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PROSITE documentation PDOC51189FAT and FATC domains profiles
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PURL: https://purl.expasy.org/prosite/documentation/PDOC51189
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.
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PROSITE methods (with tools and information) covered by this documentation:
| 1 | Authors | Keith C.T. Schreiber S.L. |
| Title | PIK-related kinases: DNA repair, recombination, and cell cycle checkpoints. | |
| Source | Science 270:50-51(1995). | |
| PubMed ID | 7569949 |
| 2 | Authors | Bosotti R. Isacchi A. Sonnhammer E.L.L. |
| Title | FAT: a novel domain in PIK-related kinases. | |
| Source | Trends Biochem. Sci. 25:225-227(2000). | |
| PubMed ID | 10782091 |
| 3 | Authors | Dames S.A. Mulet J.M. Rathgeb-Szabo K. Hall M.N. Grzesiek S. |
| Title | The solution structure of the FATC domain of the protein kinase target of rapamycin suggests a role for redox-dependent structural and cellular stability. | |
| Source | J. Biol. Chem. 280:20558-20564(2005). | |
| PubMed ID | 15772072 | |
| DOI | 10.1074/jbc.M501116200 |
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