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PROSITE documentation PDOC51189 [for PROSITE entry PS51189]

FAT and FATC domains profiles





Description

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.

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 https://prosite.expasy.org/prosite_license.html --------------------------------------------------------------------------------.

Last update:

March 2019 / Profile revised.

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Technical section

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

FAT, PS51189; FAT domain profile  (MATRIX)

FATC, PS51190; FATC domain profile  (MATRIX)


References

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
DOI10.1074/jbc.M501116200



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.

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