AGIA_ASPFN
ID AGIA_ASPFN Reviewed; 7763 AA.
AC B8NY88;
DT 11-DEC-2019, integrated into UniProtKB/Swiss-Prot.
DT 03-MAR-2009, sequence version 1.
DT 03-AUG-2022, entry version 77.
DE RecName: Full=Nonribosomal peptide synthase agiA {ECO:0000303|PubMed:31117395};
DE Short=NRPS agiA {ECO:0000303|PubMed:31117395};
DE AltName: Full=Aspergillicins biosynthesis cluster protein A {ECO:0000303|PubMed:31117395};
DE Includes:
DE RecName: Full=Nonribosomal peptide synthetase {ECO:0000303|PubMed:31117395};
DE EC=6.1.2.- {ECO:0000269|PubMed:31117395};
DE Includes:
DE RecName: Full=S-adenosyl-L-methionine-dependent N-methyltransferase {ECO:0000303|PubMed:31117395};
DE EC=2.1.1.- {ECO:0000269|PubMed:31117395};
GN Name=agiA {ECO:0000303|PubMed:31117395}; ORFNames=AFLA_010580;
OS Aspergillus flavus (strain ATCC 200026 / FGSC A1120 / IAM 13836 / NRRL 3357
OS / JCM 12722 / SRRC 167).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=332952;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 200026 / FGSC A1120 / IAM 13836 / NRRL 3357 / JCM 12722 / SRRC
RC 167;
RX PubMed=25883274; DOI=10.1128/genomea.00168-15;
RA Nierman W.C., Yu J., Fedorova-Abrams N.D., Losada L., Cleveland T.E.,
RA Bhatnagar D., Bennett J.W., Dean R., Payne G.A.;
RT "Genome sequence of Aspergillus flavus NRRL 3357, a strain that causes
RT aflatoxin contamination of food and feed.";
RL Genome Announc. 3:E0016815-E0016815(2015).
RN [2]
RP BIOTECHNOLOGY.
RX PubMed=26273902; DOI=10.1021/acs.jnatprod.5b00286;
RA Kikuchi H., Hoshikawa T., Fujimura S., Sakata N., Kurata S., Katou Y.,
RA Oshima Y.;
RT "Isolation of a Cyclic Depsipetide, Aspergillicin F, and Synthesis of
RT Aspergillicins with Innate Immune-Modulating Activity.";
RL J. Nat. Prod. 78:1949-1956(2015).
RN [3]
RP FUNCTION, DISRUPTION PHENOTYPE, CATALYTIC ACTIVITY, AND INDUCTION.
RX PubMed=31117395; DOI=10.1021/acschembio.9b00161;
RA Greco C., Pfannenstiel B.T., Liu J.C., Keller N.P.;
RT "Depsipeptide Aspergillicins Revealed by Chromatin Reader Protein
RT Deletion.";
RL ACS Chem. Biol. 14:1121-1128(2019).
CC -!- FUNCTION: Nonribosomal peptide synthase; part of the gene cluster that
CC mediates the biosynthesis of the aspergillicins A and F, 2 cryptic
CC cyclic hexa-depsipeptides (PubMed:31117395). The hexamodular NRPS agiA
CC catalyzes the condensation of the six amino acid residues including N-
CC Me-L-O-Me-tyrosine, L-proline 1, L-proline 2, D-isoleucine, O-acetyl-
CC threonine, and L-isoleucine (PubMed:31117395). The starting
CC condensation domain (C1) of agiA probably loads acetyl-CoA which is
CC condensed on the N-terminus of threonine by the first module to yield
CC O-acetyl-threonine (PubMed:26273902). The second module then loads L-
CC isoleucine. The epimerase (E) domain on module 2 is probably involved
CC in the formation of the D-isoleucine moiety (PubMed:26273902). Modules
CC 3 and 4 further load 2 successive L-prolines (PubMed:26273902). Module
CC 5 is then involved in the condensation of O-Me-L-tyrosine produced by
CC the O-methyltransferase agiB and the N-methyl transferase (NMeT) domain
CC on module 5 probably catalyzes the N-methylation to yield the N-Me-L-O-
CC Me-tyrosine moiety (PubMed:26273902). The A domain of module 5 loads
CC preferentially O-Me-L-tyrosine, but it can also accept L-phenylalanine,
CC which leads to the production of aspergillicin G (PubMed:26273902).
CC Module 6 then loads the last residue, L-isoleucine (PubMed:26273902).
CC The C-terminal thiolesterase (TE) domain probably cyclizes the peptide
CC using the hydroxy group from threonine to form the cyclic depsipeptide
CC (PubMed:26273902). {ECO:0000269|PubMed:26273902,
CC ECO:0000269|PubMed:31117395}.
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 additional domains such as epimerase (E) or methyltransferase (MeT)
CC required for further modifications are also present. Aspergillicins
CC synthetase has the C1-A1-T1-C2-A2-T2-E-C3-A3-T3-C4-A4-T4-C5-A5-T5-NMeT-
CC C6-A6-T6-TE domain organization. The epimerase (E) domain on module 2
CC is probably involved in the formation of the D-isoleucine moiety and
CC the N-methyl transferase (NMeT) domain on module 5 catalyzes the N-
CC methylation of phenylalanine/tyrosine. The C-terminal thiolesterase
CC (TE) domain probably cyclizes the peptide when releasing the final
CC product from the enzyme. {ECO:0000305|PubMed:31117395}.
CC -!- DISRUPTION PHENOTYPE: Impairs the production of aspergillicins A and F.
CC {ECO:0000269|PubMed:31117395}.
CC -!- BIOTECHNOLOGY: Aspergillicins show innate immunity-modulating activity.
CC Innate immunity is a good pharmaceutical target for the development of
CC immune regulators to suppress unwanted immune responses, such as septic
CC shock, inflammatory diseases, and autoimmune diseases. The innate
CC immune system also provides targets for the development of agents that
CC stimulate protective immune responses toward some diseases, such as
CC infections with pathogenic organisms and cancer.
CC {ECO:0000269|PubMed:31117395}.
CC -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
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DR EMBL; EQ963486; EED45174.1; -; Genomic_DNA.
DR RefSeq; XP_002385303.1; XM_002385262.1.
DR SMR; B8NY88; -.
DR STRING; 5059.CADAFLAP00013168; -.
DR EnsemblFungi; EED45174; EED45174; AFLA_010580.
DR VEuPathDB; FungiDB:AFLA_010580; -.
DR eggNOG; KOG1176; Eukaryota.
DR eggNOG; KOG1178; Eukaryota.
DR eggNOG; KOG1256; Eukaryota.
DR HOGENOM; CLU_000033_0_0_1; -.
DR OMA; WEPVPSV; -.
DR Proteomes; UP000001875; Unassembled WGS sequence.
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:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0043604; P:amide biosynthetic process; IEA:UniProt.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:1901566; P:organonitrogen compound biosynthetic process; IEA:UniProt.
DR Gene3D; 1.10.1200.10; -; 5.
DR Gene3D; 3.30.300.30; -; 7.
DR Gene3D; 3.30.559.10; -; 7.
DR Gene3D; 3.40.50.12780; -; 5.
DR Gene3D; 3.40.50.150; -; 1.
DR Gene3D; 3.40.50.1820; -; 2.
DR InterPro; IPR010071; AA_adenyl_domain.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR025110; AMP-bd_C.
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 InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR001031; Thioesterase.
DR Pfam; PF00501; AMP-binding; 6.
DR Pfam; PF13193; AMP-binding_C; 3.
DR Pfam; PF00668; Condensation; 7.
DR Pfam; PF00550; PP-binding; 6.
DR Pfam; PF00975; Thioesterase; 1.
DR SMART; SM00823; PKS_PP; 4.
DR SUPFAM; SSF47336; SSF47336; 6.
DR SUPFAM; SSF53335; SSF53335; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
DR TIGRFAMs; TIGR01733; AA-adenyl-dom; 6.
DR PROSITE; PS00455; AMP_BINDING; 6.
DR PROSITE; PS50075; CARRIER; 6.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 3.
PE 1: Evidence at protein level;
KW Isomerase; Ligase; Methyltransferase; Multifunctional enzyme;
KW Phosphopantetheine; Phosphoprotein; Repeat; Transferase.
FT CHAIN 1..7763
FT /note="Nonribosomal peptide synthase agiA"
FT /id="PRO_0000448728"
FT DOMAIN 995..1071
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 2090..2166
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 3667..3743
FT /note="Carrier 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 4806..4880
FT /note="Carrier 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 6306..6381
FT /note="Carrier 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 7446..7522
FT /note="Carrier 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 20..168
FT /note="Condensation 1"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:31117395"
FT REGION 469..866
FT /note="Adenylation 1"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:31117395"
FT REGION 1104..1526
FT /note="Condensation 2"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:31117395"
FT REGION 1562..1968
FT /note="Adenylation 2"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:31117395"
FT REGION 2212..2556
FT /note="Epimerase (E)"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:31117395"
FT REGION 2676..3016
FT /note="Condensation 3"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:31117395"
FT REGION 3136..3531
FT /note="Adenylation 3"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:31117395"
FT REGION 3789..4238
FT /note="Condensation 4"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:31117395"
FT REGION 4321..4687
FT /note="Adenylation 4"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:31117395"
FT REGION 4902..5339
FT /note="Condensation 5"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:31117395"
FT REGION 5361..5765
FT /note="Adenylation 5"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:31117395"
FT REGION 5820..5975
FT /note="S-adenosyl-L-methionine-dependent N-
FT methyltransferase"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:31117395"
FT REGION 6378..6399
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 6424..6883
FT /note="Condensation 6"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:31117395"
FT REGION 6913..7327
FT /note="Adenylation 6"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:31117395"
FT REGION 7542..7638
FT /note="Thioesterase (TE)"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:31117395"
FT COMPBIAS 6378..6397
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1032
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 2127
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 3704
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 4840
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 6341
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 7483
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 7763 AA; 858957 MW; B9F2EBD7DDF09788 CRC64;
MGSIGNVQSP LPRCVQSMHA PSVMQEEMIV STIADPSHKS YFETYHFSAQ GIVDPDQLNG
AIHAVARKHA VLRSVFVHPT EFDSTNVQIA VLDQAYTLHR AKLLSLQPIG EEIRFGILPL
ESIGTDEWDG VMPWKFSLVV CEREQKSYIT VRYHHALLDG WSARALLELV QQEMLNPGAV
LKGSDFFSLV RQPLKRDWKQ DETLLRERLA QIETSPILSP GPVANGDLRV GEVTREVSIS
SDIWLPDRPA VPARLLRLAL GMTISVFRNS DDSLFLEITS ARSRLFPKDQ QVLGPVLAPQ
VRNIHLKEHT TLGECMQLLR SSNDPQHNFS VSQLKSFLTE SSRDLDVCLV CQTNESYPSN
GVGHWEWIKG EARNDLPFIL EILPPKEGVF FAKIRYHQNR FEKQFADSFL EFFCQTLTWM
QATGNSIDHQ TFAAAVSEIC RQGDYRQHYL ALNPRGVSDD PVNVHDLIEQ AASKWPSKIA
LEAEHNQFMT YAELSNESDR VAKGLRHCLP RDQKDQPLVP ICFDKSVDMV VAIVAVLKAG
GAYVPLDPSQ PRDRLVSILS ACHATVVIAG QTDLQDVLHS TCSELSILVT SIENLSEHDK
STDELSGSEH PPPSSLAYVL FTSGSTGTPK GVMVEHRNLV AFMKAGEGNA DGTWTSTRLQ
LAAYSFDASI GDIFANLYRG GRLALVQRNK MLSNLNHWLE EMLITHLALT PTIGDLIISH
LPPRLQTLMF GGEPFHQSFL AQAPAEARVW NTCGPTETVV DVACCILQKE NPDVPIGRPF
GQCQIYILRR GGSNTAVPPN AIGEICVAGP QVSRGYLERP DLTSLGFVTD PFRPSQRMYR
TGDLGRLNHR GMLEHLGRAD GQIKLRGLRV ETGEVEVTIK QSSSIIAQVT VSVNHLEGYD
REALVAWIVP EASQGSQDIE LAWQEDIMPS CQRRLVPYMI PEVWIMISYL PLTVSGKLNR
GTLASWVEHV ATGGTHDGLY VITAPWKTQE ITQRLPESPA ERLLVATCAN ILGTTLHAVS
MDSTFIALGG NSLLAMRLLA ALRQEGMNCS LRDLLTPMTL GDVARAMSPS STPKKQITKA
FYHEDSWERI VADSSIAADT IDAIYPCTPQ QEGLIQTSLH GDKSAYFATI TVHLGDSLNL
RTFHAAWNRL VFGCDMLRTA FVSFSEVQHP PVSESNILQV VLSQSAEDVR RLVSLDNRDI
AFQFGVVPLS AGISQGSVNE PWRLHLKIHH ALYDEAFLSR IVAELCIVYE ALEMESSEAA
LPPSRPFSAF VESLCNDDPE VSKGFWKKYM HEVAPATWPV ASGIRRMREE NGQDVEMTVV
KSWTGNAVAL GQKFQATPAS IVRAALALAL AQYSQTDDVV FGEVSSGRFD HDRFTLGPCL
ATHPVRIQID RKSSSGMLKL VTQALESYLA TTPYQHCGLA SIHRQTADPD LMAFQVLFAH
QEAFVEYTAG SRFHVKSAKL RNIGFPLVLE SRCDRSTGNL AFECSFDRRY LGDQDVDWFL
RSICRTLDMF SAGARDGLSD QKLITGVVDE EMRRAIEKWS TKRTPFGSTF TRNAEICAHE
LFEMQADMTP QKIALQVNQS EFITYKELNK RCNQLSNALV NWLDSLGLEQ SRDQQIVPLC
FSNAVDMVIA MIAVLKAGAA YLPIDQNHPQ ERIQQILSLS GARAMLGDGE AETLEKLQAA
SKQANSTLIT SKRLRTLYGG QTAKKPSFRP TPASLAYVIF TSGSTGKPKG VMVEHGNLAA
FMQANEPEAV GTWTSVRLQL ATATFDAATG ETFGTLGCGG RLILGQTHEI LAGLPDWLER
TNITHLFVTP RVAANFLTEI HPPYLRTLHI GGEAFDPSIL PHMPPGCDVY NVFGPTETTI
YATHYKIRKG DGIRRNIPIG YPFGGCRLYI LNPETLEQVP IGVIGEICIG GPQVTRGYQG
RPELTSRSFL SDPHIVGERM YRSGDLGRLC GDGSIEHHGR IDSQIKLRGL RIEISEIESV
CLEHAIATAC TVIVLDREDG QVLVAFVQTQ KDQQTSTCSQ DWAETESILH RHLDSRLPSY
MVPSRFVPIE VMPLTTSGKV DRRQLGARAE TMDQAGELFT SQHTNHAGSW EQGSIEDKIA
DAWVQVLGID RANITPNVAF SRLGGDSIRA IRLLSLLRKA GLKLNMTDVS NASTIFSQAK
CATSHTVAAK KSTEDATDID AHTGPVALGP IAGRYAGIQL KYASQRGEQI IDHFNQSVLL
DVTTLCPLRL QQALQRLRNH HDPLRAIVHW SLDIPVEEWT IRILPCSDIK PLVLDSPRTL
TLQALREQIQ HRITGLDIRR GKVMDAELYR LDGDSRVFLF WTVHHFVVDI VSWQILRDDL
NVLVRAKEEP ESIALQPATM SFLAWTREGQ MKSQDASLAT GSIPEEPDIL LSSSDSDQLP
LWVRQPELVP IHPVNRTTTS ASLSPCITAL LLGRSNNVLS TEPLDLLLAG LAMTISKHFA
RAVDRLVVGL ETHGRHTGTN TADLSRSIGW FTAIIPMILD CRCESSSIES VVRRVKDQRR
LLMENDRGFR HFVASRWSTA NARKSEIMPL VFNYQGVRHD PHDHDEMMLH PVQIPGLSWI
ESSPHAIPLS HAAFELYVHD RQAYIEATWP SDGEMDQEDV ATLMGEQITN ICQYLAEKDV
LGKTSISASS TSAFGLLPDD CFDRVFSLYP EDTLDDIIPC TPMQRALLYE GIADHESRSY
VTCRIWRIPT DQAICSQIEG AVKSLIQRHG ILRTVFHIDP EVGPLALVLR DTQSPTASAV
GHVKVKDHTE MEERVTSLLC NPDYGNPMKQ AFYVRIVHAA DGSGARLIWL LHHSLIDAWS
QDLLLSELTQ ILVDGCPTKS LIPRPSFGSF ARYVTSDSRA DHSHGKFWSE TLNGVQPKSL
PLSLMSSSPI NAAAVVVEQA CNLAILSENC ISPAALVSLA WSLVLSEILD TDDVTHGMLF
SGRQLPVDGV ADIIGPCIST VPIRTHLNRH GKVLDLLQST EAAIRLAGSH STVGVDGVAR
AAGVEAPALV NTLLNFFGVR TDVLENDGLN SILELDSVDD GLPPSITLSC WQREVDANIM
VMRLERRHPL QIGIAQCLVK RMAWYCHTLS HHMDRKLDSV LSITSNEDQL LTKWSQPVDS
RPSDSYPCIH DLITGWAAQV PEKVAVQVAE SQFVTYGEIE KKSTAIARVI ERLVDPRSGS
TPPLIPICCD RGVDMVIAIL AILKAGAAYV PLNISDPEGR LEAILRQTGS TILVDGLLDK
GSRRKLHALG DRTSTTVYTV DGLSILPPSE VSLRKAHSES LAYVLFTSGS TGEPKGVMIE
HRNLTSFITT QHNEIIGRWT SCRMPVAAYT FDVSMADLLI SLAIGARVAL VDSEKMLASM
PYWADRTLAT TLSMTPTLAS LLARSLPPHV AVLMLAGEVF DPNIMKALPR ECRVWNGYGP
TETFYASFHP VDAQPTHAQV PIGRSFGGNR IYILRPGSNY RQPIGAIGEI CIGGTQVARG
YLGREDLTSR SFTRDPYNTQ TVLYRTGDLG RFTDCGVVEY LGRMDDQIKI RGQRAEPAEI
ESVVHAASPR VAHAIVDLYQ SKRGGGLPRL IAFISTKDPV PPSLCKTFLQ EEVEPSCRNQ
LPGHMMPSTW IYVRTVPLTS SGKADKRMLR SWMARLEEGE TVPEASIIEL SLSTQMNSET
HQDISGGPES PTEIMLRQSC AQLFKVNEDI ISLDKSFISS GGDSLLALQL NARLREKGLK
CTPRDIVEAQ SLAELATILN TSYEAVSPVH MADWTLDLNE MARLPDNGIQ GWETIVQRVG
IDPGQVRCVM PCTPFQEGVL SSNDESGSSA GYLAHMTVGL GKEIDVEALK YAWQETVDHE
DMLRTTFIPA DMDMTDIRGL GQGSSLLQVV LYPESPQAGR VKTMKTVSTP ATPNAALPSY
PSLQGKAQQG HIPVAALVAI GSQDGEGQEC TLLITMHHAL YDEAYLSLLL KDLSGRYRSI
ACNEVVPQVP EDQRIPFSTY VRFVHSKLGT APSTSTAGKF WKSYLADATP STWPLPHGMQ
SSITSVKSPE TAVLEWTGNL RAAASKVQVT AAAIARAALA LTVAEHTNVT DVVLGEVSKG
RPDIRGPGDA RARFITGPCA TTHPVRIRIA DEGASKRRTM LQLLRESFTS YMETLPHQFY
GLSRIREQSC RVDLLPFQVL FVYQDAFRQK EGLAGDDAFQ IQGGNLGQMG FPIVLECSCL
SGDSGVVFHC TYAPDVIDKP RIEWFLHHIS QSIDALVQVD PARSDSLRSA RVPLSAQETR
QLELWSRCHA AKDVEKVDDT MPTETSSITH AFDDTARNLH EKRSTSLSMA LQRHIVSLDD
VGSQQPIIPI CFERSTDMVV AILAILKAGA AFVPLEPGYP PERLISIVRT ARASLMICGK
EDKSNEILVS VCHATNTKLI TLEDLKSRPA SSDQAVISRY CRDDSRIAYV LFTSGSTGTP
KGVVITHRNL LAFMRHNNPD VHGRWYNSRM PVASYTFDVS MADIITTLCC GGRVVLVPVQ
KLLPSLGAWV DASITSHISL TPTIANMLWE PVKNAEIAFP FLSVLLLAGE VFDAQLMSYV
PKECRVWNGY GPTETFYVTF YRVPKAHAKE QTSVSIGYPF GENVIHLLGF ESNDHVPVGC
IGEICVMGPQ VAQGYLGQPE LTKQRFKRGV ISQAPEGFLY RTGDIGRFHP DGKLEYLGRF
DRQIKIRGQR VELAEIEMAI AQHSFVDGCA VVVVNTPTGD SLVGFCVKTS SQTPGKGWDA
NTAVQIKTWI STRLPAHMVP SYLFPLEGEL PRVPSGKVDR QLLAQRATDL LADSLLSSQG
QDTYIAPTTE REKVICEIFE ETLAQRVSVL DNFLHLGGHS ILAIRAVSKI NHRLHANLTF
KDVFDFATAR DLARQLESTA TNHRSYTSIP RLTQDKMIVR QSFAQGRLWF LDQLHPGSTW
YLMPFGLRIQ GDLHLDALEA AVSAIEERHE TLRTTFEHRD GENVQVVHPF AHRQLRVVEV
PPAVDEEGLL GALKEEQSTP FDLQVHPGWR PLVLRQNKRS HILSIVIHHI ICDGWSVAVL
LKELSTFYSA ALHGKPIHAQ LPPLPIQYRD FSAWESQKEQ RVEHDRQLKY WIEKLTGSKP
AEFICDKRRP QAPSRQAIFE EVRIDGAMYD QLRQYCKQHQ LTPFIVLLAV FRATHYRLTR
EADATIGTPI ANRGREELHD IIGLFVNVQC IRLKVDDHHT TFEDLVNQAQ STATEAFAHQ
DIPFDRIVSA LQPDRETTQN PLVQTVFAVH PQTQGKEELE GLLTEQILLS RTTRFDLEFH
LFQEEDGLSG QVVFAQDIFF PETVKAMISV FYAVLECGLN QPSISVASMA LLNDLSMHDM
DDLLSINQTD YPRDATVVDL FRQEARSHPD SIAIVHEGKE VTYGELDRQS DNIERWLRSL
HLDRETIVGV LAARSAEAIT VFLGIMKADL AYLPLDASTP QTRICSVLSC ISERITVIVV
DGAQVAVPDV SLAHVDFVAL SNLLDDQRHK PSDNQKFESE SSISATSLAC VLFTSGSTGR
PKGVMIEHRA IVRLAKDFNF AKAAGKPLAH MASLSFDVST WEVFMPLLSG GVVVCVDAMT
VLDYKALSDV YARHHVRAAM FTPALFKQCL HDSPSIVKNL DLLILGGDRL DPEDVFQAKQ
LTQGIILNGY GPTENTGAST IYPIPDEESC VNGVPIGKPI GNSGAYVMDD SLNVVPKGVV
GELVVTGDGL ARGYTDPEKN EGRFVHVVIG QDTVRAYRTG DYARWRPIDG QLEYFGRRDD
QVKIRGNRVE IGEIEHNILS HSAVRSAAVV MNGVGAEADL AAFVTLHPIH DDVAETERVD
AWKNVFDTEA YDSFTHQPNR LGRDFVGWLS MYDGCNIDLT EMDEWLDDTL QTLLNGQDPG
KVLEIGTGSG MILFNITKGL EEYVGIELVP KLAHMVEQVA NADQRLAGRV KVHPGVADRV
EDFIPGFIPD LVIINSVAQY FPSAGYLSEI VQKLVRLQGV KSLFFGDIRS YPLYDEFLVS
KALHNAGARA TQDQIRKCIE ESKAAETELL VDPAFFTSLT NQFPDQVAHV EILPKLMNAT
NELSCYRFSA VVHLKHATAA TRIACQVKKA DWIDYTARSL NSRSLLEHLR SSHDNTIIAV
ENIPNRRTIL ERYIVDALKE GVEPRSMDTK SHWQVRHRNR AAQSSALLPG DLVAIANQAG
FQVEISWARQ SSQRGAFDAI FHRMGPNSRR QRVLFDFPVD HQCRDVDSFT NHPVQGQQDQ
QCIFELKESL RAQLPAYMIP RTITILDQLP LTDRGKVDRQ ALRQRIIKQE PVATESESSA
GRVTVEYGSE MERILCDVFA EVLGLQSVDR ESSFFSLGGH SLLAPRLASR VSKRLDCTAT
VRDLFDCPTP VRLADRLLSK QSDSNTEANT STDGKTQHSA LDKVKYHNTL RDWGVQSSEV
GHLMPCTPFQ EGVLSNSLAV PGDSGYLSVV RLGLQSQLDT KAMRLAWQKV VEREETLRTA
FIPVAEDLSS ACITSSTFWQ CIFNINSREV QRLLCIEGRN SGVDRSALGF GHIPVSLILT
DVPTVCKARG VGSTQLELTI HHALYDEAYF RWIIHELSRE YHKARLAKDY VPLRAPQTSM
NRIPFSIFVS QLQAMPKESA TSFWKSYLNG APAACWPVAR GLESGRITEI DEFSSRSLIW
KGNMHNLAGA RGVTPAAISR AAVALVVAEH SGVEDIVLGE VSSGRSITDG AAGFVAGPCI
STHPIRIRMQ QRQGSRSSQH RLSFDQLVKQ SLNSYLETVP YHQLGLPSIR RQSDAPDLLP
FQVLFVYQQA FDFETDSREE ASHNFKVQGG HLGRFEFPVV LQASCHPVTG HMSLQCMFDP
TVLITEDIEW FLEHISQVLS SIADSSSQPV ARLTVGDAEE AALTKLSCAK DQTPELPLGT
DSESLCAHDL ISRQAMESPC KIAVQYELSQ FMTYGELDRE STKLSIVIRA FFDHLSKSVS
HEQPLVPISF DKGLDMIVTM LAVLKAGAAY IPLDISHSEQ RLRMICQSAQ AKLILWDGQN
GFDKLRAIGH SSGATISTVD ELSDAVDGWG STPRSGEKPN LSSLAYIIYT SGSTGVPKGV
MVNHANLVSF MRSATNETYM SWTANRLQIA SYAFDMSVSD IFPVLAVGGR VLLARQQSLW
SDLAGWVDAF AVNQLMTTPT VADMMLSSAL SDGFLLAHLR DVIVGGEAVK RDILDKAPTE
MVFWIQYGPT ETTVVVTGCM FRGPTYYQPV PHSQITTIGF PLRGCRVYIL QPGTSNRVPI
GVPGELCISG PQVTMGYRGG GDPSESPFVP DPFWAGQTMY RSRDIAKVHG DGMIEWVGRM
DSQVKLRGLR IDLGEIESAA RQLNGVQSCA VVKLALEDKE TLLAFIEVAK SHQTHITPVT
IQQHIAQNVP SYMVPAHLRL LDKPLPRTAS DKLDRKGIHA LAQQLVDNGD LLSSCTSRIP
PADLRPSPGT LEATLASYWG TILGIDQEVI SLETPFSHLG GDSVRAISLL ALLRRNNFQL
NLTDLGSFST IRSQAFRILC DVQPQKLPAY MQLTTRSTSR ATMVLIHPFF GQSSVFDHVV
PALSEQYDIV QVSDPFFGKP DGPASLRDWA AHYLEALHVH LEQDRPVVLV GYSFGGLLVL
EMARLLEMTG KGSPFSTVIV DTRCYDPDQP FFKDEEERQT AADDAVRLFG PGQTSMIEEH
FDKHAHIWEN SVCPDKYLGR SLYLATPEAV ESGIVDWWRN QCPHIEVQRV ECSHGEIFEP
AMTGRVSALI NGHCDLDFTR IEP
