Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNII6GZ)

• DOT Name: Desmocollin-1 (DSC1)
• Synonyms: Cadherin family member 1; Desmosomal glycoprotein 2/3; DG2/DG3
• Gene Name: DSC1
• Related Disease:
  Carcinoma
  Colorectal carcinoma
  Advanced cancer
  Alzheimer disease
  Arteriosclerosis
  Atherosclerosis
  Atopic dermatitis
  Autoimmune disease
  Breast cancer
  Breast carcinoma
  Melanoma
  Neoplasm
  Oral cancer
  Oral lichen planus
  Pemphigus
  Triple negative breast cancer
  Adenocarcinoma
  Colitis
  Colorectal neoplasm
  Periodontitis
  Head-neck squamous cell carcinoma
• UniProt ID: DSC1_HUMAN
• PDB ID: 5IRY
• Pfam ID: PF00028 ; PF08758
• Sequence:
  MALASAAPGSIFCKQLLFSLLVLTLLCDACQKVYLRVPSHLQAETLVGKVNLEECLKSAS
  LIRSSDPAFRILEDGSIYTTHDLILSSERKSFSIFLSDGQRREQQEIKVVLSARENKSPK
  KRHTKDTALKRSKRRWAPIPASLMENSLGPFPQHVQQIQSDAAQNYTIFYSISGPGVDKE
  PFNLFYIEKDTGDIFCTRSIDREKYEQFALYGYATTADGYAPEYPLPLIIKIEDDNDNAP
  YFEHRVTIFTVPENCRSGTSVGKVTATDLDEPDTLHTRLKYKILQQIPDHPKHFSIHPDT
  GVITTTTPFLDREKCDTYQLIMEVRDMGGQPFGLFNTGTITISLEDENDNPPSFTETSYV
  TEVEENRIDVEILRMKVQDQDLPNTPHSKAVYKILQGNENGNFIISTDPNTNEGVLCVVK
  PLNYEVNRQVILQVGVINEAQFSKAASSQTPTMCTTTVTVKIIDSDEGPECHPPVKVIQS
  QDGFPAGQELLGYKALDPEISSGEGLRYQKLGDEDNWFEINQHTGDLRTLKVLDRESKFV
  KNNQYNISVVAVDAVGRSCTGTLVVHLDDYNDHAPQIDKEVTICQNNEDFAVLKPVDPDG
  PENGPPFQFFLDNSASKNWNIEEKDGKTAILRQRQNLDYNYYSVPIQIKDRHGLVATHML
  TVRVCDCSTPSECRMKDKSTRDVRPNVILGRWAILAMVLGSVLLLCILFTCFCVTAKRTV
  KKCFPEDIAQQNLIVSNTEGPGEEVTEANIRLPMQTSNICDTSMSVGTVGGQGIKTQQSF
  EMVKGGYTLDSNKGGGHQTLESVKGVGQGDTGRYAYTDWQSFTQPRLGEKVYLCGQDEEH
  KHCEDYVCSYNYEGKGSLAGSVGCCSDRQEEEGLEFLDHLEPKFRTLAKTCIKK
• Function: Component of intercellular desmosome junctions. Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion. May contribute to epidermal cell positioning (stratification) by mediating differential adhesiveness between cells that express different isoforms. Linked to the keratinization of epithelial tissues.
• Tissue Specificity: Strongly expressed in epidermis, less in lymph node and tongue.
• Reactome Pathway:
  Keratinization (R-HSA-6805567)
  Formation of the cornified envelope (R-HSA-6809371)
  Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

21 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma	DISH9F1N	Definitive	Altered Expression	[1]
Colorectal carcinoma	DIS5PYL0	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[3]
Arteriosclerosis	DISK5QGC	Strong	Altered Expression	[4]
Atherosclerosis	DISMN9J3	Strong	Altered Expression	[4]
Atopic dermatitis	DISTCP41	Strong	Biomarker	[5]
Autoimmune disease	DISORMTM	Strong	Biomarker	[6]
Breast cancer	DIS7DPX1	Strong	Biomarker	[7]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[7]
Melanoma	DIS1RRCY	Strong	Biomarker	[8]
Neoplasm	DISZKGEW	Strong	Biomarker	[7]
Oral cancer	DISLD42D	Strong	Biomarker	[9]
Oral lichen planus	DISVEAJA	Strong	Altered Expression	[9]
Pemphigus	DISZAZ6M	Strong	Biomarker	[10]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[7]
Adenocarcinoma	DIS3IHTY	moderate	Altered Expression	[11]
Colitis	DISAF7DD	moderate	Altered Expression	[11]
Colorectal neoplasm	DISR1UCN	moderate	Biomarker	[11]
Periodontitis	DISI9JOI	moderate	Biomarker	[12]
Head-neck squamous cell carcinoma	DISF7P24	Limited	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Desmocollin-1 (DSC1).	[13]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Desmocollin-1 (DSC1).	[14]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Desmocollin-1 (DSC1).	[15]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Desmocollin-1 (DSC1).	[16]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Desmocollin-1 (DSC1).	[16]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Desmocollin-1 (DSC1).	[13]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Desmocollin-1 (DSC1).	[17]
Alitretinoin	DMME8LH	Approved	Alitretinoin decreases the expression of Desmocollin-1 (DSC1).	[13]
Ibuprofen	DM8VCBE	Approved	Ibuprofen affects the expression of Desmocollin-1 (DSC1).	[18]
Rofecoxib	DM3P5DA	Approved	Rofecoxib affects the expression of Desmocollin-1 (DSC1).	[18]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Desmocollin-1 (DSC1).	[19]
all-trans-4-oxo-retinoic acid	DMM2R1N	Investigative	all-trans-4-oxo-retinoic acid decreases the expression of Desmocollin-1 (DSC1).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Desmocollin-1 (DSC1).	[20]

References

• [1] Loss of desmocollin 1-3 and homeobox genes PITX1 and CDX2 are associated with tumor progression and survival in colorectal carcinoma.Int J Colorectal Dis. 2012 Nov;27(11):1391-9. doi: 10.1007/s00384-012-1460-4. Epub 2012 Mar 23.
• [2] Lower DSC1 expression is related to the poor differentiation and prognosis of head and neck squamous cell carcinoma (HNSCC).J Cancer Res Clin Oncol. 2016 Dec;142(12):2461-2468. doi: 10.1007/s00432-016-2233-1. Epub 2016 Sep 6.
• [3] Association of DSC1, a gene modulated by adrenergic stimulation, with Alzheimer's disease.Neurosci Lett. 2006 Nov 20;408(3):203-8. doi: 10.1016/j.neulet.2006.09.005. Epub 2006 Oct 2.
• [4] HDLs and the pathogenesis of atherosclerosis.Curr Opin Cardiol. 2018 May;33(3):311-316. doi: 10.1097/HCO.0000000000000508.
• [5] Expression of keratin 1, keratin 10, desmoglein 1 and desmocollin 1 in the epidermis: possible downregulation by interleukin-4 and interleukin-13 in atopic dermatitis.Eur J Dermatol. 2017 Jun 1;27(3):247-253. doi: 10.1684/ejd.2017.2985.
• [6] Matching NLR Immune Receptors to Autoimmunity in camta3 Mutants Using Antimorphic NLR Alleles.Cell Host Microbe. 2017 Apr 12;21(4):518-529.e4. doi: 10.1016/j.chom.2017.03.005.
• [7] Proteomics Identification and Validation of Desmocollin-1 and Catechol-O-Methyltransferase as Proteins Associated with Breast Cancer Cell Migration and Metastasis.Proteomics. 2019 Nov;19(21-22):e1900073. doi: 10.1002/pmic.201900073. Epub 2019 Oct 28.
• [8] Exome sequencing identifies recurrent somatic MAP2K1 and MAP2K2 mutations in melanoma.Nat Genet. 2011 Dec 25;44(2):133-9. doi: 10.1038/ng.1026.
• [9] Desmocollin expression in oral atrophic lichen planus correlates with clinical behavior and DNA content.J Cutan Pathol. 2008 Sep;35(9):832-8. doi: 10.1111/j.1600-0560.2007.00903.x. Epub 2008 Apr 18.
• [10] Nonclassical pemphigus with exclusively IgG anti-desmocollin 3-specific antibodies.Australas J Dermatol. 2019 Aug;60(3):e217-e219. doi: 10.1111/ajd.12991. Epub 2019 Jan 22.
• [11] Desmocollin switching in colorectal cancer.Br J Cancer. 2006 Nov 20;95(10):1367-70. doi: 10.1038/sj.bjc.6603453. Epub 2006 Oct 31.
• [12] Altered gene expression in leukocyte transendothelial migration and cell communication pathways in periodontitis-affected gingival tissues.J Periodontal Res. 2011 Jun;46(3):345-53. doi: 10.1111/j.1600-0765.2011.01349.x. Epub 2011 Mar 7.
• [13] Retinoic acid and its 4-oxo metabolites are functionally active in human skin cells in vitro. J Invest Dermatol. 2005 Jul;125(1):143-53.
• [14] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [15] Comparative Analysis of Transcriptomic Changes including mRNA and microRNA Expression Induced by the Xenoestrogens Zearalenone and Bisphenol A in Human Ovarian Cells. Toxins (Basel). 2023 Feb 9;15(2):140. doi: 10.3390/toxins15020140.
• [16] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [17] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [18] Rofecoxib modulates multiple gene expression pathways in a clinical model of acute inflammatory pain. Pain. 2007 Mar;128(1-2):136-47.
• [19] 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.
• [20] 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.