Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT873IYM)

• DOT Name: Lipid transferase CIDEB (CIDEB)
• Synonyms: Cell death activator CIDE-B; Cell death-inducing DFFA-like effector B
• Gene Name: CIDEB
• Related Disease:
  Hepatitis B virus infection
  Coronary heart disease
• UniProt ID: CIDEB_HUMAN
• PDB ID: 1D4B
• Pfam ID: PF02017
• Sequence:
  MEYLSALNPSDLLRSVSNISSEFGRRVWTSAPPPQRPFRVCDHKRTIRKGLTAATRQELL
  AKALETLLLNGVLTLVLEEDGTAVDSEDFFQLLEDDTCLMVLQSGQSWSPTRSGVLSYGL
  GRERPKHSKDIARFTFDVYKQNPRDLFGSLNVKATFYGLYSMSCDFQGLGPKKVLRELLR
  WTSTLLQGLGHMLLGISSTLRHAVEGAEQWQQKGRLHSY
• Function: Lipid transferase specifically expressed in hepatocytes, which 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. Promotes lipid exchange and lipid droplet fusion in both small and large lipid droplet-containing hepatocytes. In addition to its role in lipid droplet fusion, also involved in cytoplasmic vesicle biogenesis and transport. Required for very-low-density lipoprotein (VLDL) lipidation and maturation. Probably involved in the biogenesis of VLDL transport vesicles by forming a COPII vesicle coat and facilitating the formation of endoplasmic reticulum-derived large vesicles. Also involved in sterol-regulated export of the SCAP-SREBP complex, composed of SCAP, SREBF1/SREBP1 and SREBF2/SREBP2, by promoting loading of SCAP-SREBP into COPII vesicles. May also activate apoptosis ; (Microbial infection) Involved in Hepatatis C virus (HCV) assembly and required for HCV entry into hepatocytes.
• Tissue Specificity: Highly expressed in liver and small intestine and, at lower levels, in colon, kidney and spleen.
• KEGG Pathway: Cholesterol metabolism (hsa04979)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[1]
Coronary heart disease	DIS5OIP1	Limited	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Lipid transferase CIDEB (CIDEB).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Lipid transferase CIDEB (CIDEB).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Lipid transferase CIDEB (CIDEB).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Lipid transferase CIDEB (CIDEB).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Lipid transferase CIDEB (CIDEB).	[3]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Lipid transferase CIDEB (CIDEB).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Lipid transferase CIDEB (CIDEB).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Lipid transferase CIDEB (CIDEB).	[9]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Lipid transferase CIDEB (CIDEB).	[10]
Folic acid	DMEMBJC	Approved	Folic acid affects the expression of Lipid transferase CIDEB (CIDEB).	[11]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Lipid transferase CIDEB (CIDEB).	[12]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Lipid transferase CIDEB (CIDEB).	[13]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Lipid transferase CIDEB (CIDEB).	[13]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Lipid transferase CIDEB (CIDEB).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Lipid transferase CIDEB (CIDEB).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Lipid transferase CIDEB (CIDEB).	[16]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Lipid transferase CIDEB (CIDEB).	[17]

References

• [1] Hepatitis B virus prevents excessive viral production via reduction of cell death-inducing DFF45-like effectors.J Gen Virol. 2017 Jul;98(7):1762-1773. doi: 10.1099/jgv.0.000813.
• [2] Integrated microRNAgene analysis of coronary artery disease based on miRNA and gene expression profiles.Mol Med Rep. 2016 Apr;13(4):3063-73. doi: 10.3892/mmr.2016.4936. Epub 2016 Feb 23.
• [3] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Analysis of the in vitro synergistic effect of 5-fluorouracil and cisplatin on cervical carcinoma cells. Int J Gynecol Cancer. 2006 May-Jun;16(3):1321-9.
• [7] 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.
• [8] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [9] Classification of heavy-metal toxicity by human DNA microarray analysis. Environ Sci Technol. 2007 May 15;41(10):3769-74.
• [10] Proteomic analysis of antiproliferative effects by treatment of 5-fluorouracil in cervical cancer cells. DNA Cell Biol. 2004 Nov;23(11):769-76.
• [11] Effects of folate deficiency on gene expression in the apoptosis and cancer pathways in colon cancer cells. Carcinogenesis. 2006 May;27(5):916-24. doi: 10.1093/carcin/bgi312. Epub 2005 Dec 16.
• [12] Bortezomib induces caspase-dependent apoptosis in Hodgkin lymphoma cell lines and is associated with reduced c-FLIP expression: a gene expression profiling study with implications for potential combination therapies. Leuk Res. 2008 Feb;32(2):275-85. doi: 10.1016/j.leukres.2007.05.024. Epub 2007 Jul 19.
• [13] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [14] 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.
• [15] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [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.