EYA transcriptional coactivator and phosphatase 3 (EYA3)

EYA transcriptional coactivator and phosphatase 3 (EYA3) is a member of the Eyes absent (EYA) family, uniquely defined by dual functionality as a transcriptional coactivator and a protein phosphatase. Its C-terminal EYA domain confers tyrosine phosphatase activity, critical for dephosphorylating the 'Tyr-142' residue of histone H2AX, thereby promoting DNA repair and modulating apoptotic responses. Its N-terminal domain associates with the PP2A holoenzyme, imparting threonine phosphatase activity that regulates key cell cycle proteins such as c-Myc, stabilizing them and promoting cell proliferation, motility, and survival. EYA3 serves as a transcriptional coactivator, partnering with SIX1 and related proteins to regulate transcription and developmental processes. Aberrant EYA3 activity or expression is implicated in diverse pathologies, most notably metastatic cancers and developmental syndromes, making it a candidate therapeutic target under ongoing investigation.

Other names

Eyes absent homolog 3Eyes absent protein 3

Inhibitors would block phosphatase activity (tyrosine and threonine) and transcriptional coactivation, affecting cell proliferation, survival, and DNA repair, thereby reducing tumor growth/metastasis. Mechanism is context-dependent; modulation of PP2A interaction disrupts threonine phosphatase function.