ERYA1_SACER
ID ERYA1_SACER Reviewed; 3491 AA.
AC Q03131;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1993, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=6-deoxyerythronolide-B synthase EryA1, modules 1 and 2 {ECO:0000305};
DE Short=DEBS 1 {ECO:0000303|PubMed:1618327};
DE EC=2.3.1.94 {ECO:0000269|PubMed:21095573};
DE AltName: Full=6-deoxyerythronolide B synthase I {ECO:0000303|PubMed:1618327};
DE AltName: Full=Erythronolide synthase;
DE AltName: Full=ORF C {ECO:0000305};
GN Name=eryA;
OS Saccharopolyspora erythraea (Streptomyces erythraeus).
OC Bacteria; Actinobacteria; Pseudonocardiales; Pseudonocardiaceae;
OC Saccharopolyspora.
OX NCBI_TaxID=1836;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND SUBUNIT.
RX PubMed=2024119; DOI=10.1126/science.2024119;
RA Donadio S., Staver M.J., McAlpine J.B., Swanson S.J., Katz L.;
RT "Modular organization of genes required for complex polyketide
RT biosynthesis.";
RL Science 252:675-679(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 3474-3491.
RX PubMed=8386127; DOI=10.1016/0378-1119(93)90604-2;
RA Donadio S., Staver M.J.;
RT "IS1136, an insertion element in the erythromycin gene cluster of
RT Saccharopolyspora erythraea.";
RL Gene 126:147-151(1993).
RN [3]
RP IDENTIFICATION.
RX PubMed=1618327; DOI=10.1016/0014-5793(92)80624-p;
RA Caffrey P., Bevitt D.J., Staunton J., Leadlay P.F.;
RT "Identification of DEBS 1, DEBS 2 and DEBS 3, the multienzyme polypeptides
RT of the erythromycin-producing polyketide synthase from Saccharopolyspora
RT erythraea.";
RL FEBS Lett. 304:225-228(1992).
RN [4]
RP FUNCTION, PATHWAY, AND SUBUNIT.
RX PubMed=17328673; DOI=10.1146/annurev.biochem.76.053105.093515;
RA Khosla C., Tang Y., Chen A.Y., Schnarr N.A., Cane D.E.;
RT "Structure and mechanism of the 6-deoxyerythronolide B synthase.";
RL Annu. Rev. Biochem. 76:195-221(2007).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=21095573; DOI=10.1016/j.chembiol.2010.09.013;
RA Zhang H., Wang Y., Wu J., Skalina K., Pfeifer B.A.;
RT "Complete biosynthesis of erythromycin A and designed analogs using E. coli
RT as a heterologous host.";
RL Chem. Biol. 17:1232-1240(2010).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.79 ANGSTROMS) OF 1391-1872 IN COMPLEX WITH NADP,
RP FUNCTION, MUTAGENESIS OF ASP-1705 AND PHE-1748, COFACTOR, ACTIVE SITE, AND
RP SUBUNIT.
RX PubMed=16564177; DOI=10.1016/j.str.2006.01.009;
RA Keatinge-Clay A.T., Stroud R.M.;
RT "The structure of a ketoreductase determines the organization of the beta-
RT carbon processing enzymes of modular polyketide synthases.";
RL Structure 14:737-748(2006).
RN [7]
RP STRUCTURE BY NMR OF 3318-3408.
RX PubMed=17893358; DOI=10.1110/ps.073011407;
RA Alekseyev V.Y., Liu C.W., Cane D.E., Puglisi J.D., Khosla C.;
RT "Solution structure and proposed domain domain recognition interface of an
RT acyl carrier protein domain from a modular polyketide synthase.";
RL Protein Sci. 16:2093-2107(2007).
CC -!- FUNCTION: Involved in the biosynthesis of antibiotic erythromycin via
CC the biosynthesis of its aglycone precursor, 6-deoxyerythronolide B (6-
CC dEB). {ECO:0000269|PubMed:16564177, ECO:0000269|PubMed:21095573,
CC ECO:0000305|PubMed:17328673}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=6 (S)-methylmalonyl-CoA + 12 H(+) + 6 NADPH + propanoyl-CoA =
CC 6-deoxyerythronolide B + 6 CO2 + 7 CoA + H2O + 6 NADP(+);
CC Xref=Rhea:RHEA:23068, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16089, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57327, ChEBI:CHEBI:57392, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; EC=2.3.1.94;
CC Evidence={ECO:0000269|PubMed:21095573};
CC -!- COFACTOR:
CC Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC Evidence={ECO:0000305|PubMed:16564177};
CC Note=Binds 3 phosphopantetheines covalently. {ECO:0000305};
CC -!- PATHWAY: Antibiotic biosynthesis; erythromycin biosynthesis.
CC {ECO:0000305|PubMed:17328673, ECO:0000305|PubMed:21095573}.
CC -!- SUBUNIT: Homodimer (PubMed:16564177). Erythronolide synthase is
CC composed of EryAI, EryAII and EryAIII multimodular (2 modules)
CC polypeptides each coding for a functional synthase subunit which
CC participates in 2 of the six FAS-like elongation steps required for
CC formation of the polyketide. Module 1, 2, 3, 4, 5, and 6 participating
CC in biosynthesis steps 1, 2, 3, 4, 5, and 6, respectively.
CC {ECO:0000269|PubMed:16564177, ECO:0000305|PubMed:17328673,
CC ECO:0000305|PubMed:2024119}.
CC -!- MISCELLANEOUS: Type I modular polyketide synthases (PKSs) catalyze the
CC step-wise condensation of simple carboxylic acid derivatives.
CC Organizationally, type I PKSs are arranged into modules, wherein each
CC module is comprised of a set of catalytic activities that is
CC responsible for a single elongation of the polyketide chain and the
CC appropriate reductive processing of the beta-keto functionality. A
CC minimal elongation module contains an acyl transferase (AT) domain, an
CC acyl-carrier protein (ACP) domain, and a ketosynthase (KS) domain. The
CC AT domain is responsible for loading the methylmalonyl-CoA extender
CC unit onto the phosphopantetheinylated ACP domain. Subsequently, the KS
CC domain decarboxylates and then condenses the ACP-bound extender unit
CC with the growing polyketide chain obtained from the preceding module to
CC yield an ACP-bound beta-ketoacyl intermediate. In addition to the three
CC core domains, each elongation module may contain up to three additional
CC domains: a ketoreductase (KR), dehydratase (DH), and an enoyl reductase
CC (ER) that are responsible for the reductive processing of the beta-keto
CC functionality prior to the next extension step. The presence of a KR
CC domain alone gives rise to a beta-hydroxyl functionality, the presence
CC of both a KR and a DH domain generates an alkene, while the combination
CC of KR, DH, and ER results in complete reduction to the alkane. Finally,
CC a thioesterase (TE) domain, typically found at the terminus of the last
CC elongation module, catalyzes the termination of polyketide
CC biosynthesis. The activity of this domain results in cleavage of the
CC acyl chain from the adjacent ACP and formation of the macrocyclic ring.
CC KR controls the stereochemistry of the beta-hydroxyl group of a
CC polyketide (PubMed:16564177). {ECO:0000269|PubMed:16564177,
CC ECO:0000305|PubMed:17328673}.
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DR EMBL; M63676; AAA26493.2; -; Genomic_DNA.
DR EMBL; L07626; AAA26504.1; -; Genomic_DNA.
DR PIR; T43231; T43231.
DR PDB; 2FR0; X-ray; 1.81 A; A=1391-1872.
DR PDB; 2FR1; X-ray; 1.79 A; A=1391-1872.
DR PDB; 2JU1; NMR; -; A=3318-3408.
DR PDB; 2JU2; NMR; -; A=3318-3408.
DR PDB; 6W7S; X-ray; 2.25 A; A=1395-1875.
DR PDB; 6WH9; X-ray; 2.75 A; A/D/G=1395-1875.
DR PDBsum; 2FR0; -.
DR PDBsum; 2FR1; -.
DR PDBsum; 2JU1; -.
DR PDBsum; 2JU2; -.
DR PDBsum; 6W7S; -.
DR PDBsum; 6WH9; -.
DR SMR; Q03131; -.
DR PRIDE; Q03131; -.
DR ABCD; Q03131; 2 sequenced antibodies.
DR BioCyc; MetaCyc:MON-17077; -.
DR BRENDA; 2.3.1.94; 5518.
DR UniPathway; UPA00240; -.
DR EvolutionaryTrace; Q03131; -.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0047879; F:erythronolide synthase activity; IDA:UniProtKB.
DR GO; GO:0031177; F:phosphopantetheine binding; TAS:UniProtKB.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:InterPro.
DR GO; GO:0033068; P:macrolide biosynthetic process; IDA:UniProtKB.
DR Gene3D; 1.10.1200.10; -; 3.
DR Gene3D; 3.40.366.10; -; 3.
DR Gene3D; 3.40.47.10; -; 2.
DR InterPro; IPR001227; Ac_transferase_dom_sf.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR014043; Acyl_transferase.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR InterPro; IPR018201; Ketoacyl_synth_AS.
DR InterPro; IPR014031; Ketoacyl_synth_C.
DR InterPro; IPR014030; Ketoacyl_synth_N.
DR InterPro; IPR016036; Malonyl_transacylase_ACP-bd.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR032821; PKS_assoc.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR013968; PKS_KR.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 3.
DR Pfam; PF16197; KAsynt_C_assoc; 2.
DR Pfam; PF00109; ketoacyl-synt; 2.
DR Pfam; PF02801; Ketoacyl-synt_C; 2.
DR Pfam; PF08659; KR; 2.
DR Pfam; PF00550; PP-binding; 3.
DR SMART; SM00827; PKS_AT; 3.
DR SMART; SM00825; PKS_KS; 2.
DR SMART; SM00823; PKS_PP; 3.
DR SUPFAM; SSF47336; SSF47336; 3.
DR SUPFAM; SSF51735; SSF51735; 4.
DR SUPFAM; SSF52151; SSF52151; 3.
DR SUPFAM; SSF53901; SSF53901; 2.
DR SUPFAM; SSF55048; SSF55048; 3.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 2.
DR PROSITE; PS50075; CARRIER; 3.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Acyltransferase; Antibiotic biosynthesis;
KW Multifunctional enzyme; NADP; Phosphopantetheine; Phosphoprotein; Repeat;
KW Transferase.
FT CHAIN 1..3491
FT /note="6-deoxyerythronolide-B synthase EryA1, modules 1 and
FT 2"
FT /id="PRO_0000180293"
FT DOMAIN 412..487
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 1886..1961
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 3329..3407
FT /note="Carrier 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 1..484
FT /note="Loading domain"
FT /evidence="ECO:0000305"
FT REGION 57..372
FT /note="Acyltransferase 1"
FT /evidence="ECO:0000305"
FT REGION 386..410
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 507..1958
FT /note="Module 1"
FT /evidence="ECO:0000305"
FT REGION 507..931
FT /note="Beta-ketoacyl synthase 1"
FT /evidence="ECO:0000305"
FT REGION 1031..1352
FT /note="Acyltransferase 2"
FT /evidence="ECO:0000305"
FT REGION 1613..1790
FT /note="Beta-ketoacyl reductase 1"
FT /evidence="ECO:0000305"
FT REGION 1982..3404
FT /note="Module 2"
FT /evidence="ECO:0000305"
FT REGION 1982..2405
FT /note="Beta-ketoacyl synthase 2"
FT /evidence="ECO:0000305"
FT REGION 2508..2827
FT /note="Acyltransferase 3"
FT /evidence="ECO:0000305"
FT REGION 3057..3233
FT /note="Beta-ketoacyl reductase 2"
FT /evidence="ECO:0000305"
FT REGION 3456..3491
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 145
FT /note="Acyl-ester intermediate; for acyltransferase 1
FT activity"
FT /evidence="ECO:0000305"
FT ACT_SITE 677
FT /note="Acyl-thioester intermediate; for beta-ketoacyl
FT synthase 1 activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 1128
FT /note="Acyl-ester intermediate; for acyltransferase 2
FT activity"
FT /evidence="ECO:0000250|UniProtKB:Q03133,
FT ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 1760
FT /note="For beta-ketoacyl reductase 1 activity"
FT /evidence="ECO:0000250|UniProtKB:Q03132,
FT ECO:0000305|PubMed:16564177"
FT ACT_SITE 2148
FT /note="Acyl-thioester intermediate; for beta-ketoacyl
FT synthase 2 activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 2598
FT /note="Acyl-ester intermediate; for acyltransferase 3
FT activity"
FT /evidence="ECO:0000250|UniProtKB:Q03133,
FT ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 3203
FT /note="For beta-ketoacyl reductase 2 activity"
FT /evidence="ECO:0000305"
FT BINDING 1621..1624
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:16564177"
FT BINDING 1644..1647
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:16564177"
FT BINDING 1673..1674
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:16564177"
FT BINDING 1723
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:16564177"
FT BINDING 1745..1746
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:16564177"
FT BINDING 3065..3068
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT BINDING 3088..3091
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT BINDING 3117..3118
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT BINDING 3168
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT BINDING 3188..3189
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT SITE 1748
FT /note="Could be the principal determinant of
FT stereospecificity"
FT /evidence="ECO:0000305|PubMed:16564177"
FT MOD_RES 447
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 1921
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 3367
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MUTAGEN 1705
FT /note="D->A: Still able to produce the triketide lactone
FT (TKL), albeit at reduced titer (40%) compared to the wild-
FT type. Still able to produce the triketide lactone (TKL),
FT albeit at reduced titer (10%) compared to the wild-type;
FT when associated with G-1748."
FT /evidence="ECO:0000269|PubMed:16564177"
FT MUTAGEN 1748
FT /note="F->G: Still able to produce the triketide lactone
FT (TKL), albeit at reduced titer (10%) compared to the wild-
FT type; when associated with A-1705."
FT /evidence="ECO:0000269|PubMed:16564177"
FT HELIX 1397..1399
FT /evidence="ECO:0007829|PDB:2FR1"
FT STRAND 1400..1408
FT /evidence="ECO:0007829|PDB:2FR1"
FT STRAND 1419..1425
FT /evidence="ECO:0007829|PDB:2FR1"
FT HELIX 1431..1442
FT /evidence="ECO:0007829|PDB:2FR1"
FT TURN 1443..1445
FT /evidence="ECO:0007829|PDB:2FR0"
FT STRAND 1447..1452
FT /evidence="ECO:0007829|PDB:2FR1"
FT HELIX 1459..1466
FT /evidence="ECO:0007829|PDB:2FR1"
FT STRAND 1473..1477
FT /evidence="ECO:0007829|PDB:2FR1"
FT TURN 1479..1482
FT /evidence="ECO:0007829|PDB:2FR1"
FT HELIX 1490..1492
FT /evidence="ECO:0007829|PDB:2FR1"
FT HELIX 1494..1508
FT /evidence="ECO:0007829|PDB:2FR1"
FT STRAND 1515..1521
FT /evidence="ECO:0007829|PDB:2FR1"
FT HELIX 1534..1536
FT /evidence="ECO:0007829|PDB:2FR1"
FT HELIX 1537..1549
FT /evidence="ECO:0007829|PDB:2FR1"
FT HELIX 1551..1553
FT /evidence="ECO:0007829|PDB:2FR1"
FT STRAND 1554..1560
FT /evidence="ECO:0007829|PDB:2FR1"
FT HELIX 1568..1576
FT /evidence="ECO:0007829|PDB:2FR1"
FT STRAND 1584..1588
FT /evidence="ECO:0007829|PDB:2FR1"
FT STRAND 1591..1599
FT /evidence="ECO:0007829|PDB:2FR1"
FT STRAND 1613..1618
FT /evidence="ECO:0007829|PDB:2FR1"
FT TURN 1619..1621
FT /evidence="ECO:0007829|PDB:2FR1"
FT HELIX 1623..1635
FT /evidence="ECO:0007829|PDB:2FR1"
FT STRAND 1638..1646
FT /evidence="ECO:0007829|PDB:2FR1"
FT HELIX 1647..1649
FT /evidence="ECO:0007829|PDB:2FR1"
FT HELIX 1653..1662
FT /evidence="ECO:0007829|PDB:2FR1"
FT STRAND 1666..1671
FT /evidence="ECO:0007829|PDB:2FR1"
FT HELIX 1677..1685
FT /evidence="ECO:0007829|PDB:2FR1"
FT STRAND 1689..1691
FT /evidence="ECO:0007829|PDB:2FR0"
FT STRAND 1693..1698
FT /evidence="ECO:0007829|PDB:2FR1"
FT HELIX 1708..1710
FT /evidence="ECO:0007829|PDB:2FR1"
FT HELIX 1713..1719
FT /evidence="ECO:0007829|PDB:2FR1"
FT HELIX 1721..1734
FT /evidence="ECO:0007829|PDB:2FR1"
FT STRAND 1740..1747
FT /evidence="ECO:0007829|PDB:2FR1"
FT HELIX 1748..1751
FT /evidence="ECO:0007829|PDB:2FR1"
FT TURN 1758..1760
FT /evidence="ECO:0007829|PDB:2FR1"
FT HELIX 1761..1776
FT /evidence="ECO:0007829|PDB:2FR1"
FT STRAND 1782..1786
FT /evidence="ECO:0007829|PDB:2FR1"
FT STRAND 1789..1793
FT /evidence="ECO:0007829|PDB:2FR0"
FT TURN 1804..1807
FT /evidence="ECO:0007829|PDB:2FR1"
FT HELIX 1813..1825
FT /evidence="ECO:0007829|PDB:2FR1"
FT HELIX 1838..1845
FT /evidence="ECO:0007829|PDB:2FR1"
FT STRAND 1847..1849
FT /evidence="ECO:0007829|PDB:2FR1"
FT TURN 1853..1856
FT /evidence="ECO:0007829|PDB:2FR1"
FT HELIX 1858..1861
FT /evidence="ECO:0007829|PDB:2FR1"
FT HELIX 3318..3322
FT /evidence="ECO:0007829|PDB:2JU1"
FT HELIX 3327..3345
FT /evidence="ECO:0007829|PDB:2JU1"
FT HELIX 3351..3353
FT /evidence="ECO:0007829|PDB:2JU1"
FT STRAND 3356..3358
FT /evidence="ECO:0007829|PDB:2JU1"
FT HELIX 3360..3363
FT /evidence="ECO:0007829|PDB:2JU1"
FT HELIX 3368..3377
FT /evidence="ECO:0007829|PDB:2JU1"
FT HELIX 3378..3380
FT /evidence="ECO:0007829|PDB:2JU1"
FT HELIX 3389..3392
FT /evidence="ECO:0007829|PDB:2JU1"
FT HELIX 3396..3407
FT /evidence="ECO:0007829|PDB:2JU1"
SQ SEQUENCE 3491 AA; 365029 MW; 682BFC32C90FA8C4 CRC64;
MSGPRSRTTS RRTPVRIGAV VVASSTSELL DGLAAVADGR PHASVVRGVA RPSAPVVFVF
PGQGAQWAGM AGELLGESRV FAAAMDACAR AFEPVTDWTL AQVLDSPEQS RRVEVVQPAL
FAVQTSLAAL WRSFGVTPDA VVGHSIGELA AAHVCGAAGA ADAARAAALW SREMIPLVGN
GDMAAVALSA DEIEPRIARW DDDVVLAGVN GPRSVLLTGS PEPVARRVQE LSAEGVRAQV
INVSMAAHSA QVDDIAEGMR SALAWFAPGG SEVPFYASLT GGAVDTRELV ADYWRRSFRL
PVRFDEAIRS ALEVGPGTFV EASPHPVLAA ALQQTLDAEG SSAAVVPTLQ RGQGGMRRFL
LAAAQAFTGG VAVDWTAAYD DVGPNPALCR SSRRPRRKTS RPSPASTGTR HRTCCERLLA
VVNGETAALA GREADAEATF RELGLDSVLA AQLRAKVSAA IGREVNIALL YDHPTPRALA
EALAAGTEVA QRETRARTNE AAPGEPVAVV AMACRLPGGV STPEEFWELL SEGRDAVAGL
PTDRGWDLDS LFHPDPTRSG TAHQRGGGFL TEATAFDPAF FGMSPREALA VDPQQRLMLE
LSWEVLERAG IPPTSLQASP TGVFVGLIPQ EYGPRLAEGG EGVEGYLMTG TTTSVASGRI
AYTLGLEGPA ISVDTACSSS LVAVHLACQS LRRGESSLAM AGGVTVMPTP GMLVDFSRMN
SLAPDGRCKA FSAGANGFGM AEGAGMLLLE RLSDARRNGH PVLAVLRGTA VNSDGASNGL
SAPNGRAQVR VIQQALAESG LGPADIDAVE AHGTGTRLGD PIEARALFEA YGRDREQPLH
LGSVKSNLGH TQAAAGVAGV IKMVLAMRAG TLPRTLHASE RSKEIDWSSG AISLLDEPEP
WPAGARPRRA GVSSFGISGT NAHAIIEEAP QVVEGERVEA GDVVAPWVLS ASSAEGLRAQ
AARLAAHLRE HPGQDPRDIA YSLATGRAAL PHRAAFAPVD ESAALRVLDG LATGNADGAA
VGTSRAQQRA VFVFPGQGWQ WAGMAVDLLD TSPVFAAALR ECADALEPHL DFEVIPFLRA
EAARREQDAA LSTERVDVVQ PVMFAVMVSL ASMWRAHGVE PAAVIGHSQG EIAAACVAGA
LSLDDAARVV ALRSRVIATM PGNKGMASIA APAGEVRARI GDRVEIAAVN GPRSVVVAGD
SDELDRLVAS CTTECIRAKR LAVDYASHSS HVETIRDALH AELGEDFHPL PGFVPFFSTV
TGRWTQPDEL DAGYWYRNLR RTVRFADAVR ALAEQGYRTF LEVSAHPILT AAIEEIGDGS
GADLSAIHSL RRGDGSLADF GEALSRAFAA GVAVDWESVH LGTGARRVPL PTYPFQRERV
WLEPKPVARR STEVDEVSAL RYRIEWRPTG AGEPARLDGT WLVAKYAGTA DETSTAAREA
LESAGARVRE LVVDARCGRD ELAERLRSVG EVAGVLSLLA VDEAEPEEAP LALASLADTL
SLVQAMVSAE LGCPLWTVTE SAVATGPFER VRNAAHGALW GVGRVIALEN PAVWGGLVDV
PAGSVAELAR HLAAVVSGGA GEDQLALRAD GVYGRRWVRA AAPATDDEWK PTGTVLVTGG
TGGVGGQIAR WLARRGAPHL LLVSRSGPDA DGAGELVAEL EALGARTTVA ACDVTDRESV
RELLGGIGDD VPLSAVFHAA ATLDDGTVDT LTGERIERAS RAKVLGARNL HELTRELDLT
AFVLFSSFAS AFGAPGLGGY APGNAYLDGL AQQRRSDGLP ATAVAWGTWA GSGMAEGAVA
DRFRRHGVIE MPPETACRAL QNALDRAEVC PIVIDVRWDR FLLAYTAQRP TRLFDEIDDA
RRAAPQAPAE PRVGALASLP APEREEALFE LVRSHAAAVL GHASAERVPA DQAFAELGVD
SLSALELRNR LGAATGVRLP TTTVFDHPDV RTLAAHLAAE LGGATGAEQA APATTAPVDE
PIAIVGMACR LPGEVDSPER LWELITSGRD SAAEVPDDRG WVPDELMASD AAGTRAHGNF
MAGAGDFDAA FFGISPREAL AMDPQQRQAL ETTWEALESA GIPPETLRGS DTGVFVGMSH
QGYATGRPRP EDGVDGYLLT GNTASVASGR IAYVLGLEGP ALTVDTACSS SLVALHTACG
SLRDGDCGLA VAGGVSVMAG PEVFTEFSRQ GALSPDGRCK PFSDEADGFG LGEGSAFVVL
QRLSDARREG RRVLGVVAGS AVNQDGASNG LSAPSGVAQQ RVIRRAWARA GITGADVAVV
EAHGTGTRLG DPVEASALLA TYGKSRGSSG PVLLGSVKSN IGHAQAAAGV AGVIKVLLGL
ERGVVPPMLC RGERSGLIDW SSGEIELADG VREWSPAADG VRRAGVSAFG VSGTNAHVII
AEPPEPEPVP QPRRMLPATG VVPVVLSART GAALRAQAGR LADHLAAHPG IAPADVSWTM
ARARQHFEER AAVLAADTAE AVHRLRAVAD GAVVPGVVTG SASDGGSVFV FPGQGAQWEG
MARELLPVPV FAESIAECDA VLSEVAGFSV SEVLEPRPDA PSLERVDVVQ PVLFAVMVSL
ARLWRACGAV PSAVIGHSQG EIAAAVVAGA LSLEDGMRVV ARRSRAVRAV AGRGSMLSVR
GGRSDVEKLL ADDSWTGRLE VAAVNGPDAV VVAGDAQAAR EFLEYCEGVG IRARAIPVDY
ASHTAHVEPV RDELVQALAG ITPRRAEVPF FSTLTGDFLD GTELDAGYWY RNLRHPVEFH
SAVQALTDQG YATFIEVSPH PVLASSVQET LDDAESDAAV LGTLERDAGD ADRFLTALAD
AHTRGVAVDW EAVLGRAGLV DLPGYPFQGK RFWLLPDRTT PRDELDGWFY RVDWTEVPRS
EPAALRGRWL VVVPEGHEED GWTVEVRSAL AEAGAEPEVT RGVGGLVGDC AGVVSLLALE
GDGAVQTLVL VRELDAEGID APLWTVTFGA VDAGSPVARP DQAKLWGLGQ VASLERGPRW
TGLVDLPHMP DPELRGRLTA VLAGSEDQVA VRADAVRARR LSPAHVTATS EYAVPGGTIL
VTGGTAGLGA EVARWLAGRG AEHLALVSRR GPDTEGVGDL TAELTRLGAR VSVHACDVSS
REPVRELVHG LIEQGDVVRG VVHAAGLPQQ VAINDMDEAA FDEVVAAKAG GAVHLDELCS
DAELFLLFSS GAGVWGSARQ GAYAAGNAFL DAFARHRRGR GLPATSVAWG LWAAGGMTGD
EEAVSFLRER GVRAMPVPRA LAALDRVLAS GETAVVVTDV DWPAFAESYT AARPRPLLDR
IVTTAPSERA GEPETESLRD RLAGLPRAER TAELVRLVRT STATVLGHDD PKAVRATTPF
KELGFDSLAA VRLRNLLNAA TGLRLPSTLV FDHPNASAVA GFLDAELGTE VRGEAPSALA
GLDALEGALP EVPATEREEL VQRLERMLAA LRPVAQAADA SGTGANPSGD DLGEAGVDEL
LEALGRELDG D
