Human Gene MTOR (ENST00000361445.9) from GENCODE V41
Description: Homo sapiens mechanistic target of rapamycin kinase (MTOR), mRNA. (from RefSeq NM_004958) RefSeq Summary (NM_004958): The protein encoded by this gene belongs to a family of phosphatidylinositol kinase-related kinases. These kinases mediate cellular responses to stresses such as DNA damage and nutrient deprivation. This protein acts as the target for the cell-cycle arrest and immunosuppressive effects of the FKBP12-rapamycin complex. The ANGPTL7 gene is located in an intron of this gene. [provided by RefSeq, Sep 2008]. Gencode Transcript: ENST00000361445.9 Gencode Gene: ENSG00000198793.14 Transcript (Including UTRs) Position: hg38 chr1:11,106,535-11,262,551 Size: 156,017 Total Exon Count: 58 Strand: - Coding Region Position: hg38 chr1:11,107,485-11,259,409 Size: 151,925 Coding Exon Count: 57
ID:MTOR_HUMAN DESCRIPTION: RecName: Full=Serine/threonine-protein kinase mTOR; EC=126.96.36.199; 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.
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. BC127611 - Homo sapiens cDNA clone IMAGE:40031732, partial cds. MB485435 - JP 2019206516-A/8: ANTI-INVASIVE/ANTI-METASTATIC DRUG FOR PANCREATIC CANCER CELL. HZ473917 - WO 2016002844-A/31: 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. MB485434 - JP 2019206516-A/7: ANTI-INVASIVE/ANTI-METASTATIC DRUG FOR PANCREATIC CANCER CELL. MB485432 - JP 2019206516-A/5: ANTI-INVASIVE/ANTI-METASTATIC DRUG FOR PANCREATIC CANCER CELL.