PKS12_MYCTU
ID PKS12_MYCTU Reviewed; 4151 AA.
AC I6XD69; L0TA10;
DT 02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 1.
DT 03-AUG-2022, entry version 63.
DE RecName: Full=Mycoketide-CoA synthase {ECO:0000305};
DE EC=2.3.1.295 {ECO:0000269|PubMed:15611286, ECO:0000269|PubMed:18613748};
DE AltName: Full=Polyketide synthase Pks12 {ECO:0000305};
GN Name=pks12 {ECO:0000312|EMBL:CCP44821.1};
GN Synonyms=msl6 {ECO:0000303|PubMed:12819062};
GN OrderedLocusNames=Rv2048c {ECO:0000312|EMBL:CCP44821.1};
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP DISRUPTION PHENOTYPE.
RC STRAIN=H37Rv;
RX PubMed=12819062; DOI=10.1128/iai.71.7.3794-3801.2003;
RA Sirakova T.D., Dubey V.S., Kim H.J., Cynamon M.H., Kolattukudy P.E.;
RT "The largest open reading frame (pks12) in the Mycobacterium tuberculosis
RT genome is involved in pathogenesis and dimycocerosyl phthiocerol
RT synthesis.";
RL Infect. Immun. 71:3794-3801(2003).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=15611286; DOI=10.1084/jem.20041429;
RA Matsunaga I., Bhatt A., Young D.C., Cheng T.Y., Eyles S.J., Besra G.S.,
RA Briken V., Porcelli S.A., Costello C.E., Jacobs W.R. Jr., Moody D.B.;
RT "Mycobacterium tuberculosis pks12 produces a novel polyketide presented by
RT CD1c to T cells.";
RL J. Exp. Med. 200:1559-1569(2004).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, REACTION MECHANISM, SUBUNIT, DOMAIN, AND
RP MUTAGENESIS OF CYS-2226 AND SER-2672.
RX PubMed=18613748; DOI=10.1371/journal.pbio.0060163;
RA Chopra T., Banerjee S., Gupta S., Yadav G., Anand S., Surolia A., Roy R.P.,
RA Mohanty D., Gokhale R.S.;
RT "Novel intermolecular iterative mechanism for biosynthesis of mycoketide
RT catalyzed by a bimodular polyketide synthase.";
RL PLoS Biol. 6:e163-e163(2008).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
CC -!- FUNCTION: Involved in the synthesis of beta-D-mannosyl
CC phosphomycoketide (MPM), an antigenic mycobacterial polyketide
CC (PubMed:15611286, PubMed:18613748). Binds a fatty acyl-CoA as a starter
CC unit, and extends it by five rounds of alternative additions of
CC malonyl-CoA and methylmalonyl-CoA extender units. Depending on the
CC starter unit, the enzyme forms mycoketide-CoAs of different lengths
CC (PubMed:15611286, PubMed:18613748). Shows preference for small-/medium-
CC chain starter fatty acyl substrates (PubMed:18613748). Uses a hybrid
CC modularly iterative mechanism, by forming a supramolecular assembly to
CC perform repetitive cycles of iterations (PubMed:18613748).
CC {ECO:0000269|PubMed:15611286, ECO:0000269|PubMed:18613748}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5 (S)-methylmalonyl-CoA + a medium-chain fatty acyl-CoA + 32
CC H(+) + 5 malonyl-CoA + 22 NADPH = a mycoketide-CoA + 10 CO2 + 10 CoA
CC + 11 H2O + 22 NADP(+); Xref=Rhea:RHEA:58028, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57327, ChEBI:CHEBI:57384, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:90546, ChEBI:CHEBI:142474;
CC EC=2.3.1.295; Evidence={ECO:0000269|PubMed:15611286,
CC ECO:0000269|PubMed:18613748};
CC -!- PATHWAY: Lipid metabolism; fatty acid metabolism. {ECO:0000305}.
CC -!- SUBUNIT: Forms a large supramolecular assembly mediated through
CC specific interactions between the N- and C-terminus linkers.
CC {ECO:0000269|PubMed:18613748}.
CC -!- INTERACTION:
CC I6XD69; I6XD69: pks12; NbExp=2; IntAct=EBI-16359004, EBI-16359004;
CC -!- DOMAIN: Contains 12 catalytic domains constituting two modules. Both
CC modules contain a complete set of catalytic and auxiliary domains.
CC {ECO:0000305|PubMed:18613748}.
CC -!- DISRUPTION PHENOTYPE: Deletion of the gene completely abolishes the
CC ability of the strain to activate CD1c-restricted T cells
CC (PubMed:15611286). Growth of the mutant is attenuated in mouse alveolar
CC macrophage cell line, and the virulence of the mutant in vivo is highly
CC attenuated in a murine model (PubMed:12819062). Sirakova et al. showed
CC that disruption of the gene causes a drastic decrease in the synthesis
CC of dimycocerosyl phthiocerol (DIM), but Matsunaga et al. demonstrated
CC later that DIM is produced by the disruption mutant (PubMed:12819062,
CC PubMed:15611286). {ECO:0000269|PubMed:12819062,
CC ECO:0000269|PubMed:15611286}.
CC -!- MISCELLANEOUS: The alkane moiety distinguishes these mycobacterial
CC lipid antigens from mammalian mannosyl beta-1-phosphodolichol (MPD) and
CC is necessary for activation of CD1c-restricted T cells.
CC {ECO:0000269|PubMed:15611286}.
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DR EMBL; AL123456; CCP44821.1; -; Genomic_DNA.
DR RefSeq; NP_216564.2; NC_000962.3.
DR RefSeq; WP_010886138.1; NC_018143.2.
DR SMR; I6XD69; -.
DR STRING; 83332.Rv2048c; -.
DR PaxDb; I6XD69; -.
DR PRIDE; I6XD69; -.
DR GeneID; 888350; -.
DR KEGG; mtu:Rv2048c; -.
DR PATRIC; fig|83332.111.peg.2283; -.
DR TubercuList; Rv2048c; -.
DR eggNOG; COG0604; Bacteria.
DR eggNOG; COG3321; Bacteria.
DR BioCyc; MetaCyc:G185E-6251-MON; -.
DR UniPathway; UPA00199; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0004312; F:fatty acid synthase activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:InterPro.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0071770; P:DIM/DIP cell wall layer assembly; IBA:GO_Central.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IBA:GO_Central.
DR Gene3D; 1.10.1200.10; -; 2.
DR Gene3D; 3.10.129.110; -; 2.
DR Gene3D; 3.40.366.10; -; 2.
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; IPR013154; ADH_N.
DR InterPro; IPR011032; GroES-like_sf.
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; IPR020807; PKS_dehydratase.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR020843; PKS_ER.
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; 2.
DR Pfam; PF08240; ADH_N; 1.
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; 2.
DR Pfam; PF14765; PS-DH; 2.
DR SMART; SM00827; PKS_AT; 2.
DR SMART; SM00826; PKS_DH; 2.
DR SMART; SM00829; PKS_ER; 2.
DR SMART; SM00825; PKS_KS; 2.
DR SMART; SM00823; PKS_PP; 2.
DR SUPFAM; SSF47336; SSF47336; 2.
DR SUPFAM; SSF50129; SSF50129; 2.
DR SUPFAM; SSF51735; SSF51735; 6.
DR SUPFAM; SSF52151; SSF52151; 2.
DR SUPFAM; SSF53901; SSF53901; 2.
DR SUPFAM; SSF55048; SSF55048; 2.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 2.
DR PROSITE; PS50075; CARRIER; 2.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 2.
PE 1: Evidence at protein level;
KW Acyltransferase; Coiled coil; Fatty acid metabolism; Lipid metabolism;
KW Multifunctional enzyme; Phosphopantetheine; Phosphoprotein;
KW Reference proteome; Transferase.
FT CHAIN 1..4151
FT /note="Mycoketide-CoA synthase"
FT /id="PRO_0000451583"
FT DOMAIN 1963..2038
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 3995..4070
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 35..2038
FT /note="Module 1"
FT /evidence="ECO:0000305"
FT REGION 35..407
FT /note="Beta-ketoacyl synthase 1"
FT /evidence="ECO:0000305"
FT REGION 559..880
FT /note="Acyltransferase 1"
FT /evidence="ECO:0000305"
FT REGION 926..1194
FT /note="Dehydratase 1"
FT /evidence="ECO:0000305"
FT REGION 1366..1671
FT /note="Enoyl reductase 1"
FT /evidence="ECO:0000305"
FT REGION 1680..1858
FT /note="Beta-ketoacyl reductase 1"
FT /evidence="ECO:0000305"
FT REGION 2057..4070
FT /note="Module 2"
FT /evidence="ECO:0000305"
FT REGION 2057..2430
FT /note="Beta-ketoacyl synthase 2"
FT /evidence="ECO:0000305"
FT REGION 2582..2893
FT /note="Acyltransferase 2"
FT /evidence="ECO:0000305"
FT REGION 2940..3215
FT /note="Dehydratase 2"
FT /evidence="ECO:0000305"
FT REGION 3395..3701
FT /note="Enoyl reductase 2"
FT /evidence="ECO:0000305"
FT REGION 3710..3888
FT /note="Beta-ketoacyl reductase 2"
FT /evidence="ECO:0000305"
FT COILED 2..32
FT /evidence="ECO:0000255"
FT ACT_SITE 203
FT /note="Acyl-thioester intermediate; for beta-ketoacyl
FT synthase 1 activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 650
FT /note="Acyl-ester intermediate; for acyltransferase 1
FT activity"
FT /evidence="ECO:0000250|UniProtKB:Q03133"
FT ACT_SITE 1828
FT /note="For beta-ketoacyl reductase 1 activity"
FT /evidence="ECO:0000250|UniProtKB:Q03131"
FT ACT_SITE 2226
FT /note="Acyl-thioester intermediate; for beta-ketoacyl
FT synthase 2 activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 2672
FT /note="Acyl-ester intermediate; for acyltransferase 2
FT activity"
FT /evidence="ECO:0000250|UniProtKB:Q03133"
FT ACT_SITE 3858
FT /note="For beta-ketoacyl reductase 2 activity"
FT /evidence="ECO:0000250|UniProtKB:Q03131"
FT MOD_RES 1998
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 4030
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MUTAGEN 2226
FT /note="C->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:18613748"
FT MUTAGEN 2672
FT /note="S->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:18613748"
SQ SEQUENCE 4151 AA; 431607 MW; 433C816243C141B2 CRC64;
MVDQLQHATE ALRKALVQVE RLKRTNRALL ERSSEPIAIV GMSCRFPGGV DSPEGLWQMV
ADARDVMSEF PTDRGWDLAG LFDPDPDVRH KSYARTGGFV DGVADFDPAF FGISPSEALA
MDPQHRMLLE LSWEALERAG IDPTGLRGSA TGVFAGLIVG GYGMLAEEIE GYRLTGMTSS
VASGRVAYVL GLEGPAVSVD TACSSSLVAL HMAVGSLRSG ECDLALAGGV TVNATPTVFV
EFSRHRGLAP DGRCKPYAGR ADGVGWSEGG GMLVLQRLSD ARRLGHPVLA VVVGSAVNQD
GASNGLTAPN GPSQQRVVRA ALANAGLSAA EVDVVEGHGT GTTLGDPIEA QALLATYGQD
RGEPGEPLWL GSVKSNMGHT QAAAGVAGVI KMVLAMRHEL LPATLHVDVP SPHVDWSAGA
VELLTAPRVW PAGARTRRAG VSSFGISGTN AHVIIEAVPV VPRREAGWAG PVVPWVVSAK
SESALRGQAA RLAAYVRGDD GLDVADVGWS LAGRSVFEHR AVVVGGDRDR LLAGLDELAG
DQLGGSVVRG TATAAGKTVF VFPGQGSQWL GMGIELLDTA PAFAQQIDAC AEAFAEFVDW
SLVDVLRGAP GAPGLDRVDV VQPVLFAVMV SLAELWKSVA VHPDAVIGHS QGEIAAAYVA
GALSLRDAAR VVTLRSKLLA GLAGPGGMVS IACGADQARD LLAPFGDRVS IAVVNGPSAV
VVSGEVGALE ELIAVCSTKE LRTRRIEVDY ASHSVEVEAI RGPLAEALSG IEPRSTRTVF
FSTVTGNRLD TAGLDADYWY RNVRQTVLFD QAVRNACEQG YRTFIESSPH PALITGVEET
FAACTDGDSE AIVVPTLGRG DGGLHRFLLS AASAFVAGVA VNWRGTLDGA GYVELPTYAF
DKRRFWLSAE GSGADVSGLG LGASEHPLLG AVVDLPASGG VVLTGRLSPN VQPWLADHAV
SDVVLFPGTG FVELAIRAGD EVGCSVLDEL TLAAPLLLPA TGSVAVQVVV DAGRDSNSRG
VSIFSRADAQ AGWLLHAEGI LRPGSVEPGA DLSVWPPAGA VTVDVADGYE RLATRGYRYG
PAFRGLTAMW ARGEEIFAEV RLPEAAGGVG GFGVHPALLD AVLHAVVIAG DPDELALPFA
WQGVSLHATG ASAVRARIAP AGPSAVSVEL ADGLGLPVLS VASMVARPVT ERQLLAAVSG
SGPDRLFEVI WSPASAATSP GPTPAYQIFE SVAADQDPVA GSYVRSHQAL AAVQSWLTDH
ESGVLVVATR GAMALPREDV ADLAGAAVWG LVRSAQTEHP GRIVLVDSDA ATDDAAIAMA
LATGEPQVVL RGGQVYTARV RGSRAADAIL VPPGDGPWRL GLGSAGTFEN LRLEPVPNAD
APLGPGQVRV AMRAIAANFR DIMITLGMFT HDALLGGEGA GVVVEVGPGV TEFSVGDSVF
GFFPDGSGTL VAGDVRLLLP MPADWSYAEA AAISAVFTTA YYAFIHLADV QPGQRVLIHA
GTGGVGMAAV QLARHLGLEV FATASKGKWD TLRAMGFDDD HISDSRSLEF EDKFRAATGG
RGFDVVLDSL AGEFVDASLR LVAPGGVFLE MGKTDIRDPG VIAQQYPGVR YRAFDLFEPG
RPRMHQYMLE LATLFGDGVL RPLPVTTFDV RRAPAALRYL SQARHTGKVV MLMPGSWAAG
TVLITGGTGM AGSAVARHVV ARHGVRNLVL VSRRGPDAPG AAELVAELAA AGAQVQVVAC
DAADRAALAK VIADIPVQHP LSGVIHTAGA LDDAVVMSLT PDRVDVVLRS KVDAAWHLHE
LTRDLDVSAF VMFSSMAGLV GSSGQANYAA ANSFLDALAA HRRAHGLPAI SLGWGLWDQA
SAMTGGLDAA DLARLGREGV LALSTAEALE LFDTAMIVDE PFLAPARIDL TALRAHAVAV
PPMFSDLASA PTRRQVDDSV AAAKSKSALA HRLHGLPEAE QHAVLLGLVR LHIATVLGNI
TPEAIDPDKA FQDLGFDSLT AVEMRNRLKS ATGLSLSPTL IFDYPTPNRL ASYIRTELAG
LPQEIKHTPA VRTTSEDPIA IVGMACRYPG GVNSPDDMWD MLIQGRDVLS EFPADRGWDL
AGLYNPDPDA AGACYTRTGG FVDGVGDFDP AFFGVGPSEA LAMDPQHRML LELSWEALER
AGIDPTGLRG SATGVFAGVM TQGYGMFAAE PVEGFRLTGQ LSSVASGRVA YVLGLEGPAV
SVDTACSSSL VALHMAVGSL RSGECDLALA GGVTVNATPD IFVEFSRWRG LSPDGRCKAF
AAAADGTGFS EGGGMLVLQR LSDARRLGHP VLAVVVGSAV NQDGASNGLT APNGPSQQRV
VRAALANAGL SAAEVDVVEG HGTGTTLGDP IEAQALLATY GQDRGEPGEP LWLGSVKSNM
GHTQAAAGVA GVIKMVLAMR HELLPATLHV DVPSPHVDWS AGAVELLTAP RVWPAGARTR
RAGVSSFGIS GTNAHVIIEA VPVVPRREAG WAGPVVPWVV SAKSESALRG QAARLAAYVR
GDDGLDVADV GWSLAGRSVF EHRAVVVGGD RDRLLAGLDE LAGDQLGGSV VRGTATAAGK
TVFVFPGQGS QWLGMGMGLH AGYPVFAEAF NTVVGELDRH LLRPLREVMW GHDENLLNST
EFAQPALFAV EVALFRLLGS WGVRPDFVMG HSIGELSAAH VAGVLSLENA AVLVAARGRL
MQALPAGGAM VAVQAAEEEV RPLLSAEVDI AAVNGPASLV ISGAQNAVAA VADQLRADGR
RVHQLAVSHA FHSPLMDPMI DEFAAVAAGI AIGRPTIGVI SNVTGQLAGD DFGSAAYWRR
HIRQAVRFAD SVRFAQAAGG SRFLEVGPSG GLVASIEESL PDVAVTTMSA LRKDRPEPAT
LTNAVAQGFV TGMDLDWRAV VGEAQFVELP TYAFQRRRFW LSGDGVAADA AGLGLAASEH
ALLGAVIDLP ASGGVVLTGR LSPSVQGWLA DHSVAGVTIF PGAGFVELAI RAGDEVGCGV
VDELTLAAPL VLPASGSVAV QVVVNGPDES GVRGVSVYSR GDVGTGWVLH AEGALRAGSA
EPTADLAMWP PAGAVPVEVA DGYQQLAERG YGYGPAFRGL TAMWRRGDEV FAEVALPADA
GVSVTGFGVH PVLLDAALHA VVLSAESAER GQGSVLVPFS WQGVSLHAAG ASAVRARIAP
VGPSAVSIEL ADGLGLPVLS VASMLARPVT DQQLRAAVSS SGPDRLFEVT WSPQPSAAVE
PLPVCAWGTT EDSAAVVFES VPLAGDVVAG VYAATSSVLD VLQSWLTRDG AGVLVVMTRG
AVALPGEDVT DLAGAAVWGL VRSAQTEHPG RIVLVDSDAP LDDSALAAVV TTGEPQVLWR
RGEVYTARVH GSRAVGGLLV PPSDRPWRLA MSTAGTFENL RLELIPDADA PLGPGQVRVA
VSAIAANFRD VMIALGLYPD PDAVMGVEAC GVVIETSLNK GSFAVGDRVM GLFPEGTGTV
ASTDQRLLVK VPAGWSHTAA ATTSVVFATA HYALVDLAAA RSGQRVLIHA GTGGVGMAAV
QLARHLGLEV FATASKGKWD TLRAMGFDDD HISDSRSLEF EDKFRAATGG RGFDVVLDSL
AGEFVDASLR LVAPGGVFLE MGKTDIRDPG VIAQQYPGVR YRAFDLFEPG PDRIAQILAE
LATLFGDGVL RPLPVTTFDV RCAPAALRYL SQARHTGKVV MLMPGSWAAG TVLITGGTGM
AGSAVARHVV ARHGVRNLVL VSRRGPDAPG AAELVAELAA AGAQVQVVAC DAADRAALAK
VIADIPVQHP LSGVIHTAGA LDDAVVMSLT PDRVDVVLRS KVDAAWHLHE LTRDLDVSAF
VMFSSMAGLV GSSGQANYAA ANSFLDALAA HRRAHGLPAI SLGWGLWDQA SAMTGGLATV
DFKRFARDGI VAMSSADALQ LFDTAMIVDE PFMLPAHIDF AALKVKFDGG TLPPMFVDLI
NAPTRRQVDD SLAAAKSKSA LLQRLEGLPE DEQHAVLLDL VRSHIATVLG SASPEAIDPD
RAFQELGFDS LTAVEMRNRL KSATGLALSP TLIFDYPNSA ALAGYMRREL LGSSPQDTSA
VAAGEAELQR IVASIPVKRL RQAGVLDLLL ALANETETSG QDPALAPTAE QEIADMDLDD
LVNAAFRNDD E
