Details of Drug Off-Target (DOT)

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

• DOT Name: Inositol hexakisphosphate kinase 2 (IP6K2)
• Synonyms: InsP6 kinase 2; InsP6K2; EC 2.7.4.-; P(i)-uptake stimulator; PiUS
• Gene Name: IP6K2
• Related Disease:
  Advanced cancer
  Ovarian cancer
  Parkinson disease
  Huntington disease
  Juvenile Huntington disease
• UniProt ID: IP6K2_HUMAN
• EC Number: 2.7.4.-
• Pfam ID: PF03770
• Sequence:
  MSPAFRAMDVEPRAKGVLLEPFVHQVGGHSCVLRFNETTLCKPLVPREHQFYETLPAEMR
  KFTPQYKGVVSVRFEEDEDRNLCLIAYPLKGDHGIVDIVDNSDCEPKSKLLRWTTNKKHH
  VLETEKTPKDWVRQHRKEEKMKSHKLEEEFEWLKKSEVLYYTVEKKGNISSQLKHYNPWS
  MKCHQQQLQRMKENAKHRNQYKFILLENLTSRYEVPCVLDLKMGTRQHGDDASEEKAANQ
  IRKCQQSTSAVIGVRVCGMQVYQAGSGQLMFMNKYHGRKLSVQGFKEALFQFFHNGRYLR
  RELLGPVLKKLTELKAVLERQESYRFYSSSLLVIYDGKERPEVVLDSDAEDLEDLSEESA
  DESAGAYAYKPIGASSVDVRMIDFAHTTCRLYGEDTVVHEGQDAGYIFGLQSLIDIVTEI
  SEESGE
• Function: Converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5).
• KEGG Pathway: Phosphatidylinositol sig.ling system (hsa04070)
• Reactome Pathway:
  Interferon alpha/beta signaling (R-HSA-909733)
  Synthesis of IPs in the nucleus (R-HSA-1855191)
• BioCyc Pathway: MetaCyc:HS00942-MONOMER

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	Altered Expression	[1]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[2]
Parkinson disease	DISQVHKL	Strong	Genetic Variation	[3]
Huntington disease	DISQPLA4	moderate	Biomarker	[4]
Juvenile Huntington disease	DIS1IQJG	moderate	Biomarker	[4]

1 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 Inositol hexakisphosphate kinase 2 (IP6K2).	[5]

10 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 Inositol hexakisphosphate kinase 2 (IP6K2).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Inositol hexakisphosphate kinase 2 (IP6K2).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Inositol hexakisphosphate kinase 2 (IP6K2).	[8]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Inositol hexakisphosphate kinase 2 (IP6K2).	[9]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Inositol hexakisphosphate kinase 2 (IP6K2).	[10]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Inositol hexakisphosphate kinase 2 (IP6K2).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Inositol hexakisphosphate kinase 2 (IP6K2).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Inositol hexakisphosphate kinase 2 (IP6K2).	[13]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Inositol hexakisphosphate kinase 2 (IP6K2).	[14]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of Inositol hexakisphosphate kinase 2 (IP6K2).	[15]

References

• [1] Identification of novel Sp1 targets involved in proliferation and cancer by functional genomics.Biochem Pharmacol. 2012 Dec 15;84(12):1581-91. doi: 10.1016/j.bcp.2012.09.014. Epub 2012 Sep 25.
• [2] Inositol hexakisphosphate kinase 2 sensitizes ovarian carcinoma cells to multiple cancer therapeutics.Oncogene. 2002 Mar 14;21(12):1882-9. doi: 10.1038/sj.onc.1205265.
• [3] A meta-analysis of genome-wide association studies identifies 17 new Parkinson's disease risk loci.Nat Genet. 2017 Oct;49(10):1511-1516. doi: 10.1038/ng.3955. Epub 2017 Sep 11.
• [4] Inositol hexakisphosphate kinases induce cell death in Huntington disease.J Biol Chem. 2011 Jul 29;286(30):26680-6. doi: 10.1074/jbc.M111.220749. Epub 2011 Jun 7.
• [5] 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.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [9] Influence of Iron on Cytotoxicity and Gene Expression Profiles Induced by Arsenic in HepG2 Cells. Int J Environ Res Public Health. 2019 Nov 14;16(22):4484. doi: 10.3390/ijerph16224484.
• [10] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [13] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [14] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [15] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.