Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN9QJKG)

• DOT Name: Small proline-rich protein 3 (SPRR3)
• Synonyms: 22 kDa pancornulin; Cornifin beta; Esophagin
• Gene Name: SPRR3
• Related Disease:
  Advanced cancer
  Atopic dermatitis
  Esophageal squamous cell carcinoma
  Neoplasm
  Skin disease
  Squamous cell carcinoma
  Adenocarcinoma
  Carcinoma
  Carcinoma of esophagus
  Esophageal cancer
  Eosinophilic esophagitis
  Neoplasm of esophagus
• UniProt ID: SPRR3_HUMAN
• Pfam ID: PF02389
• Sequence:
  MSSYQQKQTFTPPPQLQQQQVKQPSQPPPQEIFVPTTKEPCHSKVPQPGNTKIPEPGCTK
  VPEPGCTKVPEPGCTKVPEPGCTKVPEPGCTKVPEPGCTKVPEPGYTKVPEPGSIKVPDQ
  GFIKFPEPGAIKVPEQGYTKVPVPGYTKLPEPCPSTVTPGPAQQKTKQK
• Function: Cross-linked envelope protein of keratinocytes.
• Reactome Pathway: Formation of the cornified envelope (R-HSA-6809371)

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Atopic dermatitis	DISTCP41	Strong	Biomarker	[2]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[3]
Neoplasm	DISZKGEW	Strong	Altered Expression	[3]
Skin disease	DISDW8R6	Strong	Altered Expression	[4]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[5]
Adenocarcinoma	DIS3IHTY	moderate	Biomarker	[6]
Carcinoma	DISH9F1N	Disputed	Altered Expression	[7]
Carcinoma of esophagus	DISS6G4D	Disputed	Altered Expression	[7]
Esophageal cancer	DISGB2VN	Disputed	Altered Expression	[7]
Eosinophilic esophagitis	DISR8WSB	Limited	Altered Expression	[8]
Neoplasm of esophagus	DISOLKAQ	Limited	Altered Expression	[9]

7 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 Small proline-rich protein 3 (SPRR3).	[10]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil affects the expression of Small proline-rich protein 3 (SPRR3).	[12]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Small proline-rich protein 3 (SPRR3).	[13]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Small proline-rich protein 3 (SPRR3).	[10]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Small proline-rich protein 3 (SPRR3).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Small proline-rich protein 3 (SPRR3).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Small proline-rich protein 3 (SPRR3).	[16]

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 Small proline-rich protein 3 (SPRR3).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Small proline-rich protein 3 (SPRR3).	[14]

References

• [1] Mesenchymal stem/progenitors and other endometrial cell types from women with polycystic ovary syndrome (PCOS) display inflammatory and oncogenic potential.J Clin Endocrinol Metab. 2013 Sep;98(9):3765-75. doi: 10.1210/jc.2013-1923. Epub 2013 Jul 3.
• [2] Expression of Cornified Envelope Proteins in Skin and Its Relationship with Atopic Dermatitis Phenotype.Acta Derm Venereol. 2017 Jan 4;97(1):36-41. doi: 10.2340/00015555-2482.
• [3] Quantitative evaluation of SPRR3 expression in esophageal squamous cell carcinoma by qPCR and its potential use as a biomarker.Exp Mol Pathol. 2011 Oct;91(2):584-9. doi: 10.1016/j.yexmp.2011.06.006. Epub 2011 Jul 12.
• [4] Differential expression of human cornifin alpha and beta in squamous differentiating epithelial tissues and several skin lesions.J Invest Dermatol. 1997 Feb;108(2):200-4. doi: 10.1111/1523-1747.ep12334240.
• [5] Exogenous expression of Esophagin/SPRR3 attenuates the tumorigenicity of esophageal squamous cell carcinoma cells via promoting apoptosis.Int J Cancer. 2008 Jan 15;122(2):260-6. doi: 10.1002/ijc.23104.
• [6] Progression of Barrett's metaplasia to adenocarcinoma is associated with the suppression of the transcriptional programs of epidermal differentiation.Cancer Res. 2005 Apr 15;65(8):3146-54. doi: 10.1158/0008-5472.CAN-04-2490.
• [7] Decreased expression of SPRR3 in Chinese human oesophageal cancer.Carcinogenesis. 2000 Dec;21(12):2147-50. doi: 10.1093/carcin/21.12.2147.
• [8] Coordinate interaction between IL-13 and epithelial differentiation cluster genes in eosinophilic esophagitis.J Immunol. 2010 Apr 1;184(7):4033-41. doi: 10.4049/jimmunol.0903069. Epub 2010 Mar 5.
• [9] Esophagin cDNA cloning and characterization: a tissue-specific member of the small proline-rich protein family that is not expressed in esophageal tumors.Cell Growth Differ. 1996 Jul;7(7):855-60.
• [10] Retinoic acid and hydroquinone induce inverse expression patterns on cornified envelope-associated proteins: implication in skin irritation. J Dermatol Sci. 2014 Nov;76(2):112-9. doi: 10.1016/j.jdermsci.2014.08.003. Epub 2014 Aug 26.
• [11] 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.
• [12] Multi-level gene expression profiles affected by thymidylate synthase and 5-fluorouracil in colon cancer. BMC Genomics. 2006 Apr 3;7:68. doi: 10.1186/1471-2164-7-68.
• [13] Gene microarray analysis of human renal cell carcinoma: the effects of HDAC inhibition and retinoid treatment. Cancer Biol Ther. 2008 Oct;7(10):1607-18.
• [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] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [16] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.