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Symbol MTOR contributors: mct/shn - updated : 27-03-2018
HGNC name mechanistic target of rapamycin (serine/threonine kinase)
HGNC id 3942
Corresponding disease
FCDBC2 focal cortical dysplasia of Taylor balloon cell type 2
MSMR macrocephaly, seizures, mental retardation
Location 1p36.22      Physical location : 11.166.588 - 11.322.608
Synonym name
  • FK506 binding protein 12-rapamycin associated protein 2
  • rapamycin target protein
  • mammalian target of rapamycin complex 1
  • FKBP12-rapamycin complex-associated protein 1
  • FKBP-rapamycin associated protein
  • rapamycin associated protein FRAP2
  • dJ576K7.1 (FK506 binding protein 12-rapamycin associated protein 1)
  • mammalian target of rapamycin
  • mammalian TOR complex 1
  • Synonym symbol(s) RAFT1, FRAP2, FRAP1, FRAP, FLJ44809, RAPT1, mTORC1
    TYPE functioning gene
    SPECIAL FEATURE arranged in tandem
    STRUCTURE 156.02 kb     58 Exon(s)
    MAPPING cloned Y linked   status confirmed
    Map pter - D1S2736 - D1S1635 - MTOR - D1S1151 - D1S2667 - cen
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    57 - 8733 289 2549 - 1994 7809080
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   lowly
    Digestiveintestinesmall intestine  moderately
    Endocrineparathyroid   highly
     thyroid   highly
    Lymphoid/Immunelymph node   highly
     thymus   highly
    Nervousbrain   lowly
    Reproductivefemale systemplacenta  lowly
     female systemovary  moderately
     male systemtestis  highly
    Visualeyeretina  predominantly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow   
    Muscularstriatumskeletal highly
    SystemCellPubmedSpeciesStageRna symbol
    cell lineage
    cell lines Mg-63 and Jurkat cells
    at STAGE
  • N-terminal half of the protein contains 20 tandem HEAT repeats
  • C-terminal half contains a :
  • large FRAP-ATM domain
  • TRRAP domain
  • FAT domain
  • FKB12 and rapamycin-binding domain
  • serine/threonine kinase catalytic domain
  • negative regulatory domain and a C-terminal FAT (FATC) domain necessary for MTOR activity
    interspecies homolog to yeast TOR1 and TOR2
    ortholog to Frap1, Rattus norvegicus
    ortholog to Frap1, Mus musculus
    ortholog to frap1, Danio rerio
  • phosphatidylinositol kinase related, PI3/PI4-kinase family
  • ataxia telangiectasia mutated-related family of proteins
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
  • MTOR is localized to late endosomal/lysosomal compartments in mammalian cells
  • basic FUNCTION
  • involved in cell cycle progression, DNA recombination and DNA damage detection
  • T-cell binding protein, involved in the rapamycin pathway, leading to G1 cell cyle progression
  • controlling the expression of ribosomal protein genes via FHL1
  • involved in suppression of Kv1.1 channel mRNA translation in dendrites
  • stimulates the creatine transporter SLC6A8 through mechanisms at least partially shared by the serum and glucocorticoid-inducible kinase SGK1
  • involved in signaling pathways controlling cell growth
  • the human mTOR/FRAP pathway acts as an ATP sensor
  • mTOR signaling plays a role in the brain mechanisms that respond to nutrient availability, regulating energy balance
  • mTOR is a cellular fuel sensor whose hypothalamic activity is directly tied to the regulation of energy intake
  • mTOR is necessary for the maintenance of mitochondrial oxidative function
  • signaling complex that promotes protein translation and cell growth by phosphorylating components of the translation machinery
  • controls 4E-BP1 and p70(s6k) phosphorylation indirectly by restraining a phosphatase (
  • may play a major role in IL-12-induced IFN-gamma production by activated T cells (
  • regulating SREBF1, contributing to Akt-dependent cell growth
  • the insulin/mTOR pathway can partially account for cone death in rod dystrophies
  • in a healthy retina inhibits autophagy of rod and cone photoreceptors
  • nutrient-sensing protein kinase that regulates numerous cellular processes
  • modulation of its signaling contributes to chondrocyte differentiation, perhaps through its ability to regulate IHH
  • regulates MAF1 nucleoplasm-to-nucleolus translocation
  • involved in the regulation of F3 expression
  • controls cell growth mostly through inhibition of EIF4EBP1 and EIF4EBP2 and activation of S6K kinase
  • associates with GTF3C1, is recruited to pol III-transcribed genes, and relieves their repression by MAF1
  • major sensor of nutrient and energy availability in the cell and regulates a variety of cellular processes, including growth, proliferation, and metabolism
  • negative feedback responses from the MTOR pathway to receptors required to transduce niche-derived self-renewal signals in the loss of stem cell potential
  • controls MAF1, a key repressor of RNA polymerase III transcription, and add a new branch to the signal transduction cascade immediately downstream of CRTC1
  • integrates numerous environmental and upstream signaling inputs to function as a key controller of cell size, proliferation and metabolism
  • phosphorylates its target sites in AKT1 and PKC when these sites are accessible during translation
  • controls dendritic arbor morphology by enhancing cross talk between dynamic microtubules and actin through CLIP1 and IQGAP1
  • highly conserved serine-threonine kinase activated in response to growth factors and nutrients
  • MTOR signaling is a downstream pathway regulated by the MID1/PP2A axis, suggesting that MTOR plays a key role in Opitz syndrome pathogenesis
  • implicated in the mechanical regulation of skeletal muscle mass
  • RPS6KB1 and MTOR regulate RAC1-driven platelet activation and aggregation
  • important, highly conserved, regulator of cell growth
  • essential for skeletal myogenesis through controlling distinct cellular pathways
  • MTOR signaling network functions as a pivotal regulatory cascade during the development of the cerebral cortex
  • is an essential mediator of AKT1-induced senescence
  • master growth regulator that is stimulated by amino acids
  • regulates mitochondrial activity through PPARGC1A and regulates glycogen levels through PKB/AKT1
  • major function of MTOR is to regulate protein synthesis, which it is thought to control through several substrates, including the S6 kinases (S6Ks), the inhibitory eIF4E-binding proteins (4E-BPs), and the eIF4G initiation factors
  • novel role for MTOR in the maintenance of cellular homeostasis by regulating autophagy at the transcriptional level
  • is an integral component of the signaling pathway that mediates cellular senescence
  • critical role for the MTOR pathway in the maintenance of primordial ovarian follicle pool
  • PI3K- and insulin-dependent dendritic growth depends on the activation of both MTOR and CRTC2, and MTOR can act downstream of CRTC2 in developing mammalian neurons
  • MTOR but not CRTC2 is required for TNF-induced RPE cell migration
  • novel function of MTOR in regulating potassium homeostasis, demonstrating that loss of TSC1 and activation of MTOR results in dedifferentiation and dysfunction of the collecting ducts and causes hyperkalemia
  • TSC1-MTOR signaling contributes to the brown-to-white adipocyte phenotypic switch
  • MTOR is a critical regulator of CDK8 and its activating partner CCNC
  • role for NPRL2 and MTOR in the regulation of lysosomal-dependent cobalamin processing, methionine synthesis, and maintenance of cellular re-methylation potential, which are important during hematopoiesis
  • is a central regulator of lipid storage and metabolism
  • role of mammalian target of rapamycin (MTOR) in controlling and shaping the effector responses of innate immune cells
  • plays a role in controlling lysosome morphology and trafficking by modulating microtubule-based motor activity in leukocytes
  • MTOR inhibition coordinately activates the ubiquitin proteasome system (UPS) and autophagy, which provide essential amino acids and, together with the enhanced ubiquitination of anabolic proteins, help slow growth
  • kinase MTOR is a crucial signaling integrator of pro- and anti-inflammatory cytokines in NK cells
  • MTOR-mediated inhibition of PKD1 expression drives renal cyst formation in tuberous sclerosis complex
  • MTOR regulates the nutritional support of spermatogenesis by human Sertoli cell (hSC) and redox balance in these cells
  • when activated, MTOR phosphorylates AKT1S1 to enhance protein synthesis and simultaneously to facilitate the assembly of the beta subunits for forming immunoproteasomes
  • MTOR couples elevated protein synthesis with immunoproteasome biogenesis to protect cells against protein stress
  • CELLULAR PROCESS cell cycle
    protein, translation/synthesis
  • involved in cell cycle progression, DNA recombination and DNA damage detection
  • regulates translation initiation and entry into the cell cycle
  • mTOR/FRAP functions in regulatory pathways that control ribosome biogenesis and cell growth
  • PI3K/AKT/MTOR signaling pathway is involved in regulation of SPHK1, with AKT2 playing a key role in PDGF-induced SPHK1 expression in coronary artery smooth muscle cells
  • MTOR signaling plays an important role in EPO-mediated bone homeostasis
  • RHEB-MTOR/RPTOR pathway negatively regulates myogenic differentiation by suppressing IRS1-PIK3CA-AKT signaling
  • unique role for the TOR pathway in regulating cilia size through protein synthesis and suggest that appropriate and defined lengths are necessary for proper function of the cilium
  • PIK3CA/AKT1/MTOR signaling pathway, which was overactivated in aldosterone-producing adenomas (APAs), idiopathic hyperaldosteronism (IHA)compared with normal zona glomerulosa, may mediate aldosterone hypersecretion and participate in the development of primary aldosteronism (PA)
  • EPHB4/RASA1/MTOR signaling in endothelial cells promotes vascular malformation
  • MTOR signaling pathway may be involved in regulating the intestinal epithelial cells renewal along crypt-villus axis (CVA) and it may partly through affecting the antioxidant capacity and gene expression of intestinal epithelial cells
  • a component
  • complexed with RAPTOR
  • forms a multi-protein complex with FGFR1 in vascular smooth muscle cells
  • part of two distinct multiprotein complexes referred to as mTOR complex 1 (mTORC1) and 2 (mTORC2)
  • EYA2-SIX1 complex binds to and enhances the expression of MTOR in a synergistic manner
    small molecule other,
  • RAD001/everolimus
  • protein
  • FKBP12-rapamycin complex (
  • gephyrin, GPHN
  • activates and posphorylates STAT3
  • 14-3-3tau
  • protein kinase cdelta, PKCdelta (
  • c-Abl
  • a direct target of the PI3K-AKT signaling pathway in mitogen-stimulated cells
  • ubiquilin 1, UBQLN1
  • regulatory associated protein of MTOR, complex 1, RPTOR
  • CLIP-170
  • GbetaL
  • RPTOR independent companion of MTOR, complex 2, RICTOR
  • Ras homolog enriched in brain, RHEB (
  • Rheb like-1 protein, RhebL1
  • eukaryotic translation initiation factor 3, EIF3
  • eukaryotic translation initiation factor 4E binding protein 1, 4EBP1
  • phospholipase D2, PLD2
  • proline-rich Akt/PKB substrate 40 kDa, PRAS40 (
  • F-box and WD repeat domain containing 7, FBXW7 (
  • PRR5L binds MTOR via Raptor, and is an MTOR phosphorylation substrate
  • folliculin, FLCN
  • specific interaction between MTOR and RPS6K2 with HNRNPF is implicated in the regulation of cell proliferation
  • AKT1S1 is a MTOR binding protein that has complex effects on cell metabolism
  • MAF1 homolog (S. cerevisiae), MAF1 and general transcription factor IIIC, polypeptide 1, alpha 220kDa, GTF3C1 in nuclei
  • IQ motif containing GTPase activating protein 1, IQGAP1 and AKT
  • an intact CRTC2 is required for efficient binding of MTOR, and rictor to translating ribosomes
  • RHEB is required for MTOR and myelination in postnatal brain development
  • influences cellular growth by phosphorylating RPS6KA1, a serine/threonine kinase that regulates S6 ribosomal protein and other members of the translational machinery
  • interacting with DGKZ (DGKZ and TCR engagement activate signaling in both MTOR complexes 1 and 2 through the activation of the Ras-Mek1/2-Erk1/2-AP-1 pathway
  • RAC1 is a critical regulator of both MTOR and CRTC2 in response to growth-factor stimulation (binding of RAC1 to MTOR does not depend on the GTP-bound state of RAC1, but on the integrity of its C-terminal domain)
  • interaction with PPP1R15A (PPP1R15A induced by starvation serves to suppress the MTOR pathway)
  • activation of MTOR is regulated by a small G-protein, RHEB
  • regulates SREBF by controlling the nuclear entry of LPIN1, a phosphatidic acid phosphatase
  • interacting with LPIN1 (constitutively dephosphorylated, nuclear form of LPIN1 is both necessary and sufficient for mediating the effects of MTOR inhibition on the expression of nuclear SREBF proteins)
  • MTOR is linked to a critical component of the late endosome/lysosome, ATP6V1H
  • AKT1 induces senescence in cells via MTOR and TP53 in the absence of DNA damage
  • SQSTM1 interacts in an amino acid-dependent manner with MTOR and RAPTOR
  • MTOR signaling is important to regulate the expression, activity and secretion of matrix metalloproteinases MMP9
  • DEPTOR is an inhibitor of the MTOR kinase that is highly regulated at the posttranslational level
  • ATP6V0D2 is required for amino acid signaling to MTOR and functions between amino acids and the nucleotide loading of the Rag GTPases
  • phospholipase D, a PI(3)P effector, has been proposed to be a positive regulator of MTOR signaling and localization
  • influences the expression of PPARGC1A and therefore mitochondrial biogenesis through formation of a complex with PPARGC1A and the transcription factor YY1
  • KHDRBS1 regulates MTOR alternative splicing during adipogenesis
  • LARS is a key mediator for amino acid signaling to MTOR
  • RAB5A is implicated in the activation of MTOR by insulin and nutrients
  • Wortmannin inhibits MTOR activity, independent of AKT1
  • DDIT4 is a negative regulator of MTOR and its overexpression delays the onset of replicative senescence
  • CCL5 simultaneously activates AMPK and MTOR signaling cascades to regulate glucose uptake and chemotaxis in activated T cells
  • MARK4 is an AMP-activated kinase-related kinase, and a negative regulator of MTOR
  • RRAGA have a critical role in nutrient sensing by MTOR and in neonatal survival during fasting
  • UCHL1 is a key regulator of the dichotomy between MTOR and CRTC2 signaling
  • WDFY1 and LAMP2 can likely influence MTOR activity and regulate autophagy
  • RAB12 promotes constitutive degradation of SLC36A4, whose accumulation in RAB12-knockdown cells modulates MTOR activity and autophagy
  • during cellular stress the dual specificity kinase DYRK3 regulates the stability of P-granule-like structures and MTOR signaling
  • when DYRK3 is active, it allows stress granule dissolution, releasing MTOR for signaling and promoting its activity by directly phosphorylating the MTOR inhibitor AKT1S1
  • specific domains of MTOR, RICTOR, or MAPKAP1 interacted with the internal domain (AA. 221-402) of NBN
  • BRSK2 is a unique pancreas-specific effector protein of MTOR signaling
  • link between HAP1 and TSC1 that regulates neuronal MTOR signaling and neuronal morphogenesis
  • controls mitochondrial activity and biogenesis by selectively promoting translation of nucleus-encoded mitochondria-related mRNAs via inhibition of the eukaryotic translation initiation factor EIF4EBP1, EIF4EBP2
  • RPTOR in MTOR complex 1 is believed to recruit EIF4EBP1, facilitating phosphorylation of EIF4EBP1 by the kinase MTOR
  • liver MTOR controls IGF1 bioavailability by regulation of protein kinase CSNK2A1 and IGFBP1 phosphorylation in fetal growth restriction
  • GNGT1, GNG2, GNB1, GNB2, GNB3, interacts with MTOR and promotes its activation
  • CIP2A is a key modulator of MTOR and autophagy
  • TSC1, TSC2, negatively regulates the mammalian target of rapamycin complex 1 (MTOR) a master regulator of protein synthesis, cell growth and autophagy
  • AKT1S1 appears to reduce brain injury by converting cell signaling from AKT1 to MTOR
  • RAB12 regulates MTOR activity and autophagy through controlling SLC36A4 trafficking from recycling endosomes to lysosomes, where SLC36A4 is degraded
  • STX12 translation is regulated by MTOR in injured neurons to promote axon regeneration
  • nutrient-sensing MTOR kinase pathway controls the nucleolar targeting of SENP3 by regulating its interaction with NPM1
  • MTOR activation inhibits eukaryotic translation initiation factor 4E-binding protein (EIF4EBP1) and activates ribosomal protein S6 kinase 1 (RPS6KB1), both of which stimulate translation
  • neuron-specific ARHGEF9 interacts with EIF3A, and its binding partner GPHN associates with MTOR
  • MTOR signaling inhibition ameliorates vascular calcification via Klotho upregulation
  • regulation of EIF4EBP1 in skeletal muscle may serve as an important conduit through which MTOR controls metabolism
  • BORCS6 is a LAMTOR1-interacting protein that regulates MTOR activity through its interaction with LAMTOR1 at the lysosome
  • interacts with both MTOR and its regulator RAB1A on the Golgi
  • MTOR is a functionally relevant target of FBXW7 in oligodendrocytes
  • sustained activation of MTOR signaling in skeletal muscle regulated whole-body metabolism through the induction of FGF21, which, over the long term, caused severe lipodystrophy
  • NPRL2 interacts with RPTOR in amino acid sufficiency to activate MTOR
  • CUL1 promoted MTOR activity and cap-dependent translation by enhancing the ubiquitination and degradation of DEPTOR
  • WAC is a regulator of energy-mediated MTOR activity
  • PKM activates MTOR signaling through phosphorylating MTOR inhibitor AKT1 substrate 1 (AKT1S1)
  • ZNRF2 appeared to augment MTOR and its downstream targets CCND1 and CDK in non-small cell lung cancer cells
  • phosphorylation of S348/S409 in LARP6 by MTOR stimulates the interaction of LARP6 and STRAP to coordinate translation of collagen mRNAs and to release LARP6 from the ER for new round of translation
  • function of RHEB to activate MTOR signaling
  • TFEB nucleo-cytoplasmic shuttling suggest an unpredicted role of MTOR in nuclear export
  • distinct roles of RHEB and RPTOR in activating MTOR for the self-renewal of hematopoietic stem cells
  • MTOR activation by RHEB and inhibition by AKT1S1
  • TFEB-mediated endocytosis is a critical process leading to activation of MTOR and autophagic function, thus identifying the importance of the dynamic endolysosomal system in cellular clearance
  • biphasic roles of MTOR in osteoclastogenesis, dosage-dependent effects of rapamycin on bone, and a calcineurin-MTOR-NFATC1 phosphorylation-regulatory signaling cascade
  • SLC36A1 can likely negatively regulate MTOR by controlling the cellular nutrient signal level
  • WDR35 is associated with RRAGA, RRAGB, RRAGC and might negatively influence MTOR activity
  • SLC1A5 is critical for activation of MTOR activity by amino acids, and is a transcriptional target of MYC
  • PKD1 is required to couple mechanical deflection of cilia to MTOR in tubular cells
  • FNIP1 modulates autophagy and energy response pathways in part through the regulation of AMPK, MTOR, and TFE3 in B cell progenitors
  • TFE3 transcriptional activity
  • OTUD5 is a novel positive regulator of the MTOR and CRTC2 signaling pathways (PMISD: 33110214)
  • MTOR directly phosphorylated OTUD5 and activated its DUB activity
  • the amino acid-mediated activation of MTOR is regulated by the N-terminal domain of SLC38A9
  • MTOR specifically controls TFEB and TFE3 cytosolic retention, whereas AMPK is essential for TFEB and
  • cell & other
    activated by coactivator of FHL1
    IKBKB through inactivation of TSC1 (dysregulation of the TSC1/FRAP1 signaling pathway by IKBKB significantly contributes to inflammation-mediated cancer pathogenesis)
    Phosphatidic acid
    G protein beta subunit-like protein
    insulin (
    directly activated by the small guanosine triphosphatase Ras homolog enriched in brain (RHEB), in a farnesylation-dependent manner
    ketamine which rapidly activated the mammalian target of rapamycin (MTOR) pathway, leading to increased synaptic signaling proteins
    inhibited by corepressor of FHL1
    The PML tumor suppressor protein
    RHEB, a Ras-like small GTPase, via FKBP38 binding to mTOR
    phosphatase and tensin homolog, PTEN
    TSC1 gene
    TXNIP that inhibits MTOR activity by binding to and stabilizing DDIT4 protein
    Phosphorylated by S6 kinase 1, S6K1 (
    Other targeted for ubiquitination and consequent degradation by binding to the tumor suppressor protein FBXW7
    Ragulator-Rag complex (MAPKSP1, ROBLD3 and C11ORF59) targets MTOR to the lysosomal surface and is necessary for its activation by amino acids
    bending of the cilia by flow is required for mTOR downregulation and cell-size control (
    cell-type-dependent regulation of MTOR by DDIT4 and the tumor suppressors TSC1/TSC2 and STK11 in response to hypoxia
    likely positive feedback loop between OTUD5 and MTOR signaling pathway
    corresponding disease(s) FCDBC2 , MSMR
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       gain of function
    in cyst-lining epithelial cells in polycystic kidney disease
    tumoral       gain of function
    activation is very strongly associated with malignant, compared to benign, melanocytic lesions
    constitutional       loss of function
    dysfunctional MTOR signaling in OS patients with MID1 mutations is therefore likely to significantly contribute to the Opitz phenotype
    constitutional somatic mutation      
    leading to focal cortical dysplasia type II (FCDII)
  • to variation of corneal curvature
  • Variant & Polymorphism SNP
  • seven single nucleotide polymorphisms (SNPs)associated with variation of corneal curvature
  • Candidate gene
    Therapy target
    . rapamycin and related drugs targeting the FRAP1 pathway are candidate for therapeutic approach to prevent or delay the onset of PKD
    . therapy for Lhermitte-Duclos disease (LDD), rare cerebellar tumor associated with Cowden disease through pharmacologic inhibition of MTOR
    inhibition may be needed for the development of an effective form of therapy for patients with BHD-associated kidney cancer
    RHEB and MTOR may be targets for melanoma therapy
    NMDA receptor blockade and stimulation of MTOR signaling will provide novel therapeutic targets for antidepressant drug development
    targeted therapy with mTOR inhibitors may have a role as an additional novel component in a subset of multiple myeloma patients
    MTOR-PTTG1 signaling axis may be targeted for the treatment of tumors with MTOR hyperactivation
    inhibition of SOCS5 and mTOR may be a potential therapeutic approach to inhibit hepatocellular carcinoma metastasis and prolong patient survival
  • in cell models, transgenic mice, and human brains of Huntington disease, mTOR is sequestered in polyglutamine aggregates that impairs its kinase activity, induces autophagy and reduces toxicity of polyglutamine expansions
  • homozygous mouse embryos, disrupted for the mTOR kinase domain, died shortly after implantation due to impaired cell proliferation in both embryonic and extraembryonic compartments (
  • embryonic development of homozygous mTOR(-/-) mice appears to be arrested at E5.5; such embryos are severely runted and display an aberrant developmental phenotype and a lesion in inner cell mass proliferation (
  • mTOR(+/-) mice do not display any overt phenotype, although mouse embryonic fibroblasts derived from these mice show a 50% reduction in mTOR protein levels (
  • skeletal muscle-specific inactivation of Mtor in mice results in smaller muscle fibers, fewer mitochondria, increased glycogen stores, and a progressive myopathy that causes premature death