FMQA_ASPFU
ID FMQA_ASPFU Reviewed; 3955 AA.
AC Q4WLW5;
DT 18-APR-2012, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 112.
DE RecName: Full=Nonribosomal peptide synthetase fmqA {ECO:0000303|PubMed:16962256};
DE EC=6.3.2.- {ECO:0000269|PubMed:20225828};
DE AltName: Full=Fumiquinazoline biosynthesis cluster protein A {ECO:0000303|PubMed:24612080};
GN Name=fmqA {ECO:0000303|PubMed:24612080};
GN Synonyms=NRPS12 {ECO:0000303|PubMed:16962256},
GN pesM {ECO:0000303|PubMed:17464044}; ORFNames=AFUA_6G12080;
OS Neosartorya fumigata (strain ATCC MYA-4609 / Af293 / CBS 101355 / FGSC
OS A1100) (Aspergillus fumigatus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Fumigati.
OX NCBI_TaxID=330879;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100;
RX PubMed=16372009; DOI=10.1038/nature04332;
RA Nierman W.C., Pain A., Anderson M.J., Wortman J.R., Kim H.S., Arroyo J.,
RA Berriman M., Abe K., Archer D.B., Bermejo C., Bennett J.W., Bowyer P.,
RA Chen D., Collins M., Coulsen R., Davies R., Dyer P.S., Farman M.L.,
RA Fedorova N., Fedorova N.D., Feldblyum T.V., Fischer R., Fosker N.,
RA Fraser A., Garcia J.L., Garcia M.J., Goble A., Goldman G.H., Gomi K.,
RA Griffith-Jones S., Gwilliam R., Haas B.J., Haas H., Harris D.E.,
RA Horiuchi H., Huang J., Humphray S., Jimenez J., Keller N., Khouri H.,
RA Kitamoto K., Kobayashi T., Konzack S., Kulkarni R., Kumagai T., Lafton A.,
RA Latge J.-P., Li W., Lord A., Lu C., Majoros W.H., May G.S., Miller B.L.,
RA Mohamoud Y., Molina M., Monod M., Mouyna I., Mulligan S., Murphy L.D.,
RA O'Neil S., Paulsen I., Penalva M.A., Pertea M., Price C., Pritchard B.L.,
RA Quail M.A., Rabbinowitsch E., Rawlins N., Rajandream M.A., Reichard U.,
RA Renauld H., Robson G.D., Rodriguez de Cordoba S., Rodriguez-Pena J.M.,
RA Ronning C.M., Rutter S., Salzberg S.L., Sanchez M., Sanchez-Ferrero J.C.,
RA Saunders D., Seeger K., Squares R., Squares S., Takeuchi M., Tekaia F.,
RA Turner G., Vazquez de Aldana C.R., Weidman J., White O., Woodward J.R.,
RA Yu J.-H., Fraser C.M., Galagan J.E., Asai K., Machida M., Hall N.,
RA Barrell B.G., Denning D.W.;
RT "Genomic sequence of the pathogenic and allergenic filamentous fungus
RT Aspergillus fumigatus.";
RL Nature 438:1151-1156(2005).
RN [2]
RP NOMENCLATURE.
RX PubMed=16962256; DOI=10.1016/j.gene.2006.07.008;
RA Cramer R.A. Jr., Stajich J.E., Yamanaka Y., Dietrich F.S., Steinbach W.J.,
RA Perfect J.R.;
RT "Phylogenomic analysis of non-ribosomal peptide synthetases in the genus
RT Aspergillus.";
RL Gene 383:24-32(2006).
RN [3]
RP REVIEW ON FUNCTION, AND DOMAIN.
RX PubMed=17464044; DOI=10.1099/mic.0.2006/006908-0;
RA Stack D., Neville C., Doyle S.;
RT "Nonribosomal peptide synthesis in Aspergillus fumigatus and other fungi.";
RL Microbiology 153:1297-1306(2007).
RN [4]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, PHOSPHOPANTETHEINYLATION, DOMAIN,
RP AND PATHWAY.
RX PubMed=20225828; DOI=10.1021/bi100198y;
RA Ames B.D., Walsh C.T.;
RT "Anthranilate-activating modules from fungal nonribosomal peptide assembly
RT lines.";
RL Biochemistry 49:3351-3365(2010).
RN [5]
RP FUNCTION.
RX PubMed=20804163; DOI=10.1021/bi1012029;
RA Ames B.D., Liu X., Walsh C.T.;
RT "Enzymatic processing of fumiquinazoline F: a tandem oxidative-acylation
RT strategy for the generation of multicyclic scaffolds in fungal indole
RT alkaloid biosynthesis.";
RL Biochemistry 49:8564-8576(2010).
RN [6]
RP FUNCTION.
RX PubMed=21899262; DOI=10.1021/bi201302w;
RA Ames B.D., Haynes S.W., Gao X., Evans B.S., Kelleher N.L., Tang Y.,
RA Walsh C.T.;
RT "Complexity generation in fungal peptidyl alkaloid biosynthesis: oxidation
RT of fumiquinazoline A to the heptacyclic hemiaminal fumiquinazoline C by the
RT flavoenzyme Af12070 from Aspergillus fumigatus.";
RL Biochemistry 50:8756-8769(2011).
RN [7]
RP FUNCTION, DISRUPTION PHENOTYPE, INDUCTION, SUBCELLULAR LOCATION, AND
RP PATHWAY.
RX PubMed=24612080; DOI=10.1111/cmi.12284;
RA Lim F.Y., Ames B., Walsh C.T., Keller N.P.;
RT "Co-ordination between BrlA regulation and secretion of the oxidoreductase
RT FmqD directs selective accumulation of fumiquinazoline C to conidial
RT tissues in Aspergillus fumigatus.";
RL Cell. Microbiol. 16:1267-1283(2014).
RN [8]
RP FUNCTION, INDUCTION, AND INTERACTION WITH MPKA.
RX PubMed=33705521; DOI=10.1093/genetics/iyab036;
RA Rocha M.C., Fabri J.H.T.M., da Silva L.P., Angolini C.F.F., Bertolini M.C.,
RA da Cunha A.F., Valiante V., Goldman G.H., Fill T.P., Malavazi I.;
RT "Transcriptional control of the production of Aspergillus fumigatus
RT conidia-borne secondary metabolite fumiquinazoline C important for
RT phagocytosis protection.";
RL Genetics 0:0-0(2021).
CC -!- FUNCTION: Nonribosomal peptide synthetase; part of the gene cluster
CC that mediates the biosynthesis of the antitumor fumiquinazolines that
CC confer a dual-usage capability to defend against phagocytes in the
CC environment and animal hosts (PubMed:20225828, PubMed:20804163,
CC PubMed:21899262, PubMed:24612080, PubMed:33705521). The simplest member
CC is fumiquinazoline F (FQF) with a 6-6-6 tricyclic core derived from
CC anthranilic acid (Ant), tryptophan (Trp), and alanine (Ala)
CC (PubMed:20225828). The trimodular NRPS fmqA is responsible for FQF
CC formation (PubMed:20225828). Modules 1, 2 and 3 of fmqA are predicted
CC to activate and load Ant, Trp and Ala, respectively, providing for the
CC assembly of an Ant-Trp-Ala-S-enzyme intermediate that would undergo
CC double cyclization for chain release and generation of the tricyclic 6-
CC 6-6 product fumiquinazoline F (PubMed:20225828). The presence of an E
CC domain predicted for module 2 of fmqA is consistent with epimerization
CC of L-Trp to D-Trp during assembly to generate the R-stereocenter at C14
CC of FQF (PubMed:20225828). The FAD-dependent monooxygenase fmqB and the
CC monomodular NRPS fmqC then maturate FQF to FQA (PubMed:20804163). FmqB
CC oxidizes the 2',3'-double bond of the indole side chain of FQF, and
CC fmqC activates L-Ala as the adenylate, installs it as the pantetheinyl
CC thioester on its carrier protein domain, and acylates the oxidized
CC indole for subsequent intramolecular cyclization to create the 6-5-5-
CC imidazolindolone of FQA (PubMed:20804163). The FAD-linked
CC oxidoreductase fmqD introduces a third layer of scaffold complexity by
CC converting FQA to the spirohemiaminal FQC, presumably by catalyzing the
CC formation of a transient imine within the pyrazinone ring
CC (PubMed:21899262). FQC subsequently converts nonenzymatically to the
CC known cyclic aminal FQD (PubMed:21899262).
CC {ECO:0000269|PubMed:20225828, ECO:0000269|PubMed:20804163,
CC ECO:0000269|PubMed:21899262, ECO:0000269|PubMed:24612080,
CC ECO:0000269|PubMed:33705521}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=18 uM for anthranilate {ECO:0000269|PubMed:20225828};
CC KM=230 uM for ATP {ECO:0000269|PubMed:20225828};
CC KM=17 uM for salicylic acid {ECO:0000269|PubMed:20225828};
CC KM=29 uM for 2-chlorobenzoic acid {ECO:0000269|PubMed:20225828};
CC KM=32 uM for 4-chlorobenzoic acid {ECO:0000269|PubMed:20225828};
CC KM=74 uM for benzoic acid {ECO:0000269|PubMed:20225828};
CC KM=416 uM for 3-aminobenzoic acidATP {ECO:0000269|PubMed:20225828};
CC KM=1900 uM for 4-aminobenzoic acid {ECO:0000269|PubMed:20225828};
CC -!- PATHWAY: Alkaloid biosynthesis. {ECO:0000269|PubMed:20225828,
CC ECO:0000269|PubMed:24612080}.
CC -!- SUBUNIT: Interacts with the mitogen-activated protein kinase mpkA.
CC {ECO:0000269|PubMed:33705521}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle
CC {ECO:0000269|PubMed:24612080}. Note=Does not localize to endocytic
CC vesicles, vacuoles nor mitochondria (PubMed:24612080).
CC {ECO:0000269|PubMed:24612080}.
CC -!- INDUCTION: Expression is positively regulated by brlA, a conidiation-
CC specific transcription factor involved in the early stage of asexual
CC development and necessary for conidiophore formation (PubMed:24612080).
CC Expression is also induced by the cell wall integrity (CWI) signaling
CC pathway that includes the mitogen-activated protein kinase mpkA and the
CC transcription factor rlmA (PubMed:33705521). Expression is negatively
CC regulated by the transcription factor sebA (PubMed:33705521).
CC {ECO:0000269|PubMed:24612080, ECO:0000269|PubMed:33705521}.
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 (PubMed:17464044). Each module is responsible for the
CC recognition (via the A domain) and incorporation of a single amino acid
CC into the growing peptide product (PubMed:17464044). Thus, an NRP
CC synthetase is generally composed of one or more modules and can
CC terminate in a thioesterase domain (TE) that releases the newly
CC synthesized peptide from the enzyme (PubMed:17464044). Occasionally,
CC epimerase (E) domains (responsible for L- to D- amino acid conversion)
CC are present within the NRP synthetase (PubMed:17464044). NRPS12 has the
CC following architecture: A-T-C-A-T-E-C-A-T-C (PubMed:17464044,
CC PubMed:20225828). {ECO:0000269|PubMed:17464044}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of all fumiquinazolines
CC (PubMed:24612080). {ECO:0000269|PubMed:24612080}.
CC -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
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DR EMBL; AAHF01000006; EAL89049.1; -; Genomic_DNA.
DR RefSeq; XP_751087.1; XM_745994.1.
DR SMR; Q4WLW5; -.
DR STRING; 746128.CADAFUBP00007610; -.
DR PRIDE; Q4WLW5; -.
DR EnsemblFungi; EAL89049; EAL89049; AFUA_6G12080.
DR GeneID; 3508392; -.
DR KEGG; afm:AFUA_6G12080; -.
DR VEuPathDB; FungiDB:Afu6g12080; -.
DR eggNOG; KOG1176; Eukaryota.
DR eggNOG; KOG1178; Eukaryota.
DR HOGENOM; CLU_000022_60_4_1; -.
DR InParanoid; Q4WLW5; -.
DR OMA; YEWLMAF; -.
DR OrthoDB; 4243at2759; -.
DR BioCyc; MetaCyc:MON-18827; -.
DR Proteomes; UP000002530; Chromosome 6.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:AspGD.
DR GO; GO:0000036; F:acyl carrier activity; IBA:GO_Central.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IBA:GO_Central.
DR GO; GO:1900781; P:fumiquinazoline C biosynthetic process; IDA:GO_Central.
DR GO; GO:0019184; P:nonribosomal peptide biosynthetic process; ISM:AspGD.
DR GO; GO:0019748; P:secondary metabolic process; IGC:AspGD.
DR Gene3D; 1.10.1200.10; -; 3.
DR Gene3D; 3.30.300.30; -; 3.
DR Gene3D; 3.30.559.10; -; 4.
DR Gene3D; 3.40.50.12780; -; 3.
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; 3.
DR Pfam; PF00668; Condensation; 4.
DR Pfam; PF00550; PP-binding; 3.
DR SMART; SM00823; PKS_PP; 3.
DR SUPFAM; SSF47336; SSF47336; 3.
DR TIGRFAMs; TIGR01733; AA-adenyl-dom; 3.
DR PROSITE; PS00455; AMP_BINDING; 2.
DR PROSITE; PS50075; CARRIER; 3.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 2.
PE 1: Evidence at protein level;
KW Cytoplasmic vesicle; Ligase; Phosphopantetheine; Phosphoprotein;
KW Reference proteome; Repeat; Virulence.
FT CHAIN 1..3955
FT /note="Nonribosomal peptide synthetase fmqA"
FT /id="PRO_0000416553"
FT DOMAIN 806..879
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:17464044, ECO:0000305|PubMed:20225828"
FT DOMAIN 1880..1956
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:17464044, ECO:0000305|PubMed:20225828"
FT DOMAIN 3422..3498
FT /note="Carrier 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:17464044, ECO:0000305|PubMed:20225828"
FT REGION 293..691
FT /note="Adenylation 1"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:17464044,
FT ECO:0000305|PubMed:20225828"
FT REGION 916..1187
FT /note="Condensation 1"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:17464044,
FT ECO:0000305|PubMed:20225828"
FT REGION 1371..1766
FT /note="Adenylation 2"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:17464044,
FT ECO:0000305|PubMed:20225828"
FT REGION 1970..2261
FT /note="Epimerase"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:17464044,
FT ECO:0000305|PubMed:20225828"
FT REGION 2438..2724
FT /note="Condensation 2"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:17464044,
FT ECO:0000305|PubMed:20225828"
FT REGION 2906..3299
FT /note="Adenylation 3"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:17464044,
FT ECO:0000305|PubMed:20225828"
FT REGION 3541..3805
FT /note="Condensation 3"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:17464044,
FT ECO:0000305|PubMed:20225828"
FT MOD_RES 840
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 1917
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 3459
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 3955 AA; 437813 MW; C66E17E07E1F5296 CRC64;
MERLEAKNQT TKHGERMAPQ RYSVLRDEKC LFPVRNDGKL LVDEWRVTEL AISSGEKGLK
LCRTTCPTAG ADPRYLAAAA WALLLWRFAE VDTVQIGLQD IPPGANEDIL EAGLKRGMKV
LAASRRQVQL LNELWQGDTW SISDADPTCY SYFDTGIVIC RGNSQDCLAK CRSPNQLRKA
NGEACNVLLV LELDLDSNWR KCFLAYKTTV LTDIQATHLK SSFEEVVELA RAGRGIPLSE
ICLVSRRQLD QIGKWNERAL VQPKFKAMHQ VVHDRATDRR HHPAVIAADR ALSYSELETL
SLKVAYRLRG SGVQPGDLIP VCFCKSSWAI VAMLAINKLG AAFVPLDPSQ PVNRLKSITR
QLDATLAVTS PENQSLVEDL VTTTVVVSET TVSELVDVHN EIVLPACDPG APAYCLFTSG
STGKPKGCVV DHAALASVAT HSHALHLGPT SRVLQFASFT FGVSLIEVWC TLAAGGTVCL
PSDSDRVSRL ADAIRSMGVD WCILTPTVLA TLEPEAVPNL RTILVAGEPL KKAQFSLWAE
RARLFQAYGF TEWAGICCVS PQIRSIGDVG IIGTPANARC WLVEPGNPNQ LAPIGAVAEL
AVEGPSLAQG YLHDPEKTAA TLIPPPRWRA QYGHADGKRI YTTGDLVYYD SNGMLRYVSR
KDRQVKIRGQ RIDLAEPEYH IAQACCTIRN VVLDAIVPAD SNGDAILVAF VLPSRDESSS
NGGHDSPLFA VPDDHFTSSV RQLTSFLEDK LPDYMVPRLF LQLKETPVTI TGKIARQKLR
EAAEALRHDE LVALAGLETR VLPPNTHKET LIHQLVVELL HLPPEMVGMN HNFFSLGGDS
VSVMKLVSRA KRVGLSFTVK DVFRSPQLGD LARLTDVVNS GAAQHMPPFS LLDRGAQPGL
LSMAAKICQV ESSMIQDIYP CTPLQEGMMT LSAAKAGSYI ARFVYRLEEH VDSPRFRRAW
EMTVEATPIL RTRIISASDG RLYQVVIQEK FRWDDDGQPS GECVQNGQDR HMLLGEPLTH
AALVRDRNQD GSLSTVFVLT MHHSVCDRWS VGLIMDSVET AYTGQTLTTN SMGPFLQYIQ
QLQGGDAFWR SQFVGVKAEV FPSLPSPEYT PTPTETIDLS VELRDAVPGG HTIANAIRLA
WALVISHYTS CSDVVFGVTI SGRAVPVPDI ERIIGPIIAT VPLRVRLKES STVLEALKAI
QDQSMEMIPF EQLGLRQIRK LSPEAEEACN FQSQLVVQPA WGDENRSLFA TCEAGAAAEG
GFAAYALSMI CQLVGSSQID VRTEFDPKVI QAPIMQRIVH HFVYTLQYLL AHPDARVAEI
PVVSPGEKQL LRQWNGIVPP ASHQCVHEII QQRQIERPTS TAVWAWDGQL TYAELGELSD
RLAEYLATKG VQPEVIVPVC LEKSYWTTVA MLGISKAGGA FALLDPSQPE QRLQSICHQL
NSAVILTSEK NRDLAGKLAS HPIVLSLQSS RRWGHGPAKQ APATARPDHT LYVAFTSGST
GTPKGVVIEH RSFCTSALAL NRITGVNSES RMLQFAGYSF DGSIMEMLSA LMAGACVCVP
SEFQRRNELV AAAAKFELTH AHLTPSVARH LLRGNPEFTK TLVSVGEPMT ASDVADWASN
GQCKVMNGYG PAECAVSTTI QAAVTSASDP KNIGFPVAGV CWVVHPENHD ILLPPGAVGE
LLIEGPTLAR GYLNEPDKTA AAFIPLPAWI KDIRPEQPHG RLYKSGDLVR YNADGSFQYI
GRRDSQIKLR GQRIELDEVE KHVYQCWPGV IAVVAVEMVS FTPATQTLVA FVVVEEHVDT
TGDILAAPTQ EFTGQVAVAQ ARLREAIPAF MVPEIFIPLL VLPQSASGKT DRRRLRSIAT
ACTREKLAAY GAVGTGTKRE PTSVAEREMQ AIWAQALNLP LAEIGMDDSF YQLGGDSITA
MQVVAHARSK GLAVTMDSIL RLKSISKIMS HESSLSPAIV HIDEEEDVWF ALSPIQQMFF
DRQPSGWDRF SQVFLLRVSQ PVTASQLQMA LHTLVSKHPM LRARFAKQHD GSWRQVITSK
IQESYRCRSH RLNRRSSVDG VVSSGACSLS IQKGPLIAVD LMSREDGAQY LSIVIHHLVV
DLVSWRIILA DLEAMLRGEN PMANHSTPFQ TWCRLQAEYA RQYLSPQHAF PTDLPDHYHQ
DPSVFWGLAG QPNLVRDSRR QVFTLDEHTT RQLLGAANAA FATRTDEVLH AVLLYSFLKV
FPHRIAPLTF SEGHGREPWD SAIDLSQTVG WFTTMWPVVA ELQQNHSFLE VVCRVKDARR
AVPCNGWAYF VSRYLNPSGR QAFQQFHPVE LVFNYAGEYQ QFNQAGAFFI PDMPEYQGSL
DAGEQIQRFG IFEVFASVVR GCLQFQFMYN RYMKHQLEIQ KWIESCRQTL IEGCSTLIAA
KPSRTLSDFP LLPLTYSTLR ELLDVTLPTA GVSVENVEDI YPCSPSQRGM LIAQAKAAHN
YNASVTWSIR SRIDSRPNVA RLKAAWCEVV KRHAILRTVF VESPWPESYM DQVVLQNVSP
EFVFCRGSDS LPQSISSPGQ TRWSKGQCQH IMRVWERDNG DILCRLDLSH AIMDRTTLAI
IQKDLSLAYD ERLLPGRAPL YRDYISYIYQ QDSESARQYW QGYLEGVEPC EFPTLNPVDP
SITKEWGNLY RTLEDRRRLE EFCRTHSVTP WNVAGLAWAM VLRSFTRTDS VCFGYVKSGR
DLPIDGIAGT AGPVFNPLPC RVHLTERLTV RETIGRLQEE YLQSLAHQSF PLSDIHRLAG
VTSGVLFNTS VAVQTEVASE AEEAKRSLEF TTVAMEDGTE DDMVITLVPR GGELVLHLRH
RSRTLTTDQA STVLATFEKA LCSILANAEA PMTSIDVFSD HDKAILWSRN RRVPDAVESC
VHELIQKHCV ERPHSPAVNA WDGAFTYGQL DELSSRLAVY LAAQGVGPNV VVPLCFEKTR
WTPIAMMGVM KAGGAFLLLD PSYPLQRLKD ICADIDCRLV VSSTTHEAMS RELASTVVVV
GEDRHHWQLE NTSHTITMPK VRPADALYVV FTSGSTGKPK GVVIEHRSYC SGALDHIRSY
NLTPQSRVLQ FSSYAFDISI VEQLSVLIAG GCICVISESQ RKNSLGEAAT ALQANHAMLI
PSVARLVRHE DLSTITSLSL AGECMQETDV SYWAQHVRLM NGYGPAECSA LSLVQPCVLP
HSDPHDIGYP VGSVAWVVDP HDHHKLVPNG AVGELLIEGP IVGRGYINNA EKTAEVFIEP
PTWLRTLRGH CTSRLYKTGD LVRANPSGSL SILGRKDRQV KLRGQRLELG EVEANVQHCF
PGALDVVADL LPSSRGGKPQ LVAMVFQNAE RAARIAPESD SKLIAEPSVD FMQSATTAET
RLRQTVPNFM VPSMFLPLAQ IPRTHSDKVD RNSLLKAVAA MSSIELQAYK ASVDAGHCST
RAPSTEEEKK LAEIWADVLK VPVEHIGADD NFLLSGGDSI DAMKAAAFCR AAGMALSVAD
IFAHPVLSDL AKVAVPKSLN GSSTSHQPFS LSPVDSPKDL HMSLMEQGLV PPGSALADLL
PGTQAQQFFI ERGTFHSYNF SIRGPLDRCR LQKTCTAILS RHSILRTKFL QYEGRLIQIV
LDNLETPFTH YTTDGDLLEF CKSLWERDLA ALDGLGRLPC KFTLVSRSEQ EHVFTIQISH
AQWDGVSIPR LFSDIAAIYN QIPLPSTTHF ADYVYHRSSR DERPAFDFWK KYLRGSSMPV
PFPATNCQDR EHKTQWTFQG IKNPRLPAGI TMASLVKAAC GFHLCQLLSQ NDVVFGHTVN
GRNLALDNVE ALLGCCLNFI PLRVMLQPSW TVLDLLAHVQ EQYTRALPHE HLELRDIFRH
STPWPADTQL SFIVQHQNIE LHHNIALDGL QVQYSKFAQF DPLTEVWIFS EPHPDRLEIQ
VCANTRVLSE DQARALCRRL CDLIEFFSAS PDCPLSKVVD HMDRPGLLAE EKVLN
