ACYLT_MYCTU
ID ACYLT_MYCTU Reviewed; 316 AA.
AC P9WMB5; L0TCW4; O06203; Q7D6W7;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 42.
DE RecName: Full=Phosphatidylinositol mannoside acyltransferase;
DE Short=PIM acyltransferase;
DE EC=2.3.1.265 {ECO:0000250|UniProtKB:A0QWG5};
GN Name=patA {ECO:0000303|PubMed:33468587}; OrderedLocusNames=Rv2611c;
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 SEQUENCE REVISION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=12368430; DOI=10.1099/00221287-148-10-2967;
RA Camus J.-C., Pryor M.J., Medigue C., Cole S.T.;
RT "Re-annotation of the genome sequence of Mycobacterium tuberculosis
RT H37Rv.";
RL Microbiology 148:2967-2973(2002).
RN [3]
RP FUNCTION AS AN ACYLTRANSFERASE, SUBCELLULAR LOCATION, AND PATHWAY.
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 [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).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=H37Rv;
RX PubMed=33468587; DOI=10.1128/jb.00439-20;
RA Boldrin F., Anso I., Alebouyeh S., Sevilla I.A., Geijo M., Garrido J.M.,
RA Marina A., Mazzabo L.C., Segafreddo G., Guerin M.E., Manganelli R.,
RA Prados-Rosales R.;
RT "The phosphatidyl-myo-inositol dimannoside acyltransferase PatA is
RT essential for Mycobacterium tuberculosis growth in vitro and in vivo.";
RL J. Bacteriol. 203:0-0(2021).
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) (PubMed:12851411). Essential for growth and survival
CC in axenic cultures and during macrophage infection and in a mouse model
CC of infection (PubMed:33468587). {ECO:0000269|PubMed:12851411,
CC ECO:0000269|PubMed:33468587}.
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:0000250|UniProtKB:A0QWG5};
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:0000250|UniProtKB:A0QWG5};
CC -!- PATHWAY: Phospholipid metabolism; phosphatidylinositol metabolism.
CC {ECO:0000269|PubMed:12851411}.
CC -!- SUBCELLULAR LOCATION: Cell inner membrane
CC {ECO:0000269|PubMed:12851411}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:A0QWG5}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:A0QWG5}. Note=Permanently associated with the
CC membrane. {ECO:0000250|UniProtKB:A0QWG5}.
CC -!- DISRUPTION PHENOTYPE: Essential, gene silencing is bactericidal
CC (PubMed:33468587). Depletion of PatA causes a block in the biosynthesis
CC of PIMs, resulting in severe changes in the composition of the
CC mycobacterial cell wall membrane, which correlates with the loss of
CC viability (PubMed:33468587). {ECO:0000269|PubMed:33468587}.
CC -!- SIMILARITY: Belongs to the LpxL/LpxM/LpxP family. {ECO:0000305}.
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DR EMBL; AL123456; CCP45408.1; -; Genomic_DNA.
DR PIR; B70571; B70571.
DR RefSeq; NP_217127.1; NC_000962.3.
DR RefSeq; WP_003917024.1; NZ_NVQJ01000023.1.
DR AlphaFoldDB; P9WMB5; -.
DR SMR; P9WMB5; -.
DR STRING; 83332.Rv2611c; -.
DR SwissLipids; SLP:000001362; -.
DR PaxDb; P9WMB5; -.
DR DNASU; 888618; -.
DR GeneID; 888618; -.
DR KEGG; mtu:Rv2611c; -.
DR TubercuList; Rv2611c; -.
DR eggNOG; COG1560; Bacteria.
DR OMA; GMRSYMR; -.
DR PhylomeDB; P9WMB5; -.
DR BioCyc; MetaCyc:G185E-6854-MON; -.
DR BRENDA; 2.3.1.265; 3445.
DR UniPathway; UPA00949; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0016021; C:integral component of membrane; IEA:InterPro.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016746; F:acyltransferase activity; IGI:UniProtKB.
DR GO; GO:0009247; P:glycolipid biosynthetic process; IGI: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 Acyltransferase; Cell inner membrane; Cell membrane; Lipid biosynthesis;
KW Lipid metabolism; Membrane; Phospholipid biosynthesis;
KW Phospholipid metabolism; Reference proteome; Transferase; Virulence.
FT CHAIN 1..316
FT /note="Phosphatidylinositol mannoside acyltransferase"
FT /id="PRO_0000393105"
FT ACT_SITE 137
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:A0QWG5"
FT ACT_SITE 211
FT /evidence="ECO:0000250|UniProtKB:A0QWG5"
FT BINDING 137
FT /ligand="hexadecanoyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57379"
FT /evidence="ECO:0000250|UniProtKB:A0QWG5"
FT BINDING 175
FT /ligand="hexadecanoyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57379"
FT /evidence="ECO:0000250|UniProtKB:A0QWG5"
FT BINDING 240
FT /ligand="hexadecanoyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57379"
FT /evidence="ECO:0000250|UniProtKB:A0QWG5"
SQ SEQUENCE 316 AA; 35126 MW; FAC694945B22DA32 CRC64;
MIAGLKGLKL PKDPRSSVTR TATDWAYAAG WMAVRALPEF AVRNAFDTGA RYFARHGGPE
QLRKNLARVL GVPPAAVPDP LMCASLESYG RYWREVFRLP TINHRKLARQ LDRVIGGLDH
LDAALAAGLG AVLALPHSGN WDMAGMWLVQ RHGTFTTVAE RLKPESLYQR FIDYRESLGF
EVLPLSGGER PPFEVLSERL RNNRVVCLMA ERDLTRTGVE VDFFGEPTRM PVGPAKLAVE
TGAALLPTHC WFEGRGWGFQ VYPALDCTSG DVAAITQALA DRFAQNIAAH PADWHMLQPQ
WLADLSESRR AQLRSR
