Details of Drug Off-Target (DOT)

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

DOT Name F-box/LRR-repeat protein 19 (FBXL19)
Synonyms F-box and leucine-rich repeat protein 19
Gene Name FBXL19
Related Disease
Carcinoma of esophagus ( )
Esophageal cancer ( )
Neoplasm of esophagus ( )
Non-small-cell lung cancer ( )
Palmoplantar pustulosis ( )
Psoriasis ( )
Psoriatic arthritis ( )
UniProt ID
FXL19_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
6ASB
Pfam ID
PF12937 ; PF16866 ; PF02008
Sequence
MGMKVPGKGESGPSALLTPPMSSSSRGPGAGARRRRTRCRRCRACVRTECGDCHFCRDMK
KFGGPGRMKQSCLLRQCTAPVLPHTAVCLLCGEAGKEDTVEGEEEKFGLSLMECTICNEI
VHPGCLKMGKAEGVINAEIPNCWECPRCTQEGRTSKDSGEGPGRRRADNGEEGASLGSGW
KLTEEPPLPPPPPRRKGPLPAGPPPEDVPGPPKRKEREAGNEPPTPRKKVKGGRERHLKK
VGGDACLLRGSDPGGPGLLPPRVLNPSQAFSSCHPGLPPENWEKPKPPLASAEGPAVPSP
SPQREKLERFKRMCQLLERVPDTSSSSSDSDSDSDSSGTSLSEDEAPGEARNGRRPARGS
SGEKENRGGRRAVRPGSGGPLLSWPLGPAPPPRPPQLERHVVRPPPRSPEPDTLPLAAGS
DHPLPRAAWLRVFQHLGPRELCICMRVCRTWSRWCYDKRLWPRMDLSRRKSLTPPMLSGV
VRRQPRALDLSWTGVSKKQLMWLLNRLQGLQELVLSGCSWLSVSALGSAPLPALRLLDLR
WIEDVKDSQLRELLLPPPDTKPGQTESRGRLQGVAELRLAGLELTDASLRLLLRHAPQLS
ALDLSHCAHVGDPSVHLLTAPTSPLRETLVHLNLAGCHRLTDHCLPLFRRCPRLRRLDLR
SCRQLSPEACARLAAAGPPGPFRCPEEKLLLKDS
Function
Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex that plays a role in different processes including cell migration, cell proliferation or cytoskeletal reorganization. Mediates RHOA ubiquitination and degradation in a ERK2-dependent manner. Induces RAC1 and RAC3 degradation by the proteasome system and thereby regulates TGFB1-induced E-cadherin down-regulation and cell migration. Mediates also ubiquitination and degradation of IL-33-induced receptor IL1RL1 and subsequently blocks IL-33-mediated apoptosis. Within the nucleus, binds to DNA containing unmethylated cytidine-phosphate-guanosine (CpG) dinucleotides. Recruits CDK-mediator to chromatin and targets CDK8 to promoters of silent developmental genes leading to induction of these genes during cell differentiation. In addition, plays a critical role in the recruitment of RNF20 to histone H2B leading to H2B mono-ubiquitination.
Reactome Pathway
Antigen processing (R-HSA-983168 )
Neddylation (R-HSA-8951664 )

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Carcinoma of esophagus DISS6G4D Strong Altered Expression [1]
Esophageal cancer DISGB2VN Strong Altered Expression [1]
Neoplasm of esophagus DISOLKAQ Strong Altered Expression [1]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [2]
Palmoplantar pustulosis DISCNSWD Strong Biomarker [3]
Psoriasis DIS59VMN Strong Genetic Variation [4]
Psoriatic arthritis DISLWTG2 moderate Genetic Variation [5]
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⏷ Show the Full List of 7 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of F-box/LRR-repeat protein 19 (FBXL19). [6]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of F-box/LRR-repeat protein 19 (FBXL19). [7]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of F-box/LRR-repeat protein 19 (FBXL19). [8]
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1 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the expression of F-box/LRR-repeat protein 19 (FBXL19). [9]
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References

1 F-box protein complex FBXL19 regulates TGF1-induced E-cadherin down-regulation by mediating Rac3 ubiquitination and degradation.Mol Cancer. 2014 Apr 1;13:76. doi: 10.1186/1476-4598-13-76.
2 LncRNA FBXL19-AS1 promotes proliferation and metastasis via regulating epithelial-mesenchymal transition in non-small cell lung cancer.Eur Rev Med Pharmacol Sci. 2019 Jun;23(11):4800-4806. doi: 10.26355/eurrev_201906_18065.
3 Genome-wide association analysis identifies three psoriasis susceptibility loci.Nat Genet. 2010 Nov;42(11):1000-4. doi: 10.1038/ng.693. Epub 2010 Oct 17.
4 Genome-wide comparative analysis of atopic dermatitis and psoriasis gives insight into opposing genetic mechanisms.Am J Hum Genet. 2015 Jan 8;96(1):104-20. doi: 10.1016/j.ajhg.2014.12.004.
5 What have genome-wide studies told us about psoriatic arthritis?.Curr Rheumatol Rep. 2012 Aug;14(4):364-8. doi: 10.1007/s11926-012-0255-5.
6 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.
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 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.
9 Comparative proteomics reveals concordant and discordant biochemical effects of caffeine versus epigallocatechin-3-gallate in human endothelial cells. Toxicol Appl Pharmacol. 2019 Sep 1;378:114621. doi: 10.1016/j.taap.2019.114621. Epub 2019 Jun 10.