Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT47NVYM)

• DOT Name: Myotubularin-related protein 7 (MTMR7)
• Synonyms: Inositol 1,3-bisphosphate phosphatase; EC 3.1.3.-; Phosphatidylinositol-3-phosphate phosphatase; EC 3.1.3.64
• Gene Name: MTMR7
• Related Disease:
  Advanced cancer
  Colorectal carcinoma
  Creutzfeldt Jacob disease
  Neoplasm
  Non-insulin dependent diabetes
• UniProt ID: MTMR7_HUMAN
• EC Number: 3.1.3.-; 3.1.3.64
• Pfam ID: PF06602 ; PF21098
• Sequence:
  MEHIRTPKVENVRLVDRVSPKKAALGTLYLTATHVIFVENSPDPRKETWILHSQISTIEK
  QATTATGCPLLIRCKNFQIIQLIIPQERDCHDVYISLIRLARPVKYEELYCFSFNPMLDK
  EEREQGWVLIDLSEEYTRMGLPNHYWQLSDVNRDYRVCDSYPTELYVPKSATAHIIVGSS
  KFRSRRRFPVLSYYYKDNHASICRSSQPLSGFSARCLEDEQMLQAIRKANPGSDFVYVVD
  TRPKLNAMANRAAGKGYENEDNYSNIKFQFIGIENIHVMRNSLQKMLEVCELKSPSMSDF
  LWGLENSGWLRHIKAIMDAGIFIAKAVSEEGASVLVHCSDGWDRTAQVCSVASLLLDPHY
  RTLKGFMVLIEKDWISFGHKFNHRYGNLDGDPKEISPVIDQFIECVWQLMEQFPCAFEFN
  ERFLIHIQHHIYSCQFGNFLCNSQKERRELKIQERTYSLWAHLWKNRADYLNPLFRADHS
  QTQGTLHLPTTPCNFMYKFWSGMYNRFEKGMQPRQSVTDYLMAVKEETQQLEEELEALEE
  RLEKIQKVQLNCTKVKSKQSEPSKHSGFSTSDNSIANTPQDYSGNMKSFPSRSPSQGDED
  SALILTQDNLKSSDPDLSANSDQESGVEDLSCRSPSGGEHAPSEDSGKDRDSDEAVFLTA
• Function: Phosphatase that specifically dephosphorylates phosphatidylinositol 3-phosphate (PtdIns(3)P) and inositol 1,3-bisphosphate (Ins(1,3)P2).
• Tissue Specificity: Expressed specifically in brain.
• KEGG Pathway:
  Inositol phosphate metabolism (hsa00562)
  Metabolic pathways (hsa01100)
  Phosphatidylinositol sig.ling system (hsa04070)
• Reactome Pathway:
  Synthesis of IP2, IP, and Ins in the cytosol (R-HSA-1855183)
  Synthesis of PIPs at the late endosome membrane (R-HSA-1660517)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[1]
Creutzfeldt Jacob disease	DISCB6RX	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Myotubularin-related protein 7 (MTMR7).	[3]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Myotubularin-related protein 7 (MTMR7).	[4]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Myotubularin-related protein 7 (MTMR7).	[7]
Cycloheximide	DMGDA3C	Investigative	Cycloheximide increases the expression of Myotubularin-related protein 7 (MTMR7).	[8]

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 Myotubularin-related protein 7 (MTMR7).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of Myotubularin-related protein 7 (MTMR7).	[6]

References

• [1] Myotubularin-related protein 7 inhibits insulin signaling in colorectal cancer.Oncotarget. 2016 Aug 2;7(31):50490-50506. doi: 10.18632/oncotarget.10466.
• [2] Genetics of prion diseases.Curr Opin Genet Dev. 2013 Jun;23(3):345-51. doi: 10.1016/j.gde.2013.02.012. Epub 2013 Mar 19.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [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] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [7] 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.
• [8] Comparative analysis of AhR-mediated TCDD-elicited gene expression in human liver adult stem cells. Toxicol Sci. 2009 Nov;112(1):229-44.