title: The Eyes Absent proteins in development and disease.
abstract: The Eyes Absent (EYA) proteins, first described in the context of fly eye development, are now implicated in processes as disparate as organ development, innate immunity, DNA damage repair, photoperiodism, angiogenesis, and cancer metastasis. These functions are associated with an unusual combination of biochemical activities: tyrosine phosphatase and threonine phosphatase activities in separate domains, and transactivation potential when associated with a DNA-binding partner. EYA mutations are linked to multiorgan developmental disorders, as well as to adult diseases ranging from dilated cardiomyopathy to late-onset sensorineural hearing loss. With the growing understanding of EYA biochemical and cellular activity, biological function, and association with disease, comes the possibility that the EYA proteins are amenable to the design of targeted therapeutics. The availability of structural information, direct links to disease states, available animal models, and the fact that they utilize unconventional reaction mechanisms that could allow specificity, suggest that EYAs are well-positioned for drug discovery efforts. This review provides a summary of EYA structure, activity, and function, as they relate to development and disease, with particular emphasis on recent findings.
authors.affiliation: Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Tadjuidje
authors.forename: Rashmi S
authors.initials: RS
authors.lastname: Hegde
mesh_terms: D000818:Animals; D019280:Branchio-Oto-Renal Syndrome / Q000235:genetics / Q000473:pathology; D002465:Cell Movement / Q000235:genetics; D016764:Cell Polarity / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D029721:Drosophila Proteins / Q000737:chemistry / Q000502:physiology*; D047108:Embryonic Development / Q000235:genetics*; D005136:Eye Proteins / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D009369:Neoplasms / Q000235:genetics / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000235:genetics; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C117736:EYA4 protein, human; D005136:Eye Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D015534:Trans-Activators; C092694:eya protein, Drosophila; C104381:EYA1 protein, human; C106938:EYA2 protein, human; C540714:EYA3 protein, human; D017027:Protein Tyrosine Phosphatases