CDS_DROME
ID CDS_DROME Reviewed; 447 AA.
AC P56079; Q9VSE0;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 2.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Phosphatidate cytidylyltransferase, photoreceptor-specific;
DE EC=2.7.7.41 {ECO:0000269|PubMed:7816135, ECO:0000305|PubMed:24603715, ECO:0000305|PubMed:26791243};
DE AltName: Full=CDP-DAG synthase {ECO:0000303|PubMed:26791243};
DE AltName: Full=CDP-DG synthase;
DE AltName: Full=CDP-diacylglycerol synthase {ECO:0000312|FlyBase:FBgn0010350};
DE Short=CDS;
DE AltName: Full=CDP-diglyceride pyrophosphorylase;
DE AltName: Full=CDP-diglyceride synthase;
DE AltName: Full=CTP:phosphatidate cytidylyltransferase;
GN Name=Cds {ECO:0000312|FlyBase:FBgn0010350};
GN Synonyms=CdsA {ECO:0000303|PubMed:26791243,
GN ECO:0000312|FlyBase:FBgn0010350};
GN ORFNames=CG7962 {ECO:0000312|FlyBase:FBgn0010350};
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]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, AND
RP PATHWAY.
RC TISSUE=Retina;
RX PubMed=7816135; DOI=10.1038/373216a0;
RA Wu L., Niemeyer B., Colley N., Socolich M., Zuker C.S.;
RT "Regulation of PLC-mediated signalling in vivo by CDP-diacylglycerol
RT synthase.";
RL Nature 373:216-222(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
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 [3]
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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-30; SER-34; SER-35 AND
RP SER-40, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Embryo;
RX PubMed=18327897; DOI=10.1021/pr700696a;
RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL J. Proteome Res. 7:1675-1682(2008).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, DEVELOPMENTAL STAGE, AND DISRUPTION
RP 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]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBCELLULAR LOCATION, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=26791243; DOI=10.1098/rsob.150169;
RA Laurinyecz B., Peter M., Vedelek V., Kovacs A.L., Juhasz G., Maroy P.,
RA Vigh L., Balogh G., Sinka R.;
RT "Reduced expression of CDP-DAG synthase changes lipid composition and leads
RT to male sterility in Drosophila.";
RL Open Biol. 6:50169-50169(2016).
CC -!- FUNCTION: Catalyzes the conversion of phosphatidic acid (PA) to CDP-
CC diacylglycerol (CDP-DAG), an important precursor for the synthesis of
CC phosphatidylinositol (PtdIns) and phosphatidylglycerol (PG)
CC (PubMed:7816135, PubMed:24603715). Required for the regeneration of the
CC signaling molecule phosphatidylinositol 4,5-bisphosphate (PtdInsP2)
CC from PA and maintenance of its steady supply during signaling thus
CC playing an essential role during phospholipase C-mediated transduction
CC (PubMed:7816135). In the salivary glands and possibly other adipose
CC tissues, function is essential for regulating cell growth and neutral
CC lipid storage by coordinating PtdIns metabolism and insulin pathway
CC activity (PubMed:24603715). Acts by positively regulating activity of
CC the insulin pathway through synthesis of PtdIns, and in turn the
CC insulin pathway up-regulates the synthesis of CdsA (PubMed:24603715).
CC This CdsA-insulin positive feedback loop may be one of the mechanisms
CC for coordinating cell growth and fat storage; switching to fat storage
CC when cells reach homeostasis or converting from growth to fat storage
CC under nutrient-poor conditions (PubMed:24603715). Required for
CC spermatid individualization by regulating lipid compositions and lipid-
CC mediated signaling during spermatogenesis (PubMed:26791243).
CC {ECO:0000269|PubMed:24603715, ECO:0000269|PubMed:26791243,
CC ECO:0000269|PubMed:7816135}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphate + CTP + H(+) = a CDP-1,2-
CC diacyl-sn-glycerol + diphosphate; Xref=Rhea:RHEA:16229,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:37563,
CC ChEBI:CHEBI:58332, ChEBI:CHEBI:58608; EC=2.7.7.41;
CC Evidence={ECO:0000269|PubMed:7816135, ECO:0000305|PubMed:24603715,
CC ECO:0000305|PubMed:26791243};
CC -!- PATHWAY: Phospholipid metabolism; CDP-diacylglycerol biosynthesis; CDP-
CC diacylglycerol from sn-glycerol 3-phosphate: step 3/3.
CC {ECO:0000269|PubMed:7816135, ECO:0000305|PubMed:24603715,
CC ECO:0000305|PubMed:26791243}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:26791243}; Multi-pass membrane protein
CC {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Retina. Localized to the photoreceptor neurons,
CC both in the compound eyes and ocelli.
CC -!- DEVELOPMENTAL STAGE: In 3rd instar larvae, expressed in various tissues
CC including the brain, salivary glands, fat body, proventriculus, hind
CC gut, muscle, Malpighian tubules and tracheal tubes. Relatively low
CC levels of expression in the brain compared to expression levels in the
CC salivary gland, fat body and gut. {ECO:0000269|PubMed:24603715}.
CC -!- DISRUPTION PHENOTYPE: Lethal during the late embryonic to early larval
CC stages (PubMed:24603715). Hypomorphic mutants are viable but male
CC adults are sterile, whereas female adults remain fertile
CC (PubMed:26791243). Impairs spermatid individualization showing abnormal
CC mitochondria morphology and defects in lipid compositions and lipid-
CC mediated signaling (PubMed:26791243). RNAi-mediated knockdown results
CC in low insulin pathway activity and defective cell growth in certain
CC tissues (PubMed:24603715). Various non-adipose tissues display
CC excessive fat accumulation such as the salivary glands, proventriculus,
CC hind gut, Malpighian tubules and trachea (PubMed:24603715). In addition
CC gross reduction in cell size results in smaller salivary glands,
CC imaginal disks and brains compared to controls (PubMed:24603715). RNAi-
CC mediated knockdown in both the salivary glands and fat body, results in
CC decreased levels of phosphatidylinositol (PtdIns) in the whole larvae
CC and in the salivary glands (PubMed:24603715). Whole larvae also display
CC decreased levels of phosphatidylglycerol (PG) and increased levels of
CC phosphatidic acid (PA) (PubMed:24603715). Larvae display low insulin
CC pathway activity with reduced levels of phosphatidylinositol 4,5-
CC bisphosphate (PtdInsP2) and phosphatidylinositol 3,4,5-trisphosphate
CC (Ptdinsp3), and decreased levels of 'S-505' phosphorylated Akt1
CC (PubMed:24603715). RNAi-mediated knockdown specifically in the fat
CC body, results in a decrease in PtdIns levels but there is no effect on
CC the growth and neutral lipid storage in the fat body (PubMed:24603715).
CC This is likely due to unknown compensatory mechanisms as there is an
CC increase in the levels of diphosphate diacylglycerol and
CC phosphatidylethanolamine in the fat body (PubMed:24603715).
CC {ECO:0000269|PubMed:24603715, ECO:0000269|PubMed:26791243}.
CC -!- SIMILARITY: Belongs to the CDS family. {ECO:0000305}.
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DR EMBL; AE014296; AAF50483.1; -; Genomic_DNA.
DR RefSeq; NP_001286976.1; NM_001300047.1.
DR RefSeq; NP_524661.1; NM_079922.4.
DR AlphaFoldDB; P56079; -.
DR BioGRID; 68739; 20.
DR DIP; DIP-23447N; -.
DR IntAct; P56079; 3.
DR STRING; 7227.FBpp0076411; -.
DR iPTMnet; P56079; -.
DR PaxDb; P56079; -.
DR PRIDE; P56079; -.
DR EnsemblMetazoa; FBtr0076688; FBpp0076411; FBgn0010350.
DR EnsemblMetazoa; FBtr0346546; FBpp0312164; FBgn0010350.
DR GeneID; 43950; -.
DR KEGG; dme:Dmel_CG7962; -.
DR CTD; 43950; -.
DR FlyBase; FBgn0010350; Cds.
DR VEuPathDB; VectorBase:FBgn0010350; -.
DR eggNOG; KOG1440; Eukaryota.
DR HOGENOM; CLU_023471_0_1_1; -.
DR InParanoid; P56079; -.
DR OMA; FIMNNIF; -.
DR OrthoDB; 1072976at2759; -.
DR PhylomeDB; P56079; -.
DR BRENDA; 2.7.7.41; 1994.
DR Reactome; R-DME-1483148; Synthesis of PG.
DR Reactome; R-DME-1483226; Synthesis of PI.
DR UniPathway; UPA00557; UER00614.
DR BioGRID-ORCS; 43950; 0 hits in 3 CRISPR screens.
DR ChiTaRS; CdsA; fly.
DR GenomeRNAi; 43950; -.
DR PRO; PR:P56079; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0010350; Expressed in head capsule and 26 other tissues.
DR ExpressionAtlas; P56079; baseline and differential.
DR Genevisible; P56079; DM.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0004605; F:phosphatidate cytidylyltransferase activity; IDA:FlyBase.
DR GO; GO:0016024; P:CDP-diacylglycerol biosynthetic process; NAS:FlyBase.
DR GO; GO:0008610; P:lipid biosynthetic process; IMP:FlyBase.
DR GO; GO:0010868; P:negative regulation of triglyceride biosynthetic process; IMP:FlyBase.
DR GO; GO:0007602; P:phototransduction; IMP:FlyBase.
DR GO; GO:0010513; P:positive regulation of phosphatidylinositol biosynthetic process; IMP:FlyBase.
DR GO; GO:0010883; P:regulation of lipid storage; IMP:FlyBase.
DR GO; GO:0016056; P:rhodopsin mediated signaling pathway; IMP:FlyBase.
DR GO; GO:0007291; P:sperm individualization; IMP:FlyBase.
DR GO; GO:0007430; P:terminal branching, open tracheal system; HMP:FlyBase.
DR GO; GO:0043052; P:thermotaxis; IDA:FlyBase.
DR GO; GO:0007601; P:visual perception; IEA:UniProtKB-KW.
DR InterPro; IPR000374; PC_trans.
DR InterPro; IPR016720; PC_Trfase_euk.
DR PANTHER; PTHR13773; PTHR13773; 1.
DR PIRSF; PIRSF018269; PC_trans_euk; 1.
DR PROSITE; PS01315; CDS; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Lipid biosynthesis; Lipid metabolism; Membrane;
KW Nucleotidyltransferase; Phospholipid biosynthesis; Phospholipid metabolism;
KW Phosphoprotein; Reference proteome; Sensory transduction; Transferase;
KW Transmembrane; Transmembrane helix; Vision.
FT CHAIN 1..447
FT /note="Phosphatidate cytidylyltransferase, photoreceptor-
FT specific"
FT /id="PRO_0000090720"
FT TRANSMEM 88..108
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 147..167
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 180..200
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 203..223
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 227..247
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 276..296
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 350..370
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 1..49
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..15
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 30..49
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 30
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 34
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 35
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 40
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT CONFLICT 444
FT /note="D -> H (in Ref. 1; no nucleotide entry)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 447 AA; 51511 MW; 2E690CD02D3F4187 CRC64;
MAEVRRRKGE DEPLEDTAIS GSDAANKRNS AADSSDHVDS EEEKIPEEKF VDELAKNLPQ
GTDKTPEILD SALKDLPDRW KNWVIRGIFT WIMICGFALI IYGGPLALMI TTLLVQVKCF
QEIISIGYQV YRIHGLPWFR SLSWYFLLTS NYFFYGENLV DYFGVVINRV EYLKFLVTYH
RFLSFALYII GFVWFVLSLV KKYYIKQFSL FAWTHVSLLI VVTQSYLIIQ NIFEGLIWFI
VPVSMIVCND VMAYVFGFFF GRTPLIKLSP KKTWEGFIGG GFATVLFGIL FSYVLCNYQY
FICPIQYSEE QGRMTMSCVP SYLFTPQEYS LKLFGIGKTL NLYPFIWHSI SLSLFSSIIG
PFGGFFASGF KRAFKIKDFG DMIPGHGGIM DRFDCQFLMA TFVNVYISSF IRTPSPAKLL
TQIYNLKPDQ QYQIYQSLKD NLGDMLT
