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Symbol RHEB contributors: mct/pgu - updated : 04-09-2018
HGNC name Ras homolog enriched in brain
HGNC id 10011
TYPE functioning gene
STRUCTURE 53.91 kb     8 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status confirmed
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
8 - 2092 20.4 184 - 2007 17991864
Type widely
   expressed in (based on citations)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart   highly Mus musculusAdult
 vessel   highly
Digestivesalivary gland   highly
Hearing/Equilibriumear   highly
Nervousbrainhindbrainmedulla oblongata   Mus musculusAdult
 brainlimbic systemhippocampus   Mus musculusAdult
 brainforebraincerebral cortex   Mus musculusAdult
 brainhindbraincerebellum   Mus musculusAdult
Olfactory (smell)olfactory bulb     Mus musculusAdult
Reproductivefemale systemplacenta  highly
Skin/Tegumentskin   highly
Urinarybladder     Mus musculusAdult
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connectiveadipose  highly
Muscularstriatumskeletal   Mus musculusFetal
SystemCellPubmedSpeciesStageRna symbol
not specificfibroblast
cell lineage
cell lines breast carcinoma
physiological period fetal
Text brain
  • five repeats of the RAS-related GTP-binding region
  • targeted to endomembranes via its C-terminal CAAX (C=cysteine, A=aliphatic, X=terminal amino acid) motif, a substrate for posttranslational modification by a farnesyl isoprenoid
  • conjugated LipoP , Other
    mono polymer complex
    interspecies homolog to murine Rheb (98.9 pc)
    intraspecies homolog to Ras (enriched in brain)
  • Ras-oncogene superfamily member
  • small GTPase superfamily
  • Rheb family
  • CATEGORY immunity/defense , protooncogene , signaling growth factor
    SUBCELLULAR LOCALIZATION     plasma membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
  • lipid-anchorto the cytoplasmic side
  • RHEB and RHEBL1 localize primarily to the endoplasmic reticulum and Golgi apparatus
  • RHEB is activated at the Golgi from where it will travel to lysosomes
  • basic FUNCTION
  • exhibiting intrinsic GTPase activity
  • may control growth
  • promoting mTOR-dependent S6 kinase activation in a rapamycin- and farnesylation-dependent manner
  • stimulating phosphorylation of 4EBP1
  • playing an important role in cellular responses to energy limitation and nutrient starvation
  • may also control BCL2-dependent apoptosis and calcineurin-dependent transcription through FKBP8
  • activating FRAP1 by antagonizing its endogenous inhibitor, FKBP8
  • playing a vital role in regulation of growth and cell cycle progression due to its role in the insulin/TOR/S6K signaling pathway
  • directly activating MTOR, in a farnesylation-dependent manner
  • critical for embryonic survival and MTOR signaling
  • essential for MTOR signaling and myelination in the brain, suggesting that MTOR signaling plays a role in selective cellular adaptations, rather than general cellular viability
  • negatively regulates myoblast differentiation through suppression of IRS1 and inhibition of AKT activation
  • function of RPTOR and RHEB in myogenesis is mediated by IRS1
  • essential role of RHEB in diverse aspects of spermatogenesis, suggesting the existence of functionally redundant factors that can compensate for RHEB deficiency within oocytes
  • oligodendrocyte progenitor cells (OPCs) -intrinsic MTOR activity mediated by RHEB is critical for differentiation of OPCs to mature oligodendrocytes, but that mature oligodendrocytes do not require RHEB to make myelin or maintain it in the adult brain
  • possible role of RHEB and RHEBL1 in regulating de novo pyrimidine nucleotide synthesis
  • expression pattern of RHEB suggests that it likely plays a ubiquitous role in the development of the early embryo with more tissue-specific roles in later development
  • RHEB induces a distinct gene expression signature that maintained the innate chondrogenic properties over a long period
  • is critical for macrophage production and phagocytosis and executes these activities possibly via MTOR-dependent pathway
  • distinct roles of RHEB and RPTOR in activating MTOR for the self-renewal of hematopoietic stem cells
  • CELLULAR PROCESS cell life, proliferation/growth
    protein, translation regulation
    signaling signal transduction
    long term, activity dependent, neuronal response
    a component
  • spliceosome
    small molecule nucleotide,
  • GTP
  • protein
  • binding tuberous sclerosis complex 2 (TSC2)
  • interacting with FKBP8
  • positive upstream regulator of the target of rapamycin (TOR) complex 1 in mammalian cells and can bind directly to MTOR
  • direct regulation of RHEB by MAPKAPK5 integrates a stress pathway with the MTOR pathway in response to energy depletion
  • activation of MTOR is regulated by a small G-protein, RHEB
  • IRS1 is a critical mediator of the myogenic functions of raptor and RHEB
  • RHEB and EFNA5 come together at the lysosome to activate MTOR
  • RHEB interacts with BACE1 and degrades it through proteasomal and lysosomal pathways
  • RHEB proteins binds to CAD protein (RHEB and RHEBL1 binds CAD in a GTP- and effector domain-dependent manner)
  • RHEB and RHEBL1 are unique members of the Ras superfamily and play central roles in regulating protein synthesis and cell growth by activating MTOR
  • PDZ protein SDCBP preferentially binds to the GDP-bound form of RHEB
  • RASSF1 inhibits the ability of RHEB to suppress autophagy and enhance cell growth, and RHEB may complex with RASSF1 to coordinate Hippo and MTOR signaling
  • RHEB interaction with BRAF is crucial for inhibiting RAF/MEK/ERK signaling
  • function of RHEB to activate MTOR signaling
  • MTOR activation by RHEB and inhibition by AKT1S1
  • cell & other
    activated by TSC2/TSC1 complex, (its GTPase activity is activated by the complex of TSC1 and TSC2 whose mutations cause tuberous sclerosis complex (TSC)
    inhibited by a farnesyl transferase inhibitor
    Other post-translationally modified by the farnesyl lipid, for attachment to membranes
    methylated and prenylated
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   amplification    
    in human prostate cancers
    constitutional     --low  
    inhibited the monocyte-to-macrophage differentiation process
    constitutional     --low  
    RHEB levels are down-regulated in the Alzheimer disease brain, which is consistent with an increased BACE1 expression
    Variant & Polymorphism
    Candidate gene for holoprosencephaly type 3 and/or sacral agenesis
    Therapy target
  • absolute number of macrophages decreased in the bone marrow (BM) of Rheb1-deficient mice