Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6Q6FBD)

• DOT Name: Electron transfer flavoprotein subunit beta (ETFB)
• Synonyms: Beta-ETF
• Gene Name: ETFB
• Related Disease:
  Multiple acyl-CoA dehydrogenase deficiency
  Advanced cancer
  Behcet disease
  Neoplasm
  Dorfman-Chanarin disease
  Neutral lipid storage myopathy
  Systemic primary carnitine deficiency disease
• UniProt ID: ETFB_HUMAN
• PDB ID: 1EFV; 1T9G; 2A1T; 2A1U
• Pfam ID: PF01012
• Sequence:
  MAELRVLVAVKRVIDYAVKIRVKPDRTGVVTDGVKHSMNPFCEIAVEEAVRLKEKKLVKE
  VIAVSCGPAQCQETIRTALAMGADRGIHVEVPPAEAERLGPLQVARVLAKLAEKEKVDLV
  LLGKQAIDDDCNQTGQMTAGFLDWPQGTFASQVTLEGDKLKVEREIDGGLETLRLKLPAV
  VTADLRLNEPRYATLPNIMKAKKKKIEVIKPGDLGVDLTSKLSVISVEDPPQRTAGVKVE
  TTEDLVAKLKEIGRI
• Function: Heterodimeric electron transfer flavoprotein that accepts electrons from several mitochondrial dehydrogenases, including acyl-CoA dehydrogenases, glutaryl-CoA and sarcosine dehydrogenase. It transfers the electrons to the main mitochondrial respiratory chain via ETF-ubiquinone oxidoreductase (Probable). Required for normal mitochondrial fatty acid oxidation and normal amino acid metabolism. ETFB binds an AMP molecule that probably has a purely structural role.
• Tissue Specificity: Abundant in liver, heart and skeletal muscle. A weak expression is seen in the brain, placenta, lung, kidney and pancreas.
• Reactome Pathway:
  Protein methylation (R-HSA-8876725)
  Respiratory electron transport (R-HSA-611105)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Multiple acyl-CoA dehydrogenase deficiency	DISEFBN7	Definitive	Autosomal recessive	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Behcet disease	DISSYMBS	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Dorfman-Chanarin disease	DISKKT3R	Limited	Biomarker	[4]
Neutral lipid storage myopathy	DISR9UYD	Limited	Biomarker	[4]
Systemic primary carnitine deficiency disease	DIS9OPZ4	Limited	Biomarker	[4]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Electron transfer flavoprotein subunit beta (ETFB) affects the response to substance of Fluorouracil.	[21]
Vinblastine	DM5TVS3	Approved	Electron transfer flavoprotein subunit beta (ETFB) affects the response to substance of Vinblastine.	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Electron transfer flavoprotein subunit beta (ETFB).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Electron transfer flavoprotein subunit beta (ETFB).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Electron transfer flavoprotein subunit beta (ETFB).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Electron transfer flavoprotein subunit beta (ETFB).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Electron transfer flavoprotein subunit beta (ETFB).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Electron transfer flavoprotein subunit beta (ETFB).	[10]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Electron transfer flavoprotein subunit beta (ETFB).	[11]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Electron transfer flavoprotein subunit beta (ETFB).	[12]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Electron transfer flavoprotein subunit beta (ETFB).	[14]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Electron transfer flavoprotein subunit beta (ETFB).	[15]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Electron transfer flavoprotein subunit beta (ETFB).	[16]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Electron transfer flavoprotein subunit beta (ETFB).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Electron transfer flavoprotein subunit beta (ETFB).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Electron transfer flavoprotein subunit beta (ETFB).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Electron transfer flavoprotein subunit beta (ETFB).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Electron transfer flavoprotein subunit beta (ETFB).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Electron transfer flavoprotein subunit beta (ETFB).	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Electron transfer flavoprotein subunit beta (ETFB).	[13]

References

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• [8] 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.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [11] Bisphenol-A and estradiol exert novel gene regulation in human MCF-7 derived breast cancer cells. Mol Cell Endocrinol. 2004 Jun 30;221(1-2):47-55. doi: 10.1016/j.mce.2004.04.010.
• [12] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [13] 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.
• [14] 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.
• [15] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [16] Proteomics-based identification of differentially abundant proteins from human keratinocytes exposed to arsenic trioxide. J Proteomics Bioinform. 2014 Jul;7(7):166-178.
• [17] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [18] 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.
• [19] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [20] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [21] Mechanistic and predictive profiling of 5-Fluorouracil resistance in human cancer cells. Cancer Res. 2004 Nov 15;64(22):8167-76. doi: 10.1158/0008-5472.CAN-04-0970.
• [22] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.