Eyes absent homolog 2 (EYA2) (EYA2)

Eyes absent homolog 2 (EYA2) is a multi-functional protein that acts as both a transcriptional coactivator and a protein tyrosine phosphatase (UniProt). It is a member of the EYA family, characterized by a highly conserved C-terminal Eya Domain (ED) that exhibits a unique haloacid dehalogenase (HAD)-like phosphatase activity, making it the only known HAD-family member with tyrosine phosphatase function (MDPI, 2021). EYA2 plays a critical role in embryonic development and organogenesis, while in adult tissues, its expression is generally low (GeneCards). However, EYA2 is frequently upregulated in various malignancies, including breast cancer, glioblastoma, and medulloblastoma, where it promotes tumor growth, metastasis, and survival (NIH, 2023). It achieves this by dephosphorylating substrates like H2AX to promote DNA repair over apoptosis and by stabilizing oncoproteins such as MYC (Journal of Experimental Medicine, 2021). Consequently, the EYA2 tyrosine phosphatase domain is a significant therapeutic target, with research focusing on allosteric inhibitors that disrupt its catalytic activity by preventing the binding of essential magnesium ions (NIH, 2021).

Other names

EYA2Eyes absent 2Protein phosphatase EYA2EYA transcriptional coactivator and phosphatase 2

Allosteric inhibition of the C-terminal haloacid dehalogenase (HAD)-like tyrosine phosphatase domain, which prevents magnesium ion binding and enzymatic activity (NIH, 2021; NIH, 2022).