Property Summary

NCBI Gene PubMed Count 88
PubMed Score 190.13
PubTator Score 134.19

Knowledge Summary

Patent

No data available

Expression

  Differential Expression (2)

Disease log2 FC p
adult high grade glioma -1.300 5.3e-03
group 3 medulloblastoma 1.200 4.0e-02

Gene RIF (60)

PMID Text
26742086 By interfering with TSC-Rheb complex, arginine relieves allosteric inhibition of Rheb by TSC. Arginine cooperates with growth factor signaling which further promotes dissociation of TSC2 from lysosomes and activation of mTORC1.
26319900 RGS10 could serve in a novel, and previously unknown, role by accelerating the hydrolysis of GTP from Rheb in ovarian cancer cells.
26255626 Mutations in the TSC2-RHEB-mTOR signaling axis may lead to a loss of inhibitory inputs thus conferring a survival advantage to a dividing tumor cell.
25799580 Activation of CNTF/CNTFRalpha signaling pathway by hRheb(S16H) transduction of dopaminergic neurons
25594310 Data show that Rheb/p27 axis induces autophagy-dependent cancer cell survival under stress conditions.
25476905 In TSC2-deficient angiomyolipoma patient cells, IRF7 is a pivotal factor in the Rheb/mTOR pathway.
25422319 These results establish CAD as a downstream effector of Rheb and suggest a possible role of Rheb in regulating de novo pyrimidine nucleotide synthesis.(Rheb small GTPases, which consist of Rheb1 and Rheb2 (also known as RhebL1)
24648513 Data indicate that Rheb G63A stimulated phosphorylation of the mTORC1 substrate p70S6 kinase more strongly than wild-type, thus offering a new tool for mammalian target of rapamycin (mTOR) signaling.
24403554 In vitro data indicated that miR-155 suppressed the macrophage-mediated bacterial phagocytosis and intracellular killing of Pseudomonas aeruginosa by targeting Rheb (Ras homolog enriched in brain).
24368770 study defines Rheb as a novel physiological regulator of BACE1 levels and Abeta generation, and the Rheb-BACE1 circuitry may have a role in brain biology and disease.
23863162 Maturation of endosomes into lysosomes may be required to assure a continuous supply of GTP-bound Rheb for mTORC1 activation, which may help to drive the maturation process
23409921 The propose models of membrane-dependent signal regulation by Rheb that shed light on previously unexplained in vivo properties of this GTPase.
21784859 Redox regulates mammalian target of rapamycin complex 1 (mTORC1) activity by modulating the TSC1/TSC2-Rheb GTPase pathway.
21437936 Adenoassociated virus-mediated transduction of substantia nigra dopaminergic neurons with constitutively active forms of kinase Akt and Ras homolog enriched in brain (Rheb) induces regrowth of axons after they have been destroyed by neurotoxin lesion.
21412983 TSC1, TSC2 and Rheb function independently of TORC1 in tuberous sclerosis complex.[Review]
21336308 Rheb inactivation by PRAK-mediated phosphorylation is essential for energy-depletion-induced suppression of mTORC1
21135540 In a human embryonic brain cDNA library mTOR-activating GTPase Rheb is screened as an interacting protein of the NMDAR subunit NR3A.
21048031 Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
20837708 results suggest a novel regulatory mechanism for mTORC1 in which the cAMP-determined dynamic interaction between Rheb and PDE4D provides a key, unique regulatory event, and propose a new role for PDE4 as a molecular transducer for cAMP signaling.
20818424 Rheb controls proliferation of TSC2-deficient cells by a mechanism that involves regulation of AMPK and p27, and that Rheb is a potential target for TSC/LAM therapy.
20732420 The activating transcription factor (ATF)6alpha/Rheb pathway is altered in Huntington's disease, as the decrease in ATF6alpha processing is accompanied by a decrease in the accumulation of Rheb.
20685651 Ras homolog enriched in brain (Rheb) enhances apoptotic signaling
20554106 Results suggest that Rheb is a critical target for farnesyltransferase inhibitor therapy in non-small cell lung cancer cells.
20388784 RHEB is an MTOR activator that facilitates multistage carcinogenesis through induction of multiple oncogenic mechanisms
20375271 Findings illustrate a mechanism for the cardioprotective effects of lovastatin through inhibition of Rheb and mTORC1 and promotion of a differentiated vascular smooth muscle cell phenotype.
20354165 Observational study of gene-disease association. (HuGE Navigator)
20127734 Rheb potentiates proliferation of prostate cancer cells
20053679 integrity of late endosomes is essential for amino acid- and insulin-stimulated mTORC1 signaling and blocking the early/late endosomal conversion prevents mTOR from interacting with Rheb in the late endosomal compartment
20048149 Rheb GTPase controls apoptosis by regulating interaction of FKBP38 with Bcl-2 and Bcl-XL
19838215 Data inidicate that FTS could be a promising treatment for Rheb- and mTOR-dependent cancers.
19636822 Backbone and side chain assignments were obtained from three dimensional NMR spectra.
19570981 TCTP interacts with hRheb and accelerates its GDP release in vitro.
19222999 FKBP38 is not the long-sought Rheb effector linking Rheb to mTORC1 activation.
18948269 RalGDS and RalA act downstream of Rheb and that RalA activation is a crucial step in nutrient-induced mTORC1 activation
18842593 Inhibition of PI3K or mTOR reduced the level of Rap1B, which acts downstream of Rheb and mTOR. The ubiquitin E3 ligase Smurf2 mediates the restriction of Rap1B by initiating its degradation.
18708578 RHEB overexpression accelerates lymphomagenesis in the Eu-myc model
18708577 Rheb overexpression is associated with prostate cancer
18658153 FKBP38 is a bona fide effector of Rheb and the ability to interact with FKBP38 is important for Rheb as an activator of mTOR
18650380 ATF6alpha-Rheb-mTOR signaling promotes survival of dormant tumor cells in vivo
18550814 PLD1 is required for Rheb activation of the mTOR pathway.
18521078 Constitutively active Rheb induces oncogenic transformation.
18324915 RHEB could be used cytopathologically to distinguish fibroadenoma from malignant breast carcinomas as a secondary diagnostic tool.
17991864 findings suggest that FKBP38 is an endogenous inhibitor of mTOR, whose inhibitory activity is antagonized by Rheb in response to growth factor stimulation and nutrient availability
17928295 Bnip3, a hypoxia-inducible Bcl-2 homology 3 domain-containing protein, directly binds Rheb and inhibits the mTOR pathway.
17470430 Rheb signaling to mTOR in vivo requires a Rheb switch 2-dependent interaction with an element other than the three known polypeptide components of TOR complex 1
17018601 The TSC/Rheb/mTOR pathway plays a critical role in the regulation of E(2)-induced proliferation.
16803888 Rheb has a central role in the regulation of the Ras/B-Raf/C-Raf/MEK signaling network
16631613 Our results demonstrate that Ebp1 is a new dsRNA-binding protein that acts as a cellular inhibitor of eIF2alpha phosphorylation suggesting that it could be involved in protein translation control
16098514 Data show that Rheb like-1 protein (RhebL1) rescues mTOR signaling during nutrient withdrawal, and identify critical residues in Rheb and RhebL1 which are required for their efficient activation of mTOR signaling.
16006564 Data show that the farnesyl transferase inhibitor (FTI) SCH66336 (lonafarnib) inhibits Rheb farnesylation and mTOR signaling.
15878852 binding of Rheb to endogenous and recombinant mTOR is reversibly inhibited by withdrawal of all extracellular amino acids or just leucine
15854902 The target of rapamycin (TOR) complex 1 is a direct target of Rheb-GTP, whose binding enables activation of the TOR kinase.
15809346 results suggest that Rheb regulates endocytic trafficking pathway independent of the previously identified mTOR pathway.
15728574 Rheb forms a new group of the Ras/Rap subfamily and uses a novel GTP hydrolysis mechanism that utilizes Asn1643 of the tuberous sclerosis complex 2 GTPase-activating protein domain instead of Gln64 of Rheb as the catalytic residue
15388940 The GTPase domain of human Rheb (hRheb) has been recombinantly expressed in Escherichia coli, purified and cocrystallized in complexes with GDP, GTP and GppNHp.
15340059 To investigate the function of TSC2 and Rheb in mTOR signaling, we analyzed the TSC2-stimulated Rheb GTPase activity.
15150271 Rheb has a role in regulation of B-Raf kinase activity along with tuberin but without involvement of mTOR
12869586 Rheb acts downstream of TSC1/TSC2 and upstream of mTOR to regulate cell growth
12869548 transient expression of the wild type Rheb1 or Rheb2 causes activation of p70S6K, while expression of Rheb1D60K mutant results in inhibition of basal level activity of p70S6K
12842888 Rheb binds tuberous sclerosis complex 2 (TSC2) and promotes S6 kinase activation in a rapamycin- and farnesylation-dependent manner

AA Sequence

MPQSKSRKIAILGYRSVGKSSLTIQFVEGQFVDSYDPTIENTFTKLITVNGQEYHLQLVDTAGQDEYSIF      1 - 70
PQTYSIDINGYILVYSVTSIKSFEVIKVIHGKLLDMVGKVQIPIMLVGNKKDLHMERVISYEEGKALAES     71 - 140
WNAAFLESSAKENQTAVDVFRRIILEAEKMDGAASQGKSSCSVM                              141 - 184
//

Text Mined References (92)

PMID Year Title
26742086 2016 Control of TSC2-Rheb signaling axis by arginine regulates mTORC1 activity.
26319900 2015 Suppression of the GTPase-activating protein RGS10 increases Rheb-GTP and mTOR signaling in ovarian cancer cells.
26255626 2015 Point mutations of the mTOR-RHEB pathway in renal cell carcinoma.
25799580 2015 Activation of CNTF/CNTFR? signaling pathway by hRheb(S16H) transduction of dopaminergic neurons in vivo.
25594310 2016 Rheb promotes cancer cell survival through p27Kip1-dependent activation of autophagy.
25476905 2014 Analysis of gene expression array in TSC2-deficient AML cells reveals IRF7 as a pivotal factor in the Rheb/mTOR pathway.
25422319 2015 Rheb protein binds CAD (carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, and dihydroorotase) protein in a GTP- and effector domain-dependent manner and influences its cellular localization and carbamoyl-phosphate synthetase (CPSase) activity.
24648513 2014 Structure-guided mutation of the conserved G3-box glycine in Rheb generates a constitutively activated regulator of mammalian target of rapamycin (mTOR).
24403554 2014 miR-155 suppresses bacterial clearance in Pseudomonas aeruginosa-induced keratitis by targeting Rheb.
24368770 2014 Rheb GTPase regulates ?-secretase levels and amyloid ? generation.
23863162 2013 Rheb and Rags come together at the lysosome to activate mTORC1.
23559067 2013 The interplay between RPGR, PDE? and Arl2/3 regulate the ciliary targeting of farnesylated cargo.
23409921 2013 Membrane-dependent modulation of the mTOR activator Rheb: NMR observations of a GTPase tethered to a lipid-bilayer nanodisc.
23376485 2013 Proteomic analysis of podocyte exosome-enriched fraction from normal human urine.
22002721 2011 Arl2-GTP and Arl3-GTP regulate a GDI-like transport system for farnesylated cargo.
21784859 2011 Redox regulates mammalian target of rapamycin complex 1 (mTORC1) activity by modulating the TSC1/TSC2-Rheb GTPase pathway.
21437936 2011 Dopaminergic pathway reconstruction by Akt/Rheb-induced axon regeneration.
21412983 2011 Non-canonical functions of the tuberous sclerosis complex-Rheb signalling axis.
21336308 2011 Inactivation of Rheb by PRAK-mediated phosphorylation is essential for energy-depletion-induced suppression of mTORC1.
21269460 2011 Initial characterization of the human central proteome.
21135540 2010 Association of the small GTPase Rheb with the NMDA receptor subunit NR3A.
21048031 2011 Single nucleotide polymorphisms of matrix metalloproteinase 9 (MMP9) and tumor protein 73 (TP73) interact with Epstein-Barr virus in chronic lymphocytic leukemia: results from the European case-control study EpiLymph.
20837708 2010 Cyclic AMP controls mTOR through regulation of the dynamic interaction between Rheb and phosphodiesterase 4D.
20818424 2010 Rheb activates AMPK and reduces p27Kip1 levels in Tsc2-null cells via mTORC1-independent mechanisms: implications for cell proliferation and tumorigenesis.
20732420 2011 Impaired ATF6? processing, decreased Rheb and neuronal cell cycle re-entry in Huntington's disease.
20685651 2010 Ras homolog enriched in brain (Rheb) enhances apoptotic signaling.
20554106 2010 Ras homologue enriched in brain is a critical target of farnesyltransferase inhibitors in non-small cell lung cancer cells.
20458337 MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis.
20388784 2010 Mammalian target of rapamycin activator RHEB is frequently overexpressed in human carcinomas and is critical and sufficient for skin epithelial carcinogenesis.
20381137 2010 Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids.
20375271 2010 Lovastatin induces VSMC differentiation through inhibition of Rheb and mTOR.
20354165 2010 Energy balance, the PI3K-AKT-mTOR pathway genes, and the risk of bladder cancer.
20127734 2010 Regulation of androgen receptor transactivity and mTOR-S6 kinase pathway by Rheb in prostate cancer cell proliferation.
20053679 2010 The late endosome is essential for mTORC1 signaling.
20048149 2010 Rheb GTPase controls apoptosis by regulating interaction of FKBP38 with Bcl-2 and Bcl-XL.
19838215 2010 Differential requirement of CAAX-mediated posttranslational processing for Rheb localization and signaling.
19636822 2007 Sequence-specific 1H, 13C, and 15N backbone assignment of the GTPase rRheb in its GDP-bound form.
19570981 2009 Molecular basis of the acceleration of the GDP-GTP exchange of human ras homolog enriched in brain by human translationally controlled tumor protein.
19258434 2009 Upregulation of the mammalian target of rapamycin complex 1 pathway by Ras homolog enriched in brain in pancreatic beta-cells leads to increased beta-cell mass and prevention of hyperglycemia.
19222999 2009 Reassessment of the role of FKBP38 in the Rheb/mTORC1 pathway.
19056867 2009 Large-scale proteomics and phosphoproteomics of urinary exosomes.
18948269 2008 RalA functions as an indispensable signal mediator for the nutrient-sensing system.
18842593 2008 Rheb and mTOR regulate neuronal polarity through Rap1B.
18708578 2008 Tumorigenic activity and therapeutic inhibition of Rheb GTPase.
18708577 2008 Aberrant Rheb-mediated mTORC1 activation and Pten haploinsufficiency are cooperative oncogenic events.
18658153 2008 The switch I region of Rheb is critical for its interaction with FKBP38.
18650380 2008 ATF6alpha-Rheb-mTOR signaling promotes survival of dormant tumor cells in vivo.
18550814 2008 Phospholipase D1 is an effector of Rheb in the mTOR pathway.
18521078 2008 Constitutively active Rheb induces oncogenic transformation.
18324915 2008 RHEB expression in fibroadenomas of the breast.
17991864 2007 Rheb activates mTOR by antagonizing its endogenous inhibitor, FKBP38.
17928295 2007 Bnip3 mediates the hypoxia-induced inhibition on mammalian target of rapamycin by interacting with Rheb.
17470430 2007 The Rheb switch 2 segment is critical for signaling to target of rapamycin complex 1.
17018601 2006 Estrogen-induced activation of mammalian target of rapamycin is mediated via tuberin and the small GTPase Ras homologue enriched in brain.
16959974 2006 The consensus coding sequences of human breast and colorectal cancers.
16803888 2006 Rheb inhibits C-raf activity and B-raf/C-raf heterodimerization.
16631613 2006 Localization of Rheb to the endomembrane is critical for its signaling function.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
16098514 2005 Analysis of mTOR signaling by the small G-proteins, Rheb and RhebL1.
16006564 2005 The farnesyl transferase inhibitor (FTI) SCH66336 (lonafarnib) inhibits Rheb farnesylation and mTOR signaling. Role in FTI enhancement of taxane and tamoxifen anti-tumor activity.
15951850 2005 The GAPs, GEFs, and GDIs of heterotrimeric G-protein alpha subunits.
15878852 2005 Rheb binding to mammalian target of rapamycin (mTOR) is regulated by amino acid sufficiency.
15854902 2005 Rheb binds and regulates the mTOR kinase.
15809346 2005 Novel role of the small GTPase Rheb: its implication in endocytic pathway independent of the activation of mammalian target of rapamycin.
15809305 2005 Structure of S6 kinase 1 determines whether raptor-mTOR or rictor-mTOR phosphorylates its hydrophobic motif site.
15755954 2005 Signaling by target of rapamycin proteins in cell growth control.
15728574 2005 Structural basis for the unique biological function of small GTPase RHEB.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15388940 2004 Expression, purification, crystallization and preliminary structural characterization of the GTPase domain of human Rheb.
15340059 2004 Biochemical and functional characterizations of small GTPase Rheb and TSC2 GAP activity.
15308774 2004 A tagging-via-substrate technology for detection and proteomics of farnesylated proteins.
15150271 2004 Regulation of B-Raf kinase activity by tuberin and Rheb is mammalian target of rapamycin (mTOR)-independent.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
12906785 2003 Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb.
12869586 2003 Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling.
12869548 2003 Identification of dominant negative mutants of Rheb GTPase and their use to implicate the involvement of human Rheb in the activation of p70S6K.
12853948 2003 The DNA sequence of human chromosome 7.
12842888 2003 Rheb binds tuberous sclerosis complex 2 (TSC2) and promotes S6 kinase activation in a rapamycin- and farnesylation-dependent manner.
12820960 2003 Insulin activation of Rheb, a mediator of mTOR/S6K/4E-BP signaling, is inhibited by TSC1 and 2.
12771962 2003 Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins.
12690205 2003 Human chromosome 7: DNA sequence and biology.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12271141 2002 Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling.
11980706 2002 The complex of Arl2-GTP and PDE delta: from structure to function.
10924367 2000 Search for UV-responsive genes in human cells by differential mRNA display: involvement of human ras-related GTP-binding protein, Rheb, in UV susceptibility.
9847074 1998 Toward a complete human genome sequence.
9099708 1997 The Ras-related protein Rheb is farnesylated and antagonizes Ras signaling and transformation.
9001246 1997 Rheb interacts with Raf-1 kinase and may function to integrate growth factor- and protein kinase A-dependent signals.
8889548 1996 Normalization and subtraction: two approaches to facilitate gene discovery.
8661031 1996 Isolation of cDNA and genomic clones of a human Ras-related GTP-binding protein gene and its chromosomal localization to the long arm of chromosome 7, 7q36.
8543055 1995 A novel approach for expression cloning of small GTPases: identification, tissue distribution and chromosome mapping of the human homolog of rheb.
8206940 1994 rheb, a growth factor- and synaptic activity-regulated gene, encodes a novel Ras-related protein.