Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGX30AO)

DOT Name E3 ubiquitin-protein ligase DTX4 (DTX4)
Synonyms EC 2.3.2.27; Protein deltex-4; Deltex4; RING finger protein 155; RING-type E3 ubiquitin transferase DTX4
Gene Name DTX4
Related Disease
Wilms tumor ( )
UniProt ID
DTX4_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
PF18102 ; PF02825 ; PF00097
Sequence
MLLASAVVVWEWLNEHGRWRPYSPAVSHHIEAVVRAGPRAGGSVVLGQVDSRLAPYIIDL
QSMNQFRQDTGTLRPVRRNYYDPSSAPGKGVVWEWENDNGSWTPYDMEVGITIQHAYEKQ
HPWIDLTSIGFSYVIDFNTMGQINRQTQRQRRVRRRLDLIYPMVTGTLPKAQSWPVSPGP
ATSPPMSPCSCPQCVLVMSVKAAVVNGSTGPLQLPVTRKNMPPPGVVKLPPLPGSGAKPL
DSTGTIRGPLKTAPSQVIRRQASSMPTGTTMGSPASPPGPNSKTGRVALATLNRTNLQRL
AIAQSRVLIASGVPTVPVKNLNGSSPVNPALAGITGILMSAAGLPVCLTRPPKLVLHPPP
VSKSEIKSIPGVSNTSRKTTKKQAKKGKTPEEVLKKYLQKVRHPPDEDCTICMERLTAPS
GYKGPQPTVKPDLVGKLSRCGHVYHIYCLVAMYNNGNKDGSLQCPTCKTIYGVKTGTQPP
GKMEYHLIPHSLPGHPDCKTIRIIYSIPPGIQGPEHPNPGKSFSARGFPRHCYLPDSEKG
RKVLKLLLVAWDRRLIFAIGTSSTTGESDTVIWNEVHHKTEFGSNLTGHGYPDANYLDNV
LAELAAQGISEDSTAQEKD
Function
Regulator of Notch signaling, a signaling pathway involved in cell-cell communications that regulates a broad spectrum of cell-fate determinations. Functions as a ubiquitin ligase protein in vivo, mediating 'Lys48'-linked polyubiquitination and promoting degradation of TBK1, targeting to TBK1 requires interaction with NLRP4.
KEGG Pathway
Notch sig.ling pathway (hsa04330 )
Reactome Pathway
Activated NOTCH1 Transmits Signal to the Nucleus (R-HSA-2122948 )
Regulation of innate immune responses to cytosolic DNA (R-HSA-3134975 )
IRF3-mediated induction of type I IFN (R-HSA-3270619 )
IRF3 mediated activation of type 1 IFN (R-HSA-1606341 )

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Wilms tumor DISB6T16 Strong Genetic Variation [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
14 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 DTX4 (DTX4). [2]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of E3 ubiquitin-protein ligase DTX4 (DTX4). [3]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of E3 ubiquitin-protein ligase DTX4 (DTX4). [4]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of E3 ubiquitin-protein ligase DTX4 (DTX4). [5]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of E3 ubiquitin-protein ligase DTX4 (DTX4). [6]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of E3 ubiquitin-protein ligase DTX4 (DTX4). [7]
Azathioprine DMMZSXQ Approved Azathioprine decreases the expression of E3 ubiquitin-protein ligase DTX4 (DTX4). [8]
Amphotericin B DMTAJQE Approved Amphotericin B decreases the expression of E3 ubiquitin-protein ligase DTX4 (DTX4). [9]
Enzalutamide DMGL19D Approved Enzalutamide affects the expression of E3 ubiquitin-protein ligase DTX4 (DTX4). [10]
Genistein DM0JETC Phase 2/3 Genistein increases the expression of E3 ubiquitin-protein ligase DTX4 (DTX4). [11]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of E3 ubiquitin-protein ligase DTX4 (DTX4). [12]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide decreases the expression of E3 ubiquitin-protein ligase DTX4 (DTX4). [13]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of E3 ubiquitin-protein ligase DTX4 (DTX4). [14]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of E3 ubiquitin-protein ligase DTX4 (DTX4). [15]
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⏷ Show the Full List of 14 Drug(s)

References

1 Combined Methylome and Transcriptome Analysis During Rat Hepatic Stellate Cell Activation.Stem Cells Dev. 2017 Dec 15;26(24):1759-1770. doi: 10.1089/scd.2017.0128. Epub 2017 Nov 28.
2 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.
3 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.
4 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.
5 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.
6 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
7 Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
8 A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
9 Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
10 NOTCH signaling is activated in and contributes to resistance in enzalutamide-resistant prostate cancer cells. J Biol Chem. 2019 May 24;294(21):8543-8554. doi: 10.1074/jbc.RA118.006983. Epub 2019 Apr 2.
11 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.
12 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.
13 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
14 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.
15 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.