PIMA_MYCTU
ID PIMA_MYCTU Reviewed; 378 AA.
AC P9WMZ5; L0TD24; O06204; Q8VJF2;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 43.
DE RecName: Full=Phosphatidyl-myo-inositol mannosyltransferase {ECO:0000303|PubMed:15939292};
DE EC=2.4.1.345 {ECO:0000269|PubMed:15939292};
DE AltName: Full=Alpha-mannosyltransferase {ECO:0000303|PubMed:15939292};
DE AltName: Full=GDP-mannose-dependent alpha-(1-2)-phosphatidylinositol mannosyltransferase {ECO:0000303|PubMed:15939292};
DE AltName: Full=Guanosine diphosphomannose-phosphatidyl-inositol alpha-mannosyltransferase {ECO:0000305};
DE AltName: Full=Phosphatidylinositol alpha-mannosyltransferase {ECO:0000303|PubMed:15939292};
DE Short=PI alpha-mannosyltransferase {ECO:0000303|PubMed:15939292};
GN Name=pimA {ECO:0000303|PubMed:15939292}; OrderedLocusNames=Rv2610c;
GN ORFNames=MTCY01A10.23;
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 FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND COFACTOR.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=15939292; DOI=10.1016/j.pep.2005.03.015;
RA Gu X., Chen M., Wang Q., Zhang M., Wang B., Wang H.;
RT "Expression and purification of a functionally active recombinant GDP-
RT mannosyltransferase (PimA) from Mycobacterium tuberculosis H37Rv.";
RL Protein Expr. Purif. 42:47-53(2005).
RN [3]
RP IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
RX PubMed=19099550; DOI=10.1186/1752-0509-2-109;
RA Raman K., Yeturu K., Chandra N.;
RT "targetTB: a target identification pipeline for Mycobacterium tuberculosis
RT through an interactome, reactome and genome-scale structural analysis.";
RL BMC Syst. Biol. 2:109-109(2008).
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=ATCC 25618 / H37Rv;
RX PubMed=25049093; DOI=10.1128/jb.01346-13;
RA Boldrin F., Ventura M., Degiacomi G., Ravishankar S., Sala C.,
RA Svetlikova Z., Ambady A., Dhar N., Kordulakova J., Zhang M., Serafini A.,
RA Vishwas K.G., Vishwas V.G., Kolly G.S., Kumar N., Palu G., Guerin M.E.,
RA Mikusova K., Cole S.T., Manganelli R.;
RT "The phosphatidyl-myo-inositol mannosyltransferase PimA is essential for
RT Mycobacterium tuberculosis growth in vitro and in vivo.";
RL J. Bacteriol. 196:3441-3451(2014).
CC -!- FUNCTION: Involved in the biosynthesis of phosphatidyl-myo-inositol
CC mannosides (PIM) which are early precursors in the biosynthesis of
CC lipomannans (LM) and lipoarabinomannans (LAM). Catalyzes the addition
CC of a mannosyl residue from GDP-D-mannose (GDP-Man) to the position 2 of
CC the carrier lipid phosphatidyl-myo-inositol (PI) to generate a
CC phosphatidyl-myo-inositol bearing an alpha-1,2-linked mannose residue
CC (PIM1) (PubMed:15939292). PimA plays an essential role for growth in
CC macrophages and during both the acute and chronic phases of infection
CC (PubMed:25049093). {ECO:0000269|PubMed:15939292,
CC ECO:0000269|PubMed:25049093}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) + GDP-
CC alpha-D-mannose = a 1,2-diacyl-sn-glycero-3-phospho-[alpha-D-
CC mannopyranosyl-(1<->6)-D-myo-inositol] + GDP + H(+);
CC Xref=Rhea:RHEA:47368, ChEBI:CHEBI:15378, ChEBI:CHEBI:57527,
CC ChEBI:CHEBI:57880, ChEBI:CHEBI:58189, ChEBI:CHEBI:87673;
CC EC=2.4.1.345; Evidence={ECO:0000269|PubMed:15939292};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:15939292};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=18 uM for mannose {ECO:0000269|PubMed:15939292};
CC Vmax=0.05 nmol/min/ug enzyme {ECO:0000269|PubMed:15939292};
CC pH dependence:
CC Optimum pH is about 7. {ECO:0000269|PubMed:15939292};
CC -!- PATHWAY: Phospholipid metabolism; phosphatidylinositol metabolism.
CC {ECO:0000305|PubMed:25049093}.
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:A0QWG6}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:A0QWG6};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:A0QWG6}; Cytoplasmic
CC side {ECO:0000250|UniProtKB:A0QWG6}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene are unable to produce PIM
CC and show an increase of phosphatidyl-myo-inositol (PI).
CC {ECO:0000269|PubMed:25049093}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC {ECO:0000269|PubMed:19099550}.
CC -!- SIMILARITY: Belongs to the glycosyltransferase group 1 family.
CC Glycosyltransferase 4 subfamily. {ECO:0000305}.
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DR EMBL; AL123456; CCP45407.1; -; Genomic_DNA.
DR PIR; A70571; A70571.
DR RefSeq; NP_217126.1; NC_000962.3.
DR RefSeq; WP_003413478.1; NZ_NVQJ01000023.1.
DR AlphaFoldDB; P9WMZ5; -.
DR SMR; P9WMZ5; -.
DR STRING; 83332.Rv2610c; -.
DR PaxDb; P9WMZ5; -.
DR DNASU; 888627; -.
DR GeneID; 45426613; -.
DR GeneID; 888627; -.
DR KEGG; mtu:Rv2610c; -.
DR TubercuList; Rv2610c; -.
DR eggNOG; COG0438; Bacteria.
DR OMA; VCPYSWD; -.
DR PhylomeDB; P9WMZ5; -.
DR BRENDA; 2.4.1.345; 3445.
DR UniPathway; UPA00949; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005886; C:plasma membrane; IDA:MTBBASE.
DR GO; GO:0004377; F:GDP-Man:Man3GlcNAc2-PP-Dol alpha-1,2-mannosyltransferase activity; ISS:UniProtKB.
DR GO; GO:0016757; F:glycosyltransferase activity; IBA:GO_Central.
DR GO; GO:0000287; F:magnesium ion binding; IDA:MTBBASE.
DR GO; GO:0000030; F:mannosyltransferase activity; IDA:MTBBASE.
DR GO; GO:0043750; F:phosphatidylinositol alpha-mannosyltransferase activity; IDA:MTBBASE.
DR GO; GO:0009247; P:glycolipid biosynthetic process; IDA:MTBBASE.
DR GO; GO:0046488; P:phosphatidylinositol metabolic process; ISS:UniProtKB.
DR GO; GO:0008654; P:phospholipid biosynthetic process; IEA:UniProtKB-KW.
DR InterPro; IPR028098; Glyco_trans_4-like_N.
DR Pfam; PF13439; Glyco_transf_4; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Glycosyltransferase; Lipid biosynthesis; Lipid metabolism;
KW Magnesium; Membrane; Phospholipid biosynthesis; Phospholipid metabolism;
KW Reference proteome; Transferase; Virulence.
FT CHAIN 1..378
FT /note="Phosphatidyl-myo-inositol mannosyltransferase"
FT /id="PRO_0000080302"
FT BINDING 9
FT /ligand="GDP-alpha-D-mannose"
FT /ligand_id="ChEBI:CHEBI:57527"
FT /evidence="ECO:0000250|UniProtKB:A0QWG6"
FT BINDING 16
FT /ligand="GDP-alpha-D-mannose"
FT /ligand_id="ChEBI:CHEBI:57527"
FT /evidence="ECO:0000250|UniProtKB:A0QWG6"
FT BINDING 18
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol)"
FT /ligand_id="ChEBI:CHEBI:57880"
FT /evidence="ECO:0000250|UniProtKB:A0QWG6"
FT BINDING 62..63
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol)"
FT /ligand_id="ChEBI:CHEBI:57880"
FT /evidence="ECO:0000250|UniProtKB:A0QWG6"
FT BINDING 68
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol)"
FT /ligand_id="ChEBI:CHEBI:57880"
FT /evidence="ECO:0000250|UniProtKB:A0QWG6"
FT BINDING 196
FT /ligand="GDP-alpha-D-mannose"
FT /ligand_id="ChEBI:CHEBI:57527"
FT /evidence="ECO:0000250|UniProtKB:A0QWG6"
FT BINDING 201..202
FT /ligand="GDP-alpha-D-mannose"
FT /ligand_id="ChEBI:CHEBI:57527"
FT /evidence="ECO:0000250|UniProtKB:A0QWG6"
FT BINDING 251..253
FT /ligand="GDP-alpha-D-mannose"
FT /ligand_id="ChEBI:CHEBI:57527"
FT /evidence="ECO:0000250|UniProtKB:A0QWG6"
FT BINDING 256
FT /ligand="GDP-alpha-D-mannose"
FT /ligand_id="ChEBI:CHEBI:57527"
FT /evidence="ECO:0000250|UniProtKB:A0QWG6"
FT BINDING 274..278
FT /ligand="GDP-alpha-D-mannose"
FT /ligand_id="ChEBI:CHEBI:57527"
FT /evidence="ECO:0000250|UniProtKB:A0QWG6"
FT BINDING 282
FT /ligand="GDP-alpha-D-mannose"
FT /ligand_id="ChEBI:CHEBI:57527"
FT /evidence="ECO:0000250|UniProtKB:A0QWG6"
FT SITE 118
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000250|UniProtKB:A0QWG6"
SQ SEQUENCE 378 AA; 40445 MW; 637B8E8467717F1A CRC64;
MRIGMICPYS FDVPGGVQSH VLQLAEVMRT RGHLVSVLAP ASPHAALPDY FVSGGRAVPI
PYNGSVARLR FGPATHRKVK KWLAHGDFDV LHLHEPNAPS LSMLALNIAE GPIVATFHTS
TTKSLTLTVF QGILRPMHEK IVGRIAVSDL ARRWQMEALG SDAVEIPNGV DVDSFASAAR
LDGYPRQGKT VLFLGRYDEP RKGMAVLLDA LPKVVQRFPD VQLLIVGHGD ADQLRGQAGR
LAAHLRFLGQ VDDAGKASAM RSADVYCAPN TGGESFGIVL VEAMAAGTAV VASDLDAFRR
VLRDGEVGHL VPVDPPDLQA AALADGLIAV LENDVLRERY VAAGNAAVRR YDWSVVASQI
MRVYETVAGS GAKVQVAS
