RHEB
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]
Function
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]
Interactions
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]
References
- ^ 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.
- ^ "Entrez Gene: RHEB Ras homolog enriched in brain". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6009.
- ^ 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.
- ^ 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.
- ^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=231818.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=196227.
- ^ 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.
- ^ 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.
- ^ 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.
Further reading
- Yamagata K, Sanders LK, Kaufmann WE et al. (1994). "rheb, a growth factor- and synaptic activity-regulated gene, encodes a novel Ras-related protein". J. Biol. Chem. 269 (23): 16333–9. PMID 8206940.
- Gromov PS, Madsen P, Tomerup N, Celis JE (1996). "A novel approach for expression cloning of small GTPases: identification, tissue distribution and chromosome mapping of the human homolog of rheb". FEBS Lett. 377 (2): 221–6. doi:10.1016/0014-5793(95)01349-0. PMID 8543055.
- Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
- Yee WM, Worley PF (1997). "Rheb interacts with Raf-1 kinase and may function to integrate growth factor- and protein kinase A-dependent signals". Mol. Cell. Biol. 17 (2): 921–33. PMC 231818. PMID 9001246. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=231818.
- Clark GJ, Kinch MS, Rogers-Graham K et al. (1997). "The Ras-related protein Rheb is farnesylated and antagonizes Ras signaling and transformation". J. Biol. Chem. 272 (16): 10608–15. doi:10.1074/jbc.272.16.10608. PMID 9099708.
- Inohara N, Ding L, Chen S, Núñez G (1997). "harakiri, a novel regulator of cell death, encodes a protein that activates apoptosis and interacts selectively with survival-promoting proteins Bcl-2 and Bcl-X(L)". EMBO J. 16 (7): 1686–94. doi:10.1093/emboj/16.7.1686. PMC 1169772. PMID 9130713. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1169772.
- <Please add first missing authors to populate metadata.> (1999). "Toward a complete human genome sequence". Genome Res. 8 (11): 1097–108. doi:10.1101/gr.8.11.1097. PMID 9847074.
- Kita K, Wu YP, Sugaya S et al. (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". Biochem. Biophys. Res. Commun. 274 (3): 859–64. doi:10.1006/bbrc.2000.3220. PMID 10924367.
- Hanzal-Bayer M, Renault L, Roversi P et al. (2002). "The complex of Arl2-GTP and PDEδ: from structure to function". EMBO J. 21 (9): 2095–106. doi:10.1093/emboj/21.9.2095. PMC 125981. PMID 11980706. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=125981.
- Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
- Scherer SW, Cheung J, MacDonald JR et al. (2003). "Human Chromosome 7: DNA Sequence and Biology". Science 300 (5620): 767–72. doi:10.1126/science.1083423. PMC 2882961. PMID 12690205. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2882961.
- Zhang Y, Gao X, Saucedo LJ et al. (2003). "Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins". Nat. Cell Biol. 5 (6): 578–81. doi:10.1038/ncb999. PMID 12771962.
- Garami A, Zwartkruis FJ, Nobukuni T et al. (2003). "Insulin activation of Rheb, a mediator of mTOR/S6K/4E-BP signaling, is inhibited by TSC1 and 2". Mol. Cell 11 (6): 1457–66. doi:10.1016/S1097-2765(03)00220-X. PMID 12820960.
- Castro AF, Rebhun JF, Clark GJ, Quilliam LA (2003). "Rheb binds tuberous sclerosis complex 2 (TSC2) and promotes S6 kinase activation in a rapamycin- and farnesylation-dependent manner". J. Biol. Chem. 278 (35): 32493–6. doi:10.1074/jbc.C300226200. PMID 12842888.
- Hillier LW, Fulton RS, Fulton LA et al. (2003). "The DNA sequence of human chromosome 7". Nature 424 (6945): 157–64. doi:10.1038/nature01782. PMID 12853948.
- Tabancay AP, Gau CL, Machado IM et al. (2003). "Identification of dominant negative mutants of Rheb GTPase and their use to implicate the involvement of human Rheb in the activation of p70S6K". J. Biol. Chem. 278 (41): 39921–30. doi:10.1074/jbc.M306553200. PMID 12869548.
- Inoki K, Li Y, Xu T, Guan KL (2003). "Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling". Genes Dev. 17 (15): 1829–34. doi:10.1101/gad.1110003. PMC 196227. PMID 12869586. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=196227.
- Tee AR, Manning BD, Roux PP et al. (2004). "Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb". Curr. Biol. 13 (15): 1259–68. doi:10.1016/S0960-9822(03)00506-2. PMID 12906785.
- Ota T, Suzuki Y, Nishikawa T et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
External links
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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PDB gallery
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1xtq: Structure of small GTPase human Rheb in complex with GDP
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1xtr: Structure of small GTPase human Rheb in complex with GppNHp
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1xts: Structure of small GTPase human Rheb in complex with GTP
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| 3.6.1 |
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| 3.6.2 |
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| 3.6.3-4: ATPase |
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| 3.6.5: GTPase |
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Rho family of GTPases: Cdc42 (CDC42, TC10, TCL) • RhoUV (RhoU, RhoV) • Rac (Rac1, 2, 3, RhoG) • RhoBTB (1, 2) • RhoH • Rho (A, B, C) • Rnd (1, 2, 3) • RhoDF (RhoF, RhoD)
other: Ras ( HRAS, KRAS, NRAS) · Rab ( RAB23, RAB27) · Arf ( ARF6, SAR1B, ARL13B, ARL6) · Ran · Rheb · Rap
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B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 3.1.3.48, 3.4.21/22/23/24, 4.1/2/3/4/5/6, 5.1/2/3/4/99, 6.1-3/4/5-6
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