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

More general terms

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

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=2140
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:2140
• OMIM: https://mirror.omim.org/entry/601655
• UniProt: http://www.uniprot.org/uniprot/Q99504.html