Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTF6DB4O)

• DOT Name: Myotubularin-related protein 10 (MTMR10)
• Synonyms: Inactive phosphatidylinositol 3-phosphatase 10
• Gene Name: MTMR10
• UniProt ID: MTMRA_HUMAN
• Pfam ID: PF12578 ; PF06602
• Sequence:
  MFSLKPPKPTFRSYLLPPPQTDDKINSEPKIKKLEPVLLPGEIVVNEVNFVRKCIATDTS
  QYDLWGKLICSNFKISFITDDPMPLQKFHYRNLLLGEHDVPLTCIEQIVTVNDHKRKQKV
  LGPNQKLKFNPTELIIYCKDFRIVRFRFDESGPESAKKVCLAIAHYSQPTDLQLLFAFEY
  VGKKYHNSANKINGIPSGDGGGGGGGGNGAGGGSSQKTPLFETYSDWDREIKRTGASGWR
  VCSINEGYMISTCLPEYIVVPSSLADQDLKIFSHSFVGRRMPLWCWSHSNGSALVRMALI
  KDVLQQRKIDQRICNAITKSHPQRSDVYKSDLDKTLPNIQEVQAAFVKLKQLCVNEPFEE
  TEEKWLSSLENTRWLEYVRAFLKHSAELVYMLESKHLSVVLQEEEGRDLSCCVASLVQVM
  LDPYFRTITGFQSLIQKEWVMAGYQFLDRCNHLKRSEKESPLFLLFLDATWQLLEQYPAA
  FEFSETYLAVLYDSTRISLFGTFLFNSPHQRVKQSTEFAISKNIQLGDEKGLKFPSVWDW
  SLQFTAKDRTLFHNPFYIGKSTPCIQNGSVKSFKRTKKSYSSTLRGMPSALKNGIISDQE
  LLPRRNSLILKPKPDPAQQTDSQNSDTEQYFREWFSKPANLHGVILPRVSGTHIKLWKLC
  YFRWVPEAQISLGGSITAFHKLSLLADEVDVLSRMLRQQRSGPLEACYGELGQSRMYFNA
  SGPHHTDTSGTPEFLSSSFPFSPVGNLCRRSILGTPLSKFLSGAKIWLSTETLANED
• Reactome Pathway: Synthesis of PIPs at the early endosome membrane (R-HSA-1660516)

Molecular Interaction Atlas (MIA) of This DOT

6 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 Myotubularin-related protein 10 (MTMR10).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Myotubularin-related protein 10 (MTMR10).	[2]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Myotubularin-related protein 10 (MTMR10).	[3]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Myotubularin-related protein 10 (MTMR10).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Myotubularin-related protein 10 (MTMR10).	[7]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Myotubularin-related protein 10 (MTMR10).	[8]

3 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 Myotubularin-related protein 10 (MTMR10).	[5]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Myotubularin-related protein 10 (MTMR10).	[6]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Myotubularin-related protein 10 (MTMR10).	[6]

References

• [1] 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.
• [2] 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.
• [3] 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.
• [4] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [5] 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.
• [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] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [8] 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.