Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBX9H9D)

• DOT Name: Transmembrane protein 134 (TMEM134)
• Gene Name: TMEM134
• Related Disease: Hepatitis E virus infection
• UniProt ID: TM134_HUMAN
• Pfam ID: PF05915
• Sequence:
  MSAARPQFSIDDAFELSLEDGGPGPESSGVARFGPLHFERRARFEVADEDKQSRLRYQNL
  ENDEDGAQASPEPDGGVGTRDSSRTSIRSSQWSFSTISSSTQRSYNTCCSWTQHPLIQKN
  RRVVLASFLLLLLGLVLILVGVGLEATPSPGVSSAIFFVPGFLLLVPGVYHVIFIYCAVK
  GHRGFQFFYLPYFEK

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatitis E virus infection	DIS0TXIR	Disputed	Biomarker	[1]

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Transmembrane protein 134 (TMEM134) affects the response to substance of Doxorubicin.	[10]
Paclitaxel	DMLB81S	Approved	Transmembrane protein 134 (TMEM134) affects the response to substance of Paclitaxel.	[10]
Vinblastine	DM5TVS3	Approved	Transmembrane protein 134 (TMEM134) affects the response to substance of Vinblastine.	[10]

7 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 Transmembrane protein 134 (TMEM134).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Transmembrane protein 134 (TMEM134).	[3]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Transmembrane protein 134 (TMEM134).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Transmembrane protein 134 (TMEM134).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Transmembrane protein 134 (TMEM134).	[6]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Transmembrane protein 134 (TMEM134).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Transmembrane protein 134 (TMEM134).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Transmembrane protein 134 (TMEM134).	[8]

References

• [1] Systematic identification of hepatitis E virus ORF2 interactome reveals that TMEM134 engages in ORF2-mediated NF-B pathway.Virus Res. 2017 Jan 15;228:102-108. doi: 10.1016/j.virusres.2016.11.027. Epub 2016 Nov 27.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [5] 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.
• [6] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [7] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [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] 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.
• [10] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.