Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3ERKQI)

• DOT Name: Protein S100-A16 (S100A16)
• Synonyms: Aging-associated gene 13 protein; Protein S100-F; S100 calcium-binding protein A16
• Gene Name: S100A16
• Related Disease:
  Gastric cancer
  Glioma
  Lung adenocarcinoma
  Stomach cancer
  Advanced cancer
  Bladder cancer
  Cervical carcinoma
  Colorectal carcinoma
  Fatty liver disease
  Neoplasm
  Urinary bladder cancer
  Urinary bladder neoplasm
  Breast cancer
  Breast carcinoma
  Obesity
  Small-cell lung cancer
  Squamous cell carcinoma
  Prostate cancer
  Prostate carcinoma
  Leukemia
• UniProt ID: S10AG_HUMAN
• PDB ID: 2L50; 2L51; 3NXA
• Pfam ID: PF01023
• Sequence:
  MSDCYTELEKAVIVLVENFYKYVSKYSLVKNKISKSSFREMLQKELNHMLSDTGNRKAAD
  KLIQNLDANHDGRISFDEYWTLIGGITGPIAKLIHEQEQQSSS
• Function: Calcium-binding protein. Binds one calcium ion per monomer. Can promote differentiation of adipocytes (in vitro). Overexpression in preadipocytes increases their proliferation, enhances adipogenesis and reduces insulin-stimulated glucose uptake.
• Tissue Specificity: Ubiquitous . Highly expressed in esophagus, adipose tissues and colon. Expressed at lower level in lung, brain, pancreas and skeletal muscle. Expression is up-regulated in tumors of bladder, lung, thyroid gland, pancreas and ovary . Expressed in astrocytes .

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gastric cancer	DISXGOUK	Definitive	Biomarker	[1]
Glioma	DIS5RPEH	Definitive	Altered Expression	[2]
Lung adenocarcinoma	DISD51WR	Definitive	Altered Expression	[3]
Stomach cancer	DISKIJSX	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[4]
Bladder cancer	DISUHNM0	Strong	Biomarker	[5]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[6]
Fatty liver disease	DIS485QZ	Strong	Altered Expression	[7]
Neoplasm	DISZKGEW	Strong	Altered Expression	[6]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[5]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	moderate	Genetic Variation	[8]
Breast carcinoma	DIS2UE88	moderate	Genetic Variation	[8]
Obesity	DIS47Y1K	moderate	Altered Expression	[9]
Small-cell lung cancer	DISK3LZD	moderate	Altered Expression	[10]
Squamous cell carcinoma	DISQVIFL	moderate	Biomarker	[6]
Prostate cancer	DISF190Y	Disputed	Altered Expression	[11]
Prostate carcinoma	DISMJPLE	Disputed	Altered Expression	[11]
Leukemia	DISNAKFL	Limited	Biomarker	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Protein S100-A16 (S100A16).	[13]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein S100-A16 (S100A16).	[14]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein S100-A16 (S100A16).	[15]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein S100-A16 (S100A16).	[16]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Protein S100-A16 (S100A16).	[17]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Protein S100-A16 (S100A16).	[18]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein S100-A16 (S100A16).	[19]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Protein S100-A16 (S100A16).	[20]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Protein S100-A16 (S100A16).	[21]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Protein S100-A16 (S100A16).	[22]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Protein S100-A16 (S100A16).	[23]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein S100-A16 (S100A16).	[25]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein S100-A16 (S100A16).	[26]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein S100-A16 (S100A16).	[27]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Protein S100-A16 (S100A16).	[28]

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 decreases the methylation of Protein S100-A16 (S100A16).	[24]

References

• [1] MicroRNA-6884-5p Regulates the Proliferation, Invasion, and EMT of Gastric Cancer Cells by Directly Targeting S100A16.Oncol Res. 2020 May 29;28(3):225-236. doi: 10.3727/096504019X15753718797664. Epub 2019 Dec 3.
• [2] Transfection with liver-type glutaminase cDNA alters gene expression and reduces survival, migration and proliferation of T98G glioma cells.Glia. 2009 Jul;57(9):1014-23. doi: 10.1002/glia.20825.
• [3] Prognostic significance of S100A16 subcellular localization in lung adenocarcinoma.Hum Pathol. 2018 Apr;74:148-155. doi: 10.1016/j.humpath.2018.01.001. Epub 2018 Jan 7.
• [4] S100A16 up-regulates Oct4 and Nanog expression in cancer stem-like cells of Yumoto human cervical carcinoma cells.Oncol Lett. 2018 Jun;15(6):9929-9933. doi: 10.3892/ol.2018.8568. Epub 2018 Apr 25.
• [5] S100A16 regulated by Snail promotes the chemoresistance of nonmuscle invasive bladder cancer through the AKT/Bcl-2 pathway.Cancer Manag Res. 2019 Mar 27;11:2449-2456. doi: 10.2147/CMAR.S196450. eCollection 2019.
• [6] S100A16 is a prognostic marker for colorectal cancer.J Surg Oncol. 2018 Feb;117(2):275-283. doi: 10.1002/jso.24822. Epub 2017 Sep 6.
• [7] S100A16, a novel lipogenesis promoting factor in livers of mice and hepatocytes in vitro.J Cell Physiol. 2019 Nov;234(11):21395-21406. doi: 10.1002/jcp.28748. Epub 2019 May 8.
• [8] Co-expression of S100A14 and S100A16 correlates with a poor prognosis in human breast cancer and promotes cancer cell invasion.BMC Cancer. 2015 Feb 13;15:53. doi: 10.1186/s12885-015-1059-6.
• [9] S100A16-induced adipogenesis is associated with up-regulation of 11 -hydroxysteroid dehydrogenase type 1 (11-HSD1).Biosci Rep. 2019 Sep 9;39(9):BSR20182042. doi: 10.1042/BSR20182042. Print 2019 Sep 30.
• [10] Brain microvascular endothelial cell exosome-mediated S100A16 up-regulation confers small-cell lung cancer cell survival in brain.FASEB J. 2019 Feb;33(2):1742-1757. doi: 10.1096/fj.201800428R. Epub 2018 Sep 5.
• [11] S100A16 promotes cell proliferation and metastasis via AKT and ERK cell signaling pathways in human prostate cancer.Tumour Biol. 2016 Sep;37(9):12241-12250. doi: 10.1007/s13277-016-5096-9. Epub 2016 May 30.
• [12] S100A16 suppresses the growth and survival of leukaemia cellsand correlates with relapse and relapse free survival in adults with Philadelphia chromosome-negative B-cell acute lymphoblastic leukaemia.Br J Haematol. 2019 Jun;185(5):836-851. doi: 10.1111/bjh.15878. Epub 2019 Mar 27.
• [13] 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.
• [14] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [15] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [16] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [17] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [18] 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.
• [19] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [20] 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.
• [21] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [22] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [23] Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
• [24] 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.
• [25] 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.
• [26] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [27] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [28] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.