MSL3_MYCTU
ID MSL3_MYCTU Reviewed; 2085 AA.
AC A0A089QRB9; L0T5X5; L0T647;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2016, sequence version 2.
DT 03-AUG-2022, entry version 46.
DE RecName: Full=Mycolipanoate synthase {ECO:0000303|PubMed:12207710};
DE EC=2.3.1.252 {ECO:0000305|PubMed:12207710};
DE AltName: Full=Mycocerosic acid synthase-like polyketide synthase {ECO:0000305|PubMed:12207710};
DE Short=MAS-like PKS {ECO:0000305|PubMed:12207710};
DE AltName: Full=Mycolipanoic/mycolipenic acids synthase-like polyketide synthase {ECO:0000255|PROSITE-ProRule:PRU10022};
DE Flags: Precursor;
GN Name=msl3 {ECO:0000303|PubMed:12207710};
GN Synonyms=pks3 {ECO:0000303|PubMed:9634230},
GN pks4 {ECO:0000303|PubMed:9634230};
GN OrderedLocusNames=Rv1180/Rv1181 {ECO:0000312|EMBL:CCP43936.1,
GN ECO:0000312|EMBL:CCP43937.1};
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 PROTEIN SEQUENCE OF 502-517, AND PROBABLE SEQUENCE REVISION.
RC STRAIN=H37Rv;
RX PubMed=34915127; DOI=10.1016/j.ygeno.2021.12.001;
RA Shi J., Meng S., Wan L., Zhang Z., Jiang S., Zhu H., Dai E., Chang L.,
RA Gao H., Wan K., Zhang L., Zhao X., Liu H., Lyu Z., Zhang Y., Xu P.;
RT "Deep N-terminomics of Mycobacterium tuberculosis H37Rv extensively correct
RT annotated encoding genes.";
RL Genomics 114:292-304(2022).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE, PATHWAY, AND SEQUENCE
RP REVISION TO 489.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=12207710; DOI=10.1046/j.1365-2958.2002.03119.x;
RA Dubey V.S., Sirakova T.D., Kolattukudy P.E.;
RT "Disruption of msl3 abolishes the synthesis of mycolipanoic and mycolipenic
RT acids required for polyacyltrehalose synthesis in Mycobacterium
RT tuberculosis H37Rv and causes cell aggregation.";
RL Mol. Microbiol. 45:1451-1459(2002).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], PROTEIN
RP SEQUENCE OF 502-517, AND PROBABLE SEQUENCE REVISION.
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 involved in the biosynthesis of methyl-
CC branched fatty acids such as mycolipanoic, mycolipenic (phthienoic) and
CC mycolipodienoic acids required for the synthesis of a major class of
CC polyacylated trehaloses. Catalyzes the elongation of CoA esters of
CC long-chain fatty acids by incorporation of three methylmalonyl (but not
CC malonyl) residues, to form trimethyl-branched fatty-acids.
CC {ECO:0000269|PubMed:12207710}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3 (S)-methylmalonyl-CoA + a long-chain fatty acyl-CoA + 9 H(+)
CC + holo-[mycolipanoate synthase] + 6 NADPH = 3 CO2 + 4 CoA + 3 H2O +
CC long-chain mycolipanoyl-[mycolipanoate synthase] + 6 NADP(+);
CC Xref=Rhea:RHEA:50344, Rhea:RHEA-COMP:12617, Rhea:RHEA-COMP:12618,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57327, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:64479, ChEBI:CHEBI:83139,
CC ChEBI:CHEBI:132361; EC=2.3.1.252;
CC Evidence={ECO:0000305|PubMed:12207710};
CC -!- PATHWAY: Lipid metabolism; fatty acid biosynthesis.
CC {ECO:0000305|PubMed:12207710}.
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 -!- DISRUPTION PHENOTYPE: Cells lacking this gene do not produce
CC mycolipanoic acids, mycolipenic (phthienoic) or mycolipodienoic acids,
CC the major constituents of polyacyltrehaloses, but synthesize all of the
CC other classes of lipids. The absence of the major acyl chains that
CC anchor the surface-exposed acyltrehaloses causes a novel growth
CC morphology. {ECO:0000269|PubMed:12207710}.
CC -!- CAUTION: The previously assigned stop codon (TAA) of pks3 (Rv1180) is
CC found to be a Tyr codon (TAC), and with this change, pks3 and pks4
CC become a single open reading frame designated msl3 (PubMed:12207710).
CC Large scale proteomics studies identify protein sequence that extends
CC N-terminal to the initially annotated start site of Rv1181, more
CC evidence that a single protein is translated from this locus.
CC {ECO:0000269|PubMed:12207710, ECO:0000305|PubMed:21969609,
CC ECO:0000305|PubMed:34915127}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CCP43936.1; Type=Erroneous gene model prediction; Note=Rv1180 and Rv1181 have been merged into one gene.; Evidence={ECO:0000269|PubMed:12207710, ECO:0000269|PubMed:34915127, ECO:0000305|PubMed:21969609};
CC Sequence=CCP43937.1; Type=Erroneous gene model prediction; Note=Rv1180 and Rv1181 have been merged into one gene.; Evidence={ECO:0000269|PubMed:12207710, ECO:0000269|PubMed:34915127, ECO:0000305|PubMed:21969609};
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DR EMBL; AL123456; CCP43936.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL123456; CCP43937.1; ALT_SEQ; Genomic_DNA.
DR RefSeq; NP_215696.1; NC_000962.3.
DR RefSeq; NP_215697.1; NC_000962.3.
DR RefSeq; WP_003406192.1; NZ_NVQJ01000025.1.
DR AlphaFoldDB; A0A089QRB9; -.
DR SMR; A0A089QRB9; -.
DR STRING; 83332.Rv1181; -.
DR DNASU; 886055; -.
DR GeneID; 886055; -.
DR GeneID; 886081; -.
DR KEGG; mtu:Rv1180; -.
DR KEGG; mtu:Rv1181; -.
DR PATRIC; fig|83332.111.peg.1321; -.
DR TubercuList; Rv1180; -.
DR TubercuList; Rv1181; -.
DR eggNOG; COG0604; Bacteria.
DR eggNOG; COG1028; Bacteria.
DR eggNOG; COG3321; Bacteria.
DR HOGENOM; CLU_000022_31_5_11; -.
DR BioCyc; MetaCyc:G185E-5349-MON; -.
DR BRENDA; 2.3.1.252; 3445.
DR UniPathway; UPA00094; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0034081; C:polyketide synthase complex; NAS:UniProtKB.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:InterPro.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:1902321; P:methyl-branched fatty acid biosynthetic process; IDA:UniProtKB.
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; Direct protein sequencing; Lipoprotein;
KW Membrane; Multifunctional enzyme; NADP; Palmitate; Phosphopantetheine;
KW Phosphoprotein; Reference proteome; Signal; Transferase.
FT SIGNAL 1..15
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00303"
FT CHAIN 16..2085
FT /note="Mycolipanoate synthase"
FT /id="PRO_0000438278"
FT DOMAIN 2005..2081
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 6..429
FT /note="Beta-ketoacyl synthase (KS)"
FT /evidence="ECO:0000250|UniProtKB:A0R1E8"
FT REGION 430..534
FT /note="Linker domain (LD)"
FT /evidence="ECO:0000250|UniProtKB:A0R1E8"
FT REGION 535..834
FT /note="Acyltransferase (AT)"
FT /evidence="ECO:0000250|UniProtKB:A0R1E8"
FT REGION 893..1175
FT /note="Dehydratase (DH)"
FT /evidence="ECO:0000250|UniProtKB:A0R1E8"
FT REGION 1211..1371
FT /note="Pseudo beta-ketoacyl reductase (PsiKR)"
FT /evidence="ECO:0000250|UniProtKB:A0R1E8"
FT REGION 1399..1723
FT /note="Enoylreductase (ER)"
FT /evidence="ECO:0000250|UniProtKB:A0R1E8"
FT REGION 1745..1984
FT /note="Beta-ketoacyl reductase (KR)"
FT /evidence="ECO:0000250|UniProtKB:A0R1E8"
FT ACT_SITE 178
FT /note="Acyl-thioester intermediate; for beta-ketoacyl
FT synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 626
FT /note="Acyl-ester intermediate; for acyltransferase
FT activity"
FT /evidence="ECO:0000250|UniProtKB:A0R1E8"
FT ACT_SITE 931
FT /note="Proton acceptor; for dehydratase activity"
FT /evidence="ECO:0000250|UniProtKB:Q03132"
FT ACT_SITE 1097
FT /note="Proton donor; for dehydratase activity"
FT /evidence="ECO:0000250|UniProtKB:Q03132"
FT BINDING 1753..1756
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q03131"
FT BINDING 1776..1779
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q03131"
FT BINDING 1804..1805
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q03131"
FT BINDING 1877..1878
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q03131"
FT MOD_RES 2040
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT LIPID 16
FT /note="N-palmitoyl cysteine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00303"
FT LIPID 16
FT /note="S-diacylglycerol cysteine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00303"
SQ SEQUENCE 2085 AA; 220462 MW; 13B171F97272F48A CRC64;
MRTATATSVA VIGMACRLPG GIDSPQRLWE ALLRGDDLVG EIPADRWDAN VYYDPEPGVP
GRSVSRWGAF LDDVGGFDCD FFGLTEREAT AIDPQHRLLL EVSWEAIEHA GVDPATLAES
QTGVFVGLTH GDYELLSADC GAAEGPYGFT GTSNSFASGR VAYTLGLHGP AVTVDTACSS
GLTAVHQACR SLDDGESDLA LAGGVVVTLE PRKSVSGSLQ GMLSPTGRCH AFDEAADGFV
SGEGCVVLLL KRLPDAVRDG DRVLAIVRGT AANQDGRTVN IAAPSAQAQI AVYQQALAAA
GVEASTVGMV EAHGTGTPVG DPVEYASLAA VYGTEGPCAL TSVKTNFGHL QSASGPLGLM
KTILALRHGV VPQNLHFCRL PDQLAEIDTE LFVPQANTSW PDNTGQPRRA AVSSYGMSGT
NVHAILEQAP VSEPAASGPE LTPEAGGLAL FPVSATSAEQ LHVTAARLAD WVDQNGNAGS
RVSMRDLGYT LSCRRAHRPV RTVVTASSFD ELSAALRDVA GDQIPYQPAV GHDDRGPVWV
FSGQGSQWPG MGTELLVAEP VFAATVAAME PVIARESGFS VTEAMSAPQT VSGIDRVQPT
IFAVQVALAA ALKSYGVRPG AIIGHSLGEA AAAVVAGALS LHDGLRVICR RSRLMSRIAG
SGAMASVELP GQQVLSELAI RGISDVVLSV VASPTSTVVG GATQSIRDLV AAWEQQDVLA
REVAVDVASH TPQVDPILDE LLEVLAEVDP TAPEIPYYSA TLWDPRERPS FTGEYWVENL
RYTVRFAAAV QAALKDGYRV FGELAPHPLL TYAVEQNAAS LDMPIATLAA MRRGEQLPFG
LRGFVADVHN AGAKVDFSVQ YPDGRLVDAP LPSWTHRTLM LSREDSHRSH TGAVQAVHPL
LGAHVHLLEE PERHVWQAGV GTGAHPWLGD HRIHNVAAFP GAAYCEMALA AARTTLGELS
EVRDIKFEQT LLLDEQTVVS SAATIAAPGI LQFAVESHQE GEPARRASAM LHALEEMPQP
PGYDTNALTA AHESSMSGEE LRKMFNSLGI QYGPAFSGLV AVHTARGDVT TVLAEVALPG
AIRSQQSAYA SHPALLDACF QSVLVHPEVQ KATVGGLMLP VGVRRLRNYH STRSAHYCLA
RVTSSSRAGE CEADLDVFDQ AGTVLLTVEG LRLAAGISEH ERANRVFDER LLTIEWERGE
LPEVPQIDAG SWLLLSASEA DPLTAQLADA LNAVGAQSTS VASASDVAQL RSLLGGRLTG
VVVVTGPPTG GLTQCGRDYV SQLVGIAREL AELPGEPPRL FVVTRSAASV LPSDLANLEQ
AGLRGLMRVI DSEHPHLGAT AIDVDNDETV AALVASQLQS GSQEDETAWR NGIWYTARLR
PGPLRPAERR TAVVEYRRDG MRLQIRTPGD LESLEFVTFD RVAPGPGEIE VAVTASSVNF
ADVLVAFGRY PTFEGYRQQL GIDFAGVVTA VGPDVTEHRI GDHVGGMSAN GCWSTFVRCD
ARLAVTLPPE LPVAAAAAVP TASATAWYAL HDLARICSDD KVLIHSGTGG VGQAAIAIAR
AAGCEIFATA GSAQRRQLLH DMGVEHVYDS RSTEFAEQIR GDTDGYGVDV VLNSLPGAAQ
RAGIELLAFG GRFVEIGKRD IYGDTRLGLF PFRRNLSLYA VDLALLTHSH PHTVRRLLKT
VYQHTVEGTL PVPQTTHYPI HDAAVAIRLV GGAGHTGKVV LDVPRTGEGV AVVPPEQVRT
SRPDGAYLVT GGLGGLGLFL AGELAAAGCG RIVLNSRSTP SPHATRVIER LRAAGADIQV
ECGDIADAAT AHRVVAVATA SGLPVRGVLH AAAVVEDATL ANVTDELIDR CWAPKVHGAW
NIHRATAAQP LEWFCLFSSA AALVGSPGQG AYAAANSWLD AFAHWRRAQG LPATSIAWGA
WAEIGRATAL AEGTGAAIAP AEGARAFQTL LRYGRAYSGY APIMGTPWLT AFAQRSRFAE
AFHATGQNQP ATGKFLAELG SLPREEWPRT VRRLVSDQIS LLLRRTIDPD RPLSDYGLDS
LGNLELRTRI ETETGIRVSP TKITTVRGLA EHVCDELAAA QSAPV
