Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8NQ79G)

• DOT Name: Transmembrane protein 243 (TMEM243)
• Synonyms: MDR1- and mitochondrial taxol resistance-associated protein; MM-TRAG
• Gene Name: TMEM243
• Related Disease: Advanced cancer
• UniProt ID: TM243_HUMAN
• Pfam ID: PF10856
• Sequence:
  MEDFATRTYGTSGLDNRPLFGETSAKDRIINLVVGSLTSLLILVTLISAFVFPQLPPKPL
  NIFFAVCISLSSITACILIYWYRQGDLEPKFRKLIYYIIFSIIMLCICANLYFHDVGR
• Tissue Specificity: Widely expressed.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]

12 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 Transmembrane protein 243 (TMEM243).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Transmembrane protein 243 (TMEM243).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Transmembrane protein 243 (TMEM243).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Transmembrane protein 243 (TMEM243).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Transmembrane protein 243 (TMEM243).	[1]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Transmembrane protein 243 (TMEM243).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Transmembrane protein 243 (TMEM243).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Transmembrane protein 243 (TMEM243).	[9]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Transmembrane protein 243 (TMEM243).	[10]
Paclitaxel	DMLB81S	Approved	Paclitaxel increases the expression of Transmembrane protein 243 (TMEM243).	[1]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Transmembrane protein 243 (TMEM243).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Transmembrane protein 243 (TMEM243).	[12]

References

• [1] MM-TRAG (MGC4175), a novel intracellular mitochondrial protein, is associated with the taxol- and doxorubicin-resistant phenotype in human cancer cell lines. Gene. 2004 Sep 29;340(1):53-9. doi: 10.1016/j.gene.2004.06.013.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] 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.
• [4] Systems analysis of transcriptome and proteome in retinoic acid/arsenic trioxide-induced cell differentiation/apoptosis of promyelocytic leukemia. Proc Natl Acad Sci U S A. 2005 May 24;102(21):7653-8.
• [5] 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.
• [6] MM-TRAG (MGC4175), a novel intracellular mitochondrial protein, is associated with the taxol- and doxorubicin-resistant phenotype in human cancer cell lines. Gene. 2004 Sep 29;340(1):53-9. doi: 10.1016/j.gene.2004.06.013.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [10] 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.
• [11] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [12] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.