PIPS_MYCBP
ID PIPS_MYCBP Reviewed; 217 AA.
AC A0A0H3MFZ3;
DT 16-OCT-2019, integrated into UniProtKB/Swiss-Prot.
DT 16-SEP-2015, sequence version 1.
DT 03-AUG-2022, entry version 26.
DE RecName: Full=Phosphatidylinositol phosphate synthase {ECO:0000303|PubMed:23225597};
DE Short=PIP synthase {ECO:0000303|PubMed:23225597};
DE EC=2.7.8.- {ECO:0000269|PubMed:20798167, ECO:0000269|PubMed:23225597};
DE AltName: Full=CDP-diacylglycerol--D-myo-inositol-3-phosphate 3-phosphatidyltransferase;
GN Name=pgsA1 {ECO:0000312|EMBL:CAL72625.1};
GN OrderedLocusNames=BCG_2637c {ECO:0000312|EMBL:CAL72625.1};
OS Mycobacterium bovis (strain BCG / Pasteur 1173P2).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=410289;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=BCG / Pasteur 1173P2;
RX PubMed=17372194; DOI=10.1073/pnas.0700869104;
RA Brosch R., Gordon S.V., Garnier T., Eiglmeier K., Frigui W., Valenti P.,
RA Dos Santos S., Duthoy S., Lacroix C., Garcia-Pelayo C., Inwald J.K.,
RA Golby P., Garcia J.N., Hewinson R.G., Behr M.A., Quail M.A., Churcher C.,
RA Barrell B.G., Parkhill J., Cole S.T.;
RT "Genome plasticity of BCG and impact on vaccine efficacy.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:5596-5601(2007).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RC STRAIN=BCG;
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 [3]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION, AND
RP SUBCELLULAR LOCATION.
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.
CC {ECO:0000269|PubMed:20798167, ECO:0000269|PubMed:23225597}.
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, ECO:0000269|PubMed:23225597};
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, ECO:0000269|PubMed:23225597};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:23225597};
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). {ECO:0000269|PubMed:23225597}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 8.5. {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:0000269|PubMed:23225597};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the CDP-alcohol phosphatidyltransferase class-I
CC family. {ECO:0000255|HAMAP-Rule:MF_02241, ECO:0000305}.
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; AM408590; CAL72625.1; -; Genomic_DNA.
DR RefSeq; WP_003413482.1; NC_008769.1.
DR AlphaFoldDB; A0A0H3MFZ3; -.
DR SMR; A0A0H3MFZ3; -.
DR KEGG; mbb:BCG_2637c; -.
DR HOGENOM; CLU_080384_0_1_11; -.
DR OMA; DGNMARQ; -.
DR BRENDA; 2.7.8.B13; 3494.
DR UniPathway; UPA00220; -.
DR Proteomes; UP000001472; Chromosome.
DR GO; GO:0005887; C:integral component of plasma membrane; IEA:UniProtKB-UniRule.
DR GO; GO:0000287; F:magnesium ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0016780; F:phosphotransferase activity, for other substituted phosphate groups; IEA:UniProtKB-UniRule.
DR GO; GO:0008654; P:phospholipid biosynthetic process; IEA:UniProtKB-UniRule.
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; Magnesium; Membrane; Metal-binding; Transferase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..217
FT /note="Phosphatidylinositol phosphate synthase"
FT /id="PRO_0000448359"
FT TRANSMEM 28..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..200
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 217 AA; 23252 MW; 49BCA9781E35AF2C CRC64;
MSKLPFLSRA AFARITTPIA RGLLRVGLTP DVVTILGTTA SVAGALTLFP MGKLFAGACV
VWFFVLFDML DGAMARERGG GTRFGAVLDA TCDRISDGAV FCGLLWWIAF HMRDRPLVIA
TLICLVTSQV ISYIKARAEA SGLRGDGGFI ERPERLIIVL TGAGVSDFPF VPWPPALSVG
MWLLAVASVI TCVQRLHTVW TSPGAIDRMA IPGKGDR
