MCAS_MYCBO
ID MCAS_MYCBO Reviewed; 2111 AA.
AC Q02251; A0A1R3Y3F3; X2BLY1;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2003, sequence version 2.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Mycocerosic acid synthase;
DE EC=2.3.1.111 {ECO:0000269|PubMed:3880746};
GN Name=mas; OrderedLocusNames=BQ2027_MB2965C;
OS Mycobacterium bovis (strain ATCC BAA-935 / AF2122/97).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=233413;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PROTEIN SEQUENCE OF 1-20; 1437-1453;
RP 1823-1840 AND 1858-1870.
RX PubMed=1527058; DOI=10.1016/s0021-9258(18)41788-7;
RA Mathur M., Kolattukudy P.E.;
RT "Molecular cloning and sequencing of the gene for mycocerosic acid
RT synthase, a novel fatty acid elongating multifunctional enzyme, from
RT Mycobacterium tuberculosis var. bovis Bacillus Calmette-Guerin.";
RL J. Biol. Chem. 267:19388-19395(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC BAA-935 / AF2122/97;
RX PubMed=12788972; DOI=10.1073/pnas.1130426100;
RA Garnier T., Eiglmeier K., Camus J.-C., Medina N., Mansoor H., Pryor M.,
RA Duthoy S., Grondin S., Lacroix C., Monsempe C., Simon S., Harris B.,
RA Atkin R., Doggett J., Mayes R., Keating L., Wheeler P.R., Parkhill J.,
RA Barrell B.G., Cole S.T., Gordon S.V., Hewinson R.G.;
RT "The complete genome sequence of Mycobacterium bovis.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:7877-7882(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND GENOME REANNOTATION.
RC STRAIN=ATCC BAA-935 / AF2122/97;
RX PubMed=28385856; DOI=10.1128/genomea.00157-17;
RA Malone K.M., Farrell D., Stuber T.P., Schubert O.T., Aebersold R.,
RA Robbe-Austerman S., Gordon S.V.;
RT "Updated reference genome sequence and annotation of Mycobacterium bovis
RT AF2122/97.";
RL Genome Announc. 5:E00157-E00157(2017).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND COFACTOR.
RX PubMed=3880746; DOI=10.1016/s0021-9258(18)89777-0;
RA Rainwater D.L., Kolattukudy P.E.;
RT "Fatty acid biosynthesis in Mycobacterium tuberculosis var. bovis Bacillus
RT Calmette-Guerin. Purification and characterization of a novel fatty acid
RT synthase, mycocerosic acid synthase, which elongates n-fatty acyl-CoA with
RT methylmalonyl-CoA.";
RL J. Biol. Chem. 260:616-623(1985).
CC -!- FUNCTION: Catalyzes the elongation of long-chain fatty acyl-CoA with 3
CC or 4 methylmalonyl-CoA (not malonyl-CoA) as the elongating agent to
CC form tri- or tetramethylated-branched fatty acids known as mycocerosyl
CC lipids. {ECO:0000269|PubMed:3880746}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3 (R)-methylmalonyl-CoA + 9 H(+) + long-chain fatty acyl-
CC [mycocerosate synthase] + 6 NADPH = 3 CO2 + 3 CoA + 3 H2O + 6 NADP(+)
CC + trimethylated-mycocerosoyl-[mycocerosate synthase];
CC Xref=Rhea:RHEA:50352, Rhea:RHEA-COMP:12643, Rhea:RHEA-COMP:13239,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57326, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:132570, ChEBI:CHEBI:133243;
CC EC=2.3.1.111; Evidence={ECO:0000269|PubMed:3880746};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4 (R)-methylmalonyl-CoA + 12 H(+) + long-chain fatty acyl-
CC [mycocerosate synthase] + 8 NADPH = 4 CO2 + 4 CoA + 4 H2O + 8 NADP(+)
CC + tetramethylated-mycocerosoyl-[mycocerosate synthase];
CC Xref=Rhea:RHEA:10588, Rhea:RHEA-COMP:12642, Rhea:RHEA-COMP:13239,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57326, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:132569, ChEBI:CHEBI:133243;
CC EC=2.3.1.111; Evidence={ECO:0000269|PubMed:3880746};
CC -!- COFACTOR:
CC Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC Evidence={ECO:0000269|PubMed:3880746};
CC Note=Binds 1 phosphopantetheine covalently.
CC {ECO:0000269|PubMed:3880746};
CC -!- SUBUNIT: Homodimer whose monomers probably have a head to tail
CC arrangement. {ECO:0000269|PubMed:3880746}.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Peripheral membrane protein.
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DR EMBL; M95808; AAA25369.1; -; Genomic_DNA.
DR EMBL; LT708304; SIU01586.1; -; Genomic_DNA.
DR PIR; B44110; B44110.
DR RefSeq; NP_856610.1; NC_002945.3.
DR RefSeq; WP_010950802.1; NC_002945.4.
DR AlphaFoldDB; Q02251; -.
DR SMR; Q02251; -.
DR EnsemblBacteria; SIU01586; SIU01586; BQ2027_MB2965C.
DR PATRIC; fig|233413.5.peg.3254; -.
DR OMA; PSPKIDF; -.
DR BioCyc; MetaCyc:MON-17224; -.
DR Proteomes; UP000001419; Chromosome.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0050111; F:mycocerosate synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-KW.
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; IPR006162; Ppantetheine_attach_site.
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; PS00012; PHOSPHOPANTETHEINE; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Direct protein sequencing; Fatty acid biosynthesis;
KW Fatty acid metabolism; Hydrolase; Ligase; Lipid biosynthesis;
KW Lipid metabolism; Membrane; Multifunctional enzyme; NADP; Oxidoreductase;
KW Phosphopantetheine; Phosphoprotein; Transferase.
FT CHAIN 1..2111
FT /note="Mycocerosic acid synthase"
FT /id="PRO_0000180298"
FT DOMAIN 2025..2100
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 1..430
FT /note="Beta-ketoacyl synthase"
FT REGION 533..852
FT /note="Acyltransferase"
FT ACT_SITE 177
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 623
FT /note="For acyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT BINDING 1562..1579
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="1"
FT /ligand_note="for enoyl reductase activity"
FT BINDING 1766..1781
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="2"
FT /ligand_note="for ketoreductase activity"
FT MOD_RES 2060
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT CONFLICT 196
FT /note="A -> R (in Ref. 1; AAA25369)"
FT /evidence="ECO:0000305"
FT CONFLICT 492
FT /note="A -> R (in Ref. 1; AAA25369)"
FT /evidence="ECO:0000305"
FT CONFLICT 800..801
FT /note="EL -> DV (in Ref. 1; AAA25369)"
FT /evidence="ECO:0000305"
FT CONFLICT 1063..1150
FT /note="AEAGAATVLAEVALPASIRFQQGAYRIHPALLDACFQSVGAGVQAGTATGGL
FT LLPLGVRSLRAYGPTRNARYCYTRLTKAFNDGTRGG -> PRREPRRCWPRSRCPRRSG
FT SSRAPTESTRRCWTLVSSRSARASSRYGHWWPAVAVGCAQPACLRAYPQCPLLLHAVDQ
FT GLQRRDPRW (in Ref. 1; AAA25369)"
FT /evidence="ECO:0000305"
FT CONFLICT 1648
FT /note="A -> P (in Ref. 1; AAA25369)"
FT /evidence="ECO:0000305"
FT CONFLICT 1758
FT /note="A -> R (in Ref. 1; AAA25369)"
FT /evidence="ECO:0000305"
FT CONFLICT 1926
FT /note="R -> P (in Ref. 1; AAA25369)"
FT /evidence="ECO:0000305"
FT CONFLICT 2087
FT /note="N -> K (in Ref. 1; AAA25369)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 2111 AA; 224396 MW; 5CE2B96E083660FC CRC64;
MESRVTPVAV IGMGCRLPGG INSPDKLWES LLRGDDLVTE IPPDRWDADD YYDPEPGVPG
RSVSRWGGFL DDVAGFDAEF FGISEREATS IDPQQRLLLE TSWEAIEHAG LDPASLAGSS
TAVFTGLTHE DYLVLTTTAG GLASPYVVTG LNNSVASGRI AHTLGLHGPA MTFDTACSSG
LMAVHLACRS LHDGEADLAL AGGCAVLLEP HACVAASAQG MLSSTGRCHS FDADADGFVR
SEGCAMVLLK RLPDALRDGN RIFAVVRGTA TNQDGRTETL TMPSEDAQVA VYRAALAAAG
VQPETVGVVE AHGTGTPIGD PIEYRSLARV YGAGTPCALG SAKSNMGHST ASAGTVGLIK
AILSLRHGVV PPLLHFNRLP DELSDVETGL FVPQAVTPWP NGNDHTPKRV AVSSFGMSGT
NVHAIVEEAP AEASAPESSP GDAEVGPRLF MLSSTSSDAL RQTARQLATW VEEHQDCVAA
SDLAYTLARG RAHRPVRTAV VAANLPELVE GLREVADGDA LYDAAVGHGD RGPVWVFSGQ
GSQWAAMGTQ LLASEPVFAA TIAKLEPVIA AESGFSVTEA ITAQQTVTGI DKVQPAVFAV
QVALAATMEQ TYGVRPGAVV GHSMGESAAA VVAGALSLED AARVICRRSK LMTRIAGAGA
MGSVELPAKQ VNSELMARGI DDVVVSVVAS PQSTVIGGTS DTVRDLIARW EQRDVMAREV
AVDVASHSPQ VDPILDDLAA ALADIAPMTP KVPYYSATLF DPREQPVCDG AYWVDNLRNT
VQFAAAVQAA MEDGYRVFAE LSPHPLLTHA VEQTGRSLDM SVAALAGMRR EQPLPHGLRG
LLTELHRAGA ALDYSALYPA GRLVDAPLPA WTHARLFIDD DGQEQRAQGA CTITVHPLLG
SHVRLTEEPE RHVWQGDVGT SVLSWLSDHQ VHNVAALPGA AYCEMALAAA AEVFGEAAEV
RDITFEQMLL LDEQTPIDAV ASIDAPGVVN FTVETNRDGE TTRHATAALR AAEDDCPPPG
YDITALLQAH PHAVNGTAMR ESFAERGVTL GAAFGGLTTA HTAEAGAATV LAEVALPASI
RFQQGAYRIH PALLDACFQS VGAGVQAGTA TGGLLLPLGV RSLRAYGPTR NARYCYTRLT
KAFNDGTRGG EADLDVLDEH GTVLLAVRGL RMGTGTSERD ERDRLVSERL LTLGWQQRAL
PEVGDGEAGS WLLIDTSNAV DTPDMLASTL TDALKSHGPQ GTECASLSWS VQDTPPNDQA
GLEKLGSQLR GRDGVVIVYG PRVGDPDEHS LLAGREQVRH LVRITRELAE FEGELPRLFV
VTRQAQIVKP HDSGERANLE QAGLRGLLRV ISSEHPMLRT TLIDVDEHTD VERVAQQLLS
GSEEDETAWR NGDWYVARLT PSPLGHEERR TAVLDPDHDG MRVQVRRPGD LQTLEFVASD
RVPPGPGQIE VAVSMSSINF ADVLIAFGRF PIIDDREPQL GMDFVGVVTA VGEGVTGHQV
GDRVGGFSEG GCWRTFLTCD ANLAVTLPPG LTDEQAITAA TAHATAWYGL NDLAQIKAGD
KVLIHSATGG VGQAAISIAR AKGAEIFATA GNPAKRAMLR DMGVEHVYDS RSVEFAEQIR
RDTDGYGVDI VLNSLTGAAQ RAGLELLAFG GRFVEIGKAD VYGNTRLGLF PFRRGLTFYY
LDLALMSVTQ PDRVRELLAT VFKLTADGVL TAPQCTHYPL AEAADAIRAM SNAEHTGKLV
LDVPRSGRRS VAVTPEQAPL YRRDGSYIIT GGLGGLGLFF ASKLAAAGCG RIVLTARSQP
NPKARQTIEG LRAAGADIVV ECGNIAEPDT ADRLVSAATA TGLPLRGVLH SAAVVEDATL
TNITDELIDR DWSPKVFGSW NLHRATLGQP LDWFCLFSSG AALLGSPGQG AYAAANSWVD
VFAHWRRAQG LPVSAIAWGA WGEVGRATFL AEGGEIMITP EEGAYAFETL VRHDRAYSGY
IPILGAPWLA DLVRRSPWGE MFASTGQRSR GPSKFRMELL SLPQDEWAGR LRRLLVEQAS
VILRRTIDAD RSFIEYGLDS LGMLEMRTHV ETETGIRLTP KVIATNNTAR ALAQYLADTL
AEEQAAAPAA S
