PIPS_MYCS2
ID PIPS_MYCS2 Reviewed; 222 AA.
AC Q9F7Y9; A0QWG4;
DT 23-MAR-2010, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 66.
DE RecName: Full=Phosphatidylinositol phosphate synthase {ECO:0000303|PubMed:20798167};
DE Short=PIP synthase {ECO:0000303|PubMed:20798167};
DE EC=2.7.8.- {ECO:0000269|PubMed:20798167};
DE AltName: Full=CDP-diacylglycerol--D-myo-inositol-3-phosphate 3-phosphatidyltransferase;
GN Name=pgsA {ECO:0000303|PubMed:10889206};
GN OrderedLocusNames=MSMEG_2933 {ECO:0000312|EMBL:ABK73364.1};
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 [GENOMIC DNA], FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=10889206; DOI=10.1074/jbc.m004658200;
RA Jackson M., Crick D.C., Brennan P.J.;
RT "Phosphatidylinositol is an essential phospholipid of mycobacteria.";
RL J. Biol. Chem. 275:30092-30099(2000).
RN [2]
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 [3]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND SUBCELLULAR LOCATION.
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=20798167; DOI=10.1093/jb/mvq093;
RA Morii H., Ogawa M., Fukuda K., Taniguchi H., Koga Y.;
RT "A revised biosynthetic pathway for phosphatidylinositol in Mycobacteria.";
RL J. Biochem. 148:593-602(2010).
RN [4]
RP ACTIVITY REGULATION.
RX PubMed=23225597; DOI=10.1093/jb/mvs141;
RA Morii H., Okauchi T., Nomiya H., Ogawa M., Fukuda K., Taniguchi H.;
RT "Studies of inositol 1-phosphate analogues as inhibitors of the
RT phosphatidylinositol phosphate synthase in mycobacteria.";
RL J. Biochem. 153:257-266(2013).
CC -!- FUNCTION: Catalyzes the conjugation of the 1'-hydroxyl group of D-myo-
CC inositol-3-phosphate (also named L-myo-inositol-1-phosphate) with a
CC lipid tail of cytidine diphosphate diacylglycerol (CDP-DAG), forming
CC phosphatidylinositol phosphate (PIP) and CMP. PIP is a precursor of
CC phosphatidylinositol (PI) which is an essential lipid for mycobacteria
CC required for formation of their cell wall (PubMed:20798167). Is
CC essential to the survival of M.smegmatis (PubMed:10889206).
CC {ECO:0000269|PubMed:10889206, ECO:0000269|PubMed:20798167}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1D-myo-inositol 3-phosphate + a CDP-1,2-diacyl-sn-glycerol = a
CC 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3-phosphate) + CMP +
CC H(+); Xref=Rhea:RHEA:60504, ChEBI:CHEBI:15378, ChEBI:CHEBI:58088,
CC ChEBI:CHEBI:58332, ChEBI:CHEBI:58401, ChEBI:CHEBI:60377;
CC Evidence={ECO:0000269|PubMed:20798167};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-di-(9Z-octadecenoyl)-sn-glycero-3-cytidine-5'-diphosphate
CC + 1D-myo-inositol 3-phosphate = 1,2-di-(9Z-octadecenoyl)-sn-glycero-
CC 3-phospho-(1D-myo-inositol-3-phosphate) + CMP + H(+);
CC Xref=Rhea:RHEA:61216, ChEBI:CHEBI:15378, ChEBI:CHEBI:58401,
CC ChEBI:CHEBI:60377, ChEBI:CHEBI:85356, ChEBI:CHEBI:144472;
CC Evidence={ECO:0000269|PubMed:20798167};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-dihexadecanoyl-sn-glycero-3-CDP + 1D-myo-inositol 3-
CC phosphate = 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol-
CC 3-phosphate) + CMP + H(+); Xref=Rhea:RHEA:61220, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:58401, ChEBI:CHEBI:60377, ChEBI:CHEBI:77190,
CC ChEBI:CHEBI:78995; Evidence={ECO:0000269|PubMed:20798167};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P9WPG7};
CC Note=Contains a di-nuclear catalytic Mg(2+) center.
CC {ECO:0000250|UniProtKB:P9WPG7};
CC -!- ACTIVITY REGULATION: Competitively inhibited by several inositol 1-
CC phosphate analogs, including the phosphonate analog 1-deoxy-1-
CC phosphonomethyl-myo-inositol (Ino-C-P) (By similarity). This leads to
CC inhibition of M.smegmatis growth (PubMed:23225597).
CC {ECO:0000250|UniProtKB:A0A0H3MFZ3, ECO:0000269|PubMed:23225597}.
CC -!- PATHWAY: Phospholipid metabolism; phosphatidylinositol phosphate
CC biosynthesis. {ECO:0000269|PubMed:20798167}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P9WPG7}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}. Secreted, cell wall
CC {ECO:0000269|PubMed:20798167}.
CC -!- DISRUPTION PHENOTYPE: Allelic exchange at the pgsA chromosomal locus is
CC achievable only when a rescue copy of the pgsA gene is provided to the
CC bacterium, demonstrating gene essentiality.
CC {ECO:0000269|PubMed:10889206}.
CC -!- SIMILARITY: Belongs to the CDP-alcohol phosphatidyltransferase class-I
CC family. {ECO:0000255|HAMAP-Rule:MF_02241, ECO:0000305}.
CC -!- CAUTION: Was orginally thought to be a phosphatidylinositol (PI)
CC synthase. {ECO:0000305|PubMed:10889206}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF265558; AAG17336.1; -; Genomic_DNA.
DR EMBL; CP000480; ABK73364.1; -; Genomic_DNA.
DR RefSeq; WP_011728701.1; NZ_SIJM01000002.1.
DR RefSeq; YP_887252.1; NC_008596.1.
DR AlphaFoldDB; Q9F7Y9; -.
DR SMR; Q9F7Y9; -.
DR STRING; 246196.MSMEI_2859; -.
DR EnsemblBacteria; ABK73364; ABK73364; MSMEG_2933.
DR GeneID; 66734341; -.
DR KEGG; msm:MSMEG_2933; -.
DR PATRIC; fig|246196.19.peg.2896; -.
DR eggNOG; COG0558; Bacteria.
DR OMA; DGNMARQ; -.
DR OrthoDB; 1232102at2; -.
DR UniPathway; UPA00220; -.
DR Proteomes; UP000000757; Chromosome.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-KW.
DR GO; GO:0005887; C:integral component of plasma membrane; IEA:UniProtKB-UniRule.
DR GO; GO:0003881; F:CDP-diacylglycerol-inositol 3-phosphatidyltransferase activity; ISS:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0008654; P:phospholipid biosynthetic process; ISS:UniProtKB.
DR Gene3D; 1.20.120.1760; -; 1.
DR HAMAP; MF_02241; PIP_synthase; 1.
DR InterPro; IPR000462; CDP-OH_P_trans.
DR InterPro; IPR043130; CDP-OH_PTrfase_TM_dom.
DR InterPro; IPR044268; PIP_synthase_PgsA1.
DR Pfam; PF01066; CDP-OH_P_transf; 1.
DR PROSITE; PS00379; CDP_ALCOHOL_P_TRANSF; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cell wall; Lipid biosynthesis; Lipid metabolism; Magnesium;
KW Membrane; Metal-binding; Phospholipid biosynthesis;
KW Phospholipid metabolism; Reference proteome; Secreted; Transferase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..222
FT /note="Phosphatidylinositol phosphate synthase"
FT /id="PRO_0000393109"
FT TRANSMEM 32..49
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 55..74
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 95..112
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 118..136
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 156..173
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 179..196
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ACT_SITE 93
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P9WPG7"
FT BINDING 31..34
FT /ligand="a CDP-1,2-diacyl-sn-glycerol"
FT /ligand_id="ChEBI:CHEBI:58332"
FT /evidence="ECO:0000250|UniProtKB:P9WPG7"
FT BINDING 68
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P9WPG7"
FT BINDING 68
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P9WPG7"
FT BINDING 71
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P9WPG7"
FT BINDING 72
FT /ligand="a CDP-1,2-diacyl-sn-glycerol"
FT /ligand_id="ChEBI:CHEBI:58332"
FT /evidence="ECO:0000250|UniProtKB:P9WPG7"
FT BINDING 76
FT /ligand="a CDP-1,2-diacyl-sn-glycerol"
FT /ligand_id="ChEBI:CHEBI:58332"
FT /evidence="ECO:0000250|UniProtKB:P9WPG7"
FT BINDING 82
FT /ligand="a CDP-1,2-diacyl-sn-glycerol"
FT /ligand_id="ChEBI:CHEBI:58332"
FT /evidence="ECO:0000250|UniProtKB:P9WPG7"
FT BINDING 89
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P9WPG7"
FT BINDING 89
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P9WPG7"
FT BINDING 93
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P9WPG7"
SQ SEQUENCE 222 AA; 23335 MW; 36F52D5A78C8CD51 CRC64;
MSNVYLMTRA AYVKLSRPVA KAALRAGLTP DIVTLAGTAA AVIGALTLFP IGQLWWGAVV
VSFFVLADML DGAMAREQGG GTRFGAVLDA TCDRLGDGAV FAGLTWWAAF GLDSPSLVVA
TLICLVTSQV ISYIKARAEA SGLRGDGGII ERPERLVIVL IGAGLSDLPF FPLPWTLHVA
MWVLAVASVV TLLQRVHAVR TSPGAMEPLH PANGEKPETS EP
