CDIPT_DROME
ID CDIPT_DROME Reviewed; 224 AA.
AC Q8SX37; F3YDD4; Q8IR29; Q9VXR7;
DT 12-SEP-2018, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=CDP-diacylglycerol--inositol 3-phosphatidyltransferase {ECO:0000250|UniProtKB:P70500};
DE Short=CDIPT {ECO:0000250|UniProtKB:P70500};
DE EC=2.7.8.11 {ECO:0000269|PubMed:17151285};
DE AltName: Full=Phosphatidylinositol synthase {ECO:0000303|PubMed:17151285};
GN Name=Pis {ECO:0000303|PubMed:17151285, ECO:0000312|FlyBase:FBgn0030670};
GN ORFNames=CG9245 {ECO:0000312|FlyBase:FBgn0030670};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1] {ECO:0000312|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2] {ECO:0000312|Proteomes:UP000000803}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3] {ECO:0000312|EMBL:AAM11219.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Carlson J., Booth B., Frise E., Park S., Wan K., Yu C., Celniker S.;
RL Submitted (APR-2011) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=17151285; DOI=10.1523/jneurosci.3673-06.2006;
RA Wang T., Montell C.;
RT "A phosphoinositide synthase required for a sustained light response.";
RL J. Neurosci. 26:12816-12825(2006).
RN [5] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24603715; DOI=10.1371/journal.pgen.1004172;
RA Liu Y., Wang W., Shui G., Huang X.;
RT "CDP-diacylglycerol synthetase coordinates cell growth and fat storage
RT through phosphatidylinositol metabolism and the insulin pathway.";
RL PLoS Genet. 10:E1004172-E1004172(2014).
RN [6] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP ASP-75 AND CYS-107.
RX PubMed=24828534; DOI=10.1073/pnas.1407351111;
RA Devergne O., Tsung K., Barcelo G., Schuepbach T.;
RT "Polarized deposition of basement membrane proteins depends on
RT Phosphatidylinositol synthase and the levels of Phosphatidylinositol 4,5-
RT bisphosphate.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:7689-7694(2014).
RN [7] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=28228250; DOI=10.1016/j.celrep.2017.02.002;
RA Devergne O., Sun G.H., Schuepbach T.;
RT "Stratum, a Homolog of the Human GEF Mss4, Partnered with Rab8, Controls
RT the Basal Restriction of Basement Membrane Proteins in Epithelial Cells.";
RL Cell Rep. 18:1831-1839(2017).
CC -!- FUNCTION: Catalyzes the biosynthesis of phosphatidylinositol (PtdIns)
CC as well as PtdIns:inositol exchange reaction (PubMed:17151285,
CC PubMed:24828534, PubMed:24603715). May thus act to reduce an excessive
CC cellular PtdIns content (By similarity). The exchange activity is due
CC to the reverse reaction of PtdIns synthase and is dependent on CMP,
CC which is tightly bound to the enzyme (By similarity). Required for the
CC regeneration of the signaling molecule phosphatidylinositol 4,5-
CC bisphosphate (PtdInsP2) from phosphatidic acid (PA) and maintenance of
CC its steady supply during signaling, thus playing an essential role
CC during phospholipase C-mediated transduction (PubMed:17151285). This
CC function is essential in photoreceptors for light-activated recycling
CC of PtdInsP2 during phototransduction (PubMed:17151285). As a key enzyme
CC of the phosphoinositide pathway, indirectly involved in the polarized
CC secretion of basal membrane (BM) proteins in follicle epithelial (FE)
CC cells through promoting PtdInsP2 synthesis in the apical and lateral
CC plasma membranes of FE cells (PubMed:24828534). PtdInsP2 controls the
CC localization of Crag and perhaps the localization and expression of
CC strat, both of which are essential for restricting the secretion of BM
CC proteins to the basal surface (PubMed:24828534, PubMed:28228250).
CC {ECO:0000250|UniProtKB:P70500, ECO:0000269|PubMed:17151285,
CC ECO:0000269|PubMed:24603715, ECO:0000269|PubMed:24828534,
CC ECO:0000269|PubMed:28228250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a CDP-1,2-diacyl-sn-glycerol + myo-inositol = a 1,2-diacyl-sn-
CC glycero-3-phospho-(1D-myo-inositol) + CMP + H(+);
CC Xref=Rhea:RHEA:11580, ChEBI:CHEBI:15378, ChEBI:CHEBI:17268,
CC ChEBI:CHEBI:57880, ChEBI:CHEBI:58332, ChEBI:CHEBI:60377; EC=2.7.8.11;
CC Evidence={ECO:0000269|PubMed:17151285};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:P70500};
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P70500};
CC Note=Although Mn(2+) can act as a cofactor, it is much less effective
CC than Mg(2+). {ECO:0000250|UniProtKB:P70500};
CC -!- INTERACTION:
CC Q8SX37; B3DND5: CG12077-RA; NbExp=4; IntAct=EBI-84226, EBI-26699841;
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:24828534}; Multi-pass membrane protein
CC {ECO:0000255}. Lateral cell membrane {ECO:0000269|PubMed:24828534};
CC Multi-pass membrane protein {ECO:0000255}. Note=In follicle cells,
CC detected at the apical and lateral regions of the plasma membrane.
CC {ECO:0000269|PubMed:24828534}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=A {ECO:0000312|FlyBase:FBgn0030670};
CC IsoId=Q8SX37-1; Sequence=Displayed;
CC Name=B {ECO:0000312|FlyBase:FBgn0030670};
CC IsoId=Q8SX37-2; Sequence=VSP_059816, VSP_059817;
CC -!- TISSUE SPECIFICITY: In adults, expression is higher in the head than in
CC the body (at protein level). {ECO:0000269|PubMed:17151285}.
CC -!- DEVELOPMENTAL STAGE: Expressed throughout development, with low levels
CC of expression in embryos and 1st instar larvae, and highest levels of
CC expression in adults (at protein level). {ECO:0000269|PubMed:17151285}.
CC -!- DISRUPTION PHENOTYPE: Embryonic lethal (PubMed:17151285). In follicle
CC cells, abnormal apical accumulation of the basal membrane (BM) proteins
CC trol and vkg (PubMed:24828534). Decreased expression of strat in
CC follicle epithelial cells (PubMed:28228250). RNAi-mediated knockdown in
CC both larval salivary glands and fat body, results in small salivary
CC glands that accumulate lipid droplets. This is likely due to the
CC observed decrease in PtdIns levels that would lead to low insulin
CC pathway activity and defective cell growth. RNAi-mediated knockdown in
CC the fat body also results in a decrease in PtdIns levels in the fat
CC body and a decrease in fat body size (PubMed:24603715).
CC {ECO:0000269|PubMed:17151285, ECO:0000269|PubMed:24603715,
CC ECO:0000269|PubMed:24828534, ECO:0000269|PubMed:28228250}.
CC -!- SIMILARITY: Belongs to the CDP-alcohol phosphatidyltransferase class-I
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AEB39656.1; Type=Miscellaneous discrepancy; Evidence={ECO:0000305};
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DR EMBL; AE014298; AAF48491.2; -; Genomic_DNA.
DR EMBL; AE014298; AAN09359.1; -; Genomic_DNA.
DR EMBL; AY094866; AAM11219.1; -; mRNA.
DR EMBL; BT126295; AEB39656.1; ALT_SEQ; mRNA.
DR RefSeq; NP_573055.1; NM_132827.3. [Q8SX37-1]
DR RefSeq; NP_727878.1; NM_167456.3.
DR AlphaFoldDB; Q8SX37; -.
DR SMR; Q8SX37; -.
DR IntAct; Q8SX37; 34.
DR STRING; 7227.FBpp0073874; -.
DR PaxDb; Q8SX37; -.
DR PRIDE; Q8SX37; -.
DR DNASU; 32506; -.
DR EnsemblMetazoa; FBtr0074058; FBpp0073874; FBgn0030670. [Q8SX37-1]
DR EnsemblMetazoa; FBtr0074059; FBpp0073875; FBgn0030670.
DR GeneID; 32506; -.
DR KEGG; dme:Dmel_CG9245; -.
DR UCSC; CG9245-RA; d. melanogaster. [Q8SX37-1]
DR CTD; 32506; -.
DR FlyBase; FBgn0030670; Pis.
DR VEuPathDB; VectorBase:FBgn0030670; -.
DR eggNOG; KOG3240; Eukaryota.
DR GeneTree; ENSGT00940000154169; -.
DR HOGENOM; CLU_067602_2_0_1; -.
DR InParanoid; Q8SX37; -.
DR OMA; AQTYSEN; -.
DR OrthoDB; 1615564at2759; -.
DR PhylomeDB; Q8SX37; -.
DR Reactome; R-DME-1483226; Synthesis of PI.
DR SignaLink; Q8SX37; -.
DR BioGRID-ORCS; 32506; 1 hit in 1 CRISPR screen.
DR GenomeRNAi; 32506; -.
DR PRO; PR:Q8SX37; -.
DR Proteomes; UP000000803; Chromosome X.
DR Bgee; FBgn0030670; Expressed in seminal fluid secreting gland and 30 other tissues.
DR ExpressionAtlas; Q8SX37; baseline and differential.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016328; C:lateral plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0003881; F:CDP-diacylglycerol-inositol 3-phosphatidyltransferase activity; IDA:FlyBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0071711; P:basement membrane organization; IMP:FlyBase.
DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; IBA:GO_Central.
DR GO; GO:0007602; P:phototransduction; IMP:FlyBase.
DR Gene3D; 1.20.120.1760; -; 1.
DR InterPro; IPR000462; CDP-OH_P_trans.
DR InterPro; IPR043130; CDP-OH_PTrfase_TM_dom.
DR InterPro; IPR014387; CDP_diag_ino_3_P_euk.
DR Pfam; PF01066; CDP-OH_P_transf; 1.
DR PIRSF; PIRSF000848; CDP_diag_ino_3_P; 1.
DR PROSITE; PS00379; CDP_ALCOHOL_P_TRANSF; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Lipid biosynthesis; Lipid metabolism;
KW Magnesium; Manganese; Membrane; Metal-binding; Phospholipid biosynthesis;
KW Phospholipid metabolism; Reference proteome; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..224
FT /note="CDP-diacylglycerol--inositol 3-
FT phosphatidyltransferase"
FT /id="PRO_0000445078"
FT TRANSMEM 9..29
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 99..119
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 139..159
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 164..184
FT /note="Helical"
FT /evidence="ECO:0000255"
FT VAR_SEQ 62
FT /note="Q -> QTHCKHLSPPYWLSADIVEL (in isoform B)"
FT /id="VSP_059816"
FT VAR_SEQ 82..224
FT /note="Missing (in isoform B)"
FT /id="VSP_059817"
FT MUTAGEN 75
FT /note="D->N: In follicle epithelial cells, decreases
FT extracellular PtdInsP2 on apical and lateral sides of the
FT plasma membrane resulting in the abnormal apical
FT accumulation of basal membrane proteins such as vkg. As a
FT consequence the follicle cells display multiple layers or
FT gaps in the epithelium."
FT /evidence="ECO:0000269|PubMed:24828534"
FT MUTAGEN 107
FT /note="C->W: In follicle epithelial cells, apical
FT accumulation of the basal membrane protein vkg as apical
FT extracellular aggregates. Crag levels decrease and Crag no
FT longer accumulates at the plasma membrane, instead it has a
FT diffuse cytoplasmic distribution. No direct effect on
FT maintenance of apical-basal polarity in follicle cells."
FT /evidence="ECO:0000269|PubMed:24828534"
SQ SEQUENCE 224 AA; 25505 MW; 3B860072C597BCA2 CRC64;
MTIAEHDNVF IFVPNLIGYA RIVLALIAFW FMSTNYVISG WCYVTSALLD AVDGQAARAF
NQSTRFGAML DQLTDRCGTT GLLVTLAYFY PRYMFWFQLS IAIDVACHWL FMQTSVVVGR
SSHKVNDNFI MRLYYQKDIL TFMCCVNELF YVCLYLLHFT YGPLIFGASL FKILAFLTGP
FAVLKALISV MHAYVAGIDL AAVDVRERQE RRQKSEPVSG KKVE
