Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNM8DCP)

• DOT Name: Protein S100-A7A (S100A7A)
• Synonyms: S100 calcium-binding protein A15; S100 calcium-binding protein A7-like 1; S100 calcium-binding protein A7A
• Gene Name: S100A7A
• Related Disease:
  Acne vulgaris
  Lung cancer
  Lung carcinoma
  Psoriasis
  Adenocarcinoma
  Advanced cancer
  Arteriosclerosis
  Atherosclerosis
  Breast cancer
  Dermatitis
  Lung adenocarcinoma
  Neoplasm
  Non-small-cell lung cancer
  Polycystic ovarian syndrome
  Skin disease
  Squamous cell carcinoma
• UniProt ID: S1A7A_HUMAN
• PDB ID: 4AQI
• Pfam ID: PF01023
• Sequence:
  MSNTQAERSIIGMIDMFHKYTGRDGKIEKPSLLTMMKENFPNFLSACDKKGIHYLATVFE
  KKDKNEDKKIDFSEFLSLLGDIAADYHKQSHGAAPCSGGSQ
• Function: May be involved in epidermal differentiation and inflammation and might therefore be important for the pathogenesis of psoriasis and other diseases.
• Tissue Specificity: Overexpressed in psoriasis.
• KEGG Pathway: IL-17 sig.ling pathway (hsa04657)
• Reactome Pathway: Metal sequestration by antimicrobial proteins (R-HSA-6799990)

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acne vulgaris	DISKW8PI	Definitive	Altered Expression	[1]
Lung cancer	DISCM4YA	Definitive	Posttranslational Modification	[2]
Lung carcinoma	DISTR26C	Definitive	Posttranslational Modification	[2]
Psoriasis	DIS59VMN	Definitive	Biomarker	[3]
Adenocarcinoma	DIS3IHTY	Strong	Genetic Variation	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[3]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Dermatitis	DISY5SZC	Strong	Genetic Variation	[6]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[7]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[7]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[8]
Skin disease	DISDW8R6	Strong	Altered Expression	[6]
Squamous cell carcinoma	DISQVIFL	moderate	Biomarker	[9]

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 Protein S100-A7A (S100A7A).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Protein S100-A7A (S100A7A).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Protein S100-A7A (S100A7A).	[11]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Protein S100-A7A (S100A7A).	[11]
Glyphosate	DM0AFY7	Investigative	Glyphosate increases the expression of Protein S100-A7A (S100A7A).	[13]

References

• [1] Downregulation of S100a7a antimicrobial peptide in acne vulgaris patients after isotretinoin therapy.Dermatol Ther. 2019 Nov;32(6):e13136. doi: 10.1111/dth.13136. Epub 2019 Oct 31.
• [2] Increased S100A15 expression and decreased DNA methylation of its gene promoter are involved in high metastasis potential and poor outcome of lung adenocarcinoma.Oncotarget. 2017 Jul 11;8(28):45710-45724. doi: 10.18632/oncotarget.17391.
• [3] Serum levels of psoriasin (S100A7) and koebnerisin (S100A15) as potential markers of atherosclerosis in patients with psoriasis.Clin Exp Dermatol. 2018 Apr;43(3):262-267. doi: 10.1111/ced.13370. Epub 2018 Jan 14.
• [4] Novel S100A7 (psoriasin)/S100A15 (koebnerisin) subfamily: highly homologous but distinct in regulation and function.Amino Acids. 2011 Oct;41(4):789-96. doi: 10.1007/s00726-010-0666-4. Epub 2010 Jul 2.
• [5] Highly homologous hS100A15 and hS100A7 proteins are distinctly expressed in normal breast tissue and breast cancer.Cancer Lett. 2009 May 8;277(1):101-7. doi: 10.1016/j.canlet.2008.11.032. Epub 2009 Jan 10.
• [6] Human S100A15 splice variants are differentially expressed in inflammatory skin diseases and regulated through Th1 cytokines and calcium.Exp Dermatol. 2007 Aug;16(8):685-91. doi: 10.1111/j.1600-0625.2007.00587.x.
• [7] Peripheral immune cell gene expression changes in advanced non-small cell lung cancer patients treated with first line combination chemotherapy.PLoS One. 2013;8(2):e57053. doi: 10.1371/journal.pone.0057053. Epub 2013 Feb 25.
• [8] Progesterone resistance in PCOS endometrium: a microarray analysis in clomiphene citrate-treated and artificial menstrual cycles.J Clin Endocrinol Metab. 2011 Jun;96(6):1737-46. doi: 10.1210/jc.2010-2600. Epub 2011 Mar 16.
• [9] Inflammation-mediated skin tumorigenesis induced by epidermal c-Fos.Genes Dev. 2013 Sep 15;27(18):1959-73. doi: 10.1101/gad.223339.113. Epub 2013 Sep 12.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] Use of human neuroblastoma SH-SY5Y cells to evaluate glyphosate-induced effects on oxidative stress, neuronal development and cell death signaling pathways. Environ Int. 2020 Feb;135:105414. doi: 10.1016/j.envint.2019.105414. Epub 2019 Dec 23.