InterPro domain: IPR003152

Phosphatidylinositol kinase (PIK)-related kinases participate in meiotic andV(D)J recombination, chromosome maintenance and repair, cell cycleprogression, and cell cycle checkpoints, and their dysfunction can result in arange of diseases, including immunodeficiency, neurological disorder andcancer. The catalytic kinase domain is highly homologuous to that ofphosphatidylinositol 3- and 4-kinases. Nevertheless, membersof the PIK-related family appear functionally distinct, as none of them hasbeen shown to phosphorylate lipids, such as phosphatidylinositol; instead,many have Ser/Thr protein kinase activity. The PI-kinase domain of members ofthe PIK-related family is wedged between the ~550-amino acid-long FAT (FRAP,ATM, TRRAP) domain [ 1 ] and the ~35 residue C-terminal FATC domain [ 2 ].

It has been proposed that the FAT domain could be of importance as astructural scaffold or as a protein-binding domain, or both [ 3 ].

The TOR1 FATC domain, in its oxidized form, consists of an alpha-helix and awell structured COOH-terminal disulfide-bonded loop.Reduction of the disulfide bond dramatically increases the flexibility withinthe COOH-terminal loop region. The reduction may alter the binding behavior ofFATC to its partners [ 3 ].

1. PIK-related kinases: DNA repair, recombination, and cell cycle checkpoints. Science 270, 50-1
2. FAT: a novel domain in PIK-related kinases. Trends Biochem. Sci. 25, 225-7
3. The solution structure of the FATC domain of the protein kinase target of rapamycin suggests a role for redox-dependent structural and cellular stability. J. Biol. Chem. 280, 20558-64