Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO61OBN)

DOT Name Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 2 (PPIP5K2)
Synonyms EC 2.7.4.24; Diphosphoinositol pentakisphosphate kinase 2; Histidine acid phosphatase domain-containing protein 1; InsP6 and PP-IP5 kinase 2; VIP1 homolog 2; hsVIP2
Gene Name PPIP5K2
Related Disease
Anthrax ( )
Hearing loss, autosomal recessive 100 ( )
Hearing loss, autosomal recessive ( )
UniProt ID
VIP2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
3T54; 3T7A; 3T99; 3T9A; 3T9B; 3T9C; 3T9D; 3T9E; 3T9F; 4HN2; 4NZM; 4NZN; 4NZO; 4Q4C; 4Q4D; 5BYA; 5BYB; 5DGH; 5DGI; 6N5C
EC Number
2.7.4.24
Pfam ID
PF00328 ; PF18086
Sequence
MSEAPRFFVGPEDTEINPGNYRHFFHHADEDDEEEDDSPPERQIVVGICSMAKKSKSKPM
KEILERISLFKYITVVVFEEEVILNEPVENWPLCDCLISFHSKGFPLDKAVAYAKLRNPF
VINDLNMQYLIQDRREVYSILQAEGILLPRYAILNRDPNNPKECNLIEGEDHVEVNGEVF
QKPFVEKPVSAEDHNVYIYYPTSAGGGSQRLFRKIGSRSSVYSPESNVRKTGSYIYEEFM
PTDGTDVKVYTVGPDYAHAEARKSPALDGKVERDSEGKEVRYPVILNAREKLIAWKVCLA
FKQTVCGFDLLRANGQSYVCDVNGFSFVKNSMKYYDDCAKILGNIVMRELAPQFHIPWSI
PLEAEDIPIVPTTSGTMMELRCVIAVIRHGDRTPKQKMKMEVRHQKFFDLFEKCDGYKSG
KLKLKKPKQLQEVLDIARQLLMELGQNNDSEIEENKPKLEQLKTVLEMYGHFSGINRKVQ
LTYLPHGCPKTSSEEEDSRREEPSLLLVLKWGGELTPAGRVQAEELGRAFRCMYPGGQGD
YAGFPGCGLLRLHSTYRHDLKIYASDEGRVQMTAAAFAKGLLALEGELTPILVQMVKSAN
MNGLLDSDSDSLSSCQQRVKARLHEILQKDRDFTAEDYEKLTPSGSISLIKSMHLIKNPV
KTCDKVYSLIQSLTSQIRHRMEDPKSSDIQLYHSETLELMLRRWSKLEKDFKTKNGRYDI
SKIPDIYDCIKYDVQHNGSLKLENTMELYRLSKALADIVIPQEYGITKAEKLEIAKGYCT
PLVRKIRSDLQRTQDDDTVNKLHPVYSRGVLSPERHVRTRLYFTSESHVHSLLSILRYGA
LCNESKDEQWKRAMDYLNVVNELNYMTQIVIMLYEDPNKDLSSEERFHVELHFSPGAKGC
EEDKNLPSGYGYRPASRENEGRRPFKIDNDDEPHTSKRDEVDRAVILFKPMVSEPIHIHR
KSPLPRSRKTATNDEESPLSVSSPEGTGTWLHYTSGVGTGRRRRRSGEQITSSPVSPKSL
AFTSSIFGSWQQVVSENANYLRTPRTLVEQKQNPTVGSHCAGLFSTSVLGGSSSAPNLQD
YARTHRKKLTSSGCIDDATRGSAVKRFSISFARHPTNGFELYSMVPSICPLETLHNALSL
KQVDEFLASIASPSSDVPRKTAEISSTALRSSPIMRKKVSLNTYTPAKILPTPPATLKST
KASSKPATSGPSSAVVPNTSSRKKNITSKTETHEHKKNTGKKK
Function
Bifunctional inositol kinase that acts in concert with the IP6K kinases IP6K1, IP6K2 and IP6K3 to synthesize the diphosphate group-containing inositol pyrophosphates diphosphoinositol pentakisphosphate, PP-InsP5, and bis-diphosphoinositol tetrakisphosphate, (PP)2-InsP4. PP-InsP5 and (PP)2-InsP4, also respectively called InsP7 and InsP8, regulate a variety of cellular processes, including apoptosis, vesicle trafficking, cytoskeletal dynamics, exocytosis, insulin signaling and neutrophil activation. Phosphorylates inositol hexakisphosphate (InsP6) at position 1 to produce PP-InsP5 which is in turn phosphorylated by IP6Ks to produce (PP)2-InsP4. Alternatively, phosphorylates PP-InsP5 at position 1, produced by IP6Ks from InsP6, to produce (PP)2-InsP4. Required for normal hearing.
KEGG Pathway
Phosphatidylinositol sig.ling system (hsa04070 )
Reactome Pathway
Synthesis of pyrophosphates in the cytosol (R-HSA-1855167 )

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Anthrax DISFPT78 Strong Biomarker [1]
Hearing loss, autosomal recessive 100 DISE6QNO Moderate Autosomal recessive [2]
Hearing loss, autosomal recessive DIS8G9R9 Supportive Autosomal recessive [2]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
5 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 Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 2 (PPIP5K2). [3]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 2 (PPIP5K2). [4]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 2 (PPIP5K2). [5]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 2 (PPIP5K2). [6]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 2 (PPIP5K2). [8]
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2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Marinol DM70IK5 Approved Marinol increases the glycosylation of Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 2 (PPIP5K2). [7]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 2 (PPIP5K2). [9]
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References

1 Structure, Function and Evolution of Clostridium botulinum C2 and C3 Toxins: Insight to Poultry and Veterinary Vaccines.Curr Protein Pept Sci. 2017;18(5):412-424. doi: 10.2174/1389203717666161201203311.
2 Mutations in Diphosphoinositol-Pentakisphosphate Kinase PPIP5K2 are associated with hearing loss in human and mouse. PLoS Genet. 2018 Mar 28;14(3):e1007297. doi: 10.1371/journal.pgen.1007297. eCollection 2018 Mar.
3 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.
4 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
5 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
6 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
7 Epigenetic activation of O-linked -N-acetylglucosamine transferase overrides the differentiation blockage in acute leukemia. EBioMedicine. 2020 Apr;54:102678. doi: 10.1016/j.ebiom.2020.102678. Epub 2020 Apr 6.
8 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
9 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.