Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDSRA7P)

• DOT Name: F-box only protein 17 (FBXO17)
• Synonyms: F-box only protein 26
• Gene Name: FBXO17
• Related Disease:
  Advanced cancer
  Hepatocellular carcinoma
  Lung cancer
  Malignant glioma
  Neoplasm
  Non-small-cell lung cancer
• UniProt ID: FBX17_HUMAN
• Pfam ID: PF12937 ; PF04300
• Sequence:
  MGARLSRRRLPADPSLALDALPPELLVQVLSHVPPRSLVTRCRPVCRAWRDIVDGPTVWL
  LQLARDRSAEGRALYAVAQRCLPSNEDKEEFPLCALARYCLRAPFGRNLIFNSCGEQGFR
  GWEVEHGGNGWAIEKNLTPVPGAPSQTCFVTSFEWCSKRQLVDLVMEGVWQELLDSAQIE
  ICVADWWGARENCGCVYQLRVRLLDVYEKEVVKFSASPDPVLQWTERGCRQVSHVFTNFG
  KGIRYVSFEQYGRDVSSWVGHYGALVTHSSVRVRIRLS
• Function: Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. Able to recognize and bind denatured glycoproteins, which are modified with complex-type oligosaccharides. Also recognizes sulfated glycans. Does not bind high-mannose glycoproteins.
• Tissue Specificity: Expressed in heart, skeletal muscle, liver and kidney. Expressed at lower levels in spleen and brain.
• Reactome Pathway:
  Antigen processing (R-HSA-983168)
  Neddylation (R-HSA-8951664)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[2]
Lung cancer	DISCM4YA	Strong	Altered Expression	[1]
Malignant glioma	DISFXKOV	Strong	Altered Expression	[3]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[1]

10 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 F-box only protein 17 (FBXO17).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of F-box only protein 17 (FBXO17).	[5]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of F-box only protein 17 (FBXO17).	[6]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of F-box only protein 17 (FBXO17).	[7]
Selenium	DM25CGV	Approved	Selenium increases the expression of F-box only protein 17 (FBXO17).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of F-box only protein 17 (FBXO17).	[9]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of F-box only protein 17 (FBXO17).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of F-box only protein 17 (FBXO17).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of F-box only protein 17 (FBXO17).	[12]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of F-box only protein 17 (FBXO17).	[13]

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 F-box only protein 17 (FBXO17).	[10]

References

• [1] FBXO17 promotes cell proliferation through activation of Akt in lung adenocarcinoma cells.Respir Res. 2018 Oct 25;19(1):206. doi: 10.1186/s12931-018-0910-0.
• [2] FBXO17 promotes malignant progression of hepatocellular carcinoma by activating wnt/-catenin pathway.Eur Rev Med Pharmacol Sci. 2019 Oct;23(19):8265-8273. doi: 10.26355/eurrev_201910_19137.
• [3] Clinical significance of FBXO17 gene expression in high-grade glioma.BMC Cancer. 2018 Jul 31;18(1):773. doi: 10.1186/s12885-018-4680-3.
• [4] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [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] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [7] 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.
• [8] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] 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.
• [11] 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.
• [12] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [13] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.