Branchio‐oto‐renal syndrome associated mutations in Eyes Absent 1 result in loss of phosphatase activity

Abstract

The Eyes Absent (Eya) proteins are tyrosine phosphatases and transcriptional activators involved in cell-fate determination and organ development. Mutations in the gene encoding Eya homologue 1 have been implicated in the multi-organ developmental disorder branchio-oto-renal syndrome (BOR) and in ocular defects. Here we report that BOR-associated mutations lead to a loss of phosphatase activity in Eya1 proteins, while mutations associated with ocular defects yield Eya1 proteins with near normal levels of phosphatase activity. Furthermore we demonstrate that the N-terminal domain attenuates the catalytic activity of Eya suggesting a mechanism of regulation.