Affinage

CDS1

Phosphatidate cytidylyltransferase 1 · UniProt Q92903

Round 2 corrected
Length
461 aa
Mass
53.3 kDa
Annotated
2026-04-28
83 papers in source corpus 6 papers cited in narrative 6 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Insufficient on-target evidence to synthesize a narrative — discovery timeline does not match the canonical CDS1 protein.

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
No controlled-vocabulary terms were assigned to this entry.

Evidence

Reading pass · 6 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 The yeast CDS1 gene on chromosome II encodes CDP-diacylglycerol synthase (CDS), an integral membrane protein essential for vegetative growth and spore germination. Null cds1 mutants are inviable, and CDS1 accounts for the majority (if not all) of CDP-diacylglycerol synthase activity in S. cerevisiae. Overexpression elevates phosphatidylinositol synthesis relative to phosphatidylserine, while reduced expression has the opposite effect, demonstrating that CDS1 activity controls the flux between these two phospholipid branches. Null mutant construction, GAL1-driven overexpression/depletion, enzymatic activity assays, phospholipid labeling The Journal of biological chemistry High 8557688
2019 In H9c2 cardiomyoblasts, sustained vasopressin-induced phospholipase C activation selectively upregulates CDS1 mRNA (not CDS2 or TAMM41) through a pathway requiring protein kinase C and the transcription factor cFos (AP-1). CDS1 and CDS2 proteins localize to the endoplasmic reticulum, while TAMM41 localizes to mitochondria. This upregulation provides a compensatory mechanism to maintain phosphatidylinositol levels during chronic PLC signaling. Pharmacological inhibition (PKC inhibitor, AP-1 inhibitor T-5224), real-time PCR, immunoblotting for cFos, subcellular localization studies Biochimica et biophysica acta. Molecular and cell biology of lipids Medium 30862571
2025 CDS1 and CDS2 form a synthetic lethal pair: CDS2 is an essential gene specifically in cancer cells with low CDS1 expression. CDS2 knockout disrupts phosphoinositide synthesis and induces apoptosis, and re-expression of CDS1 rescues the cell fitness defect, demonstrating functional redundancy between the two CDP-diacylglycerol synthase paralogs in maintaining phosphoinositide homeostasis. Genome-wide CRISPR-Cas9 single-gene and combinatorial paired-gene screening, CDS1 re-expression rescue assays, phosphoinositide synthesis measurement, in vivo xenograft validation Nature genetics High 40615675
2025 Loss of CDS1 in nasopharyngeal carcinoma cells reduces CDP-diacylglycerol production, leading to accumulation of intracellular lipid droplets. CDS1 re-expression suppresses cell growth, migration, invasion, and tumor formation in vivo, and promotes NF-κB pathway activation with elevated inflammatory cytokines, suggesting CDS1 suppresses NPC by modulating lipid droplet levels and tumor immunogenicity. CDS1 knockdown and re-expression (loss-of-function/gain-of-function), colony formation assay, migration/invasion assays, in vivo tumor model, NF-κB pathway analysis, cytokine measurement Cell adhesion & migration Medium 40566856
2025 CDS1 catalyzes synthesis and secretion of CDP-diacylglycerol (CDP-DAG), which binds to transcription factor CEBPG and induces ferroptosis in myeloid-derived suppressor cells (MDSCs), thereby relieving MDSC-mediated immunosuppression and enhancing cytotoxic T lymphocyte infiltration in colorectal cancer. CDP-DAG exhibits synergistic anti-tumor effects with anti-PDL1 therapy. Bioinformatic analysis, in vitro cellular models, in vivo tumor systems, CEBPG binding assays, ferroptosis assays, immune cell profiling, combination therapy experiments Cellular signalling Medium 41161459
2025 In a mouse model of allergic asthma, bacterial cellulose downregulates epithelial CDS1 expression, resulting in decreased phosphatidylinositol (PI) and PI(4,5)P2 synthesis and suppression of PI3K/AKT signaling. CDS1 overexpression reverses these effects in vivo, confirming that CDS1-dependent PI synthesis is required to sustain PI3K/AKT pathway activity in airway epithelial cells. Mouse asthma model, intranasal treatment, single-cell RNA sequencing, metabolomics of BALF, CDS1 overexpression in vivo, PI/PIP2 quantification, PI3K/AKT pathway analysis International journal of biological macromolecules Medium 41407218

Source papers

Stage 0 corpus · 83 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science (New York, N.Y.) 2519 17525332
2009 Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion. Nature cell biology 1754 19597488
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
1997 Mitotic and G2 checkpoint control: regulation of 14-3-3 protein binding by phosphorylation of Cdc25C on serine-216. Science (New York, N.Y.) 1191 9278512
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2005 ATM activation by DNA double-strand breaks through the Mre11-Rad50-Nbs1 complex. Science (New York, N.Y.) 1109 15790808
1998 Linkage of ATM to cell cycle regulation by the Chk2 protein kinase. Science (New York, N.Y.) 1094 9836640
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2000 DNA damage-induced activation of p53 by the checkpoint kinase Chk2. Science (New York, N.Y.) 1050 10710310
2010 The ATM-Chk2 and ATR-Chk1 pathways in DNA damage signaling and cancer. Advances in cancer research 1019 21034966
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2004 Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21(CIP1), but not p16(INK4a). Molecular cell 1014 15149599
2013 Large-scale genotyping identifies 41 new loci associated with breast cancer risk. Nature genetics 895 23535729
2002 Low-penetrance susceptibility to breast cancer due to CHEK2(*)1100delC in noncarriers of BRCA1 or BRCA2 mutations. Nature genetics 867 11967536
2001 The ATM-Chk2-Cdc25A checkpoint pathway guards against radioresistant DNA synthesis. Nature 854 11298456
1999 The DNA sequence of human chromosome 22. Nature 808 10591208
2000 The human homologs of checkpoint kinases Chk1 and Cds1 (Chk2) phosphorylate p53 at multiple DNA damage-inducible sites. Genes & development 725 10673501
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
1999 Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome. Science (New York, N.Y.) 705 10617473
2000 Ataxia telangiectasia-mutated phosphorylates Chk2 in vivo and in vitro. Proceedings of the National Academy of Sciences of the United States of America 700 10973490
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2000 Chk2/hCds1 functions as a DNA damage checkpoint in G(1) by stabilizing p53. Genes & development 618 10673500
2004 Direct activation of the ATM protein kinase by the Mre11/Rad50/Nbs1 complex. Science (New York, N.Y.) 601 15064416
2017 Associations Between Cancer Predisposition Testing Panel Genes and Breast Cancer. JAMA oncology 471 28418444
2007 Phosphorylation of HuR by Chk2 regulates SIRT1 expression. Molecular cell 470 17317627
2003 Chk1 regulates the S phase checkpoint by coupling the physiological turnover and ionizing radiation-induced accelerated proteolysis of Cdc25A. Cancer cell 456 12676583
2000 hCds1-mediated phosphorylation of BRCA1 regulates the DNA damage response. Nature 449 10724175
2001 Initiation of a G2/M checkpoint after ultraviolet radiation requires p38 kinase. Nature 444 11333986
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2004 CHEK2 is a multiorgan cancer susceptibility gene. American journal of human genetics 428 15492928
1998 S-phase-specific activation of Cds1 kinase defines a subpathway of the checkpoint response in Schizosaccharomyces pombe. Genes & development 342 9450932
1998 Replication checkpoint requires phosphorylation of the phosphatase Cdc25 by Cds1 or Chk1. Nature 314 9774107
1998 Replication checkpoint enforced by kinases Cds1 and Chk1. Science (New York, N.Y.) 286 9572736
2000 Threonine 68 is required for radiation-induced phosphorylation and activation of Cds1. Nature cell biology 266 11025670
1999 A human homologue of the checkpoint kinase Cds1 directly inhibits Cdc25 phosphatase. Current biology : CB 240 9889122
2000 Damage tolerance protein Mus81 associates with the FHA1 domain of checkpoint kinase Cds1. Molecular and cellular biology 238 11073977
1999 A human Cds1-related kinase that functions downstream of ATM protein in the cellular response to DNA damage. Proceedings of the National Academy of Sciences of the United States of America 238 10097108
2001 Mrc1 channels the DNA replication arrest signal to checkpoint kinase Cds1. Nature cell biology 207 11715017
2000 Chk1 and Cds1: linchpins of the DNA damage and replication checkpoint pathways. Journal of cell science 179 11058076
1999 Cdc25 inhibited in vivo and in vitro by checkpoint kinases Cds1 and Chk1. Molecular biology of the cell 176 10198041
2003 Swi1 prevents replication fork collapse and controls checkpoint kinase Cds1. Molecular and cellular biology 139 14560029
1996 The CDS1 gene encoding CDP-diacylglycerol synthase in Saccharomyces cerevisiae is essential for cell growth. The Journal of biological chemistry 120 8557688
2005 Replication checkpoint kinase Cds1 regulates Mus81 to preserve genome integrity during replication stress. Genes & development 109 15805465
1999 Basis for the checkpoint signal specificity that regulates Chk1 and Cds1 protein kinases. Molecular and cellular biology 92 10330167
2002 Checking in on Cds1 (Chk2): A checkpoint kinase and tumor suppressor. BioEssays : news and reviews in molecular, cellular and developmental biology 83 12111733
1999 Role of human Cds1 (Chk2) kinase in DNA damage checkpoint and its regulation by p53. The Journal of biological chemistry 80 10531348
2003 Replication checkpoint kinase Cds1 regulates recombinational repair protein Rad60. Molecular and cellular biology 77 12897162
2006 Two-stage mechanism for activation of the DNA replication checkpoint kinase Cds1 in fission yeast. Genes & development 74 16618806
2000 Response of Xenopus Cds1 in cell-free extracts to DNA templates with double-stranded ends. Molecular biology of the cell 70 10793133
1999 Genetic control of telomere integrity in Schizosaccharomyces pombe: rad3(+) and tel1(+) are parts of two regulatory networks independent of the downstream protein kinases chk1(+) and cds1(+). Genetics 59 10430579
2001 Threonine-11, phosphorylated by Rad3 and atm in vitro, is required for activation of fission yeast checkpoint kinase Cds1. Molecular and cellular biology 50 11313465
2002 CDS1 and promoter single nucleotide polymorphisms of the CTLA-4 gene in human myasthenia gravis. Genes and immunity 37 11857062
2018 Hydrolase CehA and Monooxygenase CfdC Are Responsible for Carbofuran Degradation in Sphingomonas sp. Strain CDS-1. Applied and environmental microbiology 29 29884759
2004 Cds1 phosphorylation by Rad3-Rad26 kinase is mediated by forkhead-associated domain interaction with Mrc1. The Journal of biological chemistry 29 15173168
2001 Critical role of Caenorhabditis elegans homologs of Cds1 (Chk2)-related kinases in meiotic recombination. Molecular and cellular biology 29 11158318
2008 Cds1 controls the release of Cdc14-like phosphatase Flp1 from the nucleolus to drive full activation of the checkpoint response to replication stress in fission yeast. Molecular biology of the cell 28 18385517
2005 Rad3-Cds1 mediates coupling of initiation of meiotic recombination with DNA replication. Mei4-dependent transcription as a potential target of meiotic checkpoint. The Journal of biological chemistry 27 16286472
2009 Autoinhibition and autoactivation of the DNA replication checkpoint kinase Cds1. The Journal of biological chemistry 21 19357077
1993 Iminium salt of copper benzochlorin (CDS1), a novel photosensitizer for photodynamic therapy: mechanism of cell killing. Photochemistry and photobiology 19 8378428
2001 Inactivation of the checkpoint kinase Cds1 is dependent on cyclin B-Cdc2 kinase activation at the meiotic G(2)/M-phase transition in Xenopus oocytes. Journal of cell science 18 11591827
2006 HIV-1 Vpr induces G2 cell cycle arrest in fission yeast associated with Rad24/14-3-3-dependent, Chk1/Cds1-independent Wee1 upregulation. Microbes and infection 16 16968670
2008 Involvement of fission yeast Clr6-HDAC in regulation of the checkpoint kinase Cds1. Nucleic acids research 14 18440981
2025 The synthetic lethal interaction between CDS1 and CDS2 is a vulnerability in uveal melanoma and across multiple tumor types. Nature genetics 10 40615675
2014 Meiotic nuclear movements in fission yeast are regulated by the transcription factor Mei4 downstream of a Cds1-dependent replication checkpoint pathway. Genes to cells : devoted to molecular & cellular mechanisms 10 25492408
2009 A Cds1-mediated checkpoint protects the MBF activator Rep2 from ubiquitination by anaphase-promoting complex/cyclosome-Ste9 at S-phase arrest in fission yeast. Molecular and cellular biology 10 19596787
2004 Xenopus Cds1 is regulated by DNA-dependent protein kinase and ATR during the cell cycle checkpoint response to double-stranded DNA ends. Molecular and cellular biology 10 15509799
2019 Sustained phospholipase C stimulation of H9c2 cardiomyoblasts by vasopressin induces an increase in CDP-diacylglycerol synthase 1 (CDS1) through protein kinase C and cFos. Biochimica et biophysica acta. Molecular and cell biology of lipids 9 30862571
2015 Casein kinase 1γ ensures monopolar growth polarity under incomplete DNA replication downstream of Cds1 and calcineurin in fission yeast. Molecular and cellular biology 8 25691662
2007 Characterization and physical mapping of the porcine CDS1 and CDS2 genes. Animal biotechnology 8 17364441
2005 Chk2/Cds1 protein kinase blocks apoptosis during early development of Xenopus laevis. Developmental dynamics : an official publication of the American Association of Anatomists 8 15937936
2008 Crosstalk between Nap1 protein and Cds1 checkpoint kinase to maintain chromatin integrity. Biochimica et biophysica acta 7 18474252
2014 Pcf1, a large subunit of CAF-1, required for maintenance of checkpoint kinase Cds1 activity. SpringerPlus 5 24478943
2009 The Schizosaccharomyces pombe checkpoint kinases Chk1 and Cds1 are important for cell survival in response to cisplatin. PloS one 4 19587778
2006 Methylation Inactivates Expression of CDP-diacylglycerol Synthase 1 (CDS1) in Hepatocellular Carcinoma. Cancer genomics & proteomics 4 31394702
2018 Nutrient Limitation Inactivates Mrc1-to-Cds1 Checkpoint Signalling in Schizosaccharomyces pombe. Cells 3 29473861
2004 Evolutionary conservation of a novel splice variant of the Cds1/CHK2 checkpoint kinase restricted to its regulatory domain. Cell cycle (Georgetown, Tex.) 3 15467464
2020 Mutation in histone deacetylase clr6 promotes the survival of S. pombe cds1 null mutant in response to hydroxyurea. Molecular genetics and genomics : MGG 1 32124033
2025 Loss of CDS1 impairs the tumorigenic characteristics of nasopharyngeal carcinoma by modulating lipid metabolism. Cell adhesion & migration 0 40566856
2025 CDS1 deficiency promotes colorectal cancer progression by suppressing CDP-DAG-induced ferroptosis in MDSCs. Cellular signalling 0 41161459
2025 Bacterial cellulose repairs asthmatic epithelial injury by reprogramming CDS1-mediated phosphatidylinositol metabolism to inhibit PI3K/AKT signaling. International journal of biological macromolecules 0 41407218
2007 [Dds20 operates in cds1-independent mechanism of tolerance to UV-induced DNA damage in Schizosaccharomyces pombe cells]. Genetika 0 17486762
2006 [Construction of double-labelled carbofuran-degrading bacterium Sphingomonas sp. CDS-1]. Wei sheng wu xue bao = Acta microbiologica Sinica 0 17037065