Details of Drug Off-Target (DOT)

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

• DOT Name: EEF1A lysine methyltransferase 3 (EEF1AKMT3)
• Synonyms: EC 2.1.1.-; Hepatocellular carcinoma-associated antigen 557a; Methyltransferase-like protein 21B; Protein-lysine methyltransferase METTL21B; eEF1A-KMT3
• Gene Name: EEF1AKMT3
• Related Disease: Multiple sclerosis
• UniProt ID: EFMT3_HUMAN
• PDB ID: 4QPN
• EC Number: 2.1.1.-
• Pfam ID: PF10294
• Sequence:
  MADPGPDPESESESVFPREVGLFADSYSEKSQFCFCGHVLTITQNFGSRLGVAARVWDAA
  LSLCNYFESQNVDFRGKKVIELGAGTGIVGILAALQGGDVTITDLPLALEQIQGNVQANV
  PAGGQAQVRALSWGIDHHVFPANYDLVLGADIVYLEPTFPLLLGTLQHLCRPHGTIYLAS
  KMRKEHGTESFFQHLLPQHFQLELAQRDEDENVNIYRARHREPRPA
• Function: Protein-lysine methyltransferase that selectively mono-, di- and trimethylates 'Lys-165' of the translation elongation factors EEF1A1 and EEF1A2 in an aminoacyl-tRNA and GTP-dependent manner. EEF1A1 methylation by EEF1AKMT3 is dynamic as well as inducible by stress conditions, such as ER-stress, and plays a regulatory role on mRNA translation.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of EEF1A lysine methyltransferase 3 (EEF1AKMT3).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of EEF1A lysine methyltransferase 3 (EEF1AKMT3).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of EEF1A lysine methyltransferase 3 (EEF1AKMT3).	[4]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of EEF1A lysine methyltransferase 3 (EEF1AKMT3).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of EEF1A lysine methyltransferase 3 (EEF1AKMT3).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of EEF1A lysine methyltransferase 3 (EEF1AKMT3).	[8]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of EEF1A lysine methyltransferase 3 (EEF1AKMT3).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of EEF1A lysine methyltransferase 3 (EEF1AKMT3).	[11]

2 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 EEF1A lysine methyltransferase 3 (EEF1AKMT3).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of EEF1A lysine methyltransferase 3 (EEF1AKMT3).	[10]

References

• [1] Integrative analysis revealed potential causal genetic and epigenetic factors for multiple sclerosis.J Neurol. 2019 Nov;266(11):2699-2709. doi: 10.1007/s00415-019-09476-w. Epub 2019 Jul 18.
• [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] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [4] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [5] 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.
• [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] 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.
• [8] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [9] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [10] 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.
• [11] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.