an atypical kinase belonging to the PIKK family of kinases. A central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals. Is the catalytic subunit of two structurally and functionally distinct signaling complexes: mTORC1 and mTORC2 (mTOR complex 1 and 2). mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. It phosphorylates 4EBP1, releasing its inhibition of elongation initiation factor 4E (eiF4E); RPS6KB1 and -2, promoting protein synthesis by modulating the activity of their downstream targets including ribosomal protein S6, eukaryotic translation initiation factor EIF4B, and the inhibitor of translation initiation PDCD4. Stimulates ribosome synthesis by phosphorylating and inhibiting MAF1, an RNA polymerase III-repressor. mTORC1 negatively regulates autophagy through phosphorylation of ULK1. Also prevents autophagy through phosphorylation of the autophagy inhibitor DAP. It exerts negative feedback regulation on upstream growth factor signaling by phosphorylating and activating GRB10, an inhibitor of insulin, EGF and PDGF signaling. mTORC1 contains Raptor, a positive regulatory subunit and scaffold for recruiting substrates, two negative regulators, PRAS40 and DEPTOR, and mLST8; it is a target for the cell-cycle arrest and immunosuppressive effects of the FKBP12-rapamycin complex. mTORC2 is insensitive to rapamycin, and is a downstream effector of PI3K, regulating cellular processes including survival and organization of the cytoskeleton. Phosphorylates Ser473 of AKT1, a pro-survival effector of phosphoinositide 3-kinase, and Ser422 of SGK1, inhibiting apoptosis. Regulates osteoclastogenesis by adjusting the expression of CEBPB isoforms. Plays an important regulatory role in the circadian clock function; regulates period length and rhythm amplitude of the suprachiasmatic nucleus (SCN) and liver clocks. mTORC2 contains regulatory subunits Rictor and mSIN1, PROTOR, mLST8, and the negative regulator DEPTOR. mTORC1 suppresses PI3K activity via a strong negative feedback loop that involves S6K1. Inhibiting mTORC1 ablates this negative feedback loop and potentiates PI3K signaling. Note: This description may include information from UniProtKB.
Protein type: ATYPICAL group; Autophagy; EC 220.127.116.11; FRAP subfamily; Kinase, protein; Motility/polarity/chemotaxis; PIKK family; Protein kinase, Ser/Thr (non-receptor); Protein kinase, atypical
Molecular Function: ATP binding; identical protein binding; kinase activity; phosphoprotein binding; protein binding; protein domain specific binding; protein kinase activity; protein kinase binding; protein serine/threonine kinase activity; ribosome binding; RNA polymerase III type 1 promoter DNA binding; RNA polymerase III type 2 promoter DNA binding; RNA polymerase III type 3 promoter DNA binding; TFIIIC-class transcription factor complex binding; translation regulator activity
Biological Process: 'de novo' pyrimidine nucleobase biosynthetic process; activation of protein kinase B activity; anoikis; brain development; cardiac muscle cell development; cardiac muscle contraction; cell aging; cell cycle arrest; cellular response to amino acid starvation; cellular response to amino acid stimulus; cellular response to hypoxia; cellular response to leucine; cellular response to leucine starvation; cellular response to nutrient levels; cellular response to starvation; energy reserve metabolic process; germ cell development; heart morphogenesis; heart valve morphogenesis; long-term memory; maternal process involved in female pregnancy; mRNA stabilization; multicellular organism growth; negative regulation of autophagy; negative regulation of calcineurin-NFAT signaling cascade; negative regulation of cell size; negative regulation of cholangiocyte apoptotic process; negative regulation of iodide transmembrane transport; negative regulation of macroautophagy; negative regulation of muscle atrophy; negative regulation of protein phosphorylation; negative regulation of protein ubiquitination; peptidyl-serine phosphorylation; peptidyl-threonine phosphorylation; phosphorylation; positive regulation of actin filament polymerization; positive regulation of cell growth involved in cardiac muscle cell development; positive regulation of cholangiocyte proliferation; positive regulation of cytoplasmic translational initiation; positive regulation of dendritic spine development; positive regulation of eating behavior; positive regulation of endothelial cell proliferation; positive regulation of epithelial to mesenchymal transition; positive regulation of gene expression; positive regulation of glial cell proliferation; positive regulation of granulosa cell proliferation; positive regulation of keratinocyte migration; positive regulation of lamellipodium assembly; positive regulation of lipid biosynthetic process; positive regulation of myotube differentiation; positive regulation of neuron death; positive regulation of neuron maturation; positive regulation of nitric oxide biosynthetic process; positive regulation of oligodendrocyte differentiation; positive regulation of peptidyl-tyrosine phosphorylation; positive regulation of phosphoprotein phosphatase activity; positive regulation of protein kinase B signaling; positive regulation of protein phosphorylation; positive regulation of sensory perception of pain; positive regulation of skeletal muscle hypertrophy; positive regulation of smooth muscle cell proliferation; positive regulation of stress fiber assembly; positive regulation of transcription by RNA polymerase III; positive regulation of transcription of nucleolar large rRNA by RNA polymerase I; positive regulation of translation; positive regulation of wound healing, spreading of epidermal cells; post-embryonic development; protein autophosphorylation; protein catabolic process; protein phosphorylation; regulation of actin cytoskeleton organization; regulation of brown fat cell differentiation; regulation of carbohydrate utilization; regulation of cell growth; regulation of cell size; regulation of cellular response to heat; regulation of circadian rhythm; regulation of fatty acid beta-oxidation; regulation of glycogen biosynthetic process; regulation of GTPase activity; regulation of locomotor rhythm; regulation of macroautophagy; regulation of membrane permeability; regulation of myelination; regulation of osteoclast differentiation; regulation of response to food; regulation of translation at synapse, modulating synaptic transmission; response to activity; response to amino acid; response to cocaine; response to insulin; response to morphine; response to nutrient; response to nutrient levels; ruffle organization; social behavior; spinal cord development; T-helper 1 cell lineage commitment; TOR signaling; TORC1 signaling; visual learning; voluntary musculoskeletal movement; wound healing
Alt. Names/Synonyms: FK506 binding protein 12-rapamycin associated protein 1; FK506 binding protein 12-rapamycin associated protein 2; FK506-binding protein 12-rapamycin complex-associated protein 1; FKBP-rapamycin associated protein; FKBP12-rapamycin complex-associated protein; FKBP12-rapamycin complex-associated protein 1; FLJ44809; FRAP; FRAP1; FRAP2; Mammalian target of rapamycin; Mechanistic target of rapamycin; mechanistic target of rapamycin (serine/threonine kinase); mechanistic target of rapamycin kinase; mTOR; RAFT1; rapamycin and FKBP12 target 1; rapamycin associated protein FRAP2; Rapamycin target protein 1; RAPT1; Serine/threonine-protein kinase mTOR; SKS