Eyes absent homolog 2 (EYA2)

Eyes absent homolog 2 (EYA2) is a multifunctional human protein that serves as both a transcriptional coactivator and an aspartate-based protein tyrosine phosphatase, belonging structurally to the haloacid dehalogenase (HAD) superfamily[1][3][4]. EYA2 cooperates with SIX family transcription factors to drive gene expression during embryogenesis, organ development, and tissue regeneration. It also dephosphorylates specific tyrosine residues (notably pY142 on H2AX), regulating DNA damage responses, cell cycle progression, and apoptosis[2][3]. EYA2 mutations are linked to human developmental syndromes (such as branchio-oto-renal syndrome and congenital deafness) and overexpression/activity of EYA2 has been implicated in tumorigenesis, particularly in cancers where it can promote tumor progression by aiding proliferation, DNA repair, and invasion[1][3]. EYA2 is considered a promising therapeutic target in oncology due to its dual enzymatic and transcriptional functions contributing to cancer cell survival and proliferation, with small-molecule inhibitors currently under investigation[3][4].

Other names

Eyes absent homolog 2Protein phosphatase EYA2EYA2EAB1

Allosteric inhibition of phosphatase activity (e.g., 9987 binds and inhibits EYA2 tyrosine phosphatase domain)