ID CHEA_CHAGB Reviewed; 4699 AA.
AC Q2HEW5;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2006, sequence version 1.
DT 27-NOV-2024, entry version 118.
DE RecName: Full=PKS-NRPS hybrid synthetase cheA {ECO:0000303|PubMed:33622536};
DE Short=PKS-NRPS cheA {ECO:0000303|PubMed:33622536};
DE EC=2.3.1.- {ECO:0000305|PubMed:23611317};
DE EC=6.3.2.- {ECO:0000305|PubMed:23611317};
DE AltName: Full=Chaetoglobosin A biosynthesis cluster protein A {ECO:0000303|PubMed:33622536};
DE AltName: Full=Prochaetoglobin I synthase {ECO:0000305};
GN Name=cheA {ECO:0000303|PubMed:33622536}; ORFNames=CHGG_01239;
OS Chaetomium globosum (strain ATCC 6205 / CBS 148.51 / DSM 1962 / NBRC 6347 /
OS NRRL 1970) (Soil fungus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Sordariomycetidae; Sordariales; Chaetomiaceae; Chaetomium.
OX NCBI_TaxID=306901;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 6205 / CBS 148.51 / DSM 1962 / NBRC 6347 / NRRL 1970;
RX PubMed=25720678; DOI=10.1128/genomea.00021-15;
RA Cuomo C.A., Untereiner W.A., Ma L.-J., Grabherr M., Birren B.W.;
RT "Draft genome sequence of the cellulolytic fungus Chaetomium globosum.";
RL Genome Announc. 3:E0002115-E0002115(2015).
RN [2]
RP FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX PubMed=23611317; DOI=10.1021/ja402828w;
RA Ishiuchi K., Nakazawa T., Yagishita F., Mino T., Noguchi H., Hotta K.,
RA Watanabe K.;
RT "Combinatorial generation of complexity by redox enzymes in the
RT chaetoglobosin A biosynthesis.";
RL J. Am. Chem. Soc. 135:7371-7377(2013).
RN [3]
RP FUNCTION, AND INDUCTION.
RX PubMed=33622536; DOI=10.1016/j.funbio.2020.10.010;
RA Cheng M., Zhao S., Liu H., Liu Y., Lin C., Song J., Thawai C.,
RA Charoensettasilp S., Yang Q.;
RT "Functional analysis of a chaetoglobosin A biosynthetic regulator in
RT Chaetomium globosum.";
RL Fungal Biol. 125:201-210(2021).
RN [4]
RP INDUCTION.
RX PubMed=35949485; DOI=10.1016/j.synbio.2022.07.002;
RA Wang Z., Zhao S., Zhang K., Lin C., Ru X., Yang Q.;
RT "CgVeA, a light signaling responsive regulator, is involved in regulation
RT of chaetoglobosin A biosynthesis and conidia development in Chaetomium
RT globosum.";
RL Synth. Syst. Biotechnol. 7:1084-1094(2022).
CC -!- FUNCTION: PKS-NRPS hybrid synthetase; part of the gene cluster that
CC mediates the biosynthesis of chaetoglobosin A which has a unique
CC inhibitory activity against actin polymerization in mammalian cells
CC (PubMed:23611317, PubMed:33622536). Chaetoglobosin A and its
CC intermediates are involved in the morphological differentiation of
CC C.globosum (PubMed:33622536). The first step of the pathway is the
CC synthesis of prochaetoglobosin I via condensation of one acetyl-CoA, 8
CC malonyl-CoA, and a L-tryptophan molecule by the PKS-NRPS hybrid
CC synthetase cheA, followed by reduction of backbone double bond to
CC install desired geometry by the enoyl reductase cheB (PubMed:23611317).
CC Further multiple oxidation steps performed by the cytochrome P450
CC monooxygenases cheE and cheG, as well as by the FAD-linked
CC oxidoreductase cheF, lead to the formation of chaetoglobosin A
CC (PubMed:23611317). Depending on the order of action of these
CC reductases, distinct intermediates can be identified (PubMed:23611317).
CC Within the pathway, the cytochrome P450 monooxygenase cheE catalyzes a
CC stereospecific epoxidation on prochaetoglobosin I, cytoglobosin D, and
CC chaetoglobosin J intermediates (PubMed:23611317). The FAD-linked
CC oxidoreductase cheF performs dehydrogenation of the C-20 hydroxyl
CC groups in the 20-dihyrochaetoglobosin A and cytoglobosin D
CC intermediates (PubMed:23611317). Finally, the cytochrome P450
CC monooxygenase cheG can catalyze the stereospecific dihydroxylation of
CC prochaetoglobosin I and prochaetoglobosin IV at C-19 and C-20,
CC respectively (PubMed:23611317). The Diels-Alderase cheD may play a role
CC in the post-PKS-NRPS biosynthetic steps catalyzing Diels-Alder
CC cyclization (Probable). {ECO:0000269|PubMed:23611317,
CC ECO:0000269|PubMed:33622536, ECO:0000305|PubMed:33622536}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:23611317}.
CC -!- INDUCTION: Expression is positively regulated by the cluster-specific
CC transcription factor cheR that binds directly to an asymmetric direct
CC repeat present in the promoter (PubMed:33622536). Expression is also
CC regulated by the developmental and secondary metabolism regulator veA,
CC but this regulation seems to be indirect, probably via cheR
CC (PubMed:35949485). {ECO:0000269|PubMed:33622536,
CC ECO:0000269|PubMed:35949485}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of chaetoglobosin A and
CC 20-dihyrochaetoglobosin A (PubMed:23611317).
CC {ECO:0000269|PubMed:23611317}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the NRP synthetase
CC family. {ECO:0000305}.
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DR EMBL; CH408029; EAQ93004.1; -; Genomic_DNA.
DR RefSeq; XP_001220460.1; XM_001220459.1.
DR SMR; Q2HEW5; -.
DR GeneID; 4387645; -.
DR VEuPathDB; FungiDB:CHGG_01239; -.
DR eggNOG; KOG1178; Eukaryota.
DR eggNOG; KOG1202; Eukaryota.
DR HOGENOM; CLU_000022_37_5_1; -.
DR InParanoid; Q2HEW5; -.
DR OMA; AMIMKET; -.
DR OrthoDB; 2556330at2759; -.
DR BioCyc; MetaCyc:MONOMER-19094; -.
DR Proteomes; UP000001056; 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; IEA:TreeGrafter.
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:0009403; P:toxin biosynthetic process; IEA:UniProt.
DR CDD; cd05930; A_NRPS; 1.
DR CDD; cd02440; AdoMet_MTases; 1.
DR CDD; cd19532; C_PKS-NRPS; 1.
DR CDD; cd00833; PKS; 1.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.30.70.3290; -; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR Gene3D; 3.40.50.980; -; 1.
DR Gene3D; 1.10.1200.10; ACP-like; 2.
DR Gene3D; 3.30.559.10; Chloramphenicol acetyltransferase-like domain; 1.
DR Gene3D; 3.40.366.10; Malonyl-Coenzyme A Acyl Carrier Protein, domain 2; 1.
DR Gene3D; 3.40.50.12780; N-terminal domain of ligase-like; 1.
DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 2.
DR Gene3D; 3.30.559.30; Nonribosomal peptide synthetase, condensation domain; 1.
DR Gene3D; 3.10.129.110; Polyketide synthase dehydratase; 1.
DR Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 1.
DR InterPro; IPR001227; Ac_transferase_dom_sf.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR014043; Acyl_transferase_dom.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR000873; AMP-dep_Synth/Lig_com.
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; IPR018289; MULE_transposase_dom.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR020807; PKS_DH.
DR InterPro; IPR049551; PKS_DH_C.
DR InterPro; IPR049552; PKS_DH_N.
DR InterPro; IPR013968; PKS_KR.
DR InterPro; IPR049900; PKS_mFAS_DH.
DR InterPro; IPR050091; PKS_NRPS_Biosynth_Enz.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR054514; RhiE-like_linker.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR016039; Thiolase-like.
DR PANTHER; PTHR43775; FATTY ACID SYNTHASE; 1.
DR PANTHER; PTHR43775:SF20; HYBRID PKS-NRPS SYNTHETASE APDA; 1.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF00501; AMP-binding; 2.
DR Pfam; PF00668; Condensation; 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; PF10551; MULE; 1.
DR Pfam; PF07993; NAD_binding_4; 1.
DR Pfam; PF21089; PKS_DH_N; 1.
DR Pfam; PF00550; PP-binding; 2.
DR Pfam; PF14765; PS-DH; 1.
DR Pfam; PF22336; RhiE-like_linker; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00826; PKS_DH; 1.
DR SMART; SM00822; PKS_KR; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 2.
DR SUPFAM; SSF56801; Acetyl-CoA synthetase-like; 1.
DR SUPFAM; SSF47336; ACP-like; 2.
DR SUPFAM; SSF52777; CoA-dependent acyltransferases; 2.
DR SUPFAM; SSF52151; FabD/lysophospholipase-like; 1.
DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 2.
DR SUPFAM; SSF55048; Probable ACP-binding domain of malonyl-CoA ACP transacylase; 1.
DR SUPFAM; SSF53335; S-adenosyl-L-methionine-dependent methyltransferases; 1.
DR SUPFAM; SSF53901; Thiolase-like; 2.
DR PROSITE; PS50075; CARRIER; 2.
DR PROSITE; PS00606; KS3_1; 1.
DR PROSITE; PS52004; KS3_2; 1.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
DR PROSITE; PS52019; PKS_MFAS_DH; 1.
PE 2: Evidence at transcript level;
KW Acyltransferase; Isomerase; Ligase; Methyltransferase;
KW Multifunctional enzyme; NADP; Oxidoreductase; Phosphopantetheine;
KW Phosphoprotein; Reference proteome; Repeat; Transferase.
FT CHAIN 1..4699
FT /note="PKS-NRPS hybrid synthetase cheA"
FT /id="PRO_0000438205"
FT DOMAIN 737..1138
FT /note="Ketosynthase family 3 (KS3)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT DOMAIN 1644..1947
FT /note="PKS/mFAS DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT DOMAIN 3076..3153
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 4236..4316
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 1..38
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 136..165
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 172..520
FT /note="N-terminal acylcarrier protein transacylase domain
FT (SAT)"
FT /evidence="ECO:0000255"
FT REGION 625..836
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1250..1573
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 1644..1777
FT /note="N-terminal hotdog fold"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT REGION 1645..1941
FT /note="Dehydratase (DH) domain"
FT /evidence="ECO:0000255"
FT REGION 1794..1947
FT /note="C-terminal hotdog fold"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT REGION 2050..2241
FT /note="Methyltransferase (MT) domain"
FT /evidence="ECO:0000255"
FT REGION 2794..2967
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255"
FT REGION 3164..3265
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3268..3696
FT /note="Condensation (C) domain"
FT /evidence="ECO:0000255"
FT REGION 3730..4113
FT /note="Adenylation (A) domain"
FT /evidence="ECO:0000255"
FT REGION 4241..4313
FT /note="Thiolation and peptide carrier (T) domain"
FT /evidence="ECO:0000255"
FT REGION 4367..4598
FT /note="Reductase (R) domain"
FT /evidence="ECO:0000255"
FT COMPBIAS 1..18
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 635..649
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 662..687
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 709..723
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 799..818
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3196..3233
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 873
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT ACT_SITE 1012
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT ACT_SITE 1058
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT ACT_SITE 1676
FT /note="Proton acceptor; for dehydratase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT ACT_SITE 1854
FT /note="Proton donor; for dehydratase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT MOD_RES 3113
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 4276
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 4699 AA; 510655 MW; C090C064D8568ED3 CRC64;
MSDNDDEWNG FSDDNGEDDG PPEPGRPSQI DGQPWDVPDS ALLQGDVIPN PKDSDFATDF
AKIEELQGAI NAWARSRGFA VVRRHGRNKQ DGLYTRFDIL CDRFGSPRAP RGAGVRETAT
RKCDCKWKAA ASRTKDGWRF HSHPDPQHSV HNHGPSLHPS AHTQHRMSNS ESLDTIAELS
NHASIRAREI RSVVNQEHDT IYTRKDIYNV RAKMRKVNLD GYTAAGALIK ALDNVDGDTA
NHYEVEWADA AETIFCSLVW GFESCLEATS IYHDCMLIDL TYNTNYMGMP LYQVNCLTSV
GKTLSTMFGL VSDETTQTFR WLMKATKKLR DKFNIPEPAV IVTDHCKELK QAISEVFPDS
QQQTCIFHVI KNVMLNTKRK FKYPGRDEVD SEDEEYRADF EDYDGVSPQE RAAMEKDHAE
RLLSRNTSTS KVTKPISHDP RGVEEMFKAM QWMSCRDQWA HCYTRHYRNF GVRTTSPTES
NNMSIKSYLI NGRSSAYSLV SVSQDLCKEQ VQQNVEEMAK QAIRARHDFL SRPWLGALPL
RVSYKALDLI VGEYRRAKAA MPSTRPSQSI RRPLEPCHPD TCTATIQYSI PCRHDIYKKL
AEGERLELRE VHTHWHLQMS LVKPPLPSVE DNVADPKIVE NRKGRPKNSA RPLPDGLGIP
SSPKTPRSQR RDGTQGSQGS QGRRTPGSTP GPPRGNAPRL QPSIRRVLSA HETVEEPRPP
QAAPKRRGRP PGSKNKKKDQ APAPAESQLS AAERAEPRTT LVIASAPRRG LRAAPAAETT
ASEKRKAQAG GDSAPAPKRT RATASTPRAQ SDQGTGNVAI PSLPAPAGAP GARVTRSGRA
VRLTAKAAKA ASGGRISYFF DWHGPSITID TACSSSLIAV HQAVQSLRNG EVPLAIAAGA
NLLLGPSQYV AESKLKMLSP GGLSRMWDEE ADGYARGDGF ASVVLKPLKD AIRDGDRIEC
IIRETGSNQD GRTQGITMPS PIAQSALIRE TYQRAGLDLS RPADRPQYFE AHGTGTPAGD
PVESEAISTA FFGPDSRFKR QPGDAKLLVG SIKTVLGHTE GTAGLASLIK VSLALQNGKV
PPNLHFNRLS PSVKPHYQNL QIPTSLLDWP EVPEGGVRRA SVNSFGFGGA NAHAILEAYT
PATAKELLTA PSPFSFAPLL FSAASDTALA ANIAAHADFV EKASDVNLGD IAHTLHSHRS
ALAKRAVFAA ASRSDLVARL RGHAAEDKAK SDAAAPLGRS LSSRPRTLGV FTGQGAQWPR
MGAELIERSE AVSRIVDELE ASLATLPQQD RPSWSLRAEM LAPAASSQIG KAEFSQPLCT
ALQIILVDVL REAGVVFDAV VGHSSGEIAA AYAAGVVTAS EAMRIAYYRG FHTHRCGGAG
GQSGAMMAVG TSFEDAQELC ALDAFKGRLS VAASNSSSSI TLSGDADAVA EAAVVCEEEN
KFHRALRVDK AYHSHHMVPC LGPYVESLRG ACNISPTPQN GSGSGCVWIS SVYATDIADV
QDDIGSEYWA KNMGQTVLFS QALETALRER GPFDQVVELG AHPALKGPAM QVIEETTREK
IPYVGTLLRQ RDATEALAES LGALWAANGR ASVDLAKYEA FLSGGRVHQV LADELPRYQW
DHQTAYYHDS RLLKALRTSS IKPNELLGTR IMDNSPSEAR WRNRLSANEV PWLRDHRVQN
QAIFPGAGYI ATGLEAVREL LGNEPLLLVN MQDIFIGQAL IIPEPGSVET LVSVTNIVRG
ADKITARFTF FADEGRADSV SMAEKASANL IISLGEPDPD ALPPRPEPGR DYHMLDVPAE
RFYDAVGSLG FGYTGPFRAL SGLSRKMDYA TGSVVQPEPT EGFGRLLVHP AALDAAVQSI
ILAYCFPGDT RLRTTHLPTR IDSLRVNIPL CEADRSAQTP FRSSVPSGGG VELSDINGDV
DLYDENGSTL IQLQGLHTKP LVPPTPSTDL PLFTEWVWGP LSPHGRDLTL RGAEAEAERD
LFNDLERVAY FYLRRLDAAI PPEQRVDLPA HQTALFRIDL ELMHAVGENL ASVIRGEMNM
LEPMMQDNKL NRFYIEALGM SRYLEELSRM AAQISHRYPQ MHVLEVGAGT GGATKVLLRH
LEGGFESYAY TDISSGFFPS ARETFEAYTD KMTFKTLDIE KDIAEQGYQE ESFDLVIANL
VVHATKDLQV TVRNLRRLVK PGGYLLLLEI TDNDPLRFGF IFGGLPGWWL GEEEDRGLSP
CVEVATWDRI LRNTGFSGAD EVTVRDPNNP LSVILTQALD DRVELLRQPL TAQPSSEGVQ
LDSLTILGAE TGRAAELARD VEALLSPYFR RSRTVSSLVG LGPQDLPLMG TVLSLVELDT
PVFKGITPER LRGFQQVFQQ SKNVLWVTTG YKADDPYSAM VYGVGRNVVL EMSHLRLQFL
DLETLAAADP RILAECVLRF EFSDMWEQAA DKRPLLWTTE PDLAYEEGRL RMPRIKVSKE
RNARYNSSRR PVTKEVDPIA SPLALQPLDD TGKDYALVAP SGRLAAGTRL DTVKIRVAKS
ILRAVRVLAT NYLFVVAGFA ENGTSPLVAV SDSQASVVEV DRAWTMPIQH SEGAADTAVE
TAMEQAMVAL YDGLLAQALL QDVEHGRALA VLDASPSLTR ALRSSGRYRG VQVVSLASKA
AASGVPGTIP VHPRESVRSL KSKLPAHVDK LANFSDRADL ARTVASCLPT RCDFQDWQSL
TRPGAVITER TLLGLADCEV PSVLRAAWAH VKVDQRSTDL AGVLRADPTS LSQAAVVPGD
AANQVCLVDW ARRPTLPARI QPLVTTITFS PDKTYWLVGL TGGLGQSLCR WMVERGARYL
VLTSRNPKLD PRWLAGVEAL GAVVRAFPND ITSRDAVQAA YRTITATMPP IGGVAHGAMV
LHDSMFAEVT VEKMDKVLRP KVDGAIHLDE IFYDAPLDWF VYLSSVVVIT GNKGQGIYAA
ANMFLNSMTM QRRKRGVPAA AVNIGAVLGN GYVTRELNHQ QQTFLQEVGN NWLSEQDFLT
IFAEGVAASR VDSTEAVEIT TGLRMLSSRD ENVTWATNPK FQYLVQAHVA SAAAKLAKSS
NVSLKKQLED VKTIQDASEI LEDAYTSKLR AVLQIAPDRD VLSAALDDLG MDSLVAVEIR
SWVLKELSAD ITVLEVLNSG TAGALFELVK ERALASLALL DSGEQPDQVK SPRAAPLDLV
SGHGGGDRRP STVVDVADTS LDQGSSWDSG SLREASNGHD STILSSTAPS SPISKPAGVD
ASDLEQTPIP EDSEEPVASS PDAGLARSVP LSFSQARFWF LRHFLPDQSA FNITSVVRMH
GRPDMERLAR AIKAVGNHHE ALRTAFRVGE GNEPVQAVLK ETVLVLEHRD ISDADDVTPA
YEAVQRHVYD LEAGETMRLQ VLTLSPTEHF LILGYHHINM DGISFEVLFN DLQKAYRGVE
FTPGVAQYPA FSILERDEYR LGKWKTELDF WKAEFAHLPE PLPLLPLSQR ASRPAVAQYA
TLRVERRIPA DLSATIKSAA RKFGAGVFAF YLAVLKALVV RYVDVDNLCI GLADANRRRA
EVLESIGLYL NLVPLNVPCD RTQPFSDALR EMHTKYQRAF ANARVPFDVL LHELDVPRSS
SHPPLFQVFM NYRQGVSEAR EFCDCECEGE LVSGGQLAYD IAVDVVENPG GETNVMLSVQ
QSLYNAASAE VLLDSFFSLM EGFAANPISR ISKPPLHRQT AIEQAVELAN GPILDLAWAP
TVSHRIDEMI QAHPDKLALT DGQGTDLTYA QLGASVNGIV QGLREVRASN VVGVLQHPTP
AAICSILAVL KAGLTYVPLD PRVGPAKLAA IVGEAKPSCI LVDDATEVDI GSFSLDDTAK
VRNVASLPPS EDRLPIEAVP AGTAVLHCAA ASRRPVSELA VQEGSETILQ QTAFSFDISL
FQSLLALTTA STLVVAPREV RGDPAALAKL MLIAGVTVTA ATPTEYVHLI GHGASQLKQN
DKWRLALCGG EKLSDQVVSG FRSLNRPELT LVNDYGPAEA TFRCSTTVVP YQEEDGQELA
RTTPLKTCAN SAVYILGDDM KPLPVGLTGE VCVGGAGVGL GYLNNHQLSA QRFIANPYAS
PAFVARGWTT MHPTGDRGRL SPDGGLILEG RIDGDTQVKL GGIRIELEEV ERAVINDSQG
AIREAAVSVR TDEASGTEYL VAHAVMQDRA DSTPAHVDWL QQLQSRLSLP RYMAPSAIVP
VAALPLSVSG KLDRRALREL PVATALTTQT PAEESEGLPA MQHLIKQLWE QVIPNGLLAG
RDIGPKTDFF NVGGSSLLLV QLQALLREQF SVAPLVQELF QASTLETMAA LVASGSGSST
QQGSDTTPAP IDWEAEAGLL QDAYYNSTTE KKQSGPAVAN PPKVVVLTGS TGFLGRHLLE
RLLRTSHIEK VYCVAVRKQP AELPGIFNDP RVEVFPGDLS LAGLGLSDAD TERVFSTADA
VLHNGADVSF MKTYISLRPT NVAATQQLAA LAQRQGRRIP FHFVSSAAVT QLTPLDEVGE
VSVAAYPPAV SSPSSSSSAG GYVAAKWVSE RHLEQVAQAH GLPVTIHRPS SILGNDASDV
DLMGNLFRYV ERLQAVPESR DWKGYFDLIS VHTVAAAIVK AVVAAREEEQ EEEEGHEKGG
PAGRVRYQYE AGEIVYPLST VADMGELEAA GFVLKTLPLE EWVAQAEGAG LNPLLAAYLK
AAAGGGVRWA FPKLVSSTV
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