PIMA_MYCS2
ID PIMA_MYCS2 Reviewed; 386 AA.
AC A0QWG6; I7FCT3;
DT 20-APR-2010, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 1.
DT 03-AUG-2022, entry version 104.
DE RecName: Full=Phosphatidyl-myo-inositol mannosyltransferase {ECO:0000303|PubMed:12068013};
DE EC=2.4.1.345 {ECO:0000269|PubMed:12068013, ECO:0000269|PubMed:19638342};
DE AltName: Full=Alpha-mannosyltransferase {ECO:0000303|PubMed:12068013};
DE AltName: Full=GDP-mannose-dependent alpha-(1-2)-phosphatidylinositol mannosyltransferase {ECO:0000303|PubMed:12068013};
DE AltName: Full=Guanosine diphosphomannose-phosphatidyl-inositol alpha-mannosyltransferase {ECO:0000305};
DE AltName: Full=Phosphatidylinositol alpha-mannosyltransferase {ECO:0000303|PubMed:12068013};
DE Short=PI alpha-mannosyltransferase {ECO:0000303|PubMed:12068013};
GN Name=pimA {ECO:0000303|PubMed:12068013};
GN OrderedLocusNames=MSMEG_2935, MSMEI_2861;
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 A MANNOSYLTRANSFERASE, CATALYTIC ACTIVITY, AND SUBCELLULAR
RP LOCATION.
RX PubMed=12068013; DOI=10.1074/jbc.m204060200;
RA Kordulakova J., Gilleron M., Mikusova K., Puzo G., Brennan P.J.,
RA Gicquel B., Jackson M.;
RT "Definition of the first mannosylation step in phosphatidylinositol
RT mannoside synthesis. PimA is essential for growth of mycobacteria.";
RL J. Biol. Chem. 277:31335-31344(2002).
RN [5]
RP FUNCTION IN AC1PIM2 BIOSYNTHESIS, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=19638342; DOI=10.1074/jbc.m109.030593;
RA Guerin M.E., Kaur D., Somashekar B.S., Gibbs S., Gest P., Chatterjee D.,
RA Brennan P.J., Jackson M.;
RT "New insights into the early steps of phosphatidylinositol mannoside
RT biosynthesis in mycobacteria: PimB' is an essential enzyme of Mycobacterium
RT smegmatis.";
RL J. Biol. Chem. 284:25687-25696(2009).
RN [6]
RP FUNCTION, MUTAGENESIS OF GLN-18; TYR-62; ASN-63; SER-65; ARG-68; ARG-70;
RP LYS-123; ARG-196 AND GLU-199, SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=19520856; DOI=10.1074/jbc.m109.003947;
RA Guerin M.E., Schaeffer F., Chaffotte A., Gest P., Giganti D.,
RA Kordulakova J., van der Woerd M., Jackson M., Alzari P.M.;
RT "Substrate-induced conformational changes in the essential peripheral
RT membrane-associated mannosyltransferase PimA from mycobacteria:
RT implications for catalysis.";
RL J. Biol. Chem. 284:21613-21625(2009).
RN [7]
RP SUBUNIT.
RX PubMed=23963451; DOI=10.1074/jbc.m113.462705;
RA Giganti D., Alegre-Cebollada J., Urresti S., Albesa-Jove D.,
RA Rodrigo-Unzueta A., Comino N., Kachala M., Lopez-Fernandez S.,
RA Svergun D.I., Fernandez J.M., Guerin M.E.;
RT "Conformational plasticity of the essential membrane-associated
RT mannosyltransferase PimA from mycobacteria.";
RL J. Biol. Chem. 288:29797-29808(2013).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH GDP AND GDP-MANNOSE,
RP AND MUTAGENESIS OF TYR-9; 77-ARG--LYS-81; HIS-118; THR-126; ARG-201 AND
RP GLU-274.
RX PubMed=17510062; DOI=10.1074/jbc.m702087200;
RA Guerin M.E., Kordulakova J., Schaeffer F., Svetlikova Z., Buschiazzo A.,
RA Giganti D., Gicquel B., Mikusova K., Jackson M., Alzari P.M.;
RT "Molecular recognition and interfacial catalysis by the essential
RT phosphatidylinositol mannosyltransferase PimA from mycobacteria.";
RL J. Biol. Chem. 282:20705-20714(2007).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS), AND MUTAGENESIS OF THR-126 AND
RP VAL-359.
RX PubMed=25402770; DOI=10.1038/nchembio.1694;
RA Giganti D., Albesa-Jove D., Urresti S., Rodrigo-Unzueta A., Martinez M.A.,
RA Comino N., Barilone N., Bellinzoni M., Chenal A., Guerin M.E., Alzari P.M.;
RT "Secondary structure reshuffling modulates glycosyltransferase function at
RT the membrane.";
RL Nat. Chem. Biol. 11:16-18(2015).
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:12068013, PubMed:19638342, PubMed:19520856). In contrary
CC to PimB, the mannosyltransferase PimA is unable to transfer a mannose
CC residue to the position 6 of the phosphatidyl-myo-inositol of PIM1
CC (PubMed:19638342). {ECO:0000269|PubMed:12068013,
CC ECO:0000269|PubMed:19520856, ECO:0000269|PubMed:19638342}.
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:12068013,
CC ECO:0000269|PubMed:19638342};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P9WMZ5};
CC -!- PATHWAY: Phospholipid metabolism; phosphatidylinositol metabolism.
CC {ECO:0000305|PubMed:19638342}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:19520856,
CC ECO:0000269|PubMed:23963451}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305|PubMed:12068013,
CC ECO:0000305|PubMed:19520856}; Peripheral membrane protein
CC {ECO:0000305|PubMed:19520856}; Cytoplasmic side
CC {ECO:0000305|PubMed:19520856}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the glycosyltransferase group 1 family.
CC Glycosyltransferase 4 subfamily. {ECO:0000305}.
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DR EMBL; CP000480; ABK72422.1; -; Genomic_DNA.
DR EMBL; CP001663; AFP39325.1; -; Genomic_DNA.
DR RefSeq; WP_011728703.1; NZ_SIJM01000002.1.
DR RefSeq; YP_887254.1; NC_008596.1.
DR PDB; 2GEJ; X-ray; 2.60 A; A=1-386.
DR PDB; 2GEK; X-ray; 2.40 A; A=1-386.
DR PDB; 4N9W; X-ray; 1.94 A; A=1-386.
DR PDB; 4NC9; X-ray; 3.19 A; A/B/C/D=1-386.
DR PDBsum; 2GEJ; -.
DR PDBsum; 2GEK; -.
DR PDBsum; 4N9W; -.
DR PDBsum; 4NC9; -.
DR AlphaFoldDB; A0QWG6; -.
DR SMR; A0QWG6; -.
DR STRING; 246196.MSMEI_2861; -.
DR CAZy; GT4; Glycosyltransferase Family 4.
DR PRIDE; A0QWG6; -.
DR EnsemblBacteria; ABK72422; ABK72422; MSMEG_2935.
DR EnsemblBacteria; AFP39325; AFP39325; MSMEI_2861.
DR GeneID; 66734343; -.
DR KEGG; msg:MSMEI_2861; -.
DR KEGG; msm:MSMEG_2935; -.
DR PATRIC; fig|246196.19.peg.2898; -.
DR eggNOG; COG0438; Bacteria.
DR OMA; VCPYSWD; -.
DR OrthoDB; 948440at2; -.
DR BRENDA; 2.4.1.345; 3512.
DR UniPathway; UPA00949; -.
DR EvolutionaryTrace; A0QWG6; -.
DR Proteomes; UP000000757; Chromosome.
DR Proteomes; UP000006158; Chromosome.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004377; F:GDP-Man:Man3GlcNAc2-PP-Dol alpha-1,2-mannosyltransferase activity; IDA:UniProtKB.
DR GO; GO:0043750; F:phosphatidylinositol alpha-mannosyltransferase activity; IDA:UniProtKB.
DR GO; GO:0009247; P:glycolipid biosynthetic process; IDA:UniProtKB.
DR GO; GO:0046488; P:phosphatidylinositol metabolic process; IDA: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 3D-structure; Cell membrane; Glycosyltransferase; Lipid biosynthesis;
KW Lipid metabolism; Magnesium; Membrane; Phospholipid biosynthesis;
KW Phospholipid metabolism; Reference proteome; Transferase; Virulence.
FT CHAIN 1..386
FT /note="Phosphatidyl-myo-inositol mannosyltransferase"
FT /id="PRO_0000393732"
FT BINDING 9
FT /ligand="GDP-alpha-D-mannose"
FT /ligand_id="ChEBI:CHEBI:57527"
FT /evidence="ECO:0000305|PubMed:17510062"
FT BINDING 16
FT /ligand="GDP-alpha-D-mannose"
FT /ligand_id="ChEBI:CHEBI:57527"
FT /evidence="ECO:0000269|PubMed:17510062,
FT ECO:0000269|PubMed:19520856"
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:0000305|PubMed:19520856"
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:0000305|PubMed:19520856"
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:0000305|PubMed:19520856"
FT BINDING 196
FT /ligand="GDP-alpha-D-mannose"
FT /ligand_id="ChEBI:CHEBI:57527"
FT /evidence="ECO:0000269|PubMed:17510062,
FT ECO:0000305|PubMed:19520856"
FT BINDING 201..202
FT /ligand="GDP-alpha-D-mannose"
FT /ligand_id="ChEBI:CHEBI:57527"
FT /evidence="ECO:0000269|PubMed:17510062,
FT ECO:0000305|PubMed:19520856"
FT BINDING 251..253
FT /ligand="GDP-alpha-D-mannose"
FT /ligand_id="ChEBI:CHEBI:57527"
FT /evidence="ECO:0000269|PubMed:17510062,
FT ECO:0000269|PubMed:19520856"
FT BINDING 256
FT /ligand="GDP-alpha-D-mannose"
FT /ligand_id="ChEBI:CHEBI:57527"
FT /evidence="ECO:0000269|PubMed:17510062,
FT ECO:0000269|PubMed:19520856"
FT BINDING 274..278
FT /ligand="GDP-alpha-D-mannose"
FT /ligand_id="ChEBI:CHEBI:57527"
FT /evidence="ECO:0000269|PubMed:17510062"
FT BINDING 282
FT /ligand="GDP-alpha-D-mannose"
FT /ligand_id="ChEBI:CHEBI:57527"
FT /evidence="ECO:0000269|PubMed:17510062,
FT ECO:0000269|PubMed:19520856"
FT SITE 118
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000269|PubMed:17510062"
FT MUTAGEN 9
FT /note="Y->A: Loss of mannosyltransferase activity."
FT /evidence="ECO:0000269|PubMed:17510062"
FT MUTAGEN 18
FT /note="Q->A: Strong decrease of mannosyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:19520856"
FT MUTAGEN 62
FT /note="Y->A: Loss of mannosyltransferase activity."
FT /evidence="ECO:0000269|PubMed:19520856"
FT MUTAGEN 63
FT /note="N->A: Loss of mannosyltransferase activity."
FT /evidence="ECO:0000269|PubMed:19520856"
FT MUTAGEN 65
FT /note="S->A: Same activity as the wild-type."
FT /evidence="ECO:0000269|PubMed:19520856"
FT MUTAGEN 68
FT /note="R->A: Loss of mannosyltransferase activity."
FT /evidence="ECO:0000269|PubMed:19520856"
FT MUTAGEN 70
FT /note="R->A: Same activity as the wild-type."
FT /evidence="ECO:0000269|PubMed:19520856"
FT MUTAGEN 77..81
FT /note="RKVKK->SSVSS: Loss of mannosyltransferase activity
FT and the ability to bind phospholipid aggregates."
FT /evidence="ECO:0000269|PubMed:17510062"
FT MUTAGEN 118
FT /note="H->A: Loss of mannosyltransferase activity."
FT /evidence="ECO:0000269|PubMed:17510062"
FT MUTAGEN 123
FT /note="K->A: 23% less active than the wild-type."
FT /evidence="ECO:0000269|PubMed:19520856"
FT MUTAGEN 126
FT /note="T->C: Interacts only marginally with GDP and is
FT inactive; when associated with C-359."
FT /evidence="ECO:0000269|PubMed:25402770"
FT MUTAGEN 126
FT /note="T->W: No change in the activity."
FT /evidence="ECO:0000269|PubMed:17510062"
FT MUTAGEN 196
FT /note="R->A: Loss of mannosyltransferase activity."
FT /evidence="ECO:0000269|PubMed:19520856"
FT MUTAGEN 199
FT /note="E->A: Loss of mannosyltransferase activity."
FT /evidence="ECO:0000269|PubMed:19520856"
FT MUTAGEN 201
FT /note="R->A: Loss of mannosyltransferase activity."
FT /evidence="ECO:0000269|PubMed:17510062"
FT MUTAGEN 274
FT /note="E->A: Loss of mannosyltransferase activity."
FT /evidence="ECO:0000269|PubMed:17510062"
FT MUTAGEN 359
FT /note="V->C: Interacts only marginally with GDP and is
FT inactive; when associated with C-126."
FT /evidence="ECO:0000269|PubMed:25402770"
FT STRAND 2..6
FT /evidence="ECO:0007829|PDB:4N9W"
FT HELIX 16..30
FT /evidence="ECO:0007829|PDB:4N9W"
FT STRAND 34..40
FT /evidence="ECO:0007829|PDB:4N9W"
FT STRAND 51..53
FT /evidence="ECO:0007829|PDB:4N9W"
FT STRAND 57..59
FT /evidence="ECO:0007829|PDB:4N9W"
FT STRAND 66..71
FT /evidence="ECO:0007829|PDB:4N9W"
FT HELIX 73..86
FT /evidence="ECO:0007829|PDB:4N9W"
FT STRAND 89..94
FT /evidence="ECO:0007829|PDB:4N9W"
FT STRAND 98..100
FT /evidence="ECO:0007829|PDB:4N9W"
FT HELIX 101..108
FT /evidence="ECO:0007829|PDB:4N9W"
FT STRAND 109..117
FT /evidence="ECO:0007829|PDB:4N9W"
FT HELIX 120..123
FT /evidence="ECO:0007829|PDB:4N9W"
FT HELIX 124..126
FT /evidence="ECO:0007829|PDB:4N9W"
FT HELIX 128..131
FT /evidence="ECO:0007829|PDB:4N9W"
FT HELIX 132..134
FT /evidence="ECO:0007829|PDB:4N9W"
FT HELIX 135..138
FT /evidence="ECO:0007829|PDB:4N9W"
FT STRAND 143..146
FT /evidence="ECO:0007829|PDB:4N9W"
FT HELIX 149..159
FT /evidence="ECO:0007829|PDB:2GEK"
FT STRAND 163..165
FT /evidence="ECO:0007829|PDB:2GEK"
FT HELIX 172..176
FT /evidence="ECO:0007829|PDB:4N9W"
FT STRAND 190..195
FT /evidence="ECO:0007829|PDB:4N9W"
FT HELIX 200..202
FT /evidence="ECO:0007829|PDB:4N9W"
FT HELIX 204..217
FT /evidence="ECO:0007829|PDB:4N9W"
FT STRAND 222..227
FT /evidence="ECO:0007829|PDB:4N9W"
FT HELIX 231..238
FT /evidence="ECO:0007829|PDB:4N9W"
FT HELIX 239..244
FT /evidence="ECO:0007829|PDB:4N9W"
FT STRAND 245..250
FT /evidence="ECO:0007829|PDB:4N9W"
FT HELIX 253..262
FT /evidence="ECO:0007829|PDB:4N9W"
FT STRAND 264..268
FT /evidence="ECO:0007829|PDB:4N9W"
FT HELIX 278..286
FT /evidence="ECO:0007829|PDB:4N9W"
FT STRAND 289..293
FT /evidence="ECO:0007829|PDB:4N9W"
FT HELIX 296..301
FT /evidence="ECO:0007829|PDB:4N9W"
FT HELIX 303..305
FT /evidence="ECO:0007829|PDB:4N9W"
FT STRAND 307..311
FT /evidence="ECO:0007829|PDB:4N9W"
FT HELIX 316..328
FT /evidence="ECO:0007829|PDB:4N9W"
FT HELIX 330..343
FT /evidence="ECO:0007829|PDB:4N9W"
FT HELIX 344..347
FT /evidence="ECO:0007829|PDB:4N9W"
FT HELIX 349..363
FT /evidence="ECO:0007829|PDB:4N9W"
FT STRAND 371..373
FT /evidence="ECO:0007829|PDB:4NC9"
SQ SEQUENCE 386 AA; 41220 MW; 1A5A6B5A2E36BC2E CRC64;
MRIGMVCPYS FDVPGGVQSH VLQLAEVLRD AGHEVSVLAP ASPHVKLPDY VVSGGKAVPI
PYNGSVARLR FGPATHRKVK KWIAEGDFDV LHIHEPNAPS LSMLALQAAE GPIVATFHTS
TTKSLTLSVF QGILRPYHEK IIGRIAVSDL ARRWQMEALG SDAVEIPNGV DVASFADAPL
LDGYPREGRT VLFLGRYDEP RKGMAVLLAA LPKLVARFPD VEILIVGRGD EDELREQAGD
LAGHLRFLGQ VDDATKASAM RSADVYCAPH LGGESFGIVL VEAMAAGTAV VASDLDAFRR
VLADGDAGRL VPVDDADGMA AALIGILEDD QLRAGYVARA SERVHRYDWS VVSAQIMRVY
ETVSGAGIKV QVSGAANRDE TAGESV
