Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZUMPH2)

• DOT Name: Ubiquitin thioesterase OTUB2 (OTUB2)
• Synonyms: EC 3.4.19.12; Deubiquitinating enzyme OTUB2; OTU domain-containing ubiquitin aldehyde-binding protein 2; Otubain-2; Ubiquitin-specific-processing protease OTUB2
• Gene Name: OTUB2
• Related Disease:
  Thyroid gland papillary carcinoma
  Advanced cancer
  Neoplasm
  Non-small-cell lung cancer
  Acute myelogenous leukaemia
• UniProt ID: OTUB2_HUMAN
• PDB ID: 1TFF; 4FJV; 5QIO; 5QIP; 5QIQ; 5QIR; 5QIS; 5QIT; 5QIU; 5QIV; 5QIW; 5QIX; 5QIY; 5QIZ; 8CMS
• EC Number: 3.4.19.12
• Pfam ID: PF10275
• Sequence:
  MSETSFNLISEKCDILSILRDHPENRIYRRKIEELSKRFTAIRKTKGDGNCFYRALGYSY
  LESLLGKSREIFKFKERVLQTPNDLLAAGFEEHKFRNFFNAFYSVVELVEKDGSVSSLLK
  VFNDQSASDHIVQFLRLLTSAFIRNRADFFRHFIDEEMDIKDFCTHEVEPMATECDHIQI
  TALSQALSIALQVEYVDEMDTALNHHVFPEAATPSVYLLYKTSHYNILYAADKH
• Function: Hydrolase that can remove conjugated ubiquitin from proteins in vitro and may therefore play an important regulatory role at the level of protein turnover by preventing degradation. Mediates deubiquitination of 'Lys-11'-,'Lys-48'- and 'Lys-63'-linked polyubiquitin chains, with a preference for 'Lys-63'-linked polyubiquitin chains.
• Tissue Specificity: Widely expressed. Expressed at higher level in brain.
• Reactome Pathway: Ovarian tumor domain proteases (R-HSA-5689896)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Thyroid gland papillary carcinoma	DIS48YMM	Definitive	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[3]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[3]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[4]

1 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 Ubiquitin thioesterase OTUB2 (OTUB2).	[5]

11 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Ubiquitin thioesterase OTUB2 (OTUB2).	[6]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Ubiquitin thioesterase OTUB2 (OTUB2).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Ubiquitin thioesterase OTUB2 (OTUB2).	[8]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Ubiquitin thioesterase OTUB2 (OTUB2).	[9]
Lucanthone	DMZLBUO	Approved	Lucanthone increases the expression of Ubiquitin thioesterase OTUB2 (OTUB2).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Ubiquitin thioesterase OTUB2 (OTUB2).	[11]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Ubiquitin thioesterase OTUB2 (OTUB2).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Ubiquitin thioesterase OTUB2 (OTUB2).	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Ubiquitin thioesterase OTUB2 (OTUB2).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Ubiquitin thioesterase OTUB2 (OTUB2).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Ubiquitin thioesterase OTUB2 (OTUB2).	[16]

References

• [1] miR-29a-3p inhibits growth, proliferation, and invasion of papillary thyroid carcinoma by suppressing NF-B signaling via direct targeting of OTUB2.Cancer Manag Res. 2018 Dec 17;11:13-23. doi: 10.2147/CMAR.S184781. eCollection 2019.
• [2] OTUB2 Promotes Cancer Metastasis via Hippo-Independent Activation of YAP and TAZ.Mol Cell. 2019 Jan 3;73(1):7-21.e7. doi: 10.1016/j.molcel.2018.10.030. Epub 2018 Nov 21.
• [3] OTUB2 stabilizes U2AF2 to promote the Warburg effect and tumorigenesis via the AKT/mTOR signaling pathway in non-small cell lung cancer.Theranostics. 2019 Jan 1;9(1):179-195. doi: 10.7150/thno.29545. eCollection 2019.
• [4] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [5] 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.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] 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.
• [8] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [9] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [10] Lucanthone is a novel inhibitor of autophagy that induces cathepsin D-mediated apoptosis. J Biol Chem. 2011 Feb 25;286(8):6602-13.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
• [13] 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.
• [14] Synergistic effect of JQ1 and rapamycin for treatment of human osteosarcoma. Int J Cancer. 2015 May 1;136(9):2055-64.
• [15] Bisphenolic compounds alter gene expression in MCF-7 cells through interaction with estrogen receptor . Toxicol Appl Pharmacol. 2020 Jul 15;399:115030. doi: 10.1016/j.taap.2020.115030. Epub 2020 May 6.
• [16] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.