R1A_IBVB
ID R1A_IBVB Reviewed; 3951 AA.
AC P0C6V3; P27920;
DT 10-JUN-2008, integrated into UniProtKB/Swiss-Prot.
DT 10-JUN-2008, sequence version 1.
DT 03-AUG-2022, entry version 77.
DE RecName: Full=Replicase polyprotein 1a;
DE Short=pp1a;
DE AltName: Full=ORF1a polyprotein;
DE Contains:
DE RecName: Full=Non-structural protein 2;
DE Short=nsp2;
DE AltName: Full=p87;
DE Contains:
DE RecName: Full=Papain-like protease;
DE Short=PL-PRO;
DE EC=3.4.19.12 {ECO:0000250|UniProtKB:P0C6U8};
DE EC=3.4.22.- {ECO:0000250|UniProtKB:P0C6U8};
DE AltName: Full=Non-structural protein 3;
DE Short=nsp3;
DE AltName: Full=p195;
DE Contains:
DE RecName: Full=Non-structural protein 4;
DE Short=nsp4;
DE AltName: Full=Peptide HD2;
DE AltName: Full=p41;
DE Contains:
DE RecName: Full=3C-like proteinase;
DE Short=3CL-PRO;
DE Short=3CLp;
DE EC=3.4.22.-;
DE AltName: Full=Main protease;
DE Short=Mpro;
DE AltName: Full=Non-structural protein 5;
DE Short=nsp5;
DE AltName: Full=p33;
DE Contains:
DE RecName: Full=Non-structural protein 6;
DE Short=nsp6;
DE AltName: Full=p34;
DE Contains:
DE RecName: Full=Non-structural protein 7;
DE Short=nsp7;
DE AltName: Full=p9;
DE Contains:
DE RecName: Full=Non-structural protein 8;
DE Short=nsp8;
DE AltName: Full=p24;
DE Contains:
DE RecName: Full=Non-structural protein 9;
DE Short=nsp9;
DE AltName: Full=p10;
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=p16;
DE Contains:
DE RecName: Full=Non-structural protein 11;
DE Short=nsp11;
GN ORFNames=1a;
OS Avian infectious bronchitis virus (strain Beaudette) (IBV).
OC Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes;
OC Nidovirales; Cornidovirineae; Coronaviridae; Orthocoronavirinae;
OC Gammacoronavirus; Igacovirus.
OX NCBI_TaxID=11122;
OH NCBI_TaxID=9031; Gallus gallus (Chicken).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=3027249; DOI=10.1099/0022-1317-68-1-57;
RA Boursnell M.E.G., Brown T.D.K., Foulds I.J., Green P.F., Tomley F.M.,
RA Binns M.M.;
RT "Completion of the sequence of the genome of the coronavirus avian
RT infectious bronchitis virus.";
RL J. Gen. Virol. 68:57-77(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=Isolate Vero cell-adapted p65;
RX PubMed=16137658; DOI=10.1016/j.bbrc.2005.08.105;
RA Fang S.G., Shen S., Tay F.P., Liu D.X.;
RT "Selection of and recombination between minor variants lead to the
RT adaptation of an avian coronavirus to primate cells.";
RL Biochem. Biophys. Res. Commun. 336:417-423(2005).
RN [3]
RP PROTEOLYTIC CLEAVAGE (REPLICASE POLYPROTEIN 1A).
RX PubMed=11831730; DOI=10.1006/viro.1995.1128;
RA Liu D.X., Tibbles K.W., Cavanagh D., Brown T.D.K., Brierley I.;
RT "Identification, expression, and processing of an 87-kDa polypeptide
RT encoded by ORF 1a of the coronavirus infectious bronchitis virus.";
RL Virology 208:48-57(1995).
RN [4]
RP CHARACTERIZATION OF 3CL-PRO, AND MUTAGENESIS OF HIS-2820; GLU-2841;
RP GLU-2843; CYS-2922 AND GLN-3928.
RX PubMed=7778277; DOI=10.1006/viro.1995.1274;
RA Liu D.X., Brown T.D.K.;
RT "Characterisation and mutational analysis of an ORF 1a-encoding proteinase
RT domain responsible for proteolytic processing of the infectious bronchitis
RT virus 1a/1b polyprotein.";
RL Virology 209:420-427(1995).
RN [5]
RP PROTEOLYTIC CLEAVAGE (REPLICASE POLYPROTEIN 1A), AND MUTAGENESIS OF
RP GLN-3672 AND GLN-3783.
RX PubMed=9032311; DOI=10.1128/jvi.71.3.1814-1820.1997;
RA Liu D.X., Xu H.Y., Brown T.D.K.;
RT "Proteolytic processing of the coronavirus infectious bronchitis virus 1a
RT polyprotein: identification of a 10-kilodalton polypeptide and
RT determination of its cleavage sites.";
RL J. Virol. 71:1814-1820(1997).
RN [6]
RP PROTEOLYTIC CLEAVAGE (REPLICASE POLYPROTEIN 1A), AND MUTAGENESIS OF
RP GLN-3462; GLN-3672 AND GLN-3783.
RX PubMed=9568037; DOI=10.1006/viro.1998.9058;
RA Ng L.F.P., Liu D.X.;
RT "Identification of a 24-kDa polypeptide processed from the coronavirus
RT infectious bronchitis virus 1a polyprotein by the 3C-like proteinase and
RT determination of its cleavage sites.";
RL Virology 243:388-395(1998).
RN [7]
RP PROTEOLYTIC CLEAVAGE (REPLICASE POLYPROTEIN 1A), CHARACTERIZATION OF
RP PAPAIN-LIKE PROTEINASE DOMAINS, AND MUTAGENESIS OF GLY-673; THR-676;
RP CYS-1274 AND HIS-1437.
RX PubMed=9636369; DOI=10.1006/viro.1998.9164;
RA Lim K.P., Liu D.X.;
RT "Characterization of the two overlapping papain-like proteinase domains
RT encoded in gene 1 of the coronavirus infectious bronchitis virus and
RT determination of the C-terminal cleavage site of an 87-kDa protein.";
RL Virology 245:303-312(1998).
RN [8]
RP PROTEOLYTIC CLEAVAGE (REPLICASE POLYPROTEIN 1A).
RX PubMed=9657947; DOI=10.1006/viro.1998.9199;
RA Liu D.X., Shen S., Xu H.Y., Wang S.F.;
RT "Proteolytic mapping of the coronavirus infectious bronchitis virus 1b
RT polyprotein: evidence for the presence of four cleavage sites of the 3C-
RT like proteinase and identification of two novel cleavage products.";
RL Virology 246:288-297(1998).
RN [9]
RP PROTEOLYTIC CLEAVAGE (REPLICASE POLYPROTEIN 1A), GLYCOSYLATION OF NSP4, AND
RP MUTAGENESIS OF ALA-2264; GLY-2265 AND GLY-2266.
RX PubMed=10644337; DOI=10.1128/jvi.74.4.1674-1685.2000;
RA Lim K.P., Ng L.F.P., Liu D.X.;
RT "Identification of a novel cleavage activity of the first papain-like
RT proteinase domain encoded by open reading frame 1a of the coronavirus avian
RT infectious bronchitis virus and characterization of the cleavage
RT products.";
RL J. Virol. 74:1674-1685(2000).
RN [10]
RP PROTEOLYTIC CLEAVAGE (REPLICASE POLYPROTEIN 1A), AND MUTAGENESIS OF
RP GLN-3086; GLN-3365 AND GLN-3379.
RX PubMed=10873746; DOI=10.1006/viro.2000.0330;
RA Ng L.F.P., Liu D.X.;
RT "Further characterization of the coronavirus infectious bronchitis virus
RT 3C-like proteinase and determination of a new cleavage site.";
RL Virology 272:27-39(2000).
RN [11]
RP PROTEOLYTIC CLEAVAGE (REPLICASE POLYPROTEIN 1A), AND SUBCELLULAR LOCATION.
RX PubMed=11601893; DOI=10.1006/viro.2001.1098;
RA Xu H.Y., Lim K.P., Shen S., Liu D.X.;
RT "Further identification and characterization of novel intermediate and
RT mature cleavage products released from the ORF 1b region of the avian
RT coronavirus infectious bronchitis virus 1a/1b polyprotein.";
RL Virology 288:212-222(2001).
RN [12]
RP CHARACTERIZATION (NON-STRUCTURAL PROTEIN 10), AND MUTAGENESIS.
RX PubMed=12021359; DOI=10.1128/jvi.76.12.6257-6267.2002;
RA Ng L.F.P., Liu D.X.;
RT "Membrane association and dimerization of a cysteine-rich, 16-kilodalton
RT polypeptide released from the C-terminal region of the coronavirus
RT infectious bronchitis virus 1a polyprotein.";
RL J. Virol. 76:6257-6267(2002).
CC -!- FUNCTION: [Isoform Replicase polyprotein 1a]: Multifunctional protein
CC involved in the transcription and replication of viral RNAs. Contains
CC the proteinases responsible for the cleavages of the polyprotein.
CC {ECO:0000305}.
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 (By similarity). Indeed, these two proteins play a role in
CC maintaining the functional integrity of the mitochondria and protecting
CC cells from various stresses (By similarity).
CC {ECO:0000250|UniProtKB:P0C6U8}.
CC -!- FUNCTION: [Papain-like protease]: Responsible for the cleavages located
CC at the N-terminus of the replicase polyprotein (By similarity). In
CC addition, PL-PRO possesses a deubiquitinating/deISGylating activity and
CC processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from
CC cellular substrates (By similarity). {ECO:0000250|UniProtKB:P0C6U8}.
CC -!- FUNCTION: [Non-structural protein 4]: Plays a role in host membrane
CC rearrangement that leads to creation of cytoplasmic double-membrane
CC vesicles (DMV) necessary for viral replication (By similarity). Alone
CC is able to induce paired membranes (By similarity). Coexpression of
CC nsp3 and nsp4 does not result in the formation of DMVs (By similarity).
CC {ECO:0000250|UniProtKB:P0C6U8}.
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. {ECO:0000255|PROSITE-ProRule:PRU00772}.
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:P0C6U8}.
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:P0C6U8}.
CC -!- FUNCTION: [Non-structural protein 9]: Plays an essential role in viral
CC replication by forming a homodimer that binds single-stranded RNA.
CC {ECO:0000250|UniProtKB:P0C6U8}.
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 (By similarity). Therefore plays an
CC essential role in viral mRNAs cap methylation (By similarity).
CC {ECO:0000250|UniProtKB:P0C6U8}.
CC -!- CATALYTIC ACTIVITY: [Papain-like protease]:
CC Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide
CC and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-
CC residue protein attached to proteins as an intracellular targeting
CC signal).; EC=3.4.19.12; Evidence={ECO:0000250|UniProtKB:P0C6U8};
CC -!- COFACTOR: [Papain-like protease]:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:P0C6U8};
CC -!- SUBUNIT: [Non-structural protein 2]: Interacts with host PHB and PHB2.
CC {ECO:0000250|UniProtKB:P0C6U8}.
CC -!- SUBUNIT: [Non-structural protein 4]: Interacts with papain-like
CC protease and non-structural protein 6. {ECO:0000250|UniProtKB:P0C6U8}.
CC -!- SUBUNIT: [3C-like proteinase]: Monomer. Homodimer. Only the homodimer
CC shows catalytic activity. {ECO:0000250|UniProtKB:P0C6U8}.
CC -!- SUBUNIT: [Non-structural protein 7]: Eight copies of nsp7 and eight
CC copies of nsp8 assemble to form a heterohexadecamer dsRNA-encircling
CC ring structure. {ECO:0000250|UniProtKB:P0C6U8}.
CC -!- SUBUNIT: [Non-structural protein 8]: Eight copies of nsp7 and eight
CC copies of nsp8 assemble to form a heterohexadecamer dsRNA-encircling
CC ring structure (By similarity). Interacts with ORF6 protein (By
CC similarity). {ECO:0000250|UniProtKB:P0C6U8}.
CC -!- SUBUNIT: [Non-structural protein 9]: Homodimer.
CC {ECO:0000250|UniProtKB:P0C6U8}.
CC -!- SUBUNIT: [Non-structural protein 10]: Homododecamer.
CC {ECO:0000250|UniProtKB:P0C6U8}.
CC -!- INTERACTION:
CC PRO_0000338322; PRO_0000338322 [P0C6V3]: 1a; NbExp=3; IntAct=EBI-25618172, EBI-25618172;
CC -!- SUBCELLULAR LOCATION: [Papain-like protease]: Host endoplasmic
CC reticulum membrane {ECO:0000250|UniProtKB:P0C6Y3}; Multi-pass membrane
CC protein {ECO:0000305}. Host cytoplasm {ECO:0000250|UniProtKB:P0C6U8}.
CC Note=Gammacoronaviruses induce membrane zippering to form zippered
CC endoplasmic reticulum (zER). {ECO:0000250|UniProtKB:P0C6Y3}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 4]: Host endoplasmic
CC reticulum membrane {ECO:0000250|UniProtKB:P0C6Y3}; Multi-pass membrane
CC protein {ECO:0000305}. Host cytoplasm {ECO:0000250|UniProtKB:P0C6U8}.
CC Note=Localizes in virally-induced cytoplasmic double-membrane vesicles
CC (By similarity). Gammacoronaviruses induce membrane zippering to form
CC zippered endoplasmic reticulum (zER) (By similarity).
CC {ECO:0000250|UniProtKB:P0C6U8, ECO:0000250|UniProtKB:P0C6Y3}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 6]: Host endoplasmic
CC reticulum membrane {ECO:0000250|UniProtKB:P0C6Y3}; Multi-pass membrane
CC protein {ECO:0000305}. Note=Gammacoronaviruses induce membrane
CC zippering to form zippered endoplasmic reticulum (zER).
CC {ECO:0000250|UniProtKB:P0C6Y3}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 7]: Host cytoplasm, host
CC perinuclear region {ECO:0000250}. Host cytoplasm
CC {ECO:0000250|UniProtKB:P0DTD1}. Host endoplasmic reticulum
CC {ECO:0000250|UniProtKB:P0DTD1}. Note=nsp7, nsp8, nsp9 and nsp10 are
CC localized in cytoplasmic foci, largely perinuclear. Late in infection,
CC they merge into confluent complexes.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 8]: Host cytoplasm, host
CC perinuclear region {ECO:0000250|UniProtKB:P0C6U8}. Host cytoplasm
CC {ECO:0000250|UniProtKB:P0DTD1}. Host endoplasmic reticulum
CC {ECO:0000250|UniProtKB:P0DTD1}. Note=nsp7, nsp8, nsp9 and nsp10 are
CC localized in cytoplasmic foci, largely perinuclear. Late in infection,
CC they merge into confluent complexes.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 9]: Host cytoplasm, host
CC perinuclear region {ECO:0000250}. Host cytoplasm
CC {ECO:0000250|UniProtKB:P0DTD1}. Host endoplasmic reticulum
CC {ECO:0000250|UniProtKB:P0DTD1}. Note=nsp7, nsp8, nsp9 and nsp10 are
CC localized in cytoplasmic foci, largely perinuclear. Late in infection,
CC they merge into confluent complexes.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 10]: Host cytoplasm, host
CC perinuclear region {ECO:0000250}. Host cytoplasm
CC {ECO:0000250|UniProtKB:P0DTD1}. Host endoplasmic reticulum
CC {ECO:0000250|UniProtKB:P0DTD1}. Note=nsp7, nsp8, nsp9 and nsp10 are
CC localized in cytoplasmic foci, largely perinuclear. Late in infection,
CC they merge into confluent complexes.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Ribosomal frameshifting; Named isoforms=2;
CC Comment=Isoform Replicase polyprotein 1ab is produced by -1 ribosomal
CC frameshifting at the 1a-1b genes boundary. Isoform Replicase
CC polyprotein 1a is produced by conventional translation.
CC {ECO:0000305};
CC Name=Replicase polyprotein 1a; Synonyms=pp1a, ORF1a polyprotein;
CC IsoId=P0C6V3-1; Sequence=Displayed;
CC Name=Replicase polyprotein 1ab; Synonyms=pp1ab;
CC IsoId=P0C6Y1-1; Sequence=External;
CC -!- DOMAIN: [Papain-like protease]: The hydrophobic region HD1 probably
CC mediates the membrane association of the replication complex.
CC {ECO:0000250|UniProtKB:P0C6U8}.
CC -!- DOMAIN: [Non-structural protein 4]: The hydrophobic region HD2 probably
CC mediates the membrane association of the replication complex.
CC {ECO:0000250|UniProtKB:P0C6U8}.
CC -!- DOMAIN: [Non-structural protein 6]: The hydrophobic region HD3 probably
CC mediates the membrane association of the replication complex.
CC {ECO:0000250|UniProtKB:P0C6U8}.
CC -!- PTM: [Isoform Replicase polyprotein 1a]: Specific enzymatic cleavages
CC in vivo by its own proteases yield mature proteins (By similarity). 3C-
CC like proteinase nsp5 liberates nsps 6-16 from the polyprotein (By
CC similarity). Papain-like and 3C-like proteinases are autocatalytically
CC processed. {ECO:0000250|UniProtKB:P0C6U8}.
CC -!- PTM: [Non-structural protein 4]: N-glycosylated.
CC {ECO:0000250|UniProtKB:P0C6Y1}.
CC -!- SIMILARITY: Belongs to the coronaviruses polyprotein 1ab family.
CC {ECO:0000305}.
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DR EMBL; M94356; AAA46223.1; -; Genomic_RNA.
DR EMBL; M95169; AAA70233.1; -; Genomic_RNA.
DR EMBL; DQ001339; AAY24431.1; -; Genomic_RNA.
DR PIR; A33094; VFIHB1.
DR PIR; B33094; VFIHB2.
DR RefSeq; NP_040829.1; NC_001451.1.
DR SMR; P0C6V3; -.
DR MEROPS; C16.005; -.
DR MEROPS; C30.002; -.
DR PRIDE; P0C6V3; -.
DR GeneID; 1489740; -.
DR BRENDA; 3.4.22.B14; 8728.
DR SABIO-RK; P0C6V3; -.
DR Proteomes; UP000006717; Genome.
DR GO; GO:0044167; C:host cell endoplasmic reticulum 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:0004197; F:cysteine-type endopeptidase activity; IEA:InterPro.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0016829; F:lyase 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:0016740; F:transferase activity; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0039520; P:induction by virus of host autophagy; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0019079; P:viral genome replication; IEA:InterPro.
DR GO; GO:0019082; P:viral protein processing; IEA:InterPro.
DR CDD; cd21512; cv_gamma-delta_Nsp2_IBV-like; 1.
DR CDD; cd21473; cv_Nsp4_TM; 1.
DR CDD; cd21559; gammaCoV-Nsp6; 1.
DR CDD; cd21667; gammaCoV_Nsp5_Mpro; 1.
DR CDD; cd21557; Macro_X_Nsp3-like; 1.
DR Gene3D; 1.10.150.420; -; 1.
DR Gene3D; 1.10.1840.10; -; 1.
DR Gene3D; 1.10.8.1190; -; 1.
DR Gene3D; 1.10.8.370; -; 1.
DR Gene3D; 2.40.10.10; -; 2.
DR Gene3D; 2.40.10.250; -; 1.
DR Gene3D; 2.60.120.1680; -; 1.
DR Gene3D; 3.30.70.3540; -; 1.
DR Gene3D; 3.40.220.10; -; 1.
DR InterPro; IPR043611; CoV_NSP3_C.
DR InterPro; IPR032505; CoV_NSP4_C.
DR InterPro; IPR043612; CoV_NSP4_N.
DR InterPro; IPR002589; Macro_dom.
DR InterPro; IPR043472; Macro_dom-like.
DR InterPro; IPR044371; Macro_X_NSP3-like.
DR InterPro; IPR036333; NSP10_sf_CoV.
DR InterPro; IPR040795; NSP2_gammaCoV.
DR InterPro; IPR044383; NSP2_IBV-like.
DR InterPro; IPR044357; NSP3_Ubl1_dom_CoV.
DR InterPro; IPR044353; Nsp3_Ubl2_dom_CoV.
DR InterPro; IPR038123; NSP4_C_sf_CoV.
DR InterPro; IPR044308; NSP5_Mpro_GammaCoV.
DR InterPro; IPR043610; NSP6_CoV.
DR InterPro; IPR044368; NSP6_gammaCoV.
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; 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; IPR043503; PLpro_palm_finger_dom_CoV.
DR InterPro; IPR043178; PLpro_thumb_sf_CoV.
DR InterPro; IPR018995; RNA_synth_NSP10_CoV.
DR Pfam; PF09401; CoV_NSP10; 1.
DR Pfam; PF19218; CoV_NSP3_C; 1.
DR Pfam; PF16348; CoV_NSP4_C; 1.
DR Pfam; PF19217; CoV_NSP4_N; 1.
DR Pfam; PF19213; CoV_NSP6; 1.
DR Pfam; PF08716; CoV_NSP7; 1.
DR Pfam; PF08717; CoV_NSP8; 1.
DR Pfam; PF08710; CoV_NSP9; 1.
DR Pfam; PF08715; CoV_peptidase; 1.
DR Pfam; PF01661; Macro; 1.
DR Pfam; PF17896; NSP2_gammaCoV; 1.
DR Pfam; PF05409; Peptidase_C30; 1.
DR SMART; SM00506; A1pp; 1.
DR SUPFAM; SSF101816; SSF101816; 1.
DR SUPFAM; SSF140367; SSF140367; 1.
DR SUPFAM; SSF143076; SSF143076; 1.
DR SUPFAM; SSF144246; SSF144246; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR SUPFAM; SSF52949; SSF52949; 1.
DR PROSITE; PS51952; COV_EXON_MTASE_COACT; 1.
DR PROSITE; PS51992; COV_NSP3_Y3; 1.
DR PROSITE; PS51943; COV_NSP3A_UBL; 1.
DR PROSITE; PS51944; COV_NSP3D_UBL; 1.
DR PROSITE; PS51946; COV_NSP4C; 1.
DR PROSITE; PS51949; COV_NSP7; 1.
DR PROSITE; PS51950; COV_NSP8; 1.
DR PROSITE; PS51951; COV_NSP9_SSRNA_BD; 1.
DR PROSITE; PS51442; M_PRO; 1.
DR PROSITE; PS51154; MACRO; 1.
DR PROSITE; PS51124; PEPTIDASE_C16; 1.
PE 1: Evidence at protein level;
KW Activation of host autophagy by virus; Host cytoplasm;
KW Host endoplasmic reticulum; Host membrane; Host-virus interaction;
KW Hydrolase; Lyase; Membrane; Metal-binding; Protease; Reference proteome;
KW Repeat; Ribosomal frameshifting; RNA-binding; Thiol protease;
KW Transmembrane; Transmembrane helix; Zinc; Zinc-finger.
FT CHAIN 1..3951
FT /note="Replicase polyprotein 1a"
FT /id="PRO_0000338314"
FT CHAIN 1..673
FT /note="Non-structural protein 2"
FT /id="PRO_0000338315"
FT CHAIN 674..2265
FT /note="Papain-like protease"
FT /id="PRO_0000338316"
FT CHAIN 2266..2779
FT /note="Non-structural protein 4"
FT /id="PRO_0000338317"
FT CHAIN 2780..3086
FT /note="3C-like proteinase"
FT /id="PRO_0000338318"
FT CHAIN 3087..3379
FT /note="Non-structural protein 6"
FT /id="PRO_0000338319"
FT CHAIN 3380..3462
FT /note="Non-structural protein 7"
FT /id="PRO_0000338320"
FT CHAIN 3463..3672
FT /note="Non-structural protein 8"
FT /id="PRO_0000338321"
FT CHAIN 3673..3783
FT /note="Non-structural protein 9"
FT /id="PRO_0000338322"
FT CHAIN 3784..3928
FT /note="Non-structural protein 10"
FT /id="PRO_0000338323"
FT CHAIN 3929..3951
FT /note="Non-structural protein 11"
FT /id="PRO_0000338324"
FT TOPO_DOM 1..1750
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P0C6U8"
FT TRANSMEM 1751..1771
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1772..1843
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P0C6U8"
FT TRANSMEM 1844..1864
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1865..2280
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P0C6U8"
FT TRANSMEM 2281..2301
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2302..2559
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P0C6U8"
FT TRANSMEM 2560..2580
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2581..2611
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P0C6U8"
FT TRANSMEM 2612..2632
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2633..2643
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P0C6U8"
FT TRANSMEM 2644..2664
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2665..3096
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P0C6U8"
FT TRANSMEM 3097..3117
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 3118..3121
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P0C6U8"
FT TRANSMEM 3122..3142
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 3143..3151
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P0C6U8"
FT TRANSMEM 3152..3172
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 3173..3188
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P0C6U8"
FT TRANSMEM 3189..3209
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 3210..3257
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P0C6U8"
FT TRANSMEM 3258..3278
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 3279..3296
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P0C6U8"
FT TRANSMEM 3297..3317
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 3318..3951
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P0C6U8"
FT DOMAIN 675..780
FT /note="Ubiquitin-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT DOMAIN 1003..1179
FT /note="Macro"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00490"
FT DOMAIN 1175..1227
FT /note="Ubiquitin-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT DOMAIN 1236..1497
FT /note="Peptidase C16"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT DOMAIN 2161..2263
FT /note="CoV Nsp3 Y3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT DOMAIN 2684..2779
FT /note="Nsp4C"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01291"
FT DOMAIN 2780..3086
FT /note="Peptidase C30"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00772"
FT DOMAIN 3380..3462
FT /note="RdRp Nsp7 cofactor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01294"
FT DOMAIN 3463..3672
FT /note="RdRp Nsp8 cofactor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01295"
FT DOMAIN 3673..3783
FT /note="Nsp9 ssRNA-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01296"
FT DOMAIN 3785..3926
FT /note="ExoN/MTase coactivator"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT ZN_FING 1353..1390
FT /note="C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT ZN_FING 3858..3878
FT /evidence="ECO:0000250"
FT ZN_FING 3904..3917
FT /evidence="ECO:0000250"
FT REGION 783..802
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1751..1864
FT /note="HD1"
FT /evidence="ECO:0000250|UniProtKB:P0C6U8"
FT REGION 2281..2664
FT /note="HD2"
FT /evidence="ECO:0000250|UniProtKB:P0C6U8"
FT REGION 3097..3317
FT /note="HD3"
FT /evidence="ECO:0000250|UniProtKB:P0C6U8"
FT ACT_SITE 1274
FT /note="For PL-PRO activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT ACT_SITE 1437
FT /note="For PL-PRO activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT ACT_SITE 1448
FT /note="For PL-PRO activity"
FT /evidence="ECO:0000250|UniProtKB:P0C6Y1"
FT ACT_SITE 2820
FT /note="For 3CL-PRO activity"
FT ACT_SITE 2922
FT /note="For 3CL-PRO activity"
FT BINDING 3858
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT BINDING 3861
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT BINDING 3867
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT BINDING 3878
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT BINDING 3904
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT BINDING 3907
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT BINDING 3915
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT BINDING 3917
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT SITE 673..674
FT /note="Cleavage; by PL-PRO"
FT /evidence="ECO:0000250|UniProtKB:P0C6U8"
FT SITE 2265..2266
FT /note="Cleavage; by PL-PRO"
FT /evidence="ECO:0000250|UniProtKB:P0C6U8"
FT SITE 2779..2780
FT /note="Cleavage; by 3CL-PRO"
FT /evidence="ECO:0000250|UniProtKB:P0C6U8"
FT SITE 3086..3087
FT /note="Cleavage; by 3CL-PRO"
FT /evidence="ECO:0000250|UniProtKB:P0C6U8"
FT SITE 3379..3380
FT /note="Cleavage; by 3CL-PRO"
FT /evidence="ECO:0000250|UniProtKB:P0C6U8"
FT SITE 3462..3463
FT /note="Cleavage; by 3CL-PRO"
FT /evidence="ECO:0000250|UniProtKB:P0C6U8"
FT SITE 3672..3673
FT /note="Cleavage; by 3CL-PRO"
FT /evidence="ECO:0000250|UniProtKB:P0C6U8"
FT SITE 3783..3784
FT /note="Cleavage; by 3CL-PRO"
FT /evidence="ECO:0000250|UniProtKB:P0C6U8"
FT SITE 3928..3929
FT /note="Cleavage; by 3CL-PRO"
FT /evidence="ECO:0000250|UniProtKB:P0C6U8"
FT VARIANT 105
FT /note="P -> S (in strain: Isolate Vero cell-adapted p65)"
FT VARIANT 919
FT /note="K -> E (in strain: Isolate Vero cell-adapted p65)"
FT VARIANT 932
FT /note="L -> I (in strain: Isolate Vero cell-adapted p65)"
FT VARIANT 948
FT /note="D -> G (in strain: Isolate Vero cell-adapted p65)"
FT VARIANT 967
FT /note="A -> D (in strain: Isolate Vero cell-adapted p65)"
FT VARIANT 1133
FT /note="L -> S (in strain: Isolate Vero cell-adapted p65)"
FT VARIANT 1388
FT /note="P -> S (in strain: Isolate Vero cell-adapted p65)"
FT VARIANT 1753
FT /note="L -> F (in strain: Isolate Vero cell-adapted p65)"
FT VARIANT 2561
FT /note="Q -> H (in strain: Isolate Vero cell-adapted p65)"
FT VARIANT 3058
FT /note="Missing (in strain: Isolate Vero cell-adapted p65)"
FT VARIANT 3242
FT /note="N -> S (in strain: Isolate Vero cell-adapted p65)"
FT VARIANT 3409
FT /note="V -> A (in strain: Isolate Vero cell-adapted p65)"
FT VARIANT 3418
FT /note="I -> T (in strain: Isolate Vero cell-adapted p65)"
FT VARIANT 3471..3472
FT /note="IP -> MT (in strain: Isolate Vero cell-adapted p65)"
FT VARIANT 3751
FT /note="V -> D (in strain: Isolate Vero cell-adapted p65)"
FT VARIANT 3870
FT /note="S -> G (in strain: Isolate Vero cell-adapted p65)"
FT VARIANT 3935
FT /note="D -> G (in strain: Isolate Vero cell-adapted p65)"
FT MUTAGEN 673
FT /note="G->A: No processing between p87 and p195."
FT /evidence="ECO:0000269|PubMed:9636369"
FT MUTAGEN 676
FT /note="T->S: No effect."
FT /evidence="ECO:0000269|PubMed:9636369"
FT MUTAGEN 1274
FT /note="C->S: Complete loss of PL-PRO activity."
FT /evidence="ECO:0000269|PubMed:9636369"
FT MUTAGEN 1437
FT /note="H->K: Complete loss of PL-PRO activity."
FT /evidence="ECO:0000269|PubMed:9636369"
FT MUTAGEN 2264
FT /note="A->N: Almost no processing between p195 and peptide
FT HD2."
FT /evidence="ECO:0000269|PubMed:10644337"
FT MUTAGEN 2265..2266
FT /note="Missing: No processing between p195 and peptide
FT HD2."
FT /evidence="ECO:0000269|PubMed:10644337"
FT MUTAGEN 2265
FT /note="G->A: No effect."
FT /evidence="ECO:0000269|PubMed:10644337"
FT MUTAGEN 2265
FT /note="G->N: Almost no processing between p195 and peptide
FT HD2."
FT /evidence="ECO:0000269|PubMed:10644337"
FT MUTAGEN 2266
FT /note="G->N: No effect."
FT /evidence="ECO:0000269|PubMed:10644337"
FT MUTAGEN 2820
FT /note="H->K,G: Complete loss of 3CL-PRO activity."
FT /evidence="ECO:0000269|PubMed:7778277"
FT MUTAGEN 2841
FT /note="E->Q: No effect."
FT /evidence="ECO:0000269|PubMed:7778277"
FT MUTAGEN 2843
FT /note="E->D,N,Q: No effect."
FT /evidence="ECO:0000269|PubMed:7778277"
FT MUTAGEN 2922
FT /note="C->A: Complete loss of 3CL-PRO activity."
FT /evidence="ECO:0000269|PubMed:7778277"
FT MUTAGEN 2922
FT /note="C->S: Partial loss of 3CL-PRO activity."
FT /evidence="ECO:0000269|PubMed:7778277"
FT MUTAGEN 3086
FT /note="Q->E: No processing between 3CL-PRO and p34."
FT /evidence="ECO:0000269|PubMed:10873746"
FT MUTAGEN 3365
FT /note="Q->E: No effect."
FT /evidence="ECO:0000269|PubMed:10873746"
FT MUTAGEN 3379
FT /note="Q->E: No processing between p34 and p9."
FT /evidence="ECO:0000269|PubMed:10873746"
FT MUTAGEN 3462
FT /note="Q->E: No processing between p9 and p24."
FT /evidence="ECO:0000269|PubMed:9568037"
FT MUTAGEN 3672
FT /note="Q->E: No processing between p24 and p10."
FT /evidence="ECO:0000269|PubMed:9032311,
FT ECO:0000269|PubMed:9568037"
FT MUTAGEN 3783
FT /note="Q->E: No processing between p10 and p16."
FT /evidence="ECO:0000269|PubMed:9032311,
FT ECO:0000269|PubMed:9568037"
FT MUTAGEN 3928
FT /note="Q->E: No processing between p16 and p100."
FT /evidence="ECO:0000269|PubMed:7778277"
SQ SEQUENCE 3951 AA; 441126 MW; 9B8B2E7E2545F50C CRC64;
MASSLKQGVS PKPRDVILVS KDIPEQLCDA LFFYTSHNPK DYADAFAVRQ KFDRSLQTGK
QFKFETVCGL FLLKGVDKIT PGVPAKVLKA TSKLADLEDI FGVSPLARKY RELLKTACQW
SLTVEALDVR AQTLDEIFDP TEILWLQVAA KIHVSSMAMR RLVGEVTAKV MDALGSNLSA
LFQIVKQQIA RIFQKALAIF ENVNELPQRI AALKMAFAKC ARSITVVVVE RTLVVKEFAG
TCLASINGAV AKFFEELPNG FMGSKIFTTL AFFKEAAVRV VENIPNAPRG TKGFEVVGNA
KGTQVVVRGM RNDLTLLDQK ADIPVEPEGW SAILDGHLCY VFRSGDRFYA APLSGNFALS
DVHCCERVVC LSDGVTPEIN DGLILAAIYS SFSVSELVTA LKKGEPFKFL GHKFVYAKDA
AVSFTLAKAA TIADVLRLFQ SARVIAEDVW SSFTEKSFEF WKLAYGKVRN LEEFVKTYVC
KAQMSIVILA AVLGEDIWHL VSQVIYKLGV LFTKVVDFCD KHWKGFCVQL KRAKLIVTET
FCVLKGVAQH CFQLLLDAIH SLYKSFKKCA LGRIHGDLLF WKGGVHKIVQ DGDEIWFDAI
DSVDVEDLGV VQEKSIDFEV CDDVTLPENQ PGHMVQIEDD GKNYMFFRFK KDENIYYTPM
SQLGAINVVC KAGGKTVTFG ETTVQEIPPP DVVPIKVSIE CCGEPWNTIF KKAYKEPIEV
DTDLTVEQLL SVIYEKMCDD LKLFPEAPEP PPFENVALVD KNGKDLDCIK SCHLIYRDYE
SDDDIEEEDA EECDTDSGEA EECDTNSECE EEDEDTKVLA LIQDPASIKY PLPLDEDYSV
YNGCIVHKDA LDVVNLPSGE ETFVVNNCFE GAVKPLPQKV VDVLGDWGEA VDAQEQLCQQ
EPLQHTFEEP VENSTGSSKT MTEQVVVEDQ ELPVVEQDQD VVVYTPTDLE VAKETAEEVD
EFILIFAVPK EEVVSQKDGA QIKQEPIQVV KPQREKKAKK FKVKPATCEK PKFLEYKTCV
GDLTVVIAKA LDEFKEFCIV NAANEHMTHG SGVAKAIADF CGLDFVEYCE DYVKKHGPQQ
RLVTPSFVKG IQCVNNVVGP RHGDNNLHEK LVAAYKNVLV DGVVNYVVPV LSLGIFGVDF
KMSIDAMREA FEGCTIRVLL FSLSQEHIDY FDVTCKQKTI YLTEDGVKYR SIVLKPGDSL
GQFGQVYAKN KIVFTADDVE DKEILYVPTT DKSILEYYGL DAQKYVIYLQ TLAQKWNVQY
RDNFLILEWR DGNCWISSAI VLLQAAKIRF KGFLTEAWAK LLGGDPTDFV AWCYASCTAK
VGDFSDANWL LANLAEHFDA DYTNAFLKKR VSCNCGIKSY ELRGLEACIQ PVRATNLLHF
KTQYSNCPTC GANNTDEVIE ASLPYLLLFA TDGPATVDCD EDAVGTVVFV GSTNSGHCYT
QAAGQAFDNL AKDRKFGKKS PYITAMYTRF AFKNETSLPV AKQSKGKSKS VKEDVSNLAT
SSKASFDNLT DFEQWYDSNI YESLKVQESP DNFDKYVSFT TKEDSKLPLT LKVRGIKSVV
DFRSKDGFIY KLTPDTDENS KAPVYYPVLD AISLKAIWVE GNANFVVGHP NYYSKSLHIP
TFWENAENFV KMGDKIGGVT MGLWRAEHLN KPNLERIFNI AKKAIVGSSV VTTQCGKLIG
KAATFIADKV GGGVVRNITD SIKGLCGITR GHFERKMSPQ FLKTLMFFLF YFLKASVKSV
VASYKTVLCK VVLATLLIVW FVYTSNPVMF TGIRVLDFLF EGSLCGPYKD YGKDSFDVLR
YCADDFICRV CLHDKDSLHL YKHAYSVEQV YKDAASGFIF NWNWLYLVFL ILFVKPVAGF
VIICYCVKYL VLNSTVLQTG VCFLDWFVQT VFSHFNFMGA GFYFWLFYKI YIQVHHILYC
KDVTCEVCKR VARSNRQEVS VVVGGRKQIV HVYTNSGYNF CKRHNWYCRN CDDYGHQNTF
MSPEVAGELS EKLKRHVKPT AYAYHVVDEA CLVDDFVNLK YKAATPGKDS ASSAVKCFSV
TDFLKKAVFL KEALKCEQIS NDGFIVCNTQ SAHALEEAKN AAIYYAQYLC KPILILDQAL
YEQLVVEPVS KSVIDKVCSI LSSIISVDTA ALNYKAGTLR DALLSITKDE EAVDMAIFCH
NHDVDYTGDG FTNVIPSYGI DTGKLTPRDR GFLINADASI ANLRVKNAPP VVWKFSELIK
LSDSCLKYLI SATVKSGVRF FITKSGAKQV IACHTQKLLV EKKAGGIVSG TFKCFKSYFK
WLLIFYILFT ACCSGYYYME VSKSFVHPMY DVNSTLHVEG FKVIDKGVLR EIVPEDTCFS
NKFVNFDAFW GRPYDNSRNC PIVTAVIDGD GTVATGVPGF VSWVMDGVMF IHMTQTERKP
WYIPTWFNRE IVGYTQDSII TEGSFYTSIA LFSARCLYLT ASNTPQLYCF NGDNDAPGAL
PFGSIIPHRV YFQPNGVRLI VPQQILHTPY VVKFVSDSYC RGSVCEYTRP GYCVSLNPQW
VLFNDEYTSK PGVFCGSTVR ELMFSMVSTF FTGVNPNIYM QLATMFLILV VVVLIFAMVI
KFQGVFKAYA TTVFITMLVW VINAFILCVH SYNSVLAVIL LVLYCYASLV TSRNTVIIMH
CWLVFTFGLI VPTWLACCYL GFIIYMYTPL FLWCYGTTKN TRKLYDGNEF VGNYDLAAKS
TFVIRGSEFV KLTNEIGDKF EAYLSAYARL KYYSGTGSEQ DYLQACRAWL AYALDQYRNS
GVEIVYTPPR YSIGVSRLQS GFKKLVSPSS AVEKCIVSVS YRGNNLNGLW LGDTIYCPRH
VLGKFSGDQW NDVLNLANNH EFEVTTQHGV TLNVVSRRLK GAVLILQTAV ANAETPKYKF
IKANCGDSFT IACAYGGTVV GLYPVTMRSN GTIRASFLAG ACGSVGFNIE KGVVNFFYMH
HLELPNALHT GTDLMGEFYG GYVDEEVAQR VPPDNLVTNN IVAWLYAAII SVKESSFSLP
KWLESTTVSV DDYNKWAGDN GFTPFSTSTA ITKLSAITGV DVCKLLRTIM VKNSQWGGDP
ILGQYNFEDE LTPESVFNQI GGVRLQSSFV RKATSWFWSR CVLACFLFVL CAIVLFTAVP
LKFYVYAAVI LLMAVLFISF TVKHVMAYMD TFLLPTLITV IIGVCAEVPF IYNTLISQVV
IFLSQWYDPV VFDTMVPWMF LPLVLYTAFK CVQGCYMNSF NTSLLMLYQF VKLGFVIYTS
SNTLTAYTEG NWELFFELVH TTVLANVSSN SLIGLFVFKC AKWMLYYCNA TYLNNYVLMA
VMVNCIGWLC TCYFGLYWWV NKVFGLTLGK YNFKVSVDQY RYMCLHKINP PKTVWEVFST
NILIQGIGGD RVLPIATVQA KLSDVKCTTV VLMQLLTKLN VEANSKMHVY LVELHNKILA
SDDVGECMDN LLGMLITLFC IDSTIDLSEY CDDILKRSTV LQSVTQEFSH IPSYAEYERA
KNLYEKVLVD SKNGGVTQQE LAAYRKAANI AKSVFDRDLA VQKKLDSMAE RAMTTMYKEA
RVTDRRAKLV SSLHALLFSM LKKIDSEKLN VLFDQASSGV VPLATVPIVC SNKLTLVIPD
PETWVKCVEG VHVTYSTVVW NIDTVIDADG TELHPTSTGS GLTYCISGAN IAWPLKVNLT
RNGHNKVDVV LQNNELMPHG VKTKACVAGV DQAHCSVESK CYYTNISGNS VVAAITSSNP
NLKVASFLNE AGNQIYVDLD PPCKFGMKVG VKVEVVYLYF IKNTRSIVRG MVLGAISNVV
VLQSKGHETE EVDAVGILSL CSFAVDPADT YCKYVAAGNQ PLGNCVKMLT VHNGSGFAIT
SKPSPTPDQD SYGGASVCLY CRAHIAHPGS VGNLDGRCQF KGSFVQIPTT EKDPVGFCLR
NKVCTVCQCW IGYGCQCDSL RQPKSSVQSV AGASDFDKNY LNGYGVAVRL G
