FUM1_GIBM7
ID FUM1_GIBM7 Reviewed; 2586 AA.
AC W7LKX1; Q9Y8A2;
DT 30-AUG-2017, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 44.
DE RecName: Full=Highly reducing polyketide synthase FUM1 {ECO:0000303|PubMed:8850615};
DE Short=HR-PKS FUM1 {ECO:0000305};
DE EC=2.3.1.- {ECO:0000269|PubMed:10413619};
DE AltName: Full=Fumonisin biosynthesis cluster protein 1 {ECO:0000303|PubMed:8850615};
GN Name=FUM1 {ECO:0000303|PubMed:8850615};
GN Synonyms=FUM5 {ECO:0000303|PubMed:10413619}; ORFNames=FVEG_00316;
OS Gibberella moniliformis (strain M3125 / FGSC 7600) (Maize ear and stalk rot
OS fungus) (Fusarium verticillioides).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Nectriaceae; Fusarium;
OC Fusarium fujikuroi species complex.
OX NCBI_TaxID=334819;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], DOMAIN, FUNCTION, DISRUPTION PHENOTYPE,
RP AND PATHWAY.
RC STRAIN=M3125 / FGSC 7600;
RX PubMed=10413619; DOI=10.1006/fgbi.1999.1141;
RA Proctor R.H., Desjardins A.E., Plattner R.D., Hohn T.M.;
RT "A polyketide synthase gene required for biosynthesis of fumonisin
RT mycotoxins in Gibberella fujikuroi mating population A.";
RL Fungal Genet. Biol. 27:100-112(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND DISRUPTION PHENOTYPE.
RC STRAIN=M3125 / FGSC 7600;
RX PubMed=12423021; DOI=10.1094/mpmi.2002.15.11.1157;
RA Desjardins A.E., Munkvold G.P., Plattner R.D., Proctor R.H.;
RT "FUM1--a gene required for fumonisin biosynthesis but not for maize ear rot
RT and ear infection by Gibberella moniliformis in field tests.";
RL Mol. Plant Microbe Interact. 15:1157-1164(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND PATHWAY.
RC STRAIN=M3125 / FGSC 7600;
RX PubMed=12620260; DOI=10.1016/s1087-1845(02)00525-x;
RA Proctor R.H., Brown D.W., Plattner R.D., Desjardins A.E.;
RT "Co-expression of 15 contiguous genes delineates a fumonisin biosynthetic
RT gene cluster in Gibberella moniliformis.";
RL Fungal Genet. Biol. 38:237-249(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=M3125 / FGSC 7600;
RX PubMed=20237561; DOI=10.1038/nature08850;
RA Ma L.-J., van der Does H.C., Borkovich K.A., Coleman J.J., Daboussi M.-J.,
RA Di Pietro A., Dufresne M., Freitag M., Grabherr M., Henrissat B.,
RA Houterman P.M., Kang S., Shim W.-B., Woloshuk C., Xie X., Xu J.-R.,
RA Antoniw J., Baker S.E., Bluhm B.H., Breakspear A., Brown D.W.,
RA Butchko R.A.E., Chapman S., Coulson R., Coutinho P.M., Danchin E.G.J.,
RA Diener A., Gale L.R., Gardiner D.M., Goff S., Hammond-Kosack K.E.,
RA Hilburn K., Hua-Van A., Jonkers W., Kazan K., Kodira C.D., Koehrsen M.,
RA Kumar L., Lee Y.-H., Li L., Manners J.M., Miranda-Saavedra D.,
RA Mukherjee M., Park G., Park J., Park S.-Y., Proctor R.H., Regev A.,
RA Ruiz-Roldan M.C., Sain D., Sakthikumar S., Sykes S., Schwartz D.C.,
RA Turgeon B.G., Wapinski I., Yoder O., Young S., Zeng Q., Zhou S.,
RA Galagan J., Cuomo C.A., Kistler H.C., Rep M.;
RT "Comparative genomics reveals mobile pathogenicity chromosomes in
RT Fusarium.";
RL Nature 464:367-373(2010).
RN [5]
RP IDENTIFICATION.
RX PubMed=8850615; DOI=10.1007/978-1-4899-1379-1_15;
RA Desjardins A.E., Plattner R.D., Proctor R.H.;
RT "Genetic and biochemical aspects of fumonisin production.";
RL Adv. Exp. Med. Biol. 392:165-173(1996).
RN [6]
RP FUNCTION.
RX PubMed=14602658; DOI=10.1128/aem.69.11.6935-6937.2003;
RA Butchko R.A., Plattner R.D., Proctor R.H.;
RT "FUM9 is required for C-5 hydroxylation of fumonisins and complements the
RT meitotically defined Fum3 locus in Gibberella moniliformis.";
RL Appl. Environ. Microbiol. 69:6935-6937(2003).
RN [7]
RP FUNCTION.
RX PubMed=12720383; DOI=10.1021/jf0262007;
RA Butchko R.A., Plattner R.D., Proctor R.H.;
RT "FUM13 encodes a short chain dehydrogenase/reductase required for C-3
RT carbonyl reduction during fumonisin biosynthesis in Gibberella
RT moniliformis.";
RL J. Agric. Food Chem. 51:3000-3006(2003).
RN [8]
RP FUNCTION.
RX PubMed=15066782; DOI=10.1128/aem.70.4.1931-1934.2004;
RA Ding Y., Bojja R.S., Du L.;
RT "Fum3p, a 2-ketoglutarate-dependent dioxygenase required for C-5
RT hydroxylation of fumonisins in Fusarium verticillioides.";
RL Appl. Environ. Microbiol. 70:1931-1934(2004).
RN [9]
RP FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX PubMed=15137825; DOI=10.1021/jf035429z;
RA Bojja R.S., Cerny R.L., Proctor R.H., Du L.;
RT "Determining the biosynthetic sequence in the early steps of the fumonisin
RT pathway by use of three gene-disruption mutants of Fusarium
RT verticillioides.";
RL J. Agric. Food Chem. 52:2855-2860(2004).
RN [10]
RP FUNCTION.
RX PubMed=15969533; DOI=10.1021/jf050062e;
RA Yi H., Bojja R.S., Fu J., Du L.;
RT "Direct evidence for the function of FUM13 in 3-ketoreduction of mycotoxin
RT fumonisins in Fusarium verticillioides.";
RL J. Agric. Food Chem. 53:5456-5460(2005).
RN [11]
RP FUNCTION.
RX PubMed=16489749; DOI=10.1021/bi052085s;
RA Zaleta-Rivera K., Xu C., Yu F., Butchko R.A., Proctor R.H.,
RA Hidalgo-Lara M.E., Raza A., Dussault P.H., Du L.;
RT "A bidomain nonribosomal peptide synthetase encoded by FUM14 catalyzes the
RT formation of tricarballylic esters in the biosynthesis of fumonisins.";
RL Biochemistry 45:2561-2569(2006).
RN [12]
RP FUNCTION.
RX PubMed=16536629; DOI=10.1021/jf0527706;
RA Proctor R.H., Plattner R.D., Desjardins A.E., Busman M., Butchko R.A.;
RT "Fumonisin production in the maize pathogen Fusarium verticillioides:
RT genetic basis of naturally occurring chemical variation.";
RL J. Agric. Food Chem. 54:2424-2430(2006).
RN [13]
RP FUNCTION.
RX PubMed=17147424; DOI=10.1021/jf0617869;
RA Butchko R.A., Plattner R.D., Proctor R.H.;
RT "Deletion analysis of FUM genes involved in tricarballylic ester formation
RT during fumonisin biosynthesis.";
RL J. Agric. Food Chem. 54:9398-9404(2006).
RN [14]
RP INDUCTION.
RC STRAIN=M3125 / FGSC 7600;
RX PubMed=17483290; DOI=10.1128/ec.00400-06;
RA Brown D.W., Butchko R.A., Busman M., Proctor R.H.;
RT "The Fusarium verticillioides FUM gene cluster encodes a Zn(II)2Cys6
RT protein that affects FUM gene expression and fumonisin production.";
RL Eukaryot. Cell 6:1210-1218(2007).
RN [15]
RP INDUCTION.
RX PubMed=22117026; DOI=10.1128/ec.05159-11;
RA Visentin I., Montis V., Doell K., Alabouvette C., Tamietti G.,
RA Karlovsky P., Cardinale F.;
RT "Transcription of genes in the biosynthetic pathway for fumonisin
RT mycotoxins is epigenetically and differentially regulated in the fungal
RT maize pathogen Fusarium verticillioides.";
RL Eukaryot. Cell 11:252-259(2012).
RN [16]
RP INDUCTION.
RX PubMed=25217721; DOI=10.1016/j.ijfoodmicro.2014.08.026;
RA Cruz A., Marin P., Magan N., Gonzalez-Jaen M.T.;
RT "Combined effects of benomyl and environmental factors on growth and
RT expression of the fumonisin biosynthetic genes FUM1 and FUM19 by Fusarium
RT verticillioides.";
RL Int. J. Food Microbiol. 191:17-23(2014).
CC -!- FUNCTION: Highly reducing polyketide synthase; part of the gene cluster
CC that mediates the biosynthesis of fumonisins B1 (FB1), B2 (FB2), B3
CC (FB3), and B4 (FB4), which are carcinogenic mycotoxins
CC (PubMed:10413619, PubMed:12620260). On the basis of the chemical
CC structures of fumonisins and precursor feeding studies, fumonisin
CC biosynthesis is predicted to include at least five groups of
CC biochemical reactions: synthesis of a linear polyketide with a single
CC terminal carbonyl function and methyl groups at C-10 and C-14;
CC condensation of the polyketide with alanine; reduction of the
CC polyketide carbonyl to a hydroxyl; hydroxylation of 2-4 polyketide
CC carbons; and esterification of six-carbon tricarboxylic acids to two of
CC the hydroxyls (PubMed:12620260). The biosynthesis starts with the
CC polyketide synthase FUM1-catalyzed carbon chain assembly from one
CC molecule of acetyl CoA, eight molecules of malonyl CoA, and two
CC molecules of methionine (PubMed:10413619). The C-18 polyketide chain is
CC released from the enzyme by a nucleophilic attack of a carbanion, which
CC is derived from R-carbon of alanine by decarboxylation, on the carbonyl
CC carbon of polyketide acyl chain (PubMed:15137825, PubMed:12720383).
CC This step is catalyzed by a pyridoxal 5'-phosphate-dependent aminoacyl
CC transferase FUM8 (PubMed:15137825, PubMed:12720383). The resultant 3-
CC keto intermediate 2-amino-3-oxo-12,16-dimethylicosane is then
CC stereospecifically reduced to the 3-hydroxyl product 2-amino-3-hydroxy-
CC 12,16-dimethylicosane by reductase FUM13 (PubMed:12720383,
CC PubMed:15137825). Subsequent oxidations at C-5, C-10, C-14 and C-15
CC followed by tricarballylic esterification of the hydroxyl groups on C-
CC 14 and C-15 furnish the biosynthesis of fumonisins (PubMed:15066782,
CC PubMed:15137825, PubMed:16489749). The C-10 hydroxylation is performed
CC by the cytochrome P450 monooxygenase FUM2 and occurs early in the
CC biosynthesis (PubMed:16536629). The C-5 hydroxylation is performed by
CC the dioxygenase FUM3 and occurs late in the biosynthesis
CC (PubMed:20237561, PubMed:15066782, PubMed:15137825, PubMed:16536629).
CC Cytochrome P450 monooxygenases FUM6 and FUM15 may be responsible for
CC the two remaining hydroxylations at positions C-14 and C-15
CC (PubMed:12620260). The FUM11 tricarboxylate transporter makes a
CC tricarboxylic acid precursor available for fumonisin biosynthesis via
CC its export from the mitochondria (PubMed:12620260). If the precursor is
CC citrate, the FUM7 dehydrogenase could remove the C-3 hydroxyl of
CC citrate to form tricarballylic acid either before or after the CoA
CC activation by the FUM10 acyl-CoA synthetase and FUM14 catalyzed
CC esterification of CoA-activated tricarballylic acid to the C-14 and C-
CC 15 hydroxyls of the fumonisin backbone (PubMed:16489749,
CC PubMed:17147424). Alternatively, if the precursor is cis-aconitate,
CC FUM7 may function to reduce the double bond (PubMed:17147424). In this
CC alternate proposal, feeding studies with tetradehydro-fumonisin B1
CC suggests that FUM7 cannot function on the tricarballylic ester and must
CC therefore act before the FUM14-mediated esterification
CC (PubMed:17147424). {ECO:0000269|PubMed:10413619,
CC ECO:0000269|PubMed:12620260, ECO:0000269|PubMed:12720383,
CC ECO:0000269|PubMed:14602658, ECO:0000269|PubMed:15066782,
CC ECO:0000269|PubMed:15137825, ECO:0000269|PubMed:15969533,
CC ECO:0000269|PubMed:16489749, ECO:0000269|PubMed:16536629,
CC ECO:0000269|PubMed:17147424}.
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:10413619,
CC ECO:0000269|PubMed:12423021, ECO:0000269|PubMed:12620260,
CC ECO:0000269|PubMed:15137825}.
CC -!- INDUCTION: Expression is positively regulated by the fumonisin gene
CC cluster-specific transcription regulator FUM21 (PubMed:17483290).
CC Expression is increased under histone deacetylase (HDAC)-inhibiting
CC conditions (PubMed:22117026). Expression is strongly reduced by benomyl
CC (PubMed:25217721). {ECO:0000269|PubMed:17483290,
CC ECO:0000269|PubMed:25217721}.
CC -!- DISRUPTION PHENOTYPE: Impairs the production of fumonisins but does not
CC affect maize ear rot and ear infection (PubMed:10413619,
CC PubMed:12423021, PubMed:15137825). {ECO:0000269|PubMed:10413619,
CC ECO:0000269|PubMed:12423021, ECO:0000269|PubMed:15137825}.
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DR EMBL; AF155773; AAD43562.2; -; Genomic_DNA.
DR EMBL; DS022242; EWG36195.1; -; Genomic_DNA.
DR RefSeq; XP_018742386.1; XM_018886754.1.
DR AlphaFoldDB; W7LKX1; -.
DR SMR; W7LKX1; -.
DR STRING; 117187.FVEG_00316T0; -.
DR PRIDE; W7LKX1; -.
DR GeneID; 30058694; -.
DR KEGG; fvr:FVEG_00316; -.
DR VEuPathDB; FungiDB:FVEG_00316; -.
DR eggNOG; KOG1202; Eukaryota.
DR OrthoDB; 19161at2759; -.
DR PHI-base; PHI:255; -.
DR Proteomes; UP000009096; Chromosome 1.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:InterPro.
DR GO; GO:1900541; P:fumonisin biosynthetic process; IMP:GO_Central.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.40.366.10; -; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR001227; Ac_transferase_dom_sf.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR014043; Acyl_transferase.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR InterPro; IPR011032; GroES-like_sf.
DR InterPro; IPR018201; Ketoacyl_synth_AS.
DR InterPro; IPR014031; Ketoacyl_synth_C.
DR InterPro; IPR014030; Ketoacyl_synth_N.
DR InterPro; IPR016036; Malonyl_transacylase_ACP-bd.
DR InterPro; IPR013217; Methyltransf_12.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR032821; PKS_assoc.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR020807; PKS_dehydratase.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR020843; PKS_ER.
DR InterPro; IPR013968; PKS_KR.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF16197; KAsynt_C_assoc; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR Pfam; PF08659; KR; 1.
DR Pfam; PF08242; Methyltransf_12; 1.
DR Pfam; PF00550; PP-binding; 1.
DR Pfam; PF14765; PS-DH; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00826; PKS_DH; 1.
DR SMART; SM00829; PKS_ER; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF50129; SSF50129; 1.
DR SUPFAM; SSF51735; SSF51735; 2.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 1.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 2.
PE 2: Evidence at transcript level;
KW Acyltransferase; Methyltransferase; Multifunctional enzyme; NADP;
KW Oxidoreductase; Phosphopantetheine; Phosphoprotein; Reference proteome;
KW Transferase.
FT CHAIN 1..2586
FT /note="Highly reducing polyketide synthase FUM1"
FT /id="PRO_0000441141"
FT DOMAIN 2486..2565
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 32..454
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255"
FT REGION 609..928
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 980..1269
FT /note="Dehydrogenase (DH) domain"
FT /evidence="ECO:0000255"
FT REGION 1450..1627
FT /note="Methyltransferase (CMet) domain"
FT /evidence="ECO:0000255"
FT REGION 1862..2172
FT /note="Enoyl reductase (ER) (ER) domain"
FT /evidence="ECO:0000255"
FT REGION 2197..2373
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255"
FT ACT_SITE 201
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 2524
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT CONFLICT 685
FT /note="D -> N (in Ref. 1; AAD43562)"
FT /evidence="ECO:0000305"
FT CONFLICT 741
FT /note="A -> V (in Ref. 1; AAD43562)"
FT /evidence="ECO:0000305"
FT CONFLICT 753
FT /note="L -> I (in Ref. 1; AAD43562)"
FT /evidence="ECO:0000305"
FT CONFLICT 917
FT /note="D -> N (in Ref. 1; AAD43562)"
FT /evidence="ECO:0000305"
FT CONFLICT 949
FT /note="V -> F (in Ref. 1; AAD43562)"
FT /evidence="ECO:0000305"
FT CONFLICT 1044
FT /note="G -> S (in Ref. 1; AAD43562)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 2586 AA; 280550 MW; 446E29F23382BEA4 CRC64;
MGVIESPSST TSGSAEEMAQ AITGHEDSVL PVAIVGMGMR LPGGIHTPDE LWGMLVEKRS
TRCEIPPTRF SVDGFHSPSS KPGSIAMRHG HFLDDKDDLH RLDTSFFSMG MTEVSDIDPQ
QRMLLEVAYE CMQSSGQTNW RGSNIGCYVG VWGEDWLDLH SKDLYDSGTY RVSGGHDFAI
SNRISYEYDL KGPSFTIKAG CSSSLIALHE AVRAIRAGDC DGAIVAGTNL VFSPTMSVAM
TEQGVLSPDA SCKTFDANAN GYARGEAINA IFLKPLNNAL REGDPIRALV RATSSNSDGK
TPGMSMPSSE SHEALIRRAY GEVFLDPKDT CFVEAHGTGT SVGDPLEATA IARVFGGSSD
NKLYIGSVKP NLGHSEGASG VSSVMKAVLA LENRTIPPNI NFSTPNPKIP FSEMNMAVPV
DAIPWPRDRP LRVSVNSFGI GGANAHCIIE TLEEYLGRSL PNESQVAPIR NGNGSVQADS
SSAVTSITAM KMEVRRKKRQ SAVEAAGLVS NLRLVADSTK IRPSKALYVL SAANPTSLRQ
SVMDYQKYLA SHKTDPVDVS YTLANRREHL SHRTYGVVTT ESTNDTPIVP DFSPLSKTNN
NSLPEINMIF TGQGAQWVGM GKELMDEYET FYNTIAYLGL VLSGLEHPPT WDLIRELSRP
AESSNVGRAE FSQPLVCAVQ VALVDLLRSW GITPAAVVGH SSGEMAAAYA AGAISSEEAI
TIAYYRGYVN QQYTRDGGMA AIGMGAQEVA PYLVEGVGVA CENSPQSVTL SGDKGVLEEV
CQKIKEQVPD CFVRQLKVNV AYHSHHMQDL GGLFENLLEG KVYSQSPTIP FFSSVTVQKI
TEPRSLDAAY WRQNLESPVR FTGAVKLLLE ARASTGSKQV FVEIGPHSAL SGPLRQIFKA
HGRGKEAYVS AMIRGEDCTE SLLKLAGELF CHGTSLQLSN VTADGDVVVD LPPYPWNHDR
EYWSESRVSK DWRFRKFPNH ELLGSRTLES SSLQPEWRNL IRLDGIPWLR DHQVLNDVVF
PCAGYLAMAV EAVRQVAGTS EIGGFTLKSV VVQSALVLTE SKPVEVLTSL RPVRLTNTLD
SAWWEFSIVA HNGTSWIKHC EGQVRPGQDA HQKTAVLPQS EPISQHYPRL VDNLYPELLR
IGLRYGPSFR GLDNVSCVPN GKKAAAMLRE TTVSESSYAI HPTTIDHCLQ LFFPASCDGA
FYRAEKLCVP TAIGRLYLAD GKSCEVESAR AEASAATNSG GSISGAATVV SKQNSTLLSL
EDGKFSPLEM DLAEDGNADL VGTARLEWKP NLDFADMCSL VRPSHASMND GPELDLVEQL
TLLAILEIHE RIDGAVTPGG HDHAHQHIPN FRGWIADQVT AAAEGRYRGV VADAREIASL
ERGARLSLMT NLRQQVLRTG AASAAVLIGR VVDHCEEIVK GELEGIELLQ AEDGLTNYYN
YVESRTDSID FFATAGHTRP TLRVLEIGAG TGGGAQVILE GLTNGKERLF STYAYTDISA
GFFVAAQERF KAYKGLDFKV LDITKDPSEQ GFESGSFDLI IAGNVIHATP TLNETLANVR
KLLAPEGYLF LQELSPKMRM VNLIMGILPG WWLGAAEGRV EEPYLDPSQW DTVLKETGFS
GVDSAIYDAP YPYHLNANII SRPAKESAPQ PRAIRGRLTL LHHADDTNSS SITQLREVLD
ARGLETDMVV FHEHEELKAG EQDVIISLLE LKKPFFSSIS AAQLESFQRI VAKLGSIEMI
WVTRPAQHGL SASDNPGFGL SLGLTRTLRS EQSLAITTLE IDQVNDESFK AVTNLAIKVL
DHREGGSTES TRGATTMDPD REYVVENGVV KVARYHPVSL SQELASRASK PEAVTLEIGR
MGLLQTLGWV PFPTSDPGYG EVTIEPRCAG LNFRDVLLCM GVVEATGVGI GLEGSGIITK
VGAGVGKFQP GDPVFYLADN CFSTQITISA QRCAKIPSQL AFEDAATMPC VYATVIHSLL
DVGGLRPGQS ILIHSACGGI GIAALNLCRN FQGLEIYTTV GNEEKVQYLV DNFGLPRSRI
FNSRDASFLY DVRAATQGRG VDLVLNSLSG DLLHASWQCV APYGKMLEIG KRDFIGKARL
EMDLFEANRS FIGIDLARFD SARCQKLLER TAAMIQTGIV QPIKPVKVFD ASDAEGAFRY
MQKGVHLGKI VVSIPPHSST ALPITPKPLQ VKLNPEASYL LVGGLGGLGR AAATWMVESG
ARYLIFFSRS AGLSVRDQAF FQELASQGCT AQAVRGDVLN LADVELAMAS APPGKPIRGV
LQMSMVLRDK PFADMSLEDW DTAVKPKVHG TWNLHLAAPK DLDFFFATGS ISGSFGTPGQ
ANYAAGNTYL TALFEHRRAL GLPASVLQIG LIEDIGYLAK NPERAEALRA AGGFFLRTRQ
LLQGLNWALL SSDPHHPEYQ LTIGLRSDKA LSDPANRVIW KKDSRAALYH NQEISTDAGA
GDDQGINAIR LLVASCEEDP GILEDPATVE LVTNEIGKRV CMFMLRPVEE MDPTASLTSL
GVDSLVTIEI RNWIKRTFGG VEVSTLEILN SGTIQGLARL TVDGLKARFA ASEQTDGDAY
LEMKAP
