ATNA_EMENI
ID ATNA_EMENI Reviewed; 7214 AA.
AC Q5AUZ6; A0A1U8QJC1; C8V3Z0;
DT 23-MAY-2018, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 03-AUG-2022, entry version 121.
DE RecName: Full=Nonribosomal peptide synthase atnA {ECO:0000303|PubMed:26563584};
DE EC=6.3.2.- {ECO:0000305|PubMed:26563584};
DE AltName: Full=Aspercryptin biosynthesis cluster protein A {ECO:0000303|PubMed:26563584};
GN Name=atnA {ECO:0000303|PubMed:26563584}; ORFNames=ANIA_07884;
OS Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 /
OS M139) (Aspergillus nidulans).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Nidulantes.
OX NCBI_TaxID=227321;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX PubMed=16372000; DOI=10.1038/nature04341;
RA Galagan J.E., Calvo S.E., Cuomo C., Ma L.-J., Wortman J.R., Batzoglou S.,
RA Lee S.-I., Bastuerkmen M., Spevak C.C., Clutterbuck J., Kapitonov V.,
RA Jurka J., Scazzocchio C., Farman M.L., Butler J., Purcell S., Harris S.,
RA Braus G.H., Draht O., Busch S., D'Enfert C., Bouchier C., Goldman G.H.,
RA Bell-Pedersen D., Griffiths-Jones S., Doonan J.H., Yu J., Vienken K.,
RA Pain A., Freitag M., Selker E.U., Archer D.B., Penalva M.A., Oakley B.R.,
RA Momany M., Tanaka T., Kumagai T., Asai K., Machida M., Nierman W.C.,
RA Denning D.W., Caddick M.X., Hynes M., Paoletti M., Fischer R., Miller B.L.,
RA Dyer P.S., Sachs M.S., Osmani S.A., Birren B.W.;
RT "Sequencing of Aspergillus nidulans and comparative analysis with A.
RT fumigatus and A. oryzae.";
RL Nature 438:1105-1115(2005).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX PubMed=19146970; DOI=10.1016/j.fgb.2008.12.003;
RA Wortman J.R., Gilsenan J.M., Joardar V., Deegan J., Clutterbuck J.,
RA Andersen M.R., Archer D., Bencina M., Braus G., Coutinho P., von Dohren H.,
RA Doonan J., Driessen A.J., Durek P., Espeso E., Fekete E., Flipphi M.,
RA Estrada C.G., Geysens S., Goldman G., de Groot P.W., Hansen K.,
RA Harris S.D., Heinekamp T., Helmstaedt K., Henrissat B., Hofmann G.,
RA Homan T., Horio T., Horiuchi H., James S., Jones M., Karaffa L.,
RA Karanyi Z., Kato M., Keller N., Kelly D.E., Kiel J.A., Kim J.M.,
RA van der Klei I.J., Klis F.M., Kovalchuk A., Krasevec N., Kubicek C.P.,
RA Liu B., Maccabe A., Meyer V., Mirabito P., Miskei M., Mos M., Mullins J.,
RA Nelson D.R., Nielsen J., Oakley B.R., Osmani S.A., Pakula T., Paszewski A.,
RA Paulsen I., Pilsyk S., Pocsi I., Punt P.J., Ram A.F., Ren Q., Robellet X.,
RA Robson G., Seiboth B., van Solingen P., Specht T., Sun J.,
RA Taheri-Talesh N., Takeshita N., Ussery D., vanKuyk P.A., Visser H.,
RA van de Vondervoort P.J., de Vries R.P., Walton J., Xiang X., Xiong Y.,
RA Zeng A.P., Brandt B.W., Cornell M.J., van den Hondel C.A., Visser J.,
RA Oliver S.G., Turner G.;
RT "The 2008 update of the Aspergillus nidulans genome annotation: a community
RT effort.";
RL Fungal Genet. Biol. 46:S2-13(2009).
RN [3]
RP IDENTIFICATION OF THE CLUSTER.
RX PubMed=23248299; DOI=10.1073/pnas.1205532110;
RA Andersen M.R., Nielsen J.B., Klitgaard A., Petersen L.M., Zachariasen M.,
RA Hansen T.J., Blicher L.H., Gotfredsen C.H., Larsen T.O., Nielsen K.F.,
RA Mortensen U.H.;
RT "Accurate prediction of secondary metabolite gene clusters in filamentous
RT fungi.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:E99-E107(2013).
RN [4]
RP FUNCTION, DISRUPTION PHENOTYPE, AND INDUCTION.
RX PubMed=27310134; DOI=10.1021/acschembio.6b00398;
RA Henke M.T., Soukup A.A., Goering A.W., McClure R.A., Thomson R.J.,
RA Keller N.P., Kelleher N.L.;
RT "New aspercryptins, lipopeptide natural products, revealed by HDAC
RT inhibition in Aspergillus nidulans.";
RL ACS Chem. Biol. 11:2117-2123(2016).
RN [5]
RP FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX PubMed=26563584; DOI=10.1002/anie.201507097;
RA Chiang Y.M., Ahuja M., Oakley C.E., Entwistle R., Asokan A., Zutz C.,
RA Wang C.C., Oakley B.R.;
RT "Development of genetic dereplication strains in Aspergillus nidulans
RT results in the discovery of aspercryptin.";
RL Angew. Chem. Int. Ed. 55:1662-1665(2016).
CC -!- FUNCTION: Nonribosomal peptide synthase; part of the gene cluster that
CC mediates the biosynthesis of aspercryptins, linear lipopeptides built
CC from six amino acids including 2 highly unusual and nonproteogenic
CC amino acids, 2-amino-octanoic acid (2aoa) and 2-amino-dodecanol (2adol)
CC (PubMed:23248299, PubMed:27310134, PubMed:26563584). The core structure
CC of aspercryptins is as follows: Ser/Ala-Thr-Ile/Val-2aoa-Asn-2adol
CC (PubMed:27310134). The first step of aspercryptin biosynthesis is the
CC generation of the fatty acid precursors, octanoic and dodecanoic acids,
CC by the FAS subunits atnF and atnM (PubMed:27310134, PubMed:26563584).
CC The fatty acid precursors are likely transformed into the corresponding
CC alpha-amino fatty acids in three steps (PubMed:27310134,
CC PubMed:26563584). First, they are hydroxylated by the cytochrome P450
CC monooxygenase atnE, then oxidized to the corresponding alpha-keto acids
CC by the NAD(P)-dependent oxidoreductase atnD, and finally converted to
CC the alpha-amino fatty acids by the PLP-dependent aminotransferases atnH
CC or atnJ (PubMed:27310134, PubMed:26563584). the alpha-amino fatty
CC acids, 2-amino-octanoic and 2-amino-dodecanoic acids, are recognized,
CC activated, and covalently tethered to the NRPS atnA by its fourth and
CC sixth adenylation domains (PubMed:27310134). The second module of atnA
CC is the Thr module and contains an epimerase (E) domain responsible for
CC the epimerization of Thr to D-allo-Thr (PubMed:26563584). Additionally,
CC despite atnA having only one epimerase domain, the first amino acid of
CC aspercryptin A1 is D-Ser, suggesting that serine is either loaded
CC directly as D-Ser on the first module or that the epimerase domain in
CC the threonine module epimerizes both L-Ser and L-Thr (PubMed:27310134).
CC After condensation of the hexapeptide of aspercryptin, the C-terminal
CC reductase (TE) domain might be involved in the reductive release and
CC production of the aldehyde hexapeptide (PubMed:26563584). Further
CC reduction would generate aspercryptins (PubMed:27310134,
CC PubMed:26563584). The variety of aspercryptins produced reflects the
CC flexibiliy of the atnA NRPS, allowing incorporation of alanine instead
CC of serine, valine for isoleucine, and a C10 fatty amino alcohol instead
CC of the C12 version (PubMed:27310134). AtnB seems to be involved in the
CC selectivity for Ile versus Val by the third module (PubMed:26563584).
CC Moreover, type B, C and D aspercryptins have an additional N-terminal
CC cichorine, acetyl and propionyl group respectively (PubMed:27310134).
CC {ECO:0000269|PubMed:23248299, ECO:0000269|PubMed:26563584,
CC ECO:0000269|PubMed:27310134}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:26563584}.
CC -!- INDUCTION: Expression is positively regulated by the aspercryptin
CC cluser-specific transcription factor atnN (PubMed:27310134).
CC {ECO:0000269|PubMed:27310134}.
CC -!- DOMAIN: NRP synthetases are composed of discrete domains (adenylation
CC (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation
CC (C) domains) which when grouped together are referred to as a single
CC module (By similarity). Each module is responsible for the recognition
CC (via the A domain) and incorporation of a single amino acid into the
CC growing peptide product (By similarity). Thus, an NRP synthetase is
CC generally composed of one or more modules and can terminate in a
CC thioesterase domain (TE) that releases the newly synthesized peptide
CC from the enzyme (By similarity). Occasionally, methyltransferase
CC domains (responsible for amino acid methylation) are present within the
CC NRP synthetase (By similarity). InpA has the following architecture: A-
CC T-C-A-T-E-C-A-T-C-A-T-C-A-T-C-A-T-TE (PubMed:27310134).
CC {ECO:0000250|UniProtKB:A0A144KPJ6, ECO:0000305|PubMed:27310134}.
CC -!- DISRUPTION PHENOTYPE: Eliminates the production of aspercryptin
CC (PubMed:27310134, PubMed:26563584). {ECO:0000269|PubMed:26563584,
CC ECO:0000269|PubMed:27310134}.
CC -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
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DR EMBL; BN001302; CBF73453.1; -; Genomic_DNA.
DR EMBL; AACD01000135; EAA59538.1; -; Genomic_DNA.
DR RefSeq; XP_681153.1; XM_676061.1.
DR SMR; Q5AUZ6; -.
DR STRING; 162425.CADANIAP00003901; -.
DR EnsemblFungi; CBF73453; CBF73453; ANIA_07884.
DR EnsemblFungi; EAA59538; EAA59538; AN7884.2.
DR GeneID; 2868928; -.
DR KEGG; ani:AN7884.2; -.
DR eggNOG; KOG1177; Eukaryota.
DR eggNOG; KOG1178; Eukaryota.
DR HOGENOM; CLU_222946_0_0_1; -.
DR InParanoid; Q5AUZ6; -.
DR OMA; SEASVWC; -.
DR OrthoDB; 4243at2759; -.
DR Proteomes; UP000000560; Chromosome II.
DR Proteomes; UP000005890; Unassembled WGS sequence.
DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0009058; P:biosynthetic process; IEA:UniProt.
DR Gene3D; 1.10.1200.10; -; 5.
DR Gene3D; 3.30.300.30; -; 6.
DR Gene3D; 3.30.559.10; -; 6.
DR Gene3D; 3.40.50.12780; -; 6.
DR InterPro; IPR010071; AA_adenyl_domain.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR020845; AMP-binding_CS.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR042099; ANL_N_sf.
DR InterPro; IPR023213; CAT-like_dom_sf.
DR InterPro; IPR001242; Condensatn.
DR InterPro; IPR013120; Far_NAD-bd.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR010080; Thioester_reductase-like_dom.
DR Pfam; PF00501; AMP-binding; 6.
DR Pfam; PF00668; Condensation; 6.
DR Pfam; PF07993; NAD_binding_4; 1.
DR Pfam; PF00550; PP-binding; 6.
DR SMART; SM00823; PKS_PP; 5.
DR SUPFAM; SSF47336; SSF47336; 5.
DR SUPFAM; SSF51735; SSF51735; 1.
DR TIGRFAMs; TIGR01733; AA-adenyl-dom; 6.
DR TIGRFAMs; TIGR01746; Thioester-redct; 1.
DR PROSITE; PS00455; AMP_BINDING; 5.
DR PROSITE; PS50075; CARRIER; 5.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 3.
PE 2: Evidence at transcript level;
KW Isomerase; Ligase; Phosphopantetheine; Phosphoprotein; Reference proteome;
KW Repeat.
FT CHAIN 1..7214
FT /note="Nonribosomal peptide synthase atnA"
FT /id="PRO_0000444121"
FT DOMAIN 786..862
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:27310134"
FT DOMAIN 1877..1953
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:27310134"
FT DOMAIN 3398..3472
FT /note="Carrier 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:27310134"
FT DOMAIN 4476..4552
FT /note="Carrier 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:27310134"
FT DOMAIN 5591..5667
FT /note="Carrier 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:27310134"
FT DOMAIN 6683..6766
FT /note="Carrier 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:27310134"
FT REGION 257..651
FT /note="Adenylation 1"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:27310134"
FT REGION 899..1318
FT /note="Condensation 1"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:27310134"
FT REGION 1340..1735
FT /note="Adenylation 2"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:27310134"
FT REGION 1962..2384
FT /note="Epimerization"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:27310134"
FT REGION 2431..2845
FT /note="Condensation 2"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:27310134"
FT REGION 2866..3262
FT /note="Adenylation 3"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:27310134"
FT REGION 3510..3904
FT /note="Condensation 3"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:27310134"
FT REGION 3943..4339
FT /note="Adenylation 4"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:27310134"
FT REGION 4601..5033
FT /note="Condensation 4"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:27310134"
FT REGION 5051..5446
FT /note="Adenylation 5"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:27310134"
FT REGION 5489..5515
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 5707..6123
FT /note="Condensation 5"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:27310134"
FT REGION 6145..6543
FT /note="Adenylation 6"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:27310134"
FT REGION 6814..7194
FT /note="Thioesterase (TE) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:27310134"
FT REGION 6895..6915
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 5489..5510
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 823
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 1914
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 3433
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 4513
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 5628
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 6725
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 7214 AA; 795763 MW; 93F7DE9B5A5D3A0D CRC64;
MPSISAAADS SAEFWKRNTA GMEISRLSHL TRSYEGQAQW RSYPLNPSIE LQRLGAFCEA
HRTSLLVILQ AAWATVLGRF LATDTATFAS CLENGDEAKH GVCSASWSQG ATTLHELLEQ
LQQWHETSFT HQDIPLAELE QLLHVVPDTG LRVKHISSPS TSLSLSGPRH NRAIEVVAQV
SPISVRISLE YNASALSSVY AQSIAGSLER SLQAVVNRGS TPVTQIDLCS KEDRESIFDW
NAYVPVTISD CVHTRIERKA LEQPHALAVA GSGGDMTYQQ LNMQADNLAA YLQELGVGAD
SYVALCFEKS TLPIVAMLAV FKAGGAYVAL NPAHPVKRQA VILSKINAQV ILTGPGYAGT
FPGLVKHSVE VTQDLLDQLA AERRATRLVR AARPETPAVV VFTSGSTGEP KGIVVEHRAL
VSSMIGHGTI MRLDSSTRAL QFATYTFDLS VGEIFNTLMH GGCVCVPSEE ERLDDLEGFI
RRLEVNWALL TPTVLNMMTP ANVPSVRTIS TGGEPMKQDI IQAWADHVQL NNMYGPAETT
ILCAGRAALS PATPASNIGH ALGARQWITN PMNPNQLCPI GAVGEVLIEG PGLARGYLHD
EEKTNAAFVG NPDWLPKASP ARRFYRSADL GFLSPDGTFN IVGRKDTQVK INGQRIELEE
VEFNIKSLLN AGWQAVVAEV IKPKGYNDQS ILGAFIQFED DENDETELLG YISEGRRQQL
RQLKEDLGLH LPAYMTPSVF VPMAHMPTTA HGKLDRRRLK DLAAGFSTED LVSFSLAGST
NTAKREPVTE TEKAVASLWS QVLKIPYESF GLNDNFFRLG GDSISAMKLS AAARSTGMSL
TVAKIFGHPT LEAMSQIAVE LSHTEIGSIK PFSLIDVENA FEFIDQLTLK WGLDRSSIED
AYPATALQEG LMAITQGEPG TYIYQNVYEL PADIDLAKFC AAWESVVNTT EILRTTLLPT
DTASTYQVVI KPSSIDWKYP ASVEEYLKSD AQQTMLYGEP LARYALVPGT PGGSLSTFIW
TAHHALYDGW SLPLLWKRVE EAYKGSGLSH QPHVAPFNRF IAHLRDMDAE ATYAFWESYL
SSSNPPKFPQ LPYQTYKPRV NNIHQHEFSL TATSQSSGIT TSTLIRAAWS LLMSQYTDAG
DDIIIGVTVA GRNVDVPGIS EMAAPMITTV PVRVQIDRDE TVTELLTRVQ TQTVEMMPFE
HAGLQNIAKI NRECRLACGF QNLLVVQPEE DESTSGSLGI KKIQSPEVGI YTYALVIQCL
LRGDKVGVQV DFDDQVLSSW QVERICCQLE HLMGVLRASP NVKIGDLSLV SQKDYTQIMN
WNHKLPVVEE RCVHEIIRGQ VLATPDAPAI CSWDGDFTYA EVDRLSSRFA RHLVSMGVGP
ETLVPHCFSK SAWTVIAMLA IIKAGGACVA LDPGHPVDRL QAIINDAEAA LVVTMPEHSH
LFNGLVNKVV ALSPQFFGSD DDLQSSETLP PRAGHKNPVF VLFTSGSTGK PKGIVIEHGM
FASSAAAHSK AFGITAQSRV FQFAAHTFDV SVGDIFTSLM KGACICIPSD LERMNNVASA
INRMKANYAF LTPTVANLLR PEQVPTLRTL TLGGEAPTRE NIRTWADSLN LILCYGPAEC
SVYCSANPPA TQQSNPAVLG HAIGGLIWLV DPVNHDKLTP VGCVGELVVQ GAIVARGYLN
EPEKTQSAFI QDPAWMPQTF PREYRRIYKT GDLARFNPDG SLSFVARKDT QAKVRGQRVE
LAEIEVHLSE SPEIQHAMVA VPAAGPYKSR LVCILSLQEL AQRSDGISRD SSRVALIQGS
SDRSHAAQTA SVVENRLAEK LPPYMIPAVW IPLKKMPLNL SGKIDRKLIK GWLEDVDEAT
YQSVAAMAAA EGTSLQQPTS DIEKKVQAAF SATLNIPVES VGLNTSFLSV GGDSISAMQV
MSRLRSQNLR ITVQDILKLR TVAALAGRAQ YIEQSTTESS APEAEVIDEW FELAPIQQLF
FRMQPKGQNH FNQSFVLKLA QDVLQTELQR ALEIVVQHHS MLRARFEQVD GSWSQKITND
VSGSFFMFPR EEGSRERMMA RFREAETLFD IKRGPMLTAQ IWVAPESQYL FLAAHHLVID
LVSWRIILQD LEDVLRTGRI NSTPTISFQN WAKLQREYVS QHLSKPDTWD LEAPTGDLAY
WNMQGEANNW GDIVTESFTI DSQRTALLLG DCNIPLRTEP TDIMVAALLH SFRHAFSDRN
VPAVYLEGHG REPWTSAIDV SRTVGWFTTM YPVSYETPED NWLDAVKRLK DSRRKIAHNG
WRYFTARSLL AGGMQDMEVV FNYLGLYQQL QRVDALFQES SITGTDCVEI SPQMQRYSLF
EIAAGVSNGR MEFTFEYNKK MSHRDTISSW INHYRQVLET GIDELMRQSE LIPTLSDFPL
LNLSYKDLDN LATSILPEAG VKSIDEIESL SPCSPMQLGL LMSQLKSEGA YEFFTIMEAT
AREGVDSAQL VAAWQQVIDR HPMLRTVFIK SAVPDRPYDQ LVLKELRAQV VELRSDDPVH
ALRTLPQTAK LHQLAICHCE NGRMFCKLEI NHALIDGTSM AIIERDLKRA YSKKLSSVPP
LAYVDYVSFL QEAKRAESVN FWNDYLQDAQ PCQFPILNDG RDQSQALESI NVELPGLTKE
TLSAFSERWG FTVANVVQTA WALVLRAFIG TDSVCYGYLT SGRDAPLDGI EDSVGPFINM
LVCRLKFDPH EPALVALKNT QDGFLKAMSH QYVSLAEMQH ALGVAAQGLF NTAMSFQRYS
PEESMDLNLR TVYDYDPTEF NITVNVATRE EGLQIDLTYW TSKLSSGQAV HLANTYSTVI
MELLSNPETV LADVNMLSPL DRASLRDWNK ELPFAVDRCM HEVIHQNARK RPHALALESW
EAAYTYRDLD RASSRLARHL IKQGVSPDDC IPLCFEKSLY TIIALVAVLK AGGGFVLLDP
KHPDDRLKGL LEDSKAKFLI VSPQTQDRCK DLISSLVVVS PKILDELPHA DEDDIPPSTA
VTPGDIMYVQ FTSGSTGKPK GAVVHHRAAC SSIEHHGKVM NYGPHSRIFQ FSSYTFDAII
LEAFTTLYHG GCVCIPSEED RMSSMVQSMR EMKVNNMFMT PTLARLFGPA DVPSLTTLML
GGEPIPQDSI NTWKDHVDLI GGYGPAECCV YCCYNPLSSS GFKPDVIGYP VGAVLWIVEA
DNHDRLVPVG AIGEIVVHGH TVGRGYLNDP TRTAASYISA PSWVADYGYP GEQTLYKTGD
LGRYNSDGTL TIVGRKDTQV KVNGQRIELG EVEHCIKTEY PQVLQVAVDA LKPEHANGRQ
ILSAFLEFEA VEGSEEFQNK NSFLRAMNDK LRETMFEIEA ILAQRLPPYM VPHLWFPLVT
MPKSASGKTD RKVLKQLCNG LSKTELQQYS LASGSRKALE TPMEETIAGL WKDLFGVSDI
GSNDNFFRVG GDSIEAMKLA AAARAQGLSL SVADIFNYPK LDDMARIVVA AYGASAVAHK
YDAPFSLVGG EESARSIVQK HIPHVQIDLV EDVYPSTSLQ EGLLALTSSH SSAYVLQAPF
LLPPNIDLDR FRDAWAKVVE ANAILRTVII STETQGTCQV TLRQSIEWSQ ASTLEEYLAQ
DRERPMGYGT ALSRYGLTLD GYFVWTAHHS IYDGWSFALM LDEVEKRYKD ESVVSRPLFA
EYIRFLQRQQ GKTDATAFWK SQLQDASSSS VFPQLPSSLY EVDVDRTFKY SFPFSTKSTV
TASTLLSAAW GLTIGRLTNS SEVIYGSTRS GRNIDLAQAT ELMGPTIATV PIRISIDTSM
SIEDFLAAVQ NQATAAIPYE HLGLQNISKI SPACKAACDF QNLFVVQPAV ISDSTILGMK
RVEIPTKGLH TYALNVECIL TEEGTATLNF EYDGKVMQDY QIQRLAGQFH HVVCQLCENE
DGRLKVGDVD AFSLDDEKQL RQWNARLKSF PEITRCAHDL VSERARLHPD LLAVTQSDGT
SLTYDELEEL STLFARHLST LKIGPGRIVP ICLKKAVWVV VSILGVLKTG AAFVCLDPSS
PSSRMHSIIE EVESEIVIVD PETKPIFNNH LQTLEIGAKS LDWIRSANAS DMIFEVHRNP
RDLMYVIFTS GSTGKPKGVM IEHASACSSF TYQGQEFGYD HESRVLQFSA LTFDASLMEI
FTTLCAGGCV CFPTEEEKQG DIVRAINNLR VNSVMLTPTV LRMIQPEDIP MVKHVVTGGE
AVSHDIVQTW SSKVILKGVY GPTETSMICI TADLVPGSSP ANIGVPLGCR SWITLPDDHN
HLAPIGSVGE LLIQGPIVGR GYYKNQKQTQ DVFIENPLWL QKRFGETGGG RLYKTGDLVY
YAQNGDLMIV GRKDSQVKLH GQRIELGEID HKMWSHPAVR QSSVVLPSQG PLKNRLVAVL
TLDGTEERIT TPHVLCPLSE EWKQYANSRI ASIRQALRES LPSYMVPTVF VAVEKMPRQT
SGKTDIKRVK KWVNELDEQT AEQALDIETT APGLTVPGSE AEKVIQGAVS KVLNIPAEKI
ALNRSFISLG GDSITAIKLM NQLRDAGVNF SIKELLRAGS IGELAGRVTS ISEGENVNPL
LSLVSQKKEK KYSLLRLGDA EIEALLAQRL ATIGLTDLTR VEDVYPCSPL QEGLLVAQTK
GVGSYDVYNI YEVTTSKNAS VSVNPHVLAK AWKEVVRRHQ ILRTIFIQGL EESTAFNQVV
LREVHNAPFV IEDVKSNDAK ALLQNLATPE YPAFEPWHSV TICSDANGTV CCGIRMHHGL
FDASSMDIIL REVAQAYNQR LSTPAPLYRD YISYLQGLQQ GGNDGLAYWQ EYLKDLEPCY
FPSINEEALG TRTPQSLQFN VPGLSRILLF SARKNVTVST ILQTAWALVL RHYTSTEEIC
FGYLSHGRDI PLDGIDNIVG PMINMMVLRV ILSGDRTLTD ILEGTRDDVL NSLPHQHTSL
AEIHHALDLQ GRSAFNTTLS FASAAADAEN YDGIAFKNLS GSGSTEYDIA VNASVVGEDL
QIHFSYWSSA LSPQQATAVA QAFTNFMDIL TDSSDLPLRD IDFTSAAMRA QLLRWNATPY
APVHTTVHEL FHRTALRYPE NQAICSTDGS FTYSELDNLT TRFASFLREK GVGPEVLVPV
CFNKSCWTIV SMLSILKAGG ACVPLDPSHP PARIQEVSSR CEAKLILAAP HLVDRLPDCN
ATVISVTDGL MQGLPNLPSN FQIDLAKPAN AAFVPFTSGS TGLPKGIILD HMGLCTMFEA
NASVVGIDHN TRTFQYAAYT FDVSIAETYI TLTQGGCVCV PTDAERMNDI AGAITRLQAN
WTFLTPSVAS LLNPIDVPTL KTLTLGGEAI SRDLHSTWAD KVRLINSYGP AECSIWTSNQ
RLFPDSSCAD IGAGITCHLW VTEPDNHDRL VPIGCVGELV VQGPNLARGY LKDEEKTAAT
YIDTPAWLRN DTRSIAKRVY KTGDLVRHCA DGHLEFVGRK DTQIKFHGQR VEIGEVEYQL
RARLPKNTQV AVEMIKPLSQ DGRQTLAGFI TTEGGSGHEN KGSPSLKGSS GDPVSLLRDP
DETFKNIVRK LEHQLAETLP SYMIPSVFIS MLNIPRNTSM KIDRKALRTL GANLTREQIA
TYSFVQGDKR APRTAMEKRL QECWASVLKI SPESIGADDS FFRIGGDSIG AMQLVSAARK
TGLSITVGDI FQHQKLSQMA NIVARNAAAT TEEISIKPFS LLPKQRPDED LVELAAFKVG
IDRTLLQDVY PCTPLQEGLI SLTARDHGLY TLQAVYRLPE MINIQEFQLA WLAVTEELDI
LRTRIVDLGH LGSYQVVISP VISQMRWVYG NSLSTYLRED KEIPVGYGKP LARYAIIEEE
EEGEQKKYFV WTAHHSIYDG WSLGLMMDLV EKKYLKTSTI PSPPFNKFIH WLTNLDKAAT
RQYWKSTFEA CSAPQFPSVP QHYRTKAKAA MTYSIRLPQK IDSEITVPTI LRTAWALNIS
QYTRSDDVVF GMTQTGRNAP IPGVTEIVAP LITTVPVRVV FNRSQTVGNV LQEVQNQMVA
MIPHEHVGLQ NISKFSAECQ AASKFENLLL IQTQQDQMVS PIGLERIPVT DLDIPAFGIV
AECEVADGQV LVSVGYDSTV VSEKQMTNIL RQFDFLVNQI GSESARNTPL VEMHLLGDNE
IKMLEALNQS PDDRVSRLAH ELIHERAVLQ PEAIAIDSQE VQLSYGELDD LSTRLAYFLI
DLGTGPDKVI PLFFRRSPWA MVAMLGVIKS GSAFVFLDPG HPIDRLEFVV QQIDAKLVLT
SPDLESTWRE KLAVFCVSPS ALQSLPRLHD GNLPVTAVTP QNILYCIFTS GSTGRPRGCV
IEHSNFLSGA VHHARRSRIS ESTRIMQIAP YTFDVSILEM LTGLIGGGCI CLPRDYHQGA
RVADIINDLN INWTFLTPSV ARTIVPSEVP SLQTLILGGE ALAKVDIQTW AGKLHLHNGY
GPSECSVAVA SNEVRDPTID PANIGSKMGC NIWVVDAENH DILLPIGAVG ELLVEGAIVG
RGYLQEPEKT AAAFIQDPAW VHYLPNTKSS ERRRFYKTGD LVRLNADGTI HFIGRKDTQI
KLRGLRIEMG EIEHHASTYR AIRHAVVAVP RAGRMKESIV VVYTLNAYDD SNEQQSDLRP
LSNTDLETSQ MSPAQLRKHL ATHLPPYMVP QTYIGVARLP LLASGKIDRP KLQRWLENMD
DATSELIAAQ VGKTATHEAG PIDPADKLAL ALSEPISRLL AGDDEAYLET LKGRNIVLSQ
SGLNSITVVS MRAMIRDKFN ADVSIDRLME STVTIQDVAR MIEHGNTAAG TDKQESAPQL
DLLAEVDRMM NSLITEASPD VQTLSQPTPR AERILLTGAT GFLGTEILRQ LLSNPASTRT
VVAIVRARDQ DHAMERIVSS AKAAQWWQEE YRSRITPWVG DLAAPRLGLS ESQWSTVEGR
DHPGSESGST AGPAEPRIDA IIHNGALVHW GADYHRLRDV NVSSVVSLLA ALTRSQAPPT
LTFVSGGHVQ LDDNETTDEE MAAVLAHSTG YGQSKFVADL VVKRFAARYS TSAVSIVKPG
LILGTAQSGV SNTDDFFWRV VATAVEIGGF NAEEPENVIL LAGAQQVASI VTDKLQLNLN
PARSRSGIPS VETKVRLAIT TQELWHMLSD EFGYPMRGMG PAEWLDAMRA AVHAQGESHR
LWPVLHFLEA GGGYMGLPVG GCQLQGATGA DQESEKEELL ASLRKSISYM RQIGYLQSDA
PHAVDKVVFG RRNV
