CDS1_RAT
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 03-AUG-2022, entry version 142.
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 1-stearoyl-2-arachidonoyl-sn-glycero-
CC 3-phosphate {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; O35052; -.
DR PRIDE; O35052; -.
DR Ensembl; ENSRNOT00000002918; ENSRNOP00000002918; ENSRNOG00000002142.
DR GeneID; 81925; -.
DR KEGG; rno:81925; -.
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; FIMNNIF; -.
DR OrthoDB; 1072976at2759; -.
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 tissues.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:RGD.
DR GO; GO:0016021; C:integral component of 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; 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; 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
