eyes absent homolog 3 (EYA3)

Function: - tyrosine phosphatase - specifically dephosphorylates Tyr-142 of histone H2AX - Tyr-142 phosphorylation of histone H2AX plays a central role in DNA repair & acts as a mark that distinguishes between apoptotic & repair responses to genotoxic stress - promotes efficient DNA repair by dephosphorylating H2AX, promoting the recruitment of DNA repair complexes containing MDC1 - its function as histone phosphatase probably explains its role in transcription regulation during organogenesis - coactivates SIX1, & seems to coactivate SIX2, SIX4 & SIX5 - repression of precursor cell proliferation in myoblasts by SIX1 is switched to activation through recruitment of EYA3 to the SIX1-DACH1 complex & seems to be dependent on EYA3 phosphatase activity - may be involved in development of the eye - phosphorylated upon DNA damage, probably by ATM or ATR - Ser-266 phosphorylation is required for localization at sites of DNA damage & directing interaction with H2AX - interacts with SIX1 & DACH1, & probably SIX2, SIX4, & SIX5 Cofactor: binds 1 Mg⁺² ion per subunit (putative) Kinetic parameters: - KM=1.8 uM for H2AX-Y142-phosphate - KM=72 uM for H2AX-S139-phosphate Structure: - belongs to the HAD-like hydrolase superfamily, EYA family Compartment: - cytoplasm (putative), nucleus - localizes at sites of DNA damage at double-strand breaks (DSBs) - with decreasing efficiency, translocalized to the nucleus by SIX2 & SIX5, & SIX4, respectively (putative) Alternative splicing: named isoforms=2

General

eyes absent homolog phosphoprotein tyrosine phosphatase (protein tyrosine phosphatate, PTP)

Properties

SIZE: entity length = 573 aa MW = 63 kD COMPARTMENT: cytoplasm cell nucleus STATE: active state MOTIF: acetylation site SITE: N-TERMINUS EFFECTOR-BOUND: acetyl Ser phosphorylation site {S266} aspartate residue {D309} Mg+2-binding site SITE: 309-309 aspartate residue {D311} Mg+2-binding site SITE: 311-311 Mg+2-binding site SITE: 537-537

Database Correlations

OMIM 601655 UniProt Q99504 Pfam PF00702 Entrez Gene 2140 Kegg hsa:2140 ENZYME 3.1.3.48