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Protein: MTOR_HUMAN

Serine/threonine-protein kinase mTOR

FUNCTION: Kinase subunit of both mTORC1 and mTORC2, which regulates cell growth and survival in response to nutrient and hormonal signals. mTORC1 is activated in response to growth factors or amino-acids. Growth factor-stimulated mTORC1 activation involves AKT1-mediated phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB GTPase that potently activates the protein kinase activity of mTORC1. Amino-acid-signaling to mTORC1 requires its relocalization to the lysosomes mediated by the Ragulator complex and the Rag GTPases. Activated mTORC1 up- regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. mTORC1 phosphorylates EIF4EBP1 and releases it from inhibiting the elongation initiation factor 4E (eiF4E). mTORC1 phosphorylates and activates S6K1 at 'Thr-421', which then promotes protein synthesis by phosphorylating PDCD4 and targeting it for degradation. Phosphorylates MAF1 leading to attenuation of its RNA polymerase III-repressive function. mTORC2 is also activated by growth. factors, but seems to be nutrient-insensitive. mTORC2 seems to function upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors. mTORC2 promotes the serum-induced formation of stress-fibers or F-actin. mTORC2 plays a critical role in AKT1 'Ser-473' phosphorylation, which may facilitate the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDK1 which is a prerequisite for full activation. mTORC2 regulates the phosphorylation of SGK1 at 'Ser-422'. mTORC2 also modulates the phosphorylation of PRKCA on 'Ser-657'. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. more...

ENZYME REGULATION: Kinase activity is positively regulated by RHEB and negatively regulated by DEPTOR.

SUBUNIT: Interacts with PPAPDC3 and PML (By similarity). Part of the mammalian target of rapamycin complex 1 (mTORC1) which contains MTOR/FRAP1, MLST8, RPTOR and AKT1S1. mTORC1 binds to and is inhibited by FKBP12-rapamycin. Part of the mammalian target of rapamycin complex 2 (mTORC2) which contains MTOR, MLST8, PROTOR1, RICTOR and MAPKAP1. Contrary to mTORC1, mTORC2 does not bind to and is not sensitive to FKBP12-rapamycin. Binds directly to PROTOR1 and RICTOR within the mTORC2 complex. Interacts with UBQLN1. Interacts with DEPTOR. Interacts with TTI1 and TELO2.

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: Autophosphorylated; when part of mTORC1 or mTORC2.

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";

GENE SYNONYMS: FRAP FRAP1 FRAP2.

COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License.

 

Organism:

  • Homo sapiens

Gene Symbol:

  • MTOR

Synonyms:

  • Mechanistic target of rapamycin
  • FK506-binding protein 12-rapamycin complex-associated protein 1
  • RAPT1
  • Mammalian target of rapamycin
  • Rapamycin target protein 1
  • FKBP12-rapamycin complex-associated protein
  • 2.7.11.1
  • mTOR

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