Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTV1X2R0)

• DOT Name: Major intrinsically disordered Notch2-binding receptor 1 (MINAR1)
• Synonyms: Membrane integral NOTCH2-associated receptor 1; Ubiquitination and mTOR signaling protein
• Gene Name: MINAR1
• Related Disease:
  Breast cancer
  Breast carcinoma
  Acute myelogenous leukaemia
• UniProt ID: MNAR1_HUMAN
• Pfam ID: PF06789
• Sequence:
  METSQETSLFLVKILEELDSKQNTVSYQDLCKSLCARFDLSQLAKLRSVLFYTACLDPNF
  PATLFKDKMKCTVNNQQSKKIMVAADIVTIFNLIQMNGGAAKEKLPTGRQKVRKKEASFE
  SCRSDTEICNAAECEPLNCELSERSFSRGYPIRQSSKCRKMDCKDCPQFVPASEPNFLLG
  VSKEVKNRAASLDRLQALAPYSVTSPQPCEMQRTYFPMNIENESISDQDSLPINQSIKET
  FISNEEPFVVQSCVQKRNIFKEDFHNLMAVSPSLVGPISKAENEHREPQSRKEPHKPPFF
  NHSFEMPYNSQYLNPVYSPVPDKRRAKHESLDDLQASTYFGPTPVMGTQEARRCLGKPNK
  QTPWPAKSWSLNTEEVPDFERSFFNRNPSEEKLHYPNASSQTPNFPAPERRPTYLVPKDQ
  QPILPIAYAAKQNGLKSKEISSPVDLEKHEPVKKFKDKSINCTSGQLSSDTSSVGTQTEH
  VLEPKKCRDLCTSGQGKYSDRHTMKHSDDDSEIVSDDISDIFRFLDDMSISGSTGVIQSS
  CYNSTGSLSQLHKSDCDSSPEHNLTKIANGVPNSKGDKGNRPENTHHSEEELKTSVCKLV
  LRIGEIERKLESLSGVRDEISQVLGKLNKLDQKMQQPEKVSVQIDLNSLTSEGPSDDSAS
  PRMFHAHSGSHGPKLENNPDWCCSDASGSNSESLRVKALKKSLFTRPSSRSLTEENSATE
  SKIASISNSPRDWRTITYTNRVGLNEEEIKDTGPGDNKDWHRKSKEADRQYDIPPQHRLP
  KQPKDGFLVEQVFSPHPYPASLKAHMKSNPLYTDMRLTELAEVKRGQPSWTIEEYARNAG
  DKGKLTALDLQTQESLNPNNLEYWMEDIYTPGYDSLLKRKEAEFRRAKVCKIAALIAAAA
  CTVILVIVVPICTMKS
• Function: Intrinsically disordered protein which may negatively regulate mTOR signaling pathway by stabilizing the mTOR complex component DEPTOR. Negatively regulates angiogenesis. Negatively regulates cell growth. Negatively regulates neurite outgrowth in hippocampal neurons.
• Tissue Specificity: Widely expressed, including in breast epithelial cells and endothelial cells (at protein level). Expression is down-regulated in advanced breast tumors (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[1]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Major intrinsically disordered Notch2-binding receptor 1 (MINAR1).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the methylation of Major intrinsically disordered Notch2-binding receptor 1 (MINAR1).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Major intrinsically disordered Notch2-binding receptor 1 (MINAR1).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Major intrinsically disordered Notch2-binding receptor 1 (MINAR1).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Major intrinsically disordered Notch2-binding receptor 1 (MINAR1).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Major intrinsically disordered Notch2-binding receptor 1 (MINAR1).	[7]

References

• [1] MINAR1 is a Notch2-binding protein that inhibits angiogenesis and breast cancer growth.J Mol Cell Biol. 2018 Jun 1;10(3):195-204. doi: 10.1093/jmcb/mjy002.
• [2] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [3] 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.
• [4] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [5] 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.
• [6] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [7] Immediate up-regulation of the calcium-binding protein S100P and its involvement in the cytokinin-induced differentiation of human myeloid leukemia cells. Biochim Biophys Acta. 2005 Sep 10;1745(2):156-65.
• [8] 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.