ID   CDS1_RAT                Reviewed;         461 AA.
AC   O35052; A0JPL6; O88208;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   30-MAY-2000, sequence version 2.
DT   24-JAN-2024, entry version 149.
DE   RecName: Full=Phosphatidate cytidylyltransferase 1 {ECO:0000305};
DE            EC=2.7.7.41 {ECO:0000269|PubMed:29253589, ECO:0000269|PubMed:30862571, ECO:0000269|PubMed:9083091, ECO:0000269|PubMed:9345289};
DE   AltName: Full=CDP-DAG synthase 1;
DE   AltName: Full=CDP-DG synthase 1;
DE   AltName: Full=CDP-diacylglycerol synthase 1;
DE            Short=CDS 1;
DE   AltName: Full=CDP-diglyceride pyrophosphorylase 1;
DE   AltName: Full=CDP-diglyceride synthase 1;
DE   AltName: Full=CTP:phosphatidate cytidylyltransferase 1;
GN   Name=Cds1 {ECO:0000312|RGD:621185}; Synonyms=Cds;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, ACTIVITY
RP   REGULATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP   BIOPHYSICOCHEMICAL PROPERTIES.
RC   STRAIN=Wistar; TISSUE=Brain;
RX   PubMed=9083091; DOI=10.1074/jbc.272.14.9503;
RA   Saito S., Goto K., Tonosaki A., Kondo H.;
RT   "Gene cloning and characterization of CDP-diacylglycerol synthase from rat
RT   brain.";
RL   J. Biol. Chem. 272:9503-9509(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Wistar; TISSUE=Brain;
RA   Hosaka K., Imai H., Nikawa J.;
RT   "Rat brain CDP-diacylglycerol synthase.";
RL   Submitted (DEC-1997) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Liver;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   SUBCELLULAR LOCATION.
RX   PubMed=6271231; DOI=10.1016/0005-2760(81)90274-5;
RA   Ballas L.M., Bell R.M.;
RT   "Topography of glycerolipid synthetic enzymes. Synthesis of
RT   phosphatidylserine, phosphatidylinositol and glycerolipid intermediates
RT   occurs on the cytoplasmic surface of rat liver microsomal vesicles.";
RL   Biochim. Biophys. Acta 665:586-595(1981).
RN   [5]
RP   FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND COFACTOR.
RC   TISSUE=Liver;
RX   PubMed=9345289; DOI=10.1006/bbrc.1997.7422;
RA   Monaco M.E., Feldman M.;
RT   "Extraction and stabilization of mammalian CDP-diacylglycerol synthase
RT   activity.";
RL   Biochem. Biophys. Res. Commun. 239:166-170(1997).
RN   [6]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-35 AND SER-37, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22673903; DOI=10.1038/ncomms1871;
RA   Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA   Olsen J.V.;
RT   "Quantitative maps of protein phosphorylation sites across 14 different rat
RT   organs and tissues.";
RL   Nat. Commun. 3:876-876(2012).
RN   [7]
RP   FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND SUBCELLULAR LOCATION.
RX   PubMed=29253589; DOI=10.1016/j.bbalip.2017.12.005;
RA   Blunsom N.J., Gomez-Espinosa E., Ashlin T.G., Cockcroft S.;
RT   "Mitochondrial CDP-diacylglycerol synthase activity is due to the
RT   peripheral protein, TAMM41 and not due to the integral membrane protein,
RT   CDP-diacylglycerol synthase 1.";
RL   Biochim. Biophys. Acta 1863:284-298(2018).
RN   [8]
RP   FUNCTION, CATALYTIC ACTIVITY, AND INDUCTION.
RX   PubMed=30862571; DOI=10.1016/j.bbalip.2019.03.002;
RA   Blunsom N.J., Gomez-Espinosa E., Ashlin T.G., Cockcroft S.;
RT   "Sustained phospholipase C stimulation of H9c2 cardiomyoblasts by
RT   vasopressin induces an increase in CDP-diacylglycerol synthase 1 (CDS1)
RT   through protein kinase C and cFos.";
RL   Biochim. Biophys. Acta 1864:1072-1082(2019).
CC   -!- FUNCTION: Catalyzes the conversion of phosphatidic acid (PA) to CDP-
CC       diacylglycerol (CDP-DAG), an essential intermediate in the synthesis of
CC       phosphatidylglycerol, cardiolipin and phosphatidylinositol
CC       (PubMed:9083091, PubMed:9345289, PubMed:29253589, PubMed:30862571).
CC       Exhibits almost no acyl chain preference for PA, showing no
CC       discrimination for the sn-1/sn-2 acyl chain composition of PAs (By
CC       similarity). Plays an important role in regulatinng the growth of lipid
CC       droplets which are storage organelles at the center of lipid and energy
CC       homeostasis (By similarity). Positively regulates the differentiation
CC       and development of adipocytes (By similarity).
CC       {ECO:0000250|UniProtKB:P98191, ECO:0000250|UniProtKB:Q92903,
CC       ECO:0000269|PubMed:29253589, ECO:0000269|PubMed:30862571,
CC       ECO:0000269|PubMed:9083091, ECO:0000269|PubMed:9345289}.
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:29253589, ECO:0000269|PubMed:30862571,
CC         ECO:0000269|PubMed:9083091, ECO:0000269|PubMed:9345289};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16230;
CC         Evidence={ECO:0000305|PubMed:9083091};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-
CC         3-phosphate + CTP + H(+) = 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-
CC         eicosatetraenoyl)-sn-glycero-3-cytidine-5'-diphosphate + diphosphate;
CC         Xref=Rhea:RHEA:45648, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019,
CC         ChEBI:CHEBI:37563, ChEBI:CHEBI:77091, ChEBI:CHEBI:85349;
CC         Evidence={ECO:0000250|UniProtKB:Q92903};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45649;
CC         Evidence={ECO:0000250|UniProtKB:Q92903};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=1-octadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-
CC         phosphate + CTP + H(+) = 1-octadecanoyl-2-(9Z,12Z-octadecadienoyl)-
CC         sn-glycero-3-cytidine-5'-diphosphate + diphosphate;
CC         Xref=Rhea:RHEA:45660, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019,
CC         ChEBI:CHEBI:37563, ChEBI:CHEBI:77098, ChEBI:CHEBI:85352;
CC         Evidence={ECO:0000250|UniProtKB:Q92903};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45661;
CC         Evidence={ECO:0000250|UniProtKB:Q92903};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-
CC         3-phosphate + CTP + H(+) = 1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-
CC         eicosatetraenoyl)-sn-glycero-3-cytidine-5'-diphosphate + diphosphate;
CC         Xref=Rhea:RHEA:45652, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019,
CC         ChEBI:CHEBI:37563, ChEBI:CHEBI:72864, ChEBI:CHEBI:85350;
CC         Evidence={ECO:0000250|UniProtKB:Q92903};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45653;
CC         Evidence={ECO:0000250|UniProtKB:Q92903};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=1,2-di-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphate
CC         + CTP + H(+) = 1,2-di-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-
CC         cytidine-5'-diphosphate + diphosphate; Xref=Rhea:RHEA:45656,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:37563,
CC         ChEBI:CHEBI:77126, ChEBI:CHEBI:85351;
CC         Evidence={ECO:0000250|UniProtKB:Q92903};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45657;
CC         Evidence={ECO:0000250|UniProtKB:Q92903};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=1-octadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphate +
CC         CTP + H(+) = 1-octadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-
CC         cytidine-5'-diphosphate + diphosphate; Xref=Rhea:RHEA:45664,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:37563,
CC         ChEBI:CHEBI:74560, ChEBI:CHEBI:85353;
CC         Evidence={ECO:0000250|UniProtKB:Q92903};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45665;
CC         Evidence={ECO:0000250|UniProtKB:Q92903};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=1-octadecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-
CC         glycero-3-phosphate + CTP + H(+) = 1-octadecanoyl-2-
CC         (4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-cytidine-5'-
CC         diphosphate + diphosphate; Xref=Rhea:RHEA:45668, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:33019, ChEBI:CHEBI:37563, ChEBI:CHEBI:77130,
CC         ChEBI:CHEBI:85354; Evidence={ECO:0000250|UniProtKB:Q92903};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45669;
CC         Evidence={ECO:0000250|UniProtKB:Q92903};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphate + CTP +
CC         H(+) = 1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycero-3-cytidine-5'-
CC         diphosphate + diphosphate; Xref=Rhea:RHEA:45672, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:33019, ChEBI:CHEBI:37563, ChEBI:CHEBI:77128,
CC         ChEBI:CHEBI:85355; Evidence={ECO:0000250|UniProtKB:Q92903};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45673;
CC         Evidence={ECO:0000250|UniProtKB:Q92903};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphate + CTP + H(+) =
CC         1,2-di-(9Z-octadecenoyl)-sn-glycero-3-cytidine-5'-diphosphate +
CC         diphosphate; Xref=Rhea:RHEA:45676, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:33019, ChEBI:CHEBI:37563, ChEBI:CHEBI:74546,
CC         ChEBI:CHEBI:85356; Evidence={ECO:0000250|UniProtKB:Q92903};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45677;
CC         Evidence={ECO:0000250|UniProtKB:Q92903};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000269|PubMed:9345289};
CC   -!- ACTIVITY REGULATION: Activated by GTP. Inhibited by CDP-diacylglycerol
CC       and by phosphatidylglycerol 4,5-bisphosphate (PPI2).
CC       {ECO:0000269|PubMed:9083091, ECO:0000269|PubMed:9345289}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=102 uM for 1-stearoyl-2-arachidonoyl-sn-glycero-3-phosphate
CC         {ECO:0000269|PubMed:9083091};
CC         KM=114 uM for 1,2-dioleoyl-sn-glycero-3-phosphate
CC         {ECO:0000269|PubMed:9083091};
CC         KM=138 uM for phosphatidic acid {ECO:0000269|PubMed:9083091};
CC         Vmax=268 pmol/min/mg enzyme for
CC         1-stearoyl-2-arachidonoyl-sn-glycero-3-phosphate
CC         {ECO:0000269|PubMed:9083091};
CC         Vmax=259 pmol/min/mg enzyme for 1,2-dioleoyl-sn-glycero-3-phosphate
CC         {ECO:0000269|PubMed:9083091};
CC         Vmax=198 pmol/min/mg enzyme for phosphatidic acid
CC         {ECO:0000269|PubMed:9083091};
CC   -!- PATHWAY: Phospholipid metabolism; CDP-diacylglycerol biosynthesis; CDP-
CC       diacylglycerol from sn-glycerol 3-phosphate: step 3/3.
CC   -!- SUBUNIT: Homodimer (PubMed:29253589). Interacts with FOS; this
CC       interaction may enhance catalytic activity (By similarity).
CC       {ECO:0000250|UniProtKB:P98191, ECO:0000269|PubMed:29253589}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000269|PubMed:29253589, ECO:0000269|PubMed:6271231,
CC       ECO:0000269|PubMed:9083091}; Multi-pass membrane protein {ECO:0000255}.
CC   -!- TISSUE SPECIFICITY: Brain, retina and testis. Found in cerebellar
CC       Purkinje cells, pineal body, inner segment of photoreceptor cells and
CC       postmitotic spermatocytes and spermatids. {ECO:0000269|PubMed:9083091}.
CC   -!- SIMILARITY: Belongs to the CDS family. {ECO:0000305}.
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DR   EMBL; AB000517; BAA22085.1; -; mRNA.
DR   EMBL; AB009999; BAA28787.1; -; mRNA.
DR   EMBL; BC127492; AAI27493.1; -; mRNA.
DR   RefSeq; NP_112521.2; NM_031242.2.
DR   AlphaFoldDB; O35052; -.
DR   STRING; 10116.ENSRNOP00000002918; -.
DR   iPTMnet; O35052; -.
DR   PhosphoSitePlus; O35052; -.
DR   PaxDb; 10116-ENSRNOP00000002918; -.
DR   Ensembl; ENSRNOT00000002918.7; ENSRNOP00000002918.3; ENSRNOG00000002142.7.
DR   Ensembl; ENSRNOT00055042434; ENSRNOP00055034653; ENSRNOG00055024648.
DR   Ensembl; ENSRNOT00060016448; ENSRNOP00060012856; ENSRNOG00060009751.
DR   Ensembl; ENSRNOT00065020331; ENSRNOP00065015629; ENSRNOG00065012493.
DR   GeneID; 81925; -.
DR   KEGG; rno:81925; -.
DR   AGR; RGD:621185; -.
DR   CTD; 1040; -.
DR   RGD; 621185; Cds1.
DR   eggNOG; KOG1440; Eukaryota.
DR   GeneTree; ENSGT00940000158223; -.
DR   HOGENOM; CLU_023471_0_1_1; -.
DR   InParanoid; O35052; -.
DR   OMA; FFAYMYF; -.
DR   OrthoDB; 5481516at2759; -.
DR   PhylomeDB; O35052; -.
DR   TreeFam; TF313464; -.
DR   BRENDA; 2.7.7.41; 5301.
DR   Reactome; R-RNO-1483226; Synthesis of PI.
DR   UniPathway; UPA00557; UER00614.
DR   PRO; PR:O35052; -.
DR   Proteomes; UP000002494; Chromosome 14.
DR   Bgee; ENSRNOG00000002142; Expressed in duodenum and 19 other cell types or tissues.
DR   GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:RGD.
DR   GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR   GO; GO:0004605; F:phosphatidate cytidylyltransferase activity; IDA:UniProtKB.
DR   GO; GO:0016024; P:CDP-diacylglycerol biosynthetic process; ISS:UniProtKB.
DR   GO; GO:0140042; P:lipid droplet formation; ISS:UniProtKB.
DR   GO; GO:0006661; P:phosphatidylinositol biosynthetic process; ISS:UniProtKB.
DR   GO; GO:0045600; P:positive regulation of fat cell differentiation; ISS:UniProtKB.
DR   InterPro; IPR000374; PC_trans.
DR   InterPro; IPR016720; PC_Trfase_euk.
DR   PANTHER; PTHR13773; PHOSPHATIDATE CYTIDYLYLTRANSFERASE; 1.
DR   PANTHER; PTHR13773:SF16; PHOSPHATIDATE CYTIDYLYLTRANSFERASE 1; 1.
DR   Pfam; PF01148; CTP_transf_1; 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; Magnesium;
KW   Membrane; Methylation; Nucleotidyltransferase; Phospholipid biosynthesis;
KW   Phospholipid metabolism; Phosphoprotein; Reference proteome; Transferase;
KW   Transmembrane; Transmembrane helix.
FT   CHAIN           1..461
FT                   /note="Phosphatidate cytidylyltransferase 1"
FT                   /id="PRO_0000090715"
FT   TRANSMEM        96..116
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        149..169
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        183..203
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        230..250
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        279..299
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        357..377
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   REGION          1..68
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        25..56
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         7
FT                   /note="Omega-N-methylarginine"
FT                   /evidence="ECO:0000250|UniProtKB:P98191"
FT   MOD_RES         35
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         37
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   CONFLICT        172
FT                   /note="R -> K (in Ref. 2; BAA28787)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        299..308
FT                   /note="SKYQYFVCPV -> VQVSVLCGARW (in Ref. 1; BAA22085)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        326
FT                   /note="L -> V (in Ref. 2; BAA28787)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   461 AA;  52970 MW;  66061B9A8AF73B3D CRC64;
     MLELRHRGGC PGPGGAGTPP PREGEAAGGD HETESTSDKE TDIDDRYGDL DARGDSDVPE
     VPPSSDRTPE ILKKALSGLS SRWKNWWIRG ILTLTMISLF FLIIYMGSFM LMLLVLGIQV
     KCFQEIITIG YRVYHSYDLP WFRTLSWYFL LCVNYFFYGE TVADYFATFV QREEQLQFLI
     RYHRFISFAL YLAGFCMFVL SLVKKHYRLQ FYMFAWTHVT LLITVTQSHL VIQNLFEGMI
     WFLVPISSVI CNDITAYLFG FFFGRTPLIK LSPKKTWEGF IGGFFSTVIF GFIAAYVLSK
     YQYFVCPVEY RSDVNSFVTE CEPSELFQLQ NYSLPPFLQA VLSRETVSLY PFQIHSIALS
     TFASLIGPFG GFFASGFKRA FKIKDFANTI PGHGGIMDRF DCQYLMATFV HVYITSFIRG
     PNPSKVLQQL LVLQPEQQLN IYRTLKIHLT EKGILQPTWK V
//