ID PKS1_MYCTU Reviewed; 1616 AA.
AC P96285; L0TB41;
DT 05-APR-2011, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 4.
DT 27-NOV-2024, entry version 162.
DE RecName: Full=Putative inactive phenolphthiocerol synthesis polyketide synthase type I Pks1;
GN Name=pks1; OrderedLocusNames=Rv2946c;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinomycetota; Actinomycetes; Mycobacteriales; 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 NATURAL FRAMESHIFT.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=12138124; DOI=10.1074/jbc.m206538200;
RA Constant P., Perez E., Malaga W., Laneelle M.A., Saurel O., Daffe M.,
RA Guilhot C.;
RT "Role of the pks15/1 gene in the biosynthesis of phenolglycolipids in the
RT Mycobacterium tuberculosis complex. Evidence that all strains synthesize
RT glycosylated p-hydroxybenzoic methyl esters and that strains devoid of
RT phenolglycolipids harbor a frameshift mutation in the pks15/1 gene.";
RL J. Biol. Chem. 277:38148-38158(2002).
RN [3]
RP DISRUPTION PHENOTYPE, AND PUTATIVE FUNCTION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=12730158; DOI=10.1128/jb.185.10.2999-3008.2003;
RA Sirakova T.D., Dubey V.S., Cynamon M.H., Kolattukudy P.E.;
RT "Attenuation of Mycobacterium tuberculosis by disruption of a mas-like gene
RT or a chalcone synthase-like gene, which causes deficiency in dimycocerosyl
RT phthiocerol synthesis.";
RL J. Bacteriol. 185:2999-3008(2003).
RN [4]
RP IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
RX PubMed=19099550; DOI=10.1186/1752-0509-2-109;
RA Raman K., Yeturu K., Chandra N.;
RT "targetTB: a target identification pipeline for Mycobacterium tuberculosis
RT through an interactome, reactome and genome-scale structural analysis.";
RL BMC Syst. Biol. 2:109-109(2008).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011445;
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: May play a role in phthiocerol biosynthesis.
CC -!- COFACTOR:
CC Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC Evidence={ECO:0000250};
CC Note=Binds 1 phosphopantetheine covalently. {ECO:0000250};
CC -!- PATHWAY: Lipid metabolism; fatty acid biosynthesis.
CC -!- DISRUPTION PHENOTYPE: Disruption of pks1 abolishes the production of
CC phthiocerol dimycocerosate (DIM) on the cell envelope, but the
CC production of mycocerosic acid is not deficient. The pks10 mutants show
CC a major attenuation of virulence. {ECO:0000269|PubMed:12730158}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC -!- CAUTION: M.bovis (strains ATCC BAA-935 / AF2122/97 and BCG / Pasteur
CC 1173P2) and M.marinum (strain ATCC BAA-535 / M) have a single fused
CC pks15/1 ORF, but M.tuberculosis (strains ATCC 25618 / H37Rv and CDC
CC 1551 / Oshkosh) have 2 separate ORFs. This is due to the natural
CC deletion of a single base, a guanine, that causes a frameshift and thus
CC the two ORFs, pks15 and pks1, instead of pks15/1. This frameshift led
CC to the inactivation of Pks15/1, which in turn caused the inability of
CC these strains to elongate the putative p-hydroxybenzoic acid precursor
CC and thus to produce phenolphthiocerol derivatives. {ECO:0000305}.
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DR EMBL; AL123456; CCP45750.1; -; Genomic_DNA.
DR RefSeq; NP_217462.1; NC_000962.3.
DR RefSeq; WP_003917711.1; NC_000962.3.
DR AlphaFoldDB; P96285; -.
DR SMR; P96285; -.
DR STRING; 83332.Rv2946c; -.
DR PaxDb; 83332-Rv2946c; -.
DR GeneID; 888122; -.
DR KEGG; mtu:Rv2946c; -.
DR KEGG; mtv:RVBD_2946c; -.
DR PATRIC; fig|83332.111.peg.3280; -.
DR TubercuList; Rv2946c; -.
DR eggNOG; COG0604; Bacteria.
DR eggNOG; COG1020; Bacteria.
DR eggNOG; COG3321; Bacteria.
DR eggNOG; COG4221; Bacteria.
DR InParanoid; P96285; -.
DR OrthoDB; 4516163at2; -.
DR PhylomeDB; P96285; -.
DR BRENDA; 2.3.1.261; 3445.
DR UniPathway; UPA00094; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0004312; F:fatty acid synthase activity; IBA:GO_Central.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:InterPro.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0071766; P:Actinobacterium-type cell wall biogenesis; IMP:UniProtKB.
DR GO; GO:0071770; P:DIM/DIP cell wall layer assembly; IMP:MTBBASE.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IBA:GO_Central.
DR GO; GO:0008610; P:lipid biosynthetic process; IMP:UniProtKB.
DR CDD; cd05195; enoyl_red; 1.
DR CDD; cd08956; KR_3_FAS_SDR_x; 1.
DR FunFam; 3.40.50.720:FF:000209; Polyketide synthase Pks12; 1.
DR FunFam; 3.40.366.10:FF:000002; Probable polyketide synthase 2; 1.
DR FunFam; 3.10.129.110:FF:000003; Probable polyketide synthase pks1; 1.
DR FunFam; 3.40.50.11460:FF:000001; Probable polyketide synthase pks1; 1.
DR FunFam; 3.90.180.10:FF:000032; Probable polyketide synthase pks1; 1.
DR FunFam; 1.10.1200.10:FF:000007; Probable polyketide synthase pks17; 1.
DR FunFam; 3.40.50.720:FF:000381; Probable polyketide synthase pks17; 1.
DR Gene3D; 3.30.70.3290; -; 1.
DR Gene3D; 3.40.50.11460; -; 1.
DR Gene3D; 1.10.1200.10; ACP-like; 1.
DR Gene3D; 3.40.366.10; Malonyl-Coenzyme A Acyl Carrier Protein, domain 2; 1.
DR Gene3D; 3.90.180.10; Medium-chain alcohol dehydrogenases, catalytic domain; 1.
DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1.
DR Gene3D; 3.10.129.110; Polyketide synthase dehydratase; 1.
DR InterPro; IPR001227; Ac_transferase_dom_sf.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR014043; Acyl_transferase_dom.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR InterPro; IPR013154; ADH-like_N.
DR InterPro; IPR011032; GroES-like_sf.
DR InterPro; IPR016036; Malonyl_transacylase_ACP-bd.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR020807; PKS_DH.
DR InterPro; IPR049551; PKS_DH_C.
DR InterPro; IPR049552; PKS_DH_N.
DR InterPro; IPR020843; PKS_ER.
DR InterPro; IPR013968; PKS_KR.
DR InterPro; IPR049900; PKS_mFAS_DH.
DR InterPro; IPR050091; PKS_NRPS_Biosynth_Enz.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR055123; SpnB-like_Rossmann.
DR PANTHER; PTHR43775; FATTY ACID SYNTHASE; 1.
DR PANTHER; PTHR43775:SF51; PHENOLPHTHIOCEROL_PHTHIOCEROL POLYKETIDE SYNTHASE SUBUNIT E; 1.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF08240; ADH_N; 1.
DR Pfam; PF13602; ADH_zinc_N_2; 1.
DR Pfam; PF22621; CurL-like_PKS_C; 1.
DR Pfam; PF08659; KR; 1.
DR Pfam; PF21089; PKS_DH_N; 1.
DR Pfam; PF00550; PP-binding; 1.
DR Pfam; PF14765; PS-DH; 1.
DR Pfam; PF22953; SpnB_Rossmann; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00826; PKS_DH; 1.
DR SMART; SM00829; PKS_ER; 1.
DR SMART; SM00822; PKS_KR; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SMART; SM01294; PKS_PP_betabranch; 1.
DR SUPFAM; SSF47336; ACP-like; 1.
DR SUPFAM; SSF52151; FabD/lysophospholipase-like; 1.
DR SUPFAM; SSF50129; GroES-like; 1.
DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 3.
DR SUPFAM; SSF55048; Probable ACP-binding domain of malonyl-CoA ACP transacylase; 1.
DR PROSITE; PS50075; CARRIER; 1.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
DR PROSITE; PS52019; PKS_MFAS_DH; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Fatty acid metabolism; Lipid metabolism;
KW Phosphopantetheine; Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..1616
FT /note="Putative inactive phenolphthiocerol synthesis
FT polyketide synthase type I Pks1"
FT /id="PRO_0000406600"
FT DOMAIN 445..719
FT /note="PKS/mFAS DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT DOMAIN 1514..1589
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 83..397
FT /note="Acyltransferase"
FT /evidence="ECO:0000250"
FT REGION 445..605
FT /note="Dehydratase"
FT /evidence="ECO:0000250"
FT REGION 445..567
FT /note="N-terminal hotdog fold"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT REGION 579..719
FT /note="C-terminal hotdog fold"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT REGION 910..1215
FT /note="Enoylreductase"
FT /evidence="ECO:0000250"
FT REGION 1228..1409
FT /note="Beta-ketoacyl reductase"
FT /evidence="ECO:0000250"
FT REGION 1588..1616
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1588..1602
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 174
FT /note="For acyltransferase activity"
FT /evidence="ECO:0000250"
FT ACT_SITE 477
FT /note="Proton acceptor; for dehydratase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT ACT_SITE 640
FT /note="Proton donor; for dehydratase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT BINDING 1040..1057
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 1229..1244
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT MOD_RES 1549
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 1616 AA; 166672 MW; D6A9DB279B69D92B CRC64;
MISARSAEAL TAQAGRLMAH VQANPGLDPI DVGCSLASRS VFEHRAVVVG ASREQLIAGL
AGLAAGEPGA GVAVGQPGSV GKTVVVFPGQ GAQRIGMGRE LYGELPVFAQ AFDAVADELD
RHLRLPLRDV IWGADADLLD STEFAQPALF AVEVASFAVL RDWGVLPDFV MGHSVGELAA
AHAAGVLTLA DAAMLVVARG RLMQALPAGG AMVAVAASED EVEPLLGEGV GIAAINAPES
VVISGAQAAA NAIADRFAAQ GRRVHQLAVS HAFHSPLMEP MLEEFARVAA RVQAREPQLG
LVSNVTGELA GPDFGSAQYW VDHVRRPVRF ADSARHLQTL GATHFIEAGP GSGLTGSIEQ
SLAPAEAMVV SMLGKDRPEL ASALGAAGQV FTTGVPVQWS AVFAGSGGRR VQLPTYAFQR
RRFWETPGAD GPADAAGLGL GATEHALLGA VVERPDSDEV VLTGRLSLAD QPWLADHVVN
GVVLFPGAGF VELVIRAGDE VGCALIEELV LAAPLVMHPG VGVQVQVVVG AADESGHRAV
SVYSRGDQSQ GWLLNAEGML GVAAAETPMD LSVWPPEGAE SVDISDGYAQ LAERGYAYGP
AFQGLVAIWR RGSELFAEVV APGEAGVAVD RMGMHPAVLD AVLHALGLAV EKTQASTETR
LPFCWRGVSL HAGGAGRVRA RFASAGADAI SVDVCDATGL PVLTVRSLVT RPITAEQLRA
AVTAAGGASD QGPLEVVWSP ISVVSGGANG SAPPAPVSWA DFCAGSDGDA SVVVWELESA
GGQASSVVGS VYAATHTALE VLQSWLGADR AATLVVLTHG GVGLAGEDIS DLAAAAVWGM
ARSAQAENPG RIVLIDTDAA VDASVLAGVG EPQLLVRGGT VHAPRLSPAP ALLALPAAES
AWRLAAGGGG TLEDLVIQPC PEVQAPLQAG QVRVAVAAVG VNFRDVVAAL GMYPGQAPPL
GAEGAGVVLE TGPEVTDLAV GDAVMGFLGG AGPLAVVDQQ LVTRVPQGWS FAQAAAVPVV
FLTAWYGLAD LAEIKAGESV LIHAGTGGVG MAAVQLARQW GVEVFVTASR GKWDTLRAMG
FDDDHIGDSR TCEFEEKFLA VTEGRGVDVV LDSLAGEFVD ASLRLLVRGG RFLEMGKTDI
RDAQEIAANY PGVQYRAFDL SEAGPARMQE MLAEVRELFD TRELHRLPVT TWDVRCAPAA
FRFMSQARHI GKVVLTMPSA LADRLADGTV VITGATGAVG GVLARHLVGA YGVRHLVLAS
RRGDRAEGAA ELAADLTEAG AKVQVVACDV ADRAAVAGLF AQLSREYPPV RGVIHAAGVL
DDAVITSLTP DRIDTVLRAK VDAAWNLHQA TSDLDLSMFA LCSSIAATVG SPGQGNYSAA
NAFLDGLAAH RQAAGLAGIS LAWGLWEQPG GMTAHLSSRD LARMSRSGLA PMSPAEAVEL
FDAALAIDHP LAVATLLDRA ALDARAQAGA LPALFSGLAR RPRRRQIDDT GDATSSKSAL
AQRLHGLAAD EQLELLVGLV CLQAAAVLGR PSAEDVDPDT EFGDLGFDSL TAVELRNRLK
TATGLTLPPT VIFDHPTPTA VAEYVAQQMS GSRPTESGDP TSQVVEPAAA EVSVHA
//
