GLIP_ASPFU
ID GLIP_ASPFU Reviewed; 2135 AA.
AC Q4WMJ7; Q1PBG5; Q5MBT9;
DT 18-APR-2012, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=Nonribosomal peptide synthetase gliP {ECO:0000303|PubMed:15979823};
DE Short=NRPS gliP {ECO:0000303|PubMed:15979823};
DE EC=6.3.2.- {ECO:0000269|PubMed:17154540};
DE AltName: Full=Gliotoxin biosynthesis protein P {ECO:0000303|PubMed:15979823};
GN Name=gliP {ECO:0000303|PubMed:15979823};
GN Synonyms=NRPS10 {ECO:0000303|PubMed:16962256},
GN pesK {ECO:0000303|PubMed:17464044}; ORFNames=AFUA_6G09660;
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 [GENOMIC DNA], AND FUNCTION.
RC STRAIN=ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100;
RX PubMed=15979823; DOI=10.1016/j.femsle.2005.05.046;
RA Gardiner D.M., Howlett B.J.;
RT "Bioinformatic and expression analysis of the putative gliotoxin
RT biosynthetic gene cluster of Aspergillus fumigatus.";
RL FEMS Microbiol. Lett. 248:241-248(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], DISRUPTION PHENOTYPE, AND FUNCTION.
RC STRAIN=ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100;
RX PubMed=16757745; DOI=10.1128/ec.00049-06;
RA Cramer R.A. Jr., Gamcsik M.P., Brooking R.M., Najvar L.K.,
RA Kirkpatrick W.R., Patterson T.F., Balibar C.J., Graybill J.R.,
RA Perfect J.R., Abraham S.N., Steinbach W.J.;
RT "Disruption of a nonribosomal peptide synthetase in Aspergillus fumigatus
RT eliminates gliotoxin production.";
RL Eukaryot. Cell 5:972-980(2006).
RN [3]
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 [4]
RP DOMAIN, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF
RP ASP-204; SER-555; ASP-1245 AND SER-1582.
RX PubMed=17154540; DOI=10.1021/bi061845b;
RA Balibar C.J., Walsh C.T.;
RT "GliP, a multimodular nonribosomal peptide synthetase in Aspergillus
RT fumigatus, makes the diketopiperazine scaffold of gliotoxin.";
RL Biochemistry 45:15029-15038(2006).
RN [5]
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 [6]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=16956378; DOI=10.1111/j.1365-2958.2006.05373.x;
RA Kupfahl C., Heinekamp T., Geginat G., Ruppert T., Hartl A., Hof H.,
RA Brakhage A.A.;
RT "Deletion of the gliP gene of Aspergillus fumigatus results in loss of
RT gliotoxin production but has no effect on virulence of the fungus in a low-
RT dose mouse infection model.";
RL Mol. Microbiol. 62:292-302(2006).
RN [7]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=17601876; DOI=10.1128/ec.00141-07;
RA Sugui J.A., Pardo J., Chang Y.C., Zarember K.A., Nardone G., Galvez E.M.,
RA Mullbacher A., Gallin J.I., Simon M.M., Kwon-Chung K.J.;
RT "Gliotoxin is a virulence factor of Aspergillus fumigatus: gliP deletion
RT attenuates virulence in mice immunosuppressed with hydrocortisone.";
RL Eukaryot. Cell 6:1562-1569(2007).
RN [8]
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 [9]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=18199036; DOI=10.1086/525044;
RA Spikes S., Xu R., Nguyen C.K., Chamilos G., Kontoyiannis D.P.,
RA Jacobson R.H., Ejzykowicz D.E., Chiang L.Y., Filler S.G., May G.S.;
RT "Gliotoxin production in Aspergillus fumigatus contributes to host-specific
RT differences in virulence.";
RL J. Infect. Dis. 197:479-486(2008).
RN [10]
RP FUNCTION.
RX PubMed=20548963; DOI=10.1371/journal.ppat.1000952;
RA Schrettl M., Carberry S., Kavanagh K., Haas H., Jones G.W., O'Brien J.,
RA Nolan A., Stephens J., Fenelon O., Doyle S.;
RT "Self-protection against gliotoxin--a component of the gliotoxin
RT biosynthetic cluster, GliT, completely protects Aspergillus fumigatus
RT against exogenous gliotoxin.";
RL PLoS Pathog. 6:E1000952-E1000952(2010).
RN [11]
RP FUNCTION.
RX PubMed=21513890; DOI=10.1016/j.chembiol.2010.12.022;
RA Davis C., Carberry S., Schrettl M., Singh I., Stephens J.C., Barry S.M.,
RA Kavanagh K., Challis G.L., Brougham D., Doyle S.;
RT "The role of glutathione S-transferase GliG in gliotoxin biosynthesis in
RT Aspergillus fumigatus.";
RL Chem. Biol. 18:542-552(2011).
RN [12]
RP FUNCTION.
RX PubMed=21612254; DOI=10.1021/ja2029987;
RA Forseth R.R., Fox E.M., Chung D., Howlett B.J., Keller N.P.,
RA Schroeder F.C.;
RT "Identification of cryptic products of the gliotoxin gene cluster using
RT NMR-based comparative metabolomics and a model for gliotoxin
RT biosynthesis.";
RL J. Am. Chem. Soc. 133:9678-9681(2011).
RN [13]
RP FUNCTION.
RX PubMed=21749092; DOI=10.1021/ja201311d;
RA Scharf D.H., Remme N., Habel A., Chankhamjon P., Scherlach K.,
RA Heinekamp T., Hortschansky P., Brakhage A.A., Hertweck C.;
RT "A dedicated glutathione S-transferase mediates carbon-sulfur bond
RT formation in gliotoxin biosynthesis.";
RL J. Am. Chem. Soc. 133:12322-12325(2011).
RN [14]
RP FUNCTION.
RX PubMed=22936680; DOI=10.1002/anie.201205041;
RA Scharf D.H., Chankhamjon P., Scherlach K., Heinekamp T., Roth M.,
RA Brakhage A.A., Hertweck C.;
RT "Epidithiol formation by an unprecedented twin carbon-sulfur lyase in the
RT gliotoxin pathway.";
RL Angew. Chem. Int. Ed. 51:10064-10068(2012).
RN [15]
RP FUNCTION.
RX PubMed=22903976; DOI=10.1128/ec.00113-12;
RA Gallagher L., Owens R.A., Dolan S.K., O'Keeffe G., Schrettl M.,
RA Kavanagh K., Jones G.W., Doyle S.;
RT "The Aspergillus fumigatus protein GliK protects against oxidative stress
RT and is essential for gliotoxin biosynthesis.";
RL Eukaryot. Cell 11:1226-1238(2012).
RN [16]
RP FUNCTION.
RX PubMed=24039048; DOI=10.1002/anie.201305059;
RA Scharf D.H., Chankhamjon P., Scherlach K., Heinekamp T., Willing K.,
RA Brakhage A.A., Hertweck C.;
RT "Epidithiodiketopiperazine biosynthesis: a four-enzyme cascade converts
RT glutathione conjugates into transannular disulfide bridges.";
RL Angew. Chem. Int. Ed. 52:11092-11095(2013).
RN [17]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=23434416; DOI=10.1016/j.bmcl.2013.01.099;
RA Chang S.L., Chiang Y.M., Yeh H.H., Wu T.K., Wang C.C.;
RT "Reconstitution of the early steps of gliotoxin biosynthesis in Aspergillus
RT nidulans reveals the role of the monooxygenase GliC.";
RL Bioorg. Med. Chem. Lett. 23:2155-2157(2013).
RN [18]
RP FUNCTION.
RX PubMed=25062268; DOI=10.1021/ja5033106;
RA Scharf D.H., Habel A., Heinekamp T., Brakhage A.A., Hertweck C.;
RT "Opposed effects of enzymatic gliotoxin N- and S-methylations.";
RL J. Am. Chem. Soc. 136:11674-11679(2014).
RN [19]
RP INDUCTION.
RX PubMed=26032501; DOI=10.1016/j.bbrc.2015.05.090;
RA Shin K.S., Kim Y.H., Yu J.H.;
RT "Proteomic analyses reveal the key roles of BrlA and AbaA in biogenesis of
RT gliotoxin in Aspergillus fumigatus.";
RL Biochem. Biophys. Res. Commun. 463:428-433(2015).
RN [20]
RP FUNCTION.
RX PubMed=26150413; DOI=10.1128/ec.00055-15;
RA Owens R.A., O'Keeffe G., Smith E.B., Dolan S.K., Hammel S., Sheridan K.J.,
RA Fitzpatrick D.A., Keane T.M., Jones G.W., Doyle S.;
RT "Interplay between gliotoxin resistance, secretion, and the
RT methyl/methionine cycle in Aspergillus fumigatus.";
RL Eukaryot. Cell 14:941-957(2015).
CC -!- FUNCTION: Nonribosomal peptide synthetase; part of the gene cluster
CC that mediates the biosynthesis of gliotoxin, a member of the
CC epipolythiodioxopiperazine (ETP) class of toxins characterized by a
CC disulfide-bridged cyclic dipeptide (PubMed:15979823, PubMed:16757745,
CC PubMed:16956378, PubMed:21612254). The first step in gliotoxin
CC biosynthesis is the condensation of serine and phenylalanine to form
CC the cyclo-L-phenylalanyl-L-serine diketopiperazine (DKP) by the NRPS
CC gliP (PubMed:17154540, PubMed:21612254). GliP is also able to produce
CC the DKP cyclo-L-tryptophanyl-L-serine, suggesting that the substrate
CC specificity of the first adenylation (A) domain in gliP is sufficiently
CC relaxed to accommodate both L-Phe and L-Trp (PubMed:23434416). The
CC cytochrome P450 monooxygenase gliC has been shown to catalyze the
CC subsequent hydroxylation of the alpha-carbon of L-Phe in cyclo-L-
CC phenylalanyl-L-serine whereas the second cytochrome P450 enzyme, gliF,
CC is presumably involved in the modification of the DKP side chain
CC (PubMed:24039048, PubMed:23434416). The glutathione S-transferase (GST)
CC gliG then forms a bis-glutathionylated biosynthetic intermediate which
CC is responsible for the sulfurization of gliotoxin (PubMed:21513890,
CC PubMed:21749092). This bis-glutathionylated intermediate is
CC subsequently processed by the gamma-glutamyl cyclotransferase gliK to
CC remove both gamma-glutamyl moieties (PubMed:22903976, PubMed:24039048).
CC Subsequent processing via gliI yields a biosynthetic intermediate,
CC which is N-methylated via the N-methyltransferase gliN, before the
CC gliotoxin oxidoreductase gliT-mediated disulfide bridge closure
CC (PubMed:20548963, PubMed:22936680, PubMed:24039048, PubMed:25062268).
CC GliN-mediated amide methylation confers stability to ETP, damping the
CC spontaneous formation of tri- and tetrasulfides (PubMed:25062268).
CC Intracellular dithiol gliotoxin oxidized by gliT is subsequently
CC effluxed by gliA (PubMed:26150413). Gliotoxin contributes to
CC pathogenesis during invasive aspergillosis (PubMed:17601876,
CC PubMed:18199036). In macrophages and neutrophils, gliotoxin showed
CC inhibition of various different cell functions including cytokine
CC production, antigen presentation, phagocytosis, and production of
CC reactive oxygen species (PubMed:17601876).
CC {ECO:0000269|PubMed:16757745, ECO:0000269|PubMed:16956378,
CC ECO:0000269|PubMed:17154540, ECO:0000269|PubMed:17601876,
CC ECO:0000269|PubMed:18199036, ECO:0000269|PubMed:20548963,
CC ECO:0000269|PubMed:21513890, ECO:0000269|PubMed:21612254,
CC ECO:0000269|PubMed:21749092, ECO:0000269|PubMed:22903976,
CC ECO:0000269|PubMed:22936680, ECO:0000269|PubMed:23434416,
CC ECO:0000269|PubMed:24039048, ECO:0000269|PubMed:25062268}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=51 uM for L-phenylalanine {ECO:0000269|PubMed:17154540};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:17154540}.
CC -!- INDUCTION: Expression is positively regulated by the brlA and abaA
CC transcription factors (PubMed:26032501). {ECO:0000269|PubMed:26032501}.
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). GliP has the
CC following architecture: A-T-C-A-T-C-T (PubMed:17154540,
CC PubMed:17464044). {ECO:0000269|PubMed:17154540,
CC ECO:0000269|PubMed:17464044}.
CC -!- DISRUPTION PHENOTYPE: Impairs gliotoxin production (PubMed:16757745,
CC PubMed:16956378, PubMed:17601876). In vitro, the culture supernatant of
CC the gliP-deficient strains show a reduced cytotoxic effect on both
CC macrophage-like cells and T-cell lines. Shows attenuated virulence in
CC nonneutropenic mice immunosuppressed with corticosteroids, but normal
CC virulence in neutropenic mice (PubMed:18199036). It also has reduced
CC virulence in a Drosophila melanogaster model (PubMed:18199036).
CC {ECO:0000269|PubMed:16757745, ECO:0000269|PubMed:16956378,
CC ECO:0000269|PubMed:17601876, ECO:0000269|PubMed:18199036}.
CC -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAW03307.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AY838877; AAW03307.1; ALT_SEQ; Genomic_DNA.
DR EMBL; DQ457015; ABE60889.1; -; mRNA.
DR EMBL; AAHF01000006; EAL88817.1; -; Genomic_DNA.
DR RefSeq; XP_750855.1; XM_745762.1.
DR AlphaFoldDB; Q4WMJ7; -.
DR SMR; Q4WMJ7; -.
DR STRING; 746128.CADAFUBP00007375; -.
DR EnsemblFungi; EAL88817; EAL88817; AFUA_6G09660.
DR GeneID; 3508160; -.
DR KEGG; afm:AFUA_6G09660; -.
DR VEuPathDB; FungiDB:Afu6g09660; -.
DR eggNOG; KOG1178; Eukaryota.
DR HOGENOM; CLU_000022_0_5_1; -.
DR InParanoid; Q4WMJ7; -.
DR OMA; AVYNCYG; -.
DR OrthoDB; 4243at2759; -.
DR BioCyc; MetaCyc:MON-18847; -.
DR SABIO-RK; Q4WMJ7; -.
DR Proteomes; UP000002530; Chromosome 6.
DR GO; GO:0005737; C:cytoplasm; 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:0043041; P:amino acid activation for nonribosomal peptide biosynthetic process; IBA:GO_Central.
DR GO; GO:2001310; P:gliotoxin biosynthetic process; IMP:AspGD.
DR GO; GO:0043386; P:mycotoxin biosynthetic process; IDA:AspGD.
DR GO; GO:0019184; P:nonribosomal peptide biosynthetic process; IDA:AspGD.
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; -; 3.
DR Gene3D; 3.30.300.30; -; 2.
DR Gene3D; 3.30.559.10; -; 2.
DR Gene3D; 3.40.50.12780; -; 2.
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; 2.
DR Pfam; PF00668; Condensation; 2.
DR Pfam; PF00550; PP-binding; 3.
DR SMART; SM00823; PKS_PP; 2.
DR SUPFAM; SSF47336; SSF47336; 3.
DR TIGRFAMs; TIGR01733; AA-adenyl-dom; 1.
DR PROSITE; PS00455; AMP_BINDING; 2.
DR PROSITE; PS50075; CARRIER; 3.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 1: Evidence at protein level;
KW Ligase; Phosphopantetheine; Phosphoprotein; Reference proteome; Repeat;
KW Virulence.
FT CHAIN 1..2135
FT /note="Nonribosomal peptide synthetase gliP"
FT /id="PRO_0000416551"
FT DOMAIN 519..594
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 1544..1622
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 2061..2134
FT /note="Carrier 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 34..424
FT /note="Adenylation 1"
FT /evidence="ECO:0000255"
FT REGION 663..913
FT /note="Condensation 1"
FT /evidence="ECO:0000255"
FT REGION 1078..1458
FT /note="Adenylation 2"
FT /evidence="ECO:0000255"
FT REGION 1642..1905
FT /note="Condensation 2"
FT /evidence="ECO:0000255"
FT MOD_RES 555
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 1582
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 2095
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MUTAGEN 204
FT /note="D->A: Impairs activation of L-phenylalanine."
FT /evidence="ECO:0000269|PubMed:17154540"
FT MUTAGEN 555
FT /note="S->A: Impairs loading of L-phenylalanine and
FT formation of the dipeptide."
FT /evidence="ECO:0000269|PubMed:17154540"
FT MUTAGEN 1245
FT /note="D->A: Impairs activation of L-serine."
FT /evidence="ECO:0000269|PubMed:17154540"
FT MUTAGEN 1582
FT /note="S->A: Impairs loading of L-serine and formation of
FT the dipeptide."
FT /evidence="ECO:0000269|PubMed:17154540"
SQ SEQUENCE 2135 AA; 235835 MW; 435B5A722BE353A9 CRC64;
MPSVVALDLC QLFDRSVART PHQLAVDHES GSLTYTELDV ASSNLARKLK QEGVVPGEAV
LLLTEHGTRN VVALLAILKA HACYVPLDRS SWSSERIQAV LDGTDSRILI NTTVEPFESP
RHKVIHLTSA DVTTLSTDRS TTKVIPDIAP EDLACLIFTS GSTGVPKGVM IPHRAVANYA
QTSPFNMDVQ PGDRVLHILS VSFDASTGML FSILGNSGIV VPATMDTLFD KAQSCSILAS
TPSILATLPL PTALPDSYPY VHTILLGGES PPAPLLSSWL QFGVRILNAY GPTETTCASL
MQEVEVCQET GMINRSIIGR PMPNGPVYLL QPDTLLPVEE EGEEGEIAIA GVGLAHGYYR
NAALTAEKFI EWHGKRVYRT GDQGRWTRRN DGQRVVEFRG RSDRTVKNRG FLVNLPADVE
EPLRQMGFGV TDVYASLING LLVALVTPAT ADLDGLQSEA DRRLSSFHRP GRYLAVDQFP
LSANGKIDTK AIENMLKEYQ ARLCEGTDDE ETTGGERPTE REQVIAECMY TALGLDLPSA
SASKDFNFFA MGGNSLAALR FTSLCRERGI LLTTRDLYLH PTVRGILPYA RDLAHSGLPL
PDKEEQIDHR LSLKAEVAAA LHLLGDIDVA PLTPLQLQLS APIFQSDGTN TNQLRQSYPL
ASAEHICNAW RQVVLSEPVF RTQIALDIGP GVQIVHAQPR CQPQEITFHR REDYNAALSD
PSRLPVGLGM RLEFMKFMPN DDDDDEGEVT VVWTAHHSLI DGYSLGLILA RVQQASQGVA
SSRVSSFVDA AWNLLSVQKQ RDTEARRFWE QYLQPVRSLT KAEATTTPVA RPYLAQEVLF
KHVGGVDELH RLASSCSVTL AAVYYTAWAM TIARTTKSTL VTLGVVFSGR EILPDDAQAV
GPLMATLPLV CRIDGEASIE RQLQTTFEGL ATISTYAWSA PDQIGYRVDS LLATQYDFPT
YDQPIPPQKE QFFENTTFAL SLLVEADARF RLVYNPSVHG EQTVQQYADT FQQALQALVG
DSTMEAWLTG PTKAPLAVDQ ASDIQHVNVP NVASAFYASV DLHKDLIAVD GPGGTLPYRE
LDQKSNAVAS HIAKHFSRAQ VIAIHADGTL NWVVGILGIL KAGCAYCPLD PAYPIARRVA
VYEQSGASAL LIPNACSSSA ALLPITDLRV FTIQETETSD TSRQPSLLAN ANEDALIVFT
SGTTGRPKGV PISHRGLLAL QSNPEATMFS RPGRRIAQFM SPAFDYCANE IFSALLHGGT
LVLRDPSDPL AHLAKVDVST ITPSVLSVLN PDDYPNLDMV YATGEPVTPG LLARWGEGRA
FYNAYGPAEC SICTSFTRLE PGQQVTIGNA VRTARMYILD PDLQPVSDGQ TGEIFLAGQQ
VMRGYVGDDA KTAYSVLPDP WHPGERMYRT GDYGYWNADR QIVYIGRLDR QVKIRGFRVE
LAAVEQKMYQ EEPRLTQAAA LVVNDTLVAF VMPLDVDVSR LEQRLRESLQ PSWVPQVITA
LEEFPWTANR KVDYRKLAER ATLTRPEDSL PQQKTPAGMT AKDASIADGI ATLWKNVLRL
QAGGGSRKLC EDDDFRALGG HSVLQMMLAA RLGSTFGISV SMRDVIEHST LAEQVELVRR
KRQASTAKPR TICDAFPDHC LSPLERQTWF QYLIAADVRT FNIPVLLHLG GTFDRDRLVQ
SFNAVLASRK IFRTNFVETS LGPCRIFRDT PPRVLVCDGA LDTTKEIDRS FDLARDELIR
VFLDRRTLLV VTSHAVADLN SVQNLLQDVS GVYAGRTTPT PDRWHYPRAP AWSRQATEQE
RKFWSKYLEG APQRLDIPRY PGQMAFEGRS RVSEFKGDLV RRAVTLGQEH GLSQHQLVCA
AVAQTLQWLA GSNDVVLGSP WANRGHTVEQ ESMGLFLDRL PLRFKTPVNA DCATILQSTR
AASQAAVCNS IPFEQVLNLL HLPRTIRQHP LFEAMVTFHL KGAVEDCLAI EGLEVKREMC
FASGAKFLLM FEWTEIEADH WTLRIEYDDH QLDDATVTTI EDSIRCVLEG LADRLSRAAI
HERLNAMHKT ARTKVDWNFY RRLVGILQRE MATCLGVSLD EFPCSVSFFE AGGDSIQAWR
LSRQLKRVGL EVPICNIFDH PTAQDLAQRL YRQVL
