Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVG2MYF)

DOT Name E3 ubiquitin-protein ligase Jade-2 (JADE2)
Synonyms EC 2.3.2.27; Jade family PHD finger protein 2; PHD finger protein 15
Gene Name JADE2
Related Disease
Prostate cancer ( )
Prostate neoplasm ( )
Bipolar disorder ( )
Non-insulin dependent diabetes ( )
UniProt ID
JADE2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
2.3.2.27
Pfam ID
PF10513 ; PF13831 ; PF13832
Sequence
MEEKRRKYSISSDNSDTTDSHATSTSASRCSKLPSSTKSGWPRQNEKKPSEVFRTDLITA
MKIPDSYQLSPDDYYILADPWRQEWEKGVQVPAGAEAIPEPVVRILPPLEGPPAQASPSS
TMLGEGSQPDWPGGSRYDLDEIDAYWLELINSELKEMERPELDELTLERVLEELETLCHQ
NMARAIETQEGLGIEYDEDVVCDVCRSPEGEDGNEMVFCDKCNVCVHQACYGILKVPTGS
WLCRTCALGVQPKCLLCPKRGGALKPTRSGTKWVHVSCALWIPEVSIGCPEKMEPITKIS
HIPASRWALSCSLCKECTGTCIQCSMPSCVTAFHVTCAFDHGLEMRTILADNDEVKFKSF
CQEHSDGGPRNEPTSEPTEPSQAGEDLEKVTLRKQRLQQLEEDFYELVEPAEVAERLDLA
EALVDFIYQYWKLKRKANANQPLLTPKTDEVDNLAQQEQDVLYRRLKLFTHLRQDLERVR
NLCYMVTRRERTKHAICKLQEQIFHLQMKLIEQDLCRGLSTSFPIDGTFFNSWLAQSVQI
TAENMAMSEWPLNNGHREDPAPGLLSEELLQDEETLLSFMRDPSLRPGDPARKARGRTRL
PAKKKPPPPPPQDGPGSRTTPDKAPKKTWGQDAGSGKGGQGPPTRKPPRRTSSHLPSSPA
AGDCPILATPESPPPLAPETPDEAASVAADSDVQVPGPAASPKPLGRLRPPRESKVTRRL
PGARPDAGMGPPSAVAERPKVSLHFDTETDGYFSDGEMSDSDVEAEDGGVQRGPREAGAE
EVVRMGVLAS
Function
Scaffold subunit of some HBO1 complexes, which have a histone H4 acetyltransferase activity. Acts as an E3 ubiquitin-protein ligase mediating the ubiquitination and subsequent proteasomal degradation of target protein histone demethylase KDM1A. Also acts as a ubiquitin ligase E3 toward itself. Positive regulator of neurogenesis.
Reactome Pathway
HATs acetylate histones (R-HSA-3214847 )

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Prostate cancer DISF190Y Strong Biomarker [1]
Prostate neoplasm DISHDKGQ Strong Biomarker [1]
Bipolar disorder DISAM7J2 Limited Genetic Variation [2]
Non-insulin dependent diabetes DISK1O5Z Limited Genetic Variation [3]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
16 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of E3 ubiquitin-protein ligase Jade-2 (JADE2). [4]
Tretinoin DM49DUI Approved Tretinoin increases the expression of E3 ubiquitin-protein ligase Jade-2 (JADE2). [5]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of E3 ubiquitin-protein ligase Jade-2 (JADE2). [6]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of E3 ubiquitin-protein ligase Jade-2 (JADE2). [7]
Panobinostat DM58WKG Approved Panobinostat increases the expression of E3 ubiquitin-protein ligase Jade-2 (JADE2). [8]
Niclosamide DMJAGXQ Approved Niclosamide increases the expression of E3 ubiquitin-protein ligase Jade-2 (JADE2). [9]
Melphalan DMOLNHF Approved Melphalan decreases the expression of E3 ubiquitin-protein ligase Jade-2 (JADE2). [10]
2-deoxyglucose DMIAHVU Approved 2-deoxyglucose increases the expression of E3 ubiquitin-protein ligase Jade-2 (JADE2). [7]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of E3 ubiquitin-protein ligase Jade-2 (JADE2). [8]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of E3 ubiquitin-protein ligase Jade-2 (JADE2). [11]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of E3 ubiquitin-protein ligase Jade-2 (JADE2). [12]
Scriptaid DM9JZ21 Preclinical Scriptaid decreases the expression of E3 ubiquitin-protein ligase Jade-2 (JADE2). [7]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of E3 ubiquitin-protein ligase Jade-2 (JADE2). [4]
Acetaldehyde DMJFKG4 Investigative Acetaldehyde decreases the expression of E3 ubiquitin-protein ligase Jade-2 (JADE2). [15]
methyl p-hydroxybenzoate DMO58UW Investigative methyl p-hydroxybenzoate decreases the expression of E3 ubiquitin-protein ligase Jade-2 (JADE2). [16]
DZNep DM0JXBK Investigative DZNep increases the expression of E3 ubiquitin-protein ligase Jade-2 (JADE2). [7]
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⏷ Show the Full List of 16 Drug(s)
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 increases the phosphorylation of E3 ubiquitin-protein ligase Jade-2 (JADE2). [13]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of E3 ubiquitin-protein ligase Jade-2 (JADE2). [14]
Coumarin DM0N8ZM Investigative Coumarin affects the phosphorylation of E3 ubiquitin-protein ligase Jade-2 (JADE2). [13]
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References

1 The long tail of oncogenic drivers in prostate cancer.Nat Genet. 2018 May;50(5):645-651. doi: 10.1038/s41588-018-0078-z. Epub 2018 Apr 2.
2 Genome-wide association study identifies 30 loci associated with bipolar disorder.Nat Genet. 2019 May;51(5):793-803. doi: 10.1038/s41588-019-0397-8. Epub 2019 May 1.
3 Identification of new susceptibility loci for type 2 diabetes and shared etiological pathways with coronary heart disease.Nat Genet. 2017 Oct;49(10):1450-1457. doi: 10.1038/ng.3943. Epub 2017 Sep 4.
4 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.
5 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
6 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
7 Development and validation of the TGx-HDACi transcriptomic biomarker to detect histone deacetylase inhibitors in human TK6 cells. Arch Toxicol. 2021 May;95(5):1631-1645. doi: 10.1007/s00204-021-03014-2. Epub 2021 Mar 26.
8 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.
9 Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
10 Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
11 New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
12 Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
13 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.
14 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
15 Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
16 Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.