Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDV54V6)

• DOT Name: Adenine nucleotide translocase lysine N-methyltransferase (ANTKMT)
• Synonyms: ANT-KMT; EC 2.1.1.-
• Gene Name: ANTKMT
• Related Disease: Nasopharyngeal carcinoma
• UniProt ID: ANKMT_HUMAN
• EC Number: 2.1.1.-
• Sequence:
  MEQDDPVEALTELRERRLGALELLQAAAGSGLAAYAVWALLLQPGFRRVPLRLQVPYVGA
  SARQVEHVLSLLRGRPGKTVDLGSGDGRIVLAAHRCGLRPAVGYELNPWLVALARLHAWR
  AGCAGSVCYRRKDLWKVSLRDCRNVSVFLAPSVLPLLEDKLRTELPAGARVVSGRFPLPT
  WQPVTAVGEGLDRVWAYDVPEGGQAGEAASSRIPIQAAPGPSSAPIPGGLISQAS
• Function: Mitochondrial protein-lysine N-methyltransferase that trimethylates adenine nucleotide translocases ANT2/SLC25A5 and ANT3/SLC25A6, thereby regulating mitochondrial respiration. Probably also trimethylates ANT1/SLC25A4.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Adenine nucleotide translocase lysine N-methyltransferase (ANTKMT).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Adenine nucleotide translocase lysine N-methyltransferase (ANTKMT).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Adenine nucleotide translocase lysine N-methyltransferase (ANTKMT).	[4]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Adenine nucleotide translocase lysine N-methyltransferase (ANTKMT).	[5]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Adenine nucleotide translocase lysine N-methyltransferase (ANTKMT).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Adenine nucleotide translocase lysine N-methyltransferase (ANTKMT).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Adenine nucleotide translocase lysine N-methyltransferase (ANTKMT).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Adenine nucleotide translocase lysine N-methyltransferase (ANTKMT).	[9]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Adenine nucleotide translocase lysine N-methyltransferase (ANTKMT).	[10]

References

• [1] Serum proteomics identify potential biomarkers for nasopharyngeal carcinoma sensitivity to radiotherapy.Biosci Rep. 2019 May 14;39(5):BSR20190027. doi: 10.1042/BSR20190027. Print 2019 May 31.
• [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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [6] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [9] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [10] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.