MTOR (FK506 binding protein 12-rapamycin associated protein 1)

2008-06-01   Deborah A Altomare , Joseph R Testa 

Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA


Atlas Image



A map of the genomic organization of the human FRAP1 gene can be found at


The FRAP1 gene encompasses approximatively 156 kb and contains 58 exons. The gene resides on the minus strand. Reported location on human chromosome 1 is between 11,089,179-11,245,151 bases in NCBI36 coordinates and 11,089,180-11,245,176 bases in ensemble49 coordinates.


Transcript length is 8,680 bp.


No human pseudogene known.


Atlas Image
The amino acid residues corresponding to the FRAP1 (alias mTOR) protein domains are reported in pfam (see below: external links)
Pfam: PF00454: Phosphatidylinositol 3- and 4-kinase (2181-2431)
Pfam: PF02259: FAT domain (1513-1910)
Pfam: PF02260: FATC domain (2517-2549)
Pfam: PF08771: FKBP12 Rapamycin Binding domain (2015-2114)


The amino terminus of FRAP (alias, mTOR) consists of several tandem HEAT ( Huntingtin, EF2, A subunit of PP2A, TOR1) repeats) that are implicated in protein-protein interations (Hay and Sonenberg, 2004; Bhaskar and Hay, 2007). Each HEAT repeat contains two alpha helices of approximatively 40 amino acids.
The carboxy-terminal half contains two FAT (FRAP, ATM, TRAP) domains.
Upstream of the catalytic domain is the FRB (FKBP12-rapamycin binding) domain.
The catalytic domain has sequence similarity to the catalytic domain of phosphatidylinositol kinase (PIK), which is homologous to a family of other protein kinases termed PIKK (PIK-related kinase).
mTOR also contains a putative negative regulatory (NR) domain between the catalytic domain and FATC.
The FATC (FRAP, ATM, TRRAP C-terminal) domain is essential for the kinase activity. The FATC and FAT domains are thought to interact in a way the exposes the catalytic domain.
The protein consists of 2549 amino acids, with a predicted molecular weight of 288,891 Da.
The ternary complex of human FK506-binding protein ( FKBP12), the inhibitor rapamycin, and the FKBP12-rapamycin-binding (FRB) domain of human FRAP has been crystallized at a resolution of 2.7 angstroms (Choi et al., 1996), and then refined at 2.2 angstroms (Liang et al., 1999).
Phosphorylation sites of FRAP (alias, mTOR) are reported in .
Atlas Image


Expressed is found in numerous tissues, with high levels in testis.


Localization is predominantly cytoplasmic, but the protein is also associated with mitochondrial, endoplasmic reticulum and Golgi membranes (Guertin and Sabatini, 2007). A fraction of protein also may shuttle between the nucleus and cytoplasm.


There are more than 2500 articles specifically referring to FRAP1 or mTOR in PubMed. mTOR is central to several key cellular pathways including insulin signaling, regulation of eIF4e and p70S6 kinase, and hypoxia induced factor 1alpha ( HIF1alpha ) stimulation of vascular endothelial growth factor ( VEGF ). These pathways affect several processes including cell growth (size), protein translation, ribosome biogenesis, regulation of cell cycle progression, response to nutrients and cellular stress, angiogenesis, cell polarity and cytoskeletal reorganization. mTOR also has been shown to play a role in the regulation of autophagy (Pattingre et al., 2008), an adaptive cellular response to nutrient starvation whereby a cytoplasmic vacuole or autophagosome engulfs cellular macromolecules and organelles for degradation.
mTOR protein exists in two functionally distinct complexes named mTOR complex 1 (mTORC1) and complex 2 (mTORC2) (see figure under "Implicated in"). The regulator of mTORC1 signaling and kinase activity is the ras-like small GTPase Rheb (Ras homologue enriched in brain), which binds directly to the mTOR catalytic domain and enables mTORC1 to attain an active configuration (Avruch et al., 2006). Insulin/IGF stimulates the accumulation of Rheb-GTP through activated AKT and subsequent inhibition of the Rheb-GTPase-activating function of the tuberous sclerosis ( TSC1 / TSC2 ) heterodimer. Energy depletion decreases Rheb-GTP through the action of adenosine monophosphate-activated protein kinase (AMPK) to phosphorylate TSC2 and stimulate its Rheb-GTPase activating function and also HIFalpha-mediated transcriptional responses that act upstream of the TSC1/2 complex. Amino-acid depletion inhibits mTORC1 by acting predominantly downstream of the TSC complex, by interfering with the ability of Rheb to bind to mTOR.
As shown below, mTORC1 contains the core components mTOR, Raptor (regulatory associated protein of mTOR), and mLST8/GbetaL (G protein beta-subunit-like protein). It is the mTORC1 complex that is characteristically sensitive to inhibition by rapamycin. mTORC1 is a major regulator of ribosomal biogenesis and protein synthesis, largely through the phosphorylation/inactivation of the 4E-BPs (4E-binding proteins) and the phosphorylation/activation of S6K (ribosomal S6 kinase). The binding of S6K1 and 4E-BP1 to raptor requires a TOR signaling (TOS) motif, which contains an essential phenylalanine followed by four alternating acidic and small hydrophobic amino acids (Schalm and Blenis, 2002). Recently, a TOS motif also has been identified in the N terminus of HIF1alpha, which has been shown to interact with Raptor (Land and Tee, 2007). Furthermore, activation of mTOR by Rheb overexpression enhanced HIF1alpha activity and VEGF-A secretion under hypoxic conditions, whereas the mTOR inhibitor rapamycin blocked the pathway.
PRAS40 (proline-rich AKT substrate 40 kDa) is a novel mTOR binding partner that mediates AKT signals to mTOR independently of TSC1/TSC2 (Vander Haar et al., 2007). Hence, PRAS40 and Rheb are postulated to co-regulate mTORC1 (Guertin and Sabatini, 2007). PRAS40 binds mTORC1 via Raptor, and is an mTOR phosphorylation substrate (Thedieck et al., 2007). Moreover, PRAS40 binds the mTOR kinase domain and its interaction with mTOR is induced under conditions that inhibit mTOR signaling, such as nutrient or serum deprivation or mitochondrial metabolic inhibition (Vander Haar et al., 2007). PRAS40 contains a variant TOS motif and competes with S6K1 and 4E-BP1 by functioning as a direct inhibitor of substrate binding (Oshiro et al., 2007, Wang et al., 2007).
mTORC2 contains mTOR, Rictor (rapamycin-insensitive companion of mTOR), SIN1 (SAPK interacting protein) and mLST8/GbetaL. Proline rich protein 5-like (PRR5) protein also binds specifically to mTORC2, via Rictor and/or SIN1 (Thedieck et al., 2007). mTORC2 has been shown to regulate cell-cycle-dependent polarization of the actin cytoskeleton. Although not as sensitive to rapamycin as mTOR1, mTORC2 may be affected by prolonged rapamycin exposure in some cell types (Sarbassov et al., 2006; Zeng et al., 2007). However, the regulation of mTORC2 is largely unknown and does not function downstream of Rheb (Blaskar and Hay, 2007).
Direct genetic evidence for the importance of various components of the mTORC1 and/or mTORC2 complexes was provided by targeted disruption studies in mice (Guertin et al., 2006). Mice null for mTOR, as well as those lacking Raptor die early in embryonic development. However, mLST8-null embryos survive until e10.5 and resemble embryos missing Rictor. Collectively, mTORC1 function was found to be essential in early development, mLST8 was required only for mTORC2 signaling, and mTORC2 was found to be a necessary component of the AKT-FOXO and PKCalphaalpha pathways.


mouse (Mus musculus): Frap1, 99 % Amino Acid Similarity with Human FRAP1
rat (Rattus norvegicus): Frap1, 99% Amino Acid Similarity with Human FRAP1
dog (Canis familiaris): FRAP1, 99% Amino Acid Similarity with Human FRAP1
worm (Caenorhabditis elegans): B0261.2b, 51% Amino Acid Similarity with Human FRAP1
fruit fly (Drosophila melanogaster): Tor, 64% Amino Acid Similarity with Human FRAP1



No mutations are reported to date.

Implicated in

Entity name
Various cancers and hamartoma syndromes
Activation of mTOR signaling is associated with several hamartoma syndromes, as well as in cancer.
Among the dominantly inherited disorders classified as phakomatoses are tuberous sclerosis 1 and 2, Peutz-Jeghers syndrome, Cowden disease, neurofibromatosis 1 and neurofibromatosis 2, and von-Hippel-Lindau disease (Tucker et al., 2000). These disorders are characterized by scattered hamartomatous or adenomatous "two-hit" lesions that have a low probability of becoming malignant. These particular disorders are caused by germline mutations of certain tumor suppressor genes, i.e., TSC2 / TSC1, LKB1, PTEN, NF1 / NF2 and VHL, respectively, encoding proteins that intersect with the AKT/mTOR signaling pathway (Altomare and Testa, 2005).
Germline mutations of TSC1 and TSC2 each give rise to the hereditary disorder known as tuberous sclerosis complex (TSC) (Astrinidis and Henske, 2005; Jozwiak et al., 2008). Hamartomas arise in the central nervous system, kidney, heart, lung, and skin, with occasional tumors progressing to malignancy (i.e., renal cell carcinoma). In TSC tumor cells, biallelic inactivation of TSC2 or TSC1 results in constitutive mTOR activity, independent of AKT activation status. Aside from TSC, another rare lung disease known as pulmonary lymphangioleiomyomatosis (LAM) occurs from somatic or genetic mutations of TSC1 or TSC2 that lead to the activation of downstream mTOR (Krymskaya, 2008). These findings have provided rationale for the first rapamycin clinical trial for LAM (Goncharova and Krymskaya, 2008).
The LKB1 tumor suppressor/AMPK pathway is an alternate means of inactivating TSC2 and contributing to constitutive mTOR activation (Inoki et al., 2005; Kwiatkowski and Manning, 2005). The kinase controlling AMPK (AMP-activated protein kinase) has been identified as LKB1, which is encoded by the gene inactivated in Peutz-Jeghers syndrome, a disorder characterized by multiple gastrointestinal hamartomatous polyps. There is now experimental evidence that Peutz-Jeghers polyposis could be suppressed by targeting mTOR (Wei et al., 2008).
Germline PTEN mutations occur in 80% of patients with Cowden disease, a heritable multiple hamartoma syndrome with a high risk of breast, thyroid and endometrial carcinomas (Gustafson, et al., 2007). Decreased or absent expression of PTEN results in constitutive activation of the AKT/mTOR pathway.
Loss-of-function mutations in NF1 contributes to the neurofibromatosis type I familial cancer syndrome, which is characterized by benign neurofibromas and occasional malignant peripheral nerve sheath tumors (MPNSTs), as well as hamartomatous lesions of the eye, myeloid malignancies, gliomas, and pheochromocytomas. The NF1-encoded protein, neurofibromin, functions as a Ras-GAP, and deregulation of Ras due to NF1 inactivation is postulated to contribute to tumor development. Activated Ras signaling to PI3K results in activation of the AKT/mTOR pathway (Johannessen et al., 2005). The mTOR inhibitor rapamycin has been shown to suppress the growth of NF1-associated malignancies in a genetically modified mouse model (Johannessen et al., 2008). Like NF1, NF2 also can regulate AKT/mTOR signaling (Scoles, 2008); the NF2-encoded protein, merlin, does so by binding to PIKE (phosphatidylinositol 3-kinase enhancer).
Germline inactivation of the von Hippel-Lindau tumor suppressor gene (VHL) causes hamartomatous tumors associated with the von-Hippel-Lindau syndrome. Moreover, most renal cell carcinomas have biallelic alterations in the von VHL gene, resulting in the accumulation of hypoxia-inducible factors 1 and 2 , and downstream targets including vascular endothelial growth factor (VEGF) (Cho et al., 2007). The observed clinical efficacy of mTOR inhibitors in patients with renal cell carcinoma may be mediated in part by the dependence of efficient hypoxia-inducible factor translation.
Hybrid gene
A schematic model of mTOR signaling depicts various environmental and molecular interactions that influence the pathway. mTOR protein exists in two functionally distinct complexes named mTORC1 and mTORC2. Components are described above, under the Protein Function section. The classical phosphorylation substrates of mTORC1 are S6 kinases and 4E-BP1, although HIF1alpha and PRAS40 also have been shown to have TOR signaling motifs. Because mTOR is shared by both mTORC1 and mTORC2, there may be equilibrium between the two complexes, as well as competition for mTOR (Bhuskar and Hay, 2007). Insulin and other growth factors activate mTORC1 via activation of phosphatidylinositol 3-OH kinase (PI3K) and downstream AKT. Constitutive activation of mTORC1 can occur in the absence of TSC1 or TSC2. Once mTORC1 is activated, it is able to elicit a negative feedback loop to inhibit AKT activity. In opposition, mTORC2 is an activator of AKT, which places this pathway under both positive and negative controls mediated by mTOR. In contrast to growth factor activation of mTORC1, responses to cellular stresses such as energy depletion and amino acid deprivation are mediated by TSC1/2 and/or Rheb (Hay and Sonenberg, 2004; Guertin and Sabatini, 2007). AMPK is activated by reduced intracellular ATP levels and a concomitant increase in intracellular AMP. Under conditions of energy depletion, TSC2 is phosphorylated and activated by AMPK, thereby inhibiting mTORC1 activity. Amino acid starvation also elicits a decrease in mTORC1 activity through Rheb. Abundant evidence suggests that a deregulation between signaling components in the PI3K-AKT-TSC2-Rheb-mTORC1 pathway is a critical step in tumorigenesis. Tumor suppressor genes involved in predisposition to hamartomatous lesions are discussed above in the Implicated Diseases section.
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Entity name
Human malignant tumors
Activation of mTOR signaling has been reported in several types of human malignant tumors.
Clinical results have been reported for the mTOR inhibitors CCI-799 (Wyeth), RAD001 (Novartis) and AP23573 (Ariad Pharmaceuticals), all rapamycin analogs (Guertin and Sabatini, 2007). Therapeutic response is highly variable, suggesting that biomarkers still are needed for predicting response to rapamycin therapy. To date, some of the best clinical response rates to rapamycin have been observed in patients suffering from Kaposis sarcoma or mantle-cell lymphoma. Patients with renal cell carcinomas exhibiting a nonclear cell histology also appear to benefit from treatment with mTOR inhibitors (Hanna et al., 2008). Patients with advanced sarcomas are yet another subset of individuals that have benefited from therapeutic mTOR inhibition (Wan and Helman, 2007).
Collectively, there are a number of mechanisms that contribute to the deregulation of the AKT/mTOR pathway in human malignant tumors (Altomare and Testa, 2005; Wan and Helman, 2007). Phospho-AKT immunohistochemical staining is frequently associated with phospho-mTOR staining. mTOR has emerged as a validated therapeutic target in cancer (Abraham and Eng, 2008).
Specific to mTOR, mTORC2 activity was found to be elevated in glioma cell lines and primary tumors as compared with normal brain tissue (Masri et al., 2007). Overexpression of Rictor increased mTORC2 activity, anchorage-independent growth in soft agar, S-phase cell cycle distribution, motility, and integrin expression, whereas knockdown of Rictor inhibited these events. Xenograft studies also supported a role for increased mTORC2 activity in tumorigenesis and enhanced tumor growth. PKCalpha activity was shown to be dependent of Rictor-expression, consistent with the known regulation of actin organization by mTORC2 via PKCalpha. Collectively, these data suggest that mTORC2 is hyperactivated in gliomas and promotes tumor cell proliferation and invasive potential due to increased complex formation in the presence of overexpressed Rictor.
Recent data suggest that inhibition of mTOR results in clinical benefit in patients with poor prognostic features, and in preclinical models this therapeutic effect involves downregulation of HIF1alpha (Hanna et al., 2008).
Entity name
Huntington disease
mTOR has been implicated in Huntington disease, an inherited neurodegenerative disorder.
Ravikumar et al. (2004) showed that mTOR is sequestered in polyglutamine aggregates in cell models, transgenic mice, and human brains. Sequestration of mTOR impaired its kinase activity and induced autophagy, a key mechanism for clearance of mutant huntingtin fragments to protect against polyglutamine toxicity. Rapamycin also attenuated huntingtin accumulation and cell death in cell models, and inhibited autophagy. Furthermore, rapamycin protected against neurodegeneration in a fly model, and the rapamycin analog CCI-779 decreased aggregate formation in a mouse model of Huntington disease.


Pubmed IDLast YearTitleAuthors
182083692008Mammalian target of rapamycin as a therapeutic target in oncology.Abraham RT et al
162882922005Perturbations of the AKT signaling pathway in human cancer.Altomare DA et al
162882942005Tuberous sclerosis complex: linking growth and energy signaling pathways with human disease.Astrinidis A et al
170416222006Insulin and amino-acid regulation of mTOR signaling and kinase activity through the Rheb GTPase.Avruch J et al
174199902007The two TORCs and Akt.Bhaskar PT et al
172553062007The role of mammalian target of rapamycin inhibitors in the treatment of advanced renal cancer.Cho D et al
86625071996Structure of the FKBP12-rapamycin complex interacting with the binding domain of human FRAP.Choi J et al
175419832008Pulmonary lymphangioleiomyomatosis (LAM): progress and current challenges.Goncharova EA et al
176134332007Defining the role of mTOR in cancer.Guertin DA et al
179208992007Cowden syndrome.Gustafson S et al
182790682008mTOR pathway in renal cell carcinoma.Hanna SC et al
153140202004Upstream and downstream of mTOR.Hay N et al
156240192005Dysregulation of the TSC-mTOR pathway in human disease.Inoki K et al
181642022008TORC1 is essential for NF1-associated malignancies.Johannessen CM et al
181778192008Possible mechanisms of disease development in tuberous sclerosis.Jozwiak J et al
180940942008Smooth muscle-like cells in pulmonary lymphangioleiomyomatosis.Krymskaya VP et al
162443232005Tuberous sclerosis: a GAP at the crossroads of multiple signaling pathways.Kwiatkowski DJ et al
175023792007Hypoxia-inducible factor 1alpha is regulated by the mammalian target of rapamycin (mTOR) via an mTOR signaling motif.Land SC et al
100893031999Refined structure of the FKBP12-rapamycin-FRB ternary complex at 2.2 A resolution.Liang J et al
180898012007mTORC2 activity is elevated in gliomas and promotes growth and cell motility via overexpression of rictor.Masri J et al
175178832007The proline-rich Akt substrate of 40 kDa (PRAS40) is a physiological substrate of mammalian target of rapamycin complex 1.Oshiro N et al
179281272008Regulation of macroautophagy by mTOR and Beclin 1 complexes.Pattingre S et al
151461842004Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease.Ravikumar B et al
166033972006Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB.Sarbassov DD et al
179801642008The merlin interacting proteins reveal multiple targets for NF2 therapy.Scoles DR et al
119671492002Identification of a conserved motif required for mTOR signaling.Schalm SS et al
180303482007PRAS40 and PRR5-like protein are new mTOR interactors that regulate apoptosis.Thedieck K et al
107499072000National Cancer Institute Workshop Report: the phakomatoses revisited.Tucker M et al
172777712007Insulin signalling to mTOR mediated by the Akt/PKB substrate PRAS40.Vander Haar E et al
177666612007The biology behind mTOR inhibition in sarcoma.Wan X et al
175100572007PRAS40 regulates mTORC1 kinase activity by functioning as a direct inhibitor of substrate binding.Wang L et al
182815512008Suppression of Peutz-Jeghers polyposis by targeting mammalian target of rapamycin signaling.Wei C et al
171792282007Rapamycin derivatives reduce mTORC2 signaling and inhibit AKT activation in AML.Zeng Z et al

Other Information

Locus ID:

NCBI: 2475
MIM: 601231
HGNC: 3942
Ensembl: ENSG00000198793


dbSNP: 2475
ClinVar: 2475
TCGA: ENSG00000198793


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
ErbB signaling pathwayKEGGko04012
Autophagy - animalKEGGko04140
mTOR signaling pathwayKEGGko04150
Jak-STAT signaling pathwayKEGGko04630
Insulin signaling pathwayKEGGko04910
Adipocytokine signaling pathwayKEGGko04920
Type II diabetes mellitusKEGGko04930
Prostate cancerKEGGko05215
Acute myeloid leukemiaKEGGko05221
ErbB signaling pathwayKEGGhsa04012
Autophagy - animalKEGGhsa04140
mTOR signaling pathwayKEGGhsa04150
Jak-STAT signaling pathwayKEGGhsa04630
Insulin signaling pathwayKEGGhsa04910
Adipocytokine signaling pathwayKEGGhsa04920
Type II diabetes mellitusKEGGhsa04930
Pathways in cancerKEGGhsa05200
Prostate cancerKEGGhsa05215
Acute myeloid leukemiaKEGGhsa05221
PI3K-Akt signaling pathwayKEGGhsa04151
PI3K-Akt signaling pathwayKEGGko04151
HIF-1 signaling pathwayKEGGhsa04066
Proteoglycans in cancerKEGGhsa05205
Proteoglycans in cancerKEGGko05205
MicroRNAs in cancerKEGGhsa05206
MicroRNAs in cancerKEGGko05206
Thyroid hormone signaling pathwayKEGGhsa04919
AMPK signaling pathwayKEGGhsa04152
AMPK signaling pathwayKEGGko04152
Central carbon metabolism in cancerKEGGhsa05230
Choline metabolism in cancerKEGGhsa05231
Central carbon metabolism in cancerKEGGko05230
Choline metabolism in cancerKEGGko05231
Diseases of signal transductionREACTOMER-HSA-5663202
PI3K/AKT Signaling in CancerREACTOMER-HSA-2219528
Constitutive Signaling by AKT1 E17K in CancerREACTOMER-HSA-5674400
Immune SystemREACTOMER-HSA-168256
Adaptive Immune SystemREACTOMER-HSA-1280218
Costimulation by the CD28 familyREACTOMER-HSA-388841
CD28 co-stimulationREACTOMER-HSA-389356
CD28 dependent PI3K/Akt signalingREACTOMER-HSA-389357
Signaling by the B Cell Receptor (BCR)REACTOMER-HSA-983705
Downstream signaling events of B Cell Receptor (BCR)REACTOMER-HSA-1168372
PIP3 activates AKT signalingREACTOMER-HSA-1257604
Innate Immune SystemREACTOMER-HSA-168249
DAP12 interactionsREACTOMER-HSA-2172127
DAP12 signalingREACTOMER-HSA-2424491
Fc epsilon receptor (FCERI) signalingREACTOMER-HSA-2454202
Role of LAT2/NTAL/LAB on calcium mobilizationREACTOMER-HSA-2730905
Signal TransductionREACTOMER-HSA-162582
Signaling by EGFRREACTOMER-HSA-177929
GAB1 signalosomeREACTOMER-HSA-180292
Signaling by Insulin receptorREACTOMER-HSA-74752
Insulin receptor signalling cascadeREACTOMER-HSA-74751
IRS-mediated signallingREACTOMER-HSA-112399
PI3K CascadeREACTOMER-HSA-109704
PKB-mediated eventsREACTOMER-HSA-109703
mTOR signallingREACTOMER-HSA-165159
mTORC1-mediated signallingREACTOMER-HSA-166208
Energy dependent regulation of mTOR by LKB1-AMPKREACTOMER-HSA-380972
Signalling by NGFREACTOMER-HSA-166520
NGF signalling via TRKA from the plasma membraneREACTOMER-HSA-187037
PI3K/AKT activationREACTOMER-HSA-198203
Signaling by PDGFREACTOMER-HSA-186797
Downstream signal transductionREACTOMER-HSA-186763
Signaling by VEGFREACTOMER-HSA-194138
VEGFR2 mediated vascular permeabilityREACTOMER-HSA-5218920
Signaling by SCF-KITREACTOMER-HSA-1433557
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)REACTOMER-HSA-2404192
IGF1R signaling cascadeREACTOMER-HSA-2428924
IRS-related events triggered by IGF1RREACTOMER-HSA-2428928
Gene ExpressionREACTOMER-HSA-74160
Generic Transcription PathwayREACTOMER-HSA-212436
Transcriptional Regulation by TP53REACTOMER-HSA-3700989
TP53 Regulates Metabolic GenesREACTOMER-HSA-5628897
Cellular responses to stressREACTOMER-HSA-2262752
Cellular response to heat stressREACTOMER-HSA-3371556
HSF1-dependent transactivationREACTOMER-HSA-3371571
Insulin resistanceKEGGhsa04931
Phospholipase D signaling pathwayKEGGko04072
Phospholipase D signaling pathwayKEGGhsa04072
Longevity regulating pathwayKEGGhsa04211
Longevity regulating pathway - multiple speciesKEGGko04213
Longevity regulating pathway - multiple speciesKEGGhsa04213
Regulation of TP53 ActivityREACTOMER-HSA-5633007
Regulation of TP53 Expression and DegradationREACTOMER-HSA-6806003
Regulation of TP53 DegradationREACTOMER-HSA-6804757
EGFR tyrosine kinase inhibitor resistanceKEGGko01521
Endocrine resistanceKEGGko01522
EGFR tyrosine kinase inhibitor resistanceKEGGhsa01521
Endocrine resistanceKEGGhsa01522
Breast cancerKEGGko05224
Breast cancerKEGGhsa05224
Th17 cell differentiationKEGGko04659
Th17 cell differentiationKEGGhsa04659
Apelin signaling pathwayKEGGhsa04371
Autophagy - otherKEGGko04136
Autophagy - otherKEGGhsa04136

Protein levels (Protein atlas)

Not detected


Entity IDNameTypeEvidenceAssociationPKPDPMIDs


Pubmed IDYearTitleCitations
157184702005Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex.2480
212583672011AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1.1800
121509252002mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery.1043
121725532002TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling.1005
203811372010Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids.860
192251512009ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery.679
192118352009Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy.642
121509262002Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action.615
187259882008Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer.600
169626532006SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt phosphorylation and substrate specificity.591


Deborah A Altomare ; Joseph R Testa

MTOR (FK506 binding protein 12-rapamycin associated protein 1)

Atlas Genet Cytogenet Oncol Haematol. 2008-06-01

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