Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTGHJ1H)

DOT Name Protein S100-A2 (S100A2)
Synonyms CAN19; Protein S-100L; S100 calcium-binding protein A2
Gene Name S100A2
Related Disease
Ependymoma ( )
Esophageal squamous cell carcinoma ( )
Advanced cancer ( )
Benign prostatic hyperplasia ( )
Bone osteosarcoma ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Carcinoma of esophagus ( )
Cholangiocarcinoma ( )
Congenital contractural arachnodactyly ( )
Dilated cardiomyopathy 1A ( )
Gastric cancer ( )
Head and neck cancer ( )
Head and neck carcinoma ( )
Head and neck neoplasm ( )
Laryngeal carcinoma ( )
Lung cancer ( )
Lung carcinoma ( )
Lung neoplasm ( )
Medulloblastoma ( )
Metastatic malignant neoplasm ( )
Osteosarcoma ( )
Prostate cancer ( )
Prostate carcinoma ( )
Stomach cancer ( )
Carcinoma ( )
Gastritis ( )
Gingivitis ( )
Hereditary breast ovarian cancer syndrome ( )
Keratoconus ( )
Melanoma ( )
Periodontal disease ( )
Periodontitis ( )
Uveal Melanoma ( )
Head-neck squamous cell carcinoma ( )
Lung adenocarcinoma ( )
Minimally invasive lung adenocarcinoma ( )
Non-small-cell lung cancer ( )
Pancreatic cancer ( )
UniProt ID
S10A2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2RGI; 4DUQ
Pfam ID
PF01023
Sequence
MMCSSLEQALAVLVTTFHKYSCQEGDKFKLSKGEMKELLHKELPSFVGEKVDEEGLKKLM
GSLDENSDQQVDFQEYAVFLALITVMCNDFFQGCPDRP
Function
May function as calcium sensor and modulator, contributing to cellular calcium signaling. May function by interacting with other proteins, such as TPR-containing proteins, and indirectly play a role in many physiological processes. May also play a role in suppressing tumor cell growth.
Tissue Specificity A subset of epithelial cells including normal human mammary epithelial cells and keratinocytes.

Molecular Interaction Atlas (MIA) of This DOT

40 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Ependymoma DISUMRNZ Definitive Biomarker [1]
Esophageal squamous cell carcinoma DIS5N2GV Definitive Biomarker [2]
Advanced cancer DISAT1Z9 Strong Altered Expression [3]
Benign prostatic hyperplasia DISI3CW2 Strong Posttranslational Modification [4]
Bone osteosarcoma DIST1004 Strong Biomarker [5]
Breast cancer DIS7DPX1 Strong Biomarker [6]
Breast carcinoma DIS2UE88 Strong Altered Expression [7]
Breast neoplasm DISNGJLM Strong Biomarker [7]
Carcinoma of esophagus DISS6G4D Strong Biomarker [2]
Cholangiocarcinoma DIS71F6X Strong Biomarker [8]
Congenital contractural arachnodactyly DISOM1K7 Strong Biomarker [8]
Dilated cardiomyopathy 1A DIS0RK9Z Strong Altered Expression [9]
Gastric cancer DISXGOUK Strong Altered Expression [10]
Head and neck cancer DISBPSQZ Strong Altered Expression [11]
Head and neck carcinoma DISOU1DS Strong Altered Expression [11]
Head and neck neoplasm DIS1OB2G Strong Altered Expression [11]
Laryngeal carcinoma DISNHCIV Strong Biomarker [12]
Lung cancer DISCM4YA Strong Altered Expression [13]
Lung carcinoma DISTR26C Strong Altered Expression [13]
Lung neoplasm DISVARNB Strong Altered Expression [14]
Medulloblastoma DISZD2ZL Strong Posttranslational Modification [15]
Metastatic malignant neoplasm DIS86UK6 Strong Posttranslational Modification [4]
Osteosarcoma DISLQ7E2 Strong Biomarker [5]
Prostate cancer DISF190Y Strong Biomarker [4]
Prostate carcinoma DISMJPLE Strong Biomarker [4]
Stomach cancer DISKIJSX Strong Biomarker [10]
Carcinoma DISH9F1N moderate Altered Expression [16]
Gastritis DIS8G07K moderate Altered Expression [17]
Gingivitis DISC8RMX moderate Altered Expression [18]
Hereditary breast ovarian cancer syndrome DISWDUGU moderate Biomarker [19]
Keratoconus DISOONXH moderate Altered Expression [20]
Melanoma DIS1RRCY moderate Biomarker [21]
Periodontal disease DISJQHVN moderate Altered Expression [18]
Periodontitis DISI9JOI moderate Biomarker [18]
Uveal Melanoma DISA7ZGL moderate Biomarker [22]
Head-neck squamous cell carcinoma DISF7P24 Limited Altered Expression [11]
Lung adenocarcinoma DISD51WR Limited Altered Expression [23]
Minimally invasive lung adenocarcinoma DIS4W83X Limited Biomarker [23]
Non-small-cell lung cancer DIS5Y6R9 Limited Biomarker [13]
Pancreatic cancer DISJC981 Limited Altered Expression [24]
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⏷ Show the Full List of 40 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
1 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 Protein S100-A2 (S100A2). [25]
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20 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 Protein S100-A2 (S100A2). [26]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Protein S100-A2 (S100A2). [27]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Protein S100-A2 (S100A2). [28]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Protein S100-A2 (S100A2). [29]
Quercetin DM3NC4M Approved Quercetin increases the expression of Protein S100-A2 (S100A2). [30]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Protein S100-A2 (S100A2). [31]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Protein S100-A2 (S100A2). [32]
Decitabine DMQL8XJ Approved Decitabine increases the expression of Protein S100-A2 (S100A2). [22]
Zoledronate DMIXC7G Approved Zoledronate decreases the expression of Protein S100-A2 (S100A2). [34]
Progesterone DMUY35B Approved Progesterone increases the expression of Protein S100-A2 (S100A2). [35]
Fluorouracil DMUM7HZ Approved Fluorouracil increases the expression of Protein S100-A2 (S100A2). [36]
Demecolcine DMCZQGK Approved Demecolcine increases the expression of Protein S100-A2 (S100A2). [37]
Nicotine DMWX5CO Approved Nicotine increases the expression of Protein S100-A2 (S100A2). [38]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Protein S100-A2 (S100A2). [39]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Protein S100-A2 (S100A2). [26]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Protein S100-A2 (S100A2). [40]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Protein S100-A2 (S100A2). [37]
chloropicrin DMSGBQA Investigative chloropicrin affects the expression of Protein S100-A2 (S100A2). [41]
Acetaldehyde DMJFKG4 Investigative Acetaldehyde increases the expression of Protein S100-A2 (S100A2). [42]
AM251 DMTAWHL Investigative AM251 increases the expression of Protein S100-A2 (S100A2). [43]
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⏷ Show the Full List of 20 Drug(s)

References

1 Investigation of chromosome 1q reveals differential expression of members of the S100 family in clinical subgroups of intracranial paediatric ependymoma.Br J Cancer. 2008 Oct 7;99(7):1136-43. doi: 10.1038/sj.bjc.6604651. Epub 2008 Sep 9.
2 Expression and clinical significance of S100A2 and p63 in esophageal carcinoma.World J Gastroenterol. 2009 Sep 7;15(33):4183-8. doi: 10.3748/wjg.15.4183.
3 Protumorigenic actions of S100A2 involve regulation of PI3/Akt signaling and functional interaction with Smad3.Carcinogenesis. 2014 Jan;35(1):14-23. doi: 10.1093/carcin/bgt287. Epub 2013 Aug 29.
4 Promoter hyper-methylation of calcium binding proteins S100A6 and S100A2 in human prostate cancer.Prostate. 2005 Dec 1;65(4):322-30. doi: 10.1002/pros.20302.
5 Gene expression profiles classify human osteosarcoma xenografts according to sensitivity to doxorubicin, cisplatin, and ifosfamide.Clin Cancer Res. 2009 Dec 1;15(23):7161-9. doi: 10.1158/1078-0432.CCR-08-2816. Epub 2009 Nov 17.
6 Repression of the candidate tumor suppressor gene S100A2 in breast cancer is mediated by site-specific hypermethylation.Cell Calcium. 1997 Oct;22(4):243-54. doi: 10.1016/s0143-4160(97)90063-4.
7 Expression of calcium-binding protein S100A2 in breast lesions.Br J Cancer. 2000 Dec;83(11):1473-9. doi: 10.1054/bjoc.2000.1488.
8 Comparative Proteomic Analysis of Human Cholangiocarcinoma Cell Lines: S100A2 as a Potential Candidate Protein Inducer of Invasion.Dis Markers. 2015;2015:629367. doi: 10.1155/2015/629367. Epub 2015 Apr 27.
9 Over-expression of S100A2 in pancreatic cancer correlates with progression and poor prognosis.J Pathol. 2007 Nov;213(3):275-82. doi: 10.1002/path.2250.
10 Clinical significance of S100A2 expression in gastric cancer.Tumour Biol. 2014 Apr;35(4):3731-41. doi: 10.1007/s13277-013-1495-3. Epub 2013 Dec 7.
11 Down-regulation of S100A2 in lymph node metastases of head and neck cancer.Head Neck. 2007 Mar;29(3):236-43. doi: 10.1002/hed.20511.
12 iTRAQ-based quantitative proteomic analysis on S100 calcium binding protein A2 in metastasis of laryngeal cancer.PLoS One. 2015 Apr 13;10(4):e0122322. doi: 10.1371/journal.pone.0122322. eCollection 2015.
13 Expression and clinicopathological significance of S100 calcium binding protein A2 in lung cancer patients of Chinese Han ethnicity.Clin Chim Acta. 2017 Jan;464:118-122. doi: 10.1016/j.cca.2016.11.027. Epub 2016 Nov 19.
14 Prognostic and diagnostic relevance of hnRNP A2/B1, hnRNP B1 and S100 A2 in non-small cell lung cancer.Cancer Detect Prev. 2006;30(5):395-402. doi: 10.1016/j.cdp.2006.04.009. Epub 2006 Oct 25.
15 Epigenetic deregulation of multiple S100 gene family members by differential hypomethylation and hypermethylation events in medulloblastoma. Br J Cancer. 2007 Jul 16;97(2):267-74. doi: 10.1038/sj.bjc.6603852. Epub 2007 Jun 19.
16 Altered gene expression in conjunctival squamous cell carcinoma.Mod Pathol. 2016 May;29(5):452-60. doi: 10.1038/modpathol.2016.41. Epub 2016 Feb 26.
17 Clinical significance of altered S100A2 expression in gastric cancer.Oncol Rep. 2013 Apr;29(4):1556-62. doi: 10.3892/or.2013.2236. Epub 2013 Jan 15.
18 S100A2 level changes are related to human periodontitis.Mol Cells. 2011 Nov;32(5):445-50. doi: 10.1007/s10059-011-0132-5. Epub 2011 Sep 9.
19 S100A2 is a BRCA1/p63 coregulated tumour suppressor gene with roles in the regulation of mutant p53 stability.Cell Death Dis. 2014 Feb 20;5(2):e1070. doi: 10.1038/cddis.2014.31.
20 Altered expression of CLC, DSG3, EMP3, S100A2, and SLPI in corneal epithelium from keratoconus patients.Cornea. 2005 Aug;24(6):661-8. doi: 10.1097/01.ico.0000153556.59407.69.
21 Regulation of S100A2 expression by TGF--induced MEK/ERK signalling and its role in cell migration/invasion.Biochem J. 2012 Oct 1;447(1):81-91. doi: 10.1042/BJ20120014.
22 Decitabine up-regulates S100A2 expression and synergizes with IFN-gamma to kill uveal melanoma cells. Clin Cancer Res. 2007 Sep 1;13(17):5219-25. doi: 10.1158/1078-0432.CCR-07-0816.
23 Establishment of an immortalized cell line from a precancerous lesion of lung adenocarcinoma, and genes highly expressed in the early stages of lung adenocarcinoma development.Cancer Sci. 2005 Oct;96(10):668-75. doi: 10.1111/j.1349-7006.2005.00100.x.
24 Expression of S100A2 calcium-binding protein predicts response to pancreatectomy for pancreatic cancer.Gastroenterology. 2009 Aug;137(2):558-68, 568.e1-11. doi: 10.1053/j.gastro.2009.04.009. Epub 2009 Apr 16.
25 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.
26 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
27 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
28 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
29 Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
30 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.
31 Proteomics-based identification of differentially abundant proteins from human keratinocytes exposed to arsenic trioxide. J Proteomics Bioinform. 2014 Jul;7(7):166-178.
32 Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
33 Decitabine up-regulates S100A2 expression and synergizes with IFN-gamma to kill uveal melanoma cells. Clin Cancer Res. 2007 Sep 1;13(17):5219-25. doi: 10.1158/1078-0432.CCR-07-0816.
34 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
35 Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
36 Apoptosis, cell cycle progression and gene expression in TP53-depleted HCT116 colon cancer cells in response to short-term 5-fluorouracil treatment. Int J Oncol. 2007 Dec;31(6):1491-500.
37 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
38 Characterizing the genetic basis for nicotine induced cancer development: a transcriptome sequencing study. PLoS One. 2013 Jun 18;8(6):e67252.
39 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
40 Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
41 Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
42 Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
43 Cannabinoid derivatives induce cell death in pancreatic MIA PaCa-2 cells via a receptor-independent mechanism. FEBS Lett. 2006 Mar 20;580(7):1733-9.