Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS93PPZ)

• DOT Name: Differentially expressed in FDCP 8 homolog (DEF8)
• Synonyms: DEF-8
• Gene Name: DEF8
• Related Disease:
  Melanoma
  Crohn disease
  Squamous cell carcinoma
  Vitiligo
  Cutaneous squamous cell carcinoma
• UniProt ID: DEFI8_HUMAN
• Pfam ID: PF00130 ; PF13901
• Sequence:
  MAILSLRAPGPWQAMQVWADRTLLTPHTGVTSQVLGVAAAVMTPLPGGHAAGRTREARWD
  AMEYDEKLARFRQAHLNPFNKQSGPRQHEQGPGEEVPDVTPEEALPELPPGEPEFRCPER
  VMDLGLSEDHFSRPVGLFLASDVQQLRQAIEECKQVILELPEQSEKQKDAVVRLIHLRLK
  LQELKDPNEDEPNIRVLLEHRFYKEKSKSVKQTCDKCNTIIWGLIQTWYTCTGCYYRCHS
  KCLNLISKPCVSSKVSHQAEYELNICPETGLDSQDYRCAECRAPISLRGVPSEARQCDYT
  GQYYCSHCHWNDLAVIPARVVHNWDFEPRKVSRCSMRYLALMVSRPVLRLREINPLLFSY
  VEELVEIRKLRQDILLMKPYFITCREAMEARLLLQLQDRQHFVENDEMYSVQDLLDVHAG
  RLGCSLTEIHTLFAKHIKLDCERCQAKGFVCELCREGDVLFPFDSHTSVCADCSAVFHRD
  CYYDNSTTCPKCARLSLRKQSLFQEPGPDVEA
• Function: Positively regulates lysosome peripheral distribution and ruffled border formation in osteoclasts. Involved in bone resorption.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Melanoma	DIS1RRCY	Definitive	Genetic Variation	[1]
Crohn disease	DIS2C5Q8	Strong	Altered Expression	[2]
Squamous cell carcinoma	DISQVIFL	Strong	Genetic Variation	[3]
Vitiligo	DISR05SL	Strong	Genetic Variation	[4]
Cutaneous squamous cell carcinoma	DIS3LXUG	Limited	Genetic Variation	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Differentially expressed in FDCP 8 homolog (DEF8).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Differentially expressed in FDCP 8 homolog (DEF8).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Differentially expressed in FDCP 8 homolog (DEF8).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Differentially expressed in FDCP 8 homolog (DEF8).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Differentially expressed in FDCP 8 homolog (DEF8).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin increases the expression of Differentially expressed in FDCP 8 homolog (DEF8).	[10]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Differentially expressed in FDCP 8 homolog (DEF8).	[11]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Differentially expressed in FDCP 8 homolog (DEF8).	[12]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Differentially expressed in FDCP 8 homolog (DEF8).	[13]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Differentially expressed in FDCP 8 homolog (DEF8).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Differentially expressed in FDCP 8 homolog (DEF8).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Differentially expressed in FDCP 8 homolog (DEF8).	[16]

References

• [1] Genome-wide association study identifies novel loci predisposing to cutaneous melanoma.Hum Mol Genet. 2011 Dec 15;20(24):5012-23. doi: 10.1093/hmg/ddr415. Epub 2011 Sep 17.
• [2] Gene expression and thiopurine metabolite profiling in inflammatory bowel disease - novel clues to drug targets and disease mechanisms?.PLoS One. 2013;8(2):e56989. doi: 10.1371/journal.pone.0056989. Epub 2013 Feb 21.
• [3] Identification of Susceptibility Loci for Cutaneous Squamous Cell Carcinoma.J Invest Dermatol. 2016 May;136(5):930-937. doi: 10.1016/j.jid.2016.01.013. Epub 2016 Jan 29.
• [4] Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants.Nat Genet. 2016 Nov;48(11):1418-1424. doi: 10.1038/ng.3680. Epub 2016 Oct 10.
• [5] A Genome-Wide Association Study of Cutaneous Squamous Cell Carcinoma among European Descendants.Cancer Epidemiol Biomarkers Prev. 2016 Apr;25(4):714-20. doi: 10.1158/1055-9965.EPI-15-1070. Epub 2016 Feb 12.
• [6] 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.
• [7] Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling. Toxicol Sci. 2012 Mar;126(1):101-13.
• [8] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [9] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [10] 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.
• [11] 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.
• [12] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [13] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [14] 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.
• [15] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [16] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.