The FHA domain is a modular phosphopeptide recognition motif

Mol Cell. 1999 Sep;4(3):387-94. doi: 10.1016/s1097-2765(00)80340-8.


FHA domains are conserved sequences of 65-100 amino acid residues found principally within eukaryotic nuclear proteins, but which also exist in certain prokaryotes. The FHA domain is thought to mediate protein-protein interactions, but its mode of action has yet to be elucidated. Here, we show that the two highly divergent FHA domains of Saccharomyces cerevisiae Rad53p, a protein kinase involved in cell cycle checkpoint control, possess phosphopeptide-binding specificity. We also demonstrate that other FHA domains bind peptides in a phospho-dependent manner. These findings indicate that the FHA domain is a phospho-specific protein-protein interaction motif and have important implications for mechanisms of intracellular signaling in both eukaryotes and prokaryotes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Binding, Competitive
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Checkpoint Kinase 2
  • Conserved Sequence
  • DNA Damage
  • Eukaryotic Cells
  • Molecular Sequence Data
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism
  • Phosphopeptides / genetics
  • Phosphopeptides / metabolism*
  • Prokaryotic Cells
  • Protein Binding
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Protein-Serine-Threonine Kinases*
  • Recombinant Fusion Proteins / metabolism
  • Saccharomyces cerevisiae Proteins*
  • Signal Transduction


  • Cell Cycle Proteins
  • Nuclear Proteins
  • Peptide Fragments
  • Phosphopeptides
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins
  • rad9 protein
  • Protein Kinases
  • Checkpoint Kinase 2
  • Protein-Serine-Threonine Kinases
  • RAD53 protein, S cerevisiae