ID:MTOR_HUMAN DESCRIPTION: RecName: Full=Serine/threonine-protein kinase mTOR; EC=2.7.11.1; AltName: Full=FK506-binding protein 12-rapamycin complex-associated protein 1; AltName: Full=FKBP12-rapamycin complex-associated protein; AltName: Full=Mammalian target of rapamycin; Short=mTOR; AltName: Full=Mechanistic target of rapamycin; AltName: Full=Rapamycin and FKBP12 target 1; AltName: Full=Rapamycin target protein 1; FUNCTION: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals. Functions as part of 2 structurally and functionally distinct signaling complexes mTORC1 and mTORC2 (mTOR complex 1 and 2). Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. This includes phosphorylation of EIF4EBP1 and release of its inhibition toward the elongation initiation factor 4E (eiF4E). Moreover, phosphorylates and activates RPS6KB1 and RPS6KB2 that promote 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. Regulates ribosome synthesis by activating RNA polymerase III-dependent transcription through phosphorylation and inhibition of MAF1 a RNA polymerase III-repressor. In parallel to protein synthesis, also regulates lipid synthesis through SREBF1/SREBP1 and LPIN1. To maintain energy homeostasis mTORC1 may also regulate mitochondrial biogenesis through regulation of PPARGC1A. mTORC1 also negatively regulates autophagy through phosphorylation of ULK1. Under nutrient sufficiency, phosphorylates ULK1 at 'Ser-758', disrupting the interaction with AMPK and preventing activation of ULK1. Also prevents autophagy through phosphorylation of the autophagy inhibitor DAP. mTORC1 exerts a feedback control on upstream growth factor signaling that includes phosphorylation and activation of GRB10 a INSR-dependent signaling suppressor. Among other potential targets mTORC1 may phosphorylate CLIP1 and regulate microtubules. As part of the mTORC2 complex MTOR may regulate other cellular processes including survival and organization of the cytoskeleton. Plays a critical role in the phosphorylation at 'Ser-473' of AKT1, a pro- survival effector of phosphoinositide 3-kinase, facilitating its activation by PDK1. mTORC2 may regulate the actin cytoskeleton, through phosphorylation of PRKCA, PXN and activation of the Rho- type guanine nucleotide exchange factors RHOA and RAC1A or RAC1B. mTORC2 also regulates the phosphorylation of SGK1 at 'Ser-422'. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. ENZYME REGULATION: Activation of mTORC1 by growth factors such as insulin involves AKT1-mediated phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB GTPase a potent activator of the protein kinase activity of mTORC1. Insulin-stimulated and amino acid-dependent phosphorylation at Ser-1261 promotes autophosphorylation and the activation of mTORC1. Activation by amino acids requires relocalization of the mTORC1 complex to lysosomes that is mediated by the Ragulator complex and the Rag GTPases RRAGA, RRAGB, RRAGC and RRAGD. On the other hand, low cellular energy levels can inhibit mTORC1 through activation of PRKAA1 while hypoxia inhibits mTORC1 through a REDD1-dependent mechanism which may also require PRKAA1. The kinase activity of MTOR within the mTORC1 complex is positively regulated by MLST8 and negatively regulated by DEPTOR and AKT1S1. MTOR phosphorylates RPTOR which in turn inhibits mTORC1. mTORC1 binds and is inhibited by the FKBP1A-rapamycin complex. mTORC2 is also activated by growth factors, but seems to be nutrient-insensitive. It may be regulated by RHEB but in an indirect manner through the PI3K signaling pathway. SUBUNIT: Part of the mammalian target of rapamycin complex 1 (mTORC1) which contains MTOR, MLST8, RPTOR, AKT1S1/PRAS40 and DEPTOR. Part of the mammalian target of rapamycin complex 2 (mTORC2) which contains MTOR, MLST8, PRR5, RICTOR, MAPKAP1 and DEPTOR. Interacts with PPAPDC3 and PML (By similarity). Interacts with PRR5 and RICTOR; the interaction is direct within the mTORC2 complex (By similarity). Interacts with UBQLN1 (By similarity). Interacts with TTI1 and TELO2 (By similarity). Interacts with CLIP1; phosphorylates and regulates CLIP1 (By similarity). INTERACTION: Q8TB45:DEPTOR; NbExp=5; IntAct=EBI-359260, EBI-2359040; Q13541:EIF4EBP1; NbExp=2; IntAct=EBI-359260, EBI-74090; Q9BVC4:MLST8; NbExp=4; IntAct=EBI-359260, EBI-1387471; Q8TCU6:PREX1; NbExp=11; IntAct=EBI-359260, EBI-1046542; Q6R327:RICTOR; NbExp=17; IntAct=EBI-359260, EBI-1387196; Q8N122:RPTOR; NbExp=12; IntAct=EBI-359260, EBI-1567928; Q96EB6:SIRT1; NbExp=2; IntAct=EBI-359260, EBI-1802965; SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side. Golgi apparatus membrane; Peripheral membrane protein; Cytoplasmic side. Mitochondrion outer membrane; Peripheral membrane protein; Cytoplasmic side. Lysosome. Cytoplasm (By similarity). Nucleus, PML body (By similarity). Note=Shuttles between cytoplasm and nucleus. Accumulates in the nucleus in response to hypoxia (By similarity). Targeting to lysosomes depends on amino acid availability and RRAGA and RRAGB. TISSUE SPECIFICITY: Expressed in numerous tissues, with highest levels in testis. PTM: Phosphorylated. Autophosphorylates when part of mTORC1 or mTORC2. Phosphorylation at Ser-1261 promotes autophosphorylation. SIMILARITY: Belongs to the PI3/PI4-kinase family. SIMILARITY: Contains 1 FAT domain. SIMILARITY: Contains 1 FATC domain. SIMILARITY: Contains 7 HEAT repeats. SIMILARITY: Contains 1 PI3K/PI4K domain. SEQUENCE CAUTION: Sequence=AAC39933.1; Type=Frameshift; Positions=956, 999; Sequence=BAE06077.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/FRAP1ID40639ch1p36.html"; WEB RESOURCE: Name=Wikipedia; Note=Mammalian target of rapamycin entry; URL="http://en.wikipedia.org/wiki/Mammalian_target_of_rapamycin"; WEB RESOURCE: Name=Target mTOR; Note=mTOR signaling pathway and mTOR inhibition resource; URL="http://www.targetmtor.com/index.jsp";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P42345
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0000166 nucleotide binding GO:0001030 RNA polymerase III type 1 promoter DNA binding GO:0001031 RNA polymerase III type 2 promoter DNA binding GO:0001032 RNA polymerase III type 3 promoter DNA binding GO:0001156 TFIIIC-class transcription factor binding GO:0004672 protein kinase activity GO:0004674 protein serine/threonine kinase activity GO:0005515 protein binding GO:0005524 ATP binding GO:0016301 kinase activity GO:0016740 transferase activity GO:0019901 protein kinase binding GO:0019904 protein domain specific binding GO:0042802 identical protein binding GO:0043022 ribosome binding GO:0044877 macromolecular complex binding GO:0051219 phosphoprotein binding
Biological Process: GO:0001558 regulation of cell growth GO:0001932 regulation of protein phosphorylation GO:0001933 negative regulation of protein phosphorylation GO:0001934 positive regulation of protein phosphorylation GO:0001938 positive regulation of endothelial cell proliferation GO:0003007 heart morphogenesis GO:0003179 heart valve morphogenesis GO:0005979 regulation of glycogen biosynthetic process GO:0006109 regulation of carbohydrate metabolic process GO:0006112 energy reserve metabolic process GO:0006207 'de novo' pyrimidine nucleobase biosynthetic process GO:0006281 DNA repair GO:0006468 protein phosphorylation GO:0007050 cell cycle arrest GO:0007165 signal transduction GO:0007281 germ cell development GO:0007420 brain development GO:0007569 cell aging GO:0007584 response to nutrient GO:0007616 long-term memory GO:0008361 regulation of cell size GO:0008542 visual learning GO:0009267 cellular response to starvation GO:0009791 post-embryonic development GO:0010507 negative regulation of autophagy GO:0010592 positive regulation of lamellipodium assembly GO:0010628 positive regulation of gene expression GO:0010718 positive regulation of epithelial to mesenchymal transition GO:0010831 positive regulation of myotube differentiation GO:0010942 positive regulation of cell death GO:0010976 positive regulation of neuron projection development GO:0014042 positive regulation of neuron maturation GO:0014736 negative regulation of muscle atrophy GO:0014823 response to activity GO:0016241 regulation of macroautophagy GO:0016242 negative regulation of macroautophagy GO:0016310 phosphorylation GO:0018105 peptidyl-serine phosphorylation GO:0018107 peptidyl-threonine phosphorylation GO:0021510 spinal cord development GO:0030030 cell projection organization GO:0030163 protein catabolic process GO:0030838 positive regulation of actin filament polymerization GO:0031397 negative regulation of protein ubiquitination GO:0031529 ruffle organization GO:0031641 regulation of myelination GO:0031669 cellular response to nutrient levels GO:0031929 TOR signaling GO:0031998 regulation of fatty acid beta-oxidation GO:0032095 regulation of response to food GO:0032148 activation of protein kinase B activity GO:0032516 positive regulation of phosphoprotein phosphatase activity GO:0032868 response to insulin GO:0032956 regulation of actin cytoskeleton organization GO:0034198 cellular response to amino acid starvation GO:0035176 social behavior GO:0035264 multicellular organism growth GO:0038202 TORC1 signaling GO:0040007 growth GO:0042060 wound healing GO:0042220 response to cocaine GO:0043087 regulation of GTPase activity GO:0043200 response to amino acid GO:0043276 anoikis GO:0043278 response to morphine GO:0043610 regulation of carbohydrate utilization GO:0045429 positive regulation of nitric oxide biosynthetic process GO:0045670 regulation of osteoclast differentiation GO:0045727 positive regulation of translation GO:0045792 negative regulation of cell size GO:0045859 regulation of protein kinase activity GO:0045945 positive regulation of transcription from RNA polymerase III promoter GO:0046777 protein autophosphorylation GO:0046889 positive regulation of lipid biosynthetic process GO:0048255 mRNA stabilization GO:0048661 positive regulation of smooth muscle cell proliferation GO:0048714 positive regulation of oligodendrocyte differentiation GO:0048738 cardiac muscle tissue development GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation GO:0050769 positive regulation of neurogenesis GO:0050882 voluntary musculoskeletal movement GO:0051496 positive regulation of stress fiber assembly GO:0051549 positive regulation of keratinocyte migration GO:0051896 regulation of protein kinase B signaling GO:0051897 positive regulation of protein kinase B signaling GO:0055006 cardiac cell development GO:0055013 cardiac muscle cell development GO:0060048 cardiac muscle contraction GO:0060135 maternal process involved in female pregnancy GO:0060252 positive regulation of glial cell proliferation GO:0060999 positive regulation of dendritic spine development GO:0061051 positive regulation of cell growth involved in cardiac muscle cell development GO:0070885 negative regulation of calcineurin-NFAT signaling cascade GO:0071230 cellular response to amino acid stimulus GO:0071233 cellular response to leucine GO:0071456 cellular response to hypoxia GO:0090335 regulation of brown fat cell differentiation GO:0090559 regulation of membrane permeability GO:1900034 regulation of cellular response to heat GO:1901216 positive regulation of neuron death GO:1901838 positive regulation of transcription of nuclear large rRNA transcript from RNA polymerase I promoter GO:1903691 positive regulation of wound healing, spreading of epidermal cells GO:1904000 positive regulation of eating behavior GO:1904056 positive regulation of cholangiocyte proliferation GO:1904058 positive regulation of sensory perception of pain GO:1904193 negative regulation of cholangiocyte apoptotic process GO:1904197 positive regulation of granulosa cell proliferation GO:1904206 positive regulation of skeletal muscle hypertrophy GO:1904213 negative regulation of iodide transmembrane transport GO:1904690 positive regulation of cytoplasmic translational initiation GO:1990253 cellular response to leucine starvation
LP830499 - Sequence 1 from Patent EP3211090. U88966 - Human protein rapamycin associated protein (FRAP2) gene, complete cds. AB209995 - Homo sapiens mRNA for FRAP1 variant protein, clone: ef01094. AK302863 - Homo sapiens cDNA FLJ60991 complete cds, highly similar to FKBP12-rapamycin complex-associated protein. AK304273 - Homo sapiens cDNA FLJ56559 complete cds, highly similar to FKBP12-rapamycin complex-associated protein. BC117166 - Homo sapiens FK506 binding protein 12-rapamycin associated protein 1, mRNA (cDNA clone MGC:150775 IMAGE:40125717), complete cds. L34075 - Human FKBP-rapamycin associated protein (FRAP) mRNA, complete cds. AB384693 - Synthetic construct DNA, clone: pF1KB1123, Homo sapiens FRAP1 gene for FKBP12-rapamycin complex-associated protein, complete cds, without stop codon, in Flexi system. AK126762 - Homo sapiens cDNA FLJ44809 fis, clone BRACE3044172, highly similar to FKBP12-rapamycin complex-associated protein. JD506378 - Sequence 487402 from Patent EP1572962. JD159533 - Sequence 140557 from Patent EP1572962. JD089021 - Sequence 70045 from Patent EP1572962. JD105180 - Sequence 86204 from Patent EP1572962. JD193187 - Sequence 174211 from Patent EP1572962. JD551053 - Sequence 532077 from Patent EP1572962. JD368094 - Sequence 349118 from Patent EP1572962. JD171795 - Sequence 152819 from Patent EP1572962. JD435342 - Sequence 416366 from Patent EP1572962. JD249010 - Sequence 230034 from Patent EP1572962. JD060421 - Sequence 41445 from Patent EP1572962. HZ473918 - WO 2016002844-A/32: ANTI-INVASIVE/ANTI-METASTATIC DRUG FOR PANCREATIC CANCER CELL. AK024393 - Homo sapiens cDNA FLJ14331 fis, clone PLACE4000320. L35478 - Homo sapiens RAPT1 (RAPT1) mRNA, partial cds. HZ473916 - WO 2016002844-A/30: ANTI-INVASIVE/ANTI-METASTATIC DRUG FOR PANCREATIC CANCER CELL. BC127611 - Homo sapiens cDNA clone IMAGE:40031732, partial cds. HZ473917 - WO 2016002844-A/31: ANTI-INVASIVE/ANTI-METASTATIC DRUG FOR PANCREATIC CANCER CELL. MB485435 - JP 2019206516-A/8: ANTI-INVASIVE/ANTI-METASTATIC DRUG FOR PANCREATIC CANCER CELL. MB485433 - JP 2019206516-A/6: ANTI-INVASIVE/ANTI-METASTATIC DRUG FOR PANCREATIC CANCER CELL. MB485434 - JP 2019206516-A/7: ANTI-INVASIVE/ANTI-METASTATIC DRUG FOR PANCREATIC CANCER CELL. HW795841 - JP 2014527827-A/1: Novel use of leucyl tRNA synthetase. LP057243 - Sequence 2 from Patent EP2758775. HZ473915 - WO 2016002844-A/29: ANTI-INVASIVE/ANTI-METASTATIC DRUG FOR PANCREATIC CANCER CELL. JD458424 - Sequence 439448 from Patent EP1572962. MB485432 - JP 2019206516-A/5: ANTI-INVASIVE/ANTI-METASTATIC DRUG FOR PANCREATIC CANCER CELL.
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
