mTOR
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.
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Protein type: ATYPICAL group; Autophagy; EC 2.7.11.1; FRAP subfamily; Kinase, protein; Motility/polarity/chemotaxis; PIKK family; Protein kinase, Ser/Thr (non-receptor); Protein kinase, atypical |
Chromosomal Location of human Ortholog: 1p36.22 |
Cellular Component:
cytoplasm; cytosol; dendrite; endomembrane system; endoplasmic reticulum membrane; Golgi membrane; lysosomal membrane; lysosome; membrane; mitochondrial outer membrane; nuclear envelope; nucleoplasm; nucleus; phagocytic vesicle; PML body; TORC1 complex; TORC2 complex
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Molecular Function:
ATP binding; identical protein binding; kinase activity; phosphoprotein binding; protein binding; protein kinase activity; protein serine kinase activity; protein serine/threonine kinase activity; ribosome binding; RNA polymerase III type 1 promoter sequence-specific DNA binding; RNA polymerase III type 2 promoter sequence-specific DNA binding; RNA polymerase III type 3 promoter sequence-specific DNA binding; TFIIIC-class transcription factor complex binding
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Biological Process:
'de novo' pyrimidine nucleobase biosynthetic process; activation of protein kinase B activity; anoikis; behavioral response to pain; calcineurin-NFAT signaling cascade; cardiac muscle cell development; cardiac muscle contraction; 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 osmotic stress; cellular response to starvation; cytoskeleton organization; DNA damage response; energy reserve metabolic process; germ cell development; heart morphogenesis; heart valve morphogenesis; inflammatory response; lysosome organization; macroautophagy; multicellular organism growth; negative regulation of apoptotic process; negative regulation of autophagy; negative regulation of calcineurin-NFAT signaling cascade; negative regulation of cell size; negative regulation of macroautophagy; negative regulation of protein localization to nucleus; neuronal action potential; nucleus localization; oligodendrocyte differentiation; peptidyl-serine phosphorylation; peptidyl-threonine phosphorylation; phosphorylation; positive regulation of actin filament polymerization; positive regulation of cell growth; positive regulation of cytoplasmic translational initiation; positive regulation of epithelial to mesenchymal transition; positive regulation of gene expression; positive regulation of glycolytic process; positive regulation of keratinocyte migration; positive regulation of lamellipodium assembly; positive regulation of lipid biosynthetic process; positive regulation of myotube differentiation; positive regulation of oligodendrocyte differentiation; positive regulation of pentose-phosphate shunt; positive regulation of peptidyl-tyrosine phosphorylation; positive regulation of phosphoprotein phosphatase activity; 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 translational initiation; 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 cell growth; regulation of cell size; regulation of cellular response to heat; regulation of circadian rhythm; regulation of GTPase activity; regulation of locomotor rhythm; regulation of macroautophagy; regulation of membrane permeability; regulation of myelination; regulation of osteoclast differentiation; regulation of protein kinase B signaling; regulation of signal transduction by p53 class mediator; response to amino acid; response to heat; response to insulin; response to nutrient; response to nutrient levels; rhythmic process; ruffle organization; T-helper 1 cell lineage commitment; TOR signaling; TORC1 signaling; voluntary musculoskeletal movement
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Disease: Focal Cortical Dysplasia Of Taylor; Smith-kingsmore Syndrome
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Reference #:
P42345
(UniProtKB)
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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
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Gene Symbols: MTOR
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Molecular weight:
288,892 Da
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Basal Isoelectric point:
6.73
Predict pI for various phosphorylation states
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CST Pathways:
AMPK Signaling
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Angiogenesis
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Autophagy Signaling
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B Cell Receptor Signaling
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ErbB/HER Signaling
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IL6 Signaling
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Insulin Receptor Signaling
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mTOR Signaling
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PI3K/Akt Signaling
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T Cell Receptor Signaling
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TGF-ß Signaling
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Translation: eIF4E and p70S6K
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Warburg Effect
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Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology®
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