General Information of Drug Off-Target (DOT) (ID: OTF3GGYY)

DOT Name Glutamate dehydrogenase 2, mitochondrial (GLUD2)
Synonyms GDH 2; EC 1.4.1.3
Gene Name GLUD2
Related Disease
Type-1/2 diabetes ( )
Epilepsy ( )
Glioma ( )
Schizophrenia ( )
Advanced cancer ( )
Parkinson disease ( )
Small lymphocytic lymphoma ( )
Adult glioblastoma ( )
Glioblastoma multiforme ( )
Neoplasm ( )
Neuroblastoma ( )
Rett syndrome ( )
UniProt ID
DHE4_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
6G2U
EC Number
1.4.1.3
Pfam ID
PF00208 ; PF02812
Sequence
MYRYLAKALLPSRAGPAALGSAANHSAALLGRGRGQPAAASQPGLALAARRHYSELVADR
EDDPNFFKMVEGFFDRGASIVEDKLVKDLRTQESEEQKRNRVRGILRIIKPCNHVLSLSF
PIRRDDGSWEVIEGYRAQHSQHRTPCKGGIRYSTDVSVDEVKALASLMTYKCAVVDVPFG
GAKAGVKINPKNYTENELEKITRRFTMELAKKGFIGPGVDVPAPDMNTGEREMSWIADTY
ASTIGHYDINAHACVTGKPISQGGIHGRISATGRGVFHGIENFINEASYMSILGMTPGFR
DKTFVVQGFGNVGLHSMRYLHRFGAKCIAVGESDGSIWNPDGIDPKELEDFKLQHGSILG
FPKAKPYEGSILEVDCDILIPAATEKQLTKSNAPRVKAKIIAEGANGPTTPEADKIFLER
NILVIPDLYLNAGGVTVSYFEWLKNLNHVSYGRLTFKYERDSNYHLLLSVQESLERKFGK
HGGTIPIVPTAEFQDSISGASEKDIVHSALAYTMERSARQIMHTAMKYNLGLDLRTAAYV
NAIEKVFKVYSEAGVTFT
Function Important for recycling the chief excitatory neurotransmitter, glutamate, during neurotransmission.
Tissue Specificity Expressed in retina, testis and, at a lower level, brain.
KEGG Pathway
Arginine biosynthesis (hsa00220 )
Alanine, aspartate and glutamate metabolism (hsa00250 )
Nitrogen metabolism (hsa00910 )
Metabolic pathways (hsa01100 )
Carbon metabolism (hsa01200 )
Necroptosis (hsa04217 )
Proximal tubule bicarbo.te reclamation (hsa04964 )
Reactome Pathway
Glutamate and glutamine metabolism (R-HSA-8964539 )
Transcriptional activation of mitochondrial biogenesis (R-HSA-2151201 )
BioCyc Pathway
MetaCyc:HS00018-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Type-1/2 diabetes DISIUHAP Definitive Biomarker [1]
Epilepsy DISBB28L Strong Biomarker [2]
Glioma DIS5RPEH Strong Biomarker [3]
Schizophrenia DISSRV2N Strong Biomarker [4]
Advanced cancer DISAT1Z9 moderate Altered Expression [5]
Parkinson disease DISQVHKL moderate Genetic Variation [6]
Small lymphocytic lymphoma DIS30POX moderate Altered Expression [7]
Adult glioblastoma DISVP4LU Limited Biomarker [8]
Glioblastoma multiforme DISK8246 Limited Altered Expression [8]
Neoplasm DISZKGEW Limited Biomarker [9]
Neuroblastoma DISVZBI4 Limited Biomarker [10]
Rett syndrome DISGG5UV Limited Altered Expression [11]
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⏷ Show the Full List of 12 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
16 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of Glutamate dehydrogenase 2, mitochondrial (GLUD2). [12]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Glutamate dehydrogenase 2, mitochondrial (GLUD2). [13]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Glutamate dehydrogenase 2, mitochondrial (GLUD2). [14]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Glutamate dehydrogenase 2, mitochondrial (GLUD2). [15]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Glutamate dehydrogenase 2, mitochondrial (GLUD2). [16]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Glutamate dehydrogenase 2, mitochondrial (GLUD2). [17]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Glutamate dehydrogenase 2, mitochondrial (GLUD2). [18]
Testosterone DM7HUNW Approved Testosterone increases the expression of Glutamate dehydrogenase 2, mitochondrial (GLUD2). [18]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Glutamate dehydrogenase 2, mitochondrial (GLUD2). [19]
Dihydrotestosterone DM3S8XC Phase 4 Dihydrotestosterone increases the expression of Glutamate dehydrogenase 2, mitochondrial (GLUD2). [20]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of Glutamate dehydrogenase 2, mitochondrial (GLUD2). [21]
Tamibarotene DM3G74J Phase 3 Tamibarotene affects the expression of Glutamate dehydrogenase 2, mitochondrial (GLUD2). [14]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Glutamate dehydrogenase 2, mitochondrial (GLUD2). [23]
Bisphenol A DM2ZLD7 Investigative Bisphenol A affects the expression of Glutamate dehydrogenase 2, mitochondrial (GLUD2). [24]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Glutamate dehydrogenase 2, mitochondrial (GLUD2). [25]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Glutamate dehydrogenase 2, mitochondrial (GLUD2). [26]
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⏷ Show the Full List of 16 Drug(s)
1 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 Glutamate dehydrogenase 2, mitochondrial (GLUD2). [22]
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References

1 Transgenic expression of the positive selected human GLUD2 gene improves in vivo glucose homeostasis by regulating basic insulin secretion.Metabolism. 2019 Nov;100:153958. doi: 10.1016/j.metabol.2019.153958. Epub 2019 Aug 7.
2 Epilepsy with myoclonic atonic seizures and chronic cerebellar symptoms associated with antibodies against glutamate receptors N2B and D2 in serum and cerebrospinal fluid.Epileptic Disord. 2017 Mar 1;19(1):94-98. doi: 10.1684/epd.2017.0895.
3 Adaptive Evolution of the GDH2 Allosteric Domain Promotes Gliomagenesis by Resolving IDH1(R132H)-Induced Metabolic Liabilities.Cancer Res. 2018 Jan 1;78(1):36-50. doi: 10.1158/0008-5472.CAN-17-1352. Epub 2017 Nov 2.
4 GluD1, linked to schizophrenia, controls the burst firing of dopamine neurons.Mol Psychiatry. 2018 Mar;23(3):691-700. doi: 10.1038/mp.2017.137. Epub 2017 Jul 11.
5 Glutamate production from ammonia via glutamate dehydrogenase 2 activity supports cancer cell proliferation under glutamine depletion.Biochem Biophys Res Commun. 2018 Jan 1;495(1):761-767. doi: 10.1016/j.bbrc.2017.11.088. Epub 2017 Nov 14.
6 Deregulation of glutamate dehydrogenase in human neurologic disorders.J Neurosci Res. 2013 Aug;91(8):1007-17. doi: 10.1002/jnr.23176. Epub 2013 Mar 6.
7 Glutamate dehydrogenase activity in lymphocytes of B-cell chronic lymphocytic leukaemia patients.Clin Biochem. 2009 Nov;42(16-17):1677-84. doi: 10.1016/j.clinbiochem.2009.08.003. Epub 2009 Aug 13.
8 Mitochondrial enzyme GLUD2 plays a critical role in glioblastoma progression.EBioMedicine. 2018 Nov;37:56-67. doi: 10.1016/j.ebiom.2018.10.008. Epub 2018 Oct 9.
9 Widening Spectrum of Cellular and Subcellular Expression of Human GLUD1 and GLUD2 Glutamate Dehydrogenases Suggests Novel Functions.Neurochem Res. 2017 Jan;42(1):92-107. doi: 10.1007/s11064-016-1986-x. Epub 2016 Jul 16.
10 Glutamate receptor 2 serum antibodies in pediatric opsoclonus myoclonus ataxia syndrome.Neurology. 2018 Aug 21;91(8):e714-e723. doi: 10.1212/WNL.0000000000006035. Epub 2018 Jul 25.
11 Evaluation of two X chromosomal candidate genes for Rett syndrome: glutamate dehydrogenase-2 (GLUD2) and rab GDP-dissociation inhibitor (GDI1).Am J Med Genet. 1998 Jun 30;78(2):169-72.
12 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
13 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.
14 Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
15 Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
16 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
17 Protein expression profiling identifies molecular targets of quercetin as a major dietary flavonoid in human colon cancer cells. Proteomics. 2004 Jul;4(7):2160-74.
18 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
19 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
20 LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
21 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
22 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.
23 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.
24 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.
25 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.
26 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.