General Information of Drug Off-Target (DOT) (ID: OTH96RA7)

DOT Name Dual specificity protein phosphatase 5 (DUSP5)
Synonyms EC 3.1.3.16; EC 3.1.3.48; Dual specificity protein phosphatase hVH3
Gene Name DUSP5
UniProt ID
DUS5_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2G6Z
EC Number
3.1.3.16; 3.1.3.48
Pfam ID
PF00782 ; PF00581
Sequence
MKVTSLDGRQLRKMLRKEAAARCVVLDCRPYLAFAASNVRGSLNVNLNSVVLRRARGGAV
SARYVLPDEAARARLLQEGGGGVAAVVVLDQGSRHWQKLREESAARVVLTSLLACLPAGP
RVYFLKGGYETFYSEYPECCVDVKPISQEKIESERALISQCGKPVVNVSYRPAYDQGGPV
EILPFLYLGSAYHASKCEFLANLHITALLNVSRRTSEACATHLHYKWIPVEDSHTADISS
HFQEAIDFIDCVREKGGKVLVHCEAGISRSPTICMAYLMKTKQFRLKEAFDYIKQRRSMV
SPNFGFMGQLLQYESEILPSTPNPQPPSCQGEAAGSSLIGHLQTLSPDMQGAYCTFPASV
LAPVPTHSTVSELSRSPVATATSC
Function Dual specificity protein phosphatase; active with phosphotyrosine, phosphoserine and phosphothreonine residues. The highest relative activity is toward ERK1.
KEGG Pathway
MAPK sig.ling pathway (hsa04010 )
Efferocytosis (hsa04148 )
Reactome Pathway
Negative regulation of MAPK pathway (R-HSA-5675221 )
RAF-independent MAPK1/3 activation (R-HSA-112409 )

Molecular Interaction Atlas (MIA) of This DOT

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 Dual specificity protein phosphatase 5 (DUSP5). [1]
TAK-243 DM4GKV2 Phase 1 TAK-243 increases the sumoylation of Dual specificity protein phosphatase 5 (DUSP5). [34]
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51 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 Dual specificity protein phosphatase 5 (DUSP5). [2]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Dual specificity protein phosphatase 5 (DUSP5). [3]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Dual specificity protein phosphatase 5 (DUSP5). [4]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Dual specificity protein phosphatase 5 (DUSP5). [5]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Dual specificity protein phosphatase 5 (DUSP5). [6]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Dual specificity protein phosphatase 5 (DUSP5). [7]
Quercetin DM3NC4M Approved Quercetin increases the expression of Dual specificity protein phosphatase 5 (DUSP5). [8]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of Dual specificity protein phosphatase 5 (DUSP5). [9]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of Dual specificity protein phosphatase 5 (DUSP5). [10]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide increases the expression of Dual specificity protein phosphatase 5 (DUSP5). [11]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Dual specificity protein phosphatase 5 (DUSP5). [12]
Testosterone DM7HUNW Approved Testosterone increases the expression of Dual specificity protein phosphatase 5 (DUSP5). [13]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Dual specificity protein phosphatase 5 (DUSP5). [14]
Decitabine DMQL8XJ Approved Decitabine affects the expression of Dual specificity protein phosphatase 5 (DUSP5). [15]
Zoledronate DMIXC7G Approved Zoledronate decreases the expression of Dual specificity protein phosphatase 5 (DUSP5). [16]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of Dual specificity protein phosphatase 5 (DUSP5). [17]
Progesterone DMUY35B Approved Progesterone increases the expression of Dual specificity protein phosphatase 5 (DUSP5). [18]
Panobinostat DM58WKG Approved Panobinostat increases the expression of Dual specificity protein phosphatase 5 (DUSP5). [19]
Demecolcine DMCZQGK Approved Demecolcine increases the expression of Dual specificity protein phosphatase 5 (DUSP5). [20]
Cannabidiol DM0659E Approved Cannabidiol increases the expression of Dual specificity protein phosphatase 5 (DUSP5). [21]
Hydroquinone DM6AVR4 Approved Hydroquinone increases the expression of Dual specificity protein phosphatase 5 (DUSP5). [22]
Rosiglitazone DMILWZR Approved Rosiglitazone increases the expression of Dual specificity protein phosphatase 5 (DUSP5). [6]
Azathioprine DMMZSXQ Approved Azathioprine increases the expression of Dual specificity protein phosphatase 5 (DUSP5). [23]
Malathion DMXZ84M Approved Malathion increases the expression of Dual specificity protein phosphatase 5 (DUSP5). [24]
Ethinyl estradiol DMODJ40 Approved Ethinyl estradiol increases the expression of Dual specificity protein phosphatase 5 (DUSP5). [25]
Cidofovir DMA13GD Approved Cidofovir increases the expression of Dual specificity protein phosphatase 5 (DUSP5). [6]
Fenofibrate DMFKXDY Approved Fenofibrate increases the expression of Dual specificity protein phosphatase 5 (DUSP5). [6]
Ibuprofen DM8VCBE Approved Ibuprofen increases the expression of Dual specificity protein phosphatase 5 (DUSP5). [6]
Bexarotene DMOBIKY Approved Bexarotene decreases the expression of Dual specificity protein phosphatase 5 (DUSP5). [26]
Febuxostat DMDEXQ0 Approved Febuxostat increases the expression of Dual specificity protein phosphatase 5 (DUSP5). [27]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Dual specificity protein phosphatase 5 (DUSP5). [28]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Dual specificity protein phosphatase 5 (DUSP5). [19]
Curcumin DMQPH29 Phase 3 Curcumin increases the expression of Dual specificity protein phosphatase 5 (DUSP5). [29]
Seocalcitol DMKL9QO Phase 3 Seocalcitol increases the expression of Dual specificity protein phosphatase 5 (DUSP5). [30]
Genistein DM0JETC Phase 2/3 Genistein decreases the expression of Dual specificity protein phosphatase 5 (DUSP5). [31]
Afimoxifene DMFORDT Phase 2 Afimoxifene increases the expression of Dual specificity protein phosphatase 5 (DUSP5). [7]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Dual specificity protein phosphatase 5 (DUSP5). [8]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Dual specificity protein phosphatase 5 (DUSP5). [32]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide increases the expression of Dual specificity protein phosphatase 5 (DUSP5). [33]
AMEP DMFELMQ Phase 1 AMEP increases the expression of Dual specificity protein phosphatase 5 (DUSP5). [35]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Dual specificity protein phosphatase 5 (DUSP5). [36]
THAPSIGARGIN DMDMQIE Preclinical THAPSIGARGIN decreases the expression of Dual specificity protein phosphatase 5 (DUSP5). [37]
Bisphenol A DM2ZLD7 Investigative Bisphenol A affects the expression of Dual specificity protein phosphatase 5 (DUSP5). [38]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Dual specificity protein phosphatase 5 (DUSP5). [39]
Milchsaure DM462BT Investigative Milchsaure affects the expression of Dual specificity protein phosphatase 5 (DUSP5). [40]
Sulforaphane DMQY3L0 Investigative Sulforaphane increases the expression of Dual specificity protein phosphatase 5 (DUSP5). [41]
chloropicrin DMSGBQA Investigative chloropicrin increases the expression of Dual specificity protein phosphatase 5 (DUSP5). [42]
Glyphosate DM0AFY7 Investigative Glyphosate affects the expression of Dual specificity protein phosphatase 5 (DUSP5). [35]
Phencyclidine DMQBEYX Investigative Phencyclidine increases the expression of Dual specificity protein phosphatase 5 (DUSP5). [43]
Resorcinol DMM37C0 Investigative Resorcinol increases the expression of Dual specificity protein phosphatase 5 (DUSP5). [23]
Bilirubin DMI0V4O Investigative Bilirubin increases the expression of Dual specificity protein phosphatase 5 (DUSP5). [44]
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⏷ Show the Full List of 51 Drug(s)

References

1 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.
2 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.
3 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
4 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
5 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
6 Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
7 Estrogenic GPR30 signalling induces proliferation and migration of breast cancer cells through CTGF. EMBO J. 2009 Mar 4;28(5):523-32.
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 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.
10 Different pathways are involved in arsenic-trioxide-induced cell proliferation and growth inhibition in human keratinocytes. Skin Pharmacol Physiol. 2010;23(2):68-78. doi: 10.1159/000265677. Epub 2009 Dec 14.
11 Novel functional view of the crocidolite asbestos-treated A549 human lung epithelial transcriptome reveals an intricate network of pathways with opposing functions. BMC Genomics. 2008 Aug 7;9:376.
12 Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
13 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
14 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
15 Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
16 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
17 Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
18 Gene expression in endometrial cancer cells (Ishikawa) after short time high dose exposure to progesterone. Steroids. 2008 Jan;73(1):116-28.
19 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
20 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
21 Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
22 Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
23 A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
24 Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
25 The genomic response of a human uterine endometrial adenocarcinoma cell line to 17alpha-ethynyl estradiol. Toxicol Sci. 2009 Jan;107(1):40-55.
26 Identification of biomarkers modulated by the rexinoid LGD1069 (bexarotene) in human breast cells using oligonucleotide arrays. Cancer Res. 2006 Dec 15;66(24):12009-18.
27 Febuxostat Increases Ventricular Arrhythmogenesis Through Calcium Handling Dysregulation in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes. Toxicol Sci. 2022 Sep 24;189(2):216-224. doi: 10.1093/toxsci/kfac073.
28 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
29 Gene-expression profiling during curcumin-induced apoptosis reveals downregulation of CXCR4. Exp Hematol. 2007 Jan;35(1):84-95.
30 Expression profiling in squamous carcinoma cells reveals pleiotropic effects of vitamin D3 analog EB1089 signaling on cell proliferation, differentiation, and immune system regulation. Mol Endocrinol. 2002 Jun;16(6):1243-56.
31 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.
32 Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
33 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
34 Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
35 Glyphosate-based herbicides at low doses affect canonical pathways in estrogen positive and negative breast cancer cell lines. PLoS One. 2019 Jul 11;14(7):e0219610. doi: 10.1371/journal.pone.0219610. eCollection 2019.
36 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.
37 Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.
38 The genomic response of Ishikawa cells to bisphenol A exposure is dose- and time-dependent. Toxicology. 2010 Apr 11;270(2-3):137-49. doi: 10.1016/j.tox.2010.02.008. Epub 2010 Feb 17.
39 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
40 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
41 Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.
42 Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
43 Differential response of Mono Mac 6, BEAS-2B, and Jurkat cells to indoor dust. Environ Health Perspect. 2007 Sep;115(9):1325-32.
44 Global changes in gene regulation demonstrate that unconjugated bilirubin is able to upregulate and activate select components of the endoplasmic reticulum stress response pathway. J Biochem Mol Toxicol. 2010 Mar-Apr;24(2):73-88.