Details of Drug Off-Target (DOT)

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

DOT Name Glucose-6-phosphate isomerase (GPI)
Synonyms GPI; EC 5.3.1.9; Autocrine motility factor; AMF; Neuroleukin; NLK; Phosphoglucose isomerase; PGI; Phosphohexose isomerase; PHI; Sperm antigen 36; SA-36
Gene Name GPI
Related Disease
Hemolytic anemia due to glucophosphate isomerase deficiency ( )
UniProt ID
G6PI_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1IAT; 1IRI; 1JIQ; 1JLH; 1NUH; 6XUH; 6XUI; 8BBH; 8P2K
EC Number
5.3.1.9
Pfam ID
PF00342
Sequence
MAALTRDPQFQKLQQWYREHRSELNLRRLFDANKDRFNHFSLTLNTNHGHILVDYSKNLV
TEDVMRMLVDLAKSRGVEAARERMFNGEKINYTEGRAVLHVALRNRSNTPILVDGKDVMP
EVNKVLDKMKSFCQRVRSGDWKGYTGKTITDVINIGIGGSDLGPLMVTEALKPYSSGGPR
VWYVSNIDGTHIAKTLAQLNPESSLFIIASKTFTTQETITNAETAKEWFLQAAKDPSAVA
KHFVALSTNTTKVKEFGIDPQNMFEFWDWVGGRYSLWSAIGLSIALHVGFDNFEQLLSGA
HWMDQHFRTTPLEKNAPVLLALLGIWYINCFGCETHAMLPYDQYLHRFAAYFQQGDMESN
GKYITKSGTRVDHQTGPIVWGEPGTNGQHAFYQLIHQGTKMIPCDFLIPVQTQHPIRKGL
HHKILLANFLAQTEALMRGKSTEEARKELQAAGKSPEDLERLLPHKVFEGNRPTNSIVFT
KLTPFMLGALVAMYEHKIFVQGIIWDINSFDQWGVELGKQLAKKIEPELDGSAQVTSHDA
STNGLINFIKQQREARVQ
Function
In the cytoplasm, catalyzes the conversion of glucose-6-phosphate to fructose-6-phosphate, the second step in glycolysis, and the reverse reaction during gluconeogenesis. Besides it's role as a glycolytic enzyme, also acts as a secreted cytokine: acts as an angiogenic factor (AMF) that stimulates endothelial cell motility. Acts as a neurotrophic factor, neuroleukin, for spinal and sensory neurons. It is secreted by lectin-stimulated T-cells and induces immunoglobulin secretion.
KEGG Pathway
Glycolysis / Gluconeogenesis (hsa00010 )
Pentose phosphate pathway (hsa00030 )
Starch and sucrose metabolism (hsa00500 )
Amino sugar and nucleotide sugar metabolism (hsa00520 )
Metabolic pathways (hsa01100 )
Carbon metabolism (hsa01200 )
Biosynthesis of nucleotide sugars (hsa01250 )
Reactome Pathway
Neutrophil degranulation (R-HSA-6798695 )
Glycolysis (R-HSA-70171 )
Gluconeogenesis (R-HSA-70263 )
TP53 Regulates Metabolic Genes (R-HSA-5628897 )
BioCyc Pathway
MetaCyc:HS02693-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Hemolytic anemia due to glucophosphate isomerase deficiency DIS1995T Strong Autosomal recessive [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 2 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Paclitaxel DMLB81S Approved Glucose-6-phosphate isomerase (GPI) affects the response to substance of Paclitaxel. [25]
Josamycin DMKJ8LB Approved Glucose-6-phosphate isomerase (GPI) decreases the response to substance of Josamycin. [26]
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22 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 Glucose-6-phosphate isomerase (GPI). [2]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Glucose-6-phosphate isomerase (GPI). [3]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Glucose-6-phosphate isomerase (GPI). [4]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Glucose-6-phosphate isomerase (GPI). [5]
Quercetin DM3NC4M Approved Quercetin increases the expression of Glucose-6-phosphate isomerase (GPI). [6]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Glucose-6-phosphate isomerase (GPI). [7]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Glucose-6-phosphate isomerase (GPI). [8]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of Glucose-6-phosphate isomerase (GPI). [9]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Glucose-6-phosphate isomerase (GPI). [10]
Selenium DM25CGV Approved Selenium increases the expression of Glucose-6-phosphate isomerase (GPI). [11]
Clozapine DMFC71L Approved Clozapine increases the expression of Glucose-6-phosphate isomerase (GPI). [12]
Benzatropine DMF7EXL Approved Benzatropine increases the expression of Glucose-6-phosphate isomerase (GPI). [12]
Tocopherol DMBIJZ6 Phase 2 Tocopherol increases the expression of Glucose-6-phosphate isomerase (GPI). [11]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the expression of Glucose-6-phosphate isomerase (GPI). [17]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Glucose-6-phosphate isomerase (GPI). [18]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Glucose-6-phosphate isomerase (GPI). [19]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Glucose-6-phosphate isomerase (GPI). [20]
3R14S-OCHRATOXIN A DM2KEW6 Investigative 3R14S-OCHRATOXIN A decreases the expression of Glucose-6-phosphate isomerase (GPI). [21]
Okadaic acid DM47CO1 Investigative Okadaic acid increases the expression of Glucose-6-phosphate isomerase (GPI). [22]
CH-223191 DMMJZYC Investigative CH-223191 increases the expression of Glucose-6-phosphate isomerase (GPI). [23]
PP-242 DM2348V Investigative PP-242 decreases the expression of Glucose-6-phosphate isomerase (GPI). [24]
Alpha-naphthoflavone DMELOIQ Investigative Alpha-naphthoflavone increases the expression of Glucose-6-phosphate isomerase (GPI). [23]
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⏷ Show the Full List of 22 Drug(s)
2 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT
Drug Name Drug ID Highest Status Interaction REF
Dihydroartemisinin DMBXVMZ Approved Dihydroartemisinin affects the binding of Glucose-6-phosphate isomerase (GPI). [13]
DNCB DMDTVYC Phase 2 DNCB affects the binding of Glucose-6-phosphate isomerase (GPI). [14]
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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 Glucose-6-phosphate isomerase (GPI). [15]
TAK-243 DM4GKV2 Phase 1 TAK-243 decreases the sumoylation of Glucose-6-phosphate isomerase (GPI). [16]
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References

1 Glucose-6-phosphate isomerase deficiency. Baillieres Best Pract Res Clin Haematol. 2000 Mar;13(1):89-101. doi: 10.1053/beha.1999.0059.
2 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.
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 Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
5 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.
6 Hypoxia-inducible factor-1 (HIF-1) pathway activation by quercetin in human lens epithelial cells. Exp Eye Res. 2009 Dec;89(6):995-1002. doi: 10.1016/j.exer.2009.08.011. Epub 2009 Sep 1.
7 Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
8 Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
9 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
10 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
11 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
12 Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
13 Untargeted Proteomics and Systems-Based Mechanistic Investigation of Artesunate in Human Bronchial Epithelial Cells. Chem Res Toxicol. 2015 Oct 19;28(10):1903-13. doi: 10.1021/acs.chemrestox.5b00105. Epub 2015 Sep 21.
14 Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
15 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.
16 Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
17 Comparative proteomics reveals concordant and discordant biochemical effects of caffeine versus epigallocatechin-3-gallate in human endothelial cells. Toxicol Appl Pharmacol. 2019 Sep 1;378:114621. doi: 10.1016/j.taap.2019.114621. Epub 2019 Jun 10.
18 Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
19 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
20 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
21 Lipid Rafts Disruption Increases Ochratoxin A Cytotoxicity to Hepatocytes. J Biochem Mol Toxicol. 2016 Feb;30(2):71-9. doi: 10.1002/jbt.21738. Epub 2015 Aug 25.
22 Whole genome mRNA transcriptomics analysis reveals different modes of action of the diarrheic shellfish poisons okadaic acid and dinophysis toxin-1 versus azaspiracid-1 in Caco-2 cells. Toxicol In Vitro. 2018 Feb;46:102-112.
23 2,3,7,8-Tetrachlorodibenzo-p-dioxin-mediated production of reactive oxygen species is an essential step in the mechanism of action to accelerate human keratinocyte differentiation. Toxicol Sci. 2013 Mar;132(1):235-49.
24 Marine biogenics in sea spray aerosols interact with the mTOR signaling pathway. Sci Rep. 2019 Jan 24;9(1):675.
25 Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.
26 A genome-wide analysis of targets of macrolide antibiotics in mammalian cells. J Biol Chem. 2020 Feb 14;295(7):2057-2067. doi: 10.1074/jbc.RA119.010770. Epub 2020 Jan 8.