GTP-binding protein Rheb

Details

Name
GTP-binding protein Rheb
Synonyms
  • Ras homolog enriched in brain
  • RHEB2
Gene Name
RHEB
Organism
Humans
Amino acid sequence
>lcl|BSEQ0013209|GTP-binding protein Rheb
MPQSKSRKIAILGYRSVGKSSLTIQFVEGQFVDSYDPTIENTFTKLITVNGQEYHLQLVD
TAGQDEYSIFPQTYSIDINGYILVYSVTSIKSFEVIKVIHGKLLDMVGKVQIPIMLVGNK
KDLHMERVISYEEGKALAESWNAAFLESSAKENQTAVDVFRRIILEAEKMDGAASQGKSS
CSVM
Number of residues
184
Molecular Weight
20497.335
Theoretical pI
Not Available
GO Classification
Functions
GTP binding / GTPase activity / metal ion binding
Processes
cell cycle arrest / gene expression / insulin receptor signaling pathway / macroautophagy / positive regulation of oligodendrocyte differentiation / positive regulation of TOR signaling / regulation of type B pancreatic cell development / signal transduction / small GTPase mediated signal transduction / transcription initiation from RNA polymerase II promoter
Components
cytosol / endoplasmic reticulum membrane / extracellular exosome / Golgi membrane / lysosomal membrane / membrane / spliceosomal complex
General Function
Metal ion binding
Specific Function
Activates the protein kinase activity of mTORC1, and thereby plays a role in the regulation of apoptosis. Stimulates the phosphorylation of S6K1 and EIF4EBP1 through activation of mTORC1 signaling. Has low intrinsic GTPase activity.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Endomembrane system
Gene sequence
>lcl|BSEQ0013210|GTP-binding protein Rheb (RHEB)
ATGCCGCAGTCCAAGTCCCGGAAGATCGCGATCCTGGGCTACCGGTCTGTGGGGAAATCC
TCATTGACGATTCAATTTGTTGAAGGCCAATTTGTGGACTCCTACGATCCAACCATAGAA
AACACTTTTACAAAGTTGATCACAGTAAATGGACAAGAATATCATCTTCAACTTGTAGAC
ACAGCCGGGCAAGATGAATATTCTATCTTTCCTCAGACATACTCCATAGATATTAATGGC
TATATTCTTGTGTATTCTGTTACATCAATCAAAAGTTTTGAAGTGATTAAAGTTATCCAT
GGCAAATTGTTGGATATGGTGGGGAAAGTACAAATACCTATTATGTTGGTTGGGAATAAG
AAAGACCTGCATATGGAAAGGGTGATCAGTTATGAAGAAGGGAAAGCTTTGGCAGAATCT
TGGAATGCAGCTTTTTTGGAATCTTCTGCTAAAGAAAATCAGACTGCTGTGGATGTTTTT
CGAAGGATAATTTTGGAGGCAGAAAAAATGGACGGGGCAGCTTCACAAGGCAAGTCTTCA
TGCTCGGTGATGTGA
Chromosome Location
7
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDQ15382
UniProtKB Entry NameRHEB_HUMAN
HGNC IDHGNC:10011
General References
  1. Gromov PS, Madsen P, Tomerup N, Celis JE: A novel approach for expression cloning of small GTPases: identification, tissue distribution and chromosome mapping of the human homolog of rheb. FEBS Lett. 1995 Dec 18;377(2):221-6. [Article]
  2. 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: 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. 1996 May 15;34(1):114-8. [Article]
  3. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
  4. Hillier LW, Fulton RS, Fulton LA, Graves TA, Pepin KH, Wagner-McPherson C, Layman D, Maas J, Jaeger S, Walker R, Wylie K, Sekhon M, Becker MC, O'Laughlin MD, Schaller ME, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Cordes M, Du H, Sun H, Edwards J, Bradshaw-Cordum H, Ali J, Andrews S, Isak A, Vanbrunt A, Nguyen C, Du F, Lamar B, Courtney L, Kalicki J, Ozersky P, Bielicki L, Scott K, Holmes A, Harkins R, Harris A, Strong CM, Hou S, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Leonard S, Rohlfing T, Rock SM, Tin-Wollam AM, Abbott A, Minx P, Maupin R, Strowmatt C, Latreille P, Miller N, Johnson D, Murray J, Woessner JP, Wendl MC, Yang SP, Schultz BR, Wallis JW, Spieth J, Bieri TA, Nelson JO, Berkowicz N, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Bedell JA, Mardis ER, Clifton SW, Chissoe SL, Marra MA, Raymond C, Haugen E, Gillett W, Zhou Y, James R, Phelps K, Iadanoto S, Bubb K, Simms E, Levy R, Clendenning J, Kaul R, Kent WJ, Furey TS, Baertsch RA, Brent MR, Keibler E, Flicek P, Bork P, Suyama M, Bailey JA, Portnoy ME, Torrents D, Chinwalla AT, Gish WR, Eddy SR, McPherson JD, Olson MV, Eichler EE, Green ED, Waterston RH, Wilson RK: The DNA sequence of human chromosome 7. Nature. 2003 Jul 10;424(6945):157-64. [Article]
  5. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  6. Tee AR, Fingar DC, Manning BD, Kwiatkowski DJ, Cantley LC, Blenis J: Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling. Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13571-6. Epub 2002 Sep 23. [Article]
  7. Inoki K, Li Y, Xu T, Guan KL: Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling. Genes Dev. 2003 Aug 1;17(15):1829-34. Epub 2003 Jul 17. [Article]
  8. Li Y, Inoki K, Guan KL: Biochemical and functional characterizations of small GTPase Rheb and TSC2 GAP activity. Mol Cell Biol. 2004 Sep;24(18):7965-75. [Article]
  9. Kho Y, Kim SC, Jiang C, Barma D, Kwon SW, Cheng J, Jaunbergs J, Weinbaum C, Tamanoi F, Falck J, Zhao Y: A tagging-via-substrate technology for detection and proteomics of farnesylated proteins. Proc Natl Acad Sci U S A. 2004 Aug 24;101(34):12479-84. Epub 2004 Aug 12. [Article]
  10. Long X, Lin Y, Ortiz-Vega S, Yonezawa K, Avruch J: Rheb binds and regulates the mTOR kinase. Curr Biol. 2005 Apr 26;15(8):702-13. [Article]
  11. Tee AR, Blenis J, Proud CG: Analysis of mTOR signaling by the small G-proteins, Rheb and RhebL1. FEBS Lett. 2005 Aug 29;579(21):4763-8. [Article]
  12. Sancak Y, Bar-Peled L, Zoncu R, Markhard AL, Nada S, Sabatini DM: Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids. Cell. 2010 Apr 16;141(2):290-303. doi: 10.1016/j.cell.2010.02.024. Epub 2010 Apr 8. [Article]
  13. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
  14. Yu Y, Li S, Xu X, Li Y, Guan K, Arnold E, Ding J: Structural basis for the unique biological function of small GTPase RHEB. J Biol Chem. 2005 Apr 29;280(17):17093-100. Epub 2005 Feb 23. [Article]
  15. Ismail SA, Chen YX, Rusinova A, Chandra A, Bierbaum M, Gremer L, Triola G, Waldmann H, Bastiaens PI, Wittinghofer A: Arl2-GTP and Arl3-GTP regulate a GDI-like transport system for farnesylated cargo. Nat Chem Biol. 2011 Oct 16;7(12):942-9. doi: 10.1038/nchembio.686. [Article]
  16. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE: The consensus coding sequences of human breast and colorectal cancers. Science. 2006 Oct 13;314(5797):268-74. Epub 2006 Sep 7. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB04137Guanosine-5'-TriphosphateexperimentalunknownDetails
DB04315Guanosine-5'-DiphosphateexperimentalunknownDetails