PROSITE documentation PDOC51189
FAT and FATC domains profiles


Phosphatidylinositol kinase (PIK)-related kinases participate in meiotic and V(D)J recombination, chromosome maintenance and repair, cell cycle progression, and cell cycle checkpoints, and their dysfunction can result in a range of diseases, including immunodeficiency, neurological disorder and cancer. The catalytic kinase domain is highly homologuous to that of phosphatidylinositol 3- and 4-kinases (see <PDOC00710>). Nevertheless, members of the PIK-related family appear functionally distinct, as none of them has been shown to phosphorylate lipids, such as phosphatidylinositol; instead, many have Ser/Thr protein kinase activity. The PI-kinase domain of members of the 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 a structural scaffold or as a protein-binding domain, or both [1].

The TOR1 FATC domain, in its oxidized form, consists of an α-helix and a well structured COOH-terminal disulfide-bonded loop (see <PDB:1W1N>). Reduction of the disulfide bond dramatically increases the flexibility within the COOH-terminal loop region. The reduction may alter the binding behavior of FATC to its partners [3].

Some proteins known to contain FAT and FATC domains are listed below:

  • Yeast protein kinase MEC1/ESR1 (mitosis entry checkpoint mutant).
  • Animal serine/threonine-protein kinase ATR.
  • Yeast target of rapamycin (TOR) 1 and 2.
  • Mammalian FKBP12-rapamycin complex-associated protein (FRAP) or mammalian target of rapamycin (MTOR).
  • Yeast telomer length regulation protein TEL1.
  • Eukaryotic ataxia telangiectasia mutant (ATM) serine/threonine-protein kinase, a key component of the signal-transduction pathway activated by DNA damage.
  • Eukaryotic ATM and Rad3-related (ATR) serine/threonine-protein kinase.
  • Yeast transcription-associated protein 1 (TRA1).
  • Mammalian transformation/Transcription Domain Associated Proteins (TRRAPs). Their PI-kinase domain lacks the catalytic residues.

The profiles we developed cover the entire FAT and FATC domains.

Last update:

March 2019 / Profile revised.


Technical section

PROSITE methods (with tools and information) covered by this documentation:

FAT, PS51189; FAT domain profile  (MATRIX)

FATC, PS51190; FATC domain profile  (MATRIX)


1AuthorsKeith C.T. Schreiber S.L.
TitlePIK-related kinases: DNA repair, recombination, and cell cycle checkpoints.
SourceScience 270:50-51(1995).
PubMed ID7569949

2AuthorsBosotti R. Isacchi A. Sonnhammer E.L.L.
TitleFAT: a novel domain in PIK-related kinases.
SourceTrends Biochem. Sci. 25:225-227(2000).
PubMed ID10782091

3AuthorsDames S.A. Mulet J.M. Rathgeb-Szabo K. Hall M.N. Grzesiek S.
TitleThe solution structure of the FATC domain of the protein kinase target of rapamycin suggests a role for redox-dependent structural and cellular stability.
SourceJ. Biol. Chem. 280:20558-20564(2005).
PubMed ID15772072

PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see prosite_license.html.


View entry in original PROSITE document format
View entry in raw text format (no links)