ID   R1AB_CVEMC              Reviewed;        7078 AA.
AC   K9N7C7;
DT   29-MAY-2013, integrated into UniProtKB/Swiss-Prot.
DT   06-MAR-2013, sequence version 1.
DT   26-FEB-2020, entry version 48.
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=Leader protein;
DE   Contains:
DE     RecName: Full=Non-structural protein 2;
DE              Short=nsp2;
DE     AltName: Full=p65 homolog;
DE   Contains:
DE     RecName: Full=Papain-like proteinase;
DE              Short=PL-PRO;
DE              EC=3.4.19.12;
DE              EC=3.4.22.69;
DE     AltName: Full=Non-structural protein 3;
DE              Short=nsp3;
DE   Contains:
DE     RecName: Full=Non-structural protein 4;
DE              Short=nsp4;
DE   Contains:
DE     RecName: Full=3C-like proteinase;
DE              Short=3CL-PRO;
DE              Short=3CLp;
DE              EC=3.4.22.-;
DE     AltName: Full=nsp5;
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   Contains:
DE     RecName: Full=Non-structural protein 8;
DE              Short=nsp8;
DE   Contains:
DE     RecName: Full=Non-structural protein 9;
DE              Short=nsp9;
DE   Contains:
DE     RecName: Full=Non-structural protein 10;
DE              Short=nsp10;
DE     AltName: Full=Growth factor-like peptide;
DE              Short=GFL;
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   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   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;
DE              EC=3.1.-.-;
DE     AltName: Full=NendoU;
DE     AltName: Full=nsp15;
DE   Contains:
DE     RecName: Full=2'-O-methyltransferase;
DE              EC=2.1.1.-;
DE     AltName: Full=nsp16;
GN   Name=rep; ORFNames=1a-1b;
OS   Middle East respiratory syndrome-related coronavirus (isolate United
OS   Kingdom/H123990006/2012) (Betacoronavirus England 1) (Human coronavirus
OS   EMC).
OC   Viruses; Riboviria; Nidovirales; Cornidovirineae; Coronaviridae;
OC   Orthocoronavirinae; Betacoronavirus; Merbecovirus.
OX   NCBI_TaxID=1263720;
OH   NCBI_TaxID=9838; Camelus dromedarius (Dromedary) (Arabian camel).
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=23078800;
RA   Bermingham A., Chand M.A., Brown C.S., Aarons E., Tong C., Langrish C.,
RA   Hoschler K., Brown K., Galiano M., Myers R., Pebody R.G., Green H.K.,
RA   Boddington N.L., Gopal R., Price N., Newsholme W., Drosten C.,
RA   Fouchier R.A., Zambon M.;
RT   "Severe respiratory illness caused by a novel coronavirus, in a patient
RT   transferred to the United Kingdom from the Middle East, September 2012.";
RL   Eurosurveillance 17:20290-20290(2012).
RN   [2]
RP   FUNCTION (PAPAIN-LIKE PROTEINASE).
RX   PubMed=25142582; DOI=10.1128/jvi.01294-14;
RA   Baez-Santos Y.M., Mielech A.M., Deng X., Baker S., Mesecar A.D.;
RT   "Catalytic function and substrate specificity of the papain-like protease
RT   domain of nsp3 from the Middle East respiratory syndrome coronavirus.";
RL   J. Virol. 88:12511-12527(2014).
RN   [3]
RP   FUNCTION (NSP1).
RX   PubMed=26311885; DOI=10.1128/jvi.01352-15;
RA   Lokugamage K.G., Narayanan K., Nakagawa K., Terasaki K., Ramirez S.I.,
RA   Tseng C.T., Makino S.;
RT   "Middle east respiratory syndrome coronavirus nsp1 inhibits host gene
RT   expression by selectively targeting mRNAs transcribed in the nucleus while
RT   sparing mRNAs of cytoplasmic origin.";
RL   J. Virol. 89:10970-10981(2015).
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]: Promotes the degradation
CC       of host mRNAs by inducing an endonucleolytic RNA cleavage in template
CC       mRNAs, and inhibits of host mRNA translation, a function that is
CC       separable from its RNA cleavage activity. By suppressing host gene
CC       expression, nsp1 facilitates efficient viral gene expression in
CC       infected cells and evasion from host immune response.
CC       {ECO:0000269|PubMed:26311885}.
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, ECO:0000269|PubMed:25142582}.
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: Proteinase 3CL-PRO: 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]: Mn(2+)-dependent,
CC       uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to
CC       the cleaved bond. {ECO:0000250|UniProtKB:P0C6X7}.
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:
CC       Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate +
CC         RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:11128, Rhea:RHEA-
CC         COMP:11129, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:83400;
CC         EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539};
CC   -!- CATALYTIC ACTIVITY:
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:
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:
CC       Reaction=TSAVLQ-|-SGFRK-NH(2) and SGVTFQ-|-GKFKK the two peptides
CC         corresponding to the two self-cleavage sites of the SARS 3C-like
CC         proteinase are the two most reactive peptide substrates. The enzyme
CC         exhibits a strong preference for substrates containing Gln at P1
CC         position and Leu at P2 position.; EC=3.4.22.69;
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide
CC         and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-
CC         residue protein attached to proteins as an intracellular targeting
CC         signal).; EC=3.4.19.12;
CC   -!- SUBUNIT: 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; Multi-
CC       pass membrane protein. Host cytoplasm {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 4]: Host membrane; Multi-
CC       pass membrane protein. Host cytoplasm. Note=Localizes in virally-
CC       induced cytoplasmic double-membrane vesicles.
CC       {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 6]: Host membrane
CC       {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 7]: Host cytoplasm, host
CC       perinuclear region {ECO:0000250}. Note=nsp7, nsp8, nsp9 and nsp10 are
CC       localized in cytoplasmic foci, largely perinuclear. Late in infection,
CC       they merge into confluent complexes (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 8]: Host cytoplasm, host
CC       perinuclear region {ECO:0000250}. Note=nsp7, nsp8, nsp9 and nsp10 are
CC       localized in cytoplasmic foci, largely perinuclear. Late in infection,
CC       they merge into confluent complexes (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 9]: Host cytoplasm, host
CC       perinuclear region {ECO:0000250}. Note=nsp7, nsp8, nsp9 and nsp10 are
CC       localized in cytoplasmic foci, largely perinuclear. Late in infection,
CC       they merge into confluent complexes (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 10]: Host cytoplasm, host
CC       perinuclear region {ECO:0000250}. Note=nsp7, nsp8, nsp9 and nsp10 are
CC       localized in cytoplasmic foci, largely perinuclear. Late in infection,
CC       they merge into confluent complexes (By similarity). {ECO:0000250}.
CC   -!- 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=K9N7C7-1; Sequence=Displayed;
CC       Name=Replicase polyprotein 1a; Synonyms=pp1a, ORF1a polyprotein;
CC         IsoId=K9N638-1; 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}.
DR   EMBL; KC164505; AFY13306.1; -; Genomic_RNA.
DR   PDB; 4WUR; X-ray; 3.16 A; A=1482-1801.
DR   PDB; 5HOL; X-ray; 1.59 A; A=1109-1275.
DR   PDB; 5KO3; X-ray; 1.95 A; A=1544-1800.
DR   PDBsum; 4WUR; -.
DR   PDBsum; 5HOL; -.
DR   PDBsum; 5KO3; -.
DR   SMR; K9N7C7; -.
DR   PRIDE; K9N7C7; -.
DR   Proteomes; UP000139997; 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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
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:0016896; F:exoribonuclease activity, producing 5'-phosphomonoesters; IEA:InterPro.
DR   GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
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-directed 5'-3' RNA polymerase activity; IEA:UniProtKB-KW.
DR   GO; GO:0036459; F:thiol-dependent ubiquitinyl hydrolase activity; IEA:UniProtKB-EC.
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:0071108; P:protein K48-linked deubiquitination; IDA:UniProtKB.
DR   GO; GO:0070536; P:protein K63-linked deubiquitination; IDA:UniProtKB.
DR   GO; GO:0039503; P:suppression by virus of host innate immune response; IDA:UniProtKB.
DR   GO; GO:0039579; P:suppression by virus of host ISG15 activity; IDA:UniProtKB.
DR   GO; GO:0039644; P:suppression by virus of host NF-kappaB transcription factor activity; IEA:UniProtKB-KW.
DR   GO; GO:0039653; P:suppression by virus of host transcription; IDA:UniProtKB.
DR   GO; GO:0039604; P:suppression by virus of host translation; IDA:UniProtKB.
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   Gene3D; 1.10.150.420; -; 1.
DR   Gene3D; 1.10.8.370; -; 1.
DR   Gene3D; 2.20.25.360; -; 1.
DR   Gene3D; 2.40.10.250; -; 1.
DR   Gene3D; 2.40.10.290; -; 1.
DR   Gene3D; 3.10.20.350; -; 1.
DR   Gene3D; 3.40.220.20; -; 1.
DR   Gene3D; 3.40.50.11020; -; 1.
DR   InterPro; IPR027351; (+)RNA_virus_helicase_core_dom.
DR   InterPro; IPR032505; Corona_NSP4_C.
DR   InterPro; IPR009461; Coronavirus_NSP16.
DR   InterPro; IPR027352; CV_ZBD.
DR   InterPro; IPR041679; DNA2/NAM7-like_AAA.
DR   InterPro; IPR037227; EndoU-like.
DR   InterPro; IPR002589; Macro_dom.
DR   InterPro; IPR032592; NAR_dom.
DR   InterPro; IPR042570; NAR_sf.
DR   InterPro; IPR036333; NSP10_sf.
DR   InterPro; IPR009466; NSP11.
DR   InterPro; IPR042515; Nsp15_N.
DR   InterPro; IPR024375; Nsp3_coronavir.
DR   InterPro; IPR038400; Nsp3_coronavir_sf.
DR   InterPro; IPR038123; NSP4_C_sf.
DR   InterPro; IPR014828; NSP7.
DR   InterPro; IPR037204; NSP7_sf.
DR   InterPro; IPR014829; NSP8.
DR   InterPro; IPR037230; NSP8_sf.
DR   InterPro; IPR014822; NSP9.
DR   InterPro; IPR036499; NSP9_sf.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   InterPro; IPR008740; Peptidase_C30.
DR   InterPro; IPR013016; Peptidase_C30/C16.
DR   InterPro; IPR009003; Peptidase_S1_PA.
DR   InterPro; IPR038083; R1a/1ab.
DR   InterPro; IPR001205; RNA-dir_pol_C.
DR   InterPro; IPR007094; RNA-dir_pol_PSvirus.
DR   InterPro; IPR009469; RNA_pol_N_coronovir.
DR   InterPro; IPR018995; RNA_synth_NSP10_coronavirus.
DR   InterPro; IPR029063; SAM-dependent_MTases.
DR   InterPro; IPR014827; Viral_protease.
DR   Pfam; PF13087; AAA_12; 1.
DR   Pfam; PF16348; Corona_NSP4_C; 1.
DR   Pfam; PF06478; Corona_RPol_N; 1.
DR   Pfam; PF01661; Macro; 1.
DR   Pfam; PF16251; NAR; 1.
DR   Pfam; PF09401; NSP10; 1.
DR   Pfam; PF06471; NSP11; 1.
DR   Pfam; PF06460; NSP16; 1.
DR   Pfam; PF08716; nsp7; 1.
DR   Pfam; PF08717; nsp8; 1.
DR   Pfam; PF08710; nsp9; 1.
DR   Pfam; PF05409; Peptidase_C30; 1.
DR   Pfam; PF00680; RdRP_1; 1.
DR   Pfam; PF11633; SUD-M; 1.
DR   Pfam; PF08715; Viral_protease; 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; SSF53335; SSF53335; 1.
DR   PROSITE; PS51653; CV_ZBD; 1.
DR   PROSITE; PS51442; M_PRO; 1.
DR   PROSITE; PS51154; MACRO; 1.
DR   PROSITE; PS51124; PEPTIDASE_C16; 1.
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   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..193
FT                   /note="Host translation inhibitor nsp1"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6X7"
FT                   /id="PRO_0000422439"
FT   CHAIN           194..853
FT                   /note="Non-structural protein 2"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6X7"
FT                   /id="PRO_0000422440"
FT   CHAIN           854..2740
FT                   /note="Papain-like proteinase"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6X7"
FT                   /id="PRO_0000422441"
FT   CHAIN           2741..3247
FT                   /note="Non-structural protein 4"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6X7"
FT                   /id="PRO_0000422442"
FT   CHAIN           3248..3553
FT                   /note="3C-like proteinase"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6X7"
FT                   /id="PRO_0000422443"
FT   CHAIN           3554..3845
FT                   /note="Non-structural protein 6"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6X7"
FT                   /id="PRO_0000422444"
FT   CHAIN           3846..3928
FT                   /note="Non-structural protein 7"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6X7"
FT                   /id="PRO_0000422445"
FT   CHAIN           3929..4127
FT                   /note="Non-structural protein 8"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6X7"
FT                   /id="PRO_0000422446"
FT   CHAIN           4128..4237
FT                   /note="Non-structural protein 9"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6X7"
FT                   /id="PRO_0000422447"
FT   CHAIN           4238..4377
FT                   /note="Non-structural protein 10"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6X7"
FT                   /id="PRO_0000422448"
FT   CHAIN           4378..5310
FT                   /note="RNA-directed RNA polymerase"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6X7"
FT                   /id="PRO_0000422449"
FT   CHAIN           5311..5908
FT                   /note="Helicase"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6X7"
FT                   /id="PRO_0000422450"
FT   CHAIN           5909..6432
FT                   /note="Guanine-N7 methyltransferase"
FT                   /evidence="ECO:0000250, ECO:0000250|UniProtKB:P0C6X7"
FT                   /id="PRO_0000422451"
FT   CHAIN           6433..6775
FT                   /note="Uridylate-specific endoribonuclease"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6X7"
FT                   /id="PRO_0000422452"
FT   CHAIN           6776..7078
FT                   /note="2'-O-methyltransferase"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6X7"
FT                   /id="PRO_0000422453"
FT   TRANSMEM        2105..2125
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2177..2197
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2281..2301
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2305..2325
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2330..2350
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2757..2777
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        3028..3048
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        3062..3082
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        3104..3124
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        3125..3145
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        3559..3579
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        3593..3613
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        3618..3638
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        3664..3684
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        3691..3711
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        3740..3760
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        3765..3785
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          1110..1276
FT                   /note="Macro"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00490"
FT   DOMAIN          1552..1823
FT                   /note="Peptidase C16"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   DOMAIN          3248..3553
FT                   /note="Peptidase C30"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00772"
FT   DOMAIN          4990..5152
FT                   /note="RdRp catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT   DOMAIN          5311..5394
FT                   /note="CV ZBD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT   ZN_FING         1672..1709
FT                   /note="C4-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   ZN_FING         4311..4327
FT   ZN_FING         4354..4367
FT   NP_BIND         5592..5599
FT                   /note="ATP"
FT                   /evidence="ECO:0000250"
FT   REGION          2040..2363
FT                   /note="HD1"
FT   REGION          2761..3171
FT                   /note="HD2"
FT   REGION          3571..3785
FT                   /note="HD3"
FT   ACT_SITE        1592
FT                   /note="For PL-PRO activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   ACT_SITE        1759
FT                   /note="For PL-PRO activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   ACT_SITE        3288
FT                   /note="For 3CL-PRO activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00772"
FT   ACT_SITE        3395
FT                   /note="For 3CL-PRO activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00772"
FT   METAL           4311
FT                   /note="Zinc"
FT   METAL           4314
FT                   /note="Zinc"
FT   METAL           4320
FT                   /note="Zinc"
FT   METAL           4327
FT                   /note="Zinc"
FT   METAL           4354
FT                   /note="Zinc"
FT   METAL           4357
FT                   /note="Zinc"
FT   METAL           4365
FT                   /note="Zinc"
FT   METAL           5315
FT                   /note="Zinc 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT   METAL           5318
FT                   /note="Zinc 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT   METAL           5326
FT                   /note="Zinc 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT   METAL           5329
FT                   /note="Zinc 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT   METAL           5336
FT                   /note="Zinc 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT   METAL           5339
FT                   /note="Zinc 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT   METAL           5343
FT                   /note="Zinc 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT   METAL           5349
FT                   /note="Zinc 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT   METAL           5360
FT                   /note="Zinc 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT   METAL           5365
FT                   /note="Zinc 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT   METAL           5382
FT                   /note="Zinc 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT   METAL           5385
FT                   /note="Zinc 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT   SITE            193..194
FT                   /note="Cleavage"
FT                   /evidence="ECO:0000250"
FT   SITE            853..854
FT                   /note="Cleavage; by PL-PRO"
FT                   /evidence="ECO:0000250"
FT   SITE            2740..2741
FT                   /note="Cleavage; by PL-PRO"
FT                   /evidence="ECO:0000250"
FT   SITE            3247..3248
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250"
FT   SITE            3553..3554
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250"
FT   SITE            3845..3846
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250"
FT   SITE            3928..3929
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250"
FT   SITE            4127..4128
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250"
FT   SITE            4237..4238
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250"
FT   SITE            4377..4378
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250"
FT   SITE            5310..5311
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250"
FT   SITE            5908..5909
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250"
FT   SITE            6432..6433
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250"
FT   SITE            6775..6776
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250"
FT   HELIX           1110..1113
FT                   /evidence="ECO:0000244|PDB:5HOL"
FT   STRAND          1116..1118
FT                   /evidence="ECO:0000244|PDB:5HOL"
FT   STRAND          1120..1128
FT                   /evidence="ECO:0000244|PDB:5HOL"
FT   HELIX           1130..1135
FT                   /evidence="ECO:0000244|PDB:5HOL"
FT   STRAND          1141..1146
FT                   /evidence="ECO:0000244|PDB:5HOL"
FT   HELIX           1156..1163
FT                   /evidence="ECO:0000244|PDB:5HOL"
FT   TURN            1164..1166
FT                   /evidence="ECO:0000244|PDB:5HOL"
FT   HELIX           1167..1179
FT                   /evidence="ECO:0000244|PDB:5HOL"
FT   STRAND          1187..1191
FT                   /evidence="ECO:0000244|PDB:5HOL"
FT   TURN            1193..1195
FT                   /evidence="ECO:0000244|PDB:5HOL"
FT   STRAND          1196..1203
FT                   /evidence="ECO:0000244|PDB:5HOL"
FT   HELIX           1207..1209
FT                   /evidence="ECO:0000244|PDB:5HOL"
FT   HELIX           1213..1215
FT                   /evidence="ECO:0000244|PDB:5HOL"
FT   HELIX           1216..1223
FT                   /evidence="ECO:0000244|PDB:5HOL"
FT   STRAND          1226..1231
FT                   /evidence="ECO:0000244|PDB:5HOL"
FT   HELIX           1243..1253
FT                   /evidence="ECO:0000244|PDB:5HOL"
FT   STRAND          1256..1263
FT                   /evidence="ECO:0000244|PDB:5HOL"
FT   HELIX           1265..1272
FT                   /evidence="ECO:0000244|PDB:5HOL"
FT   STRAND          1485..1494
FT                   /evidence="ECO:0000244|PDB:4WUR"
FT   STRAND          1496..1501
FT                   /evidence="ECO:0000244|PDB:4WUR"
FT   STRAND          1503..1505
FT                   /evidence="ECO:0000244|PDB:4WUR"
FT   HELIX           1507..1510
FT                   /evidence="ECO:0000244|PDB:4WUR"
FT   STRAND          1513..1516
FT                   /evidence="ECO:0000244|PDB:4WUR"
FT   HELIX           1528..1530
FT                   /evidence="ECO:0000244|PDB:4WUR"
FT   STRAND          1534..1537
FT                   /evidence="ECO:0000244|PDB:4WUR"
FT   HELIX           1545..1553
FT                   /evidence="ECO:0000244|PDB:5KO3"
FT   HELIX           1560..1570
FT                   /evidence="ECO:0000244|PDB:5KO3"
FT   HELIX           1571..1573
FT                   /evidence="ECO:0000244|PDB:5KO3"
FT   STRAND          1576..1579
FT                   /evidence="ECO:0000244|PDB:5KO3"
FT   STRAND          1582..1585
FT                   /evidence="ECO:0000244|PDB:5KO3"
FT   TURN            1589..1591
FT                   /evidence="ECO:0000244|PDB:5KO3"
FT   HELIX           1592..1601
FT                   /evidence="ECO:0000244|PDB:5KO3"
FT   STRAND          1607..1611
FT                   /evidence="ECO:0000244|PDB:5KO3"
FT   HELIX           1612..1622
FT                   /evidence="ECO:0000244|PDB:5KO3"
FT   HELIX           1627..1636
FT                   /evidence="ECO:0000244|PDB:5KO3"
FT   HELIX           1647..1655
FT                   /evidence="ECO:0000244|PDB:5KO3"
FT   STRAND          1658..1662
FT                   /evidence="ECO:0000244|PDB:5KO3"
FT   STRAND          1665..1672
FT                   /evidence="ECO:0000244|PDB:5KO3"
FT   TURN            1673..1675
FT                   /evidence="ECO:0000244|PDB:5KO3"
FT   STRAND          1676..1683
FT                   /evidence="ECO:0000244|PDB:5KO3"
FT   HELIX           1684..1687
FT                   /evidence="ECO:0000244|PDB:5KO3"
FT   STRAND          1688..1692
FT                   /evidence="ECO:0000244|PDB:5KO3"
FT   HELIX           1696..1700
FT                   /evidence="ECO:0000244|PDB:5KO3"
FT   STRAND          1703..1706
FT                   /evidence="ECO:0000244|PDB:5KO3"
FT   STRAND          1708..1721
FT                   /evidence="ECO:0000244|PDB:5KO3"
FT   STRAND          1723..1740
FT                   /evidence="ECO:0000244|PDB:5KO3"
FT   STRAND          1745..1752
FT                   /evidence="ECO:0000244|PDB:5KO3"
FT   STRAND          1759..1766
FT                   /evidence="ECO:0000244|PDB:5KO3"
FT   STRAND          1769..1774
FT                   /evidence="ECO:0000244|PDB:5KO3"
FT   STRAND          1777..1794
FT                   /evidence="ECO:0000244|PDB:5KO3"
FT   STRAND          1797..1799
FT                   /evidence="ECO:0000244|PDB:5KO3"
SQ   SEQUENCE   7078 AA;  789563 MW;  A944AF691D57A1E0 CRC64;
     MSFVAGVTAQ GARGTYRAAL NSEKHQDHVS LTVPLCGSGN LVEKLSPWFM DGENAYEVVK
     AMLLKKEPLL YVPIRLAGHT RHLPGPRVYL VERLIACENP FMVNQLAYSS SANGSLVGTT
     LQGKPIGMFF PYDIELVTGK QNILLRKYGR GGYHYTPFHY ERDNTSCPEW MDDFEADPKG
     KYAQNLLKKL IGGDVTPVDQ YMCGVDGKPI SAYAFLMAKD GITKLADVEA DVAARADDEG
     FITLKNNLYR LVWHVERKDV PYPKQSIFTI NSVVQKDGVE NTPPHYFTLG CKILTLTPRN
     KWSGVSDLSL KQKLLYTFYG KESLENPTYI YHSAFIECGS CGNDSWLTGN AIQGFACGCG
     ASYTANDVEV QSSGMIKPNA LLCATCPFAK GDSCSSNCKH SVAQLVSYLS ERCNVIADSK
     SFTLIFGGVA YAYFGCEEGT MYFVPRAKSV VSRIGDSIFT GCTGSWNKVT QIANMFLEQT
     QHSLNFVGEF VVNDVVLAIL SGTTTNVDKI RQLLKGVTLD KLRDYLADYD VAVTAGPFMD
     NAINVGGTGL QYAAITAPYV VLTGLGESFK KVATIPYKVC NSVKDTLTYY AHSVLYRVFP
     YDMDSGVSSF SELLFDCVDL SVASTYFLVR LLQDKTGDFM STIITSCQTA VSKLLDTCFE
     ATEATFNFLL DLAGLFRIFL RNAYVYTSQG FVVVNGKVST LVKQVLDLLN KGMQLLHTKV
     SWAGSNISAV IYSGRESLIF PSGTYYCVTT KAKSVQQDLD VILPGEFSKK QLGLLQPTDN
     STTVSVTVSS NMVETVVGQL EQTNMHSPDV IVGDYVIISE KLFVRSKEED GFAFYPACTN
     GHAVPTLFRL KGGAPVKKVA FGGDQVHEVA AVRSVTVEYN IHAVLDTLLA SSSLRTFVVD
     KSLSIEEFAD VVKEQVSDLL VKLLRGMPIP DFDLDDFIDA PCYCFNAEGD ASWSSTMIFS
     LHPVECDEEC SEVEASDLEE GESECISETS TEQVDVSHEI SDDEWAAAVD EAFPLDEAED
     VTESVQEEAQ PVEVPVEDIA QVVIADTLQE TPVVSDTVEV PPQVVKLPSE PQTIQPEVKE
     VAPVYEADTE QTQSVTVKPK RLRKKRNVDP LSNFEHKVIT ECVTIVLGDA IQVAKCYGES
     VLVNAANTHL KHGGGIAGAI NAASKGAVQK ESDEYILAKG PLQVGDSVLL QGHSLAKNIL
     HVVGPDARAK QDVSLLSKCY KAMNAYPLVV TPLVSAGIFG VKPAVSFDYL IREAKTRVLV
     VVNSQDVYKS LTIVDIPQSL TFSYDGLRGA IRKAKDYGFT VFVCTDNSAN TKVLRNKGVD
     YTKKFLTVDG VQYYCYTSKD TLDDILQQAN KSVGIISMPL GYVSHGLDLI QAGSVVRRVN
     VPYVCLLANK EQEAILMSED VKLNPSEDFI KHVRTNGGYN SWHLVEGELL VQDLRLNKLL
     HWSDQTICYK DSVFYVVKNS TAFPFETLSA CRAYLDSRTT QQLTIEVLVT VDGVNFRTVV
     LNNKNTYRSQ LGCVFFNGAD ISDTIPDEKQ NGHSLYLADN LTADETKALK ELYGPVDPTF
     LHRFYSLKAA VHKWKMVVCD KVRSLKLSDN NCYLNAVIMT LDLLKDIKFV IPALQHAFMK
     HKGGDSTDFI ALIMAYGNCT FGAPDDASRL LHTVLAKAEL CCSARMVWRE WCNVCGIKDV
     VLQGLKACCY VGVQTVEDLR ARMTYVCQCG GERHRQIVEH TTPWLLLSGT PNEKLVTTST
     APDFVAFNVF QGIETAVGHY VHARLKGGLI LKFDSGTVSK TSDWKCKVTD VLFPGQKYSS
     DCNVVRYSLD GNFRTEVDPD LSAFYVKDGK YFTSEPPVTY SPATILAGSV YTNSCLVSSD
     GQPGGDAISL SFNNLLGFDS SKPVTKKYTY SFLPKEDGDV LLAEFDTYDP IYKNGAMYKG
     KPILWVNKAS YDTNLNKFNR ASLRQIFDVA PIELENKFTP LSVESTPVEP PTVDVVALQQ
     EMTIVKCKGL NKPFVKDNVS FVADDSGTPV VEYLSKEDLH TLYVDPKYQV IVLKDNVLSS
     MLRLHTVESG DINVVAASGS LTRKVKLLFR ASFYFKEFAT RTFTATTAVG SCIKSVVRHL
     GVTKGILTGC FSFVKMLFML PLAYFSDSKL GTTEVKVSAL KTAGVVTGNV VKQCCTAAVD
     LSMDKLRRVD WKSTLRLLLM LCTTMVLLSS VYHLYVFNQV LSSDVMFEDA QGLKKFYKEV
     RAYLGISSAC DGLASAYRAN SFDVPTFCAN RSAMCNWCLI SQDSITHYPA LKMVQTHLSH
     YVLNIDWLWF AFETGLAYML YTSAFNWLLL AGTLHYFFAQ TSIFVDWRSY NYAVSSAFWL
     FTHIPMAGLV RMYNLLACLW LLRKFYQHVI NGCKDTACLL CYKRNRLTRV EASTVVCGGK
     RTFYITANGG ISFCRRHNWN CVDCDTAGVG NTFICEEVAN DLTTALRRPI NATDRSHYYV
     DSVTVKETVV QFNYRRDGQP FYERFPLCAF TNLDKLKFKE VCKTTTGIPE YNFIIYDSSD
     RGQESLARSA CVYYSQVLCK SILLVDSSLV TSVGDSSEIA TKMFDSFVNS FVSLYNVTRD
     KLEKLISTAR DGVRRGDNFH SVLTTFIDAA RGPAGVESDV ETNEIVDSVQ YAHKHDIQIT
     NESYNNYVPS YVKPDSVSTS DLGSLIDCNA ASVNQIVLRN SNGACIWNAA AYMKLSDALK
     RQIRIACRKC NLAFRLTTSK LRANDNILSV RFTANKIVGG APTWFNALRD FTLKGYVLAT
     IIVFLCAVLM YLCLPTFSMV PVEFYEDRIL DFKVLDNGII RDVNPDDKCF ANKHRSFTQW
     YHEHVGGVYD NSITCPLTVA VIAGVAGARI PDVPTTLAWV NNQIIFFVSR VFANTGSVCY
     TPIDEIPYKS FSDSGCILPS ECTMFRDAEG RMTPYCHDPT VLPGAFAYSQ MRPHVRYDLY
     DGNMFIKFPE VVFESTLRIT RTLSTQYCRF GSCEYAQEGV CITTNGSWAI FNDHHLNRPG
     VYCGSDFIDI VRRLAVSLFQ PITYFQLTTS LVLGIGLCAF LTLLFYYINK VKRAFADYTQ
     CAVIAVVAAV LNSLCICFVA SIPLCIVPYT ALYYYATFYF TNEPAFIMHV SWYIMFGPIV
     PIWMTCVYTV AMCFRHFFWV LAYFSKKHVE VFTDGKLNCS FQDAASNIFV INKDTYAALR
     NSLTNDAYSR FLGLFNKYKY FSGAMETAAY REAAACHLAK ALQTYSETGS DLLYQPPNCS
     ITSGVLQSGL VKMSHPSGDV EACMVQVTCG SMTLNGLWLD NTVWCPRHVM CPADQLSDPN
     YDALLISMTN HSFSVQKHIG APANLRVVGH AMQGTLLKLT VDVANPSTPA YTFTTVKPGA
     AFSVLACYNG RPTGTFTVVM RPNYTIKGSF LCGSCGSVGY TKEGSVINFC YMHQMELANG
     THTGSAFDGT MYGAFMDKQV HQVQLTDKYC SVNVVAWLYA AILNGCAWFV KPNRTSVVSF
     NEWALANQFT EFVGTQSVDM LAVKTGVAIE QLLYAIQQLY TGFQGKQILG STMLEDEFTP
     EDVNMQIMGV VMQSGVRKVT YGTAHWLFAT LVSTYVIILQ ATKFTLWNYL FETIPTQLFP
     LLFVTMAFVM LLVKHKHTFL TLFLLPVAIC LTYANIVYEP TTPISSALIA VANWLAPTNA
     YMRTTHTDIG VYISMSLVLV IVVKRLYNPS LSNFALALCS GVMWLYTYSI GEASSPIAYL
     VFVTTLTSDY TITVFVTVNL AKVCTYAIFA YSPQLTLVFP EVKMILLLYT CLGFMCTCYF
     GVFSLLNLKL RAPMGVYDFK VSTQEFRFMT ANNLTAPRNS WEAMALNFKL IGIGGTPCIK
     VAAMQSKLTD LKCTSVVLLS VLQQLHLEAN SRAWAFCVKC HNDILAATDP SEAFEKFVSL
     FATLMTFSGN VDLDALASDI FDTPSVLQAT LSEFSHLATF AELEAAQKAY QEAMDSGDTS
     PQVLKALQKA VNIAKNAYEK DKAVARKLER MADQAMTSMY KQARAEDKKA KIVSAMQTML
     FGMIKKLDND VLNGIISNAR NGCIPLSVIP LCASNKLRVV IPDFTVWNQV VTYPSLNYAG
     ALWDITVINN VDNEIVKSSD VVDSNENLTW PLVLECTRAS TSAVKLQNNE IKPSGLKTMV
     VSAGQEQTNC NTSSLAYYEP VQGRKMLMAL LSDNAYLKWA RVEGKDGFVS VELQPPCKFL
     IAGPKGPEIR YLYFVKNLNN LHRGQVLGHI AATVRLQAGS NTEFASNSSV LSLVNFTVDP
     QKAYLDFVNA GGAPLTNCVK MLTPKTGTGI AISVKPESTA DQETYGGASV CLYCRAHIEH
     PDVSGVCKYK GKFVQIPAQC VRDPVGFCLS NTPCNVCQYW IGYGCNCDSL RQAALPQSKD
     SNFLKRVRGS IVNARIEPCS SGLSTDVVFR AFDICNYKAK VAGIGKYYKT NTCRFVELDD
     QGHHLDSYFV VKRHTMENYE LEKHCYDLLR DCDAVAPHDF FIFDVDKVKT PHIVRQRLTE
     YTMMDLVYAL RHFDQNSEVL KAILVKYGCC DVTYFENKLW FDFVENPSVI GVYHKLGERV
     RQAILNTVKF CDHMVKAGLV GVLTLDNQDL NGKWYDFGDF VITQPGSGVA IVDSYYSYLM
     PVLSMTDCLA AETHRDCDFN KPLIEWPLTE YDFTDYKVQL FEKYFKYWDQ TYHANCVNCT
     DDRCVLHCAN FNVLFAMTMP KTCFGPIVRK IFVDGVPFVV SCGYHYKELG LVMNMDVSLH
     RHRLSLKELM MYAADPAMHI ASSNAFLDLR TSCFSVAALT TGLTFQTVRP GNFNQDFYDF
     VVSKGFFKEG SSVTLKHFFF AQDGNAAITD YNYYSYNLPT MCDIKQMLFC MEVVNKYFEI
     YDGGCLNASE VVVNNLDKSA GHPFNKFGKA RVYYESMSYQ EQDELFAMTK RNVIPTMTQM
     NLKYAISAKN RARTVAGVSI LSTMTNRQYH QKMLKSMAAT RGATCVIGTT KFYGGWDFML
     KTLYKDVDNP HLMGWDYPKC DRAMPNMCRI FASLILARKH GTCCTTRDRF YRLANECAQV
     LSEYVLCGGG YYVKPGGTSS GDATTAYANS VFNILQATTA NVSALMGANG NKIVDKEVKD
     MQFDLYVNVY RSTSPDPKFV DKYYAFLNKH FSMMILSDDG VVCYNSDYAA KGYIAGIQNF
     KETLYYQNNV FMSEAKCWVE TDLKKGPHEF CSQHTLYIKD GDDGYFLPYP DPSRILSAGC
     FVDDIVKTDG TLMVERFVSL AIDAYPLTKH EDIEYQNVFW VYLQYIEKLY KDLTGHMLDS
     YSVMLCGDNS AKFWEEAFYR DLYSSPTTLQ AVGSCVVCHS QTSLRCGTCI RRPFLCCKCC
     YDHVIATPHK MVLSVSPYVC NAPGCGVSDV TKLYLGGMSY FCVDHRPVCS FPLCANGLVF
     GLYKNMCTGS PSIVEFNRLA TCDWTESGDY TLANTTTEPL KLFAAETLRA TEEASKQSYA
     IATIKEIVGE RQLLLVWEAG KSKPPLNRNY VFTGYHITKN SKVQLGEYIF ERIDYSDAVS
     YKSSTTYKLT VGDIFVLTSH SVATLTAPTI VNQERYVKIT GLYPTITVPE EFASHVANFQ
     KSGYSKYVTV QGPPGTGKSH FAIGLAIYYP TARVVYTACS HAAVDALCEK AFKYLNIAKC
     SRIIPAKARV ECYDRFKVNE TNSQYLFSTI NALPETSADI LVVDEVSMCT NYDLSIINAR
     IKAKHIVYVG DPAQLPAPRT LLTRGTLEPE NFNSVTRLMC NLGPDIFLSM CYRCPKEIVS
     TVSALVYNNK LLAKKELSGQ CFKILYKGNV THDASSAINR PQLTFVKNFI TANPAWSKAV
     FISPYNSQNA VARSMLGLTT QTVDSSQGSE YQYVIFCQTA DTAHANNINR FNVAITRAQK
     GILCVMTSQA LFESLEFTEL SFTNYKLQSQ IVTGLFKDCS RETSGLSPAY APTYVSVDDK
     YKTSDELCVN LNLPANVPYS RVISRMGFKL DATVPGYPKL FITREEAVRQ VRSWIGFDVE
     GAHASRNACG TNVPLQLGFS TGVNFVVQPV GVVDTEWGNM LTGIAARPPP GEQFKHLVPL
     MHKGAAWPIV RRRIVQMLSD TLDKLSDYCT FVCWAHGFEL TSASYFCKIG KEQKCCMCNR
     RAAAYSSPLQ SYACWTHSCG YDYVYNPFFV DVQQWGYVGN LATNHDRYCS VHQGAHVASN
     DAIMTRCLAI HSCFIERVDW DIEYPYISHE KKLNSCCRIV ERNVVRAALL AGSFDKVYDI
     GNPKGIPIVD DPVVDWHYFD AQPLTRKVQQ LFYTEDMASR FADGLCLFWN CNVPKYPNNA
     IVCRFDTRVH SEFNLPGCDG GSLYVNKHAF HTPAYDVSAF RDLKPLPFFY YSTTPCEVHG
     NGSMIEDIDY VPLKSAVCIT ACNLGGAVCR KHATEYREYM EAYNLVSASG FRLWCYKTFD
     IYNLWSTFTK VQGLENIAFN FVKQGHFIGV EGELPVAVVN DKIFTKSGVN DICMFENKTT
     LPTNIAFELY AKRAVRSHPD FKLLHNLQAD ICYKFVLWDY ERSNIYGTAT IGVCKYTDID
     VNSALNICFD IRDNGSLEKF MSTPNAIFIS DRKIKKYPCM VGPDYAYFNG AIIRDSDVVK
     QPVKFYLYKK VNNEFIDPTE CIYTQSRSCS DFLPLSDMEK DFLSFDSDVF IKKYGLENYA
     FEHVVYGDFS HTTLGGLHLL IGLYKKQQEG HIIMEEMLKG SSTIHNYFIT ETNTAAFKAV
     CSVIDLKLDD FVMILKSQDL GVVSKVVKVP IDLTMIEFML WCKDGQVQTF YPRLQASADW
     KPGHAMPSLF KVQNVNLERC ELANYKQSIP MPRGVHMNIA KYMQLCQYLN TCTLAVPANM
     RVIHFGAGSD KGIAPGTSVL RQWLPTDAII IDNDLNEFVS DADITLFGDC VTVRVGQQVD
     LVISDMYDPT TKNVTGSNES KALFFTYLCN LINNNLALGG SVAIKITEHS WSVELYELMG
     KFAWWTVFCT NANASSSEGF LLGINYLGTI KENIDGGAMH ANYIFWRNST PMNLSTYSLF
     DLSKFQLKLK GTPVLQLKES QINELVISLL SQGKLLIRDN DTLSVSTDVL VNTYRKLR
//