Eyes absent represents a class of protein tyrosine phosphatases.
The Eyes absent proteins are members of a conserved regulatory network implicated in the development of the eye, muscle, kidney and ear. Mutations in the Eyes absent genes have been associated with several congenital disorders including the multi-organ disease bronchio-oto-renal syndrome, congenital cataracts and late-onset deafness. On the basis of previous analyses it has been shown that Eyes absent is a nuclear transcription factor, acting through interaction with homeodomain-containing Sine oculis (also known as Six) proteins. Here we show that Eyes absent is also a protein tyrosine phosphatase. It does not resemble the classical tyrosine phosphatases that use cysteine as a nucleophile and proceed by means of a thiol-phosphate intermediate. Rather, Eyes absent is the prototype for a class of protein tyrosine phosphatases that use a nucleophilic aspartic acid in a metal-dependent reaction. Furthermore, the phosphatase activity of Eyes absent contributes to its ability to induce eye formation in Drosophila.
Rayapureddi
Jayanagendra P
JP
Division of Developmental Biology, Cincinnati Childrens Hospital Research Foundation, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA.
Kattamuri
Chandramohan
C
Steinmetz
Brian D
BD
Frankfort
Benjamin J
BJ
Ostrin
Edwin J
EJ
Mardon
Graeme
G
Hegde
Rashmi S
RS
D000595:Amino Acid Sequence; D000818:Animals; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology / Q000201:enzymology* / Q000235:genetics; D005123:Eye / Q000196:embryology / Q000201:enzymology / Q000378:metabolism; D005136:Eye Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity
D029721:Drosophila Proteins; D005136:Eye Proteins; C092694:eya protein, Drosophila; D017027:Protein Tyrosine Phosphatases