Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT582SUS)

• DOT Name: Protein S100-A13 (S100A13)
• Synonyms: S100 calcium-binding protein A13
• Gene Name: S100A13
• Related Disease:
  Astrocytoma
  Lung cancer
  Lung carcinoma
  Neoplasm
  Non-small-cell lung cancer
  Cutaneous melanoma
  Melanoma
  Metastatic malignant neoplasm
  Glioma
  Thyroid gland papillary carcinoma
• UniProt ID: S10AD_HUMAN
• PDB ID: 1YUR; 1YUS; 1YUT; 1YUU; 2EGD; 2H2K; 2K8M; 2KI4; 2KI6; 2KOT; 2L5X; 2LE9
• Pfam ID: PF01023
• Sequence:
  MAAEPLTELEESIETVVTTFFTFARQEGRKDSLSVNEFKELVTQQLPHLLKDVGSLDEKM
  KSLDVNQDSELKFNEYWRLIGELAKEIRKKKDLKIRKK
• Function: Plays a role in the export of proteins that lack a signal peptide and are secreted by an alternative pathway. Binds two calcium ions per subunit. Binds one copper ion. Binding of one copper ion does not interfere with calcium binding. Required for the copper-dependent stress-induced export of IL1A and FGF1. The calcium-free protein binds to lipid vesicles containing phosphatidylserine, but not to vesicles containing phosphatidylcholine.
• Tissue Specificity: Expressed in heart and skeletal muscle.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Astrocytoma	DISL3V18	Strong	Altered Expression	[1]
Lung cancer	DISCM4YA	Strong	Altered Expression	[1]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[2]
Cutaneous melanoma	DIS3MMH9	moderate	Biomarker	[3]
Melanoma	DIS1RRCY	moderate	Altered Expression	[3]
Metastatic malignant neoplasm	DIS86UK6	moderate	Altered Expression	[3]
Glioma	DIS5RPEH	Disputed	Altered Expression	[4]
Thyroid gland papillary carcinoma	DIS48YMM	Limited	Biomarker	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein S100-A13 (S100A13).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein S100-A13 (S100A13).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Protein S100-A13 (S100A13).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Protein S100-A13 (S100A13).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Protein S100-A13 (S100A13).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Protein S100-A13 (S100A13).	[11]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Protein S100-A13 (S100A13).	[12]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein S100-A13 (S100A13).	[13]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Protein S100-A13 (S100A13).	[15]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Protein S100-A13 (S100A13).	[16]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Protein S100-A13 (S100A13).	[11]
Acocantherin	DM7JT24	Approved	Acocantherin affects the expression of Protein S100-A13 (S100A13).	[17]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Protein S100-A13 (S100A13).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Protein S100-A13 (S100A13).	[19]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Protein S100-A13 (S100A13).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Protein S100-A13 (S100A13).	[22]

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-A13 (S100A13).	[14]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Protein S100-A13 (S100A13).	[20]

References

• [1] S100A13 is a new angiogenic marker in human melanoma.Mod Pathol. 2010 Jun;23(6):804-13. doi: 10.1038/modpathol.2010.54. Epub 2010 Mar 5.
• [2] Overexpression of S100A13 protein is associated with tumor angiogenesis and poor survival in patients with early-stage non-small cell lung cancer.Thorac Cancer. 2018 Sep;9(9):1136-1144. doi: 10.1111/1759-7714.12797. Epub 2018 Jul 26.
• [3] Proteomics analysis of melanoma metastases: association between S100A13 expression and chemotherapy resistance.Br J Cancer. 2014 May 13;110(10):2489-95. doi: 10.1038/bjc.2014.169. Epub 2014 Apr 10.
• [4] S100A13, a new marker of angiogenesis in human astrocytic gliomas.J Neurooncol. 2006 Dec;80(3):251-9. doi: 10.1007/s11060-006-9189-y. Epub 2006 Jun 14.
• [5] A multiplexed, targeted mass spectrometry assay of the S100 protein family uncovers the isoform-specific expression in thyroid tumours.BMC Cancer. 2015 Mar 29;15:199. doi: 10.1186/s12885-015-1217-x.
• [6] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [7] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [8] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [9] 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.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] 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.
• [16] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [17] Proteomics analysis of the proliferative effect of low-dose ouabain on human endothelial cells. Biol Pharm Bull. 2007 Feb;30(2):247-53. doi: 10.1248/bpb.30.247.
• [18] 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.
• [19] 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.
• [20] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [21] The genome-wide expression profile of Scrophularia ningpoensis-treated thapsigargin-stimulated U-87MG cells. Neurotoxicology. 2009 May;30(3):368-76.
• [22] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.