Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7I9IXA)

• DOT Name: Transmembrane protein 121 (TMEM121)
• Gene Name: TMEM121
• UniProt ID: TM121_HUMAN
• Pfam ID: PF14997
• Sequence:
  MVLPPPDRRHVCLTTLVIMGSMAVMDAYLVEQNQGPRKIGVCIIVLVGDVCFLLVLRYVA
  VWVGAEVRTAKRGYAMILWFLYIFVLEIKLYFIFQNYKAARRGAADPVARKALTLLLSVC
  VPGLFLLLVALDRMEYVRTFRKREDLRGRLFWVALDLLDLLDMQASLWEPPRSGLPLWAE
  GLTFFYCYMLLLVLPCVALSEVSMQGEHIAPQKMMLYPVLSLATVNVVAVLARAANMALF
  RDSRVSAIFVGKNVVALATKACTFLEYRRQVRDFPPPALSLELQPPPPQRNSVPPPPPPL
  HGPPGRPHMSSPTRDPLDT
• Function: May play a role in MAPK signaling.
• Tissue Specificity: Highly expressed in heart and detected in pancreas, liver and skeletal muscle.

Molecular Interaction Atlas (MIA) of This DOT

2 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 Transmembrane protein 121 (TMEM121).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Transmembrane protein 121 (TMEM121).	[8]

9 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 Transmembrane protein 121 (TMEM121).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Transmembrane protein 121 (TMEM121).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Transmembrane protein 121 (TMEM121).	[4]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Transmembrane protein 121 (TMEM121).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Transmembrane protein 121 (TMEM121).	[6]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Transmembrane protein 121 (TMEM121).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Transmembrane protein 121 (TMEM121).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Transmembrane protein 121 (TMEM121).	[10]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Transmembrane protein 121 (TMEM121).	[11]

References

• [1] Nuclear and Mitochondrial DNA Methylation Patterns Induced by Valproic Acid in Human Hepatocytes. Chem Res Toxicol. 2017 Oct 16;30(10):1847-1854. doi: 10.1021/acs.chemrestox.7b00171. Epub 2017 Sep 13.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [8] 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.
• [9] Loss of TRIM33 causes resistance to BET bromodomain inhibitors through MYC- and TGF-beta-dependent mechanisms. Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):E4558-66.
• [10] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [11] 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.