{PDOC51189}
{PS51189; FAT}
{PS51190; FATC}
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* FAT and FATC domains profiles *
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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 alpha-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.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Last update: March 2019 / Profile revised.

[ 1] Keith C.T., Schreiber S.L.
     "PIK-related kinases: DNA repair, recombination, and cell cycle
     checkpoints."
     Science 270:50-51(1995).
     PubMed=7569949
[ 2] Bosotti R., Isacchi A., Sonnhammer E.L.L.
     "FAT: a novel domain in PIK-related kinases."
     Trends Biochem. Sci. 25:225-227(2000).
     PubMed=10782091
[ 3] Dames S.A., Mulet J.M., Rathgeb-Szabo K., Hall M.N., Grzesiek S.
     "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. 280:20558-20564(2005).
     PubMed=15772072; DOI=10.1074/jbc.M501116200

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