Details of Drug Off-Target (DOT)

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

• DOT Name: Deubiquitinase DESI2 (DESI2)
• Synonyms: EC 3.4.19.12; Desumoylating isopeptidase 2; DeSI-2; PPPDE peptidase domain-containing protein 1; Palmitoyl protein thioesterase DESI2; EC 3.1.2.22; Protein FAM152A; S-depalmitoylase DESI2
• Gene Name: DESI2
• Related Disease:
  Colorectal carcinoma
  Advanced cancer
  Colon carcinoma
  Epithelial ovarian cancer
  Gastric cancer
  Hepatocellular carcinoma
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Multiple sclerosis
  Neoplasm
  Ovarian cancer
  Ovarian neoplasm
  Prostate cancer
  Prostate carcinoma
  Skin neoplasm
  Stomach cancer
  Pancreatic cancer
  Pancreatic ductal carcinoma
• UniProt ID: DESI2_HUMAN
• EC Number: 3.1.2.22; 3.4.19.12
• Pfam ID: PF05903
• Sequence:
  MGANQLVVLNVYDMYWMNEYTSSIGIGVFHSGIEVYGREFAYGGHPYPFSGIFEISPGNA
  SELGETFKFKEAVVLGSTDFLEDDIEKIVEELGKEYKGNAYHLMHKNCNHFSSALSEILC
  GKEIPRWINRLAYFSSCIPFLQSCLPKEWLTPAALQSSVSQELQDELEEAEDAAASASVA
  STAAGSRPGRHTKL
• Function: Has deubiquitinating activity towards 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains. Deubiquitinates 'Lys-48'-linked polyubiquitination of RPS7 leading to its stabilization. Exhibits palmitoyl protein thioesterase (S-depalmitoylation) activity towards synthetic substrates 4-methylumbelliferyl-6-S-palmitoyl-beta-D-glucopyranoside and S-depalmitoylation probe 5 (DPP-5).

Molecular Interaction Atlas (MIA) of This DOT

19 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Definitive	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[3]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[4]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[5]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[6]
Lung cancer	DISCM4YA	Strong	Genetic Variation	[7]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[7]
Lung neoplasm	DISVARNB	Strong	Altered Expression	[8]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[9]
Neoplasm	DISZKGEW	Strong	Biomarker	[10]
Ovarian cancer	DISZJHAP	Strong	Therapeutic	[4]
Ovarian neoplasm	DISEAFTY	Strong	Therapeutic	[4]
Prostate cancer	DISF190Y	Strong	Biomarker	[11]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[11]
Skin neoplasm	DIS16DDV	Strong	Biomarker	[12]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[5]
Pancreatic cancer	DISJC981	Limited	Biomarker	[13]
Pancreatic ductal carcinoma	DIS26F9Q	Limited	Altered Expression	[14]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Deubiquitinase DESI2 (DESI2).	[15]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Deubiquitinase DESI2 (DESI2).	[29]

14 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 Deubiquitinase DESI2 (DESI2).	[16]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Deubiquitinase DESI2 (DESI2).	[17]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Deubiquitinase DESI2 (DESI2).	[18]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Deubiquitinase DESI2 (DESI2).	[19]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Deubiquitinase DESI2 (DESI2).	[20]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Deubiquitinase DESI2 (DESI2).	[21]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Deubiquitinase DESI2 (DESI2).	[22]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Deubiquitinase DESI2 (DESI2).	[23]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Deubiquitinase DESI2 (DESI2).	[24]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Deubiquitinase DESI2 (DESI2).	[25]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Deubiquitinase DESI2 (DESI2).	[26]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Deubiquitinase DESI2 (DESI2).	[27]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Deubiquitinase DESI2 (DESI2).	[28]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Deubiquitinase DESI2 (DESI2).	[30]

References

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• [5] Epigenetic suppression of the immunoregulator MZB1 is associated with the malignant phenotype of gastric cancer.Int J Cancer. 2016 Nov 15;139(10):2290-8. doi: 10.1002/ijc.30286. Epub 2016 Aug 6.
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• [10] Identification of novel biomarkers of hepatocellular carcinoma by high-definition mass spectrometry: Ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry and desorption electrospray ionization mass spectrometry imaging.Rapid Commun Mass Spectrom. 2020 Apr;34 Suppl 1(Suppl 1):e8551. doi: 10.1002/rcm.8551. Epub 2019 Nov 6.
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• [12] Distinguishing malignant from benign microscopic skin lesions using desorption electrospray ionization mass spectrometry imaging.Proc Natl Acad Sci U S A. 2018 Jun 19;115(25):6347-6352. doi: 10.1073/pnas.1803733115. Epub 2018 Jun 4.
• [13] Desumoylating Isopeptidase 2 (DESI2) Inhibits Proliferation and Promotes Apoptosis of Pancreatic Cancer Cells through Regulating PI3K/AKT/mTOR Signaling Pathway.Pathol Oncol Res. 2019 Apr;25(2):635-646. doi: 10.1007/s12253-018-0487-4. Epub 2018 Nov 8.
• [14] High Phosphorylation Status of AKT/mTOR Signal in DESI2-Reduced Pancreatic Ductal Adenocarcinoma.Pathol Oncol Res. 2015 Apr;21(2):267-72. doi: 10.1007/s12253-014-9817-3. Epub 2014 Jul 31.
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• [17] Retinoic acid-induced downmodulation of telomerase activity in human cancer cells. Exp Mol Pathol. 2005 Oct;79(2):108-17.
• [18] 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.
• [19] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
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• [21] 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.
• [22] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [23] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [24] Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
• [25] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
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• [27] 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.
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• [29] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [30] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.