Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTH0QZBW)

• DOT Name: Methyltransferase-like protein 22 (METTL22)
• Synonyms: EC 2.1.1.-
• Gene Name: METTL22
• UniProt ID: MET22_HUMAN
• EC Number: 2.1.1.-
• Pfam ID: PF10294
• Sequence:
  MVQLAPAAAMDEVTFRSDTVLSDVHLYTPNHRHLMVRLNSVGQPVFLSQFKLLWSQDSWT
  DSGAKGGSHRDVHTKEPPSAETGSTGSPPGSGHGNEGFSLQAGTDTTGQEVAEAQLDEDG
  DLDVVRRPRAASDSNPAGPLRDKVHPMILAQEEDDVLGEEAQGSPHDIIRIEHTMATPLE
  DVGKQVWRGALLLADYILFRQDLFRGCTALELGAGTGLASIIAATMARTVYCTDVGADLL
  SMCQRNIALNSHLAATGGGIVRVKELDWLKDDLCTDPKVPFSWSQEEISDLYDHTTILFA
  AEVFYDDDLTDAVFKTLSRLAHRLKNACTAILSVEKRLNFTLRHLDVTCEAYDHFRSCLH
  ALEQLADGKLRFVVEPVEASFPQLLVYERLQQLELWKIIAEPVT
• Function: Protein N-lysine methyltransferase. Trimethylates KIN at Lys-135 (in vitro).
• Reactome Pathway: Protein methylation (R-HSA-8876725)

Molecular Interaction Atlas (MIA) of This DOT

6 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 Methyltransferase-like protein 22 (METTL22).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Methyltransferase-like protein 22 (METTL22).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Methyltransferase-like protein 22 (METTL22).	[3]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Methyltransferase-like protein 22 (METTL22).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Methyltransferase-like protein 22 (METTL22).	[7]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Methyltransferase-like protein 22 (METTL22).	[10]

4 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 Methyltransferase-like protein 22 (METTL22).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Methyltransferase-like protein 22 (METTL22).	[6]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Methyltransferase-like protein 22 (METTL22).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of Methyltransferase-like protein 22 (METTL22).	[9]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [3] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] 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.
• [5] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [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] 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] Maternal environmental exposure to bisphenols and epigenome-wide DNA methylation in infant cord blood. Environ Epigenet. 2020 Dec 23;6(1):dvaa021. doi: 10.1093/eep/dvaa021. eCollection 2020.
• [10] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.