Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNGMN6S)

DOT Name Deubiquitinase OTUD6B (OTUD6B)
Synonyms EC 3.4.19.12; DUBA-5; OTU domain-containing protein 6B
Gene Name OTUD6B
Related Disease
Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies ( )
Intellectual disability ( )
Non-small-cell lung cancer ( )
UniProt ID
OTU6B_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
3.4.19.12
Pfam ID
PF02338
Sequence
MEAVLTEELDEEEQLLRRHRKEKKELQAKIQGMKNAVPKNDKKRRKQLTEDVAKLEKEME
QKHREELEQLKLTTKENKIDSVAVNISNLVLENQPPRISKAQKRREKKAALEKEREERIA
EAEIENLTGARHMESEKLAQILAARQLEIKQIPSDGHCMYKAIEDQLKEKDCALTVVALR
SQTAEYMQSHVEDFLPFLTNPNTGDMYTPEEFQKYCEDIVNTAAWGGQLELRALSHILQT
PIEIIQADSPPIIVGEEYSKKPLILVYMRHAYGLGEHYNSVTRLVNIVTENCS
Function
[Isoform 1]: Deubiquitinating enzyme that may play a role in the ubiquitin-dependent regulation of protein synthesis, downstream of mTORC1. May associate with the protein synthesis initiation complex and modify its ubiquitination to repress translation. May also repress DNA synthesis and modify different cellular targets thereby regulating cell growth and proliferation. May also play a role in proteasome assembly and function ; [Isoform 2]: Stimulates protein synthesis. Influences the expression of CCND1/cyclin D1 by promoting its translation and regulates MYC/c-Myc protein stability.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies DISJ9BG9 Strong Autosomal recessive [1]
Intellectual disability DISMBNXP Strong Genetic Variation [1]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [2]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
8 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Deubiquitinase OTUD6B (OTUD6B). [3]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Deubiquitinase OTUD6B (OTUD6B). [4]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Deubiquitinase OTUD6B (OTUD6B). [5]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Deubiquitinase OTUD6B (OTUD6B). [6]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Deubiquitinase OTUD6B (OTUD6B). [7]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Deubiquitinase OTUD6B (OTUD6B). [8]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Deubiquitinase OTUD6B (OTUD6B). [9]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Deubiquitinase OTUD6B (OTUD6B). [10]
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⏷ Show the Full List of 8 Drug(s)

References

1 Biallelic Variants in OTUD6B Cause an Intellectual Disability Syndrome Associated with Seizures and Dysmorphic Features. Am J Hum Genet. 2017 Apr 6;100(4):676-688. doi: 10.1016/j.ajhg.2017.03.001. Epub 2017 Mar 23.
2 Deubiquitinase OTUD6B Isoforms Are Important Regulators of Growth and Proliferation.Mol Cancer Res. 2017 Feb;15(2):117-127. doi: 10.1158/1541-7786.MCR-16-0281-T. Epub 2016 Nov 18.
3 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
4 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.
5 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.
6 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
7 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
8 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.
9 Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
10 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.