Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3VFSLG)

DOT Name DDB1- and CUL4-associated factor 8 (DCAF8)
Synonyms WD repeat-containing protein 42A
Gene Name DCAF8
Related Disease
Hereditary motor and sensory neuropathy ( )
Cardiomyopathy ( )
Giant axonal neuropathy 2 ( )
UniProt ID
DCAF8_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
3I8E
Pfam ID
PF00400
Sequence
MSSKGSSTDGRTDLANGSLSSSPEEMSGAEEGRETSSGIEVEASDLSLSLTGDDGGPNRT
STESRGTDTESSGEDKDSDSMEDTGHYSINDENRVHDRSEEEEEEEEEEEEEQPRRRVQR
KRANRDQDSSDDERALEDWVSSETSALPRPRWQALPALRERELGSSARFVYEACGARVFV
QRFRLQHGLEGHTGCVNTLHFNQRGTWLASGSDDLKVVVWDWVRRQPVLDFESGHKSNVF
QAKFLPNSGDSTLAMCARDGQVRVAELSATQCCKNTKRVAQHKGASHKLALEPDSPCTFL
SAGEDAVVFTIDLRQDRPASKLVVTKEKEKKVGLYTIYVNPANTHQFAVGGRDQFVRIYD
QRKIDENENNGVLKKFCPHHLVNSESKANITCLVYSHDGTELLASYNDEDIYLFNSSHSD
GAQYVKRYKGHRNNATVKGVNFYGPKSEFVVSGSDCGHIFLWEKSSCQIIQFMEGDKGGV
VNCLEPHPHLPVLATSGLDHDVKIWAPTAEASTELTGLKDVIKKNKRERDEDSLHQTDLF
DSHMLWFLMHHLRQRRHHRRWREPGVGATDADSDESPSSSDTSDEEEGPDRVQCMPS
Function May function as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex.
Reactome Pathway
Neddylation (R-HSA-8951664 )

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Hereditary motor and sensory neuropathy DISR0X2K Strong Genetic Variation [1]
Cardiomyopathy DISUPZRG moderate Genetic Variation [1]
Giant axonal neuropathy 2 DIS4WGVV Supportive Autosomal dominant [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
9 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 DDB1- and CUL4-associated factor 8 (DCAF8). [2]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of DDB1- and CUL4-associated factor 8 (DCAF8). [3]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of DDB1- and CUL4-associated factor 8 (DCAF8). [4]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of DDB1- and CUL4-associated factor 8 (DCAF8). [5]
Estradiol DMUNTE3 Approved Estradiol affects the expression of DDB1- and CUL4-associated factor 8 (DCAF8). [6]
Irinotecan DMP6SC2 Approved Irinotecan decreases the expression of DDB1- and CUL4-associated factor 8 (DCAF8). [7]
Dihydrotestosterone DM3S8XC Phase 4 Dihydrotestosterone increases the expression of DDB1- and CUL4-associated factor 8 (DCAF8). [8]
Tocopherol DMBIJZ6 Phase 2 Tocopherol increases the expression of DDB1- and CUL4-associated factor 8 (DCAF8). [9]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of DDB1- and CUL4-associated factor 8 (DCAF8). [10]
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⏷ Show the Full List of 9 Drug(s)

References

1 Ubiquitin ligase defect by DCAF8 mutation causes HMSN2 with giant axons. Neurology. 2014 Mar 11;82(10):873-8. doi: 10.1212/WNL.0000000000000206. Epub 2014 Feb 5.
2 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.
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 Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
7 Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
8 LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
9 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.
10 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.