PKS5_MYCTU
ID PKS5_MYCTU Reviewed; 2108 AA.
AC O53901; F2GEH5; I6XBP9; L0T6X5;
DT 07-SEP-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 2.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Mycocerosic acid synthase-like polyketide synthase {ECO:0000303|PubMed:12855735};
DE Short=MAS-like PKS {ECO:0000303|PubMed:12855735};
DE EC=2.3.1.- {ECO:0000250|UniProtKB:A0R1E8};
DE AltName: Full=Polyketide synthase Pks5;
DE Flags: Precursor;
GN Name=pks5 {ECO:0000303|PubMed:12855735, ECO:0000312|EMBL:CCP44291.1};
GN OrderedLocusNames=Rv1527c {ECO:0000312|EMBL:CCP44291.1},
GN LH57_08370 {ECO:0000312|EMBL:AIR14281.1};
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 NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 27294 / TMC 102 / H37Rv;
RA Hazbon M.H., Riojas M.A., Damon A.M., Alalade R.O., Cantwell B.J.,
RA Monaco A., King S., Sohrabi A.;
RT "Phylogenetic analysis of Mycobacterial species using whole genome
RT sequences.";
RL Submitted (SEP-2014) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, DISRUPTION PHENOTYPE, AND INDUCTION.
RC STRAIN=H37Rv;
RX PubMed=12855735; DOI=10.1099/mic.0.26278-0;
RA Rousseau C., Sirakova T.D., Dubey V.S., Bordat Y., Kolattukudy P.E.,
RA Gicquel B., Jackson M.;
RT "Virulence attenuation of two Mas-like polyketide synthase mutants of
RT Mycobacterium tuberculosis.";
RL Microbiology 149:1837-1847(2003).
RN [4]
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: Polyketide synthase likely involved in the biosynthesis of a
CC polymethyl-branched fatty acid (PMB-FA) that might only be produced
CC during host infection. Is required for the full virulence of
CC M.tuberculosis during host infection. {ECO:0000269|PubMed:12855735,
CC ECO:0000305}.
CC -!- PATHWAY: Lipid metabolism; fatty acid biosynthesis.
CC {ECO:0000250|UniProtKB:A0R1E8}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:A0R1E8}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000255|PROSITE-
CC ProRule:PRU00303}; Lipid-anchor {ECO:0000255|PROSITE-ProRule:PRU00303}.
CC -!- INDUCTION: Is expressed in bacteria grown axenically (7H9 medium) and
CC inside macrophages. {ECO:0000269|PubMed:12855735}.
CC -!- DOMAIN: Is organized in a condensing KS-AT and a modifying DH-PsiKR-ER-
CC KR region, followed by a flexibly tethered ACP domain.
CC {ECO:0000250|UniProtKB:A0R1E8}.
CC -!- DISRUPTION PHENOTYPE: Disruption of this gene causes no major change in
CC the fatty acid and lipid contents of the mutant strain in vitro; the
CC mutant produces all the major methyl-branched fatty acid containing
CC lipids, including DIM, in similar amounts to the wild-type strain. The
CC replication of this mutant is unaffected in mouse bone-marrow
CC macrophages. However, the mutant strain displays severe growth defects
CC in mice, since it multiplies much less extensively than does the
CC parental strain during the acute phase of infection in the lungs and
CC spleen of mice infected via the respiratory route.
CC {ECO:0000269|PubMed:12855735}.
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DR EMBL; AL123456; CCP44291.1; -; Genomic_DNA.
DR EMBL; CP009480; AIR14281.1; -; Genomic_DNA.
DR RefSeq; NP_216043.1; NC_000962.3.
DR RefSeq; WP_003913253.1; NZ_NVQJ01000004.1.
DR AlphaFoldDB; O53901; -.
DR SMR; O53901; -.
DR STRING; 83332.Rv1527c; -.
DR PaxDb; O53901; -.
DR PRIDE; O53901; -.
DR GeneID; 886442; -.
DR KEGG; mtu:Rv1527c; -.
DR PATRIC; fig|83332.111.peg.1704; -.
DR TubercuList; Rv1527c; -.
DR eggNOG; COG0604; Bacteria.
DR eggNOG; COG1028; Bacteria.
DR eggNOG; COG3321; Bacteria.
DR HOGENOM; CLU_000022_31_5_11; -.
DR OMA; WGIQKLN; -.
DR PhylomeDB; O53901; -.
DR Reactome; R-MTU-9635470; Dimycocersyl phthiocerol biosynthesis.
DR UniPathway; UPA00094; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; HDA:MTBBASE.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
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:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
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; -; 1.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.40.366.10; -; 1.
DR Gene3D; 3.40.47.10; -; 1.
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; IPR013149; ADH-like_C.
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; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF08240; ADH_N; 1.
DR Pfam; PF00107; ADH_zinc_N; 1.
DR Pfam; PF16197; KAsynt_C_assoc; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR Pfam; PF08659; KR; 1.
DR Pfam; PF00550; PP-binding; 1.
DR Pfam; PF14765; PS-DH; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00826; PKS_DH; 1.
DR SMART; SM00829; PKS_ER; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF50129; SSF50129; 1.
DR SUPFAM; SSF51735; SSF51735; 3.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 1.
DR PROSITE; PS51257; PROKAR_LIPOPROTEIN; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Cell membrane; Fatty acid metabolism; Lipid metabolism;
KW Lipoprotein; Membrane; Multifunctional enzyme; NADP; Oxidoreductase;
KW Palmitate; Phosphopantetheine; Phosphoprotein; Reference proteome; Signal;
KW Transferase; Virulence.
FT SIGNAL 1..23
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00303"
FT CHAIN 24..2108
FT /note="Mycocerosic acid synthase-like polyketide synthase"
FT /id="PRO_0000437078"
FT DOMAIN 2025..2101
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 14..437
FT /note="Beta-ketoacyl synthase (KS)"
FT /evidence="ECO:0000250|UniProtKB:A0R1E8"
FT REGION 438..542
FT /note="Linker domain (LD)"
FT /evidence="ECO:0000250|UniProtKB:A0R1E8"
FT REGION 543..842
FT /note="Acyltransferase (AT)"
FT /evidence="ECO:0000250|UniProtKB:A0R1E8"
FT REGION 900..1184
FT /note="Dehydratase (DH)"
FT /evidence="ECO:0000250|UniProtKB:A0R1E8"
FT REGION 1220..1391
FT /note="Pseudo beta-ketoacyl reductase (PsiKR)"
FT /evidence="ECO:0000250|UniProtKB:A0R1E8"
FT REGION 1419..1743
FT /note="Enoylreductase (ER)"
FT /evidence="ECO:0000250|UniProtKB:A0R1E8"
FT REGION 1765..2004
FT /note="Beta-ketoacyl reductase (KR)"
FT /evidence="ECO:0000250|UniProtKB:A0R1E8"
FT ACT_SITE 185
FT /note="Acyl-thioester intermediate; for beta-ketoacyl
FT synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 634
FT /note="Acyl-ester intermediate; for acyltransferase
FT activity"
FT /evidence="ECO:0000250|UniProtKB:A0R1E8"
FT ACT_SITE 938
FT /note="Proton acceptor; for dehydratase activity"
FT /evidence="ECO:0000250|UniProtKB:Q03132"
FT ACT_SITE 1108
FT /note="Proton donor; for dehydratase activity"
FT /evidence="ECO:0000250|UniProtKB:Q03132"
FT BINDING 1773..1776
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q03131"
FT BINDING 1796..1799
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q03131"
FT BINDING 1824..1825
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q03131"
FT BINDING 1897..1898
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q03131"
FT MOD_RES 2060
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT LIPID 24
FT /note="N-palmitoyl cysteine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00303"
FT LIPID 24
FT /note="S-diacylglycerol cysteine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00303"
SQ SEQUENCE 2108 AA; 223889 MW; 1E3223687968A103 CRC64;
MGKERTKTVD RTRVTPVAVI GMGCRLPGGI DSPDRLWEAL LRGDDLVTEI PADRWDIDEY
YDPEPGVPGR TDCKWGAYLD NVGDFDPEFF GIGEKEAIAI DPQHRLLLET SWEAMEHGGL
TPNQMASRTG VFVGLVHTDY ILVHADNQTF EGPYGNTGTN ACFASGRVAY AMGLQGPAIT
VDTACSSGLT AIHLACRSLH DGESDIALAG GVYVMLEPRR FASGSALGML SATGRCHAFD
VSADGFVSGE GCVMLALKRL PDALADGDRI LAVIRGTAAN QDGHTVNIAT PSRSAQVAAY
REALDVAGVD PATVGMVEAH GPGTPVGDPI EYASLAEVYG NDGPCALASV KTNFGHTQSA
AGALGLMKAV LALQHGVVPQ NLHFTALPDK LAAIETNLFV PQEITPWPGA DQETPRRAAV
SSYGMTGTNV HAIVEQAPVP APESGAPGDT PATPGIDGAL LFALSASSQD ALRQTAARLA
DWVDAQGPEL APADLAYTLA RRRGHRPVRT AVLAATTAEL TEALREVATG EPPYPPAVGQ
DDRGPVWVFS GQGSQWAGMG ADLLATEPVF AATIAAIEPL IAAESGFSVT EAMTAPEVVT
GIDRVQPTLF AMQVALAATM KSYGVAPGAV IGHSLGESAA AVVAGALCLE DGVRVICRRS
ALMTRIAGAG AMASVELPAQ QVLSELMARG VNDAVVAVVA SPQSTVIGGA TQTVRDLVAA
WEQRDVLARE VAVDVASHSP QVDPILDELA EALAEISPLQ PEIPYYSATS FDPREEPYCD
AYYWVDNLRH TVRFAAAVQA ALEDGYRVFT ELTPHPLLTH AVDQTARSLD MSAAALAGMR
REQPLPHGLR ALAGDLYAAG AAVDFAVLYP TGRLINAPLP TWNHRRLLLD DTTRRIAHAN
TVAVHPLLGS HVRLPEEPER HVWQGEVGTV TQPWLADHQI HGAAALPGAA YCEMALAAAR
AVLGEASEVR DIRFEQMLLL DDETPIGVTA TVEAPGVVPL TVETSHDGRY TRQLAAVLHV
VREADDAPDQ PPQKNIAELL ASHPHKVDGA EVRQWLDKRG HRLGPAFAGL VDAYIAEGAG
DTVLAEVNLP GPLRSQVKAY GVHPVLLDAC FQSVAAHPAV QGMADGGLLL PLGVRRLRSY
GSARHARYCC TTVTACGVGV EADLDVLDEH GAVVLAVRGL QLGTGASQAS ERARVLGERL
LSIEWHEREL PENSHAEPGA WLLISTCDAT DLVAAQLTDA LKVHDAQCTT MSWPQRADHA
AQAARLRDQL GTGGFTGVFV LTAPQTGDPD AESPVRGGEL VKHVVRIARE IPEITAQEPR
LYVLTHNAQA VLSGDRPNLE QGGMRGLLRV IGAEHPHLKA SYVDVDEQTG AESVARQLLA
ASGEDETAWR NDQWYTARLC PAPLRPEERQ TTVVDHAEAG MRLQIRTPGD LQTLEFAAFD
RVPPGPGEIE VAVTASSINF ADVLVTFGRY QTLDGRQPQL GTDFAGVVSA VGPGVSELKV
GDRVGGMSPN GCWATFVTCD ARLATRLPEG LTDAQAAAVT TASATAWYGL QDLARIKAGD
KVLIHSATGG VGQAAIAIAR AAGAQIYATA GNEKRRDLLR DMGIEHVYDS RSVEFAEQIR
RDTAGYGVDI VLNSVTGAAQ LAGLKLLALG GRFIEIGKRD IYSNTRLELL PFRRNLAFYG
LDLGLMSVSH PAAVRELLST VYRLTVEGVL PMPQSTHYPL AEAATAIRVM GAAEHTGKLI
LDVPHAGRSS VVLPPEQARV FRSDGSYIIT GGLGGLGLFL AEKMANAGAG RIVLSSRSQP
SQKALETIEL VRAIGSDVVV ECGDIAQPDT ADRLVTAATA TGLPLRGVLH AAAVVEDATL
ANITDELIER DWAPKAYGAW QLHRATADQP LDWFCSFSSA AALVGSPGQG AYAAANSWLD
TFTHWRRAQD LPATSIAWGA WGQIGRAIAF AEQTGDAIAP EEGAYAFETL LRHNRAYSGY
APVIGSPWLT AFAQHSPFAE KFQSLGQNRS GTSKFLAELV DLPREEWPDR LRRLLSKQVG
LILRRTIDTD RLLSEYGLDS LSSQELRARV EAETGIRISA TEINTTVRGL ADLMCDKLAA
DRDAPAPA
