LPSA1_CLAP2
ID LPSA1_CLAP2 Reviewed; 3584 AA.
AC M1W0X8; G8GV70;
DT 15-MAR-2017, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2013, sequence version 1.
DT 25-MAY-2022, entry version 38.
DE RecName: Full=D-lysergyl-peptide-synthetase subunit 1 {ECO:0000303|PubMed:10071219};
DE Short=LPS1 {ECO:0000303|PubMed:10071219};
DE EC=2.3.1.- {ECO:0000269|PubMed:19139103};
DE AltName: Full=Ergot alkaloid synthesis protein ps1 {ECO:0000303|PubMed:10071219};
DE AltName: Full=Nonribosomal peptide synthetase 1 {ECO:0000303|PubMed:10071219};
GN Name=lpsA1 {ECO:0000303|PubMed:17720822};
GN Synonyms=cpps1 {ECO:0000303|PubMed:10071219}; ORFNames=CPUR_04074;
OS Claviceps purpurea (strain 20.1) (Ergot fungus) (Sphacelia segetum).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Clavicipitaceae; Claviceps.
OX NCBI_TaxID=1111077;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=20.1;
RA Florea S., Oeser B., Tudzynski P., Schardl C.L.;
RL Submitted (JUN-2011) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=20.1;
RX PubMed=23468653; DOI=10.1371/journal.pgen.1003323;
RA Schardl C.L., Young C.A., Hesse U., Amyotte S.G., Andreeva K., Calie P.J.,
RA Fleetwood D.J., Haws D.C., Moore N., Oeser B., Panaccione D.G.,
RA Schweri K.K., Voisey C.R., Farman M.L., Jaromczyk J.W., Roe B.A.,
RA O'Sullivan D.M., Scott B., Tudzynski P., An Z., Arnaoudova E.G.,
RA Bullock C.T., Charlton N.D., Chen L., Cox M., Dinkins R.D., Florea S.,
RA Glenn A.E., Gordon A., Gueldener U., Harris D.R., Hollin W., Jaromczyk J.,
RA Johnson R.D., Khan A.K., Leistner E., Leuchtmann A., Li C., Liu J., Liu J.,
RA Liu M., Mace W., Machado C., Nagabhyru P., Pan J., Schmid J., Sugawara K.,
RA Steiner U., Takach J.E., Tanaka E., Webb J.S., Wilson E.V., Wiseman J.L.,
RA Yoshida R., Zeng Z.;
RT "Plant-symbiotic fungi as chemical engineers: Multi-genome analysis of the
RT Clavicipitaceae reveals dynamics of alkaloid loci.";
RL PLoS Genet. 9:E1003323-E1003323(2013).
RN [3]
RP IDENTIFICATION IN THE EAS CLUSTER, AND FUNCTION.
RC STRAIN=P1 / 1029/N5;
RX PubMed=10071219; DOI=10.1007/s004380050950;
RA Tudzynski P., Hoelter K., Correia T.H., Arntz C., Grammel N., Keller U.;
RT "Evidence for an ergot alkaloid gene cluster in Claviceps purpurea.";
RL Mol. Gen. Genet. 261:133-141(1999).
RN [4]
RP BIOTECHNOLOGY.
RC STRAIN=P1 / 1029/N5;
RX PubMed=11778866; DOI=10.1007/s002530100801;
RA Tudzynski P., Correia T., Keller U.;
RT "Biotechnology and genetics of ergot alkaloids.";
RL Appl. Microbiol. Biotechnol. 57:593-605(2001).
RN [5]
RP FUNCTION, AND DOMAIN.
RX PubMed=14700635; DOI=10.1016/j.chembiol.2003.11.013;
RA Correia T., Grammel N., Ortel I., Keller U., Tudzynski P.;
RT "Molecular cloning and analysis of the ergopeptine assembly system in the
RT ergot fungus Claviceps purpurea.";
RL Chem. Biol. 10:1281-1292(2003).
RN [6]
RP FUNCTION.
RC STRAIN=ATCC 20102 / Farmitalia FI 32/17;
RX PubMed=14732265; DOI=10.1016/j.fgb.2003.10.002;
RA Wang J., Machado C., Panaccione D.G., Tsai H.-F., Schardl C.L.;
RT "The determinant step in ergot alkaloid biosynthesis by an endophyte of
RT perennial ryegrass.";
RL Fungal Genet. Biol. 41:189-198(2004).
RN [7]
RP IDENTIFICATION IN THE EAS CLUSTER, FUNCTION, AND DOMAIN.
RX PubMed=15904941; DOI=10.1016/j.phytochem.2005.04.011;
RA Haarmann T., Machado C., Lubbe Y., Correia T., Schardl C.L.,
RA Panaccione D.G., Tudzynski P.;
RT "The ergot alkaloid gene cluster in Claviceps purpurea: extension of the
RT cluster sequence and intra species evolution.";
RL Phytochemistry 66:1312-1320(2005).
RN [8]
RP FUNCTION.
RC STRAIN=P1 / 1029/N5;
RX PubMed=16538694; DOI=10.1002/cbic.200500487;
RA Haarmann T., Ortel I., Tudzynski P., Keller U.;
RT "Identification of the cytochrome P450 monooxygenase that bridges the
RT clavine and ergoline alkaloid pathways.";
RL ChemBioChem 7:645-652(2006).
RN [9]
RP FUNCTION.
RX PubMed=17308187; DOI=10.1128/aem.00257-07;
RA Fleetwood D.J., Scott B., Lane G.A., Tanaka A., Johnson R.D.;
RT "A complex ergovaline gene cluster in epichloe endophytes of grasses.";
RL Appl. Environ. Microbiol. 73:2571-2579(2007).
RN [10]
RP FUNCTION.
RX PubMed=17720822; DOI=10.1128/aem.01040-07;
RA Lorenz N., Wilson E.V., Machado C., Schardl C.L., Tudzynski P.;
RT "Comparison of ergot alkaloid biosynthesis gene clusters in Claviceps
RT species indicates loss of late pathway steps in evolution of C.
RT fusiformis.";
RL Appl. Environ. Microbiol. 73:7185-7191(2007).
RN [11]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17560817; DOI=10.1016/j.fgb.2007.04.008;
RA Haarmann T., Lorenz N., Tudzynski P.;
RT "Use of a nonhomologous end joining deficient strain (Deltaku70) of the
RT ergot fungus Claviceps purpurea for identification of a nonribosomal
RT peptide synthetase gene involved in ergotamine biosynthesis.";
RL Fungal Genet. Biol. 45:35-44(2008).
RN [12]
RP FUNCTION, DOMAIN, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=19139103; DOI=10.1074/jbc.m807168200;
RA Ortel I., Keller U.;
RT "Combinatorial assembly of simple and complex D-lysergic acid alkaloid
RT peptide classes in the ergot fungus Claviceps purpurea.";
RL J. Biol. Chem. 284:6650-6660(2009).
RN [13]
RP FUNCTION.
RX PubMed=20118373; DOI=10.1128/aem.00737-09;
RA Lorenz N., Olsovska J., Sulc M., Tudzynski P.;
RT "Alkaloid cluster gene ccsA of the ergot fungus Claviceps purpurea encodes
RT chanoclavine I synthase, a flavin adenine dinucleotide-containing
RT oxidoreductase mediating the transformation of N-methyl-
RT dimethylallyltryptophan to chanoclavine I.";
RL Appl. Environ. Microbiol. 76:1822-1830(2010).
RN [14]
RP FUNCTION.
RC STRAIN=ATCC 20102 / Farmitalia FI 32/17;
RX PubMed=20735127; DOI=10.1021/ja105785p;
RA Cheng J.Z., Coyle C.M., Panaccione D.G., O'Connor S.E.;
RT "Controlling a structural branch point in ergot alkaloid biosynthesis.";
RL J. Am. Chem. Soc. 132:12835-12837(2010).
RN [15]
RP FUNCTION.
RX PubMed=21409592; DOI=10.1007/s00294-011-0336-4;
RA Goetz K.E., Coyle C.M., Cheng J.Z., O'Connor S.E., Panaccione D.G.;
RT "Ergot cluster-encoded catalase is required for synthesis of chanoclavine-I
RT in Aspergillus fumigatus.";
RL Curr. Genet. 57:201-211(2011).
RN [16]
RP FUNCTION.
RX PubMed=21494745; DOI=10.1039/c0ob01215g;
RA Matuschek M., Wallwey C., Xie X., Li S.M.;
RT "New insights into ergot alkaloid biosynthesis in Claviceps purpurea: an
RT agroclavine synthase EasG catalyses, via a non-enzymatic adduct with
RT reduced glutathione, the conversion of chanoclavine-I aldehyde to
RT agroclavine.";
RL Org. Biomol. Chem. 9:4328-4335(2011).
RN [17]
RP FUNCTION.
RX PubMed=24361048; DOI=10.1016/j.chembiol.2013.11.008;
RA Havemann J., Vogel D., Loll B., Keller U.;
RT "Cyclolization of D-lysergic acid alkaloid peptides.";
RL Chem. Biol. 21:146-155(2014).
CC -!- FUNCTION: D-lysergyl-peptide-synthetase subunit 1; part of the gene
CC cluster that mediates the biosynthesis of fungal ergot alkaloid
CC (PubMed:10071219, PubMed:14732265, PubMed:14700635, PubMed:15904941,
CC PubMed:17308187, PubMed:17720822). DmaW catalyzes the first step of
CC ergot alkaloid biosynthesis by condensing dimethylallyl diphosphate
CC (DMAP) and tryptophan to form 4-dimethylallyl-L-tryptophan
CC (PubMed:14732265). The second step is catalyzed by the
CC methyltransferase easF that methylates 4-dimethylallyl-L-tryptophan in
CC the presence of S-adenosyl-L-methionine, resulting in the formation of
CC 4-dimethylallyl-L-abrine (By similarity). The catalase easC and the
CC FAD-dependent oxidoreductase easE then transform 4-dimethylallyl-L-
CC abrine to chanoclavine-I which is further oxidized by easD in the
CC presence of NAD(+), resulting in the formation of chanoclavine-I
CC aldehyde (PubMed:20118373, PubMed:21409592). Agroclavine dehydrogenase
CC easG then mediates the conversion of chanoclavine-I aldehyde to
CC agroclavine via a non-enzymatic adduct reaction: the substrate is an
CC iminium intermediate that is formed spontaneously from chanoclavine-I
CC aldehyde in the presence of glutathione (PubMed:20735127,
CC PubMed:21494745). The presence of easA is not required to complete this
CC reaction (PubMed:21494745). Further conversion of agroclavine to
CC paspalic acid is a two-step process involving oxidation of agroclavine
CC to elymoclavine and of elymoclavine to paspalic acid, the second step
CC being performed by the elymoclavine oxidase cloA (PubMed:16538694,
CC PubMed:17720822). Paspalic acid is then further converted to D-lysergic
CC acid (PubMed:15904941). Ergopeptines are assembled from D-lysergic acid
CC and three different amino acids by the D-lysergyl-peptide-synthetases
CC composed each of a monomudular and a trimodular nonribosomal peptide
CC synthetase subunit (PubMed:14700635, PubMed:15904941). LpsB and lpsC
CC encode the monomodular subunits responsible for D-lysergic acid
CC activation and incorporation into the ergopeptine backbone
CC (PubMed:14700635). LpsA1 and A2 subunits encode the trimodular
CC nonribosomal peptide synthetase assembling the tripeptide portion of
CC ergopeptines (PubMed:14700635). LpsA1 is responsible for formation of
CC the major ergopeptine, ergotamine, and lpsA2 for alpha-ergocryptine,
CC the minor ergopeptine of the total alkaloid mixture elaborated by
CC C.purpurea (PubMed:17560817, PubMed:19139103). D-lysergyl-tripeptides
CC are assembled by the nonribosomal peptide synthetases and released as
CC N-(D-lysergyl-aminoacyl)-lactams (PubMed:24361048). Cyclolization of
CC the D-lysergyl-tripeptides is performed by the Fe(2+)/2-ketoglutarate-
CC dependent dioxygenase easH which introduces a hydroxyl group into N-(D-
CC lysergyl-aminoacyl)-lactam at alpha-C of the aminoacyl residue followed
CC by spontaneous condensation with the terminal lactam carbonyl group
CC (PubMed:24361048). {ECO:0000250|UniProtKB:Q50EL0,
CC ECO:0000269|PubMed:10071219, ECO:0000269|PubMed:14700635,
CC ECO:0000269|PubMed:14732265, ECO:0000269|PubMed:15904941,
CC ECO:0000269|PubMed:16538694, ECO:0000269|PubMed:17560817,
CC ECO:0000269|PubMed:19139103, ECO:0000269|PubMed:20118373,
CC ECO:0000269|PubMed:20735127, ECO:0000269|PubMed:21409592,
CC ECO:0000269|PubMed:21494745, ECO:0000269|PubMed:24361048,
CC ECO:0000305|PubMed:17308187, ECO:0000305|PubMed:17720822}.
CC -!- PATHWAY: Alkaloid biosynthesis; ergot alkaloid biosynthesis.
CC {ECO:0000269|PubMed:19139103}.
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:10071219). 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:10071219). Thus, an NRP
CC synthetase is generally composed of one or more modules and can
CC terminate in a thioesterase domain (TE) or reductase domain (R) that
CC releases the newly synthesized peptide from the enzyme
CC (PubMed:10071219). LpsA1 has a domain arrangement (A-T-C-A-T-C-A-T-Cyc)
CC with 3 A and 3 peptidyl carrier (PCP/T) domains, 2 C-domains, and a
CC terminal domain called the Cyc domain (PubMed:19139103). The Cyc domain
CC has limited similarity to both C and Cy domains of NRPS but is most
CC different in the so-called C3 and Cy3 motif of the latter domains,
CC suggesting a special mechanism in acyl diketopiperazine formation,
CC which is the final step of D-lysergyl peptide lactam synthesis
CC (PubMed:19139103). LpsA1 misses an N-terminal C domain in the first
CC module, leading to the conclusion that this C domain is located on the
CC other subunit (lpsB or lpsC) containing the D-lysergic acid module
CC (PubMed:19139103). {ECO:0000269|PubMed:10071219,
CC ECO:0000269|PubMed:14700635, ECO:0000269|PubMed:19139103}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of ergotamine but is
CC still able to produce ergocryptine (PubMed:17560817).
CC {ECO:0000269|PubMed:17560817}.
CC -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
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DR EMBL; JN186799; AET79183.1; -; Genomic_DNA.
DR EMBL; CAGA01000020; CCE30226.1; -; Genomic_DNA.
DR SMR; M1W0X8; -.
DR STRING; 1111077.M1W0X8; -.
DR EnsemblFungi; CCE30226; CCE30226; CPUR_04074.
DR VEuPathDB; FungiDB:CPUR_04074; -.
DR eggNOG; KOG1175; Eukaryota.
DR eggNOG; KOG1178; Eukaryota.
DR HOGENOM; CLU_224649_0_0_1; -.
DR OrthoDB; 4243at2759; -.
DR UniPathway; UPA00327; -.
DR Proteomes; UP000016801; Unassembled WGS sequence.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0035835; P:indole alkaloid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 1.10.1200.10; -; 3.
DR Gene3D; 3.30.300.30; -; 3.
DR Gene3D; 3.30.559.10; -; 3.
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; 3.
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; 2.
PE 1: Evidence at protein level;
KW Ligase; Phosphopantetheine; Phosphoprotein; Reference proteome; Repeat;
KW Transferase.
FT CHAIN 1..3584
FT /note="D-lysergyl-peptide-synthetase subunit 1"
FT /id="PRO_0000439106"
FT DOMAIN 848..917
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:19139103"
FT DOMAIN 1948..2016
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:19139103"
FT DOMAIN 3041..3109
FT /note="Carrier 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:19139103"
FT REGION 25..44
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 307..706
FT /note="Adenylation (A) domain 1"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:19139103"
FT REGION 962..1353
FT /note="Condensation (C) domain 1"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:19139103"
FT REGION 1396..1803
FT /note="Adenylation (A) domain 2"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:19139103"
FT REGION 2066..2483
FT /note="Condensation (C) domain 2"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:19139103"
FT REGION 2508..2906
FT /note="Adenylation (A) domain 3"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:19139103"
FT REGION 3174..3472
FT /note="Cyclization (Cyc) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:19139103"
FT MOD_RES 880
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 1980
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 3073
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 3584 AA; 393878 MW; BB81DE26ADAB2C78 CRC64;
MSIPIPEKLQ DLTAVKSPSA FGNSIESING DKNKSERHTA SSSAVSTSEI GHPCLLTNFK
LAVACSGPAI TKVATVNDKD SGSKLKNVIN GKDISASEVF KGAWSVVLGT YLAKSHVSLD
YGVMKPKGLG PETSCNARVP SENSEMSTSS FLLRANDTLL DIIRQNSMCA HTELRQKSSL
DDVESPKRCN TCVIYWPEIS CSEQLQIDAW MTILEENDQL TQYDCMIHFA SDMRCMLSYR
DQFMSENQAR HLAATMRVVL SSIASAPQQS LADVDVCSSL DYQTLSRWNL KAPIVSEVCV
HDLIEKSCCS RPNSQAVVSW DGCLTYNEMD RLSSHLAQRL RDAGVEPGVF VALCLDRCKW
AVIGIVAVMK AGGAFCALDP SYPVSRLKEM CRDLGITIVL TVKSNIQHAS PLASKVFALD
DDVYFESALS SAHESASWVS VSPHDPVYAV FTSGSTGKPK GIIMEHASFS ACALSSVKPL
QIADQDRVLH FASYAFDASV IEILAPLIAG ATVAIPSERA RLEDLPRAMT DLKATWAFLT
PTVARLYRPE QMPTLKTLCL GGEAVNASDT RSWSSKNLIS GYNPAECCPL GISGPLNDRM
PRSLGSTFAS QTAWIVDPKD HEKLLPAGAI GELAIEGPVV ARGYIHDVTC SDPSTPFVVK
LPPWLRRFRA TANRGNRIYL TGDLARLDCD DGSVHYLGRK DDQVKIHGQR VELAEIEHHL
EQHFVSLATK AVVMLLRPIS GRTVLAALIM PHQRLQHGNK SLESLLMEPG DVSQDFRANL
ASAASKLRLA LPSHMVPSVY LPIRHFSTTK SGKIDRGHLQ SLLLSLSPEN LYGCEETTHR
GEEPKSDREK LLQALFAQSL DLPCTRIDLD SNFFQLGGDS LSAMRLLALA LEEGISSIAY
QDIFSHPTLR EIVIVSTSAT SREPLYSETV ETPPFSLIKD PEMLIQIASE QCGSGVGKAD
IEDIYPCTHL QQSLMASTAH NPNAYVAILA FKLKSGVDRT RLERAWHIAC SGHAILRTRL
VQTDTGDCYQ VVVKKPPHWT ETNEVSDDGS TNSLLRTSFG LGRPLIQLHL TTDQLFVAMH
HALYDGWSLP MLIGELDLAY RELSVRRLPC LKNYVKYAMD SADAAASFWQ AELQDADPVH
FPAPSSLDYK PQPCAAMTIS VPLVNSPRRN VTLATEIQFA WAMTVYTYTG CKDVIFGLIS
SGRAAPVAQI ESILGPTFAC TPLRVSIDPQ GKLGEALDDL QYTIVEQSMF VHFGAQAIRQ
LGPNAAAACN FQTVLAVEAD GPETGEEEGS WFTRYDFLSD VASFSSYALT LRCKLSTRGV
EINAVYDKLM VDERQMGRIL AQFEHILTQI HSNETVHDDI GGLDKLSVSD WRQLQAWNSN
LPPAHPKGLG AHQAIQAKCQ AQPDATAIDA WDGCVTYGEL ERRAEKLAGL VRSHVSKPDQ
VVVLYFSKSW LTVVAQLAVL KAGAAFITLE ISQPVHYLQR VISALGPVLV LTSEDLFSAA
EDLQDNAVPV MAVDKDDLSD ATARTSQASS SACTVECDLM YIIATSGTTG MPKIVMTDHQ
AFMTNASPLM NGLGITSDSR VFQFCGYSFD LLIVEHFLTL LAGGCICIPS LHNRNNRFAA
SIVELEANWV GSPSSVLQLL DPQTVPTVKT IMQAGERLQQ GLVDRWASHV RLINAYGPAE
CSVGALARDT VRPDTDDVQN LGFATGSVCW IVNAETSEKL LPVPIGAEGE LIIEGHTLSR
GYLGDADKTN ASFLRLPNWL RDFRADRGQS QGHRVYLTGD IVRQNSDGSM SFVRRKDAQV
KIRGQRVELT DVEHQVERCF IGAHQVVTDI VQIPNSQSSI LVALVLTKDA MTNHKQQESL
LDQKSAGGLS ILAPTSSFTA NANAAETALQ DRMPAYMVPD LFVPVSDLPR EASGKIGRKA
IKQYLASLTQ QDWSRYSSTR KVPPSNATEH EISAIWARVL QIEPHTFGVH DSFFRLGGDS
ISGMQVAAAC GAAGISVTVK DMFEYRTIRK LALARGETQQ LTVGTTSTVS NASGIRQKKA
LHPFYPEGRL EVYMERMQSR LGQAIERIYP CSPIQQGILM SHARNPHHYD EVIQWKVAGD
VSCDISRMQR AWREVVSRHG ILRTLFLQVS EDSFLDQVVL KNYSPDISVC TNEEDVEPYR
PFEDSVPMHH LLVFQRSADD VTVYLRIHHA LVDGLSLHII RRDLELAYQG RLDELAQPPG
YHEYISYLQE KRSRKSLQEY WSSYLQGATG SLFPAVQDEP ASDGQYFGAV EIELGSIAKL
TQFCEEHKLG VTVVLHVVWA IIVQRYAATD EVCFGYMTSG RHVPVTNVEN VVGPLFNMLI
GRVKLAYHLS VLSTMYAYQE NFINSLDHQH QSLVETLHSI GSSAGDLFNT LITVVNDQPE
DHVSQSALRL VGDSVQSRSE YPITLNILNH ADKIKMQLSY HTSLLSGVSA NTIAKAFRFV
LQRTLEQPHE LLRALPVLDE DQMNNEFQKN RSVPPQVEEL IHDTIHQQCI RCPDSPSVCA
WDGNFTYRQL DDLSSALSEE IVRKGAGPEV TIPIVLEKTR WTPVAMLAVL KSGSSFVLMD
STHPAARLGA IIQDVGHPVI IVSAQTRSKV ATFSTDVVEV GDWLAREILV AKQQITRQNG
LLQATNAAYL VFTSGSTGKP KGAIVEHASL STAAKYMASR LHIDSASRVL QFSSHAWDIP
VTEVLVTLRM GGCVCVPSEE ERTGNLAKAS ERMKVNWALW TPTVARLFKP EEFPHLETLV
FAGEALSAAD LETWCDRVRL IQGYGPAECS LISTVTDPLT RSDNPRCIGL PSGCVAWVVN
RDTHELLAPP GAIGELVLEG PIVGRGYLGD PERAASAFIS PPAWLMKLRG SGSSIRLYKT
GDLVRQHVSS GLLTFVGRND DQVKVRGQRV EPGEVEGQVA QVFPGSQVIV LVVKRSAGAV
LAALVLQNGE DRSSAGETAN LFPPPSLAFA ALAKAAFSKL RETMPTYMIP SIILPLSYLP
KAATGKADRN LLRDRVASLS DEEIEAYVAA SVSHRPASTA MEAELQQLVG QVLQRPLHSI
SLDEDLFRLG MDSLTAMTIA SAARRRGWEV SVPIIFQHSR LSDLARIVEQ GQHGTSSRSQ
LEEARAILNK RLVSLLPEIC TKWDLREDQI THIAPTTYYQ HMALASDHEA FFGLYFSKPM
ASEALKAAAS RVVKLHSILR TAFVPLEDTY VQLTLCDFDL PSQEIQTNQA EVSAAMELFC
RDAADKTAGF GVPVTKLILM LDRQGDCLSL LLRLQRAQFD GVSVMRIMAD WRSALEHASC
SWEPAPSLDY ADFALGRVAQ NTPDVFGMWR DVLQGSSMTY LIPQEKYISM TDRAHAERLV
TSSCDIPLPE PAPGYTMATV AKAAWAICLA RETESEDLLF LQLVRNRHLA LDGIDKMVGC
SLNYVPVRVP LRRDWKISDL LHWLHQQHIR TMAGDTADWP DVVAKSTTWS SDTEFGSVIH
YLSAPAAPVY HFPGDTVAQF QLYDEKMTHT CPLVTCVEFP GPAEDSGRQM KILVTSAVGG
QDMVDRLLAV FRSLLCEANA QLDQPLSNIL QGLRDGDDAT GKAR
