CDS2_HUMAN
ID CDS2_HUMAN Reviewed; 445 AA.
AC O95674; B2RDC6; D3DW04; Q5TDY2; Q5TDY3; Q5TDY4; Q5TDY5; Q9BYK5; Q9NTT2;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Phosphatidate cytidylyltransferase 2 {ECO:0000305};
DE EC=2.7.7.41 {ECO:0000269|PubMed:25375833};
DE AltName: Full=CDP-DAG synthase 2;
DE AltName: Full=CDP-DG synthase 2;
DE AltName: Full=CDP-diacylglycerol synthase 2;
DE Short=CDS 2;
DE AltName: Full=CDP-diglyceride pyrophosphorylase 2;
DE AltName: Full=CDP-diglyceride synthase 2;
DE AltName: Full=CTP:phosphatidate cytidylyltransferase 2;
GN Name=CDS2 {ECO:0000312|HGNC:HGNC:1801};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=9889000; DOI=10.1006/geno.1998.5610;
RA Volta M., Bulfone A., Gattuso C., Rossi E., Mariani M., Consalez G.G.,
RA Zuffardi O., Ballabio A., Banfi S., Franco B.;
RT "Identification and characterization of CDS2, a mammalian homolog of the
RT Drosophila CDP-diacylglycerol synthase gene.";
RL Genomics 55:68-77(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 25-445 (ISOFORM 1).
RC TISSUE=Retina;
RX PubMed=9806839; DOI=10.1006/geno.1998.5547;
RA Halford S., Dulai K.S., Daw S.C.M., Fitzgibbon J., Hunt D.M.;
RT "Isolation and chromosomal localization of two human CDP-diacylglycerol
RT synthase (CDS) genes.";
RL Genomics 54:140-144(1998).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=18318008; DOI=10.1002/pmic.200700884;
RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,
RA Zou H., Gu J.;
RT "Large-scale phosphoproteome analysis of human liver tissue by enrichment
RT and fractionation of phosphopeptides with strong anion exchange
RT chromatography.";
RL Proteomics 8:1346-1361(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21; SER-33 AND SER-35, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-31 AND SER-33, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [17]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND ACTIVITY REGULATION.
RX PubMed=25375833; DOI=10.1021/bi501250m;
RA D'Souza K., Kim Y.J., Balla T., Epand R.M.;
RT "Distinct properties of the two isoforms of CDP-diacylglycerol synthase.";
RL Biochemistry 53:7358-7367(2014).
RN [18]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=26946540; DOI=10.1194/jlr.m060574;
RA Qi Y., Kapterian T.S., Du X., Ma Q., Fei W., Zhang Y., Huang X.,
RA Dawes I.W., Yang H.;
RT "CDP-diacylglycerol synthases regulate the growth of lipid droplets and
RT adipocyte development.";
RL J. Lipid Res. 57:767-780(2016).
RN [19]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=31548309; DOI=10.1074/jbc.ra119.009992;
RA Xu Y., Mak H.Y., Lukmantara I., Li Y.E., Hoehn K.L., Huang X., Du X.,
RA Yang H.;
RT "CDP-DAG synthase 1 and 2 regulate lipid droplet growth through distinct
RT mechanisms.";
RL J. Biol. Chem. 294:16740-16755(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:25375833). Exhibits specificity for the nature of the acyl
CC chains at the sn-1 and sn-2 positions in the substrate, PA and the
CC preferred acyl chain composition is 1-stearoyl-2-arachidonoyl-sn-
CC phosphatidic acid (PubMed:25375833). Plays an important role in
CC regulating the growth and maturation of lipid droplets which are
CC storage organelles at the center of lipid and energy homeostasis
CC (PubMed:26946540, PubMed:31548309). {ECO:0000269|PubMed:25375833,
CC ECO:0000269|PubMed:26946540, ECO:0000269|PubMed:31548309}.
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:25375833};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16230;
CC Evidence={ECO:0000305|PubMed:25375833};
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:0000269|PubMed:25375833};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45649;
CC Evidence={ECO:0000305|PubMed:25375833};
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:0000269|PubMed:25375833};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45661;
CC Evidence={ECO:0000305|PubMed:25375833};
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:0000269|PubMed:25375833};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45653;
CC Evidence={ECO:0000305|PubMed:25375833};
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:0000269|PubMed:25375833};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45657;
CC Evidence={ECO:0000305|PubMed:25375833};
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:0000269|PubMed:25375833};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45665;
CC Evidence={ECO:0000305|PubMed:25375833};
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:0000269|PubMed:25375833};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45669;
CC Evidence={ECO:0000305|PubMed:25375833};
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:0000269|PubMed:25375833};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45673;
CC Evidence={ECO:0000305|PubMed:25375833};
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:0000269|PubMed:25375833};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45677;
CC Evidence={ECO:0000305|PubMed:25375833};
CC -!- ACTIVITY REGULATION: Inhibited by its anionic phospholipid end
CC products, with phosphatidylinositol-(4,5)- bisphosphate (PIP2) showing
CC the strongest inhibition. Inhibition is also acyl chain specific, with
CC 1-stearoyl-2-arachidonoyl-snphosphatidylinositol showing the strongest
CC inhibition. {ECO:0000269|PubMed:25375833}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.4 uM for 1-stearoyl-2-arachidonoyl-sn-phosphatidic acid
CC {ECO:0000269|PubMed:25375833};
CC KM=0.9 uM for 1-stearoyl-2-linoleoyl-sn-phosphatidic acid
CC {ECO:0000269|PubMed:25375833};
CC Vmax=9.3 umol/min/mg enzyme for 1-stearoyl-2-arachidonoyl-sn-
CC phosphatidic acid {ECO:0000269|PubMed:25375833};
CC Vmax=3.5 umol/min/mg enzyme for 1-stearoyl-2-linoleoyl-sn-
CC phosphatidic acid {ECO:0000269|PubMed:25375833};
CC -!- PATHWAY: Phospholipid metabolism; CDP-diacylglycerol biosynthesis; CDP-
CC diacylglycerol from sn-glycerol 3-phosphate: step 3/3.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q91XU8}.
CC -!- INTERACTION:
CC O95674; Q92870-2: APBB2; NbExp=3; IntAct=EBI-3913685, EBI-21535880;
CC O95674; P55212: CASP6; NbExp=3; IntAct=EBI-3913685, EBI-718729;
CC O95674; P28329-3: CHAT; NbExp=3; IntAct=EBI-3913685, EBI-25837549;
CC O95674; Q7Z7G2: CPLX4; NbExp=3; IntAct=EBI-3913685, EBI-18013275;
CC O95674; G5E9A7: DMWD; NbExp=3; IntAct=EBI-3913685, EBI-10976677;
CC O95674; Q9Y282: ERGIC3; NbExp=3; IntAct=EBI-3913685, EBI-781551;
CC O95674; Q5JX71: FAM209A; NbExp=3; IntAct=EBI-3913685, EBI-18304435;
CC O95674; P22607: FGFR3; NbExp=3; IntAct=EBI-3913685, EBI-348399;
CC O95674; Q8TDT2: GPR152; NbExp=3; IntAct=EBI-3913685, EBI-13345167;
CC O95674; Q8TED1: GPX8; NbExp=3; IntAct=EBI-3913685, EBI-11721746;
CC O95674; Q14957: GRIN2C; NbExp=3; IntAct=EBI-3913685, EBI-8285963;
CC O95674; P06396: GSN; NbExp=3; IntAct=EBI-3913685, EBI-351506;
CC O95674; P31937: HIBADH; NbExp=3; IntAct=EBI-3913685, EBI-11427100;
CC O95674; P01112: HRAS; NbExp=3; IntAct=EBI-3913685, EBI-350145;
CC O95674; P42858: HTT; NbExp=9; IntAct=EBI-3913685, EBI-466029;
CC O95674; Q13651: IL10RA; NbExp=3; IntAct=EBI-3913685, EBI-1031656;
CC O95674; Q96MG2: JSRP1; NbExp=3; IntAct=EBI-3913685, EBI-11305455;
CC O95674; P13473-2: LAMP2; NbExp=3; IntAct=EBI-3913685, EBI-21591415;
CC O95674; A8MZ59: LEUTX; NbExp=3; IntAct=EBI-3913685, EBI-17490413;
CC O95674; Q8TAF8: LHFPL5; NbExp=3; IntAct=EBI-3913685, EBI-2820517;
CC O95674; Q95460-2: MR1; NbExp=3; IntAct=EBI-3913685, EBI-12201447;
CC O95674; Q9H2K0: MTIF3; NbExp=3; IntAct=EBI-3913685, EBI-3923617;
CC O95674; Q9HB07: MYG1; NbExp=3; IntAct=EBI-3913685, EBI-709754;
CC O95674; O75400-2: PRPF40A; NbExp=3; IntAct=EBI-3913685, EBI-5280197;
CC O95674; P62826: RAN; NbExp=3; IntAct=EBI-3913685, EBI-286642;
CC O95674; Q9H9V4: RNF122; NbExp=3; IntAct=EBI-3913685, EBI-2129998;
CC O95674; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-3913685, EBI-5235340;
CC O95674; Q8WWF3: SSMEM1; NbExp=3; IntAct=EBI-3913685, EBI-17280858;
CC O95674; P31948: STIP1; NbExp=3; IntAct=EBI-3913685, EBI-1054052;
CC O95674; Q9NPL8: TIMMDC1; NbExp=3; IntAct=EBI-3913685, EBI-6268651;
CC O95674; Q8IV31: TMEM139; NbExp=3; IntAct=EBI-3913685, EBI-7238458;
CC O95674; Q96B21: TMEM45B; NbExp=3; IntAct=EBI-3913685, EBI-3923061;
CC O95674; Q9Y320: TMX2; NbExp=3; IntAct=EBI-3913685, EBI-6447886;
CC O95674; Q86WV8: TSC1; NbExp=3; IntAct=EBI-3913685, EBI-12806590;
CC O95674; O95859: TSPAN12; NbExp=3; IntAct=EBI-3913685, EBI-2466403;
CC O95674; Q9UMX0: UBQLN1; NbExp=3; IntAct=EBI-3913685, EBI-741480;
CC O95674; Q9Y649; NbExp=3; IntAct=EBI-3913685, EBI-25900580;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:25375833, ECO:0000269|PubMed:26946540,
CC ECO:0000269|PubMed:31548309}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O95674-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O95674-2; Sequence=VSP_015477, VSP_015480, VSP_015482;
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed in heart, brain and
CC retina, and to a lesser extent in placenta, lung, liver, skeletal
CC muscle, kidney and pancreas. {ECO:0000269|PubMed:9889000}.
CC -!- DEVELOPMENTAL STAGE: No expression detected at E10.5 in the developing
CC brain. At E12.5 expression is detected in the developing sentral
CC nervous system and peripheral nervous system. At E17.5 high levels of
CC expression are detected in a number of sites, including the dorsal root
CC ganglia of the peripheral nervous system and the ganglion cell layer of
CC the neural retina in the developing eye. At this stage expression in
CC the brain is restricted to the ventricular zone of the telencephalon,
CC in particular in the basal ganglia and the cerebral cortex.
CC {ECO:0000269|PubMed:9889000}.
CC -!- SIMILARITY: Belongs to the CDS family. {ECO:0000305}.
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DR EMBL; Y16521; CAA76270.1; -; mRNA.
DR EMBL; AK315489; BAG37873.1; -; mRNA.
DR EMBL; AL121755; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL121924; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471133; EAX10424.1; -; Genomic_DNA.
DR EMBL; CH471133; EAX10426.1; -; Genomic_DNA.
DR EMBL; BC025751; AAH25751.1; -; mRNA.
DR EMBL; AF069532; AAC78305.1; -; mRNA.
DR CCDS; CCDS13088.1; -. [O95674-1]
DR RefSeq; NP_003809.1; NM_003818.3. [O95674-1]
DR AlphaFoldDB; O95674; -.
DR BioGRID; 114295; 133.
DR IntAct; O95674; 59.
DR MINT; O95674; -.
DR STRING; 9606.ENSP00000419879; -.
DR SwissLipids; SLP:000001138; -.
DR GlyGen; O95674; 1 site, 2 N-linked glycans (1 site).
DR iPTMnet; O95674; -.
DR PhosphoSitePlus; O95674; -.
DR SwissPalm; O95674; -.
DR BioMuta; CDS2; -.
DR EPD; O95674; -.
DR jPOST; O95674; -.
DR MassIVE; O95674; -.
DR MaxQB; O95674; -.
DR PaxDb; O95674; -.
DR PeptideAtlas; O95674; -.
DR PRIDE; O95674; -.
DR ProteomicsDB; 50988; -. [O95674-1]
DR Antibodypedia; 8142; 151 antibodies from 23 providers.
DR DNASU; 8760; -.
DR Ensembl; ENST00000450570.1; ENSP00000403205.1; ENSG00000101290.14. [O95674-2]
DR Ensembl; ENST00000460006.6; ENSP00000419879.1; ENSG00000101290.14. [O95674-1]
DR GeneID; 8760; -.
DR KEGG; hsa:8760; -.
DR MANE-Select; ENST00000460006.6; ENSP00000419879.1; NM_003818.4; NP_003809.1.
DR UCSC; uc002wls.4; human. [O95674-1]
DR CTD; 8760; -.
DR DisGeNET; 8760; -.
DR GeneCards; CDS2; -.
DR HGNC; HGNC:1801; CDS2.
DR HPA; ENSG00000101290; Low tissue specificity.
DR MIM; 603549; gene.
DR neXtProt; NX_O95674; -.
DR OpenTargets; ENSG00000101290; -.
DR PharmGKB; PA26347; -.
DR VEuPathDB; HostDB:ENSG00000101290; -.
DR eggNOG; KOG1440; Eukaryota.
DR GeneTree; ENSGT00940000158877; -.
DR HOGENOM; CLU_023471_0_1_1; -.
DR InParanoid; O95674; -.
DR OMA; REVAIMP; -.
DR OrthoDB; 1072976at2759; -.
DR PhylomeDB; O95674; -.
DR TreeFam; TF313464; -.
DR BRENDA; 2.7.7.41; 2681.
DR PathwayCommons; O95674; -.
DR Reactome; R-HSA-1483148; Synthesis of PG.
DR SignaLink; O95674; -.
DR SIGNOR; O95674; -.
DR UniPathway; UPA00557; UER00614.
DR BioGRID-ORCS; 8760; 172 hits in 1088 CRISPR screens.
DR ChiTaRS; CDS2; human.
DR GeneWiki; CDS2; -.
DR GenomeRNAi; 8760; -.
DR Pharos; O95674; Tbio.
DR PRO; PR:O95674; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; O95674; protein.
DR Bgee; ENSG00000101290; Expressed in lateral nuclear group of thalamus and 210 other tissues.
DR Genevisible; O95674; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005743; C:mitochondrial inner membrane; TAS:Reactome.
DR GO; GO:0004605; F:phosphatidate cytidylyltransferase activity; IDA:UniProtKB.
DR GO; GO:0016024; P:CDP-diacylglycerol biosynthetic process; IDA:UniProtKB.
DR GO; GO:0140042; P:lipid droplet formation; IMP:UniProtKB.
DR GO; GO:0006655; P:phosphatidylglycerol biosynthetic process; TAS:Reactome.
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 Alternative splicing; Endoplasmic reticulum; Lipid biosynthesis;
KW Lipid metabolism; Membrane; Nucleotidyltransferase;
KW Phospholipid biosynthesis; Phospholipid metabolism; Phosphoprotein;
KW Reference proteome; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..445
FT /note="Phosphatidate cytidylyltransferase 2"
FT /id="PRO_0000090716"
FT TRANSMEM 79..99
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 132..152
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 166..186
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 213..233
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 262..282
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 340..360
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 1..49
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..35
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 21
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 31
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 33
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 35
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 37
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 51
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q99L43"
FT VAR_SEQ 1..55
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_015477"
FT VAR_SEQ 56..64
FT /note="NRALSNLSS -> MSRLRHPRT (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_015480"
FT VAR_SEQ 306..445
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_015482"
SQ SEQUENCE 445 AA; 51418 MW; 7DAD6A3C1D5587D6 CRC64;
MTELRQRVAH EPVAPPEDKE SESEAKVDGE TASDSESRAE SAPLPVSADD TPEVLNRALS
NLSSRWKNWW VRGILTLAMI AFFFIIIYLG PMVLMIIVMC VQIKCFHEII TIGYNVYHSY
DLPWFRTLSW YFLLCVNYFF YGETVTDYFF TLVQREEPLR ILSKYHRFIS FTLYLIGFCM
FVLSLVKKHY RLQFYMFGWT HVTLLIVVTQ SHLVIHNLFE GMIWFIVPIS CVICNDIMAY
MFGFFFGRTP LIKLSPKKTW EGFIGGFFAT VVFGLLLSYV MSGYRCFVCP VEYNNDTNSF
TVDCEPSDLF RLQEYNIPGV IQSVIGWKTV RMYPFQIHSI ALSTFASLIG PFGGFFASGF
KRAFKIKDFA NTIPGHGGIM DRFDCQYLMA TFVNVYIASF IRGPNPSKLI QQFLTLRPDQ
QLHIFNTLRS HLIDKGMLTS TTEDE
