFNICQAV SANVCSLMAC
NGHKIEDLSI RELQKRLYSN VYRADHVDPA FVSEYYEFLN KHFSMMILSD DGVVCYNSEF
ASKGYIANIS AFQQVLYYQN NVFMSEAKCW VETDIEKGPH EFCSQHTMLV KMDGDEVYLP
YPDPSRILGA GCFVDDLLKT DSVLLIERFV SLAIDAYPLV YHENPEYQNV FRVYLEYIKK
LYNDLGNQIL DSYSVILSTC DGQKFTDETF YKNMYLRSAV LQSVGACVVC SSQTSLRCGS
CIRKPLLCCK CAYDHVMSTD HKYVLSVSPY VCNSPGCDVN DVTKLYLGGM SYYCEDHKPQ
YSFKLVMNGM VFGLYKQSCT GSPYIEDFNK IASCKWTEVD DYVLANECTE RLKLFAAETQ
KATEEAFKQC YASATIREIV SDRELILSWE IGKVRPPLNK NYVFTGYHFT NNGKTVLGEY
VFDKSELTNG VYYRATTTYK LSVGDVFILT SHAVSSLSAP TLVPQENYTS IRFASVYSVP
ETFQNNVPNY QHIGMKRYCT VQGPPGTGKS HLAIGLAVYY CTARVVYTAA SHAAVDALCE
KAHKFLNIND CTRIVPAKVR VDCYDKFKVN DTTRKYVFTT INALPELVTD IIVVDEVSML
TNYELSVINS RVRAKHYVYI GDPAQLPAPR VLLNKGTLEP RYFNSVTKLM CCLGPDIFLG
TCYRCPKEIV DTVSALVYNN KLKAKNDNSS MCFKVYYKGQ TTHESSSAVN MQQIHLISKF
LKANPSWSNA VFISPYNSQN YVAKRVLGLQ TQTVDSAQGS EYDFVIYSQT AETAHSVNVN
RFNVAITRAK KGILCVMSSM QLFESLNFTT LTLDKINNPR LQCTTNLFKD CSRSYVGYHP
AHAPSFLAVD DKYKVGGDLA VCLNVADSAV TYSRLISLMG FKLDLTLDGY CKLFITRDEA
IKRVRAWVGF DAEGAHAIRD SIGTNFPLQL GFSTGIDFVV EATGMFAERD GYVFKKAAAR
APPGEQFKHL IPLMSRGQKW DVVRIRIVQM LSDHLVDLAD SVVLVTWAAS FELTCLRYFA
KVGREVVCSV CTKRATCFNS RTGYYGCWRH SYSCDYLYNP LIVDIQQWGY TGSLTSNHDP
ICSVHKGAHV ASSDAIMTRC LAVHDCFCKS VNWNLEYPII SNEVSVNTSC RLLQRVMFRA
AMLCNRYDVC YDIGNPKGLA CVKGYDFKFY DASPVVKSVK QFVYKYEAHK DQFLDGLCMF
WNCNVDKYPA NAVVCRFDTR VLNKLNLPGC NGGSLYVNKH AFHTSPFTRA AFENLKPMPF
FYYSDTPCVY MEGMESKQVD YVPLRSATCI TRCNLGGAVC LKHAEEYREY LESYNTATTA
GFTFWVYKTF DFYNLWNTFT RLQSLENVVY NLVNAGHFDG RAGELPCAVI GEKVIAKIQN
EDVVVFKNNT PFPTNVAVEL FAKRSIRPHP ELKLFRNLNI DVCWSHVLWD YAKDSVFCSS
TYKVCKYTDL QCIESLNVLF DGRDNGALEA FKKCRNGVYI NTTKIKSLSM IKGPQRADLN
GVVVEKVGDS DVEFWFAVRK DGDDVIFSRT GSLEPSHYRS PQGNPGGNRV GDLSGNEALA
RGTIFTQSRL LSSFTPRSEM EKDFMDLDDD VFIAKYSLQD YAFEHVVYGS FNQKIIGGLH
LLIGLARRQQ KSNLVIQEFV TYDSSIHSYF ITDENSGSSK SVCTVIDLLL DDFVDIVKSL
NLKCVSKVVN VNVDFKDFQF MLWCNEEKVM TFYPRLQAAA DWKPGYVMPV LYKYLESPLE
RVNLWNYGKP ITLPTGCMMN VAKYTQLCQY LSTTTLAVPA NMRVLHLGAG SDKGVAPGSA
VLRQWLPAGS ILVDNDVNPF VSDSVASYYG NCITLPFDCQ WDLIISDMYD PLTKNIGEYN
VSKDGFFTYL CHLIRDKLAL GGSVAIKITE FSWNAELYSL MGKFAFWTIF CTNVNASSSE
GFLIGINWLN KTRTEIDGKT MHANYLFWRN STMWNGGAYS LFDMSKFPLK AAGTAVVSLK
PDQINDLVLS LIEKGKLLVR DTRKEVFVGD SLVNVK
