Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS4AO4A)

DOT Name Guanylate-binding protein 5 (GBP5)
Synonyms EC 3.6.5.-; GBP-TA antigen; GTP-binding protein 5; GBP-5; Guanine nucleotide-binding protein 5
Gene Name GBP5
Related Disease
Acute myocardial infarction ( )
Adenocarcinoma ( )
Melanoma ( )
Mismatch repair cancer syndrome ( )
Neoplasm ( )
Tuberculosis ( )
Epstein barr virus infection ( )
Coeliac disease ( )
Toxoplasmosis ( )
UniProt ID
GBP5_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
7CKF; 7E59; 7E5A
EC Number
3.6.5.-
Pfam ID
PF02263 ; PF02841
Sequence
MALEIHMSDPMCLIENFNEQLKVNQEALEILSAITQPVVVVAIVGLYRTGKSYLMNKLAG
KNKGFSVASTVQSHTKGIWIWCVPHPNWPNHTLVLLDTEGLGDVEKADNKNDIQIFALAL
LLSSTFVYNTVNKIDQGAIDLLHNVTELTDLLKARNSPDLDRVEDPADSASFFPDLVWTL
RDFCLGLEIDGQLVTPDEYLENSLRPKQGSDQRVQNFNLPRLCIQKFFPKKKCFIFDLPA
HQKKLAQLETLPDDELEPEFVQQVTEFCSYIFSHSMTKTLPGGIMVNGSRLKNLVLTYVN
AISSGDLPCIENAVLALAQRENSAAVQKAIAHYDQQMGQKVQLPMETLQELLDLHRTSER
EAIEVFMKNSFKDVDQSFQKELETLLDAKQNDICKRNLEASSDYCSALLKDIFGPLEEAV
KQGIYSKPGGHNLFIQKTEELKAKYYREPRKGIQAEEVLQKYLKSKESVSHAILQTDQAL
TETEKKKKEAQVKAEAEKAEAQRLAAIQRQNEQMMQERERLHQEQVRQMEIAKQNWLAEQ
QKMQEQQMQEQAAQLSTTFQAQNRSLLSELQHAQRTVNNDDPCVLL
Function
Interferon (IFN)-inducible GTPase that plays important roles in innate immunity against a diverse range of bacterial, viral and protozoan pathogens. Hydrolyzes GTP, but in contrast to other family members, does not produce GMP. 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. As an activator of NLRP3 inflammasome assembly: promotes selective NLRP3 inflammasome assembly in response to microbial and soluble, but not crystalline, agents. Independently of its GTPase activity, acts as an inhibitor of various viruses infectivity, such as HIV-1, Zika and influenza A viruses, by inhibiting FURIN-mediated maturation of viral envelope proteins ; Antigenic tumor-specific truncated splice form.
Tissue Specificity Expressed in peripheral blood monocytes (at protein level).
KEGG Pathway
NOD-like receptor sig.ling pathway (hsa04621 )
Reactome Pathway
Interferon gamma signaling (R-HSA-877300 )

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Acute myocardial infarction DISE3HTG Strong Altered Expression [1]
Adenocarcinoma DIS3IHTY Strong Altered Expression [2]
Melanoma DIS1RRCY Strong Altered Expression [3]
Mismatch repair cancer syndrome DISIXHJ2 Strong Biomarker [2]
Neoplasm DISZKGEW Strong Altered Expression [2]
Tuberculosis DIS2YIMD Strong Biomarker [4]
Epstein barr virus infection DISOO0WT moderate Altered Expression [5]
Coeliac disease DISIY60C Limited Biomarker [6]
Toxoplasmosis DISYP8FH Limited Biomarker [7]
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⏷ Show the Full List of 9 Disease(s)
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 decreases the methylation of Guanylate-binding protein 5 (GBP5). [8]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Guanylate-binding protein 5 (GBP5). [18]
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12 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin increases the expression of Guanylate-binding protein 5 (GBP5). [9]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Guanylate-binding protein 5 (GBP5). [10]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Guanylate-binding protein 5 (GBP5). [11]
Arsenic DMTL2Y1 Approved Arsenic affects the expression of Guanylate-binding protein 5 (GBP5). [12]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Guanylate-binding protein 5 (GBP5). [13]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of Guanylate-binding protein 5 (GBP5). [14]
Malathion DMXZ84M Approved Malathion increases the expression of Guanylate-binding protein 5 (GBP5). [15]
Nabiximols DMHKJ5I Phase 3 Nabiximols decreases the expression of Guanylate-binding protein 5 (GBP5). [16]
GSK2110183 DMZHB37 Phase 2 GSK2110183 increases the expression of Guanylate-binding protein 5 (GBP5). [17]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Guanylate-binding protein 5 (GBP5). [19]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Guanylate-binding protein 5 (GBP5). [20]
Microcystin-LR DMTMLRN Investigative Microcystin-LR increases the expression of Guanylate-binding protein 5 (GBP5). [21]
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⏷ Show the Full List of 12 Drug(s)

References

1 Biomarkers identification for acute myocardial infarction detection via weighted gene co-expression network analysis.Medicine (Baltimore). 2017 Nov;96(47):e8375. doi: 10.1097/MD.0000000000008375.
2 Expression of PD-L1, indoleamine 2,3-dioxygenase and the immune microenvironment in gastric adenocarcinoma.Histopathology. 2018 Jul;73(1):124-136. doi: 10.1111/his.13504. Epub 2018 Apr 17.
3 GBP-5 splicing variants: New guanylate-binding proteins with tumor-associated expression and antigenicity.J Invest Dermatol. 2004 Jun;122(6):1510-7. doi: 10.1111/j.0022-202X.2004.22613.x.
4 Blood Transcriptomic Stratification of Short-term Risk in Contacts of Tuberculosis.Clin Infect Dis. 2020 Feb 14;70(5):731-737. doi: 10.1093/cid/ciz252.
5 Oligonucleotide microarray analysis of gene expression profiles followed by real-time reverse-transcriptase polymerase chain reaction assay in chronic active Epstein-Barr virus infection.J Infect Dis. 2008 Mar 1;197(5):663-6. doi: 10.1086/527330.
6 Celiac disease biomarkers identified by transcriptome analysis of small intestinal biopsies.Cell Mol Life Sci. 2018 Dec;75(23):4385-4401. doi: 10.1007/s00018-018-2898-5. Epub 2018 Aug 10.
7 NADPH Oxidase and Guanylate Binding Protein 5 Restrict Survival of Avirulent Type III Strains of Toxoplasma gondii in Naive Macrophages.mBio. 2018 Aug 28;9(4):e01393-18. doi: 10.1128/mBio.01393-18.
8 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.
9 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.
10 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.
11 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
12 Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population. Environ Health Perspect. 2008 Apr;116(4):524-31. doi: 10.1289/ehp.10861.
13 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.
14 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
15 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.
16 Clinical response to Nabiximols correlates with the downregulation of immune pathways in multiple sclerosis. Eur J Neurol. 2018 Jul;25(7):934-e70. doi: 10.1111/ene.13623. Epub 2018 Apr 16.
17 Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
18 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.
19 Low dose of bisphenol a modulates ovarian cancer gene expression profile and promotes epithelial to mesenchymal transition via canonical Wnt pathway. Toxicol Sci. 2018 Aug 1;164(2):527-538.
20 Regulation of chromatin assembly and cell transformation by formaldehyde exposure in human cells. Environ Health Perspect. 2017 Sep 21;125(9):097019.
21 Gene expression network regulated by DNA methylation and microRNA during microcystin-leucine arginine induced malignant transformation in human hepatocyte L02 cells. Toxicol Lett. 2018 Jun 1;289:42-53. doi: 10.1016/j.toxlet.2018.03.003. Epub 2018 Mar 5.