APDA_EMENI
ID APDA_EMENI Reviewed; 3930 AA.
AC Q5ATG8; C8VEB3;
DT 30-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=Hybrid PKS-NRPS synthetase apdA {ECO:0000303|PubMed:17369821};
DE EC=2.3.1.- {ECO:0000269|PubMed:20828130, ECO:0000269|PubMed:25494235};
DE EC=6.3.2.- {ECO:0000269|PubMed:20828130, ECO:0000269|PubMed:25494235};
DE AltName: Full=Aspyridones biosynthesis protein A {ECO:0000303|PubMed:17369821};
GN Name=apdA {ECO:0000303|PubMed:17369821}; ORFNames=AN8412;
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 FUNCTION, INDUCTION, AND PATHWAY.
RX PubMed=17369821; DOI=10.1038/nchembio869;
RA Bergmann S., Schuemann J., Scherlach K., Lange C., Brakhage A.A.,
RA Hertweck C.;
RT "Genomics-driven discovery of PKS-NRPS hybrid metabolites from Aspergillus
RT nidulans.";
RL Nat. Chem. Biol. 3:213-217(2007).
RN [4]
RP FUNCTION, DOMAIN, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=20828130; DOI=10.1021/ja107084d;
RA Xu W., Cai X., Jung M.E., Tang Y.;
RT "Analysis of intact and dissected fungal polyketide synthase-nonribosomal
RT peptide synthetase in vitro and in Saccharomyces cerevisiae.";
RL J. Am. Chem. Soc. 132:13604-13607(2010).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX DOI=10.1039/c3sc51785c;
RA Wasil Z., Pahirulzaman K.A.K., Butts C., Simpson T.J., Lazarus C.M.,
RA Cox R.J.;
RT "One pathway, many compounds: Heterologous expression of a fungal
RT biosynthetic pathway reveals its intrinsic potential for diversity.";
RL Chem. Sci. 4:3845-3856(2013).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, DOMAIN, AND PATHWAY.
RX PubMed=25494235; DOI=10.1021/ol503179v;
RA Zou Y., Xu W., Tsunematsu Y., Tang M., Watanabe K., Tang Y.;
RT "Methylation-dependent acyl transfer between polyketide synthase and
RT nonribosomal peptide synthetase modules in fungal natural product
RT biosynthesis.";
RL Org. Lett. 16:6390-6393(2014).
CC -!- FUNCTION: Hybrid PKS-NRPS synthetase; part of the gene cluster that
CC mediates the biosynthesis of aspyridones (PubMed:17369821,
CC PubMed:20828130, Ref.5). The polyketide-amino acid backbone
CC preaspyridone A is first assembled by the PKS-NRPS hybrid apdA
CC (PubMed:17369821, PubMed:20828130). The assembly of preaspyridone A is
CC initiated by loading of malonyl-CoA onto apdA, followed by
CC decarboxylation to yield the acetyl starter unit (PubMed:20828130). The
CC growing polyketide chain then elongates into a tetraketide
CC (PubMed:20828130). The adpA PKS module catalyzes three Claisen
CC condensations, as well as beta-keto processing and methylation
CC (PubMed:17369821, PubMed:20828130). Alpha-methylation step during
CC polyketide synthesis is a prerequisite and a key checkpoint for chain
CC transfer between PKS and NRPS modules (PubMed:25494235). The downstream
CC NRPS module contains the condensation (C), adenylation (A), and
CC thiolation (T) domains and catalyzes the incorporation of tyrosine via
CC the formation of the L-tyrosinyl-thioester and the amide linkage
CC between L-tyrosinyl-thioester and the tetraketide (PubMed:20828130).
CC The bimodular assembly line is terminated with a reductase (R) domain
CC that facilitates formation and release of the tetramic acid product
CC (PubMed:20828130). Because apdA lacks a designated enoylreductase (ER)
CC domain, the required activity is provided the enoyl reductase apdC
CC (PubMed:17369821, PubMed:20828130, Ref.5). ApdC appears to operate with
CC different stereoselectivity in different PKS cycle (Ref.5). Combined
CC with apdC, apdA is proposed to synthesize preaspyridone A via about 20
CC enzymatic steps (PubMed:20828130). A number of oxidative steps
CC performed successively by the cytochrome P450 monooxygenases apdE and
CC apdB are required for the conversion of preaspyridone A to aspyridone A
CC (PubMed:17369821). The cytochrome P450 monooxygenase apdE is
CC responsible for the oxidative dephenylation of preaspyridone A (Ref.5).
CC Finally, the predicted FAD-dependent monooxygenase apdD and the acyl-
CC CoA dehydrogenase apdG may be involved in the transformation of
CC aspyridone A into aspyridone B (PubMed:17369821) (Probable).
CC {ECO:0000269|PubMed:17369821, ECO:0000269|PubMed:20828130,
CC ECO:0000269|PubMed:25494235, ECO:0000269|Ref.5, ECO:0000305|Ref.5}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:17369821, ECO:0000269|PubMed:20828130,
CC ECO:0000269|Ref.5}.
CC -!- INDUCTION: Expression is positively regulated by the aspyridones
CC cluster specific transcription regulator apdR (PubMed:17369821).
CC {ECO:0000269|PubMed:17369821}.
CC -!- DOMAIN: ApdA has the following domain architecture: KS-MAT-DH-MT-KR-
CC ACP-C-A-T-R (Probable). The apdA PKS module (domains KS to ACP) is
CC responsible for the biosynthesis of the polyketide chain and catalyzes
CC three Claisen condensations, as well as beta-keto processing and
CC methylation (PubMed:20828130, PubMed:25494235). The downstream NRPS
CC module contains the condensation (C), adenylation (A), and thiolation
CC (T) domains and catalyzes the formation of the L-tyrosinyl-thioester
CC and the amide linkage between L-tyrosinyl-thioester and the tetraketide
CC (PubMed:20828130, PubMed:25494235). The bimodular assembly line is
CC terminated with a putative reductase (R) domain that facilitates
CC formation and release of the tetramic acid product (PubMed:20828130,
CC PubMed:25494235). {ECO:0000269|PubMed:20828130,
CC ECO:0000269|PubMed:25494235, ECO:0000305|PubMed:20828130}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the NRP synthetase
CC family. {ECO:0000305}.
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DR EMBL; BN001305; CBF80487.1; -; Genomic_DNA.
DR EMBL; AACD01000153; EAA67034.1; -; Genomic_DNA.
DR RefSeq; XP_681681.1; XM_676589.1.
DR SMR; Q5ATG8; -.
DR STRING; 162425.CADANIAP00002886; -.
DR PRIDE; Q5ATG8; -.
DR EnsemblFungi; CBF80487; CBF80487; ANIA_08412.
DR EnsemblFungi; EAA67034; EAA67034; AN8412.2.
DR GeneID; 2868624; -.
DR KEGG; ani:AN8412.2; -.
DR VEuPathDB; FungiDB:AN8412; -.
DR eggNOG; KOG1178; Eukaryota.
DR eggNOG; KOG1202; Eukaryota.
DR HOGENOM; CLU_000022_37_4_1; -.
DR InParanoid; Q5ATG8; -.
DR OMA; ETDVHHA; -.
DR OrthoDB; 19161at2759; -.
DR Proteomes; UP000000560; Chromosome V.
DR Proteomes; UP000005890; Unassembled WGS sequence.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0004312; F:fatty acid synthase activity; IBA:GO_Central.
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; IBA:GO_Central.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0019748; P:secondary metabolic process; NAS:AspGD.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IBA:GO_Central.
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; IPR010071; AA_adenyl_domain.
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; 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; 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; PF08242; Methyltransf_12; 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 TIGRFAMs; TIGR01733; AA-adenyl-dom; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 2.
PE 1: Evidence at protein level;
KW Ligase; Methyltransferase; Multifunctional enzyme; Oxidoreductase;
KW Phosphopantetheine; Phosphoprotein; Reference proteome; Repeat;
KW Transferase.
FT CHAIN 1..3930
FT /note="Hybrid PKS-NRPS synthetase apdA"
FT /id="PRO_0000438440"
FT DOMAIN 2326..2403
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 3493..3572
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 5..443
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:17369821"
FT REGION 557..879
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:17369821"
FT REGION 948..1251
FT /note="Dehydratase (DH) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:17369821"
FT REGION 1389..1588
FT /note="Methyltransferase (MT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:17369821"
FT REGION 2088..2229
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:17369821"
FT REGION 2414..2433
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2444..2494
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2509..2937
FT /note="Condensation (C) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:17369821"
FT REGION 2971..3371
FT /note="Adenylation (A) (KR) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:17369821"
FT REGION 2971..3371
FT /note="Reductase (RED) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:17369821"
FT COMPBIAS 2448..2482
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 176
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 2363
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 3532
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 3930 AA; 431297 MW; 4CD5C02C4D322E2B CRC64;
MQDLIAIVGS ACRFPGQSDS PSKLWTRLKE PIDLRKTFPP QRLNLARFYH PDGEHHGSTD
VRGTSYLLSE DPRQFDASFF NINPREAEGM DPQQRLLLET AFEALEAAGY SLEAMNGSKT
SVHVGVMNSD FSNIQLRDPE VLPTYNATGT AISILSNRLS YFFNLKGPSV TIDTACSSSL
VALHQAVQGL RAGDATAAIV AGANLIFDPA MYIAESSLHM LSPDSCSRMW DKDANGYARG
EGVGVLVLKP LSRAIMDGDH VEAVIRSTGV NSDGRTKGIT MPNAESQTEL IRQTYRDAGL
DPIRDRCQYF ECHGTGTATG DPIEARAVHD AFFPTETRTA SNTLIPDGKL YVGSVKTIIG
HLEGCAGIAG VLKAVLAIKN RTIPPNMHFH EPNPRVIPFC DRLEIPTVPI PWPDTGRSPL
RASINSFGFG GTNAHAIIEG YDALSSPVRE ATITPDDLFI GPLLFSANSS SSLVANVKNM
AERIRSDPSI DLESLVWTLY ARRSVLPVKA FFTGGTVQRL LNFMDRFVAE SEETTSSTAG
IKYQPLNPTE TPGILGIFTG QGAQWALMGF SLLQQNHVFR AAIERCQAAL ATLHDSPSWS
LLDELVKGAD ESRIGEAALS QPLCTALQIG LVDMLHSAGI KLDAVVGHSS GEIAAVYAAG
IINADAAIKI AYYRGYYAKL AAGARGQAGR MMATAMSFDE AEEFCAQPQW RGRLAAAASN
SPQSVTLSGD IDAIEEALQL FEAEKKFARI LRTDTAYHSH HMQPCAERYL KSLQACQIKV
SPPRKDCVWI SSVRGDTQLL EGDLSTLADQ YWVDNMCNPV LFSQAVETSI WNGGPFDVAV
ELGPHPALKG PVEQTIKAVY GPIPAYAGLM RRGDNEIEAF SGGVGFVWSR LGPDYVDMSG
YRKGFIGADR LRPQVLKDLP VYCWDHSKLY WKESRISRQY RLRQDTPHEL LGRRVPDDSD
DSRRWRNVLR LSELPWIRGH VFQGQVLFPG AGYVAMALEA ARELTEGRPA TLFEIENVSL
RRALVISEQA GIETAFTARV IDAKEGRNDT NRLEADFACY FCSAEGNEPL VKACTGRLII
NYGDPAAEAL PQRTRLPSNN VPVDMGRFYD AMNSVGLDYQ GIFRGLVHGK RSLGCSSVKA
AWGEDMQIDN YVVNPGFLDV AFQSVYTAFS SPASGEIWAP YLPIHIERLA VNPNVSYRSA
KDEVQMEADA FVTVSNSTLL KGDIQLYQID SQHAAIQVEG ISMKSMSEPQ PENDRCLFSE
TVWGPDVSLG VSEVTSRATE DDTPLVEALD RVSLFYWQNL LQEVGAEEIA QFQWYHQRMF
DAVRFQVSSV RSGQHPIAKP EWLEDDWETI LAVSEPYASR VDMRLIHAVG ENLASVVRED
TQLLEVMVQD DMLNRFYMEG YGFSVINNAV SDALEQITFK YPHANILEIG AGTGGTTRSI
LDRIGSRYGS YTYTDISPAF FEAAAEKFED AREKIQFKVL DVEKEVGAQG FDEHGYDVIV
AANVLHATRK LEETMKNARA LLKPGGYLVL MEITGPDVLR TQFIMGGLPG WWYGVDDGRV
LSPAISAQQW NQLLLDTGFS GLDCLAPDML DEYKHSFSLM VSQAIDEKIQ MLRDPVLSKT
LLPAADVLII GGRTHSNVIH EIRRYLSAWT SRVEVWDRIQ TKQLDQLAEF ENIICLEELD
QPLFSTTMTS ETLLALQKVL SGTKNVVWAI NSAKSQNPHV NMTVGLGRAM RTEVPGLNLL
FVDIDAVENP IACAQLLSQM LLQLRTGSLT AAENTLWAAE LEIRVQDGRR LIPRVLPMTQ
MNETYNASRR VISKPVDIET TCVKMEDSAG SLRLVPGACM VDGPVQRGHN RLRIHRSLPL
AFGGGTPCYL CSGDLRENGL PALALSTSNA NLADIPNDMV FALDQDQPCD AAMLEATGRQ
LLARDICNRL PASNRILVYQ PSHDFAQALL LTGRHFSFVS ADKASCFSDW VYIHSRASRR
AIQSRLPKDF DALIDCTGEL PENLIACLSR NCRVLNMTLH QLDGSLLGPA YSAALAHVSS
SSIGPSIRVK DLPLATPSKL PMVDWTGVDT VELTLQPLSM RKLFSSSATY LLAGMTGDLG
LSLCRWMIDN GARNIALTSR NPNVGEELLQ DMRRSGADIR VFRNDITDQN AVRTLVENIR
LSMPPIAGVF NACMVLRDGL FSEMDVDTLN DPLAPKVDGS KILDDIFQDD SLDFFVLFSS
LASIIGNAAN PTTTLQTCSS LVLPPTAARR VWQPSPHNSS RQHEIILGLE PFIDSPNATK
RPPWEHNPMF SHYVSRPLLQ ETPAATTVEA AADVKQLLRS TVSGEAVIPI VQEAFARKLE
SMMQLPANSI NLNVPLIDLG CDSLLAIEIR RWFIKELGID VPVLKVLSGD TTAQICEDAV
RQFLALQLEK QDTVAPNMTE KPETKSHPSS NATIIDNDAL DKADAANGDY ESSSQGDDSR
GNSSSSSSHT SPSIQATTPD IKPNTPVPLD VDADPLGRGF QRTMIRAEPA SFAQSRLWFL
TQYLHDPTTY NVTVRYDVRG NLPASRIVSS LNRTICHHQS LQTCFFMDSD KETLMQGVLS
PSYSSIKHIP SGSEQTVREE YNRLRSRVWD LQKGETFAVT VVSLSPEQHT IIFGYHHIVM
DGVSWHLFLR DLDLAYRLRP LPSIEMEYID WSKKQFQSAQ RGDFTRPLEY WRKQHSPPPS
VMPLLPMAQT SSRKPLTSYD SHVISVQIDR QLVSHIRLVS QSLGVTPFHF HLAVIQSILC
RLLKTEDLCI GVVDANRTSE AHSGTVGFFL NLLPVRFTTR EHSTFQDLVS STKRTILGAI
SNSEAPFDLI LEDLKVLRSI EHSPLFQVAV NYRMGAMLQV PLGDGTMEVA AADDAKNPYD
LSFGITETST GTCLLELTSQ KQLYTEQSTE LLLQMYMDVL RASSDNPSLP VNQLPVTLEP
STGKALAVAK GPRAEYSWPN TLWERYDAIR KSFPEETAIK DGKSELSYSQ LTRSVEKLAA
MLISQGVTAG DSVGVLLHPS IDAIACMLAL LRVGCIYTPL DTRLPVARLS IIVNRSKSSL
VLYHASTHDV ALELGKFSKL ANVEDMCESG QAQVPAIAPQ SNPASFLFYT SGSTGTPKGI
LLSQQNFVNH LAAKTDKLNL GREVVLQQSS LGFDMSVVQT FCALGNGGTL VIAPKEARGD
PIALSTIMAK ERVTLTIATP SEYSLLLRFG LEQLQRPYSW RHACMGGEVV SRQLVQQFCQ
LDHPDLQLTN CYGPTEITAA ATFQDISLQM KDQSTTDGSL VGKALPNYSV YIMDASSGSP
VPIGVTGEIC IGGAGVSLGY LNSLEQTDAK FVRDPFASPE DITRGWTKMY RTGDMGCLTE
DGTLIFMGRM DGDNQVKLNG LRIELDEIAN SILTTGNDLV SEAVVTVHSG SGSGSPLLVA
HVVPLGDNVD NSRLQQLARD LPLPQYMLPS VVVSLDRLPI NANGKVDRKA IMALPLPTQR
TESAAGTGTD TARHLSLAEG ELRLLWEKVL PASGGPSRLD ADSDFFMRGG TSMLLVRLQG
AIKESIGVSI PVAELYQFPT LGQMARRISR RKEDHQASHA TVINWDSETA LTQDLIYAAK
NQFSTRQTKA HDRQDILLTG STSFLGKNIL QSLLHNPLVE RVHCVAVPAE DIPRLPASEK
ISIYTGSLLT PSLGLTKTEI AVLQSSLDVI IHAGSTGHCL NNYSSLRASN VDSTKFLAAI
ALLCRIPIHF ISSNRVTLLS GSTSLPPASV SSSLPNTDGS EGFTASKWAS ERLLESVANL
ASGLPVTIHR PCAVFGEEAP NEDALNALLK YSKLTRCVPR FENFEGYLDF EDVHRVAATI
AADALSAESR ESKSAARVRH HSSGHKVSMK DFKGRMETLF ACPFKEVSMA EWTERALQAG
IDPLITGYLE AMTMKGEIIR FPYMGEAGSL
