Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSHNL5K)

• DOT Name: MTRF1L release factor glutamine methyltransferase (HEMK1)
• Synonyms: EC 2.1.1.297; HemK methyltransferase family member 1; M.HsaHemKP
• Gene Name: HEMK1
• Related Disease: Psoriatic arthritis
• UniProt ID: HEMK1_HUMAN
• EC Number: 2.1.1.297
• Pfam ID: PF05175 ; PF17827
• Sequence:
  MELWGRMLWALLSGPGRRGSTRGWAFSSWQPQPPLAGLSSAIELVSHWTGVFEKRGIPEA
  RESSEYIVAHVLGAKTFQSLRPALWTQPLTSQQLQCIRELSSRRLQRMPVQYILGEWDFQ
  GLSLRMVPPVFIPRPETEELVEWVLEEVAQRSHAVGSPGSPLILEVGCGSGAISLSLLSQ
  LPQSRVIAVDKREAAISLTHENAQRLRLQDRIWIIHLDMTSERSWTHLPWGPMDLIVSNP
  PYVFHQDMEQLAPEIRSYEDPAALDGGEEGMDIITHILALAPRLLKDSGSIFLEVDPRHP
  ELVSSWLQSRPDLYLNLVAVRRDFCGRPRFLHIRRSGP
• Function: N5-glutamine methyltransferase responsible for the methylation of the glutamine residue in the universally conserved GGQ motif of the mitochondrial translation release factors MTRF1, MTRF1L, MRPL58/ICT1 and MTRFR.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Psoriatic arthritis	DISLWTG2	Strong	Biomarker	[1]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Camptothecin	DM6CHNJ	Phase 3	MTRF1L release factor glutamine methyltransferase (HEMK1) decreases the response to substance of Camptothecin.	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of MTRF1L release factor glutamine methyltransferase (HEMK1).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of MTRF1L release factor glutamine methyltransferase (HEMK1).	[6]

5 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 MTRF1L release factor glutamine methyltransferase (HEMK1).	[3]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of MTRF1L release factor glutamine methyltransferase (HEMK1).	[4]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of MTRF1L release factor glutamine methyltransferase (HEMK1).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of MTRF1L release factor glutamine methyltransferase (HEMK1).	[7]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE decreases the expression of MTRF1L release factor glutamine methyltransferase (HEMK1).	[8]

References

• [1] Evidence for a Role of TGF--Activated Kinase 1 and MAP3K7 Binding Protein 3 in Peanut-Specific T-Cell Responses.Int Arch Allergy Immunol. 2019;179(1):10-16. doi: 10.1159/000496438. Epub 2019 Mar 20.
• [2] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [3] 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.
• [4] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [5] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [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] 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] Preferential induction of the AhR gene battery in HepaRG cells after a single or repeated exposure to heterocyclic aromatic amines. Toxicol Appl Pharmacol. 2010 Nov 15;249(1):91-100.
• [9] ATR inhibitors VE-821 and VX-970 sensitize cancer cells to topoisomerase i inhibitors by disabling DNA replication initiation and fork elongation responses. Cancer Res. 2014 Dec 1;74(23):6968-79.