Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5TV22K)

• DOT Name: Protein-lysine N-methyltransferase EEF2KMT (EEF2KMT)
• Synonyms: EC 2.1.1.-; eEF2-lysine methyltransferase; eEF2-KMT
• Gene Name: EEF2KMT
• UniProt ID: EF2KT_HUMAN
• PDB ID: 8FZB
• EC Number: 2.1.1.-
• Pfam ID: PF14904 ; PF10294
• Sequence:
  MAPEENAGTELLLQSFERRFLAARTLRSFPWQSLEAKLRDSSDSELLRDILHKTVKHPVC
  VKHPPSVKYARCFLSELIKKHEAVHTEPLDELYEALAETLMAKESTQGHRSYLLPSGGSV
  TLSESTAIISYGTTGLVTWDAALYLAEWAIENPAVFTNRTVLELGSGAGLTGLAICKMCR
  PRAYIFSDCHSRVLEQLRGNVLLNGLSLEADITAKLDSPRVTVAQLDWDVATVHQLSAFQ
  PDVVIAADVLYCPEAIMSLVGVLRRLAACREHQRAPEVYVAFTVRNPETCQLFTTELGRA
  GIRWEVEPRHEQKLFPYEEHLEMAMLNLTL
• Function: Catalyzes the trimethylation of eukaryotic elongation factor 2 (EEF2) on 'Lys-525'.
• 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 Protein-lysine N-methyltransferase EEF2KMT (EEF2KMT).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein-lysine N-methyltransferase EEF2KMT (EEF2KMT).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein-lysine N-methyltransferase EEF2KMT (EEF2KMT).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Protein-lysine N-methyltransferase EEF2KMT (EEF2KMT).	[4]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Protein-lysine N-methyltransferase EEF2KMT (EEF2KMT).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Protein-lysine N-methyltransferase EEF2KMT (EEF2KMT).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Protein-lysine N-methyltransferase EEF2KMT (EEF2KMT).	[7]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [7] Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int J Oncol. 2012 Jul;41(1):369-77.