Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT509SQF)

• DOT Name: Electron transfer flavoprotein regulatory factor 1 (ETFRF1)
• Synonyms: LYR motif-containing protein 5
• Gene Name: ETFRF1
• UniProt ID: ETFR1_HUMAN
• Pfam ID: PF05347
• Sequence:
  MKMANSLRGEVLKLYKNLLYLGRDYPKGADYFKKRLKNIFLKNKDVKNPEKIKELIAQGE
  FVMKELEALYFLRKYRAMKQRYYSDTNKTN
• Function: Acts as a regulator of the electron transfer flavoprotein by promoting the removal of flavin from the ETF holoenzyme (composed of ETFA and ETFB).

Molecular Interaction Atlas (MIA) of This DOT

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Electron transfer flavoprotein regulatory factor 1 (ETFRF1).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Electron transfer flavoprotein regulatory factor 1 (ETFRF1).	[6]

10 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 Electron transfer flavoprotein regulatory factor 1 (ETFRF1).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Electron transfer flavoprotein regulatory factor 1 (ETFRF1).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Electron transfer flavoprotein regulatory factor 1 (ETFRF1).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Electron transfer flavoprotein regulatory factor 1 (ETFRF1).	[5]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Electron transfer flavoprotein regulatory factor 1 (ETFRF1).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Electron transfer flavoprotein regulatory factor 1 (ETFRF1).	[8]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Electron transfer flavoprotein regulatory factor 1 (ETFRF1).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Electron transfer flavoprotein regulatory factor 1 (ETFRF1).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Electron transfer flavoprotein regulatory factor 1 (ETFRF1).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Electron transfer flavoprotein regulatory factor 1 (ETFRF1).	[12]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] 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.
• [3] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [6] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [7] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Epigallocatechin-3-gallate (EGCG) protects against chromate-induced toxicity in vitro. Toxicol Appl Pharmacol. 2012 Jan 15;258(2):166-75.
• [10] 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.
• [11] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.