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Gene Review

CDS1  -  CDP-diacylglycerol synthase (phosphatidate...

Homo sapiens

Synonyms: CDP-DAG synthase 1, CDP-DG synthase 1, CDP-diacylglycerol synthase 1, CDP-diglyceride pyrophosphorylase 1, CDP-diglyceride synthase 1, ...
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Disease relevance of CDS1


High impact information on CDS1

  • In yeast the DNA damage response and the replication-block checkpoint are mediated partly through the Cds1 kinase family [6].
  • Threonine 68 is required for radiation-induced phosphorylation and activation of Cds1 [7].
  • During S phase, the Cds1 kinase is activated in response to DNA damage and DNA replication blocks [8].
  • First DNA-PK phosphorylates serine 39, a site not previously recognized as important in Cds1 regulation [9].
  • Xenopus Cds1 is regulated by DNA-dependent protein kinase and ATR during the cell cycle checkpoint response to double-stranded DNA ends [9].

Biological context of CDS1

  • Cds1, on the other hand, shows a high level of expression in the photoreceptor layer of adult retina, which strongly suggests a role for Cds1 in phototransduction [10].
  • A critical step in the supply of substrate for the phosphoinositide signal transduction pathway is the formation of the liponucleotide intermediate, CDP-diacylglycerol, catalyzed by CDP-diacylglycerol synthase [2].
  • The frequency of allele G and genotype G/G at position +49 in CDS1 was increased in patients with thymoma when compared with patients with normal and hyperplastic thymic histopathology [3].
  • Cds1 activation triggers Rad60 phosphorylation and nuclear delocalization [11].
  • Genome integrity is protected by Cds1 (Chk2), a checkpoint kinase that stabilizes arrested replication forks [11].

Anatomical context of CDS1

  • Expression of the human cDNA in COS cells resulted in a more than fourfold increase in CDP-diacylglycerol synthase activity [2].
  • Cloning of CDP-diacylglycerol synthase from a human neuronal cell line [2].
  • Among these are the CDS for synthesis of molybdopterin and for synthesis of the carbon monoxide dehydrogenase/acetyl-coenzyme A synthase complex, which explains why M. stadtmanae cannot reduce CO2 to methane or oxidize methanol to CO2 and why this archaeon is dependent on acetate for biosynthesis of cell components [12].

Associations of CDS1 with chemical compounds

  • These data illustrate that the levels of Cds1 and Pis1 protein expression are not critical determinants of cellular PtdIns content and argue against a determining role for the activity of either of these enzymes in the regulation of PtdIns biosynthesis [13].
  • Substitution of threonine-11 with alanine (T11A) abolished Cds1 activation that occurs when DNA replication is inhibited by hydroxyurea (HU) treatment [14].
  • A photoreceptor-specific form of the enzyme CDP-diacylglycerol synthase (CDS), which catalyzes the formation of CDP-diacylglycerol from phosphatidic acid, is a key regulator of the amount of PIP2 available for signalling. cds mutants develop light-induced retinal degeneration [15].
  • Assays in vitro for the enzymes involved in the synthesis of neutral lipids and acidic phospholipids revealed that phosphatidate phosphatase and CTP: phosphatidate cytidylyltransferase activities were stimulated by methyl-lidocaine [16].
  • A 1909 bp 5' upstream sequence was isolated and found to be transcriptionally active thus constituting a functional CDS promoter [17].

Other interactions of CDS1


Analytical, diagnostic and therapeutic context of CDS1

  • There were two mRNA species (3.9 and 5.6 kilobases) detected on Northern blots hybridized with the cds1 probe that were expressed at distinctly different levels in various human tissues [13].
  • Moreover, CDS-1 sera reacted strongly with a lipid component co-migrating with phosphatidylethanolamine (PE) in high performance thin-layer chromatography (HPTLC)-immunostaining of HEp-2 cell total lipid extracts [5].
  • The CDS-1 major molecular targets were established by electrospray ionization-mass spectrometry (ESI-MS), HPTLC-immunostaining and chemiluminescent enzyme-linked immunosorbent assay as diacyl-PE species, containing preferentially a cis-C18 : 1 fatty acid chain at C-2 of the glycerol moiety, namely 1,2-cis-C18 : 1-PE and 1-C16 : 0-2-cis-C18 : 1-PE [5].
  • A PCR approach was used to isolate a phytoene synthase (Psy) cDNA from sunflower (Helianthus annuus L.). A reconstructed full-length sequence (1598 bp) of the Psy cDNA was obtained; it contained a 1242 bp CDS, 172-nucleotides of 5'-untranslated region (UTR), and 170-nucleotides of 3'-UTR [20].


  1. Isolation and chromosomal localization of two human CDP-diacylglycerol synthase (CDS) genes. Halford, S., Dulai, K.S., Daw, S.C., Fitzgibbon, J., Hunt, D.M. Genomics (1998) [Pubmed]
  2. Cloning of CDP-diacylglycerol synthase from a human neuronal cell line. Heacock, A.M., Uhler, M.D., Agranoff, B.W. J. Neurochem. (1996) [Pubmed]
  3. CDS1 and promoter single nucleotide polymorphisms of the CTLA-4 gene in human myasthenia gravis. Wang, X.B., Kakoulidou, M., Qiu, Q., Giscombe, R., Huang, D., Pirskanen, R., Lefvert, A.K. Genes Immun. (2002) [Pubmed]
  4. Requirement of phosphatidylglycerol for photosynthetic function in thylakoid membranes. Sato, N., Hagio, M., Wada, H., Tsuzuki, M. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  5. Human autoantibodies to diacyl-phosphatidylethanolamine recognize a specific set of discrete cytoplasmic domains. Laurino, C.C., Fritzler, M.J., Mortara, R.A., Silva, N.P., Almeida, I.C., Andrade, L.E. Clin. Exp. Immunol. (2006) [Pubmed]
  6. hCds1-mediated phosphorylation of BRCA1 regulates the DNA damage response. Lee, J.S., Collins, K.M., Brown, A.L., Lee, C.H., Chung, J.H. Nature (2000) [Pubmed]
  7. Threonine 68 is required for radiation-induced phosphorylation and activation of Cds1. Melchionna, R., Chen, X.B., Blasina, A., McGowan, C.H. Nat. Cell Biol. (2000) [Pubmed]
  8. Analysis of Rad3 and Chk1 protein kinases defines different checkpoint responses. Martinho, R.G., Lindsay, H.D., Flaggs, G., DeMaggio, A.J., Hoekstra, M.F., Carr, A.M., Bentley, N.J. EMBO J. (1998) [Pubmed]
  9. Xenopus Cds1 is regulated by DNA-dependent protein kinase and ATR during the cell cycle checkpoint response to double-stranded DNA ends. McSherry, T.D., Mueller, P.R. Mol. Cell. Biol. (2004) [Pubmed]
  10. Identification and characterization of CDS2, a mammalian homolog of the Drosophila CDP-diacylglycerol synthase gene. Volta, M., Bulfone, A., Gattuso, C., Rossi, E., Mariani, M., Consalez, G.G., Zuffardi, O., Ballabio, A., Banfi, S., Franco, B. Genomics (1999) [Pubmed]
  11. Replication checkpoint kinase Cds1 regulates recombinational repair protein Rad60. Boddy, M.N., Shanahan, P., McDonald, W.H., Lopez-Girona, A., Noguchi, E., Yates III, J.R., Russell, P. Mol. Cell. Biol. (2003) [Pubmed]
  12. The genome sequence of Methanosphaera stadtmanae reveals why this human intestinal archaeon is restricted to methanol and H2 for methane formation and ATP synthesis. Fricke, W.F., Seedorf, H., Henne, A., Krüer, M., Liesegang, H., Hedderich, R., Gottschalk, G., Thauer, R.K. J. Bacteriol. (2006) [Pubmed]
  13. The role of CDP-diacylglycerol synthetase and phosphatidylinositol synthase activity levels in the regulation of cellular phosphatidylinositol content. Lykidis, A., Jackson, P.D., Rock, C.O., Jackowski, S. J. Biol. Chem. (1997) [Pubmed]
  14. Threonine-11, phosphorylated by Rad3 and atm in vitro, is required for activation of fission yeast checkpoint kinase Cds1. Tanaka, K., Boddy, M.N., Chen, X.B., McGowan, C.H., Russell, P. Mol. Cell. Biol. (2001) [Pubmed]
  15. Isolation and characterization of murine Cds (CDP-diacylglycerol synthase) 1 and 2. Inglis-Broadgate, S.L., Ocaka, L., Banerjee, R., Gaasenbeek, M., Chapple, J.P., Cheetham, M.E., Clark, B.J., Hunt, D.M., Halford, S. Gene (2005) [Pubmed]
  16. The effect of methyl-lidocaine on the biosynthesis of phospholipids de novo in the isolated hamster heart. Tardi, P.G., Man, R.Y., Choy, P.C. Biochem. J. (1992) [Pubmed]
  17. A 24 bp cis-acting element essential for the transcriptional activity of Plasmodium falciparum CDP-diacylglycerol synthase gene promoter. Osta, M., Gannoun-Zaki, L., Bonnefoy, S., Roy, C., Vial, H.J. Mol. Biochem. Parasitol. (2002) [Pubmed]
  18. myo-[3H]-inositol loaded erythrocytes and white ghosts: two models to investigate the phosphatidylinositol synthesis in human red cells. Piatti, E., Piacentini, M.P., Fraternale, D., Bucchini, A., Mangani, F., Accorsi, A. Biochimie (1999) [Pubmed]
  19. Phospholipid biosynthesis in some anaerobic bacteria. Silber, P., Borie, R.P., Mikowski, E.J., Goldfine, H. J. Bacteriol. (1981) [Pubmed]
  20. cDNA cloning and expression of the phytoene synthase gene in sunflower. Salvini, M., Bernini, A., Fambrini, M., Pugliesi, C. J. Plant Physiol. (2005) [Pubmed]
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