Details of Drug Off-Target (DOT)

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

• DOT Name: Guanylate-binding protein 4 (GBP4)
• Synonyms: EC 3.6.5.-; GTP-binding protein 4; GBP-4; Guanine nucleotide-binding protein 4
• Gene Name: GBP4
• Related Disease: Neoplasm
• UniProt ID: GBP4_HUMAN
• EC Number: 3.6.5.-
• Pfam ID: PF02263 ; PF02841
• Sequence:
  MGERTLHAAVPTPGYPESESIMMAPICLVENQEEQLTVNSKALEILDKISQPVVVVAIVG
  LYRTGKSYLMNRLAGKRNGFPLGSTVQSETKGIWMWCVPHLSKPNHTLVLLDTEGLGDVE
  KSNPKNDSWIFALAVLLSSSFVYNSVSTINHQALEQLHYVTELAELIRAKSCPRPDEAED
  SSEFASFFPDFIWTVRDFTLELKLDGNPITEDEYLENALKLIPGKNPKIQNSNMPRECIR
  HFFRKRKCFVFDRPTNDKQYLNHMDEVPEENLERHFLMQSDNFCSYIFTHAKTKTLREGI
  IVTGKRLGTLVVTYVDAINSGAVPCLENAVTALAQLENPAAVQRAADHYSQQMAQQLRLP
  TDTLQELLDVHAACEREAIAVFMEHSFKDENHEFQKKLVDTIEKKKGDFVLQNEEASAKY
  CQAELKRLSEHLTESILRGIFSVPGGHNLYLEEKKQVEWDYKLVPRKGVKANEVLQNFLQ
  SQVVVEESILQSDKALTAGEKAIAAERAMKEAAEKEQELLREKQKEQQQMMEAQERSFQE
  YMAQMEKKLEEERENLLREHERLLKHKLKVQEEMLKEEFQKKSEQLNKEINQLKEKIEST
  KNEQLRLLKILDMASNIMIVTLPGASKLLGVGTKYLGSRI
• Function: Interferon (IFN)-inducible GTPase that plays important roles in innate immunity against a diverse range of bacterial, viral and protozoan pathogens. Negatively regulates the antiviral response by inhibiting activation of IRF7 transcription factor.
• KEGG Pathway: NOD-like receptor sig.ling pathway (hsa04621)
• Reactome Pathway: Interferon gamma signaling (R-HSA-877300)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

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

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 4 (GBP4).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Guanylate-binding protein 4 (GBP4).	[11]

9 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 4 (GBP4).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Guanylate-binding protein 4 (GBP4).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Guanylate-binding protein 4 (GBP4).	[5]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Guanylate-binding protein 4 (GBP4).	[6]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Guanylate-binding protein 4 (GBP4).	[7]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Guanylate-binding protein 4 (GBP4).	[8]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Guanylate-binding protein 4 (GBP4).	[9]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Guanylate-binding protein 4 (GBP4).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Guanylate-binding protein 4 (GBP4).	[12]

References

• [1] Up-regulation of GTPBP4 in colorectal carcinoma is responsible for tumor metastasis.Biochem Biophys Res Commun. 2016 Nov 4;480(1):48-54. doi: 10.1016/j.bbrc.2016.10.010. Epub 2016 Oct 5.
• [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] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [4] 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.
• [5] 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.
• [6] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [7] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
• [8] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [9] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [10] 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.
• [11] 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.
• [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.