LPSA2_CLAP2
ID LPSA2_CLAP2 Reviewed; 3584 AA.
AC M1W5Z4; G8GV71;
DT 15-MAR-2017, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2013, sequence version 1.
DT 25-MAY-2022, entry version 37.
DE RecName: Full=D-lysergyl-peptide-synthetase subunit 1 {ECO:0000305};
DE EC=2.3.1.- {ECO:0000305|PubMed:15904941};
DE AltName: Full=Ergot alkaloid synthesis protein ps4 {ECO:0000303|PubMed:15904941};
DE AltName: Full=Nonribosomal peptide synthetase 1 {ECO:0000303|PubMed:15904941};
GN Name=lpsA2 {ECO:0000303|PubMed:17720822};
GN Synonyms=cpps4 {ECO:0000303|PubMed:15904941}; ORFNames=CPUR_04073;
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 {ECO:0000312|EMBL:AET79184.1};
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 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 [4]
RP FUNCTION.
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 [5]
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 [6]
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 [7]
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 [8]
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 [9]
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 [10]
RP FUNCTION.
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 [11]
RP FUNCTION, AND DOMAIN.
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 [12]
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 [13]
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 [14]
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 [15]
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 [16]
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:14732265, PubMed:14700635, PubMed:15904941, PubMed:17308187,
CC PubMed:17720822). DmaW catalyzes the first step of ergot alkaloid
CC biosynthesis by condensing dimethylallyl diphosphate (DMAP) and
CC tryptophan to form 4-dimethylallyl-L-tryptophan (PubMed:14732265). The
CC second step is catalyzed by the methyltransferase easF that methylates
CC 4-dimethylallyl-L-tryptophan in the presence of S-adenosyl-L-
CC methionine, resulting in the formation of 4-dimethylallyl-L-abrine (By
CC similarity). The catalase easC and the FAD-dependent oxidoreductase
CC easE then transform 4-dimethylallyl-L-abrine to chanoclavine-I which is
CC further oxidized by easD in the presence of NAD(+), resulting in the
CC formation of chanoclavine-I aldehyde (PubMed:20118373,
CC PubMed:21409592). Agroclavine dehydrogenase easG then mediates the
CC conversion of chanoclavine-I aldehyde to agroclavine via a non-
CC enzymatic adduct reaction: the substrate is an iminium intermediate
CC that is formed spontaneously from chanoclavine-I aldehyde in the
CC presence of glutathione (PubMed:20735127, PubMed:21494745). The
CC presence of easA is not required to complete this reaction
CC (PubMed:21494745). Further conversion of agroclavine to paspalic acid
CC is a two-step process involving oxidation of agroclavine to
CC 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:14700635, ECO:0000269|PubMed:14732265,
CC ECO:0000269|PubMed:15904941, ECO:0000269|PubMed:16538694,
CC ECO:0000269|PubMed:17560817, ECO:0000269|PubMed:19139103,
CC ECO:0000269|PubMed:20118373, ECO:0000269|PubMed:20735127,
CC ECO:0000269|PubMed:21409592, ECO:0000269|PubMed:21494745,
CC ECO:0000269|PubMed:24361048, ECO:0000305|PubMed:17308187,
CC ECO:0000305|PubMed:17720822}.
CC -!- PATHWAY: Alkaloid biosynthesis; ergot alkaloid biosynthesis.
CC {ECO:0000305|PubMed:15904941}.
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 (By similarity). Each module is responsible for the recognition
CC (via the A domain) and incorporation of a single amino acid into the
CC growing peptide product (By similarity). Thus, an NRP synthetase is
CC generally composed of one or more modules and can terminate in a
CC thioesterase domain (TE) or reductase domain (R) that releases the
CC newly synthesized peptide from the enzyme (By similarity). LpsA2 has a
CC domain arrangement (A-T-C-A-T-C-A-T-Cyc) with 3 A and 3 peptidyl
CC carrier (PCP/T) domains, 2 C-domains, and a terminal domain called the
CC Cyc domain (PubMed:15904941, PubMed:19139103). The Cyc domain has
CC 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 (By
CC similarity). LpsA2 misses an N-terminal C domain in the first module,
CC leading to the conclusion that this C domain is located on the other
CC subunit (lpsB or lpsC) containing the D-lysergic acid module (By
CC similarity). {ECO:0000250|UniProtKB:O94205,
CC ECO:0000269|PubMed:15904941, ECO:0000269|PubMed:19139103}.
CC -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
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DR EMBL; JN186799; AET79184.1; -; Genomic_DNA.
DR EMBL; CAGA01000020; CCE30225.1; -; Genomic_DNA.
DR SMR; M1W5Z4; -.
DR STRING; 1111077.M1W5Z4; -.
DR EnsemblFungi; CCE30225; CCE30225; CPUR_04073.
DR VEuPathDB; FungiDB:CPUR_04073; -.
DR eggNOG; KOG1175; Eukaryota.
DR eggNOG; KOG1178; Eukaryota.
DR HOGENOM; CLU_000022_60_4_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; 3.
DR SUPFAM; SSF47336; SSF47336; 3.
DR TIGRFAMs; TIGR01733; AA-adenyl-dom; 2.
DR PROSITE; PS00455; AMP_BINDING; 2.
DR PROSITE; PS50075; CARRIER; 3.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 2.
PE 3: Inferred from homology;
KW Ligase; Phosphopantetheine; Phosphoprotein; Reference proteome; Repeat;
KW Transferase.
FT CHAIN 1..3584
FT /note="D-lysergyl-peptide-synthetase subunit 1"
FT /id="PRO_0000439109"
FT DOMAIN 843..920
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 1943..2019
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 3036..3112
FT /note="Carrier 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
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 2019..2044
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2066..2483
FT /note="Condensation (C) domain 2"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:19139103"
FT REGION 2507..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; 394110 MW; 1A638D7641DDAA0C CRC64;
MSIPIPEKLQ DLTAVKSPSA FGNSIESINR DKSNSEWHIS SGSAVSTFEA HQPCLLTNFK
SAATYSGPAI TQVVKVNDKT SGSKLNNAVN DRDLYAAEVF KGAWAVVLGT YLAKSHVSLD
YGIMSPKGLV PETACNARFT SETSEMSTSS FLLRANDTLL DIIRKNSMYA HTESRQNLAL
DDAEGAKWCN TCVMYWPEIS CSKPLQTDAW MAVLVETKQL TQYDCMVHFA SDMRCMLSYR
DQFMSESQAR HLAATMRVVL SSIVSAPQQS LADVDMCSSL DYQTLSRWNL KAPIVSEVCV
HDLIEKSCCS RPNSQAVVSW DGCLTYNEMD RLSSHLAQRL RDAGVEPGVF VALCLDRCKW
AVIGIVAVLK AGGAFCALDP SYPVSRLKKM CQDLGITSVL TVKSNIQHAS PLASKVFVLD
DNLHSESALS STKEHAARSC VSPHDPVYAI FTSGSTGKPK GIIVEHASFS ACALGSKEAF
SFEPRDRVLH FSSYAFDASV VEILAPLIAG ATVAIPSERA RLEDLPRAMT ELGVTWAFLT
PTVARLYRPT QMPSLNTLCL VGEAVNASDV KAWSSKRLIS GYNPAECCPA GISGPINHNM
SRRLGSTFPS QVAWIVDSKD HEKLLPVGAI GELAIEGSVV ARGYIHDPTC SDPLTPFVVK
PPSWLRRFRT NVNRGNRIYL TGDLARRDCD DGSVHYLGRK DNQVKIHGQR VELAEIEHHL
EQHFSSLAIK VVVMLLQPVS GHTALIALIM PDQRLDNSDK VSKSLLIELE DVSQDLRAQL
ASAASKLRLA LPSHMVPSVY LPVRHFPTLK SGKIDRNHLQ LLLLSLSSES LYGSGETKHR
GEEPKSDREI LLRDLFAQAL DLPRTEIDLD SNFFQLGGDS LSAMRLLALA LEEGISSIAY
QDIFSHPTLT QLVLVSTSAA SLEPLSSATV EMAPFSLIKD SEMLIQMASK QCGSGVGKAD
IEDIYPCTHL QQSLMASTDH NPNAYVAILA FKLKSGIDRT RLGRAWHIAC SGHAILRTRL
VQTDTGDCYQ VVVKKPPHWT ETNEVSDDGS TIPLSCTSFG LGYPLIQLHL TSNRLFVAMH
HALYDGWSLP VLIGELDLAY RELSVRRLPC LKNYVKYTMD SADAAASFWR AELQDADPVH
FPEPSGLDYK PQPCAAMTVS VPLANSRCRN VTLATEIQFA WAMTVYTYTG CKDVIFGLIS
SGRAAPVAQI ESMLGPTFAC TPLRVSIDPQ GKLGEALDDL QYTVVEQSLF VHFGAQAIRQ
LGPNAAAACN FQTVLAVEAD GPDAGEEEGC WFTRYDFLSE VASFSSHALT LRCKLSTRGV
EINAVYDKAV VDERQMGRIL AQFEHILTQI HSNETINDSI GGLDKLSGSD WRQLQAWNSD
LPPLHPKGLG AHQAIQAKCQ AQPDATAIDA WDGRVTYGEL ERRAERLADL VRGHVSEPDQ
VVVLYFTKSW LTVVAQLAVL KASAAFITLD ITQPPHYLRR IIAALGPILI LTSEELYSAA
EELQEDEVPV MAVDKDNLSH ATAIASQTSS SACTVDCELM YVVATSGTTG MPKIIMTNHQ
SFMTNASPLT NRMGITAESR VFQFCGYSFD LMIAEHLLTL LAGGCICIPS LHNRDNRFAA
SIVEFKANWI GSPSSVLQLL DPQTVPTVKT IMQGGERLLQ GLVDRWASHA RLLNAYGPSE
CTMIMSVSDT VRPDTRDVQN VGFSTGCICW IVDAQHPDKL LPVPIGAEGE LIIEGHILSR
GYLGDADKTN AAFLALPGWL KDFRADRGQS QGHRVYRTGD MVRQNSDGSI SFVRRKDAQV
KVRGQRVELA DVEHQVERCF SGAHQAVTDI VQIPGSQSSM LVALILTKEI MTNHEHQEPS
SDQTPAGGLS ILIPNSSFTA DANAAQTALQ DRMPAYMVPD LFVPVSEFPR EASGKVGRKA
IKQYLASLTQ QDWARYSSTR KVPPSNATEH EIHAIWARVL QIEPHTFGVH DSFFRLGGDS
ISSMQVAAAC GAAGISVTVK DMFEYRIIRK LALARGATPQ GDIATTSTKG DESGSKHETA
PHGFYPEGRL EVYMERMQSR LGQALERIYP CSPIQQGILM SHARNPHHYD EMIQWRVAGD
VPCDISRMQR AWREVVSRHG ILRTLFLQVS EDSFLDQVVL KNYSPDISVY TDREDGEAYR
PFEDSVPMHQ LLVFQRSADD VIVSLRIHHA LVDGISLHII RRDLELAYQG CLHELAEPPA
YHEYISYLQE TRLRKSPEEY WKSYLRGATG ALFPAVQDEP ARDGMYFGAV EVELGPSANL
AQFCEEHKLG VTVVLHVVWA IIVQRYAATD DVCFGYMTSG RHVSVVNAEN MVGPLFNMLI
GRVKLAYHLS LLSAMYTYQE DFINSLDHQH QSLVETLHSI GSSAGDLFNT LITVVNDQPE
EHASRSALRL VGDAVQSRSE YPITLNILNR TDKMKMQLSY HTSLLSSVSA NTIAKTFRFV
LQRTLERPHE LLRALQVLDE DQMNIVFAQN RCVPPEVDDF IHDTIHQQCL RCPDSPSVCA
WDGNFTYRQL DELSSALSEE IVRKGAGPEV TIPIVLEKTR WTPVAMLAVL KSGSSFVLMD
STHPAARLGA IVQAIGPPVI IVSAQTRSKV ATFSTDVVEV GNWLAREILV AKQHVTRQNG
LLQATNAAYL VFTSGSTGKP KGAIVEHASL STAAKYMASR LHIDSASRVL QFSSHAWDIP
VTEVLVTLRM GGCVCVPSEE ERTGNLAKAS ERMKVNWALW TPTVARLFKP EEFPHLETLV
FAGEALSATD LETWCDRVRL VQGYGPAECS LISTVTDPLT RSDNPRCIGL PSGCVAWVVN
RDTHELLAPP GAIGELVLEG PIVGRGYLGD PGRAASAFIS PPAWLMRLRG SGSSIRLYKT
GDLVRQHVSS GLLTFVGRND DQVKVRGQRV EPGEVEGQVA QVFPGSQVIV LVVKRSSGAV
LAALVLQNGE DRSSAGETAN LFPPPSLAFA ALAKAAFSKL RETMPTYMIP SIILPLSYLP
KAATGKADRN LLRDRVASLS DAEIEAYVAA SVSHRPASTA MEAELQQLVG QVLQRPLHSI
SLDEDLFRLG MDSLTAMTLA SAARRRGWEV SVPIIFQHSR VSDLARIVEQ GQHGTSSRSQ
LEEARAVLNK RLVSLLPEIC TKWDLREDQI THIAPTTYYQ HMALASDHEA FFGLYFSKPV
ASEALKAAAS RVVKLHSILR TAFVPLEDTY VQLTLCDFDL PSQEIQTNEA EVSAAMELFC
RDAADKTAGF GVPVTKLILM LDRQGDCPSL LLRLQRAQFD GVSVMRIMAD WRSALEHASC
SWEPAPSLDY ADFALGRVAQ NTPDVFGMWR DVLQGSSMTY LVPQQEYISM TDRAHAERLV
TSSCDIPLPE PAPGYTMATV AKAAWAICLS RETQSEDLLF LQLVRNRHLA LDGIDKMVGC
SLNYVPVRVP LRRDWKTSDL LHWLHQQHIR TMTGHTADWP DLVAKSTTWS SDTEFGSVIH
YLSAPAAPVY HFPGDTVAQF QLYDEKMTHT CPLVTCIEFP GPTEDSGRQM KILVTSAVGG
QDMVDRLLAV FRSLLCEANA QLDQSVSNIL QGLRDGDDAM GKAR
