EYA transcriptional coactivator and phosphatase 4 (EYA4)

EYA transcriptional coactivator and phosphatase 4 (EYA4) is a dual-function protein with an unusual combination of enzymatic and transcriptional coactivator activities. It belongs to the Eyes absent (EYA) family and exhibits both tyrosine and serine/threonine phosphatase activities in distinct domains, contributing to transcription regulation, DNA damage repair, and organ development, particularly in the ear and heart[1][3][4][5]. EYA4 interacts with and dephosphorylates substrates such as histone H2AX and Polo-like kinase 1 (PLK1), affecting centrosome function and mitotic progression[2]. It promotes the innate immune response and is indispensable for cardiac and auditory integrity, while its dysregulation has been implicated in hereditary hearing loss, dilated cardiomyopathy, and cancer. Mutations or altered regulation of EYA4 are associated with disease, and its unique phosphatase activity is a potential therapeutic target in oncology and immunology, though no established drugs currently exist[1][2][3][4][5].

Other names

Protein phosphatase EYA4Eyes absent homolog 4CMD1JDFNA10dJ78N10.1 (eyes absent)Eyes absent-like protein 4

Inhibition of phosphatase activity (tyrosine/serine-threonine): Blocks EYA4-dependent dephosphorylation of substrates, disrupts downstream signaling (mitotic progression, gene regulation), induces cell death in cancer models