Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIMMWZ6)

• DOT Name: Transmembrane protein 25 (TMEM25)
• Gene Name: TMEM25
• Related Disease:
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Colorectal carcinoma
  Epilepsy
• UniProt ID: TMM25_HUMAN
• Pfam ID: PF08205
• Sequence:
  MALPPGPAALRHTLLLLPALLSSGWGELEPQIDGQTWAERALRENERHAFTCRVAGGPGT
  PRLAWYLDGQLQEASTSRLLSVGGEAFSGGTSTFTVTAHRAQHELNCSLQDPRSGRSANA
  SVILNVQFKPEIAQVGAKYQEAQGPGLLVVLFALVRANPPANVTWIDQDGPVTVNTSDFL
  VLDAQNYPWLTNHTVQLQLRSLAHNLSVVATNDVGVTSASLPAPGLLATRVEVPLLGIVV
  AAGLALGTLVGFSTLVACLVCRKEKKTKGPSRHPSLISSDSNNLKLNNVRLPRENMSLPS
  NLQLNDLTPDSRAVKPADRQMAQNNSRPELLDPEPGGLLTSQGFIRLPVLGYIYRVSSVS
  SDEIWL
• Function: In neurons, modulates the degradation of NMDA receptor GRIN2B subunit. Plays a role in the regulation of neuronal excitability.
• Tissue Specificity: Expressed throughout the brain with higher levels in the pyramidal cell layer of the hippocampal CA1 and CA3 regions. Also highly expressed within the hippocampal dentate gyrus region and cerebellum and in scattered neurons in the cerebral cortex.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Posttranslational Modification	[1]
Epilepsy	DISBB28L	Strong	Biomarker	[3]

8 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 25 (TMEM25).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Transmembrane protein 25 (TMEM25).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transmembrane protein 25 (TMEM25).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Transmembrane protein 25 (TMEM25).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Transmembrane protein 25 (TMEM25).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Transmembrane protein 25 (TMEM25).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Transmembrane protein 25 (TMEM25).	[11]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Transmembrane protein 25 (TMEM25).	[12]

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 affects the methylation of Transmembrane protein 25 (TMEM25).	[9]

References

• [1] TMEM25 is a candidate biomarker methylated and down-regulated in colorectal cancer.Dis Markers. 2013;34(2):93-104. doi: 10.3233/DMA-120948.
• [2] TMEM25, REPS2 and Meis 1: favourable prognostic and predictive biomarkers for breast cancer.Tumour Biol. 2009;30(4):200-9. doi: 10.1159/000239795. Epub 2009 Sep 21.
• [3] TMEM25 modulates neuronal excitability and NMDA receptor subunit NR2B degradation.J Clin Invest. 2019 Sep 3;129(9):3864-3876. doi: 10.1172/JCI122599.
• [4] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [5] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [6] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [9] 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.
• [10] 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.
• [11] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.
• [12] 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.