Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFNIW98)

DOT Name Desumoylating isopeptidase 1 (DESI1)
Synonyms DeSI-1; EC 3.4.-.-; PPPDE peptidase domain-containing protein 2; Palmitoyl protein thioesterase DESI1; EC 3.1.2.22; Polyubiquitinated substrate transporter; POST; S-depalmitoylase DESI1
Gene Name DESI1
Related Disease
Laron syndrome ( )
Advanced cancer ( )
Analgesia ( )
Atopic dermatitis ( )
Atrial fibrillation ( )
Autism ( )
Depression ( )
Epilepsy ( )
Gastric cancer ( )
Growth delay due to insulin-like growth factor type 1 deficiency ( )
Hemolytic-uremic syndrome ( )
Inborn error of immunity ( )
Kidney failure ( )
Leukemia ( )
Mucopolysaccharidosis II ( )
Myotonic dystrophy ( )
Neoplasm ( )
Non-insulin dependent diabetes ( )
Obesity ( )
Polycystic ovarian syndrome ( )
Schizophrenia ( )
Stomach cancer ( )
Coronary atherosclerosis ( )
Myocardial ischemia ( )
Pancreatic cancer ( )
Sensorineural hearing loss disorder ( )
Werner syndrome ( )
Acute myelogenous leukaemia ( )
Breast cancer ( )
Breast carcinoma ( )
Colorectal carcinoma ( )
Hyperglycemia ( )
Metastatic melanoma ( )
Occipital horn syndrome ( )
Overhydrated hereditary stomatocytosis ( )
Prostate cancer ( )
Prostate carcinoma ( )
Type-1 diabetes ( )
Type-1/2 diabetes ( )
UniProt ID
DESI1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
3EBQ
EC Number
3.1.2.22; 3.4.-.-
Pfam ID
PF05903
Sequence
MEPPNLYPVKLYVYDLSKGLARRLSPIMLGKQLEGIWHTSIVVHKDEFFFGSGGISSCPP
GGTLLGPPDSVVDVGSTEVTEEIFLEYLSSLGESLFRGEAYNLFEHNCNTFSNEVAQFLT
GRKIPSYITDLPSEVLSTPFGQALRPLLDSIQIQPPGGSSVGRPNGQS
Function
Protease which deconjugates SUMO1, SUMO2 and SUMO3 from some substrate proteins. Has isopeptidase but not SUMO-processing activity. Desumoylates ZBTB46. Collaborates with UBQLN4 in the export of ubiquitinated proteins from the nucleus to the cytoplasm. 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

39 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Laron syndrome DISW9H7W Definitive Genetic Variation [1]
Advanced cancer DISAT1Z9 Strong Biomarker [2]
Analgesia DISK3TVI Strong Biomarker [3]
Atopic dermatitis DISTCP41 Strong Biomarker [4]
Atrial fibrillation DIS15W6U Strong Biomarker [5]
Autism DISV4V1Z Strong Biomarker [6]
Depression DIS3XJ69 Strong Genetic Variation [7]
Epilepsy DISBB28L Strong Genetic Variation [8]
Gastric cancer DISXGOUK Strong Altered Expression [9]
Growth delay due to insulin-like growth factor type 1 deficiency DISHA2HH Strong Biomarker [10]
Hemolytic-uremic syndrome DISSCBGW Strong Biomarker [11]
Inborn error of immunity DISNGCMN Strong Biomarker [12]
Kidney failure DISOVQ9P Strong Biomarker [11]
Leukemia DISNAKFL Strong Genetic Variation [13]
Mucopolysaccharidosis II DIS87GLG Strong Altered Expression [14]
Myotonic dystrophy DISNBEMX Strong Biomarker [15]
Neoplasm DISZKGEW Strong Biomarker [16]
Non-insulin dependent diabetes DISK1O5Z Strong Biomarker [17]
Obesity DIS47Y1K Strong Altered Expression [18]
Polycystic ovarian syndrome DISZ2BNG Strong Biomarker [19]
Schizophrenia DISSRV2N Strong Biomarker [20]
Stomach cancer DISKIJSX Strong Altered Expression [9]
Coronary atherosclerosis DISKNDYU moderate Biomarker [21]
Myocardial ischemia DISFTVXF moderate Biomarker [21]
Pancreatic cancer DISJC981 moderate Biomarker [22]
Sensorineural hearing loss disorder DISJV45Z moderate Biomarker [23]
Werner syndrome DISZY45W moderate Biomarker [24]
Acute myelogenous leukaemia DISCSPTN Limited Biomarker [25]
Breast cancer DIS7DPX1 Limited Genetic Variation [26]
Breast carcinoma DIS2UE88 Limited Genetic Variation [26]
Colorectal carcinoma DIS5PYL0 Limited Biomarker [27]
Hyperglycemia DIS0BZB5 Limited Biomarker [28]
Metastatic melanoma DISSL43L Limited Biomarker [29]
Occipital horn syndrome DISBA58S Limited Biomarker [30]
Overhydrated hereditary stomatocytosis DIS6TF7I Limited Biomarker [30]
Prostate cancer DISF190Y Limited Genetic Variation [31]
Prostate carcinoma DISMJPLE Limited Genetic Variation [31]
Type-1 diabetes DIS7HLUB Limited Biomarker [32]
Type-1/2 diabetes DISIUHAP Limited Biomarker [33]
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⏷ Show the Full List of 39 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
1 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 Desumoylating isopeptidase 1 (DESI1). [34]
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7 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 Desumoylating isopeptidase 1 (DESI1). [35]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Desumoylating isopeptidase 1 (DESI1). [36]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Desumoylating isopeptidase 1 (DESI1). [35]
Isotretinoin DM4QTBN Approved Isotretinoin decreases the expression of Desumoylating isopeptidase 1 (DESI1). [37]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Desumoylating isopeptidase 1 (DESI1). [35]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Desumoylating isopeptidase 1 (DESI1). [38]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Desumoylating isopeptidase 1 (DESI1). [39]
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⏷ Show the Full List of 7 Drug(s)

References

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5 Predictors of Direct Oral Anticoagulants Utilization for Thromboembolism Prevention in Atrial Fibrillation.J Pharm Pharm Sci. 2017;20:8-14. doi: 10.18433/J30W4F.
6 Evidence for alterations in stimulatory G proteins and oxytocin levels in children with autism.Psychoneuroendocrinology. 2014 Feb;40:159-69. doi: 10.1016/j.psyneuen.2013.11.014. Epub 2013 Nov 26.
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9 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.
10 Insulin-like growth factor-I deficiency caused by a partial deletion of the IGF-I gene: effects of rhIGF-I therapy.Growth Horm IGF Res. 1999 Jun;9 Suppl B:47-51; discussion 51-2. doi: 10.1016/s1096-6374(99)80081-1.
11 A post-partum hemolytic-uremic-like-syndrome in a patient with pre-eclampsia: description of a clinical case.Transfus Apher Sci. 2006 Feb;34(1):11-4. doi: 10.1016/j.transci.2005.09.007. Epub 2006 Jan 20.
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14 Distribution of heparan sulfate and dermatan sulfate in mucopolysaccharidosis type II mouse tissues pre- and post-enzyme-replacement therapy determined by UPLC-MS/MS.Bioanalysis. 2019 Apr;11(8):727-740. doi: 10.4155/bio-2018-0306. Epub 2019 Apr 17.
15 Receptor and post-receptor abnormalities contribute to insulin resistance in myotonic dystrophy type 1 and type 2 skeletal muscle.PLoS One. 2017 Sep 15;12(9):e0184987. doi: 10.1371/journal.pone.0184987. eCollection 2017.
16 POST-TEXT III and IV Hepatoblastoma: Extended Hepatic Resection Avoids Liver Transplantation in Selected Cases.Ann Surg. 2017 Aug;266(2):318-323. doi: 10.1097/SLA.0000000000001936.
17 Heterogeneity within type II and MODY diabetes.Adv Exp Med Biol. 1985;189:65-87. doi: 10.1007/978-1-4757-1850-8_5.
18 Insulin inhibits leptin receptor signalling in HEK293 cells at the level of janus kinase-2: a potential mechanism for hyperinsulinaemia-associated leptin resistance.Diabetologia. 2001 Sep;44(9):1125-32. doi: 10.1007/s001250100614.
19 Polycystic ovary syndrome is associated with genetic polymorphism in the insulin signaling gene IRS-1 but not ENPP1 in a Japanese population.Life Sci. 2007 Aug 16;81(10):850-4. doi: 10.1016/j.lfs.2007.07.023. Epub 2007 Aug 7.
20 Antipsychotic drug actions on gene modulation and signaling mechanisms.Pharmacol Ther. 2009 Oct;124(1):74-85. doi: 10.1016/j.pharmthera.2009.06.001. Epub 2009 Jun 21.
21 Post receptor determinants of acute platelet response to clopidogrel in patients with symptomatic myocardial ischemia.Vascul Pharmacol. 2015 Feb-Mar;65-66:17-22. doi: 10.1016/j.vph.2014.11.003. Epub 2014 Nov 20.
22 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.
23 Altered Functional Connectivity in Patients With Sloping Sensorineural Hearing Loss.Front Hum Neurosci. 2019 Aug 22;13:284. doi: 10.3389/fnhum.2019.00284. eCollection 2019.
24 Molecular analysis of insulin receptor gene in Werner's syndrome.Diabetes Res Clin Pract. 1994 Dec 31;26(3):171-6. doi: 10.1016/0168-8227(94)90058-2.
25 p91 STAT1 activation in interleukin-3-stimulated primary acute myeloid leukemia cells.Oncogene. 1996 Sep 5;13(5):1017-26.
26 Association between polymorphisms in the thymidylate synthase gene and risk of breast cancer in a Mexican population.Genet Mol Res. 2014 Oct 27;13(4):8749-56. doi: 10.4238/2014.October.27.16.
27 Impact of genetic counseling and testing on colorectal cancer screening behavior.Genet Test. 2002 Winter;6(4):303-6. doi: 10.1089/10906570260471831.
28 Insulin resistance in non-insulin dependent (type II) and insulin dependent (type I) diabetes mellitus.Adv Exp Med Biol. 1985;189:176-205.
29 Survival trends among patients with metastatic melanoma in the pretargeted and the post-targeted era: a US population-based study.Melanoma Res. 2018 Feb;28(1):56-60. doi: 10.1097/CMR.0000000000000394.
30 DNA Methylation Profiling of Blood Monocytes in Patients With Obesity Hypoventilation Syndrome: Effect of Positive Airway Pressure Treatment.Chest. 2016 Jul;150(1):91-101. doi: 10.1016/j.chest.2016.02.648. Epub 2016 Feb 26.
31 Targeting androgen receptor action for prostate cancer treatment: does the post-receptor level provide novel opportunities?.Int J Biol Sci. 2014 Jun 1;10(6):576-87. doi: 10.7150/ijbs.8479. eCollection 2014.
32 Comparison between preprandial vs. postprandial insulin aspart in patients with type 1 diabetes on insulin pump and real-time continuous glucose monitoring.Diabetes Metab Res Rev. 2018 Sep;34(6):e3019. doi: 10.1002/dmrr.3019. Epub 2018 Jun 1.
33 SAFETY AND EFFICACY OF PERSONALIZED GLYCEMIC CONTROL IN CRITICALLY ILL PATIENTS: A 2-YEAR BEFORE AND AFTER INTERVENTIONAL TRIAL.Endocr Pract. 2017 Mar;23(3):318-330. doi: 10.4158/EP161532.OR. Epub 2016 Dec 14.
34 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.
35 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.
36 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
37 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.
38 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.
39 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.