RHEB_HUMAN
ID RHEB_HUMAN Reviewed; 184 AA.
AC Q15382; B3KWN6; D3DX13; Q53Y56; Q99444;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 225.
DE RecName: Full=GTP-binding protein Rheb;
DE AltName: Full=Ras homolog enriched in brain;
DE Flags: Precursor;
GN Name=RHEB; Synonyms=RHEB2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Psoriatic skin;
RX PubMed=8543055; DOI=10.1016/0014-5793(95)01349-0;
RA Gromov P.S., Madsen P., Tomerup N., Celis J.E.;
RT "A novel approach for expression cloning of small GTPases: identification,
RT tissue distribution and chromosome mapping of the human homolog of rheb.";
RL FEBS Lett. 377:221-226(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Skin;
RX PubMed=8661031; DOI=10.1006/geno.1996.0248;
RA Mizuki N., Kimura M., Ohno S., Miyata S., Sato M., Ando H., Ishihara M.,
RA Goto K., Watanabe S., Yamazaki M., Ono A., Taguchi S., Okumura K.,
RA Nogami M., Taguchi H., Ando A., Inoko H.;
RT "Isolation of cDNA and genomic clones of a human Ras-related GTP-binding
RT protein gene and its chromosomal localization to the long arm of chromosome
RT 7, 7q36.";
RL Genomics 34:114-118(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Mammary carcinoma;
RA Weidenmueller U., Tur M.K., Tawadros S., Engert A., Barth S.;
RT "Detection of membrane-associated proteins using serum of mice immunized
RT with membrane fractions of breast carcinoma cells.";
RL Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RA Puhl H.L. III, Ikeda S.R., Aronstam R.S.;
RT "cDNA clones of human proteins involved in signal transduction sequenced by
RT the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Muscle, and Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP FUNCTION.
RX PubMed=12271141; DOI=10.1073/pnas.202476899;
RA Tee A.R., Fingar D.C., Manning B.D., Kwiatkowski D.J., Cantley L.C.,
RA Blenis J.;
RT "Tuberous sclerosis complex-1 and -2 gene products function together to
RT inhibit mammalian target of rapamycin (mTOR)-mediated downstream
RT signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:13571-13576(2002).
RN [11]
RP FUNCTION.
RX PubMed=12869586; DOI=10.1101/gad.1110003;
RA Inoki K., Li Y., Xu T., Guan K.-L.;
RT "Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR
RT signaling.";
RL Genes Dev. 17:1829-1834(2003).
RN [12]
RP FUNCTION, AND MUTAGENESIS OF ARG-15; SER-20; ASP-60; GLN-64 AND CYS-181.
RX PubMed=15340059; DOI=10.1128/mcb.24.18.7965-7975.2004;
RA Li Y., Inoki K., Guan K.-L.;
RT "Biochemical and functional characterizations of small GTPase Rheb and TSC2
RT GAP activity.";
RL Mol. Cell. Biol. 24:7965-7975(2004).
RN [13]
RP ISOPRENYLATION AT CYS-181.
RX PubMed=15308774; DOI=10.1073/pnas.0403413101;
RA Kho Y., Kim S.C., Jiang C., Barma D., Kwon S.W., Cheng J., Jaunbergs J.,
RA Weinbaum C., Tamanoi F., Falck J., Zhao Y.;
RT "A tagging-via-substrate technology for detection and proteomics of
RT farnesylated proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:12479-12484(2004).
RN [14]
RP FUNCTION, INTERACTION WITH MTOR; MLST8; RPTOR AND TSC2, AND MUTAGENESIS OF
RP SER-20; THR-38; ILE-39 AND ASN-41.
RX PubMed=15854902; DOI=10.1016/j.cub.2005.02.053;
RA Long X., Lin Y., Ortiz-Vega S., Yonezawa K., Avruch J.;
RT "Rheb binds and regulates the mTOR kinase.";
RL Curr. Biol. 15:702-713(2005).
RN [15]
RP FUNCTION, MUTAGENESIS OF THR-38; GLU-40; ASN-41; PHE-43; LEU-46; THR-48;
RP VAL-49; GLU-53; TYR-54 AND LEU-56, AND INTERACTION WITH MTOR.
RX PubMed=16098514; DOI=10.1016/j.febslet.2005.07.054;
RA Tee A.R., Blenis J., Proud C.G.;
RT "Analysis of mTOR signaling by the small G-proteins, Rheb and RhebL1.";
RL FEBS Lett. 579:4763-4768(2005).
RN [16]
RP FUNCTION.
RX PubMed=20381137; DOI=10.1016/j.cell.2010.02.024;
RA Sancak Y., Bar-Peled L., Zoncu R., Markhard A.L., Nada S., Sabatini D.M.;
RT "Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is
RT necessary for its activation by amino acids.";
RL Cell 141:290-303(2010).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-169 IN COMPLEX WITH MAGNESIUM;
RP GDP AND GTP.
RX PubMed=15728574; DOI=10.1074/jbc.m501253200;
RA Yu Y., Li S., Xu X., Li Y., Guan K., Arnold E., Ding J.;
RT "Structural basis for the unique biological function of small GTPase
RT RHEB.";
RL J. Biol. Chem. 280:17093-17100(2005).
RN [19] {ECO:0007744|PDB:3T5G}
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 1-181 IN COMPLEX WITH GDP AND
RP PDE6D, ISOPRENYLATION AT CYS-181, METHYLATION AT CYS-181, INTERACTION WITH
RP PDE6D, AND SUBCELLULAR LOCATION.
RX PubMed=22002721; DOI=10.1038/nchembio.686;
RA Ismail S.A., Chen Y.X., Rusinova A., Chandra A., Bierbaum M., Gremer L.,
RA Triola G., Waldmann H., Bastiaens P.I., Wittinghofer A.;
RT "Arl2-GTP and Arl3-GTP regulate a GDI-like transport system for
RT farnesylated cargo.";
RL Nat. Chem. Biol. 7:942-949(2011).
RN [20]
RP VARIANT [LARGE SCALE ANALYSIS] LYS-139.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Activates the protein kinase activity of mTORC1, and thereby
CC plays a role in the regulation of apoptosis. Stimulates the
CC phosphorylation of S6K1 and EIF4EBP1 through activation of mTORC1
CC signaling. Has low intrinsic GTPase activity.
CC {ECO:0000269|PubMed:12271141, ECO:0000269|PubMed:12869586,
CC ECO:0000269|PubMed:15340059, ECO:0000269|PubMed:15854902,
CC ECO:0000269|PubMed:16098514, ECO:0000269|PubMed:20381137}.
CC -!- ACTIVITY REGULATION: Alternates between an inactive form bound to GDP
CC and an active form bound to GTP. Inactivated by TSC1-TSC2 via the
CC GTPase activating protein (GAP) domain of TSC2.
CC -!- SUBUNIT: Binds to mTORC1 in a guanyl nucleotide-independent manner.
CC Interacts directly with MTOR, MLST8 and RPTOR. Interacts with TSC2.
CC Interacts (when prenylated) with PDE6D; this promotes release from
CC membranes. {ECO:0000269|PubMed:15728574, ECO:0000269|PubMed:15854902,
CC ECO:0000269|PubMed:16098514, ECO:0000269|PubMed:22002721}.
CC -!- INTERACTION:
CC Q15382; Q92624: APPBP2; NbExp=3; IntAct=EBI-1055287, EBI-743771;
CC Q15382; P55212: CASP6; NbExp=3; IntAct=EBI-1055287, EBI-718729;
CC Q15382; P06307: CCK; NbExp=3; IntAct=EBI-1055287, EBI-6624398;
CC Q15382; P22607: FGFR3; NbExp=3; IntAct=EBI-1055287, EBI-348399;
CC Q15382; Q14957: GRIN2C; NbExp=3; IntAct=EBI-1055287, EBI-8285963;
CC Q15382; O00291: HIP1; NbExp=3; IntAct=EBI-1055287, EBI-473886;
CC Q15382; P13473-2: LAMP2; NbExp=4; IntAct=EBI-1055287, EBI-21591415;
CC Q15382; P42345: MTOR; NbExp=2; IntAct=EBI-1055287, EBI-359260;
CC Q15382; Q13393: PLD1; NbExp=2; IntAct=EBI-1055287, EBI-2827556;
CC Q15382; O75400-2: PRPF40A; NbExp=3; IntAct=EBI-1055287, EBI-5280197;
CC Q15382; P62826: RAN; NbExp=3; IntAct=EBI-1055287, EBI-286642;
CC Q15382; P13693: TPT1; NbExp=2; IntAct=EBI-1055287, EBI-1783169;
CC Q15382; Q9UMX0: UBQLN1; NbExp=3; IntAct=EBI-1055287, EBI-741480;
CC Q15382; Q9Y649; NbExp=3; IntAct=EBI-1055287, EBI-25900580;
CC PRO_0000082708; O43924: PDE6D; NbExp=5; IntAct=EBI-6860739, EBI-712685;
CC -!- SUBCELLULAR LOCATION: Endomembrane system {ECO:0000269|PubMed:22002721,
CC ECO:0000305}; Lipid-anchor {ECO:0000269|PubMed:22002721, ECO:0000305};
CC Cytoplasmic side {ECO:0000269|PubMed:15489334, ECO:0000305}. Golgi
CC apparatus membrane {ECO:0000269|PubMed:22002721}; Lipid-anchor
CC {ECO:0000305|PubMed:22002721}; Cytoplasmic side
CC {ECO:0000305|PubMed:22002721}. Cytoplasm, cytosol
CC {ECO:0000269|PubMed:22002721}. Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:22002721}; Lipid-anchor
CC {ECO:0000269|PubMed:22002721}; Cytoplasmic side
CC {ECO:0000269|PubMed:22002721}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. Highest levels observed in skeletal and
CC cardiac muscle. {ECO:0000269|PubMed:8543055}.
CC -!- PTM: Farnesylation is important for efficiently activating mTORC1-
CC mediated signaling.
CC -!- PTM: Phosphorylation by MAPKAPK5 impairs GTP-binding and inactivation.
CC {ECO:0000250|UniProtKB:Q921J2}.
CC -!- MISCELLANEOUS: The conserved catalytic Gln-64 found in other Ras-like
CC GTPases seems not to be involved in GTP hydrolysis in RHEB.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rheb family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; Z29677; CAA82774.1; -; mRNA.
DR EMBL; D78132; BAA11211.1; -; mRNA.
DR EMBL; AF148645; AAF73125.1; -; mRNA.
DR EMBL; AF493921; AAM12635.1; -; mRNA.
DR EMBL; AK125446; BAG54198.1; -; mRNA.
DR EMBL; BT006958; AAP35604.1; -; mRNA.
DR EMBL; AC005996; AAD15548.1; -; Genomic_DNA.
DR EMBL; CH471173; EAW53989.1; -; Genomic_DNA.
DR EMBL; BC016155; AAH16155.1; -; mRNA.
DR EMBL; BC107705; AAI07706.1; -; mRNA.
DR CCDS; CCDS5927.1; -.
DR PIR; S68419; S41960.
DR RefSeq; NP_005605.1; NM_005614.3.
DR PDB; 1XTQ; X-ray; 2.00 A; A=1-169.
DR PDB; 1XTR; X-ray; 2.65 A; A=1-169.
DR PDB; 1XTS; X-ray; 2.80 A; A=1-169.
DR PDB; 3SEA; X-ray; 2.00 A; A/B=3-169.
DR PDB; 3T5G; X-ray; 1.70 A; A=1-181.
DR PDB; 5YXH; X-ray; 2.04 A; A/B/C/D=2-169.
DR PDB; 6BCU; EM; 3.43 A; R/S=1-184.
DR PDB; 6BSX; X-ray; 1.65 A; A/B/C/D=1-169.
DR PDB; 6BT0; X-ray; 2.60 A; A/B/C/D=1-169.
DR PDB; 7BTA; X-ray; 2.60 A; A/B=1-169.
DR PDB; 7BTC; X-ray; 2.10 A; A/B/C/D=1-169.
DR PDB; 7BTD; X-ray; 2.00 A; A=1-169.
DR PDBsum; 1XTQ; -.
DR PDBsum; 1XTR; -.
DR PDBsum; 1XTS; -.
DR PDBsum; 3SEA; -.
DR PDBsum; 3T5G; -.
DR PDBsum; 5YXH; -.
DR PDBsum; 6BCU; -.
DR PDBsum; 6BSX; -.
DR PDBsum; 6BT0; -.
DR PDBsum; 7BTA; -.
DR PDBsum; 7BTC; -.
DR PDBsum; 7BTD; -.
DR AlphaFoldDB; Q15382; -.
DR BMRB; Q15382; -.
DR SMR; Q15382; -.
DR BioGRID; 111941; 89.
DR DIP; DIP-42816N; -.
DR IntAct; Q15382; 48.
DR MINT; Q15382; -.
DR STRING; 9606.ENSP00000262187; -.
DR BindingDB; Q15382; -.
DR ChEMBL; CHEMBL3108656; -.
DR DrugBank; DB04315; Guanosine-5'-Diphosphate.
DR DrugBank; DB04137; Guanosine-5'-Triphosphate.
DR iPTMnet; Q15382; -.
DR MetOSite; Q15382; -.
DR PhosphoSitePlus; Q15382; -.
DR SwissPalm; Q15382; -.
DR BioMuta; RHEB; -.
DR DMDM; 6919957; -.
DR EPD; Q15382; -.
DR jPOST; Q15382; -.
DR MassIVE; Q15382; -.
DR MaxQB; Q15382; -.
DR PaxDb; Q15382; -.
DR PeptideAtlas; Q15382; -.
DR PRIDE; Q15382; -.
DR ProteomicsDB; 60554; -.
DR TopDownProteomics; Q15382; -.
DR Antibodypedia; 18765; 495 antibodies from 40 providers.
DR DNASU; 6009; -.
DR Ensembl; ENST00000262187.10; ENSP00000262187.5; ENSG00000106615.10.
DR GeneID; 6009; -.
DR KEGG; hsa:6009; -.
DR MANE-Select; ENST00000262187.10; ENSP00000262187.5; NM_005614.4; NP_005605.1.
DR UCSC; uc003wkh.1; human.
DR CTD; 6009; -.
DR DisGeNET; 6009; -.
DR GeneCards; RHEB; -.
DR HGNC; HGNC:10011; RHEB.
DR HPA; ENSG00000106615; Low tissue specificity.
DR MIM; 601293; gene.
DR neXtProt; NX_Q15382; -.
DR OpenTargets; ENSG00000106615; -.
DR PharmGKB; PA34389; -.
DR VEuPathDB; HostDB:ENSG00000106615; -.
DR eggNOG; KOG0395; Eukaryota.
DR GeneTree; ENSGT00940000159945; -.
DR HOGENOM; CLU_041217_9_8_1; -.
DR InParanoid; Q15382; -.
DR OMA; MPIHTEL; -.
DR OrthoDB; 1320427at2759; -.
DR PhylomeDB; Q15382; -.
DR TreeFam; TF314986; -.
DR BRENDA; 3.6.5.2; 2681.
DR PathwayCommons; Q15382; -.
DR Reactome; R-HSA-1632852; Macroautophagy.
DR Reactome; R-HSA-165159; MTOR signalling.
DR Reactome; R-HSA-166208; mTORC1-mediated signalling.
DR Reactome; R-HSA-380972; Energy dependent regulation of mTOR by LKB1-AMPK.
DR Reactome; R-HSA-5628897; TP53 Regulates Metabolic Genes.
DR Reactome; R-HSA-8943724; Regulation of PTEN gene transcription.
DR Reactome; R-HSA-9639288; Amino acids regulate mTORC1.
DR SABIO-RK; Q15382; -.
DR SignaLink; Q15382; -.
DR SIGNOR; Q15382; -.
DR BioGRID-ORCS; 6009; 516 hits in 1053 CRISPR screens.
DR ChiTaRS; RHEB; human.
DR EvolutionaryTrace; Q15382; -.
DR GeneWiki; RHEB; -.
DR GenomeRNAi; 6009; -.
DR Pharos; Q15382; Tbio.
DR PRO; PR:Q15382; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q15382; protein.
DR Bgee; ENSG00000106615; Expressed in ventricular zone and 141 other tissues.
DR ExpressionAtlas; Q15382; baseline and differential.
DR Genevisible; Q15382; HS.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005765; C:lysosomal membrane; TAS:Reactome.
DR GO; GO:0016020; C:membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0014069; C:postsynaptic density; IDA:SynGO.
DR GO; GO:0005681; C:spliceosomal complex; IEA:Ensembl.
DR GO; GO:0019003; F:GDP binding; IMP:CAFA.
DR GO; GO:0005525; F:GTP binding; IMP:CAFA.
DR GO; GO:0003924; F:GTPase activity; IBA:GO_Central.
DR GO; GO:0000287; F:magnesium ion binding; IMP:CAFA.
DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
DR GO; GO:0120163; P:negative regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0048709; P:oligodendrocyte differentiation; IEA:Ensembl.
DR GO; GO:0048714; P:positive regulation of oligodendrocyte differentiation; IEA:Ensembl.
DR GO; GO:0032008; P:positive regulation of TOR signaling; IMP:UniProtKB.
DR GO; GO:0051726; P:regulation of cell cycle; TAS:Reactome.
DR GO; GO:0016241; P:regulation of macroautophagy; TAS:Reactome.
DR GO; GO:2000074; P:regulation of type B pancreatic cell development; IMP:CACAO.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IBA:GO_Central.
DR DisProt; DP00364; -.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR037586; RHEB.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR001806; Small_GTPase.
DR InterPro; IPR020849; Small_GTPase_Ras-type.
DR PANTHER; PTHR24070; PTHR24070; 1.
DR PANTHER; PTHR24070:SF264; PTHR24070:SF264; 1.
DR Pfam; PF00071; Ras; 1.
DR SMART; SM00174; RHO; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51421; RAS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Endoplasmic reticulum; Golgi apparatus;
KW GTP-binding; Lipoprotein; Magnesium; Membrane; Metal-binding; Methylation;
KW Nucleotide-binding; Phosphoprotein; Prenylation; Reference proteome.
FT CHAIN 1..181
FT /note="GTP-binding protein Rheb"
FT /id="PRO_0000082708"
FT PROPEP 182..184
FT /note="Removed in mature form"
FT /id="PRO_0000281365"
FT MOTIF 35..43
FT /note="Effector region"
FT /evidence="ECO:0000305"
FT BINDING 16..21
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:15728574,
FT ECO:0000269|PubMed:22002721"
FT BINDING 20
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:15728574"
FT BINDING 32..38
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:15728574,
FT ECO:0000269|PubMed:22002721"
FT BINDING 38
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:15728574"
FT BINDING 63
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q8TAI7"
FT BINDING 119..122
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:15728574,
FT ECO:0000269|PubMed:22002721"
FT BINDING 149..150
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:15728574,
FT ECO:0000269|PubMed:22002721"
FT MOD_RES 130
FT /note="Phosphoserine; by MAPKAPK5"
FT /evidence="ECO:0000250|UniProtKB:Q921J2"
FT MOD_RES 181
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000269|PubMed:15308774,
FT ECO:0000269|PubMed:22002721, ECO:0007744|PDB:3T5G"
FT LIPID 181
FT /note="S-farnesyl cysteine"
FT /evidence="ECO:0000269|PubMed:15308774,
FT ECO:0000269|PubMed:22002721, ECO:0007744|PDB:3T5G"
FT VARIANT 139
FT /note="E -> K (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036310"
FT MUTAGEN 15
FT /note="R->G: Partially resistant to inactivation by TSC1-
FT TSC2."
FT /evidence="ECO:0000269|PubMed:15340059"
FT MUTAGEN 20
FT /note="S->N: Deficient in guanine nucleotide binding.
FT Unable to rescue S6K1 from inactivation by amino-acid
FT withdrawal."
FT /evidence="ECO:0000269|PubMed:15340059,
FT ECO:0000269|PubMed:15854902"
FT MUTAGEN 38
FT /note="T->M: Slightly impairs signaling through mTORC1, but
FT still binds guanine nucleotides normally."
FT /evidence="ECO:0000269|PubMed:15854902,
FT ECO:0000269|PubMed:16098514"
FT MUTAGEN 39
FT /note="I->K: Impairs S6K1 activation, but still binds
FT guanine nucleotides normally."
FT /evidence="ECO:0000269|PubMed:15854902"
FT MUTAGEN 40
FT /note="E->G: No effect."
FT /evidence="ECO:0000269|PubMed:16098514"
FT MUTAGEN 41
FT /note="N->A: Impairs interaction with MTOR. Impairs
FT signaling through mTORC1, but still binds guanine
FT nucleotides normally."
FT /evidence="ECO:0000269|PubMed:15854902,
FT ECO:0000269|PubMed:16098514"
FT MUTAGEN 43
FT /note="F->C: No effect."
FT /evidence="ECO:0000269|PubMed:16098514"
FT MUTAGEN 46
FT /note="L->A: Causes slight reduction in S6K1 activation."
FT /evidence="ECO:0000269|PubMed:16098514"
FT MUTAGEN 48
FT /note="T->A: Causes slightly reduced phosphorylation of
FT EIF4EBP1."
FT /evidence="ECO:0000269|PubMed:16098514"
FT MUTAGEN 49
FT /note="V->A: Causes slightly reduced phosphorylation of
FT EIF4EBP1."
FT /evidence="ECO:0000269|PubMed:16098514"
FT MUTAGEN 53
FT /note="E->A: Causes slightly reduced phosphorylation of
FT EIF4EBP1."
FT /evidence="ECO:0000269|PubMed:16098514"
FT MUTAGEN 54
FT /note="Y->A: Partially deficient in guanine nucleotide
FT binding. Fully impairs EIF4EBP1 phosphorylation and S6K1
FT activation."
FT /evidence="ECO:0000269|PubMed:16098514"
FT MUTAGEN 56
FT /note="L->A: Partially deficient in guanine nucleotide
FT binding. Fully impairs EIF4EBP1 phosphorylation and S6K1
FT activation."
FT /evidence="ECO:0000269|PubMed:16098514"
FT MUTAGEN 60
FT /note="D->I: Deficient in guanine nucleotide binding.
FT Unable to rescue S6K1 from inactivation by amino-acid
FT withdrawal."
FT /evidence="ECO:0000269|PubMed:15340059"
FT MUTAGEN 64
FT /note="Q->L: Has a higher basal GTPase level, however, is
FT still sensitive to TSC2 GAP activity."
FT /evidence="ECO:0000269|PubMed:15340059"
FT MUTAGEN 181
FT /note="C->S: Reduces the ability to rescue S6K1 from
FT inactivation by amino-acid withdrawal."
FT /evidence="ECO:0000269|PubMed:15340059"
FT CONFLICT 118
FT /note="G -> W (in Ref. 2; BAA11211)"
FT /evidence="ECO:0000305"
FT STRAND 5..14
FT /evidence="ECO:0007829|PDB:6BSX"
FT HELIX 19..28
FT /evidence="ECO:0007829|PDB:6BSX"
FT STRAND 39..49
FT /evidence="ECO:0007829|PDB:6BSX"
FT STRAND 52..60
FT /evidence="ECO:0007829|PDB:6BSX"
FT STRAND 66..68
FT /evidence="ECO:0007829|PDB:7BTA"
FT HELIX 72..75
FT /evidence="ECO:0007829|PDB:6BSX"
FT STRAND 80..86
FT /evidence="ECO:0007829|PDB:6BSX"
FT HELIX 90..107
FT /evidence="ECO:0007829|PDB:6BSX"
FT STRAND 114..119
FT /evidence="ECO:0007829|PDB:6BSX"
FT HELIX 124..126
FT /evidence="ECO:0007829|PDB:6BSX"
FT HELIX 131..140
FT /evidence="ECO:0007829|PDB:6BSX"
FT STRAND 145..147
FT /evidence="ECO:0007829|PDB:6BSX"
FT HELIX 153..169
FT /evidence="ECO:0007829|PDB:6BSX"
SQ SEQUENCE 184 AA; 20497 MW; 8F4C8080BDF928FD CRC64;
MPQSKSRKIA ILGYRSVGKS SLTIQFVEGQ FVDSYDPTIE NTFTKLITVN GQEYHLQLVD
TAGQDEYSIF PQTYSIDING YILVYSVTSI KSFEVIKVIH GKLLDMVGKV QIPIMLVGNK
KDLHMERVIS YEEGKALAES WNAAFLESSA KENQTAVDVF RRIILEAEKM DGAASQGKSS
CSVM
