FAT: a novel domain in PIK-related kinases

Phosphatidylinositol kinases are found in all eukaryotes and serve important functions in phosphatidylinositol (PI) signaling pathways 1 Majerus P.W. et al. Recent insights in phosphatidylinositol signaling. Cell. 1990; 63: 459-465 Abstract Full Text PDF PubMed Scopus (232) Google Scholar . In addition to the PI-kinase domain, most of these proteins have a number of accessory domains, usually involved in protein–protein interactions, that specify the role in a given pathway. A few examples of such domain organizations are shown in Fig. 1aFig. 1b. Recently, a new subfamily of the PI-kinase superfamily has emerged, called PIK-related 2 Carr A.M. Control of cell cycle arrest by the Mec1sc/Rad3sp DNA structure checkpoint pathway. Curr. Opin. Genet. Dev. 1997; 7: 93-98 Crossref PubMed Scopus (73) Google Scholar , 3 Hoekstra M.F. Responses to DNA damage and regulation of cell cycle checkpoints by the ATM protein kinase family. Curr. Opin. Genet. Dev. 1997; 7: 170-175 Crossref PubMed Scopus (148) Google Scholar . Although these proteins are large (2000–4000 amino acids), they only share similarity to classical PI kinases in the ∼300-amino-acid kinase domain. Figure 1b(b) Multiple alignment of the FAT domain in all known sequences. Residues were colored by Belvu based on average pairwise BLOSUM62 score exceeding 0.3 (gray shade) or 1.3 (blue). Sequence names are either the Swissprot ID or a TREMBL accession number followed by a dot and a name mimicking a Swissprot ID, except for TRRAP_HUMAN for which only an EMBL accession number is available. Because Q22258 could not be classified unambiguously we used a question mark. View Large Image Figure Viewer Download Hi-res image