Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTX5ERUD)

DOT Name Inositol-trisphosphate 3-kinase A (ITPKA)
Synonyms EC 2.7.1.127; Inositol 1,4,5-trisphosphate 3-kinase A; IP3 3-kinase A; IP3K A; InsP 3-kinase A
Gene Name ITPKA
Related Disease
Breast cancer ( )
Breast carcinoma ( )
Glioma ( )
Lung adenocarcinoma ( )
Lung cancer ( )
Lung carcinoma ( )
Squamous cell carcinoma ( )
Advanced cancer ( )
Asthma ( )
UniProt ID
IP3KA_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1W2C; 1W2D; 1W2F; 4UPU
EC Number
2.7.1.127
Pfam ID
PF03770
Sequence
MTLPGGPTGMARPGGARPCSPGLERAPRRSVGELRLLFEARCAAVAAAAAAGEPRARGAK
RRGGQVPNGLPRAPPAPVIPQLTVTAEEPDVPPTSPGPPERERDCLPAAGSSHLQQPRRL
STSSVSSTGSSSLLEDSEDDLLSDSESRSRGNVQLEAGEDVGQKNHWQKIRTMVNLPVIS
PFKKRYAWVQLAGHTGSFKAAGTSGLILKRCSEPERYCLARLMADALRGCVPAFHGVVER
DGESYLQLQDLLDGFDGPCVLDCKMGVRTYLEEELTKARERPKLRKDMYKKMLAVDPEAP
TEEEHAQRAVTKPRYMQWREGISSSTTLGFRIEGIKKADGSCSTDFKTTRSREQVLRVFE
EFVQGDEEVLRRYLNRLQQIRDTLEVSEFFRRHEVIGSSLLFVHDHCHRAGVWLIDFGKT
TPLPDGQILDHRRPWEEGNREDGYLLGLDNLIGILASLAER
Function Catalyzes the phosphorylation of 1D-myo-inositol 1,4,5-trisphosphate (InsP3) into 1D-myo-inositol 1,3,4,5-tetrakisphosphate and participates to the regulation of calcium homeostasis.
Tissue Specificity Expressed in brain.
KEGG Pathway
Inositol phosphate metabolism (hsa00562 )
Metabolic pathways (hsa01100 )
Calcium sig.ling pathway (hsa04020 )
Phosphatidylinositol sig.ling system (hsa04070 )
Reactome Pathway
Synthesis of IP3 and IP4 in the cytosol (R-HSA-1855204 )
BioCyc Pathway
MetaCyc:HS06405-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

9 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]
Glioma DIS5RPEH Strong Genetic Variation [2]
Lung adenocarcinoma DISD51WR Strong Altered Expression [1]
Lung cancer DISCM4YA Strong Biomarker [3]
Lung carcinoma DISTR26C Strong Biomarker [3]
Squamous cell carcinoma DISQVIFL Strong Altered Expression [4]
Advanced cancer DISAT1Z9 Limited Altered Expression [1]
Asthma DISW9QNS Limited Genetic Variation [5]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 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 Inositol-trisphosphate 3-kinase A (ITPKA). [6]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Inositol-trisphosphate 3-kinase A (ITPKA). [15]
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9 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-trisphosphate 3-kinase A (ITPKA). [7]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Inositol-trisphosphate 3-kinase A (ITPKA). [8]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Inositol-trisphosphate 3-kinase A (ITPKA). [9]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Inositol-trisphosphate 3-kinase A (ITPKA). [10]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Inositol-trisphosphate 3-kinase A (ITPKA). [11]
Marinol DM70IK5 Approved Marinol increases the expression of Inositol-trisphosphate 3-kinase A (ITPKA). [12]
Phenobarbital DMXZOCG Approved Phenobarbital increases the expression of Inositol-trisphosphate 3-kinase A (ITPKA). [13]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Inositol-trisphosphate 3-kinase A (ITPKA). [7]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Inositol-trisphosphate 3-kinase A (ITPKA). [14]
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⏷ Show the Full List of 9 Drug(s)

References

1 Inositol-1,4,5-trisphosphate 3-kinase-A (ITPKA) is frequently over-expressed and functions as an oncogene in several tumor types.Biochem Pharmacol. 2017 Aug 1;137:1-9. doi: 10.1016/j.bcp.2017.03.023. Epub 2017 Apr 2.
2 Mining the glioma susceptibility genes in children from gene expression profiles and a methylation database.Oncol Lett. 2017 Sep;14(3):3473-3479. doi: 10.3892/ol.2017.6579. Epub 2017 Jul 15.
3 Effect of the actin- and calcium-regulating activities of ITPKB on the metastatic potential of lung cancer cells.Biochem J. 2018 Jun 26;475(12):2057-2071. doi: 10.1042/BCJ20180238.
4 Down-regulation of 1D-myo-inositol 1,4,5-trisphosphate 3-kinase A protein expression in oral squamous cell carcinoma.Int J Oncol. 2006 Apr;28(4):873-81.
5 Genetic Architectures of Childhood- and Adult-Onset Asthma Are Partly Distinct.Am J Hum Genet. 2019 Apr 4;104(4):665-684. doi: 10.1016/j.ajhg.2019.02.022. Epub 2019 Mar 28.
6 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.
7 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.
8 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
9 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
10 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
11 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.
12 Genomic and proteomic analysis of the effects of cannabinoids on normal human astrocytes. Brain Res. 2008 Jan 29;1191:1-11.
13 Dose- and time-dependent effects of phenobarbital on gene expression profiling in human hepatoma HepaRG cells. Toxicol Appl Pharmacol. 2009 Feb 1;234(3):345-60.
14 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.
15 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.