ACYLT_MYCS2
ID ACYLT_MYCS2 Reviewed; 304 AA.
AC A0QWG5; I7G9X8;
DT 20-APR-2010, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 1.
DT 03-AUG-2022, entry version 90.
DE RecName: Full=Phosphatidylinositol mannoside acyltransferase;
DE Short=PIM acyltransferase;
DE EC=2.3.1.265 {ECO:0000269|PubMed:24810911};
GN Name=patA {ECO:0000303|PubMed:26965057};
GN OrderedLocusNames=MSMEG_2934, MSMEI_2860;
OS Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155) (Mycobacterium
OS smegmatis).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycolicibacterium.
OX NCBI_TaxID=246196;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155;
RA Fleischmann R.D., Dodson R.J., Haft D.H., Merkel J.S., Nelson W.C.,
RA Fraser C.M.;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=17295914; DOI=10.1186/gb-2007-8-2-r20;
RA Deshayes C., Perrodou E., Gallien S., Euphrasie D., Schaeffer C.,
RA Van-Dorsselaer A., Poch O., Lecompte O., Reyrat J.-M.;
RT "Interrupted coding sequences in Mycobacterium smegmatis: authentic
RT mutations or sequencing errors?";
RL Genome Biol. 8:R20.1-R20.9(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=18955433; DOI=10.1101/gr.081901.108;
RA Gallien S., Perrodou E., Carapito C., Deshayes C., Reyrat J.-M.,
RA Van Dorsselaer A., Poch O., Schaeffer C., Lecompte O.;
RT "Ortho-proteogenomics: multiple proteomes investigation through orthology
RT and a new MS-based protocol.";
RL Genome Res. 19:128-135(2009).
RN [4]
RP FUNCTION AS AN ACYLTRANSFERASE, SUBSTRATE SPECIFICITY, SUBCELLULAR
RP LOCATION, PATHWAY, AND DISRUPTION PHENOTYPE.
RX PubMed=12851411; DOI=10.1074/jbc.m303639200;
RA Kordulakova J., Gilleron M., Puzo G., Brennan P.J., Gicquel B.,
RA Mikusova K., Jackson M.;
RT "Identification of the required acyltransferase step in the biosynthesis of
RT the phosphatidylinositol mannosides of mycobacterium species.";
RL J. Biol. Chem. 278:36285-36295(2003).
RN [5]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=24810911; DOI=10.1016/j.pep.2014.04.014;
RA Svetlikova Z., Barath P., Jackson M., Kordulakova J., Mikusova K.;
RT "Purification and characterization of the acyltransferase involved in
RT biosynthesis of the major mycobacterial cell envelope
RT glycolipid-- monoacylated phosphatidylinositol dimannoside.";
RL Protein Expr. Purif. 100:33-39(2014).
RN [6] {ECO:0007744|PDB:5F2T, ECO:0007744|PDB:5F2Z, ECO:0007744|PDB:5F31, ECO:0007744|PDB:5F34}
RP X-RAY CRYSTALLOGRAPHY (2.06 ANGSTROMS) OF 13-304 IN COMPLEXES WITH
RP PALMITATE AND PALMITOYL-COA ANALOG, FUNCTION, SUBUNIT, SUBCELLULAR
RP LOCATION, ACTIVE SITE, AND MUTAGENESIS OF HIS-126; ASP-131; GLU-149;
RP ARG-164; PHE-182; LEU-197; GLU-200 AND HIS-284.
RX PubMed=26965057; DOI=10.1038/ncomms10906;
RA Albesa-Jove D., Svetlikova Z., Tersa M., Sancho-Vaello E.,
RA Carreras-Gonzalez A., Bonnet P., Arrasate P., Eguskiza A., Angala S.K.,
RA Cifuente J.O., Kordulakova J., Jackson M., Mikusova K., Guerin M.E.;
RT "Structural basis for selective recognition of acyl chains by the membrane-
RT associated acyltransferase PatA.";
RL Nat. Commun. 7:10906-10906(2016).
RN [7] {ECO:0007744|PDB:5OCE}
RP X-RAY CRYSTALLOGRAPHY (2.41 ANGSTROMS) IN COMPLEX WITH PALMITATE; MANNOSE
RP AND PALMITOYL-6-MANNOSE, FUNCTION, REACTION MECHANISM, SUBCELLULAR
RP LOCATION, DOMAIN, AND ACTIVE SITE.
RX PubMed=29185694; DOI=10.1021/acschembio.7b00578;
RA Tersa M., Raich L., Albesa-Jove D., Trastoy B., Prandi J., Gilleron M.,
RA Rovira C., Guerin M.E.;
RT "The molecular mechanism of substrate recognition and catalysis of the
RT membrane acyltransferase PatA from Mycobacteria.";
RL ACS Chem. Biol. 13:131-140(2018).
CC -!- FUNCTION: Catalyzes the transfer of a palmitoyl moiety from palmitoyl-
CC CoA to the 6-position of the mannose ring linked to the 2-position of
CC myo-inositol in phosphatidyl-myo-inositol monomannoside (PIM1) or
CC dimannoside (PIM2). {ECO:0000269|PubMed:12851411,
CC ECO:0000269|PubMed:24810911, ECO:0000269|PubMed:26965057,
CC ECO:0000269|PubMed:29185694}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 2,6-O-bis(alpha-D-mannopyranosyl)-1-phosphatidyl-1D-myo-
CC inositol + an acyl-CoA = 2-O-(alpha-D-mannosyl)-6-O-(6-O-acyl-alpha-
CC D-mannosyl)-1-phosphatidyl-1D-myo-inositol + CoA;
CC Xref=Rhea:RHEA:52436, ChEBI:CHEBI:57287, ChEBI:CHEBI:58342,
CC ChEBI:CHEBI:136624, ChEBI:CHEBI:136625; EC=2.3.1.265;
CC Evidence={ECO:0000269|PubMed:24810911};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-[alpha-D-mannopyranosyl-
CC (1<->6)-D-myo-inositol] + an acyl-CoA = a 1,2-diacyl-sn-glycero-3-
CC phospho-[alpha-D-6-acyl-mannopyranosyl-(1<->6)-D-myo-inositol] + CoA;
CC Xref=Rhea:RHEA:47412, ChEBI:CHEBI:57287, ChEBI:CHEBI:58342,
CC ChEBI:CHEBI:87673, ChEBI:CHEBI:88053; EC=2.3.1.265;
CC Evidence={ECO:0000269|PubMed:24810911};
CC -!- PATHWAY: Phospholipid metabolism; phosphatidylinositol metabolism.
CC {ECO:0000269|PubMed:12851411}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:26965057}.
CC -!- SUBCELLULAR LOCATION: Cell inner membrane {ECO:0000269|PubMed:12851411,
CC ECO:0000269|PubMed:26965057, ECO:0000269|PubMed:29185694}; Peripheral
CC membrane protein {ECO:0000269|PubMed:26965057,
CC ECO:0000269|PubMed:29185694}; Cytoplasmic side
CC {ECO:0000269|PubMed:26965057, ECO:0000269|PubMed:29185694}.
CC Note=Permanently associated with the membrane.
CC {ECO:0000305|PubMed:29185694}.
CC -!- DOMAIN: The acceptor mannose ring localizes in a cavity at the end of a
CC surface-exposed long groove where the active site is located, whereas
CC the palmitate moiety accommodates into a hydrophobic pocket deeply
CC buried in the alpha/beta core of the protein.
CC {ECO:0000269|PubMed:29185694}.
CC -!- DISRUPTION PHENOTYPE: Mutant exhibits severe growth defects and
CC contains an increased amount of phosphatidylinositol mono- and
CC dimannosides and a decreased amount of acylated phosphatidylinositol
CC dimannosides compared with the wild-type parental strain.
CC {ECO:0000269|PubMed:12851411}.
CC -!- SIMILARITY: Belongs to the LpxL/LpxM/LpxP family. {ECO:0000305}.
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DR EMBL; CP000480; ABK72658.1; -; Genomic_DNA.
DR EMBL; CP001663; AFP39324.1; -; Genomic_DNA.
DR RefSeq; WP_011728702.1; NZ_SIJM01000002.1.
DR RefSeq; YP_887253.1; NC_008596.1.
DR PDB; 5F2T; X-ray; 2.06 A; A/B=13-304.
DR PDB; 5F2Z; X-ray; 2.90 A; A/B/C/D=13-304.
DR PDB; 5F31; X-ray; 2.43 A; A=13-304.
DR PDB; 5F34; X-ray; 3.28 A; A/B/C/D=13-304.
DR PDB; 5OCE; X-ray; 2.41 A; A/B/C/D=1-304.
DR PDB; 7OJT; X-ray; 3.67 A; A/B/C/D=2-304.
DR PDBsum; 5F2T; -.
DR PDBsum; 5F2Z; -.
DR PDBsum; 5F31; -.
DR PDBsum; 5F34; -.
DR PDBsum; 5OCE; -.
DR PDBsum; 7OJT; -.
DR AlphaFoldDB; A0QWG5; -.
DR SMR; A0QWG5; -.
DR STRING; 246196.MSMEI_2860; -.
DR PRIDE; A0QWG5; -.
DR EnsemblBacteria; ABK72658; ABK72658; MSMEG_2934.
DR EnsemblBacteria; AFP39324; AFP39324; MSMEI_2860.
DR GeneID; 66734342; -.
DR KEGG; msg:MSMEI_2860; -.
DR KEGG; msm:MSMEG_2934; -.
DR PATRIC; fig|246196.19.peg.2897; -.
DR eggNOG; COG1560; Bacteria.
DR OMA; GMRSYMR; -.
DR OrthoDB; 1106624at2; -.
DR BRENDA; 2.3.1.265; 3512.
DR UniPathway; UPA00949; -.
DR Proteomes; UP000000757; Chromosome.
DR Proteomes; UP000006158; Chromosome.
DR GO; GO:0016021; C:integral component of membrane; IEA:InterPro.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016746; F:acyltransferase activity; IMP:UniProtKB.
DR GO; GO:0009247; P:glycolipid biosynthetic process; IMP:UniProtKB.
DR GO; GO:0046488; P:phosphatidylinositol metabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0008654; P:phospholipid biosynthetic process; IEA:UniProtKB-KW.
DR CDD; cd07984; LPLAT_LABLAT-like; 1.
DR InterPro; IPR004960; LipA_acyltrans.
DR PANTHER; PTHR30606; PTHR30606; 1.
DR Pfam; PF03279; Lip_A_acyltrans; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acyltransferase; Cell inner membrane; Cell membrane;
KW Lipid biosynthesis; Lipid metabolism; Membrane; Phospholipid biosynthesis;
KW Phospholipid metabolism; Reference proteome; Transferase.
FT CHAIN 1..304
FT /note="Phosphatidylinositol mannoside acyltransferase"
FT /id="PRO_0000393726"
FT ACT_SITE 126
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:26965057,
FT ECO:0000305|PubMed:29185694"
FT ACT_SITE 200
FT /evidence="ECO:0000305|PubMed:26965057,
FT ECO:0000305|PubMed:29185694"
FT BINDING 126
FT /ligand="hexadecanoyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57379"
FT /evidence="ECO:0000305|PubMed:26965057"
FT BINDING 164
FT /ligand="hexadecanoyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57379"
FT /evidence="ECO:0000305|PubMed:26965057"
FT BINDING 206
FT /ligand="hexadecanoyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57379"
FT /evidence="ECO:0000305|PubMed:26965057"
FT BINDING 229
FT /ligand="hexadecanoyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57379"
FT /evidence="ECO:0000305|PubMed:26965057"
FT MUTAGEN 126
FT /note="H->A: Loss of transferase activity."
FT /evidence="ECO:0000269|PubMed:26965057"
FT MUTAGEN 131
FT /note="D->A: 65% decrease in transferase activity."
FT /evidence="ECO:0000269|PubMed:26965057"
FT MUTAGEN 149
FT /note="E->A: 25% decrease in transferase activity."
FT /evidence="ECO:0000269|PubMed:26965057"
FT MUTAGEN 164
FT /note="R->A: 20% decrease in transferase activity."
FT /evidence="ECO:0000269|PubMed:26965057"
FT MUTAGEN 182
FT /note="F->W: Loss of transferase activity; when associated
FT with W-197."
FT /evidence="ECO:0000269|PubMed:26965057"
FT MUTAGEN 197
FT /note="L->W: Loss of transferase activity; when associated
FT with W-182."
FT /evidence="ECO:0000269|PubMed:26965057"
FT MUTAGEN 200
FT /note="E->A: Loss of transferase activity."
FT /evidence="ECO:0000269|PubMed:26965057"
FT MUTAGEN 284
FT /note="H->A: 50% decrease in transferase activity."
FT /evidence="ECO:0000269|PubMed:26965057"
FT HELIX 42..45
FT /evidence="ECO:0007829|PDB:5F2T"
FT HELIX 49..61
FT /evidence="ECO:0007829|PDB:5F2T"
FT HELIX 65..67
FT /evidence="ECO:0007829|PDB:5F2T"
FT HELIX 70..89
FT /evidence="ECO:0007829|PDB:5F2T"
FT HELIX 90..92
FT /evidence="ECO:0007829|PDB:5F2T"
FT HELIX 95..101
FT /evidence="ECO:0007829|PDB:5F2T"
FT HELIX 108..115
FT /evidence="ECO:0007829|PDB:5F2T"
FT STRAND 120..124
FT /evidence="ECO:0007829|PDB:5F2T"
FT STRAND 126..128
FT /evidence="ECO:0007829|PDB:5F2T"
FT HELIX 130..140
FT /evidence="ECO:0007829|PDB:5F2T"
FT STRAND 145..148
FT /evidence="ECO:0007829|PDB:5F2T"
FT HELIX 154..166
FT /evidence="ECO:0007829|PDB:5F2T"
FT STRAND 170..179
FT /evidence="ECO:0007829|PDB:5F2T"
FT HELIX 181..190
FT /evidence="ECO:0007829|PDB:5F2T"
FT STRAND 194..198
FT /evidence="ECO:0007829|PDB:5F2T"
FT STRAND 207..212
FT /evidence="ECO:0007829|PDB:5F2T"
FT STRAND 215..219
FT /evidence="ECO:0007829|PDB:5F2T"
FT HELIX 222..230
FT /evidence="ECO:0007829|PDB:5F2T"
FT STRAND 233..242
FT /evidence="ECO:0007829|PDB:5F2T"
FT STRAND 245..250
FT /evidence="ECO:0007829|PDB:5F2T"
FT HELIX 261..278
FT /evidence="ECO:0007829|PDB:5F2T"
FT HELIX 280..282
FT /evidence="ECO:0007829|PDB:5F2T"
FT HELIX 291..293
FT /evidence="ECO:0007829|PDB:5F2T"
FT HELIX 295..301
FT /evidence="ECO:0007829|PDB:5F2T"
SQ SEQUENCE 304 AA; 33554 MW; 4AAF34D53424BBE5 CRC64;
MTLSGRIPLG GQVTDLGYAA GWRLVRAMPE AMAQGVFGAG ARYAARNGGP EQLRRNLARV
VGKPPADVPD DLIRASLASY ARYWREAFRL PAMDHGRLGE QLDVIDIDHL WSALDAGRGA
VLALPHSGNW DMAGVWLVQN YGPFTTVAER LKPESLYRRF VEYRESLGFE VLPLTGGERP
PFEVLAERLT DNRPICLMAE RDLTRSGVQV DFFGEATRMP AGPAKLAIET GAALFPVHCW
FEGDGWGMRV YPELDTSSGD VTAITQALAD RFAANIATYP ADWHMLQPQW IADLSDERRA
RLGT
