Details of Drug Off-Target (DOT)

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

• DOT Name: Transmembrane protein 40 (TMEM40)
• Gene Name: TMEM40
• Related Disease:
  Bladder cancer
  Neoplasm
  Urinary bladder cancer
  Urinary bladder neoplasm
• UniProt ID: TMM40_HUMAN
• Pfam ID: PF15817
• Sequence:
  METSASSSQPQDNSQVHRETEDVDYGETDFHKQDGKAGLFSQEQYERNKSSSSSSSSSSS
  SSSSSSSSSSESNDEDQQPRATGKHRRSLGAGYPHGNGSPGPGHGEPDVLKDELQLYGDA
  PGEVVPSGESGLRRRGSDPASGEVEASQLRRLNIKKDDEFFHFVLLCFAIGALLVCYHYY
  ADWFMSLGVGLLTFASLETVGIYFGLVYRIHSVLQGFIPLFQKFRLTGFRKTD

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bladder cancer	DISUHNM0	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[1]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[1]

7 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 40 (TMEM40).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Transmembrane protein 40 (TMEM40).	[3]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Transmembrane protein 40 (TMEM40).	[4]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Transmembrane protein 40 (TMEM40).	[5]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil affects the expression of Transmembrane protein 40 (TMEM40).	[6]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Transmembrane protein 40 (TMEM40).	[7]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Transmembrane protein 40 (TMEM40).	[10]

2 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 40 (TMEM40).	[8]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Transmembrane protein 40 (TMEM40).	[9]

References

• [1] High expression of TMEM40 is associated with the malignant behavior and tumorigenesis in bladder cancer.J Transl Med. 2018 Jan 19;16(1):9. doi: 10.1186/s12967-017-1377-3.
• [2] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [5] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [6] Multi-level gene expression profiles affected by thymidylate synthase and 5-fluorouracil in colon cancer. BMC Genomics. 2006 Apr 3;7:68. doi: 10.1186/1471-2164-7-68.
• [7] Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
• [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] 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.
• [10] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.