Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6WBFXS)

• DOT Name: Guanylate-binding protein 3 (GBP3)
• Synonyms: EC 3.6.5.-; GTP-binding protein 3; GBP-3; Guanine nucleotide-binding protein 3
• Gene Name: GBP3
• Related Disease:
  Glioma
  Neoplasm
• UniProt ID: GBP3_HUMAN
• EC Number: 3.6.5.-
• Pfam ID: PF02263 ; PF02841
• Sequence:
  MAPEIHMTGPMCLIENTNGELVANPEALKILSAITQPVVVVAIVGLYRTGKSYLMNKLAG
  KNKGFSLGSTVKSHTKGIWMWCVPHPKKPEHTLVLLDTEGLGDVKKGDNQNDSWIFTLAV
  LLSSTLVYNSMGTINQQAMDQLYYVTELTHRIRSKSSPDENENEDSADFVSFFPDFVWTL
  RDFSLDLEADGQPLTPDEYLEYSLKLTQGTSQKDKNFNLPRLCIRKFFPKKKCFVFDLPI
  HRRKLAQLEKLQDEELDPEFVQQVADFCSYIFSNSKTKTLSGGIKVNGPRLESLVLTYIN
  AISRGDLPCMENAVLALAQIENSAAVQKAIAHYDQQMGQKVQLPAETLQELLDLHRVSER
  EATEVYMKNSFKDVDHLFQKKLAAQLDKKRDDFCKQNQEASSDRCSALLQVIFSPLEEEV
  KAGIYSKPGGYCLFIQKLQDLEKKYYEEPRKGIQAEEILQTYLKSKESVTDAILQTDQIL
  TEKEKEIEVECVKAESAQASAKMVEEMQIKYQQMMEEKEKSYQEHVKQLTEKMERERAQL
  LEEQEKTLTSKLQEQARVLKERCQGESTQLQNEIQKLQKTLKKKTKRYMSHKLKI
• Function: Interferon (IFN)-inducible GTPase that plays important roles in innate immunity against a diverse range of bacterial, viral and protozoan pathogens. Hydrolyzes GTP very efficiently; GDP rather than GMP is the major reaction product. Following infection, recruited to the pathogen-containing vacuoles or vacuole-escaped bacteria and acts as a positive regulator of inflammasome assembly by promoting the release of inflammasome ligands from bacteria. Acts by promoting lysis of pathogen-containing vacuoles, releasing pathogens into the cytosol. Following pathogen release in the cytosol, promotes recruitment of proteins that mediate bacterial cytolysis: this liberates ligands that are detected by inflammasomes, such as lipopolysaccharide (LPS) that activates the non-canonical CASP4/CASP11 inflammasome or double-stranded DNA (dsDNA) that activates the AIM2 inflammasome. Exhibits antiviral activity against influenza virus ; [Isoform 2]: Shows the most prominent antiviral activity in epithelial cells.
• KEGG Pathway: NOD-like receptor sig.ling pathway (hsa04621)
• Reactome Pathway: Interferon gamma signaling (R-HSA-877300)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glioma	DIS5RPEH	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]

12 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 Guanylate-binding protein 3 (GBP3).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Guanylate-binding protein 3 (GBP3).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Guanylate-binding protein 3 (GBP3).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Guanylate-binding protein 3 (GBP3).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Guanylate-binding protein 3 (GBP3).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Guanylate-binding protein 3 (GBP3).	[8]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Guanylate-binding protein 3 (GBP3).	[8]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Guanylate-binding protein 3 (GBP3).	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Guanylate-binding protein 3 (GBP3).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Guanylate-binding protein 3 (GBP3).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Guanylate-binding protein 3 (GBP3).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Guanylate-binding protein 3 (GBP3).	[13]

1 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 Guanylate-binding protein 3 (GBP3).	[7]

References

• [1] GBP3 promotes glioma cell proliferation via SQSTM1/p62-ERK1/2 axis.Biochem Biophys Res Commun. 2018 Jan 1;495(1):446-453. doi: 10.1016/j.bbrc.2017.11.050. Epub 2017 Nov 8.
• [2] 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.
• [3] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [4] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [9] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [10] 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.
• [11] 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.
• [12] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [13] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.