Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNQZAX4)

• DOT Name: Electron transfer flavoprotein beta subunit lysine methyltransferase (ETFBKMT)
• Synonyms: EC 2.1.1.-; ETFB lysine methyltransferase; ETFB-KMT; Protein N-lysine methyltransferase METTL20
• Gene Name: ETFBKMT
• UniProt ID: ETKMT_HUMAN
• EC Number: 2.1.1.-
• Pfam ID: PF06325
• Sequence:
  MALSLGWKAHRNHCGLLLQALRSSGLLLFPCGQCPWRGAGSFLDPEIKAFLEENTEVTSS
  GSLTPEIQLRLLTPRCKFWWERADLWPHSDPYWAIYWPGGQALSRYLLDNPDVVRGKSVL
  DLGSGCGATAIAAKMSGASRILANDIDPIAGMAITLNCELNRLNPFPILIQNILNLEQDK
  WDLVVLGDMFYDEDLADSLHQWLKKCFWTYRTRVLIGDPGRPQFSGHSIQHHLHKVVEYS
  LLESTRQENSGLTTSTVWGFQP
• Function: Protein-lysine methyltransferase that selectively trimethylates the flavoprotein ETFB in mitochondria. Thereby, may negatively regulate the function of ETFB in electron transfer from Acyl-CoA dehydrogenases to the main respiratory chain.
• Reactome Pathway: Protein methylation (R-HSA-8876725)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Electron transfer flavoprotein beta subunit lysine methyltransferase (ETFBKMT).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Electron transfer flavoprotein beta subunit lysine methyltransferase (ETFBKMT).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Electron transfer flavoprotein beta subunit lysine methyltransferase (ETFBKMT).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Electron transfer flavoprotein beta subunit lysine methyltransferase (ETFBKMT).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Electron transfer flavoprotein beta subunit lysine methyltransferase (ETFBKMT).	[5]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [3] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] 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.