Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKU4R29)

• DOT Name: Glucocorticoid modulatory element-binding protein 2 (GMEB2)
• Synonyms: GMEB-2; DNA-binding protein p79PIF; Parvovirus initiation factor p79; PIF p79
• Gene Name: GMEB2
• UniProt ID: GMEB2_HUMAN
• Pfam ID: PF01342
• Sequence:
  MATPDVSVHMEEVVVVTTPDTAVDGSGVEGVKTVLVTTNLAPHGGDLTEDNMETENAAAA
  AAAAFTASSQLKEAVLVKMAEEGENLEAEIVYPITCGDSRANLIWRKFVCPGINVKCVQY
  DEHVISPKEFVHLAGKSTLKDWKRAIRMNGIMLRKIMDSGELDFYQHDKVCSNTCRSTKI
  DLSGARVSLSSPTSAEYIPLTPAAADVNGSPATITIETCEDPGDWTAAIGDDTFTFWRGL
  KDAGLLDEVIQEFHQELVETMRGLQQRVQDPPLQLRDAVLLNNIVQNFGMLDLVKKVLAS
  HKCQMDRSREQYARDLAALEQQCDEHRRRAKELKHKSQHLSNVLMTLTPVSLPPPVKRPR
  LARATSGPAAMASQVLTQSAQLALGPGVPVPQLTSVPLGKVVSTLPSTVLGKGSLQAPPA
  SSPASPLLGGYTVLASSGSTYPSTVEIHPDASSLTVLSTAAVQDGSTVFKVVSPLQLLTL
  PGLGPTLQNVAQASPGSSTIVTVPAGAAPGPEEHTATIEVAAMAEDHERK
• Function: Trans-acting factor that binds to glucocorticoid modulatory elements (GME) present in the TAT (tyrosine aminotransferase) promoter and increases sensitivity to low concentrations of glucocorticoids. Binds also to the transferrin receptor promoter. Essential auxiliary factor for the replication of parvoviruses.
• Tissue Specificity: Expressed in peripheral blood lymphocytes and fetal liver. Expressed preferentially in reproductive and/or developmentally important cells, such as testis, placenta, bone marrow and fetal tissues.

Molecular Interaction Atlas (MIA) of This DOT

6 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 Glucocorticoid modulatory element-binding protein 2 (GMEB2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Glucocorticoid modulatory element-binding protein 2 (GMEB2).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Glucocorticoid modulatory element-binding protein 2 (GMEB2).	[3]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Glucocorticoid modulatory element-binding protein 2 (GMEB2).	[1]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Glucocorticoid modulatory element-binding protein 2 (GMEB2).	[5]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Glucocorticoid modulatory element-binding protein 2 (GMEB2).	[8]

4 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Glucocorticoid modulatory element-binding protein 2 (GMEB2).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Glucocorticoid modulatory element-binding protein 2 (GMEB2).	[6]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Glucocorticoid modulatory element-binding protein 2 (GMEB2).	[7]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Glucocorticoid modulatory element-binding protein 2 (GMEB2).	[9]

References

• [1] A genomic approach to predict synergistic combinations for breast cancer treatment. Pharmacogenomics J. 2013 Feb;13(1):94-104. doi: 10.1038/tpj.2011.48. Epub 2011 Nov 15.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [4] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [5] 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.
• [6] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [7] 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.
• [8] 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.
• [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.