Branchio-oto-renal syndrome associated mutations in Eyes Absent 1 result in loss of phosphatase activity.
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.
Rayapureddi
Jayanagendra P
JP
Cincinnati Children's Hospital Medical Center, Division of Developmental Biology, University of Cincinnati School of Medicine, Department of Pediatrics, 3333 Burnet Avenue, Cincinnati, OH 45229, United States.
Hegde
Rashmi S
RS
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D019280:Branchio-Oto-Renal Syndrome / Q000235:genetics*; D002384:Catalysis; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics*; D010744:Phosphoric Monoester Hydrolases / Q000172:deficiency*; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000235:genetics*; D016415:Sequence Alignment; D017384:Sequence Deletion / Q000235:genetics*; D040681:Structural Homology, Protein; D013379:Substrate Specificity
D004268:DNA-Binding Proteins; C466082:Eya3 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D010744:Phosphoric Monoester Hydrolases; C501156:Eya1 protein, mouse; D017027:Protein Tyrosine Phosphatases