General Information of Drug Off-Target (DOT) (ID: OTPVLA73)

DOT Name Eyes absent homolog 2 (EYA2)
Synonyms EC 3.1.3.48
Gene Name EYA2
UniProt ID
EYA2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
3GEB; 3HB0; 3HB1; 4EGC; 5ZMA; 7F8G; 7F8H
EC Number
3.1.3.48
Pfam ID
PF00702
Sequence
MVELVISPSLTVNSDCLDKLKFNRADAAVWTLSDRQGITKSAPLRVSQLFSRSCPRVLPR
QPSTAMAAYGQTQYSAGIQQATPYTAYPPPAQAYGIPSYSIKTEDSLNHSPGQSGFLSYG
SSFSTSPTGQSPYTYQMHGTTGFYQGGNGLGNAAGFGSVHQDYPSYPGFPQSQYPQYYGS
SYNPPYVPASSICPSPLSTSTYVLQEASHNVPNQSSESLAGEYNTHNGPSTPAKEGDTDR
PHRASDGKLRGRSKRSSDPSPAGDNEIERVFVWDLDETIIIFHSLLTGTFASRYGKDTTT
SVRIGLMMEEMIFNLADTHLFFNDLEDCDQIHVDDVSSDDNGQDLSTYNFSADGFHSSAP
GANLCLGSGVHGGVDWMRKLAFRYRRVKEMYNTYKNNVGGLIGTPKRETWLQLRAELEAL
TDLWLTHSLKALNLINSRPNCVNVLVTTTQLIPALAKVLLYGLGSVFPIENIYSATKTGK
ESCFERIMQRFGRKAVYVVIGDGVEEEQGAKKHNMPFWRISCHADLEALRHALELEYL
Function
Functions both as protein phosphatase and as transcriptional coactivator for SIX1, and probably also for SIX2, SIX4 and SIX5. Tyrosine phosphatase that dephosphorylates 'Tyr-142' of histone H2AX (H2AXY142ph) and promotes efficient DNA repair via the recruitment of DNA repair complexes containing MDC1. 'Tyr-142' phosphorylation of histone H2AX plays a central role in DNA repair and acts as a mark that distinguishes between apoptotic and repair responses to genotoxic stress. Its function as histone phosphatase may contribute to its function in transcription regulation during organogenesis. Plays an important role in hypaxial muscle development together with SIX1 and DACH2; in this it is functionally redundant with EYA1.
Tissue Specificity Highest expression in muscle with lower levels in kidney, placenta, pancreas, brain and heart.
Reactome Pathway
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks (R-HSA-5693565 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Chlorothiazide DMLHESP Approved Eyes absent homolog 2 (EYA2) increases the Metabolic disorder ADR of Chlorothiazide. [11]
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10 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Eyes absent homolog 2 (EYA2). [1]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Eyes absent homolog 2 (EYA2). [2]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Eyes absent homolog 2 (EYA2). [3]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Eyes absent homolog 2 (EYA2). [4]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Eyes absent homolog 2 (EYA2). [5]
Selenium DM25CGV Approved Selenium increases the expression of Eyes absent homolog 2 (EYA2). [6]
Benzbromarone DMC3YUA Approved Benzbromarone decreases the activity of Eyes absent homolog 2 (EYA2). [7]
Tocopherol DMBIJZ6 Phase 2 Tocopherol increases the expression of Eyes absent homolog 2 (EYA2). [6]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Eyes absent homolog 2 (EYA2). [8]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Eyes absent homolog 2 (EYA2). [10]
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⏷ Show the Full List of 10 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Eyes absent homolog 2 (EYA2). [9]
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References

1 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
2 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.
3 Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
4 Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
5 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.
6 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
7 The EYA tyrosine phosphatase activity is pro-angiogenic and is inhibited by benzbromarone. PLoS One. 2012;7(4):e34806. doi: 10.1371/journal.pone.0034806. Epub 2012 Apr 24.
8 Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
9 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.
10 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
11 Genome-wide association analyses suggest NELL1 influences adverse metabolic response to HCTZ in African Americans. Pharmacogenomics J. 2014 Feb;14(1):35-40. doi: 10.1038/tpj.2013.3. Epub 2013 Feb 12.