title: FHA domains as phospho-threonine binding modules in cell signaling.
abstract: Forkhead-associated (FHA) domains are present in >200 diverse proteins in all phyla from bacteria to mammals and seem to be particularly prevalent in proteins with cell cycle control functions. Recent work from several laboratories has considerably improved our understanding of the structure and function of these domains that were virtually unknown a few years ago, and the first disease associations of FHA domains have now emerged. FHA domains form 11-stranded beta-sandwiches that contain some 100-180 amino acid residues with a high degree of sequence diversity. FHA domains act as phosphorylation-dependent protein-protein interaction modules that preferentially bind to phospho-threonine residues in their targets. Interestingly, point mutations in the human CHK2 gene that lead to single-residue amino acid substitutions in the FHA domain of this cell cycle checkpoint kinase have been found to cause a subset of cases of the Li-Fraumeni multi-cancer syndrome.
authors.affiliation: St. Vincent's Institute of Medical Research, Fitzroy, Victoria 3065, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Hammet
authors.forename: Brietta L
authors.initials: BL
authors.lastname: Pike
authors.forename: Carolyn J
authors.initials: CJ
authors.lastname: McNees
authors.forename: Lindus A
authors.initials: LA
authors.lastname: Conlan
authors.forename: Nora
authors.initials: N
authors.lastname: Tenis
authors.forename: Jörg
authors.initials: J
authors.lastname: Heierhorst
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010769:Phosphothreonine / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D010769:Phosphothreonine