Eyes absent represents a class of protein tyrosine phosphatases

Nature. 2003 Nov 20;426(6964):295-8. doi: 10.1038/nature02093.


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.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Drosophila Proteins / antagonists & inhibitors
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / embryology
  • Drosophila melanogaster / enzymology*
  • Drosophila melanogaster / genetics
  • Eye / embryology
  • Eye / enzymology
  • Eye / metabolism
  • Eye Proteins / antagonists & inhibitors
  • Eye Proteins / chemistry
  • Eye Proteins / metabolism*
  • Molecular Sequence Data
  • Mutation
  • Phosphorylation
  • Protein Tyrosine Phosphatases / antagonists & inhibitors
  • Protein Tyrosine Phosphatases / chemistry
  • Protein Tyrosine Phosphatases / metabolism*
  • Substrate Specificity


  • Drosophila Proteins
  • Eye Proteins
  • eya protein, Drosophila
  • Protein Tyrosine Phosphatases