Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUGGD6M)

• DOT Name: DDB1- and CUL4-associated factor 10 (DCAF10)
• Synonyms: WD repeat-containing protein 32
• Gene Name: DCAF10
• UniProt ID: DCA10_HUMAN
• Pfam ID: PF00400
• Sequence:
  MFPFGPHSPGGDGSAGAGAEEPTPHEGQAAATGPPSPLHPGADATHPPPPARSPRRPGAP
  SLSPAPRSGELGLPGAPESSTASAPGEPSPPSPPCRRPGPDCRAKSRGRHGLGAGLGGPG
  ARLFGWLKERSLGRGLFVDPARDNFRTMTSLYGSIHPADSVYLSTRTHGAVFNLEYSPDG
  SVLTVACEQTEVLLFDPISSKHIKTLSEAHEDCVNNIRFLDNRLFATCSDDTTIALWDLR
  KLNTKVCTLHGHTSWVKNIEYDTNTRLLVTSGFDGNVIIWDTNRYTEDGCPHKKFFHTRF
  LMRMRLTPDCSKMLISTSSGYLLILHDLDLTKSLEVGSYPILRARRTTSSSDLTTSSSSS
  GPRVSGSPCHHSDSNSSEKHMSRASQREGVSPRNSLEVVTPEVLGESDHGNCITSLQLHP
  KGWATLLRCSSNSDDEECTCVYEFQEGAPVRPVSPRCSLRLTHYIEEANVGRGYIKELCF
  SPDGRMISSPHGYGIRLLGFDKQCSELVDCLPKEASPLRVIRSLYSHNDVVLTTKFSPTH
  CQIASGCLSGRVSLYQPKF
• 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

8 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of DDB1- and CUL4-associated factor 10 (DCAF10).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of DDB1- and CUL4-associated factor 10 (DCAF10).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of DDB1- and CUL4-associated factor 10 (DCAF10).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of DDB1- and CUL4-associated factor 10 (DCAF10).	[4]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of DDB1- and CUL4-associated factor 10 (DCAF10).	[5]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of DDB1- and CUL4-associated factor 10 (DCAF10).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of DDB1- and CUL4-associated factor 10 (DCAF10).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of DDB1- and CUL4-associated factor 10 (DCAF10).	[9]

2 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 decreases the phosphorylation of DDB1- and CUL4-associated factor 10 (DCAF10).	[8]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of DDB1- and CUL4-associated factor 10 (DCAF10).	[8]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [3] 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.
• [4] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [5] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [6] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [7] 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.
• [8] 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.
• [9] 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.