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FKBP12-rapamycin complex-associated protein; FK506-binding protein 12-rapamycin complex-associated protein 1; rapamycin target protein; RAPT1; mammalian target of rapamycin; mTOR (FRAP1, FRAP, FRAP2)
Function:
- role in cell cycle progression
- interacts with the FKBP12-rapamycin complex
- acts as the target for the cell-cycle arrest & immunosuppressive effects of the FKBP12-rapamycin complex
- rapamycin inhibits mTOR pathway
- component of the TORC1 complex
- component of the TORC2 complex
- role in actin cytoskeleton organization
- binds directly to PRR5 & RICTOR within the TORC2 complex
- forms complex with raptor
- binds UBQLN1
- upstream regulator of HIF-1 in cancer cells
- downstream targets include S6K1 & 4EBP1/eIF4E
- inhibited by several natural products [4]
- tuberin
- hamartin
- curcumin
- resveratrol
- epigallocatechin gallate
- caffeine
Structure:
- belongs to the PI3/PI4-kinase family
- contains 1 FAT domain
- contains 1 FATC domain
- contains 7 HEAT repeats
- contains 1 PI3K/PI4K domain
Expression:
- expressed in numerous tissues, with highest levels in testis
Notes:
- inhibition of FRAPA1 & the TORC1 complex may account for some of the benefits of caloric restriction
General
HEAT repeat-containing protein (HEATR)
protein kinase
Properties
SIZE: entity length = 2549 aa
MW = 289 kD
MOTIF: HEAT repeat {16-53}
Ser phosphorylation site {S567}
HEAT repeat {650-688}
HEAT repeat {859-897}
HEAT repeat {988-1025}
HEAT repeat {1069-1106}
HEAT repeat {1109-1148}
HEAT repeat {1150-1186}
MOTIF: Thr phosphorylation site {T1162}
Ser phosphorylation site {S1261}
FAT domain
NAME: FAT domain
SITE: 1382-1982
MOTIF: Tyr phosphorylation site
binding site
FOR-BINDING-OF: Paxillin
PI3K/PI4K {2182-2516}
MOTIF: Ser phosphorylation site {S2478}
Ser phosphorylation site {S2481}
FATC {2517-2549}
STATE: active state
References
- UniProt :accession P42345
- Entrez Gene :accession 2475
- Atlas of Genetics & Cytogenetics in Oncology & Haematology
http://atlasgeneticsoncology.org/genes/FRAP1ID40639ch1p36.html
- Hongyu Zhou,1 Yan Luo,1 and Shile Huang1,
Updates of mTOR inhibitors
Anticancer Agents Med Chem. 2010 September 1, 10(7):571-581
PMID: 20812900
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2980558/
Component-of
target of rapamycin 2 complex (TORC2 complex)
Databases & Figures
OMIM 601231
UniProt P42345
PFAM correlations
Entrez Gene 2475
Kegg hsa:2475
RTK -> PI-3-kinase -> Akt -> ...