ID   CPAS_ASPOZ              Reviewed;        3907 AA.
AC   B6F209;
DT   10-OCT-2018, integrated into UniProtKB/Swiss-Prot.
DT   16-DEC-2008, sequence version 1.
DT   03-AUG-2022, entry version 85.
DE   RecName: Full=Cyclo-acetoacetyl-L-tryptophan synthase {ECO:0000303|PubMed:19663400};
DE            EC=2.3.1.- {ECO:0000269|PubMed:19663400};
DE   AltName: Full=Cyclopiazonic acid biosynthesis cluster protein A {ECO:0000303|PubMed:18854220};
DE   AltName: Full=Polyketide synthase-nonribosomal peptide synthetase cpaA;
DE            Short=PKS-NRPS cpaA {ECO:0000303|PubMed:18854220};
GN   Name=cpaA {ECO:0000303|PubMed:18854220};
GN   Synonyms=cpaS {ECO:0000303|PubMed:19663400};
OS   Aspergillus oryzae (Yellow koji mold).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC   Aspergillus subgen. Circumdati.
OX   NCBI_TaxID=5062;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], DISRUPTION PHENOTYPE, FUNCTION, AND
RP   PATHWAY.
RC   STRAIN=NBRC 4177;
RX   PubMed=18854220; DOI=10.1016/j.fgb.2008.09.006;
RA   Tokuoka M., Seshime Y., Fujii I., Kitamoto K., Takahashi T., Koyama Y.;
RT   "Identification of a novel polyketide synthase-nonribosomal peptide
RT   synthetase (PKS-NRPS) gene required for the biosynthesis of cyclopiazonic
RT   acid in Aspergillus oryzae.";
RL   Fungal Genet. Biol. 45:1608-1615(2008).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], DISRUPTION PHENOTYPE, FUNCTION, AND
RP   PATHWAY.
RC   STRAIN=NBRC 4177;
RX   PubMed=21608094; DOI=10.1002/cbic.201000672;
RA   Kato N., Tokuoka M., Shinohara Y., Kawatani M., Uramoto M., Seshime Y.,
RA   Fujii I., Kitamoto K., Takahashi T., Takahashi S., Koyama Y., Osada H.;
RT   "Genetic safeguard against mycotoxin cyclopiazonic acid production in
RT   Aspergillus oryzae.";
RL   ChemBioChem 12:1376-1382(2011).
RN   [3]
RP   FUNCTION, CATALYTIC ACTIVITY, DOMAIN, AND PATHWAY.
RX   PubMed=19663400; DOI=10.1021/bi901123r;
RA   Liu X., Walsh C.T.;
RT   "Cyclopiazonic acid biosynthesis in Aspergillus sp.: characterization of a
RT   reductase-like R* domain in cyclopiazonate synthetase that forms and
RT   releases cyclo-acetoacetyl-L-tryptophan.";
RL   Biochemistry 48:8746-8757(2009).
RN   [4]
RP   FUNCTION.
RX   PubMed=19877600; DOI=10.1021/bi901597j;
RA   Liu X., Walsh C.T.;
RT   "Characterization of cyclo-acetoacetyl-L-tryptophan
RT   dimethylallyltransferase in cyclopiazonic acid biosynthesis: substrate
RT   promiscuity and site directed mutagenesis studies.";
RL   Biochemistry 48:11032-11044(2009).
CC   -!- FUNCTION: Hybrid PKS-NRPS synthetase; part of the gene cluster that
CC       mediates the biosynthesis of the fungal neurotoxin cyclopiazonic acid
CC       (CPA), a nanomolar inhibitor of Ca(2+)-ATPase with a unique pentacyclic
CC       indole tetramic acid scaffold (PubMed:18854220, PubMed:21608094,
CC       PubMed:19663400). The hybrid two module polyketide synthase-
CC       nonribosomal peptide synthetase (PKS-NRPS) cpaS incorporates acetyl-
CC       CoA, malonyl-CoA, and tryptophan (Trp) and utilizes a C-terminal redox-
CC       incompetent reductase domain to make and release the tryptophan
CC       tetramic acid, cyclo-acetoacetyl-L-tryptophan (c-AATrp), as the first
CC       intermediate in the pathway. CpaS catalyzes a Dieckmann-type
CC       cyclization on the N-acetoacetyl-Trp intermediate bound in thioester
CC       linkage to the phosphopantetheinyl arm of the T domain to form and
CC       release c-AATrp (PubMed:18854220, PubMed:21608094, PubMed:19663400).
CC       CpaD than regiospecifically dimethylallylates c-AATrp to form beta-
CC       cyclopiazonic acid. CpaD discriminates against free Trp but accepts
CC       tryptophan-containing thiohydantoins, diketopiperazines, and linear
CC       peptides as substrates for C4-prenylation and also acts as
CC       regiospecific O-dimethylallyltransferase (DMAT) on a tyrosine-derived
CC       tetramic acid (PubMed:19877600). The beta-cyclopiazonate dehydrogenase
CC       cpaO then carries out the dehydrogenation of beta-CPA to yield an
CC       unstable enimine product, which is captured by intramolecular
CC       cyclization to create the pentacyclic fused scaffold of alpha-
CC       cyclopiazonate (PubMed:21608094). Fimally, the cytochrome P450
CC       monooxygenase cpaH mediates the conversion of CPA into the less toxic
CC       2-oxocyclopiazonic acid, the end product of the CPA pathway in A.oryza
CC       (PubMed:21608094). {ECO:0000269|PubMed:18854220,
CC       ECO:0000269|PubMed:19663400, ECO:0000269|PubMed:19877600,
CC       ECO:0000269|PubMed:21608094}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=acetyl-CoA + L-tryptophan + malonyl-CoA = CO2 + 2 CoA + cyclo-
CC         acetoacetyl-L-tryptophan + H2O; Xref=Rhea:RHEA:66900,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC         ChEBI:CHEBI:57288, ChEBI:CHEBI:57384, ChEBI:CHEBI:57912,
CC         ChEBI:CHEBI:167552; Evidence={ECO:0000269|PubMed:19663400};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66901;
CC         Evidence={ECO:0000269|PubMed:19663400};
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:18854220, ECO:0000269|PubMed:19663400,
CC       ECO:0000269|PubMed:21608094}.
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. Each module is responsible for the recognition (via the A
CC       domain) and incorporation of a single amino acid into the growing
CC       peptide product. Thus, an NRP synthetase is generally composed of one
CC       or more modules and can terminate in a thioesterase domain (TE) that
CC       releases the newly synthesized peptide from the enzyme. Occasionally,
CC       epimerase (E) domains (responsible for L- to D- amino acid conversion)
CC       are present within the NRP synthetase. CpaA contains also a polyketide
CC       synthase module (PKS) consisting of several catalytic domains including
CC       a ketoacyl synthase domain (KS), an acyl transferase domain (AT), a
CC       dehydratase domain (DH), a methyltransferase domain (MT), and a
CC       ketoreductase domain (KR). Instead of a thioesterase domain (TE), CpaA
CC       finishes with a reductase-like domain (RED) for peptide release. CpaA
CC       has the following architecture: KS-AT-DH-KR-PCP-C-A-T-RED.
CC       {ECO:0000305|PubMed:19663400}.
CC   -!- DISRUPTION PHENOTYPE: Impairs the production of cyclopiazonic acid and
CC       of its biosynthetic intermediates cyclo-acetoacetyl-L-tryptophan and
CC       beta-cyclopiazonic acid. {ECO:0000269|PubMed:18854220,
CC       ECO:0000269|PubMed:21608094}.
CC   -!- SIMILARITY: In the C-terminal section; belongs to the NRP synthetase
CC       family. {ECO:0000305}.
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DR   EMBL; AB457185; BAG82673.1; -; Genomic_DNA.
DR   EMBL; AB506492; BAK26562.1; -; Genomic_DNA.
DR   SMR; B6F209; -.
DR   STRING; 5062.CADAORAP00007920; -.
DR   VEuPathDB; FungiDB:AO090001000277; -.
DR   BioCyc; MetaCyc:MON-18879; -.
DR   GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR   GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR   GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
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:0032259; P:methylation; IEA:UniProtKB-KW.
DR   GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR   Gene3D; 1.10.1200.10; -; 2.
DR   Gene3D; 3.10.129.110; -; 1.
DR   Gene3D; 3.30.300.30; -; 1.
DR   Gene3D; 3.30.559.10; -; 1.
DR   Gene3D; 3.40.366.10; -; 1.
DR   Gene3D; 3.40.47.10; -; 1.
DR   Gene3D; 3.40.50.12780; -; 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; 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; 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; 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; IPR013968; PKS_KR.
DR   InterPro; IPR020806; PKS_PP-bd.
DR   InterPro; IPR009081; PP-bd_ACP.
DR   InterPro; IPR029063; SAM-dependent_MTases_sf.
DR   InterPro; IPR016039; Thiolase-like.
DR   Pfam; PF00698; Acyl_transf_1; 1.
DR   Pfam; PF00501; AMP-binding; 1.
DR   Pfam; PF00668; Condensation; 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; PF07993; NAD_binding_4; 1.
DR   Pfam; PF00550; PP-binding; 2.
DR   Pfam; PF14765; PS-DH; 1.
DR   SMART; SM00827; PKS_AT; 1.
DR   SMART; SM00826; PKS_DH; 1.
DR   SMART; SM00825; PKS_KS; 1.
DR   SMART; SM00823; PKS_PP; 2.
DR   SUPFAM; SSF47336; SSF47336; 2.
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; PS00455; AMP_BINDING; 1.
DR   PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR   PROSITE; PS50075; CARRIER; 1.
PE   1: Evidence at protein level;
KW   Acyltransferase; Isomerase; Ligase; Methyltransferase;
KW   Multifunctional enzyme; NADP; Oxidoreductase; Phosphopantetheine;
KW   Phosphoprotein; Repeat; S-adenosyl-L-methionine; Transferase.
FT   CHAIN           1..3907
FT                   /note="Cyclo-acetoacetyl-L-tryptophan synthase"
FT                   /id="PRO_0000445385"
FT   DOMAIN          2356..2430
FT                   /note="Carrier 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT                   ECO:0000305|PubMed:19663400"
FT   DOMAIN          3474..3549
FT                   /note="Carrier 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT                   ECO:0000305|PubMed:19663400"
FT   REGION          3..382
FT                   /note="Ketoacyl synthase (KS) domain"
FT                   /evidence="ECO:0000255, ECO:0000305|PubMed:19663400"
FT   REGION          555..870
FT                   /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT                   /evidence="ECO:0000255, ECO:0000305|PubMed:19663400"
FT   REGION          937..1236
FT                   /note="Dehydratase (DH) domain"
FT                   /evidence="ECO:0000255, ECO:0000305|PubMed:19663400"
FT   REGION          1386..1573
FT                   /note="Methyltransferase (MT) domain"
FT                   /evidence="ECO:0000255, ECO:0000305|PubMed:19663400"
FT   REGION          2064..2238
FT                   /note="Ketoreductase (KR)domain"
FT                   /evidence="ECO:0000255, ECO:0000305|PubMed:19663400"
FT   REGION          2324..2352
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          2504..2926
FT                   /note="Condensation"
FT                   /evidence="ECO:0000255, ECO:0000305|PubMed:19663400"
FT   REGION          2959..3359
FT                   /note="Adenylation"
FT                   /evidence="ECO:0000255, ECO:0000305|PubMed:19663400"
FT   REGION          3594..3813
FT                   /note="Reductase (RED) domain"
FT                   /evidence="ECO:0000255, ECO:0000305|PubMed:19663400"
FT   MOD_RES         2390
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   MOD_RES         3509
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ   SEQUENCE   3907 AA;  430405 MW;  14CF3D59F3145046 CRC64;
     MKTPIAVVGT ACRFPGDISS PSQLWELLSN PKDVLRDLNP KRLNLTGFNH HNAEHHGATN
     VPNKSYILDD DVYRFDAAFF NISAAEAEAM DPQQRLLLET TYEALESAGY TLKQMRGSST
     SVFIGAMTSD YHDIQARDLD TISRWHATGT SPSILSNRIS YFFDLKGPSM TVNTACSSSL
     VALHQAVQSL RNGDCTAAIV GGVNLLLDPE VYISHSNLHM LSPTSRCRMW DRDADGYARG
     EGCTSIMIKT LDQALKDGDD VECIIRETAV NSDGRSAGIT MPSPEAQATL IRETYERSGL
     DPVRDRCQYF ECHGTGTQAG DPVEAQAIQQ TFYPKNAVFS PDDKLYVGSI KTLIGHLEGC
     AGLAGVMKAI MCLKNRTITP NMFFDNLNPN ISPFYDHLRI PTNTVPWPPV AHGCPLRASV
     NSFGFGGTNA HAIIESYVPS QPKRQASYCK ESNRQKYTNS GPFVFSAHTQ ESLYSNIERT
     ARYVRSNEAL DLGHLAWTLA KRTVLPFKVA ITALSREELL GNIDKAIVEY KASKASAQGP
     SPWKHPPEPH RIMGIFTGQG AQWAGMGREL LLASTVFRKS IERCEHALAT LHDGPSWSLQ
     EELLADKPSS RLSNPAISQP VTTAIEIAAY DLLCTSGVNV DVVVGHSSGE IVAAYALSII
     SAEDAMKIAY YRGLHTKPAR SGRMLAVSLS FHDARELCSW PSFSGRVVVA ASNGPASTTL
     SGDYDAILEV KALLDRKKTF ARTLQVDVAY HSHHMVPCSA AYLESLRACN IQVKSPRSGC
     TWISSVTGRN AILDGDIQSF SATYWVDNMV KPVLFSQALD KSLCGTQDLG VCIEFGPHPA
     LRGPVLDTLK SKGTSSVHYT SLLRRGQNDL NAASSAVGYL WERMADRVDL ASFLQGFRSQ
     ALQLIKGLPG YSWDHGRRYW RESRISRRYR LEGTQLHPLL GRRSADEFPN EFCWKNMLHL
     KEMPWAQGYK EEGRVVLSAA FYLCSLLSAA SSAAVCQRLV VLELNNFVVM EPITLEEYGN
     GVEYITTIRF DNEDFRTISS TILHAEASCH ACKSDESVLT KVCTARLTLH LGDARGPDCD
     CLPPRGQRND LLAPVDVADL YDSFEQAGMS YTGPFRSITS IQRSLGEATA SVAWAVDTTM
     PESVLNPAMV EASFQAIMCA FASPLTEELR TPFHAKEIRR VLVTPRLALG GVSCDIDAFV
     TGVDCGGVEG DVSLYKPDGN AMIQIEGLVM KSVPQPDTSS DRNLFSHVVW ESDPFGYSLI
     SYPTPNEDMG WKRAADIVAL YHLRRTVEEI DPLESAGFTP HHQLLYREIS HIAAAGRGSE
     YYITHPDCAQ TSEEIILAMI DKYAGIVDLQ SLHSFGKALP AILRGELDLH NTPNEPDTLE
     GFTHDAAMFS QLSKDICSIV RRIVHKHPHM NVLGLDPGPS VITHQILEAL DDKHTSYCLG
     SADPVILNKT LARLSAQHRN LYSKVIDLTT VNAGEHGSDK YDMVIAANPL HGTDTSANLF
     EVCRAMLKPG GYLVFVRVTG RVSMSLLCTC GWLPQWWQGY DQDARSWTDM STVRYDSHLR
     SKGFSGIDHI FHDSMNSNGD GLSVMVTQAV NDTVMMLREP MNSTGLAPLT ETVVFVGGKT
     LSVARLLQSI RRIVAASGTA TTVVEDIDRL EMNGLTKQHS IISLVELDEP FFSRGAFHER
     LLAFKELVAR SKHVLWLTTR NMTSISVAIG RAMRSERGAD ISLQFLGLST VANISPSAVV
     EVFLRLTWSF VPVLTDGEVL WTNEPELQWD GSTLRIPRLV WDHKRNKRYN YRHRQGRPEA
     GLPQTAVPLS PRVSTNSVAV QIKYSCLVCT DVYLWVGARI DGQGNVVGIS DHVSFVIHAR
     LDHVHNLSDE HDLSPDALRA TASFTLAYLL IKSLSGPILL YEPDELLAAA VEQDREPEQT
     VYFVTSKYND CSRGWITVHP HASRRMVERM LPRKVSAFVD LSSSDDHVVT TLRDIYSHAR
     IQAVELYRRA FAASPGQLIA DSYTQACTSL SILSHTALEV TSSTEASTNI ASVAYPKVVN
     WTSPAPIASP GDMISATTMF SSSGTYFMID MATPLGLSIL KWMATNGARK FVLAGRNPRM
     HEAWLEEMSR LGATVKPLKM DVSNKESILS AFTQIKEALP PIVGVCYAPL ALSDQGFEYT
     VEDAGGLAAT AMINAAKYLD ELFPTPTLDF FVILTSLVSV IGTPKQVAYH APSLFMTDLI
     QRRRLRGLVG SVMALGMVVD AGYFSRQGKE VIQRMMHHGY APLSESDLHH AFGEVVAAGV
     PEAEGNAEIF FGLQLIDSQI DQSRESTSVS NHLLSHFITS RSGTKEGQYA EQEDSPSLLV
     PDEQLQESGP GRNKYDDLLA RLSGKVRSIL RLGDQALDVH TPLLDLGCDS LLAVDIQAWV
     AKEFDIDITP MDALLDTVAG LCEKAVPKPN APGFVVEKEE QLVKELDFID VATTASRSEH
     SSSVQDIPLD STSSESSCVL CPSDSGFEQV RNDLEPRFTR IEKMSPHQSQ IWFAGHWMRD
     PTQYNVVISY NVEGRFPVDR FKEALEHAVS MHESLRTAFF SDPNNGDLLQ GVLKVPPPFL
     EHVRTPSAAS VSQEFDKLAS YQWRLEDGEV MRVTVVSIGK DQHTVIFGYH HIVMDGASWS
     TFLHDLKCIY EQRPRREVAQ YVDYSLMLNR DIHNGTFAKE LEFWKSELLP PPEMMPVLPL
     AKEKTRIPTD NFKVHTSTRH ISIEATERIK QASRSLRGTP FHFYLATLQV FLAGLLKIES
     LCIGMSDANR KHQQFTGTVG YFLNMLPLRF EVQQTDSFAN VFQKTSSKVL TALLNSSIPS
     NLVVDALNIP RVSNVTPLFQ VAINYRVGEI TRMSVDDFAL NYDRSVMGNA PYDISFHVTP
     CANGTSIVEV NCRDYLYSPK ATERIIDEYV RLLEIMSSNP LISVQSSVAT SAPINEDGLS
     VQRGPRISHG WPATLPERFQ DMVDQYGDRI AITDQGRDFS YLQLQAQSTR IGEALLQKGV
     RSGDTVAVLC PPSMNSVASM LAILRISAVY VPLDLSLPAA RHKAMILASP VRALVCVSST
     VEKVLELGVS TILNLSEIPD IRAPSTRFTN SAKGDSLAIL LYTSGSTGQP KGVCLPQSGF
     INYLAAKRKE LGLDSSTVVL QQSSLGFDMG LAQTLNAIMN GGKLVIVPQE LRGDSIEIAR
     IIRDQKVTFT LATPSEYLVM LQHGREYLHN YAGWRHACLG GEPFTDQLKR EFVRLGKNCP
     VVQDSYGVTE ISACTTFETM TASQLEEARS VGRTIPNTSL YIVDADCNLV ATGEPGEICI
     SGAGVALGYL NEEQTRLKFV QDPFALPDDI ARGWTRVYRT GDKAKLLDDG SLILLGRMDG
     NTEVKVRGLR IDLEDVASTM VNCHPDLLSS AIVCVKGQGV SETLVAFVAM MPGQTASDVE
     LQHLACNLPL PQYMRPSTVI CLDELPRNAN GKIDRKRIDA MPWTAPTTLS QSSKRLTLGE
     GELKLLWQVL LPGKHIQPES DFFLLGGNST LLVRLQGAIR TSIGVSLTLR EMYGASTLAQ
     MALKVDARKA ESPSMTINWL AETAIPQHIL DRASSTSNLN LPKHCQGSGC QILLTGSTSF
     LGRVLVQLLL QVPEVERVHC IAVEKEQEHV PPTSDKVSLY YGSLLDPNLG LSTAEWASLQ
     DRVDVVIHNG SNGHCLNTYN SLKGPNLGST HRLAEFALQS QVPLHYISSG RVILQSGQTA
     LGPTSVSFHP PPLDGSDGLT ATKWAGEVFL ERLAEHTDIS ISIHRPCTPI GDQAPAQDAL
     NSLLRYSVNL GATPRLTRME GYLDFQKVEI IAEEIATLVT SRFTKRSNTS SFTTRGVSFF
     HHSSNIKVPV KSFKEYMEKV HGRPFQELNL REWSSLALEQ GIEPLIPSFL EAVDDNEETL
     RYPYLGN