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Ras homolog enriched in brain
Protein RHEB PDB 1xtq.png
PDB rendering based on 1xtq.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols RHEB ; RHEB2
External IDs OMIM601293 MGI97912 HomoloGene123916 GeneCards: RHEB Gene
RNA expression pattern
PBB GE RHEB 201452 at tn.png
PBB GE RHEB 201453 x at tn.png
PBB GE RHEB 213404 s at tn.png
More reference expression data
Species Human Mouse
Entrez 6009 19744
Ensembl ENSG00000106615 ENSMUSG00000028945
UniProt Q15382 Q921J2
RefSeq (mRNA) NM_005614 NM_053075
RefSeq (protein) NP_005605 NP_444305
Location (UCSC) Chr 7:
151.16 – 151.22 Mb
Chr 5:
24.8 – 24.84 Mb
PubMed search [1] [2]

GTP-binding protein Rheb also known as Ras homolog enriched in brain (RHEB) is a protein that in humans is encoded by the RHEB gene.[1]


Rheb is a recently discovered member of the Ras superfamily that may be involved in neural plasticity. This function is novel and not typically associated with the Ras proteins.

This gene is a member of the small GTPase superfamily and encodes a lipid-anchored, cell membrane protein with five repeats of the RAS-related GTP-binding region. This protein is vital in regulation of growth and cell cycle progression due to its role in the insulin / TOR / S6K signaling pathway. The protein has GTPase activity and shuttles between a GDP-bound form and a GTP-bound form, and farnesylation of the protein is required for this activity. Three pseudogenes have been mapped, two on chromosome 10 and one on chromosome 22.[2]


RHEB has been shown to interact with C-Raf,[3][4][5] Mammalian target of rapamycin,[3][6][7][8] TSC2,[3][9][10][11][12][13] Ataxia telangiectasia mutated,[3] KIAA1303[3] and Ataxia telangiectasia and Rad3 related.[3]


  1. ^ Mizuki N, Kimura M, Ohno S, Miyata S, Sato M, Ando H, Ishihara M, Goto K, Watanabe S, Yamazaki M, Ono A, Taguchi S, Okumura K, Nogami M, Taguchi T, Ando A, Inoko H (Dec 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". Genomics 34 (1): 114–8. doi:10.1006/geno.1996.0248. PMID 8661031. 
  2. ^ "Entrez Gene: RHEB Ras homolog enriched in brain". 
  3. ^ a b c d e f Long, Xiaomeng; Lin Yenshou, Ortiz-Vega Sara, Yonezawa Kazuyoshi, Avruch Joseph (Apr 2005). "Rheb binds and regulates the mTOR kinase". Curr. Biol. (England) 15 (8): 702–13. doi:10.1016/j.cub.2005.02.053. ISSN 0960-9822. PMID 15854902. 
  4. ^ Karbowniczek, Magdalena; Cash Timothy; Cheung Mitchell; Robertson Gavin P; Astrinidis Aristotelis; Henske Elizabeth Petri (Jul 2004). "Regulation of B-Raf kinase activity by tuberin and Rheb is mammalian target of rapamycin (mTOR)-independent". J. Biol. Chem. (United States) 279 (29): 29930–7. doi:10.1074/jbc.M402591200. ISSN 0021-9258. PMID 15150271. 
  5. ^ Yee, W M; Worley P F (Feb 1997). "Rheb interacts with Raf-1 kinase and may function to integrate growth factor- and protein kinase A-dependent signals". Mol. Cell. Biol. (UNITED STATES) 17 (2): 921–33. ISSN 0270-7306. PMC 231818. PMID 9001246. 
  6. ^ Long, Xiaomeng; Ortiz-Vega Sara, Lin Yenshou, Avruch Joseph (Jun 2005). "Rheb binding to mammalian target of rapamycin (mTOR) is regulated by amino acid sufficiency". J. Biol. Chem. (United States) 280 (25): 23433–6. doi:10.1074/jbc.C500169200. ISSN 0021-9258. PMID 15878852. 
  7. ^ Smith, Ewan M; Finn Stephen G; Tee Andrew R; Browne Gareth J; Proud Christopher G (May 2005). "The tuberous sclerosis protein TSC2 is not required for the regulation of the mammalian target of rapamycin by amino acids and certain cellular stresses". J. Biol. Chem. (United States) 280 (19): 18717–27. doi:10.1074/jbc.M414499200. ISSN 0021-9258. PMID 15772076. 
  8. ^ Bernardi, Rosa; Guernah Ilhem, Jin David, Grisendi Silvia, Alimonti Andrea, Teruya-Feldstein Julie, Cordon-Cardo Carlos, Simon M Celeste, Rafii Shahin, Pandolfi Pier Paolo (Aug 2006). "PML inhibits HIF-1alpha translation and neoangiogenesis through repression of mTOR". Nature (England) 442 (7104): 779–85. doi:10.1038/nature05029. PMID 16915281. 
  9. ^ Castro, Ariel F; Rebhun John F; Clark Geoffrey J; Quilliam Lawrence A (Aug 2003). "Rheb binds tuberous sclerosis complex 2 (TSC2) and promotes S6 kinase activation in a rapamycin- and farnesylation-dependent manner". J. Biol. Chem. (United States) 278 (35): 32493–6. doi:10.1074/jbc.C300226200. ISSN 0021-9258. PMID 12842888. 
  10. ^ Inoki, Ken; Li Yong; Xu Tian; Guan Kun-Liang (Aug 2003). "Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling". Genes Dev. (United States) 17 (15): 1829–34. doi:10.1101/gad.1110003. ISSN 0890-9369. PMC 196227. PMID 12869586. 
  11. ^ Garami, Attila; Zwartkruis Fried J T; Nobukuni Takahiro; Joaquin Manel; Roccio Marta; Stocker Hugo; Kozma Sara C; Hafen Ernst; Bos Johannes L; Thomas George (Jun 2003). "Insulin activation of Rheb, a mediator of mTOR/S6K/4E-BP signaling, is inhibited by TSC1 and 2". Mol. Cell (United States) 11 (6): 1457–66. doi:10.1016/S1097-2765(03)00220-X. ISSN 1097-2765. PMID 12820960. 
  12. ^ Zhang, Yong; Gao Xinsheng; Saucedo Leslie J; Ru Binggen; Edgar Bruce A; Pan Duojia (Jun 2003). "Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins". Nat. Cell Biol. (England) 5 (6): 578–81. doi:10.1038/ncb999. ISSN 1465-7392. PMID 12771962. 
  13. ^ Cao, Yongheng; Kamioka Yuji; Yokoi Norihide; Kobayashi Toshiyuki; Hino Okio; Onodera Masafumi; Mochizuki Naoki; Nakae Jun (Dec 2006). "Interaction of FoxO1 and TSC2 induces insulin resistance through activation of the mammalian target of rapamycin/p70 S6K pathway". J. Biol. Chem. (United States) 281 (52): 40242–51. doi:10.1074/jbc.M608116200. ISSN 0021-9258. PMID 17077083. 

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This article incorporates text from the United States National Library of Medicine, which is in the public domain.