Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBZ5JQS)

• DOT Name: EEF1A lysine methyltransferase 2 (EEF1AKMT2)
• Synonyms: EC 2.1.1.-; Methyltransferase-like protein 10; Protein-lysine N-methyltransferase METTL10
• Gene Name: EEF1AKMT2
• Related Disease:
  Inflammatory bowel disease
  Ulcerative colitis
• UniProt ID: EFMT2_HUMAN
• EC Number: 2.1.1.-
• Pfam ID: PF13847
• Sequence:
  MSSGADGGGGAAVAARSDKGSPGEDGFVPSALGTREHWDAVYERELQTFREYGDTGEIWF
  GEESMNRLIRWMQKHKIPLDASVLDIGTGNGVFLVELAKFGFSNITGIDYSPSAIQLSGS
  IIEKEGLSNIKLKVEDFLNLSTQLSGFHICIDKGTFDAISLNPDNAIEKRKQYVKSLSRV
  LKVKGFFLITSCNWTKEELLNEFSEGWSTVAGFWLTAALTSWAQAIFSTSASRVGGTTGT
  HHHAWIIFVFLAETRFCHVVQAGLELLGSSDSPTWPPKVLGLYHARPSLAF
• Function: Protein-lysine methyltransferase that selectively catalyzes the trimethylation of EEF1A at 'Lys-318'.
• Reactome Pathway: Protein methylation (R-HSA-8876725)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Inflammatory bowel disease	DISGN23E	Limited	Genetic Variation	[1]
Ulcerative colitis	DIS8K27O	Limited	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of EEF1A lysine methyltransferase 2 (EEF1AKMT2).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of EEF1A lysine methyltransferase 2 (EEF1AKMT2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of EEF1A lysine methyltransferase 2 (EEF1AKMT2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of EEF1A lysine methyltransferase 2 (EEF1AKMT2).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of EEF1A lysine methyltransferase 2 (EEF1AKMT2).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of EEF1A lysine methyltransferase 2 (EEF1AKMT2).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of EEF1A lysine methyltransferase 2 (EEF1AKMT2).	[7]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of EEF1A lysine methyltransferase 2 (EEF1AKMT2).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of EEF1A lysine methyltransferase 2 (EEF1AKMT2).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of EEF1A lysine methyltransferase 2 (EEF1AKMT2).	[9]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of EEF1A lysine methyltransferase 2 (EEF1AKMT2).	[8]

References

• [1] Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease.Nat Genet. 2017 Feb;49(2):256-261. doi: 10.1038/ng.3760. Epub 2017 Jan 9.
• [2] 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.
• [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] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 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.
• [7] 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.
• [8] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [9] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [10] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.