Details of Drug Off-Target (DOT)

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

DOT Name	Protein S100-A7 (S100A7)
Synonyms	Psoriasin; S100 calcium-binding protein A7
Gene Name	S100A7
Related Disease	Arthritis ( ) Invasive breast carcinoma ( ) Adenocarcinoma ( ) Arteriosclerosis ( ) Atherosclerosis ( ) Atopic dermatitis ( ) Barrett esophagus ( ) Bladder cancer ( ) Breast neoplasm ( ) Carcinoma ( ) Cervical cancer ( ) Cervical carcinoma ( ) Dermatitis ( ) Epithelial ovarian cancer ( ) Gastric cancer ( ) Head and neck cancer ( ) Head and neck carcinoma ( ) Head-neck squamous cell carcinoma ( ) Intrahepatic cholangiocarcinoma ( ) Lung adenocarcinoma ( ) Lung cancer ( ) Lung carcinoma ( ) Melanoma ( ) Metastatic malignant neoplasm ( ) Nasal polyp ( ) Neoplasm ( ) Non-small-cell lung cancer ( ) Obesity ( ) Oral cancer ( ) Ovarian cancer ( ) Ovarian neoplasm ( ) Palmoplantar pustulosis ( ) Precancerous condition ( ) Prostate cancer ( ) Prostate carcinoma ( ) Skin cancer ( ) Skin disease ( ) Stomach cancer ( ) Urinary bladder cancer ( ) Urinary bladder neoplasm ( ) Bacterial infection ( ) Craniosynostosis ( ) Pancreatic cancer ( ) Estrogen-receptor positive breast cancer ( ) Advanced cancer ( ) Coronary heart disease ( ) Systemic sclerosis ( )
UniProt ID	S10A7_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	1PSR; 2PSR; 2WND; 2WOR; 2WOS; 3PSR; 4AQJ
Pfam ID	PF01023
Sequence	MSNTQAERSIIGMIDMFHKYTRRDDKIEKPSLLTMMKENFPNFLSACDKKGTNYLADVFE KKDKNEDKKIDFSEFLSLLGDIATDYHKQSHGAAPCSGGSQ
Tissue Specificity	Fetal ear, skin, and tongue and human cell lines. Highly up-regulated in psoriatic epidermis. Also highly expressed in the urine of bladder squamous cell carcinoma (SCC) bearing patients.
KEGG Pathway	IL-17 sig.ling pathway (hsa04657 )
Reactome Pathway	Metal sequestration by antimicrobial proteins (R-HSA-6799990 ) Neutrophil degranulation (R-HSA-6798695 )

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Arthritis	DIST1YEL	Definitive	Altered Expression	[1]
Invasive breast carcinoma	DISANYTW	Definitive	Altered Expression	[2]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[3]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[4]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[4]
Atopic dermatitis	DISTCP41	Strong	Altered Expression	[5]
Barrett esophagus	DIS416Y7	Strong	Altered Expression	[6]
Bladder cancer	DISUHNM0	Strong	Altered Expression	[7]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[8]
Carcinoma	DISH9F1N	Strong	Altered Expression	[9]
Cervical cancer	DISFSHPF	Strong	Biomarker	[10]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[10]
Dermatitis	DISY5SZC	Strong	Biomarker	[11]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[12]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[13]
Head and neck cancer	DISBPSQZ	Strong	Biomarker	[14]
Head and neck carcinoma	DISOU1DS	Strong	Biomarker	[14]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[14]
Intrahepatic cholangiocarcinoma	DIS6GOC8	Strong	Biomarker	[15]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[3]
Lung cancer	DISCM4YA	Strong	Biomarker	[3]
Lung carcinoma	DISTR26C	Strong	Biomarker	[3]
Melanoma	DIS1RRCY	Strong	Biomarker	[16]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[12]
Nasal polyp	DISLP3XE	Strong	Altered Expression	[17]
Neoplasm	DISZKGEW	Strong	Altered Expression	[13]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[18]
Obesity	DIS47Y1K	Strong	Biomarker	[19]
Oral cancer	DISLD42D	Strong	Altered Expression	[20]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[12]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[12]
Palmoplantar pustulosis	DISCNSWD	Strong	Biomarker	[21]
Precancerous condition	DISV06FL	Strong	Biomarker	[22]
Prostate cancer	DISF190Y	Strong	Altered Expression	[23]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[23]
Skin cancer	DISTM18U	Strong	Altered Expression	[7]
Skin disease	DISDW8R6	Strong	Altered Expression	[24]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[13]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[7]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[7]
Bacterial infection	DIS5QJ9S	moderate	Altered Expression	[25]
Craniosynostosis	DIS6J405	moderate	Altered Expression	[26]
Pancreatic cancer	DISJC981	moderate	Altered Expression	[27]
Estrogen-receptor positive breast cancer	DIS1H502	Disputed	Biomarker	[28]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[13]
Coronary heart disease	DIS5OIP1	Limited	Biomarker	[29]
Systemic sclerosis	DISF44L6	Limited	Altered Expression	[30]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein S100-A7 (S100A7).	[31]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Protein S100-A7 (S100A7).	[32]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Protein S100-A7 (S100A7).	[33]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Protein S100-A7 (S100A7).	[31]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Protein S100-A7 (S100A7).	[34]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Protein S100-A7 (S100A7).	[35]
Alitretinoin	DMME8LH	Approved	Alitretinoin increases the expression of Protein S100-A7 (S100A7).	[31]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Protein S100-A7 (S100A7).	[37]
all-trans-4-oxo-retinoic acid	DMM2R1N	Investigative	all-trans-4-oxo-retinoic acid increases the expression of Protein S100-A7 (S100A7).	[31]
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⏷ Show the Full List of 9 Drug(s)

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 Protein S100-A7 (S100A7).	[36]
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References

1	Low vitamin D-modulated calcium-regulating proteins in psoriasis vulgaris plaques: S100A7 overexpression depends on joint involvement.Int J Mol Med. 2016 Oct;38(4):1083-92. doi: 10.3892/ijmm.2016.2718. Epub 2016 Aug 26.
2	Molecular and cellular impact of Psoriasin (S100A7) on the healing of human wounds.Exp Ther Med. 2017 May;13(5):2151-2160. doi: 10.3892/etm.2017.4275. Epub 2017 Mar 28.
3	S100A7 promotes lung adenocarcinoma to squamous carcinoma transdifferentiation, and its expression is differentially regulated by the Hippo-YAP pathway in lung cancer cells.Oncotarget. 2017 Apr 11;8(15):24804-24814. doi: 10.18632/oncotarget.15063.
4	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.
5	Unique profile of antimicrobial peptide expression in polymorphic light eruption lesions compared to healthy skin, atopic dermatitis, and psoriasis.Photodermatol Photoimmunol Photomed. 2018 Mar;34(2):137-144. doi: 10.1111/phpp.12355. Epub 2017 Nov 13.
6	Expression of antimicrobial peptides in different subtypes of cutaneous lupus erythematosus.J Am Acad Dermatol. 2011 Jul;65(1):125-33. doi: 10.1016/j.jaad.2010.12.012. Epub 2011 Feb 25.
7	Psoriasin (S100A7) is significantly up-regulated in human epithelial skin tumours.J Cancer Res Clin Oncol. 2007 Apr;133(4):253-61. doi: 10.1007/s00432-006-0164-y. Epub 2006 Nov 29.
8	Interaction with adipocyte stromal cells induces breast cancer malignancy via S100A7 upregulation in breast cancer microenvironment.Breast Cancer Res. 2017 Jun 19;19(1):70. doi: 10.1186/s13058-017-0863-0.
9	Psoriasin (S100A7) up-regulation in oral squamous cell carcinoma and its relation to clinicopathologic features.Oral Oncol. 2009 Aug;45(8):731-6. doi: 10.1016/j.oraloncology.2008.11.012. Epub 2009 Jan 14.
10	S100A7 promotes the migration, invasion and metastasis of human cervical cancer cells through epithelial-mesenchymal transition.Oncotarget. 2017 Apr 11;8(15):24964-24977. doi: 10.18632/oncotarget.15329.
11	Overexpression of MLH-1 and psoriasin genes in cutaneous angiofibromas from tuberous sclerosis complex patients.J Cutan Pathol. 2006 Sep;33(9):608-13. doi: 10.1111/j.1600-0560.2006.00483.x.
12	S100A7 Regulates Ovarian Cancer Cell Metastasis and Chemoresistance Through MAPK Signaling and Is Targeted by miR-330-5p.DNA Cell Biol. 2018 May;37(5):491-500. doi: 10.1089/dna.2017.3953. Epub 2018 Feb 27.
13	Psoriasin overexpression confers drug resistance to cisplatin by activating ERK in gastric cancer.Int J Oncol. 2018 Sep;53(3):1171-1182. doi: 10.3892/ijo.2018.4455. Epub 2018 Jun 26.
14	Nuclear S100A7 is associated with poor prognosis in head and neck cancer.PLoS One. 2010 Aug 3;5(8):e11939. doi: 10.1371/journal.pone.0011939.
15	MicroRNA-26b-5p regulates cell proliferation, invasion and metastasis in human intrahepatic cholangiocarcinoma by targeting S100A7.Oncol Lett. 2018 Jan;15(1):386-392. doi: 10.3892/ol.2017.7331. Epub 2017 Nov 2.
16	Prediction and Analysis of Skin Cancer Progression using Genomics Profiles of Patients.Sci Rep. 2019 Oct 31;9(1):15790. doi: 10.1038/s41598-019-52134-4.
17	Epithelial genes in chronic rhinosinusitis with and without nasal polyps.Am J Rhinol. 2008 May-Jun;22(3):228-34. doi: 10.2500/ajr.2008.22.3162.
18	The TGF-induced lncRNA TBILA promotes non-small cell lung cancer progression in vitro and in vivo via cis-regulating HGAL and activating S100A7/JAB1 signaling.Cancer Lett. 2018 Sep 28;432:156-168. doi: 10.1016/j.canlet.2018.06.013. Epub 2018 Jun 15.
19	Bidirectional Association Between Psoriasis and Obesity: Benefits and Risks.J Interferon Cytokine Res. 2018 Jan;38(1):12-19. doi: 10.1089/jir.2017.0105. Epub 2017 Dec 18.
20	S100A7 has an oncogenic role in oral squamous cell carcinoma by activating p38/MAPK and RAB2A signaling pathway.Cancer Gene Ther. 2016 Nov;23(11):382-391. doi: 10.1038/cgt.2016.43. Epub 2016 Oct 21.
21	Microbicidal protein psoriasin is a multifunctional modulator of neutrophil activation.Immunology. 2008 Jul;124(3):357-67. doi: 10.1111/j.1365-2567.2007.02782.x. Epub 2008 Jan 8.
22	Identification of genes and molecular pathways involved in the progression of premalignant oral epithelia.Mol Cancer Ther. 2005 Jun;4(6):865-75. doi: 10.1158/1535-7163.MCT-05-0033.
23	Psoriasin (S100A7) is a positive regulator of survival and invasion of prostate cancer cells.Urol Oncol. 2013 Nov;31(8):1576-83. doi: 10.1016/j.urolonc.2012.05.006. Epub 2012 Jun 12.
24	Sustained Secretion of the Antimicrobial Peptide S100A7 Is Dependent on the Downregulation of Caspase-8.Cell Rep. 2019 Nov 26;29(9):2546-2555.e4. doi: 10.1016/j.celrep.2019.10.090.
25	Th2 cytokines differentially regulate psoriasin expression in human nasal epithelia.Am J Rhinol Allergy. 2014 Nov-Dec;28(6):449-53. doi: 10.2500/ajra.2014.28.4087.
26	Differential expression and role of S100 proteins in chronic rhinosinusitis.Curr Opin Allergy Clin Immunol. 2020 Feb;20(1):14-22. doi: 10.1097/ACI.0000000000000595.
27	Psoriasin promotes invasion, aggregation and survival of pancreatic cancer cells; association with disease progression.Int J Oncol. 2017 May;50(5):1491-1500. doi: 10.3892/ijo.2017.3953. Epub 2017 Apr 5.
28	miR-29b defines the pro-/anti-proliferative effects of S100A7 in breast cancer.Mol Cancer. 2015 Jan 27;14:11. doi: 10.1186/s12943-014-0275-z.
29	Weighted gene co-expression network analysis identifies specific modules and hub genes related to coronary artery disease.BMC Cardiovasc Disord. 2016 Mar 5;16:54. doi: 10.1186/s12872-016-0217-3.
30	A potential contribution of psoriasin to vascular and epithelial abnormalities and inflammation in systemic sclerosis.J Eur Acad Dermatol Venereol. 2018 Feb;32(2):291-297. doi: 10.1111/jdv.14459. Epub 2017 Aug 3.
31	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.
32	Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
33	Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
34	Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
35	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.
36	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.
37	Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.