STCA_EMENI
ID STCA_EMENI Reviewed; 2211 AA.
AC Q12397; C8VDU9; Q5AV55;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 26-MAY-2009, sequence version 2.
DT 25-MAY-2022, entry version 131.
DE RecName: Full=Norsolorinic acid synthase stcA {ECO:0000250|UniProtKB:Q12053};
DE Short=NSAS {ECO:0000250|UniProtKB:Q12053};
DE EC=2.3.1.221 {ECO:0000250|UniProtKB:Q12053};
DE AltName: Full=Non-reducing polyketide synthase stcA {ECO:0000303|PubMed:8643646};
DE AltName: Full=Sterigmatocystin biosynthesis cluster protein A {ECO:0000303|PubMed:8643646};
DE AltName: Full=Sterigmatocystin biosynthesis polyketide synthase {ECO:0000303|PubMed:7642507};
GN Name=stcA {ECO:0000303|PubMed:8643646};
GN Synonyms=pksST {ECO:0000303|PubMed:7642507}; ORFNames=AN7825;
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 [GENOMIC DNA], DOMAIN, DISRUPTION PHENOTYPE, FUNCTION,
RP AND PATHWAY.
RC STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX PubMed=7642507; DOI=10.1128/jb.177.16.4792-4800.1995;
RA Yu J.-H., Leonard T.J.;
RT "Sterigmatocystin biosynthesis in Aspergillus nidulans requires a novel
RT type I polyketide synthase.";
RL J. Bacteriol. 177:4792-4800(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], INDUCTION, FUNCTION, AND PATHWAY.
RC STRAIN=FGSC 26;
RX PubMed=8643646; DOI=10.1073/pnas.93.4.1418;
RA Brown D.W., Yu J.-H., Kelkar H.S., Fernandes M., Nesbitt T.C., Keller N.P.,
RA Adams T.H., Leonard T.J.;
RT "Twenty-five coregulated transcripts define a sterigmatocystin gene cluster
RT in Aspergillus nidulans.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:1418-1422(1996).
RN [3]
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 [4]
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 [5]
RP FUNCTION, AND INDUCTION.
RX PubMed=8017929; DOI=10.1128/aem.60.5.1444-1450.1994;
RA Keller N.P., Kantz N.J., Adams T.H.;
RT "Aspergillus nidulans verA is required for production of the mycotoxin
RT sterigmatocystin.";
RL Appl. Environ. Microbiol. 60:1444-1450(1994).
RN [6]
RP FUNCTION.
RX PubMed=7486998; DOI=10.1128/aem.61.10.3628-3632.1995;
RA Keller N.P., Segner S., Bhatnagar D., Adams T.H.;
RT "StcS, a putative P-450 monooxygenase, is required for the conversion of
RT versicolorin A to sterigmatocystin in Aspergillus nidulans.";
RL Appl. Environ. Microbiol. 61:3628-3632(1995).
RN [7]
RP FUNCTION.
RX PubMed=8900026; DOI=10.1128/aem.62.11.4296-4298.1996;
RA Kelkar H.S., Keller N.P., Adams T.H.;
RT "Aspergillus nidulans stcP encodes an O-methyltransferase that is required
RT for sterigmatocystin biosynthesis.";
RL Appl. Environ. Microbiol. 62:4296-4298(1996).
RN [8]
RP FUNCTION.
RX PubMed=8962148; DOI=10.1073/pnas.93.25.14873;
RA Brown D.W., Adams T.H., Keller N.P.;
RT "Aspergillus has distinct fatty acid synthases for primary and secondary
RT metabolism.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:14873-14877(1996).
RN [9]
RP FUNCTION.
RX PubMed=8999832; DOI=10.1074/jbc.272.3.1589;
RA Kelkar H.S., Skloss T.W., Haw J.F., Keller N.P., Adams T.H.;
RT "Aspergillus nidulans stcL encodes a putative cytochrome P-450
RT monooxygenase required for bisfuran desaturation during
RT aflatoxin/sterigmatocystin biosynthesis.";
RL J. Biol. Chem. 272:1589-1594(1997).
RN [10]
RP INDUCTION.
RX PubMed=9680223; DOI=10.1046/j.1365-2958.1998.00907.x;
RA Fernandes M., Keller N.P., Adams T.H.;
RT "Sequence-specific binding by Aspergillus nidulans aflR, a C6 zinc cluster
RT protein regulating mycotoxin biosynthesis.";
RL Mol. Microbiol. 28:1355-1365(1998).
RN [11]
RP FUNCTION.
RX PubMed=10618248; DOI=10.1128/aem.66.1.359-362.2000;
RA Keller N.P., Watanabe C.M., Kelkar H.S., Adams T.H., Townsend C.A.;
RT "Requirement of monooxygenase-mediated steps for sterigmatocystin
RT biosynthesis by Aspergillus nidulans.";
RL Appl. Environ. Microbiol. 66:359-362(2000).
RN [12]
RP REVIEW ON STERIGMATOCYSTIN BIOSYNTHESIS.
RX PubMed=24957370; DOI=10.3390/metabo2010100;
RA Klejnstrup M.L., Frandsen R.J., Holm D.K., Nielsen M.T., Mortensen U.H.,
RA Larsen T.O., Nielsen J.B.;
RT "Genetics of polyketide metabolism in Aspergillus nidulans.";
RL Metabolites 2:100-133(2012).
CC -!- FUNCTION: Non-reducing polyketide synthase; part of the gene cluster
CC that mediates the biosynthesis of sterigmatocystin (ST), a polyketide-
CC derived furanocoumarin which is part of the most toxic and carcinogenic
CC compounds among the known mycotoxins (PubMed:7642507, PubMed:8643646).
CC The first step in the biosynthesis of sterigmatocystin is the
CC production of hexanoate by the fatty acid synthase (FAS) units stcJ and
CC stcK (PubMed:8962148). The polyketide backbone is assembled by the non-
CC reducing polyketide synthase stcA by condensation of the starter
CC hexanoyl-CoA and 7 malonyl-CoA extender units followed by cyclization
CC and release of norsolorinic acid (By similarity). Norsolorinic acid is
CC the first stable intermediate in the biosynthesis of sterigmatocystin
CC and is converted into averantin (AVN) by the ketoreductase stcE which
CC reduces the hexanoate ketone to an alcohol (PubMed:8643646) (Probable).
CC Averantin is then oxidized into 5'-hydroxyaverantin (HAVN) by the
CC cytochrome P450 monooxygenase stcF (PubMed:10618248). 5'-
CC hydroxyaverantin is further converted to 5'-oxyaverantin (OAVN) by the
CC 5'-hydroxyaverantin dehydrogenase stcG (PubMed:24957370). The next step
CC is the conversion of OAVN into averufin (AVF) which is catalyzed by a
CC yet to be identified enzyme (PubMed:24957370). The cytochrome P450
CC monoxygenase stcB and the flavin-binding monooxygenase stcW are both
CC required for the conversion of averufin to 1-hydroxyversicolorone
CC (PubMed:10618248). The esterase stcI probably catalyzes the formation
CC of versiconal hemiacetal acetate from 1-hydroxyversicolorone
CC (PubMed:24957370). The oxydoreductase stcN then probably catalyzes the
CC biosynthetic step from versiconal to versicolorin B (VERB)
CC (PubMed:24957370). The next step is performed by the versicolorin B
CC desaturase stcL to produce versicolorin A (VERA) (PubMed:8999832). The
CC ketoreductase stcU and the cytochrome P450 monooxygenase stcS are
CC involved in the conversion of versicolorin A to
CC demethylsterigmatocystin (PubMed:7486998). The Baeyer-Villiger oxidas
CC stcQ and the reductase stcR might be involved in the biosynthetic step
CC from versicolorin A to demethylsterigmatocystin (PubMed:24957370). The
CC final step in the biosynthesis of sterigmatocystin is the methylation
CC of demethylsterigmatocystin catalyzed by the methyltransferase stcP
CC (PubMed:8900026). {ECO:0000250|UniProtKB:Q12053,
CC ECO:0000269|PubMed:10618248, ECO:0000269|PubMed:7486998,
CC ECO:0000269|PubMed:7642507, ECO:0000269|PubMed:8643646,
CC ECO:0000269|PubMed:8900026, ECO:0000269|PubMed:8962148,
CC ECO:0000269|PubMed:8999832, ECO:0000303|PubMed:24957370,
CC ECO:0000305|PubMed:8643646}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=6 H(+) + hexanoyl-[ACP] + 7 malonyl-CoA = 7 CO2 + 7 CoA + 2
CC H2O + holo-[ACP] + noranthrone; Xref=Rhea:RHEA:35179, Rhea:RHEA-
CC COMP:9632, Rhea:RHEA-COMP:9685, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57384,
CC ChEBI:CHEBI:64479, ChEBI:CHEBI:77904, ChEBI:CHEBI:78459;
CC EC=2.3.1.221; Evidence={ECO:0000250|UniProtKB:Q12053};
CC -!- COFACTOR:
CC Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC Evidence={ECO:0000305};
CC Note=Binds 2 phosphopantetheines covalently. {ECO:0000305};
CC -!- PATHWAY: Mycotoxin biosynthesis; sterigmatocystin biosynthesis.
CC {ECO:0000269|PubMed:7642507, ECO:0000269|PubMed:8643646}.
CC -!- INDUCTION: The genes forming the sterigmatocystin biosynthesis cluster
CC are co-regulated and induced on oatmeal porridge or the fungal isolates
CC were grown either on oatmeal porridge or in YEC medium (0.2% yeast
CC extract, 5.0% corn steep liquor) (PubMed:8643646, PubMed:8017929).
CC Expression is positively regulated by the cluster-specific
CC transcription factor aflR that binds the palindromic sequence 5'-
CC TCG(N5)CGA-3'found in the promoter (PubMed:9680223).
CC {ECO:0000269|PubMed:8017929, ECO:0000269|PubMed:8643646,
CC ECO:0000269|PubMed:9680223}.
CC -!- DOMAIN: The domain architecture includes a starter unit:ACP
CC transacylase (SAT) domain, a beta-ketoacyl synthase (KS) domain, a
CC malonyl-CoA:ACP transacylase (MAT) domain, a product template (PT)
CC domain, 2 acyl-carrier (ACP) domains, and a thioesterase/Claisen
CC cyclase (TE/CLC) domain (By similarity). The SAT domain receives a C6-
CC fatty acid starter unit and transfers it onto the ACP for chain
CC elongation. The KS accepts the hexanoyl-ACP unit and subsequent
CC malonate extender units are loaded onto the ACP from the MAT domain for
CC chain extension to generate the linear poly-beta-keto ACP-bound
CC intermediate. The linear intermediate is then cyclized and aromatized
CC in the PT domain. The resulting bicyclic intermediate is ultimately
CC transferred from the ACP to the TE/CLC domain and undergoes Claisen-
CC type C-C bond cyclization to release the product norsolorinic acid
CC anthrone (noranthrone), which spontaneously oxidizes in vitro to
CC norsolorinic acid (By similarity). {ECO:0000250|UniProtKB:Q12053}.
CC -!- DISRUPTION PHENOTYPE: Blocks production of sterigmatocystin and all
CC sterigmatocystin intermediate substrates but does not affect
CC transcription of the pathway genes. {ECO:0000269|PubMed:7642507}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA81586.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=AAC49191.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=EAA61613.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; L39121; AAA81586.1; ALT_SEQ; Genomic_DNA.
DR EMBL; U34740; AAC49191.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AACD01000132; EAA61613.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BN001304; CBF80184.1; -; Genomic_DNA.
DR RefSeq; XP_681094.1; XM_676002.1.
DR AlphaFoldDB; Q12397; -.
DR SMR; Q12397; -.
DR STRING; 162425.CADANIAP00000967; -.
DR ESTHER; emeni-stca; Thioesterase.
DR EnsemblFungi; CBF80184; CBF80184; ANIA_07825.
DR EnsemblFungi; EAA61613; EAA61613; AN7825.2.
DR GeneID; 2869640; -.
DR KEGG; ani:AN7825.2; -.
DR VEuPathDB; FungiDB:AN7825; -.
DR eggNOG; KOG1202; Eukaryota.
DR HOGENOM; CLU_000022_6_0_1; -.
DR InParanoid; Q12397; -.
DR OMA; KWGCWLD; -.
DR OrthoDB; 68112at2759; -.
DR UniPathway; UPA00377; -.
DR Proteomes; UP000000560; Chromosome IV.
DR Proteomes; UP000005890; Unassembled WGS sequence.
DR GO; GO:0004312; F:fatty acid synthase activity; IBA:GO_Central.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:1900557; P:emericellamide biosynthetic process; IMP:AspGD.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IBA:GO_Central.
DR GO; GO:1900815; P:monodictyphenone biosynthetic process; IMP:AspGD.
DR GO; GO:1900584; P:o-orsellinic acid biosynthetic process; IMP:AspGD.
DR GO; GO:0019748; P:secondary metabolic process; NAS:AspGD.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IBA:GO_Central.
DR GO; GO:0045461; P:sterigmatocystin biosynthetic process; IMP:AspGD.
DR Gene3D; 1.10.1200.10; -; 2.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.40.366.10; -; 2.
DR Gene3D; 3.40.47.10; -; 1.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
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; IPR014031; Ketoacyl_synth_C.
DR InterPro; IPR014030; Ketoacyl_synth_N.
DR InterPro; IPR016036; Malonyl_transacylase_ACP-bd.
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; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR030918; PT_fungal_PKS.
DR InterPro; IPR032088; SAT.
DR InterPro; IPR001031; Thioesterase.
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; PF00550; PP-binding; 2.
DR Pfam; PF14765; PS-DH; 1.
DR Pfam; PF16073; SAT; 1.
DR Pfam; PF00975; Thioesterase; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 2.
DR SUPFAM; SSF47336; SSF47336; 2.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR TIGRFAMs; TIGR04532; PT_fungal_PKS; 1.
DR PROSITE; PS50075; CARRIER; 2.
PE 2: Evidence at transcript level;
KW Acyltransferase; Multifunctional enzyme; Phosphopantetheine;
KW Phosphoprotein; Reference proteome; Repeat; Transferase; Virulence.
FT CHAIN 1..2211
FT /note="Norsolorinic acid synthase stcA"
FT /id="PRO_0000180304"
FT DOMAIN 1712..1791
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 1839..1915
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 11..251
FT /note="Starter unit:ACP transacylase (SAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:7642507"
FT REGION 358..378
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 383..815
FT /note="Ketoacyl synthase (KS)domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:7642507"
FT REGION 912..1201
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:7642507"
FT REGION 1289..1316
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1340..1643
FT /note="Product template (PT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:7642507"
FT REGION 1655..1706
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1912..1947
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1969..2205
FT /note="Thioesterase/Claisen cyclase (TE/CLC) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:7642507"
FT COMPBIAS 1655..1699
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1912..1943
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 552
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000250|UniProtKB:Q12053"
FT ACT_SITE 1004
FT /note="For acyl/malonyl transferase activity"
FT /evidence="ECO:0000250|UniProtKB:Q12053"
FT ACT_SITE 2039
FT /note="For thioesterase activity"
FT /evidence="ECO:0000250|UniProtKB:Q12053"
FT MOD_RES 1749
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 1873
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT CONFLICT 1584
FT /note="D -> T (in Ref. 1; AAA81586 and 2; AAC49191)"
FT /evidence="ECO:0000305"
FT CONFLICT 1940
FT /note="E -> A (in Ref. 1; AAA81586 and 2; AAC49191)"
FT /evidence="ECO:0000305"
FT CONFLICT 2164
FT /note="K -> W (in Ref. 1; AAA81586 and 2; AAC49191)"
FT /evidence="ECO:0000305"
FT CONFLICT 2183
FT /note="V -> L (in Ref. 1; AAA81586 and 2; AAC49191)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 2211 AA; 242555 MW; 1E0319BE9F799759 CRC64;
MASHAEPTRL FLFGDQTYDF VADLRDLLNI RNNPILVAFL EQSHHVIRAQ MIRELPPKEH
KQARTASLAE LLQKYVDRKL PSAFQTALSC VTQIGLFMRQ FDDPRVLYPH ANDSYVLGVC
TGSLAAAAIS CSTSLSELLP IAVQTVLVAF RLGLWAEKVR DNLEISETNQ TQPWSAVCHV
PPEEVAIAID RFSHKKVRSP VYRAQRPWIT ATSAKTTTVS ASPDILSQLA SQAPFTNSKL
WREIPIYVPA HNNHLFSSRD VDDILATTNE NPWSTFGAQI PFLSSVTGKL AWVRNYRDLL
HLALSQCLIE PIRWDVVEAE VPRLLKDRDG LDTLTIVAFT TVLSKSLSNA LVTEGIKPAE
PPTSINKTPE RYSHRPGSDR GKLAIVSMSG RFPEAPSTDS FWDLLYKGLD VCKEVPLRRW
DVKTHVDPSG KARNKGATRW GCWLDFAGEF DPRFFSISPK EAPQMDPAQR MALMSTYEAM
ERGGIVPDTT PSTQRNRIGV FHGVTSNDWM ETNTAQNIDT YFITGGNRGF IPGRINFCFE
FSGPSYSNDT ACSSSLAAIH LACNSLWRGD CDTAVAGGTN MIFTPDGHTG LDKGFFLSRT
GNCKAFDDAA DGYCRAEGVG TVFIKRLEDA LAENDPILAT ILDIKTNHSA MSDSMTRPFK
PAQIDNMSAL LSTAGISPLD LSYIEMHGTG TQVGDAVEME SVLSLFAPDE TFRPRDKPLY
VGSAKANIGH GEGVSGVTSL IKVLLMMKND TIPPHCGIKP GSRINRNYPD LPARNVHIAF
EPKPWPRTDT PRRVLINNFS AAGGNTAVLV EDAPVRDPVT ASDPRTSHIV TVSGHVGKSL
KLNLEKLRDH LVKRPEINPS ELSYTTTARR WHHPHRVSIT GANTMEILRN VESAIARGHG
VNRPATKPKI VIACSGQGSQ YTGMGWQLYN SYPTFRSDLE RFDQLARSYG FPSFLEVYTS
KPVGDSMEDL LPVIVQLALV SLEMALGNLL GSFGLKPSAV IGHSLGEYAA LYISGVLSAA
DTLYLVGMRA KLLQERCQRG THAMLAVRAS PVTLCEVLAE SNCEVACHNG PNDTVLSGPL
KEVMNLQNSL SATGIKGTLL KLPFAFHSAQ VQPILEEFKN VARGVTFHKP QIPVLSPLLV
KVIDEKGTVD PVYLARHCRE PVKMVSVLEH ARDQHIITDR TIVIDVGPKA LMAGMIKTTL
DKDTSSALPT LGPSLDVWKS LTNILGTLYS RGLDINWVAY HEPFGSAKKV IELPSYGWDL
KDYFIPYKGE WCLHRHEIRC SCATPGKETA TSDYQLPSDE QVAAKRPSKQ DESKEAYPEI
VATTTVHRVV EEKTEPLGAT LVVETDISRP DVNQIAQGHL VDGIPLCTPS VYADIALHVG
RYSMNRLRAS HPGAMDGVVD VADMVIDKAL IPHGKSPQLL RTTLTMTWPP KAAATTRSAK
IKFATYFADG KLDTEHATCT VRFTSEAQLK SLQKKVPEYQ ERIKKLGEGL RQGQFIRYTT
KSGYKLMSSM ASFHRDYKLL NHLILNEADN EAVSTMDFSA AKSEGTFAAH PAYVDAITQV
GGFAMNANDN TDIQQEVFVN HGWDSFQVYQ PLVKGKTYEV YVRMTEDEKG DLVHGDTIVL
YGDAVVAFFK GLSLRRVPRR GLRMVLQQAS DKAARLHGNQ QAVKTQAPQR AALKQKPQSS
PTQPHASKVA YSRSATSPTA GKPVVAARDL SREGDDKFKA VLSVISEESG VALGELTADT
NFADIGIDSL SSMVIGSRLR EDLGLELGAE FSLFIDCPTV RSLKTLLSGS AVSVNNDKDE
LEPGQEAETA APEQLDLRIG DAAPSKVRDA NIEPLDLGDE LFRNVLRIVS EESGVALDEL
SAETVFADIG IDSLSSMVIT SRFREDLGMS LDSSFNLFEE VPTVARLQEF FGTTSGSTTG
SSGSGSSEDE TDSIPSTPEE YTTADTRVPE CRPTTSVVLQ GLPQMAKQIL FMLPDGGGSA
SSYLTIPRLH ADVAIVGLNC PYARDPENMN CTHQSMIQSF CNEIKRRQPE GPYHLGGWSS
GGAFAYVTAE ALINAGNEVH SLIIIDAPVP QVMEKLPTSF YEYCNNLGLF SNQPGGTTDG
TAQPPPYLIP HFQATVDVML DYRVAPLKTN RMPKVGIIWA SETVMDEDNA PKMKGMHFMV
QKRKDFGPDG WDVVCPGAVF DIVRAEGANH FTLMTKEHVY LVRELIDRVM G
