ECDA_ASPRU
ID ECDA_ASPRU Reviewed; 7260 AA.
AC K0E4D7;
DT 25-APR-2018, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2012, sequence version 1.
DT 03-AUG-2022, entry version 39.
DE RecName: Full=Nonribosomal peptide synthetase ecdA {ECO:0000303|PubMed:22998630};
DE Short=NRPS ecdA {ECO:0000303|PubMed:22998630};
DE EC=6.3.2.- {ECO:0000305|PubMed:22998630};
DE AltName: Full=Echinocandin B biosynthetic cluster protein A {ECO:0000303|PubMed:22998630};
GN Name=ecdA {ECO:0000303|PubMed:22998630};
OS Aspergillus rugulosus (Emericella rugulosa).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus.
OX NCBI_TaxID=41736;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, DISRUPTION PHENOTYPE, PATHWAY,
RP BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF SER-41 AND SER-1127, AND
RP BIOTECHNOLOGY.
RC STRAIN=ATCC 58397 / NRRL 11440;
RX PubMed=22998630; DOI=10.1021/ja307220z;
RA Cacho R.A., Jiang W., Chooi Y.H., Walsh C.T., Tang Y.;
RT "Identification and characterization of the echinocandin B biosynthetic
RT gene cluster from Emericella rugulosa NRRL 11440.";
RL J. Am. Chem. Soc. 134:16781-16790(2012).
CC -!- FUNCTION: Nonribosomal peptide synthetase; part of the gene cluster
CC that mediates the biosynthesis of echinocandin B, a fungal lipidated
CC cyclic hexapeptide that acts as an antifungal agent (PubMed:22998630).
CC Linoleoyl-AMP, produced by the fatty-acyl-AMP ligase ecdI, is
CC transferred to the initiation carrier domain (T0) of ecdA
CC (PubMed:22998630). The linoleoyl-S-phosphopantetheinyl-T0 is
CC sequentially extended with L-ornithine, L-threonine, L-proline, L-
CC homotyrosine, L-threonine, and 4R-methyl-L-proline to form the linear
CC hexapeptide (PubMed:22998630). Thereafter, the terminal condensation
CC (C7) performs macrocyclization of the NRPS product and the cyclic
CC scaffold is released from ecdA (PubMed:22998630). All six of the amino
CC acid residues are hydroxylated, including 4R,5R-dihydroxy-L-ornithine,
CC 4R-hydroxyl-L-proline, 3S,4S-dihydroxy-L-homotyrosine, and 3S-hydroxyl-
CC 4S-methyl-L-prolin (PubMed:22998630). In the pathway, all the
CC hydroxylation reactions are proposed to occur following completion of
CC the cyclic peptide, so the unhydroxylated precursor produced by ecdA
CC will undergo six rounds of hydroxylation (PubMed:22998630). Five
CC hydroxylase genes (ecdG, ecdH, ecdK, htyE and htyF) are embedded within
CC the echinocandin B (ecd) and L-homotyrosine (hty) clusters
CC (PubMed:22998630). {ECO:0000269|PubMed:22998630}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=45.4 uM for L-ornithine (L-Orn) (by adenylation 1 domain)
CC {ECO:0000269|PubMed:22998630};
CC KM=2.7 mM for 4-OH-L-Orn (by adenylation 1 domain)
CC {ECO:0000269|PubMed:22998630};
CC -!- PATHWAY: Antifungal biosynthesis. {ECO:0000269|PubMed:22998630}.
CC -!- DOMAIN: The NRPS ecdA is a multimodular enzymatic assembly that
CC contains 20 domains With the following architecture: T0-CAT1-CAT2-CAT3-
CC CAT4-CAT5-CAT6-C7 (PubMed:22998630). The initiation carrier domain (T0)
CC binds linoleoyl-AMP prodiced by ecd I (PubMed:22998630). The 6 CAT
CC modules correspond respectively to each of the 6 amino acid monomers
CC incorporated (L-ornithine, L-threonine, L-proline, L-homotyrosine, L-
CC threonine, and 4R-methyl-L-proline) (PubMed:22998630). Finally the last
CC condensation domain (C7) performs the macrocyclization of the linear
CC hexapeptide (PubMed:22998630). {ECO:0000269|PubMed:22998630}.
CC -!- DISRUPTION PHENOTYPE: Impairs the production of echinocandin B
CC (PubMed:22998630). {ECO:0000269|PubMed:22998630}.
CC -!- BIOTECHNOLOGY: Due to their effectiveness as antifungal agents,
CC echinocandin derivatives can be used for the treatment of human
CC invasive candidiasis (PubMed:22998630). {ECO:0000269|PubMed:22998630}.
CC -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
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DR EMBL; JX421684; AFT91378.1; -; Genomic_DNA.
DR SMR; K0E4D7; -.
DR BioCyc; MetaCyc:MON-19231; -.
DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR Gene3D; 1.10.1200.10; -; 7.
DR Gene3D; 3.30.300.30; -; 6.
DR Gene3D; 3.30.559.10; -; 7.
DR Gene3D; 3.40.50.12780; -; 5.
DR InterPro; IPR010071; AA_adenyl_domain.
DR InterPro; IPR036736; ACP-like_sf.
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; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR Pfam; PF00501; AMP-binding; 6.
DR Pfam; PF00668; Condensation; 7.
DR Pfam; PF00550; PP-binding; 7.
DR SMART; SM00823; PKS_PP; 6.
DR SUPFAM; SSF47336; SSF47336; 7.
DR TIGRFAMs; TIGR01733; AA-adenyl-dom; 6.
DR PROSITE; PS00455; AMP_BINDING; 5.
DR PROSITE; PS50075; CARRIER; 7.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 4.
PE 1: Evidence at protein level;
KW Isomerase; Ligase; Phosphopantetheine; Phosphoprotein; Repeat.
FT CHAIN 1..7260
FT /note="Nonribosomal peptide synthetase ecdA"
FT /id="PRO_0000443826"
FT DOMAIN 4..80
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000269|PubMed:22998630"
FT DOMAIN 1090..1166
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000269|PubMed:22998630"
FT DOMAIN 2188..2264
FT /note="Carrier 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:22998630"
FT DOMAIN 3287..3365
FT /note="Carrier 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:22998630"
FT DOMAIN 4394..4471
FT /note="Carrier 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:22998630"
FT DOMAIN 5496..5573
FT /note="Carrier 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:22998630"
FT DOMAIN 6592..6668
FT /note="Carrier 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:22998630"
FT REGION 134..549
FT /note="Condensation 1"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22998630"
FT REGION 575..965
FT /note="Adenylation 1"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:22998630"
FT REGION 1208..1628
FT /note="Condensation 2"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22998630"
FT REGION 1653..2054
FT /note="Adenylation 2"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22998630"
FT REGION 2314..2719
FT /note="Condensation 3"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22998630"
FT REGION 2763..3156
FT /note="Adenylation 3"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22998630"
FT REGION 3417..3831
FT /note="Condensation 4"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22998630"
FT REGION 3851..4248
FT /note="Adenylation 4"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22998630"
FT REGION 4510..4910
FT /note="Condensation 5"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22998630"
FT REGION 4955..5357
FT /note="Adenylation 5"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22998630"
FT REGION 5622..6043
FT /note="Condensation 6"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22998630"
FT REGION 6063..6460
FT /note="Adenylation 6"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22998630"
FT REGION 6718..7133
FT /note="Condensation 7"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22998630"
FT REGION 7241..7260
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 41
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 1127
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 2225
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 3324
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 4431
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 5533
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 6629
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MUTAGEN 41
FT /note="S->A: Prevents loading of linoleate by the
FT initiation T0 domain."
FT /evidence="ECO:0000269|PubMed:22998630"
FT MUTAGEN 1127
FT /note="S->A: Prevents loading of L-ornithine by the T1
FT domain."
FT /evidence="ECO:0000269|PubMed:22998630"
SQ SEQUENCE 7260 AA; 800194 MW; 1A451B10783C90AA CRC64;
MHRTNEMERK RVFTEICAEA LKVEIDDLDE TRSWVALGGD SMATIRLIAR CEERGMRAKT
ADVIRCASIT ELFETIQYLQ PSESIDREEV KPEDADAAPF SLWPEYHNAT TTEEKQKLLN
EVARHCNSTP NDIEDVYPST PLQEGLMAIT SRSPAAYVDR RAFTLPPTVD IARFRAALEA
LTARTHILRT RIIIDPLSGR SLQVVTRNEV VWREAMTLND YLEDDRQEGI ALGQPLSRCG
LIQDKGSDGV EETVFVWTVH HSIYDGWSAL QLYRQLAAIY NSEQLSPVVP YTRFVRYLQQ
QDPDSATQYW RDQLQGEDIM VDWPTLPTAT YQPRPRTQFQ ANILLPDVSG SGLVMMSAVL
RGAWALVMAQ YSGYSDVIFG VTLSGRNAPV PQVADITAPL ITTVPVRIRV DQKLTVAEFL
DRIQTQATEM IEYEHTGLQQ IMTFLPEYAS ALDFRNLLII QPAVERDAYR AFPGISPINI
PVEDFDSYGL NVECTLGREQ IDIQLNYDEG VITTAALTNV MEQFSTLVRK MCRPDAQATS
INEILTLPAQ DAEQIKKWNA DVPSPVHRCI HDLVQDQVRS QPAAIAVDAW DGRFTYAELA
SQSMRLAQHL TISHGVGPEQ TIGLCMDKSR WAVVAMLAIL YAGGAVLPLS GSHPLPRLQG
IVEDANTRVI LVDASQAARL VGMGRPLVIV DSTIVENLSP AQNEMRSGVT PSNMAWVVYT
SGSTGMPKGV VLEHQSLCTS LTAHAKAIGI TEHTRTLQFA AYTFDVSIMD TFSTLQAGGC
VCVPSEEERL NRLAEAAARL EVNYAELTST VTEMLSPSQV PSLTTLLLSG EPLKPAVLSI
WAKHARVFNS YGPTECSITA SNSRQLFHPD EARNIGAPME SLFWVVQSDN HQALCPIGTP
GELLIEGPLL ARGYLNDETT TNDSFITEPR FPEQIGLERT GRRMYRTGDL VQQNRDGSLL
YVGRCGGQQV KIRGQRVDVS EVEHQITQRL PGVKTVAVEL VGQGSQLSLM AVIEFAGGTS
VTAAPVFEAL REQLLHALPQ YMVPTLYMPT DQMPINASGK LDRRGLRAQL QALTIAELQE
YALNAGPKSA PSTAIEHKLQ VLWAETLKVD PACIGREDSF VLLGGDSIAA MRMASLPAAQ
ELHLSVADIF QHARLSDLAR ELEGRNLNEN MQEADPAPFA LWDTKQNQRA QRVAILAAQC
GVTAGEVEDI IPCTAMQEGL MALTTHQPTA YVGRQVYRLA ASIDTQRFQE AWKTLVYHTP
ILRTRLAVDE ASDPQTGGLV QIVVGDGLTW KYSTDLDEYL ACDEAEGMAL GQPLVRLALV
QQKEERFFIF TGHHSVYDGW SASLMFQRLA EIYLHNRIHS SPVPYSRFIR HLLKQDPVST
AGYWSTQLEG EAVVDWPPLP RADYQPRPMH RATHTITLPD NAKISTRGLS KLPHTLRAAW
ALVMATYAGG QGNRVVFGAT VSGRNAPIRG ITEMVGPTIT TVPVAVQLDT QQTVSQFLEA
VQKQAADMIP FEQTGLQIIR KLVPASCHAT LELRNLFLVQ PLPDGEETDL PGLASLPVTL
EGFDTYGLTV QCSLGPDAVT VEMRYDENVI ASARVKRIMN CFDHVVNQLY SKRNGAVPLG
DLSLLSADDS TTIARWNQTS PERIERCIHH LIEEQITARP DSQAICAWDG DLTYAELNTQ
ATQLSWYLRG LKVDAERMVG ICMDKSKFAG VAMLAVLQAG GVVVPLGVNH PPSRNEGIVE
DTAIDIILVD EQQRDRLSTM PNVQLVVIEQ SLLDTLTIQP IERELPVNVT PNNAAWVIYT
SGSTGKPKGV VLQHRALCSS IRAHGARFKM GPHTRMLQFA AHTFDACIQD YFTTLAFGGV
VCVPSEHERM SDLSTAVRKL GVTFATLTST VARLIDPNDV SAMQQLALVG EPVKADVVKR
WLDHVTVLNA YGPSECSIHS TCSEPLTDPK QSAIIGTGMG SRVWVADVRD YNRLCPIGVP
GELLIEGPIL AREYLNDPQK TEKAFITNPA FLEELGISCN SNEGRMYRTG DLVRLDEHGS
LTHLGRRDTQ IKIRGQRVEV GEIEYQITQQ LAGVRSAAVE LLEDAGKVRL TVALDFALDS
DLRRGPASEL GVLLPSPALT TGLQRLRGSL FQVLPIYMVP TAFLPIMDMP LNASGKLDRR
AVRALLEKVS FEEQRQYLAV SASESTVTPS TPTESQLRAV WADMLQLPVT QVNIHDNFFQ
LGGDSVVAMR MVATESARAL KLTVADIFQS PRLTDLANLL SSRFLKEEQD EEEYMAEDDP
EPFSLWYANE DLQRRHEQLQ QIAQDCDVRV SSIQDVYPCT PLQEAMMAIT SRQSAAYINR
QVFELDDSID VDRLQSAWRK LAQAVPTLRT RIAMSPGKAS TLVQVVVDEE IEWQVSGSLE
GYLERDQEQG MALGTPLIRF GLIHKDVSGQ RFLVWTAHHS LYDGWSSRLI YQHLADIYHA
GRVLDSPASF PRFIRFLAEQ DNAEVRSASA KYWSEELEGE VMSNWPPLPH VDYQPRPGRE
IIKVVPLRQS GPSQVITPAN VVRAAWAITM AQYAGHDDVV FAATVSGRNA PVWQVGNIVA
PTITTVPVRT HIDWTDNITS FLDTIQKQAA DMIPYEHTGL RTIKAIIPPQ LGPALDLRNV
LVVQTEGEGK TGAAPFPGVE PFSLGAAVDF DSHGLTVDCT VSATNLRVAF RFDETVLPTT
HAENILSHFT HVVQQLCDPL LVKGRTLGDM DLVSPGDRTC IFERNDTVDI SRWDACIHDL
VGKQALAQPN APAVCAWDGD LSYKELASYA SRLAHQLIAL GVGPEKKVGL CLDKSRWAVV
AMLATLQAGG AIVPLGVSHP FSRVEVMVED SAAVVILVDE QQHHRLADLP SNIPRVIVDS
QSLEKLPPQS APVTEVSPDN AAWINYTSGS TGAPKGMILE HGGLCTSMRT QSARMHISNK
TRALQFSPFT FDVSISDISA TLIYGGCVCL PSESDRMNNL AGSIQTMAVN FASLTPTVAR
LLSPAEVPTL KTLALTGEAL KPDVVALWKI VPDVALYNTY GPSEGSVCTC NGPISSPEEA
ESIGTPMATR HWVTQPHNYH QLSPIGAPGE LLIEGPLIAR GYLNNPEKTA ASFVPPPGFL
TKPSGSRIYR TGDLVRQNTD GSFTYLGRRD TQVKIRGQRV EIGEIEHQIV NHLASVQTAV
VHLLEAIGLV AVVELREAET VAEIEPAGTI APSPALCSQF SDLRQALLRV LPDYMAPALF
VPVPSIPTNV SGKLDRRAVH ELLMSLPTDN LGRWTAEQEN MPKAILQPAT EMEKMLQELW
ARMLKIPADN VSPQDDFFRL GGDSVTAMRM VATATRTSRH LRLVVTDIFQ HPRLSELAQV
LEERVQKDLE QRDIQSTEPI DPEPFALFAD GSDLDAQGRE QRLAAVAEQC SVAVEQVQDV
YPCTPLQEGL LANTSRQQAA YVSRQSYVLS NNIDLARFKA AWEALAKAAP ILRTRIVIGA
EGSCQVVVKG PIEWLHHSGA LEDYIQQDKA REMGLGQPLA RYAIVQELSG EQFFVWTAHH
SMYDGWTVRL LCQELINLYN REDHVPRPVP YTRFIRYLYE INRAGSLEFW KQQLEGDDVE
ADWPRLPHVG YEPRPRSTLS VNIADPGNDE SSGIVIANIL RAAWGLVMAQ FSGHNDIVYA
ANVSGRTAPV PGVTDIIGPT IATVPVRMHF NPRALMTVES FLHGVQTQSQ QMIDHEQTGL
IAMRNHPNLQ LRNLLVIQPA DEGDTVLDFP GIEAVPSAVE DFDSYGVNIE CVLGMTIRVQ
ARFDDHIVAA TYMKRVLDQF AYIVEQLCDP RLRALPLQQL NLLSPNDQQQ ISSWNAAAPE
SVEQCVHEMV EEQAMAHPTK LAVWAWDGKF TYQELAHLAQ LLADQLVSLG IGPERMVGVC
MDKSKWAAVA FLAILKAGGV VVPLGVSHPI RRIETILNDT MSDLVLVDAK HCQRLSVEGL
LRQRLLVVDD KLQQHGSSRP RAGQQAKPIT PDHAAWVIYT SGTTGLPKGA VLDHRALSSS
IRAHGTRYKF GPQTRKLQYS AHLFDGTIED YFTTLSWGGL CCVPSEDDRL DMRRLTAFMR
ETEVNALATT YTVAGLLTPE EVPSLQTLVL GGEPATVEVT DTWRSKVDLF NCYGPSECTV
FSSAAGPRVA VAELHNIGHP IGTRLWVVNP DNPGSLCPVG APGELLIEGP QLARGYLNDE
AKTRTAFLTD LEFMRQFKIP PSTRVYRSGD IVRQKDDGSF VYVARRNTMQ VKIRGQRVEV
GEIEHQVGLH LAETRAVAVE LLKQGVHGLP VLVAVVDFAD NSQYRLADGD QKPTPKEELL
PPTPAAQQAF TKLQVALSQV LPSHMIPSIY LPVTQLPRNI SGKLDRRALR ELLDQLSYEA
IHQYMDIDGG EKAAPATAME RTLQSLWAQT LGMDIDRIGA HDNFFQLGGD SVAAMRLAAI
VQQQEQLQLT VGDILSHPCL SDLANLLADG APTEGTTETD PEPFSLWCTV PDEDLPTIAV
KLGVAVEQIE DIYPATPLQE GFIAVTARQS AAYISRQVYK LSATLLDLDR FKASWETLVN
TTPILRTRLS IGRDGHAVQV VVRDSIGWRY GTDLSSYVAQ DREEGMRLDE PLMRYAIITE
PTSGSCYFVW TAHHSIYDAW TIRAISKSLA EIYTSTSPHS IPQPTASFSR FIRYLTNTDT
DAIKDFWHEQ LAGDVVADWP PLPQNDYQSL PRGRIQKTIK IPERSSGILE STTLRGAWSI
VMSQYAGSSD VVFAATVSGR NAPVPQINDI AGPTLTTVPV RVSVDSSLSV NQFLQSIQQQ
STDMIPYEQT GLQRIKASLP EANQSALNLR NLLVIQLAAE AESNTLALPG WEAQPAPFED
FGSFGLQIEC TPIPGSHAID VNIQYDEKVI STTAVTRVAE HFVHVAEQLF NPGLINSALT
EIQLQLSSEH KDVMLRQNTH VPPYLNRCIQ EMVYERAALQ PNAPAICAWD GNWTYAEVTD
LAASFASYLS TELQIGPTQM VGVCMDKSKW AVVAMLAILC AGGTVVPLGV NHPLSRIQVM
AQDTGLGVIL VDNKQRERLF DLNHRLITVD AQHIQGLPVL GKQERTSMTQ KTGVTPDDIA
WIIYTSGSTG IPKGVMLEHR ALATSMEAHG STFGFGTHTR ILQFAAHTFD ATIQDMFTTL
YKGGCVCIPS EYDRVNRLTE SMASMSVNCA TLTSTVASLL APEELPSMQT IILVGEPVTP
AAVALWLPHA TVLNAYGPSE CSIHSSCSDP ITDPALAPNI GRPLATNFWV VDPNNYHSLR
PIGAPGELLI EGPIQARGYL NDIDKTNAAF VIDPDFMKQL GLSGSQRRLY RTGDLVRQND
NGTLTHMGRR DLQVKIRGQR VEVGEVEYQI QRKLPSARTV AVEPLQHGDK DKHITLIAIM
DLSDRAVTDE LNAAKAPEPL PVTASLQATF HDLRNSLLQV LPAYMVPAAY LPVDRMPMNA
SNKLDRRAIR ELITHHSLED LQQYLGGGTD DNVKTAPRTV MEQQVHALWV EVLGLSEDAV
GVYDNFLQLG GDSLTAMRIV AAAGQTGEVR VSVEDIFMHP TVADLALVLS ERGSSDRAVE
QEQEDPAPYQ LWTEQNNFPA DQIEENLEAI AAQCAVDRAL IEDVYPCTPL QAGLMAITAR
QPAAYVSRQV YTMSSSIVDR ATFQKAWQQL AAGTDILRTR IVMAPDSSSQ ALQVVVRDTI
HWELGTNLDE YLRRDSERGM ALGEPLVRYG IVEEPSGKSY FIWTAHHALY DGWTLGALSK
RLGDIYQNRA LSTQSVPYSR FIRYLQHGRS SLESSASYWR EQLQGDAMAN WPRRPALDYQ
PMPRHNLQRT ISLGSSQTLV TTSTILRAAW ALVIAQYAGH NDVVFAATVS GRSAPVAGIA
DIPAPTITTV PVRIRVDGNR SVADYLQAVQ RQAIDMIYYE HTGLQTIKAL VPDLASTLDA
GSLMVIQPTD QSAMESGLDF PGLDMVPMPI APFNSHGVTL ECKLGAQDVT LDIHYDSNII
APEQLSLVID YFASLVLRLG NPAATSSPVA DLLAVSEKDE RQIRAWNSTV PPRLDKCIHE
MVQEQVARTP GEIAIQAWDG QLTYREFHDL AASLAHHLAA LGVGPETLVG VCMAKSKWGA
VAMLAIMQAG GAIMPLGVSQ PVARIQNILE TSQAAFILVD EEQMDRLNQL STPGQTPKLI
FVEDLLMEIP SYTQPPATDV TPDNASWAIF TSGSTGTPKG VIIEHGTMST SLDEQGRWLG
LSQETRFLQF ASYTFDNVIT DTFATTSFGG CVCIPSESGR MDRLEEVMVE MKVNTAMLTS
TVAQQLSPTQ LPLMQKLILT GEPVRPDVVR TWLDHAEIYN AYGPTEGSMS TCTRPYTNAF
EASNIGHPLA TRLWVVQPDN PHLLSAIGAP GELYIEGPFL ARGYLNDPVK TDALFLMDPP
FTQRLGLTGR RVYRTGDLVQ QNEDGTLIHL GRHDSQVKIR GQRVEISEIE HQITQHLPEA
STVAVFILDD NPITLVAAVE FNMKSPHRLG PHSAFKGLLA PTVAMRVDFT RLYGALSQVL
PIYMVPTVFI PMHEMSRNLS GKLDRRLVQT LLKEIPTTEL RRYRLGEGPK IAPSTAMERQ
LQSIWSKALD LPEDQVGAHD NFFHIGGDSL VAMRIIAIAR AQKLKLTVAD LFKYPCLSEV
AQVVEDRVAA SSITLAVDEE PIAPSPFSLI AAENIEIYLQ RIASRMPGCR AQDIVDILPT
TDFQALTVAE ALTTPGTANF AHFFLDGDGS CDVEALRKSC LQLIEAMPEL RTAYVFDQGR
LLQVVLRVYE PEIKILQTND ATMEEVTSDL ISKQMFQAPH LGQPFTVITI IEESASSRHR
VVLRLTHAEY DAVSMQSIWR QLRALYEGTT LKPRPTFASF LYSQRQKITT QTYNYWRTLL
DESTMTPLST PTPMPTSTIG HYPSKVAQLR PCRVHINRSS VEGITSAVFI KTAWAIALSR
LSNRQDIIFA DTVSSRGTVD ESLMEATGCC VTLLPVRVKL TPETSMQDVL LELRTQQVQS
LERAQLGFRE ILHECTNWPT STRFTSAINC ISQGGNGAFT MRGTNYWLSN FQANNATWTV
DLGVTAVMHD NGDVDLRMAY LPTRISEDAA YKYLNTLQDT LQAILDSPGL LVSNFLSRAL
GGSLGDRKGA SDPKIEVIEP EQEPQPLEST DKMTYLDLKK TPEWEEVLRG RRGIVSPGRT
SLSFSQRGGD LLDALYLSSL QKDADGGRYI SPMALLEGSR CEEAEKSASV TSSERRLATI
