Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3OO484)

• DOT Name: Transmembrane protein 115 (TMEM115)
• Synonyms: Placental protein 6; Protein PL6
• Gene Name: TMEM115
• Related Disease:
  Carcinoma
  Advanced cancer
• UniProt ID: TM115_HUMAN
• Pfam ID: PF08551
• Sequence:
  MQRALPGARQHLGAILASASVVVKALCAAVLFLYLLSFAVDTGCLAVTPGYLFPPNFWIW
  TLATHGLMEQHVWDVAISLTTVVVAGRLLEPLWGALELLIFFSVVNVSVGLLGAFAYLLT
  YMASFNLVYLFTVRIHGALGFLGGVLVALKQTMGDCVVLRVPQVRVSVMPMLLLALLLLL
  RLATLLQSPALASYGFGLLSSWVYLRFYQRHSRGRGDMADHFAFATFFPEILQPVVGLLA
  NLVHSLLVKVKICQKTVKRYDVGAPSSITISLPGTDPQDAERRRQLALKALNERLKRVED
  QSIWPSMDDDEEESGAKVDSPLPSDKAPTPPGKGAAPESSLITFEAAPPTL
• Function: May play a role in retrograde transport of proteins from the Golgi to the endoplasmic reticulum. May indirectly play a role in protein glycosylation in the Golgi.
• Tissue Specificity: Expressed strongly in kidney and skeletal muscle, followed by liver, placenta, pancreas, and lung, with low amounts in heart and only traces in brain . Widely expressed with ubiquitous expression in epithelial tissues (at protein level) .
• Reactome Pathway: COPI-mediated anterograde transport (R-HSA-6807878)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma	DISH9F1N	Strong	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Limited	Genetic Variation	[2]

4 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 115 (TMEM115).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Transmembrane protein 115 (TMEM115).	[4]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Transmembrane protein 115 (TMEM115).	[7]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Transmembrane protein 115 (TMEM115).	[9]

3 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 Transmembrane protein 115 (TMEM115).	[5]
Quercetin	DM3NC4M	Approved	Quercetin increases the phosphorylation of Transmembrane protein 115 (TMEM115).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Transmembrane protein 115 (TMEM115).	[8]

References

• [1] Loss of PL6 protein expression in renal clear cell carcinomas and other VHL-deficient tumours.J Pathol. 2008 Jan;214(1):46-57. doi: 10.1002/path.2252.
• [2] Clinical and pathological characteristic of metastatic malignant mesothelioma initially diagnosed by lymph node biopsy.Pathol Res Pract. 2017 Jun;213(6):598-605. doi: 10.1016/j.prp.2017.05.003. Epub 2017 May 13.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.