ID   R1AB_CVHNL              Reviewed;        6729 AA.
AC   P0C6X5; Q6Q1S3;
DT   10-JUN-2008, integrated into UniProtKB/Swiss-Prot.
DT   10-JUN-2008, sequence version 1.
DT   27-MAR-2024, entry version 104.
DE   RecName: Full=Replicase polyprotein 1ab;
DE            Short=pp1ab;
DE   AltName: Full=ORF1ab polyprotein;
DE   Contains:
DE     RecName: Full=Non-structural protein 1;
DE              Short=nsp1;
DE     AltName: Full=p9;
DE   Contains:
DE     RecName: Full=Non-structural protein 2;
DE              Short=nsp2;
DE     AltName: Full=p87;
DE   Contains:
DE     RecName: Full=Non-structural protein 3;
DE              Short=nsp3;
DE              EC=3.4.19.12;
DE              EC=3.4.22.-;
DE     AltName: Full=PL1-PRO/PL2-PRO;
DE     AltName: Full=PLP1/PLP2;
DE     AltName: Full=Papain-like proteinases 1/2;
DE     AltName: Full=p195;
DE   Contains:
DE     RecName: Full=Non-structural protein 4;
DE              Short=nsp4;
DE     AltName: Full=Peptide HD2;
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=p34;
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=p5;
DE   Contains:
DE     RecName: Full=Non-structural protein 8;
DE              Short=nsp8;
DE     AltName: Full=p23;
DE   Contains:
DE     RecName: Full=Viral protein genome-linked nsp9;
DE     AltName: Full=Non-structural protein 9;
DE              Short=nsp9;
DE     AltName: Full=RNA-capping enzyme subunit 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=p14;
DE   Contains:
DE     RecName: Full=RNA-directed RNA polymerase nsp12;
DE              Short=Pol;
DE              Short=RdRp;
DE              EC=2.7.7.48;
DE              EC=2.7.7.50;
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=p66;
DE     AltName: Full=p66-HEL;
DE   Contains:
DE     RecName: Full=Exoribonuclease;
DE              Short=ExoN;
DE              EC=3.1.13.-;
DE     AltName: Full=nsp14;
DE   Contains:
DE     RecName: Full=Uridylate-specific endoribonuclease;
DE              EC=4.6.1.-;
DE     AltName: Full=NendoU;
DE     AltName: Full=nsp15;
DE     AltName: Full=p41;
DE   Contains:
DE     RecName: Full=Putative 2'-O-methyl transferase;
DE              EC=2.1.1.57;
DE     AltName: Full=nsp16;
GN   Name=rep; ORFNames=1a-1b;
OS   Human coronavirus NL63 (HCoV-NL63).
OC   Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes;
OC   Nidovirales; Cornidovirineae; Coronaviridae; Orthocoronavirinae;
OC   Alphacoronavirus; Setracovirus.
OX   NCBI_TaxID=277944;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC   STRAIN=Isolate Amsterdam I;
RX   PubMed=15034574; DOI=10.1038/nm1024;
RA   Van Der Hoek L., Pyrc K., Jebbink M.F., Vermeulen-Oost W., Berkhout R.J.,
RA   Wolthers K.C., Wertheim-Van Dillen P.M., Kaandorp J., Spaargaren J.,
RA   Berkhout B.;
RT   "Identification of a new human coronavirus.";
RL   Nat. Med. 10:368-373(2004).
RN   [2]
RP   FUNCTION.
RX   PubMed=20181693; DOI=10.1128/jvi.02406-09;
RA   Clementz M.A., Chen Z., Banach B.S., Wang Y., Sun L., Ratia K.,
RA   Baez-Santos Y.M., Wang J., Takayama J., Ghosh A.K., Li K., Mesecar A.D.,
RA   Baker S.C.;
RT   "Deubiquitinating and interferon antagonism activities of coronavirus
RT   papain-like proteases.";
RL   J. Virol. 84:4619-4629(2010).
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:0000269|PubMed:20181693}.
CC   -!- FUNCTION: The papain-like proteinase 1 (PLP1) and papain-like
CC       proteinase 2 (PLP2) are responsible for the cleavages located at the N-
CC       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. PLP2
CC       also antagonizes innate immune induction of type I interferon by
CC       blocking the nuclear translocation of host IRF-3 (By similarity).
CC       {ECO:0000250}.
CC   -!- FUNCTION: [3C-like proteinase]: Responsible for the majority of
CC       cleavages as it cleaves the C-terminus of replicase polyprotein at 11
CC       sites. Recognizes substrates containing the core sequence [ILMVF]-Q-|-
CC       [SGACN]. Inhibited by the substrate-analog Cbz-Val-Asn-Ser-Thr-Leu-Gln-
CC       CMK. Also contains an ADP-ribose-1''-phosphate (ADRP)-binding function
CC       (By similarity). {ECO:0000255|PROSITE-ProRule:PRU00772}.
CC   -!- FUNCTION: The helicase which contains a zinc finger structure displays
CC       RNA and DNA duplex-unwinding activities with 5' to 3' polarity. Its
CC       ATPase activity is strongly stimulated by poly(U), poly(dT), poly(C),
CC       poly(dA), but not by poly(G). {ECO:0000269|PubMed:20181693}.
CC   -!- FUNCTION: The exoribonuclease acts on both ssRNA and dsRNA in a 3' to
CC       5' direction. {ECO:0000250}.
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: [Viral protein genome-linked nsp9]: Forms a primer, NSP9-pU,
CC       which is utilized by the polymerase for the initiation of RNA chains.
CC       Interacts with ribosome signal recognition particle RNA (SRP). Together
CC       with NSP8, suppress protein integration into the cell membrane, thereby
CC       disrupting host immune defenses. {ECO:0000250|UniProtKB:P0DTD1}.
CC   -!- FUNCTION: [RNA-directed RNA polymerase nsp12]: RNA-directed RNA
CC       polymerase that catalyzes the transcription of viral genomic and
CC       subgenomic RNAs. Acts in complex with nsp7 and nsp8 to transcribe both
CC       the minus and positive strands of genomic RNA. The kinase-like NiRAN
CC       domain of NSP12 attaches one or more nucleotides to the amino terminus
CC       of NSP9, forming a covalent RNA-protein intermediate that serves as
CC       transcription/replication primer. Subgenomic RNAs (sgRNAs) are formed
CC       by discontinuous transcription: The polymerase has the ability to pause
CC       at transcription-regulating sequences (TRS) and jump to the leader TRS,
CC       resulting in a major deletion. This creates a series of subgenomic RNAs
CC       that are replicated, transcribed and translated. In addition, Nsp12 is
CC       a subunit of the viral RNA capping enzyme that catalyzes the RNA
CC       guanylyltransferase reaction for genomic and sub-genomic RNAs.
CC       Subsequently, the NiRAN domain transfers RNA to GDP, and forms the core
CC       cap structure GpppA-RNA. {ECO:0000250|UniProtKB:P0DTD1}.
CC   -!- FUNCTION: [Uridylate-specific endoribonuclease]: Plays a role in viral
CC       transcription/replication and prevents the simultaneous activation of
CC       host cell dsRNA sensors, such as MDA5/IFIH1, OAS, and PKR (By
CC       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 (By similarity). {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- CATALYTIC ACTIVITY: [Non-structural protein 3]:
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: [RNA-directed RNA polymerase nsp12]:
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: [RNA-directed RNA polymerase nsp12]:
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:P0DTD1};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67013;
CC         Evidence={ECO:0000250|UniProtKB:P0DTD1};
CC   -!- CATALYTIC ACTIVITY: [Putative 2'-O-methyl transferase]:
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]:
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]:
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: 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   -!- INTERACTION:
CC       PRO_0000283876; Q14457: BECN1; Xeno; NbExp=3; IntAct=EBI-25622115, EBI-949378;
CC       PRO_0000283876; Q00987: MDM2; Xeno; NbExp=3; IntAct=EBI-25622115, EBI-389668;
CC       PRO_0000283876; Q96PM5: RCHY1; Xeno; NbExp=2; IntAct=EBI-25622115, EBI-947779;
CC       PRO_0000283876; Q86WV6: STING1; Xeno; NbExp=4; IntAct=EBI-25622115, EBI-2800345;
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 3]: Host membrane
CC       {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 4]: Host membrane
CC       {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 6]: Host membrane
CC       {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 7]: Host cytoplasm, host
CC       perinuclear region {ECO:0000250}. Note=nsp7, nsp8, nsp9 and nsp10 are
CC       localized in cytoplasmic foci, largely perinuclear. Late in infection,
CC       they merge into confluent complexes (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 8]: Host cytoplasm, host
CC       perinuclear region {ECO:0000250}. Note=nsp7, nsp8, nsp9 and nsp10 are
CC       localized in cytoplasmic foci, largely perinuclear. Late in infection,
CC       they merge into confluent complexes (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: [Viral protein genome-linked 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   -!- 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:0000250}.
CC   -!- SUBCELLULAR LOCATION: [Uridylate-specific endoribonuclease]: 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=P0C6X5-1; Sequence=Displayed;
CC       Name=Replicase polyprotein 1a; Synonyms=pp1a, ORF1a polyprotein;
CC         IsoId=P0C6U6-1; 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.
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}.
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DR   EMBL; AY567487; AAS58176.2; -; Genomic_RNA.
DR   RefSeq; YP_003766.2; NC_005831.2. [P0C6X5-1]
DR   PDB; 5NH0; X-ray; 2.35 A; A/C=2940-3238, B=2940-3239.
DR   PDB; 6FV1; X-ray; 2.30 A; A/B/C=2940-3240.
DR   PDB; 6FV2; X-ray; 2.95 A; A/B/C=2940-3240.
DR   PDB; 7WQH; X-ray; 2.32 A; A/B=2941-3239.
DR   PDB; 8HUU; X-ray; 1.71 A; A/B=2942-3239.
DR   PDBsum; 5NH0; -.
DR   PDBsum; 6FV1; -.
DR   PDBsum; 6FV2; -.
DR   PDBsum; 7WQH; -.
DR   PDBsum; 8HUU; -.
DR   SMR; P0C6X5; -.
DR   IntAct; P0C6X5; 75.
DR   BindingDB; P0C6X5; -.
DR   MEROPS; C30.003; -.
DR   DNASU; 2943501; -.
DR   GeneID; 2943501; -.
DR   KEGG; vg:2943501; -.
DR   SABIO-RK; P0C6X5; -.
DR   Proteomes; UP000008573; Genome.
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:0016020; C:membrane; IEA:UniProtKB-KW.
DR   GO; GO:0000175; F:3'-5'-RNA exonuclease activity; IEA:InterPro.
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:0004519; F:endonuclease activity; IEA:UniProtKB-KW.
DR   GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR   GO; GO:0004483; F:mRNA (nucleoside-2'-O-)-methyltransferase activity; IEA:InterPro.
DR   GO; GO:0004482; F:mRNA 5'-cap (guanine-N7-)-methyltransferase activity; IEA:InterPro.
DR   GO; GO:0008242; F:omega peptidase activity; IEA:InterPro.
DR   GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR   GO; GO:0003724; F:RNA helicase activity; IEA:UniProtKB-EC.
DR   GO; GO:0003968; F:RNA-dependent RNA polymerase activity; IEA:UniProtKB-KW.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0006351; P:DNA-templated transcription; IEA:InterPro.
DR   GO; GO:0039520; P:induction by virus of host autophagy; IEA:UniProtKB-KW.
DR   GO; GO:0039648; P:modulation by symbiont of host protein ubiquitination; IEA:UniProtKB-KW.
DR   GO; GO:0006508; P:proteolysis; 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: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; cd21901; alpha_betaCoV_Nsp10; 1.
DR   CDD; cd21558; alphaCoV-Nsp6; 1.
DR   CDD; cd21723; alphaCoV_Nsp13-helicase; 1.
DR   CDD; cd21660; alphaCoV_Nsp14; 1.
DR   CDD; cd21514; alphaCoV_Nsp2_HCoV-229E-like; 1.
DR   CDD; cd21665; alphaCoV_Nsp5_Mpro; 1.
DR   CDD; cd21826; alphaCoV_Nsp7; 1.
DR   CDD; cd21830; alphaCoV_Nsp8; 1.
DR   CDD; cd21897; alphaCoV_Nsp9; 1.
DR   CDD; cd21731; alphaCoV_PLPro; 1.
DR   CDD; cd21588; alphaCoV_RdRp; 1.
DR   CDD; cd20762; capping_2-OMTase_Nidovirales; 1.
DR   CDD; cd21473; cv_Nsp4_TM; 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_betaCoV_Nsp15-like; 1.
DR   CDD; cd21875; PEDV-like_alphaCoV_Nsp1; 1.
DR   CDD; cd21689; stalk_CoV_Nsp13-like; 1.
DR   CDD; cd21712; TM_Y_alphaCoV_Nsp3_C; 1.
DR   CDD; cd21401; ZBD_cv_Nsp13-like; 1.
DR   Gene3D; 1.10.8.1190; -; 2.
DR   Gene3D; 3.40.50.11580; -; 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; 3.30.160.820; Nsp15 N-terminal domain-like; 1.
DR   Gene3D; 1.10.8.370; nsp7 replicase; 1.
DR   Gene3D; 3.30.70.3540; Nsp8 replicase, head domain; 1.
DR   Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 2.
DR   Gene3D; 2.40.10.250; Replicase NSP9; 1.
DR   Gene3D; 2.40.10.10; Trypsin-like serine proteases; 2.
DR   Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 1.
DR   InterPro; IPR027351; (+)RNA_virus_helicase_core_dom.
DR   InterPro; IPR046443; a/bCoV_NSP1_glob.
DR   InterPro; IPR046440; AV_NSP11N_COV_NSP15M.
DR   InterPro; IPR043608; CoV_NSP15_M.
DR   InterPro; IPR043606; CoV_NSP15_N.
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; IPR043502; DNA/RNA_pol_sf.
DR   InterPro; IPR041679; DNA2/NAM7-like_C.
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; IPR046435; N7_MTase_CoV.
DR   InterPro; IPR043609; NendoU_nidovirus.
DR   InterPro; IPR044863; NIRAN.
DR   InterPro; IPR046438; NIV_2_O_MTASE.
DR   InterPro; IPR046436; NIV_EXON.
DR   InterPro; IPR036333; NSP10_sf_CoV.
DR   InterPro; IPR047570; NSP12_IF_CoV.
DR   InterPro; IPR044343; NSP13_1B_dom_CoV.
DR   InterPro; IPR047912; Nsp13_helicase_alphaCoV.
DR   InterPro; IPR048673; NSP13_stalk_CoV.
DR   InterPro; IPR048672; NSP13_ZBD_CoV.
DR   InterPro; IPR027352; NSP13_ZBD_CoV-like.
DR   InterPro; IPR044313; NSP14_alphaCoV.
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; IPR044385; NSP2_HCoV-229E-like.
DR   InterPro; IPR043615; NSP2_N_CoV.
DR   InterPro; IPR044357; NSP3_Ubl1_dom_CoV.
DR   InterPro; IPR044353; Nsp3_Ubl2_dom_CoV.
DR   InterPro; IPR038123; NSP4_C_sf_CoV.
DR   InterPro; IPR044309; NSP5_Mpro_alphaCoV.
DR   InterPro; IPR044369; NSP6_alphaCoV.
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; IPR011050; Pectin_lyase_fold/virulence.
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; IPR043178; PLpro_thumb_sf_CoV.
DR   InterPro; IPR044356; RdRp_alphaCoV.
DR   InterPro; IPR046441; RdRp_CoV.
DR   InterPro; IPR009469; RdRp_N_CoV.
DR   InterPro; IPR001205; RNA-dir_pol_C.
DR   InterPro; IPR007094; RNA-dir_pol_PSvirus.
DR   InterPro; IPR018995; RNA_synth_NSP10_CoV.
DR   InterPro; IPR029063; SAM-dependent_MTases_sf.
DR   PANTHER; PTHR43788; DNA2/NAM7 HELICASE FAMILY MEMBER; 1.
DR   PANTHER; PTHR43788:SF8; HELICASE WITH ZINC FINGER 2; 1.
DR   Pfam; PF13087; AAA_12; 1.
DR   Pfam; PF13604; AAA_30; 1.
DR   Pfam; PF06471; CoV_ExoN; 1.
DR   Pfam; PF06460; CoV_Methyltr_2; 1.
DR   Pfam; PF09401; CoV_NSP10; 1.
DR   Pfam; PF20631; CoV_NSP13_1B; 1.
DR   Pfam; PF20633; CoV_NSP13_stalk; 1.
DR   Pfam; PF20632; CoV_NSP13_ZBD; 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; 2.
DR   Pfam; PF19211; CoV_NSP2_N; 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; 2.
DR   Pfam; PF06478; CoV_RPol_N; 1.
DR   Pfam; PF01661; Macro; 1.
DR   Pfam; PF05409; Peptidase_C30; 1.
DR   Pfam; PF00680; RdRP_1; 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; SSF56672; DNA/RNA polymerases; 1.
DR   SUPFAM; SSF142877; EndoU-like; 1.
DR   SUPFAM; SSF52949; Macro domain-like; 1.
DR   SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
DR   SUPFAM; SSF51126; Pectin lyase-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; PS51961; AV_NSP11N_COV_NSP15M; 1.
DR   PROSITE; PS51993; COV_3ECTO; 1.
DR   PROSITE; PS51952; COV_EXON_MTASE_COACT; 1.
DR   PROSITE; PS51954; COV_N7_MTASE; 1.
DR   PROSITE; PS51962; COV_NSP1; 1.
DR   PROSITE; PS52000; COV_NSP12_IF; 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_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; 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   Disulfide bond; Endonuclease; Exonuclease; Helicase; Host cytoplasm;
KW   Host membrane; Host-virus interaction; Hydrolase;
KW   Inhibition of host innate immune response by virus;
KW   Inhibition of host IRF3 by virus; Inhibition of host RLR pathway 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; Repeat;
KW   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..110
FT                   /note="Non-structural protein 1"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000283874"
FT   CHAIN           111..898
FT                   /note="Non-structural protein 2"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000283875"
FT   CHAIN           899..2462
FT                   /note="Non-structural protein 3"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000283876"
FT   CHAIN           2463..2939
FT                   /note="Non-structural protein 4"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000283877"
FT   CHAIN           2940..3242
FT                   /note="3C-like proteinase"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000283878"
FT   CHAIN           3243..3521
FT                   /note="Non-structural protein 6"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000283879"
FT   CHAIN           3522..3604
FT                   /note="Non-structural protein 7"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000283880"
FT   CHAIN           3605..3799
FT                   /note="Non-structural protein 8"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000283881"
FT   CHAIN           3800..3908
FT                   /note="Viral protein genome-linked nsp9"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000283882"
FT   CHAIN           3909..4043
FT                   /note="Non-structural protein 10"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000283883"
FT   CHAIN           4044..4970
FT                   /note="RNA-directed RNA polymerase nsp12"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000283884"
FT   CHAIN           4971..5567
FT                   /note="Helicase"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000283885"
FT   CHAIN           5568..6085
FT                   /note="Exoribonuclease"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000283886"
FT   CHAIN           6086..6429
FT                   /note="Uridylate-specific endoribonuclease"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000283887"
FT   CHAIN           6430..6729
FT                   /note="Putative 2'-O-methyl transferase"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000283888"
FT   TRANSMEM        1903..1923
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1968..1988
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2050..2070
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2073..2093
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2111..2131
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2468..2488
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2727..2747
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2752..2769
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2772..2792
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2800..2820
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        3254..3274
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        3279..3299
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        3303..3323
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        3342..3362
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        3376..3396
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        3397..3417
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        3442..3462
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          2..109
FT                   /note="CoV Nsp1 globular"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01307"
FT   DOMAIN          112..358
FT                   /note="CoV Nsp2 N-terminal"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT   DOMAIN          388..778
FT                   /note="CoV Nsp2 middle"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01334"
FT   DOMAIN          776..898
FT                   /note="CoV Nsp2 C-terminal"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01335"
FT   DOMAIN          899..994
FT                   /note="Ubiquitin-like 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT   DOMAIN          1021..1262
FT                   /note="Peptidase C16 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   DOMAIN          1263..1421
FT                   /note="Macro"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00490"
FT   DOMAIN          1579..1633
FT                   /note="Ubiquitin-like 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT   DOMAIN          1640..1886
FT                   /note="Peptidase C16 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   DOMAIN          1983..2048
FT                   /note="3Ecto"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01337"
FT   DOMAIN          2122..2461
FT                   /note="CoV Nsp3 Y"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   DOMAIN          2844..2939
FT                   /note="Nsp4C"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01291"
FT   DOMAIN          2940..3242
FT                   /note="Peptidase C30"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00772"
FT   DOMAIN          3522..3604
FT                   /note="RdRp Nsp7 cofactor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01294"
FT   DOMAIN          3605..3799
FT                   /note="RdRp Nsp8 cofactor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01295"
FT   DOMAIN          3800..3908
FT                   /note="Nsp9 ssRNA-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01296"
FT   DOMAIN          3909..4047
FT                   /note="ExoN/MTase coactivator"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT   DOMAIN          4049..4298
FT                   /note="NiRAN"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01292"
FT   DOMAIN          4304..4402
FT                   /note="Nsp12 Interface"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01344"
FT   DOMAIN          4403..4970
FT                   /note="Nsp12 RNA-dependent RNA polymerase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01293"
FT   DOMAIN          4650..4812
FT                   /note="RdRp catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT   DOMAIN          4971..5083
FT                   /note="CV ZBD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT   DOMAIN          5228..5409
FT                   /note="(+)RNA virus helicase ATP-binding"
FT   DOMAIN          5410..5579
FT                   /note="(+)RNA virus helicase C-terminal"
FT   DOMAIN          5639..5853
FT                   /note="ExoN"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"
FT   DOMAIN          5862..6083
FT                   /note="N7-MTase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01299"
FT   DOMAIN          6086..6146
FT                   /note="Nsp15 N-terminal oligomerization"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01305"
FT   DOMAIN          6147..6269
FT                   /note="AV-Nsp11N/CoV-Nsp15M"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01306"
FT   DOMAIN          6286..6426
FT                   /note="NendoU"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01303"
FT   DOMAIN          6430..6726
FT                   /note="Nidovirus-type SAM-dependent 2'-O-MTase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01300"
FT   ZN_FING         1134..1165
FT                   /note="C4-type 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   ZN_FING         1757..1788
FT                   /note="C4-type 2; atypical"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   ZN_FING         3982..3998
FT                   /evidence="ECO:0000250"
FT   ZN_FING         4024..4037
FT                   /evidence="ECO:0000250"
FT   REGION          245..265
FT                   /note="C4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT   REGION          1903..2131
FT                   /note="HD1"
FT                   /evidence="ECO:0000250"
FT   REGION          2122..2212
FT                   /note="Y1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   REGION          2126..2139
FT                   /note="ZF1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   REGION          2172..2182
FT                   /note="ZF2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   REGION          2213..2461
FT                   /note="CoV-Y"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   REGION          2213..2302
FT                   /note="Y2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   REGION          2303..2359
FT                   /note="Y3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   REGION          2360..2461
FT                   /note="Y4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   REGION          2468..2820
FT                   /note="HD2"
FT                   /evidence="ECO:0000250"
FT   REGION          3254..3462
FT                   /note="HD3"
FT                   /evidence="ECO:0000250"
FT   REGION          4405..4619
FT                   /note="RdRp Fingers N-ter"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01293"
FT   REGION          4620..4658
FT                   /note="RdRp Palm N-ter"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01293"
FT   REGION          4659..4717
FT                   /note="RdRp Fingers C-ter"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01293"
FT   REGION          4718..4853
FT                   /note="RdRp Palm C-ter"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01293"
FT   REGION          4854..4970
FT                   /note="RdRp Thumb"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01293"
FT   REGION          5974..5988
FT                   /note="GpppA-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01299"
FT   ACT_SITE        1062
FT                   /note="For PL1-PRO activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   ACT_SITE        1212
FT                   /note="For PL1-PRO activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   ACT_SITE        1225
FT                   /note="For PL1-PRO activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   ACT_SITE        1678
FT                   /note="For PL2-PRO activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   ACT_SITE        1836
FT                   /note="For PL2-PRO activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   ACT_SITE        1841
FT                   /note="For PL2-PRO activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   ACT_SITE        2980
FT                   /note="For 3CL-PRO activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00772"
FT   ACT_SITE        3083
FT                   /note="For 3CL-PRO activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00772"
FT   ACT_SITE        4797
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01293"
FT   ACT_SITE        4798
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01293"
FT   ACT_SITE        4799
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01293"
FT   ACT_SITE        5657
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"
FT   ACT_SITE        5659
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"
FT   ACT_SITE        5758
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"
FT   ACT_SITE        5834
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"
FT   ACT_SITE        5839
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"
FT   ACT_SITE        6316
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01303"
FT   ACT_SITE        6331
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01303"
FT   ACT_SITE        6372
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01303"
FT   ACT_SITE        6474
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01300"
FT   ACT_SITE        6558
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01300"
FT   ACT_SITE        6598
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01300"
FT   ACT_SITE        6631
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01300"
FT   BINDING         245
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT   BINDING         247
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT   BINDING         264
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT   BINDING         265
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT   BINDING         1134
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   BINDING         1136
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   BINDING         1163
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   BINDING         1165
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   BINDING         1757
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   BINDING         1760
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   BINDING         1786
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   BINDING         1788
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   BINDING         2126
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   BINDING         2131
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   BINDING         2136
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   BINDING         2139
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   BINDING         2172
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   BINDING         2175
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   BINDING         2179
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   BINDING         2182
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   BINDING         3982
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="6"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT   BINDING         3985
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="6"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT   BINDING         3991
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="6"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT   BINDING         3998
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="6"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT   BINDING         4024
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="7"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT   BINDING         4027
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="7"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT   BINDING         4035
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="7"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT   BINDING         4037
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="7"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT   BINDING         4333
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="8"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01344"
FT   BINDING         4339
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="8"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01344"
FT   BINDING         4344
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="8"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01344"
FT   BINDING         4348
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="8"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01344"
FT   BINDING         4525
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="9"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01293"
FT   BINDING         4680
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="9"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01293"
FT   BINDING         4683
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="9"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01293"
FT   BINDING         4684
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="9"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01293"
FT   BINDING         4975
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="10"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT   BINDING         4978
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="10"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT   BINDING         4986
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="11"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT   BINDING         4989
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="11"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT   BINDING         4996
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="10"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT   BINDING         4999
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="10"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT   BINDING         5003
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="11"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT   BINDING         5009
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="11"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT   BINDING         5020
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="12"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT   BINDING         5025
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="12"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT   BINDING         5042
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="12"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT   BINDING         5045
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="12"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT   BINDING         5253..5260
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250"
FT   BINDING         5774
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="13"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"
FT   BINDING         5776
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="13"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"
FT   BINDING         5792
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="13"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"
FT   BINDING         5795
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="13"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"
FT   BINDING         5823
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="14"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"
FT   BINDING         5827
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="14"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"
FT   BINDING         5830
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="14"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"
FT   BINDING         5845
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="14"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"
FT   BINDING         5897..5903
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01299"
FT   BINDING         6012
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="15"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01299"
FT   BINDING         6029
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="15"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01299"
FT   BINDING         6040
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="15"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01299"
FT   BINDING         6043
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="15"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01299"
FT   SITE            110..111
FT                   /note="Cleavage; by PL1-PRO"
FT                   /evidence="ECO:0000250"
FT   SITE            898..899
FT                   /note="Cleavage; by PL1-PRO"
FT                   /evidence="ECO:0000250"
FT   SITE            2462..2463
FT                   /note="Cleavage; by PL2-PRO"
FT                   /evidence="ECO:0000250"
FT   SITE            2939..2940
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250"
FT   SITE            3242..3243
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250"
FT   SITE            3521..3522
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250"
FT   SITE            3604..3605
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250"
FT   SITE            3799..3800
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250"
FT   SITE            3908..3909
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250"
FT   SITE            4043..4044
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250"
FT   SITE            4970..4971
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250"
FT   SITE            6085..6086
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250"
FT   SITE            6429..6430
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250"
FT   DISULFID        1999..2026
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01337"
FT   DISULFID        2017..2023
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01337"
FT   HELIX           2950..2953
FT                   /evidence="ECO:0007829|PDB:6FV1"
FT   STRAND          2956..2961
FT                   /evidence="ECO:0007829|PDB:6FV1"
FT   STRAND          2964..2971
FT                   /evidence="ECO:0007829|PDB:6FV1"
FT   STRAND          2974..2978
FT                   /evidence="ECO:0007829|PDB:6FV1"
FT   HELIX           2979..2982
FT                   /evidence="ECO:0007829|PDB:6FV1"
FT   STRAND          2986..2988
FT                   /evidence="ECO:0007829|PDB:6FV1"
FT   HELIX           2992..2997
FT                   /evidence="ECO:0007829|PDB:6FV1"
FT   HELIX           3001..3003
FT                   /evidence="ECO:0007829|PDB:6FV1"
FT   STRAND          3004..3008
FT                   /evidence="ECO:0007829|PDB:6FV1"
FT   STRAND          3011..3013
FT                   /evidence="ECO:0007829|PDB:6FV1"
FT   STRAND          3015..3021
FT                   /evidence="ECO:0007829|PDB:6FV1"
FT   STRAND          3024..3031
FT                   /evidence="ECO:0007829|PDB:6FV1"
FT   STRAND          3038..3041
FT                   /evidence="ECO:0007829|PDB:6FV1"
FT   STRAND          3049..3056
FT                   /evidence="ECO:0007829|PDB:6FV1"
FT   STRAND          3059..3067
FT                   /evidence="ECO:0007829|PDB:6FV1"
FT   STRAND          3086..3090
FT                   /evidence="ECO:0007829|PDB:6FV1"
FT   STRAND          3096..3105
FT                   /evidence="ECO:0007829|PDB:6FV1"
FT   STRAND          3111..3114
FT                   /evidence="ECO:0007829|PDB:6FV1"
FT   HELIX           3121..3123
FT                   /evidence="ECO:0007829|PDB:6FV1"
FT   STRAND          3126..3129
FT                   /evidence="ECO:0007829|PDB:6FV1"
FT   HELIX           3140..3152
FT                   /evidence="ECO:0007829|PDB:6FV1"
FT   HELIX           3166..3175
FT                   /evidence="ECO:0007829|PDB:6FV1"
FT   HELIX           3184..3187
FT                   /evidence="ECO:0007829|PDB:6FV1"
FT   HELIX           3188..3194
FT                   /evidence="ECO:0007829|PDB:6FV1"
FT   HELIX           3198..3208
FT                   /evidence="ECO:0007829|PDB:6FV1"
FT   STRAND          3220..3222
FT                   /evidence="ECO:0007829|PDB:6FV1"
FT   HELIX           3229..3237
FT                   /evidence="ECO:0007829|PDB:6FV1"
SQ   SEQUENCE   6729 AA;  752702 MW;  86F9F04C687A65FA CRC64;
     MFYNQVTLAV ASDSEISGFG FAIPSVAVRT YSEAAAQGFQ ACRFVAFGLQ DCVTGINDDD
     YVIALTGTNQ LCAKILPFSD RPLNLRGWLI FSNSNYVLQD FDVVFGHGAG SVVFVDKYMC
     GFDGKPVLPK NMWEFRDYFN NNTDSIVIGG VTYQLAWDVI RKDLSYEQQN VLAIESIHYL
     GTTGHTLKSG CKLTNAKPPK YSSKVVLSGE WNAVYRAFGS PFITNGMSLL DIIVKPVFFN
     AFVKCNCGSE SWSVGAWDGY LSSCCGTPAK KLCVVPGNVV PGDVIITSTS AGCGVKYYAG
     LVVKHITNIT GVSLWRVTAV HSDGMFVASS SYDALLHRNS LDPFCFDVNT LLSNQLRLAF
     LGASVTEDVK FAASTGVIDI SAGMFGLYDD ILTNNKPWFV RKASGLFDAI WDAFVAAIKL
     VPTTTGVLVR FVKSIASTVL TVSNGVIIMC ADVPDAFQSV YRTFTQAICA AFDFSLDVFK
     IGDVKFKRLG DYVLTENALV RLTTEVVRGV RDARIKKAMF TKVVVGPTTE VKFSVIELAT
     VNLRLVDCAP VVCPKGKIVV IAGQAFFYSG GFYRFMVDPT TVLNDPVFTG DLFYTIKFSG
     FKLDGFNHQF VTASSATDAI IAVELLLLDF KTAVFVYTCV VDGCSVIVRR DATFATHVCF
     KDCYNVWEQF CIDNCGEPWF LTDYNAILQS NNPQCAIVQA SESKVLLERF LPKCPEILLS
     IDDGHLWNLF VEKFNFVTDW LKTLKLTLTS NGLLGNCAKR FRRVLVKLLD VYNGFLETVC
     SVAYTAGVCI KYYAVNVPYV VISGFVSRVI RRERCDMTFP CVSCVTFFYE FLDTCFGVSK
     PNAIDVEHLE LKETVFVEPK DGGQFFVSGD YLWYVVDDIY YPASCNGVLP VAFTKLAGGK
     ISFSDDVIVH DVEPTHKVKL IFEFEDDVVT SLCKKSFGKS IIYTGDWEGL HEVLTSAMNV
     IGQHIKLPQF YIYDEEGGYD VSKPVMISQW PISNDSNGCV VEASTDFHQL ECIVDDSVRE
     EVDIIEQPFE EVEHVLSIKQ PFSFSFRDEL GVRVLDQSDN NCWISTTLVQ LQLTKLLDDS
     IEMQLFKVGK VDSIVQKCYE LSHLISGSLG DSGKLLSELL KEKYTCSITF EMSCDCGKKF
     DDQVGCLFWI MPYTKLFQKG ECCICHKMQT YKLVSMKGTG VFVQDPAPID IDAFPVKPIC
     SSVYLGVKGS GHYQTNLYSF NKAIDGFGVF DIKNSSVNTV CFVDVDFHSV EIEAGEVKPF
     AVYKNVKFYL GDISHLVNCV SFDFVVNAAN ENLLHGGGVA RAIDILTEGQ LQSLSKDYIS
     SNGPLKVGAG VMLECEKFNV FNVVGPRTGK HEHSLLVEAY NSILFENGIP LMPLLSCGIF
     GVRIENSLKA LFSCDINKPL QVFVYSSNEE QAVLKFLDGL DLTPVIDDVD VVKPFRVEGN
     FSFFDCGVNA LDGDIYLLFT NSILMLDKQG QLLDTKLNGI LQQAALDYLA TVKTVPAGNL
     VKLFVESCTI YMCVVPSIND LSFDKNLGRC VRKLNRLKTC VIANVPAIDV LKKLLSSLTL
     TVKFVVESNV MDVNDCFKND NVVLKITEDG INVKDVVVES SKSLGKQLGV VSDGVDSFEG
     VLPINTDTVL SVAPEVDWVA FYGFEKAALF ASLDVKPYGY PNDFVGGFRV LGTTDNNCWV
     NATCIILQYL KPTFKSKGLN VLWNKFVTGD VGPFVSFIYF ITMSSKGQKG DAEEALSKLS
     EYLISDSIVT LEQYSTCDIC KSTVVEVKSA IVCASVLKDG CDVGFCPHRH KLRSRVKFVN
     GRVVITNVGE PIISQPSKLL NGIAYTTFSG SFDNGHYVVY DAANNAVYDG ARLFSSDLST
     LAVTAIVVVG GCVTSNVPTI VSEKISVMDK LDTGAQKFFQ FGDFVMNNIV LFLTWLLSMF
     SLLRTSIMKH DIKVIAKAPK RTGVILTRSF KYNIRSALFV IKQKWCVIVT LFKFLLLLYA
     IYALVFMIVQ FSPFNSLLCG DIVSGYEKST FNKDIYCGNS MVCKMCLFSY QEFNDLDHTS
     LVWKHIRDPI LISLQPFVIL VILLIFGNMY LRFGLLYFVA QFISTFGSFL GFHQKQWFLH
     FVPFDVLCNE FLATFIVCKI VLFVRHIIVG CNNADCVACS KSARLKRVPL QTIINGMHKS
     FYVNANGGTC FCNKHNFFCV NCDSFGPGNT FINGDIAREL GNVVKTAVQP TAPAYVIIDK
     VDFVNGFYRL YSGDTFWRYD FDITESKYSC KEVLKNCNVL ENFIVYNNSG SNITQIKNAC
     VYFSQLLCEP IKLVNSELLS TLSVDFNGVL HKAYVDVLCN SFFKELTANM SMAECKATLG
     LTVSDDDFVS AVANAHRYDV LLSDLSFNNF FISYAKPEDK LSVYDIACCM RAGSKVVNHN
     VLIKESIPIV WGVKDFNTLS QEGKKYLVKT TKAKGLTFLL TFNDNQAITQ VPATSIVAKQ
     GAGFKRTYNF LWYVCLFVVA LFIGVSFIDY TTTVTSFHGY DFKYIENGQL KVFEAPLHCV
     RNVFDNFNQW HEAKFGVVTT NSDKCPIVVG VSERINVVPG VPTNVYLVGK TLVFTLQAAF
     GNTGVCYDFD GVTTSDKCIF NSACTRLEGL GGDNVYCYNT DLIEGSKPYS TLQPNAYYKY
     DAKNYVRFPE ILARGFGLRT IRTLATRYCR VGECRDSHKG VCFGFDKWYV NDGRVDDGYI
     CGDGLIDLLV NVLSIFSSSF SVVAMSGHML FNFLFAAFIT FLCFLVTKFK RVFGDLSYGV
     FTVVCATLIN NISYVVTQNL FFMLLYAILY FVFTRTVRYA WIWHIAYIVA YFLLIPWWLL
     TWFSFAAFLE LLPNVFKLKI STQLFEGDKF IGTFESAAAG TFVLDMRSYE RLINTISPEK
     LKNYAASYNK YKYYSGSASE ADYRCACYAH LAKAMLDYAK DHNDMLYSPP TISYNSTLQS
     GLKKMAQPSG CVERCVVRVC YGSTVLNGVW LGDTVTCPRH VIAPSTTVLI DYDHAYSTMR
     LHNFSVSHNG VFLGVVGVTM HGSVLRIKVS QSNVHTPKHV FKTLKPGDSF NILACYEGIA
     SGVFGVNLRT NFTIKGSFIN GACGSPGYNV RNDGTVEFCY LHQIELGSGA HVGSDFTGSV
     YGNFDDQPSL QVESANLMLS DNVVAFLYAA LLNGCRWWLC STRVNVDGFN EWAMANGYTS
     VSSVECYSIL AAKTGVSVEQ LLASIQHLHE GFGGKNILGY SSLCDEFTLA EVVKQMYGVN
     LQSGKVIFGL KTMFLFSVFF TMFWAELFIY TNTIWINPVI LTPIFCLLLF LSLVLTMFLK
     HKFLFLQVFL LPTVIATALY NCVLDYYIVK FLADHFNYNV SVLQMDVQGL VNVLVCLFVV
     FLHTWRFSKE RFTHWFTYVC SLIAVAYTYF YSGDFLSLLV MFLCAISSDW YIGAIVFRLS
     RLIVFFSPES VFSVFGDVKL TLVVYLICGY LVCTYWGILY WFNRFFKCTM GVYDFKVSAA
     EFKYMVANGL HAPHGPFDAL WLSFKLLGIG GDRCIKISTV QSKLTDLKCT NVVLLGCLSS
     MNIAANSSEW AYCVDLHNKI NLCDDPEKAQ SMLLALLAFF LSKHSDFGLD GLIDSYFDNS
     STLQSVASSF VSMPSYIAYE NARQAYEDAI ANGSSSQLIK QLKRAMNIAK SEFDHEISVQ
     KKINRMAEQA ATQMYKEARS VNRKSKVISA MHSLLFGMLR RLDMSSVETV LNLARDGVVP
     LSVIPATSAS KLTIVSPDLE SYSKIVCDGS VHYAGVVWTL NDVKDNDGRP VHVKEITKEN
     VETLTWPLIL NCERVVKLQN NEIMPGKLKQ KPMKAEGDGG VLGDGNALYN TEGGKTFMYA
     YISNKADLKF VKWEYEGGCN TIELDSPCRF MVETPNGPQV KYLYFVKNLN TLRRGAVLGF
     IGATIRLQAG KQTELAVNSG LLTACAFSVD PATTYLEAVK HGAKPVSNCI KMLSNGAGNG
     QAITTSVDAN TNQDSYGGAS ICLYCRAHVP HPSMDGYCKF KGKCVQVPIG CLDPIRFCLE
     NNVCNVCGCW LGHGCACDRT TIQSVDISYL NRARGSSAAR LEPCNGTDID KCVRAFDIYN
     KNVSFLGKCL KMNCVRFKNA DLKDGYFVIK RCTKSVMEHE QSMYNLLNFS GALAEHDFFT
     WKDGRVIYGN VSRHNLTKYT MMDLVYAMRN FDEQNCDVLK EVLVLTGCCD NSYFDSKGWY
     DPVENEDIHR VYASLGKIVA RAMLKCVALC DAMVAKGVVG VLTLDNQDLN GNFYDFGDFV
     VSLPNMGVPC CTSYYSYMMP IMGLTNCLAS ECFVKSDIFG SDFKTFDLLK YDFTEHKENL
     FNKYFKHWSF DYHPNCSDCY DDMCVIHCAN FNTLFATTIP GTAFGPLCRK VFIDGVPLVT
     TAGYHFKQLG LVWNKDVNTH SVRLTITELL QFVTDPSLII ASSPALVDQR TICFSVAALS
     TGLTNQVVKP GHFNEEFYNF LRLRGFFDEG SELTLKHFFF AQNGDAAVKD FDFYRYNKPT
     ILDICQARVT YKIVSRYFDI YEGGCIKACE VVVTNLNKSA GWPLNKFGKA SLYYESISYE
     EQDALFALTK RNVLPTMTQL NLKYAISGKE RARTVGGVSL LSTMTTRQYH QKHLKSIVNT
     RNATVVIGTT KFYGGWNNML RTLIDGVENP MLMGWDYPKC DRALPNMIRM ISAMVLGSKH
     VNCCTATDRF YRLGNELAQV LTEVVYSNGG FYFKPGGTTS GDASTAYANS IFNIFQAVSS
     NINRLLSVPS DSCNNVNVRD LQRRLYDNCY RLTSVEESFI DDYYGYLRKH FSMMILSDDG
     VVCYNKDYAE LGYIADISAF KATLYYQNNV FMSTSKCWVE EDLTKGPHEF CSQHTMQIVD
     KDGTYYLPYP DPSRILSAGV FVDDVVKTDA VVLLERYVSL AIDAYPLSKH PNSEYRKVFY
     VLLDWVKHLN KNLNEGVLES FSVTLLDNQE DKFWCEDFYA SMYENSTILQ AAGLCVVCGS
     QTVLRCGDCL RKPMLCTKCA YDHVFGTDHK FILAITPYVC NASGCGVSDV KKLYLGGLNY
     YCTNHKPQLS FPLCSAGNIF GLYKNSATGS LDVEVFNRLA TSDWTDVRDY KLANDVKDTL
     RLFAAETIKA KEESVKSSYA FATLKEVVGP KELLLSWESG KVKPPLNRNS VFTCFQISKD
     SKFQIGEFIF EKVEYGSDTV TYKSTVTTKL VPGMIFVLTS HNVQPLRAPT IANQEKYSSI
     YKLHPAFNVS DAYANLVPYY QLIGKQKITT IQGPPGSGKS HCSIGLGLYY PGARIVFVAC
     AHAAVDSLCA KAMTVYSIDK CTRIIPARAR VECYSGFKPN NTSAQYIFST VNALPECNAD
     IVVVDEVSMC TNYDLSVINQ RLSYKHIVYV GDPQQLPAPR VMITKGVMEP VDYNVVTQRM
     CAIGPDVFLH KCYRCPAEIV NTVSELVYEN KFVPVKPASK QCFKVFFKGN VQVDNGSSIN
     RKQLEIVKLF LVKNPSWSKA VFISPYNSQN YVASRFLGLQ IQTVDSSQGS EYDYVIYAQT
     SDTAHACNVN RFNVAITRAK KGIFCVMCDK TLFDSLKFFE IKHADLHSSQ VCGLFKNCTR
     TPLNLPPTHA HTFLSLSDQF KTTGDLAVQI GSNNVCTYEH VISFMGFRFD ISIPGSHSLF
     CTRDFAIRNV RGWLGMDVES AHVCGDNIGT NVPLQVGFSN GVNFVVQTEG CVSTNFGDVI
     KPVCAKSPPG EQFRHLIPLL RKGQPWLIVR RRIVQMISDY LSNLSDILVF VLWAGSLELT
     TMRYFVKIGP IKYCYCGNSA TCYNSVSNEY CCFKHALGCD YVYNPYAFDI QQWGYVGSLS
     QNHHTFCNIH RNEHDASGDA VMTRCLAVHD CFVKNVDWTV TYPFIANEKF INGCGRNVQG
     HVVRAALKLY KPSVIHDIGN PKGVRCAVTD AKWYCYDKQP VNSNVKLLDY DYATHGQLDG
     LCLFWNCNVD MYPEFSIVCR FDTRTRSVFN LEGVNGGSLY VNKHAFHTPA YDKRAFVKLK
     PMPFFYFDDS DCDVVQEQVN YVPLRASSCV TRCNIGGAVC SKHANLYQKY VEAYNTFTQA
     GFNIWVPHSF DVYNLWQIFI ETNLQSLENI AFNVVKKGCF TGVDGELPVA VVNDKVFVRY
     GDVDNLVFTN KTTLPTNVAF ELFAKRKMGL TPPLSILKNL GVVATYKFVL WDYEAERPFT
     SYTKSVCKYT DFNEDVCVCF DNSIQGSYER FTLTTNAVLF STVVIKNLTP IKLNFGMLNG
     MPVSSIKGDK GVEKLVNWYI YVRKNGQFQD HYDGFYTQGR NLSDFTPRSD MEYDFLNMDM
     GVFINKYGLE DFNFEHVVYG DVSKTTLGGL HLLISQFRLS KMGVLKADDF VTASDTTLRC
     CTVTYLNELS SKVVCTYMDL LLDDFVTILK SLDLGVISKV HEVIIDNKPY RWMLWCKDNH
     LSTFYPQLQS AEWKCGYAMP QIYKLQRMCL EPCNLYNYGA GIKLPSGIML NVVKYTQLCQ
     YLNSTTMCVP HNMRVLHYGA GSDKGVAPGT TVLKRWLPPD AIIIDNDIND YVSDADFSIT
     GDCATVYLED KFDLLISDMY DGRIKFCDGE NVSKDGFFTY LNGVIREKLA IGGSVAIKIT
     EYSWNKYLYE LIQRFAFWTL FCTSVNTSSS EAFLIGINYL GDFIQGPFIA GNTVHANYIF
     WRNSTIMSLS YNSVLDLSKF ECKHKATVVV TLKDSDVNDM VLSLIKSGRL LLRNNGRFGG
     FSNHLVSTK
//