Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8ATDVX)

• DOT Name: Transmembrane protein 87A (TMEM87A)
• Synonyms: Elkin1
• Gene Name: TMEM87A
• UniProt ID: TM87A_HUMAN
• PDB ID: 8CTJ
• Pfam ID: PF06814
• Sequence:
  MAAAAWLQVLPVILLLLGAHPSPLSFFSAGPATVAAADRSKWHIPIPSGKNYFSFGKILF
  RNTTIFLKFDGEPCDLSLNITWYLKSADCYNEIYNFKAEEVELYLEKLKEKRGLSGKYQT
  SSKLFQNCSELFKTQTFSGDFMHRLPLLGEKQEAKENGTNLTFIGDKTAMHEPLQTWQDA
  PYIFIVHIGISSSKESSKENSLSNLFTMTVEVKGPYEYLTLEDYPLMIFFMVMCIVYVLF
  GVLWLAWSACYWRDLLRIQFWIGAVIFLGMLEKAVFYAEFQNIRYKGESVQGALILAELL
  SAVKRSLARTLVIIVSLGYGIVKPRLGVTLHKVVVAGALYLLFSGMEGVLRVTGAQTDLA
  SLAFIPLAFLDTALCWWIFISLTQTMKLLKLRRNIVKLSLYRHFTNTLILAVAASIVFII
  WTTMKFRIVTCQSDWRELWVDDAIWRLLFSMILFVIMVLWRPSANNQRFAFSPLSEEEEE
  DEQKEPMLKESFEGMKMRSTKQEPNGNSKVNKAQEDDLKWVEENVPSSVTDVALPALLDS
  DEERMITHFERSKME
• Function: May be involved in retrograde transport from endosomes to the trans-Golgi network (TGN). In one study, shown to be a component of a novel mechanoelectrical transduction pathway which is involved in cell adhesion and migration, and is thought to act either as a mechanically activated ion channel or as an accessory protein which modulates an unidentified mechanically activated ion channel. In another study, neither basal nor mechanically activated channel activity has been observed and, based on structural similarity with WLS, has been suggested to function as a trafficking chaperone for membrane-associated cargo.
• Reactome Pathway: RHOA GTPase cycle (R-HSA-8980692)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Transmembrane protein 87A (TMEM87A).	[1]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Transmembrane protein 87A (TMEM87A).	[14]

18 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 87A (TMEM87A).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Transmembrane protein 87A (TMEM87A).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transmembrane protein 87A (TMEM87A).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Transmembrane protein 87A (TMEM87A).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Transmembrane protein 87A (TMEM87A).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Transmembrane protein 87A (TMEM87A).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Transmembrane protein 87A (TMEM87A).	[8]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Transmembrane protein 87A (TMEM87A).	[9]
2-deoxyglucose	DMIAHVU	Approved	2-deoxyglucose increases the expression of Transmembrane protein 87A (TMEM87A).	[10]
Bleomycin	DMNER5S	Approved	Bleomycin increases the expression of Transmembrane protein 87A (TMEM87A).	[10]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Transmembrane protein 87A (TMEM87A).	[11]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Transmembrane protein 87A (TMEM87A).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Transmembrane protein 87A (TMEM87A).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Transmembrane protein 87A (TMEM87A).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Transmembrane protein 87A (TMEM87A).	[9]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Transmembrane protein 87A (TMEM87A).	[15]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid decreases the expression of Transmembrane protein 87A (TMEM87A).	[10]
DZNep	DM0JXBK	Investigative	DZNep increases the expression of Transmembrane protein 87A (TMEM87A).	[10]

References

• [1] 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.
• [2] 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.
• [3] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [7] 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.
• [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] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [10] Development and validation of the TGx-HDACi transcriptomic biomarker to detect histone deacetylase inhibitors in human TK6 cells. Arch Toxicol. 2021 May;95(5):1631-1645. doi: 10.1007/s00204-021-03014-2. Epub 2021 Mar 26.
• [11] 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.
• [12] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [13] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [14] 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.
• [15] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.