Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3W5DYL)

• DOT Name: DDB1- and CUL4-associated factor 7 (DCAF7)
• Synonyms: WD repeat-containing protein 68; WD repeat-containing protein An11 homolog
• Gene Name: DCAF7
• Related Disease:
  Alzheimer disease
  Smallpox
  Status epilepticus seizure
• UniProt ID: DCAF7_HUMAN
• Pfam ID: PF00400
• Sequence:
  MSLHGKRKEIYKYEAPWTVYAMNWSVRPDKRFRLALGSFVEEYNNKVQLVGLDEESSEFI
  CRNTFDHPYPTTKLMWIPDTKGVYPDLLATSGDYLRVWRVGETETRLECLLNNNKNSDFC
  APLTSFDWNEVDPYLLGTSSIDTTCTIWGLETGQVLGRVNLVSGHVKTQLIAHDKEVYDI
  AFSRAGGGRDMFASVGADGSVRMFDLRHLEHSTIIYEDPQHHPLLRLCWNKQDPNYLATM
  AMDGMEVVILDVRVPCTPVARLNNHRACVNGIAWAPHSSCHICTAADDHQALIWDIQQMP
  RAIEDPILAYTAEGEINNVQWASTQPDWIAICYNNCLEILRV
• Function: Involved in craniofacial development. Acts upstream of the EDN1 pathway and is required for formation of the upper jaw equivalent, the palatoquadrate. The activity required for EDN1 pathway function differs between the first and second arches. Associates with DIAPH1 and controls GLI1 transcriptional activity. Could be involved in normal and disease skin development. May function as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex.
• KEGG Pathway: Polycomb repressive complex (hsa03083)
• Reactome Pathway:
  Neddylation (R-HSA-8951664)
  Association of TriC/CCT with target proteins during biosynthesis (R-HSA-390471)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[1]
Smallpox	DIS9EABZ	Strong	Biomarker	[2]
Status epilepticus seizure	DISY3BIC	Strong	Biomarker	[3]

10 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 7 (DCAF7).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of DDB1- and CUL4-associated factor 7 (DCAF7).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of DDB1- and CUL4-associated factor 7 (DCAF7).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of DDB1- and CUL4-associated factor 7 (DCAF7).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of DDB1- and CUL4-associated factor 7 (DCAF7).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of DDB1- and CUL4-associated factor 7 (DCAF7).	[10]
Marinol	DM70IK5	Approved	Marinol increases the expression of DDB1- and CUL4-associated factor 7 (DCAF7).	[11]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of DDB1- and CUL4-associated factor 7 (DCAF7).	[10]
APR-246	DMNFADH	Phase 2	APR-246 affects the expression of DDB1- and CUL4-associated factor 7 (DCAF7).	[12]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of DDB1- and CUL4-associated factor 7 (DCAF7).	[14]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of DDB1- and CUL4-associated factor 7 (DCAF7).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of DDB1- and CUL4-associated factor 7 (DCAF7).	[13]

References

• [1] Family-based association analyses of imputed genotypes reveal genome-wide significant association of Alzheimer's disease with OSBPL6, PTPRG, and PDCL3.Mol Psychiatry. 2016 Nov;21(11):1608-1612. doi: 10.1038/mp.2015.218. Epub 2016 Feb 2.
• [2] Controlling orthopoxvirus infections--200 years after Jenner's revolutionary immunization.Arch Immunol Ther Exp (Warsz). 1996;44(5-6):373-8.
• [3] Associations between periodic social events and status epilepticus-An 11-year cohort study.Epilepsia. 2018 Jul;59(7):1381-1391. doi: 10.1111/epi.14431. Epub 2018 May 25.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [8] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [9] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [10] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [11] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [12] Mutant p53 reactivation by PRIMA-1MET induces multiple signaling pathways converging on apoptosis. Oncogene. 2010 Mar 4;29(9):1329-38. doi: 10.1038/onc.2009.425. Epub 2009 Nov 30.
• [13] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [14] Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.