Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVIZJ2R)

• DOT Name: Protein S100-A3 (S100A3)
• Synonyms: Protein S-100E; S100 calcium-binding protein A3
• Gene Name: S100A3
• UniProt ID: S10A3_HUMAN
• PDB ID: 1KSO; 3NSI; 3NSK; 3NSL; 3NSO
• Pfam ID: PF01023
• Sequence:
  MARPLEQAVAAIVCTFQEYAGRCGDKYKLCQAELKELLQKELATWTPTEFRECDYNKFMS
  VLDTNKDCEVDFVEYVRSLACLCLYCHEYFKDCPSEPPCSQ
• Function: Binds both calcium and zinc. May be involved in calcium-dependent cuticle cell differentiation, hair shaft and hair cuticular barrier formation.
• Tissue Specificity: Skin specific, specifically expressed at the inner endocuticle of hair fibers.

Molecular Interaction Atlas (MIA) of This DOT

16 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-A3 (S100A3).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein S100-A3 (S100A3).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Protein S100-A3 (S100A3).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Protein S100-A3 (S100A3).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein S100-A3 (S100A3).	[5]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Protein S100-A3 (S100A3).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Protein S100-A3 (S100A3).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Protein S100-A3 (S100A3).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Protein S100-A3 (S100A3).	[9]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Protein S100-A3 (S100A3).	[10]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Protein S100-A3 (S100A3).	[11]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of Protein S100-A3 (S100A3).	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein S100-A3 (S100A3).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein S100-A3 (S100A3).	[16]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride increases the expression of Protein S100-A3 (S100A3).	[17]
Maleic Acid	DM4L0R7	Investigative	Maleic Acid increases the expression of Protein S100-A3 (S100A3).	[18]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Protein S100-A3 (S100A3).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Protein S100-A3 (S100A3).	[14]

References

• [1] 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.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] 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.
• [6] 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.
• [7] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [9] 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.
• [10] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [11] Dissecting progressive stages of 5-fluorouracil resistance in vitro using RNA expression profiling. Int J Cancer. 2004 Nov 1;112(2):200-12. doi: 10.1002/ijc.20401.
• [12] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [13] Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.
• [18] Profiling transcriptomes of human SH-SY5Y neuroblastoma cells exposed to maleic acid. PeerJ. 2017 Apr 5;5:e3175.