Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE6O5XB)

DOT Name OTU domain-containing protein 1 (OTUD1)
Synonyms EC 3.4.19.12; DUBA-7
Gene Name OTUD1
Related Disease
Carcinoma of liver and intrahepatic biliary tract ( )
Liver cancer ( )
Neoplasm ( )
Advanced cancer ( )
Autoimmune disease ( )
Breast cancer ( )
Breast carcinoma ( )
Ovarian neoplasm ( )
Sarcoidosis ( )
UniProt ID
OTUD1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
4BOP
EC Number
3.4.19.12
Pfam ID
PF02338
Sequence
MQLYSSVCTHYPAGAPGPTAAAPAPPAAATPFKVSLQPPGAAGAAPEPETGECQPAAAAE
HREAAAVPAAKMPAFSSCFEVVSGAAAPASAAAGPPGASCKPPLPPHYTSTAQITVRALG
ADRLLLHGPDPVPGAAGSAAAPRGRCLLLAPAPAAPVPPRRGSSAWLLEELLRPDCPEPA
GLDATREGPDRNFRLSEHRQALAAAKHRGPAATPGSPDPGPGPWGEEHLAERGPRGWERG
GDRCDAPGGDAARRPDPEAEAPPAGSIEAAPSSAAEPVIVSRSDPRDEKLALYLAEVEKQ
DKYLRQRNKYRFHIIPDGNCLYRAVSKTVYGDQSLHRELREQTVHYIADHLDHFSPLIEG
DVGEFIIAAAQDGAWAGYPELLAMGQMLNVNIHLTTGGRLESPTVSTMIHYLGPEDSLRP
SIWLSWLSNGHYDAVFDHSYPNPEYDNWCKQTQVQRKRDEELAKSMAISLSKMYIEQNAC
S
Function
Deubiquitinating enzyme that specifically hydrolyzes 'Lys-63'-linked polyubiquitin to monoubiquitin. Required for the stability and translation of a subset mRNAs with a high abundance of rare codons by mediating deubiquitination of 40S ribosomal protein RPS10/eS10, thereby antagonizing ZNF598-mediated 40S ubiquitination. The abundance of rare codons in mRNAs can limit the translation rate and can lead to ribosome collisions that trigger activation of ribosome quality control (RQC) pathway by ZNF598. OTUD1-mediated deubiquitination prevents activation of the RQC and subsequent dissociation of ribosomes and stimulates formation of polysomes and translation.
Reactome Pathway
Regulation of TNFR1 signaling (R-HSA-5357905 )
TNFR1-induced NF-kappa-B signaling pathway (R-HSA-5357956 )
TNFR1-induced proapoptotic signaling (R-HSA-5357786 )

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Carcinoma of liver and intrahepatic biliary tract DIS8WA0W Definitive Biomarker [1]
Liver cancer DISDE4BI Definitive Biomarker [1]
Neoplasm DISZKGEW Definitive Biomarker [1]
Advanced cancer DISAT1Z9 Strong Altered Expression [2]
Autoimmune disease DISORMTM Strong Genetic Variation [3]
Breast cancer DIS7DPX1 Strong Biomarker [2]
Breast carcinoma DIS2UE88 Strong Biomarker [2]
Ovarian neoplasm DISEAFTY Strong Biomarker [4]
Sarcoidosis DISE5B8Z Strong Genetic Variation [5]
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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 increases the methylation of OTU domain-containing protein 1 (OTUD1). [6]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of OTU domain-containing protein 1 (OTUD1). [18]
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17 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of OTU domain-containing protein 1 (OTUD1). [7]
Tretinoin DM49DUI Approved Tretinoin increases the expression of OTU domain-containing protein 1 (OTUD1). [8]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of OTU domain-containing protein 1 (OTUD1). [9]
Testosterone DM7HUNW Approved Testosterone decreases the expression of OTU domain-containing protein 1 (OTUD1). [10]
Triclosan DMZUR4N Approved Triclosan increases the expression of OTU domain-containing protein 1 (OTUD1). [11]
Methotrexate DM2TEOL Approved Methotrexate decreases the expression of OTU domain-containing protein 1 (OTUD1). [12]
Niclosamide DMJAGXQ Approved Niclosamide increases the expression of OTU domain-containing protein 1 (OTUD1). [13]
Ethanol DMDRQZU Approved Ethanol decreases the expression of OTU domain-containing protein 1 (OTUD1). [14]
Sulindac DM2QHZU Approved Sulindac increases the expression of OTU domain-containing protein 1 (OTUD1). [15]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of OTU domain-containing protein 1 (OTUD1). [16]
DNCB DMDTVYC Phase 2 DNCB increases the expression of OTU domain-containing protein 1 (OTUD1). [17]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of OTU domain-containing protein 1 (OTUD1). [19]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of OTU domain-containing protein 1 (OTUD1). [20]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of OTU domain-containing protein 1 (OTUD1). [21]
Milchsaure DM462BT Investigative Milchsaure increases the expression of OTU domain-containing protein 1 (OTUD1). [22]
Coumestrol DM40TBU Investigative Coumestrol decreases the expression of OTU domain-containing protein 1 (OTUD1). [23]
methyl p-hydroxybenzoate DMO58UW Investigative methyl p-hydroxybenzoate increases the expression of OTU domain-containing protein 1 (OTUD1). [24]
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⏷ Show the Full List of 17 Drug(s)

References

1 The deubiquitinating enzyme OTUD1 antagonizes BH3-mimetic inhibitor induced cell death through regulating the stability of the MCL1 protein.Cancer Cell Int. 2019 Aug 27;19:222. doi: 10.1186/s12935-019-0936-5. eCollection 2019.
2 Breast cancer metastasis suppressor OTUD1 deubiquitinates SMAD7.Nat Commun. 2017 Dec 13;8(1):2116. doi: 10.1038/s41467-017-02029-7.
3 Mutations of deubiquitinase OTUD1 are associated with autoimmune disorders.J Autoimmun. 2018 Nov;94:156-165. doi: 10.1016/j.jaut.2018.07.019. Epub 2018 Aug 10.
4 Ovarian tumor domain-containing protein 1 deubiquitinates and stabilizes p53.Cell Signal. 2017 May;33:22-29. doi: 10.1016/j.cellsig.2017.02.011. Epub 2017 Feb 13.
5 Fine-mapping in African-American women confirms the importance of the 10p12 locus to sarcoidosis.Genes Immun. 2012 Oct;13(7):573-8. doi: 10.1038/gene.2012.42. Epub 2012 Sep 13.
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 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.
8 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
9 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.
10 The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
11 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
12 Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
13 Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
14 Cardiac toxicity from ethanol exposure in human-induced pluripotent stem cell-derived cardiomyocytes. Toxicol Sci. 2019 May 1;169(1):280-292.
15 Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
16 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
17 Microarray analyses in dendritic cells reveal potential biomarkers for chemical-induced skin sensitization. Mol Immunol. 2007 May;44(12):3222-33.
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 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.
20 Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
21 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
22 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
23 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
24 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.