Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCGGL6K)

• DOT Name: Protein S100-A5 (S100A5)
• Synonyms: Protein S-100D; S100 calcium-binding protein A5
• Gene Name: S100A5
• Related Disease:
  Carcinoma
  Clear cell renal carcinoma
  Renal cell carcinoma
  Asthma
  Chronic obstructive pulmonary disease
• UniProt ID: S10A5_HUMAN
• PDB ID: 2KAX; 2KAY; 4DIR; 6WN7
• Pfam ID: PF01023
• Sequence:
  METPLEKALTTMVTTFHKYSGREGSKLTLSRKELKELIKKELCLGEMKESSIDDLMKSLD
  KNSDQEIDFKEYSVFLTMLCMAYNDFFLEDNK
• Function: Binds calcium, zinc and copper. One subunit can simultaneously bind 2 calcium ions or 2 copper ions plus 1 zinc ion. Calcium and copper ions compete for the same binding sites.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma	DISH9F1N	Strong	Biomarker	[1]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[1]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[1]
Asthma	DISW9QNS	Limited	Biomarker	[2]
Chronic obstructive pulmonary disease	DISQCIRF	Limited	Biomarker	[2]

3 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-A5 (S100A5).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Protein S100-A5 (S100A5).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Protein S100-A5 (S100A5).	[12]

8 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-A5 (S100A5).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Protein S100-A5 (S100A5).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Protein S100-A5 (S100A5).	[6]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Protein S100-A5 (S100A5).	[7]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Protein S100-A5 (S100A5).	[8]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of Protein S100-A5 (S100A5).	[6]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Protein S100-A5 (S100A5).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein S100-A5 (S100A5).	[11]

References

• [1] Restricted expression of calcium-binding protein S100A5 in human kidney.Biochem Biophys Res Commun. 2002 Mar 1;291(3):623-7. doi: 10.1006/bbrc.2002.6494.
• [2] Toxicological effects of ambient fine (PM(2.5-0.18)) and ultrafine (PM(0.18)) particles in healthy and diseased 3D organo-typic mucocilary-phenotype models.Environ Res. 2019 Sep;176:108538. doi: 10.1016/j.envres.2019.108538. Epub 2019 Jun 15.
• [3] 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.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Arsenite and cadmium promote the development of mammary tumors. Carcinogenesis. 2020 Jul 14;41(7):1005-1014. doi: 10.1093/carcin/bgz176.
• [7] Inorganic arsenic exposure promotes malignant progression by HDAC6-mediated down-regulation of HTRA1. J Appl Toxicol. 2023 Aug;43(8):1214-1224. doi: 10.1002/jat.4457. Epub 2023 Mar 11.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [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.