Gene Symbol: EYA3
Description: EYA transcriptional coactivator and phosphatase 3
Alias: eyes absent homolog 3, eyes absent 3
Species: human
Products:     EYA3

Top Publications

  1. Ohto H, Kamada S, Tago K, Tominaga S, Ozaki H, Sato S, et al. Cooperation of six and eya in activation of their target genes through nuclear translocation of Eya. Mol Cell Biol. 1999;19:6815-24 pubmed
    ..Coexpression of Six2, Six4, or Six5 induced nuclear translocation of Eya1, Eya2, and Eya3, which were otherwise distributed in the cytoplasm...
  2. Ikeda K, Watanabe Y, Ohto H, Kawakami K. Molecular interaction and synergistic activation of a promoter by Six, Eya, and Dach proteins mediated through CREB binding protein. Mol Cell Biol. 2002;22:6759-66 pubmed
    ..Recruitment of CBP to the immobilized chromatin DNA template was dependent on FLAG-Dach and GAL4-Eya3. These results indicate that CBP is a mediator of the interaction between Eya and Dach...
  3. Cook P, Ju B, Telese F, Wang X, Glass C, Rosenfeld M. Tyrosine dephosphorylation of H2AX modulates apoptosis and survival decisions. Nature. 2009;458:591-6 pubmed publisher
  4. Krishnan N, Jeong D, Jung S, Ryu S, Xiao A, Allis C, et al. Dephosphorylation of the C-terminal tyrosyl residue of the DNA damage-related histone H2A.X is mediated by the protein phosphatase eyes absent. J Biol Chem. 2009;284:16066-70 pubmed publisher
    ..X. We demonstrate that EYA2 and EYA3 displayed specificity for Tyr-142 of H2A.X in assays in vitro...
  5. Miller S, Lan Z, Hardiman A, Wu J, Kordich J, Patmore D, et al. Inhibition of Eyes Absent Homolog 4 expression induces malignant peripheral nerve sheath tumor necrosis. Oncogene. 2010;29:368-79 pubmed publisher
    ..Our findings identify a role of EYA4 and possibly interacting SIX and DACH proteins in MPNSTs and suggest the EYA4 pathway as a rational therapeutic target. ..
  6. Robin T, Smith A, McKinsey E, Reaves L, Jedlicka P, Ford H. EWS/FLI1 regulates EYA3 in Ewing sarcoma via modulation of miRNA-708, resulting in increased cell survival and chemoresistance. Mol Cancer Res. 2012;10:1098-108 pubmed publisher
    ..Herein, we show that the DNA repair protein and transcriptional cofactor, EYA3, is highly expressed in Ewing sarcoma tumor samples and cell lines compared with mesenchymal stem cells, the ..
  7. Abdelhak S, Kalatzis V, Heilig R, Compain S, Samson D, Vincent C, et al. A human homologue of the Drosophila eyes absent gene underlies branchio-oto-renal (BOR) syndrome and identifies a novel gene family. Nat Genet. 1997;15:157-64 pubmed
    ..highly conserved 271-amino acid C-terminal region was also found in the products of two other human genes (EYA2 and EYA3), demonstrating the existence of a novel gene family...
  8. Borsani G, DeGrandi A, Ballabio A, Bulfone A, Bernard L, Banfi S, et al. EYA4, a novel vertebrate gene related to Drosophila eyes absent. Hum Mol Genet. 1999;8:11-23 pubmed
    ..On the basis of map position and expression pattern, EYA4 is a candidate for oculo-dento-digital (ODD) syndrome, but no EYA4 mutations were found in a panel of ODD patients. ..
  9. Li X, Oghi K, Zhang J, Krones A, Bush K, Glass C, et al. Eya protein phosphatase activity regulates Six1-Dach-Eya transcriptional effects in mammalian organogenesis. Nature. 2003;426:247-54 pubmed

More Information


  1. Tadjuidje E, Hegde R. The Eyes Absent proteins in development and disease. Cell Mol Life Sci. 2013;70:1897-913 pubmed publisher
    ..This review provides a summary of EYA structure, activity, and function, as they relate to development and disease, with particular emphasis on recent findings. ..
  2. Ikeno T, Weil Z, Nelson R. Dim light at night disrupts the short-day response in Siberian hamsters. Gen Comp Endocrinol. 2014;197:56-64 pubmed publisher
    ..that expression levels of genes implicated in the photoperiodic response, Mel-1a melatonin receptor, Eyes absent 3, thyroid stimulating hormone receptor, gonadotropin-releasing hormone, and gonadotropin-inhibitory hormone, ..
  3. Wood S, Loudon A. Clocks for all seasons: unwinding the roles and mechanisms of circadian and interval timers in the hypothalamus and pituitary. J Endocrinol. 2014;222:R39-59 pubmed publisher
    ..Summer-like melatonin signals activate a PT-expressed clock-regulated transcription regulator (EYA3), which in turn drives the expression of the TSHβ sub-unit, leading to a sustained increase in TSH expression...
  4. Ashbrook D, Delprato A, Grellmann C, Klein M, Wetzel R, Overall R, et al. Transcript co-variance with Nestin in two mouse genetic reference populations identifies Lef1 as a novel candidate regulator of neural precursor cell proliferation in the adult hippocampus. Front Neurosci. 2014;8:418 pubmed publisher
    ..of bioinformatics approaches identified six novel candidate genes involved in adult neurogenesis; Amer3, Eya3, Mtdh, Nr4a3, Polr2a, and Tbkbp1...
  5. Krueger A, Drasin D, Lea W, Patrick A, Patnaik S, Backos D, et al. Allosteric inhibitors of the Eya2 phosphatase are selective and inhibit Eya2-mediated cell migration. J Biol Chem. 2014;289:16349-61 pubmed publisher
    ..that these compounds are reversible inhibitors that selectively inhibit the phosphatase activity of Eya2, but not Eya3. Our mutagenesis results suggest that this class of compounds does not bind to the active site and the binding does ..
  6. Wang Y, Pandey R, Riffle S, Chintala H, Wikenheiser Brokamp K, Hegde R. The Protein Tyrosine Phosphatase Activity of Eyes Absent Contributes to Tumor Angiogenesis and Tumor Growth. Mol Cancer Ther. 2018;17:1659-1669 pubmed publisher
    ..Deletion of Eya3 in host endothelial cells significantly reduced tumor angiogenesis and limited tumor growth in xenografts...
  7. Majumdar G, Rani S, Kumar V. Hypothalamic gene switches control transitions between seasonal life history states in a night-migratory photoperiodic songbird. Mol Cell Endocrinol. 2015;399:110-21 pubmed publisher
    ..rhodopsin, melanopsin, neuropsin and peropsin), transduction (pax6, bmal1, clock, per2 and casr), induction (eya3, tshβ, dio2 and dio3, gnrh and gnih) and metabolism (NPY, sirtuin1, foxO1, hmgcr, citrate synthase and ..
  8. Majumdar G, Trivedi A, Gupta N, Kumar V. Circadian synchronization determines critical day length for seasonal responses. Physiol Behav. 2015;147:282-90 pubmed publisher
    ..this, we measured expression levels of genes implicated in the photoperiod-induced changes in reproduction (EYA3, TSH beta, DIO2, DIO3, GNRH and GNIH) and metabolism (SIRT1, HMGCR, FASN and PPAR alpha) in photosensitive ..
  9. Majumdar G, Yadav G, Rani S, Kumar V. Bird eyes distinguish summer from winter: Retinal response to acute photoperiod change in the night-migratory redheaded bunting. J Chem Neuroanat. 2015;68:55-60 pubmed publisher
    ..implicated in the light perception (opsins, rhodopsin, neuropsin, melanopsin, peropsin) and photoperiod induction (eya3, tsh-β, dio2, dio3) was measured at hours 15 and 19 (hour 0 = light on) on the first long day...
  10. Wood S, Christian H, Miedzinska K, Saer B, Johnson M, Paton B, et al. Binary Switching of Calendar Cells in the Pituitary Defines the Phase of the Circannual Cycle in Mammals. Curr Biol. 2015;25:2651-62 pubmed publisher
    ..We show that individual PT thyrotrophs can be in one of two binary states reflecting either a long (EYA3(+)) or short (CHGA(+)) photoperiod, with the relative proportion in each state defining the phase of the circannual ..
  11. Wang Y, Tadjuidje E, Pandey R, Stefater J, Smith L, Lang R, et al. The Eyes Absent Proteins in Developmental and Pathological Angiogenesis. Am J Pathol. 2016;186:568-78 pubmed publisher
    ..endothelial cell (EC) migration contributes to a delay in postnatal development of the retinal vasculature when Eya3 is deleted specifically in ECs...
  12. Mentel M, Badea R, Necula Petrareanu G, Mallikarjuna S, Ionescu A, Szedlacsek S. Expression, Purification, and Kinetic Analysis of PTP Domains. Methods Mol Biol. 2016;1447:39-66 pubmed publisher
    ..we provide detailed protocols for expression and purification of the catalytic domain of RPTPμ and full length Eya3 as well as the extracellular region of PTPBR7...
  13. Mishra I, Singh D, Kumar V. Seasonal alterations in the daily rhythms in hypothalamic expression of genes involved in the photoperiodic transduction and neurosteroid-dependent processes in migratory blackheaded buntings. J Neuroendocrinol. 2017;29: pubmed publisher
    ..We measured the 4-hourly mRNA expression of genes involved in the photoperiodic transduction (OPN5, EYA3, CGA, TSHβ, DIO2, DIO3) and neurosteroid-dependent processes (AR, CYP19, ERα, ERβ) in the hypothalamus of ..
  14. Mentel M, Ionescu A, Puscalau Girtu I, Helm M, Badea R, Rizzoli S, et al. WDR1 is a novel EYA3 substrate and its dephosphorylation induces modifications of the cellular actin cytoskeleton. Sci Rep. 2018;8:2910 pubmed publisher
    ..We show here that Src kinase phosphorylates tyrosine residues in two human EYA family members, EYA1 and EYA3. Both can autodephosphorylate these residues and their nuclear and cytoskeletal localization seems to be controlled ..
  15. Zhang H, Stavnezer E. Ski regulates muscle terminal differentiation by transcriptional activation of Myog in a complex with Six1 and Eya3. J Biol Chem. 2009;284:2867-79 pubmed publisher
    ..Activation of the MEF3 site required direct interaction of Ski with Six1 and Eya3 mediated by the evolutionarily conserved Dachshund homology domain of Ski...
  16. Mishra I, Bhardwaj S, Malik S, Kumar V. Concurrent hypothalamic gene expression under acute and chronic long days: Implications for initiation and maintenance of photoperiodic response in migratory songbirds. Mol Cell Endocrinol. 2017;439:81-94 pubmed publisher
    Hypothalamic expression of the thyroid hormone (TH) responsive gonadostimulatory (eya3, cga, tsh?, dio2, dio3, gnrh, gnih) and neurosteroid pathway genes (androgen receptor [ar], aromatase [cyp19], estrogen receptor [er] ? and ?) was ..
  17. Pandey R, Wang T, Tadjuidje E, McDonald M, Rettie A, Hegde R. Structure-activity relationships of benzbromarone metabolites and derivatives as EYA inhibitory anti-angiogenic agents. PLoS ONE. 2013;8:e84582 pubmed publisher
    ..Longer substituents at the 2 position of the benzofuran ring promoted EYA3 binding and inhibition, but were less effective in cellular assays, likely reflecting non-specific protein binding ..
  18. Zhang L, Zhou H, Li X, Vartuli R, Rowse M, Xing Y, et al. Eya3 partners with PP2A to induce c-Myc stabilization and tumor progression. Nat Commun. 2018;9:1047 pubmed publisher
    ..Importantly, Eya3 alters the regulation of c-Myc by PP2A, increasing c-Myc stability by enabling PP2A-B55? to dephosphorylate pT58, ..
  19. Zimmerman J, Bui Q, Steingrimsson E, Nagle D, Fu W, Genin A, et al. Cloning and characterization of two vertebrate homologs of the Drosophila eyes absent gene. Genome Res. 1997;7:128-41 pubmed
    ..Our findings support the notion that several families of genes (Pax-6/eyeless, Six-3/sine oculis, and Eya) play related and critical roles in the eye for both files and vertebrates. ..