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FHA Domains as Phospho‐Threonine Binding Modules in Cell Signaling
Author(s) -
Hammet Andrew,
Pike Brietta,
McNees Carolyn,
Conlan Lindus,
Tenis Nora,
Heierhorst Jörg
Publication year - 2003
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1080/1521654031000070636
Subject(s) - threonine , biology , phosphorylation , amino acid , peptide sequence , gene , kinase , biochemistry , cell cycle , function (biology) , amino acid residue , microbiology and biotechnology , computational biology , genetics , serine
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. IUBMB Life, 55: 23‐27, 2003