Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEC6EFU)

• DOT Name: Transmembrane protein 79 (TMEM79)
• Synonyms: Mattrin
• Gene Name: TMEM79
• Related Disease:
  Atopic dermatitis
  Dermatitis
  Prostate cancer
  Prostate carcinoma
• UniProt ID: TMM79_HUMAN
• Sequence:
  MTEQETLALLEVKRSDSPEKSSPQALVPNGRQPEGEGGAESPGAESLRVGSSAGSPTAIE
  GAEDGLDSTVSEAATLPWGTGPQPSAPFPDPPGWRDIEPEPPESEPLTKLEELPEDDANL
  LPEKAARAFVPIDLQCIERQPQEDLIVRCEAGEGECRTFMPPRVTHPDPTERKWAEAVVR
  PPGCSCGGCGSCGDREWLRAVASVGAALILFPCLLYGAYAFLPFDVPRLPTMSSRLIYTL
  RCGVFATFPIVLGILVYGLSLLCFSALRPFGEPRREVEIHRRYVAQSVQLFILYFFNLAV
  LSTYLPQDTLKLLPLLTGLFAVSRLIYWLTFAVGRSFRGFGYGLTFLPLLSMLMWNLYYM
  FVVEPERMLTATESRLDYPDHARSASDYRPRPWG
• Function: Contributes to the epidermal integrity and skin barrier function. Plays a role in the lamellar granule (LG) secretory system and in the stratum corneum (SC) epithelial cell formation.
• Tissue Specificity: Expressed in the epidermis of the skin. Expressed in epithelial cells of the outermost layer of the stratum granulosum (SG) and hair follicles (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Atopic dermatitis	DISTCP41	Strong	Genetic Variation	[1]
Dermatitis	DISY5SZC	Strong	Genetic Variation	[2]
Prostate cancer	DISF190Y	Limited	Biomarker	[3]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[3]

11 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Transmembrane protein 79 (TMEM79).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Transmembrane protein 79 (TMEM79).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Transmembrane protein 79 (TMEM79).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Transmembrane protein 79 (TMEM79).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Transmembrane protein 79 (TMEM79).	[8]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Transmembrane protein 79 (TMEM79).	[9]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Transmembrane protein 79 (TMEM79).	[7]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Transmembrane protein 79 (TMEM79).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Transmembrane protein 79 (TMEM79).	[12]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Transmembrane protein 79 (TMEM79).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Transmembrane protein 79 (TMEM79).	[14]

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 decreases the methylation of Transmembrane protein 79 (TMEM79).	[11]

References

• [1] Atopic Eczema: Genetic Associations and Potential Links to Developmental Exposures.Int J Toxicol. 2017 May/Jun;36(3):187-198. doi: 10.1177/1091581817701075. Epub 2017 Mar 30.
• [2] Increased Th2 activity and diminished skin barrier function cooperate in allergic skin inflammation.Eur J Immunol. 2016 Nov;46(11):2609-2613. doi: 10.1002/eji.201646421. Epub 2016 Aug 29.
• [3] Analysis of the Human Prostate-Specific Proteome Defined by Transcriptomics and Antibody-Based Profiling Identifies TMEM79 and ACOXL as Two Putative, Diagnostic Markers in Prostate Cancer.PLoS One. 2015 Aug 3;10(8):e0133449. doi: 10.1371/journal.pone.0133449. eCollection 2015.
• [4] 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.
• [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] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [7] 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.
• [8] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [9] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [10] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [11] 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.
• [12] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [13] Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.
• [14] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.