Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDUTSOV)

• DOT Name: Lipid transferase CIDEA (CIDEA)
• Synonyms: Cell death activator CIDE-A; Cell death-inducing DFFA-like effector A
• Gene Name: CIDEA
• Related Disease:
  Cardiac failure
  Congestive heart failure
  Endometrial carcinoma
  Liver cancer
  Obesity
  Hepatitis
  Non-alcoholic fatty liver disease
  Non-insulin dependent diabetes
• UniProt ID: CIDEA_HUMAN
• PDB ID: 2EEL
• Pfam ID: PF02017
• Sequence:
  MEAARDYAGALIRPLTFMGSQTKRVLFTPLMHPARPFRVSNHDRSSRRGVMASSLQELIS
  KTLDALVIATGLVTLVLEEDGTVVDTEEFFQTLGDNTHFMILEKGQKWMPGSQHVPTCSP
  PKRSGIARVTFDLYRLNPKDFIGCLNVKATMYEMYSVSYDIRCTGLKGLLRSLLRFLSYS
  AQVTGQFLIYLGTYMLRVLDDKEERPSLRSQAKGRFTCG
• Function: Lipid transferase that promotes unilocular lipid droplet formation by mediating lipid droplet fusion. Lipid droplet fusion promotes their enlargement, restricting lipolysis and favoring lipid storage. Localizes on the lipid droplet surface, at focal contact sites between lipid droplets, and mediates atypical lipid droplet fusion by promoting directional net neutral lipid transfer from the smaller to larger lipid droplets. The transfer direction may be driven by the internal pressure difference between the contacting lipid droplet pair and occurs at a lower rate than that promoted by CIDEC. May also act as a CEBPB coactivator in epithelial cells to control the expression of a subset of CEBPB downstream target genes, including ID2, IGF1, PRLR, SOCS1, SOCS3, XDH, but not casein. By interacting with CEBPB, strengthens the association of CEBPB with the XDH promoter, increases histone acetylation and dissociates HDAC1 from the promoter. When overexpressed, induces apoptosis; the physiological significance of its role in apoptosis is unclear.
• Tissue Specificity: Expressed in omental and subcutaneous adipose tissue (at protein level).
• KEGG Pathway: AMPK sig.ling pathway (hsa04152)
• Reactome Pathway: Lipid particle organization (R-HSA-8964572)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiac failure	DISDC067	Strong	Biomarker	[1]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[1]
Endometrial carcinoma	DISXR5CY	Strong	Posttranslational Modification	[2]
Liver cancer	DISDE4BI	Strong	Biomarker	[3]
Obesity	DIS47Y1K	Strong	Altered Expression	[4]
Hepatitis	DISXXX35	moderate	Altered Expression	[4]
Non-alcoholic fatty liver disease	DISDG1NL	moderate	Altered Expression	[4]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Altered Expression	[5]

12 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Lipid transferase CIDEA (CIDEA).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Lipid transferase CIDEA (CIDEA).	[7]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Lipid transferase CIDEA (CIDEA).	[8]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Lipid transferase CIDEA (CIDEA).	[9]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Lipid transferase CIDEA (CIDEA).	[10]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Lipid transferase CIDEA (CIDEA).	[11]
Tolcapone	DM8MNVO	Approved	Tolcapone increases the expression of Lipid transferase CIDEA (CIDEA).	[12]
Delphinidin	DMS2WIN	Phase 2	Delphinidin increases the expression of Lipid transferase CIDEA (CIDEA).	[13]
PF-02545920	DMJPE61	Phase 2	PF-02545920 increases the expression of Lipid transferase CIDEA (CIDEA).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Lipid transferase CIDEA (CIDEA).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Lipid transferase CIDEA (CIDEA).	[16]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Lipid transferase CIDEA (CIDEA).	[17]

References

• [1] Inhibition of G-protein-coupled Receptor Kinase 2 Prevents the Dysfunctional Cardiac Substrate Metabolism in Fatty Acid Synthase Transgenic Mice. J Biol Chem. 2016 Feb 5;291(6):2583-600. doi: 10.1074/jbc.M115.702688. Epub 2015 Dec 15.
• [2] Promoter hypermethylation of CIDEA, HAAO and RXFP3 associated with microsatellite instability in endometrial carcinomas.Gynecol Oncol. 2010 May;117(2):239-47. doi: 10.1016/j.ygyno.2010.02.006. Epub 2010 Mar 7.
• [3] Discriminating between adaptive and carcinogenic liver hypertrophy in rat studies using logistic ridge regression analysis of toxicogenomic data: The mode of action and predictive models.Toxicol Appl Pharmacol. 2017 Mar 1;318:79-87. doi: 10.1016/j.taap.2017.01.006. Epub 2017 Jan 18.
• [4] The Differential Expression of Cide Family Members is Associated with Nafld Progression from Steatosis to Steatohepatitis.Sci Rep. 2019 May 16;9(1):7501. doi: 10.1038/s41598-019-43928-7.
• [5] Effects of insulin and exercise training on FGF21, its receptors and target genes in obesity and type 2 diabetes.Diabetologia. 2017 Oct;60(10):2042-2051. doi: 10.1007/s00125-017-4373-5. Epub 2017 Jul 18.
• [6] Pattern of expression of apoptosis and inflammatory genes in humans exposed to arsenic and/or fluoride. Sci Total Environ. 2010 Jan 15;408(4):760-7. doi: 10.1016/j.scitotenv.2009.11.016. Epub 2009 Dec 4.
• [7] Arsenic trioxide induces different gene expression profiles of genes related to growth and apoptosis in glioma cells dependent on the p53 status. Mol Biol Rep. 2008 Sep;35(3):421-9.
• [8] CpG methylation plays a vital role in determining tissue- and cell-specific expression of the human cell-death-inducing DFF45-like effector A gene through the regulation of Sp1/Sp3 binding. Nucleic Acids Res. 2008 Jan;36(1):330-41. doi: 10.1093/nar/gkm1028. Epub 2007 Nov 22.
• [9] Dexamethasone and the inflammatory response in explants of human omental adipose tissue. Mol Cell Endocrinol. 2010 Feb 5;315(1-2):292-8.
• [10] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [11] Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
• [12] Effect of the Catechol-O-Methyltransferase Inhibitors Tolcapone and Entacapone on Fatty Acid Metabolism in HepaRG Cells. Toxicol Sci. 2018 Aug 1;164(2):477-488.
• [13] Delphinidin modulates the DNA-damaging properties of topoisomerase II poisons. Chem Res Toxicol. 2009 Mar 16;22(3):554-64. doi: 10.1021/tx800293v.
• [14] A novel thermoregulatory role for PDE10A in mouse and human adipocytes. EMBO Mol Med. 2016 Jul 1;8(7):796-812. doi: 10.15252/emmm.201506085. Print 2016 Jul.
• [15] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [16] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [17] Identification of genes associated with paraquat-induced toxicity in SH-SY5Y cells by PCR array focused on apoptotic pathways. J Toxicol Environ Health A. 2008;71(22):1457-67. doi: 10.1080/15287390802329364.