RHEB_MOUSE
ID RHEB_MOUSE Reviewed; 184 AA.
AC Q921J2;
DT 10-JAN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=GTP-binding protein Rheb;
DE AltName: Full=Ras homolog enriched in brain;
DE Flags: Precursor;
GN Name=Rheb;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [2]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [3]
RP PHOSPHORYLATION AT SER-130, AND MUTAGENESIS OF SER-130.
RX PubMed=21336308; DOI=10.1038/ncb2168;
RA Zheng M., Wang Y.H., Wu X.N., Wu S.Q., Lu B.J., Dong M.Q., Zhang H.,
RA Sun P., Lin S.C., Guan K.L., Han J.;
RT "Inactivation of Rheb by PRAK-mediated phosphorylation is essential for
RT energy-depletion-induced suppression of mTORC1.";
RL Nat. Cell Biol. 13:263-272(2011).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 1-169 IN COMPLEX WITH GTP AND
RP MAGNESIUM, FUNCTION, ACTIVITY REGULATION, AND MUTAGENESIS OF GLY-63.
RX PubMed=24648513; DOI=10.1074/jbc.c113.543736;
RA Mazhab-Jafari M.T., Marshall C.B., Ho J., Ishiyama N., Stambolic V.,
RA Ikura M.;
RT "Structure-guided mutation of the conserved G3-box glycine in Rheb
RT generates a constitutively activated regulator of mammalian target of
RT rapamycin (mTOR).";
RL J. Biol. Chem. 289:12195-12201(2014).
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:24648513, ECO:0000305}.
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 {ECO:0000269|PubMed:24648513}.
CC -!- SUBUNIT: Binds to mTORC1 in a guanyl nucleotide-independent manner.
CC Interacts directly with MTOR, MLST8 and RPTOR. Interacts with TSC2 (By
CC similarity). Interacts (when prenylated) with PDE6D; this promotes
CC release from membranes (By similarity). {ECO:0000250|UniProtKB:Q15382}.
CC -!- SUBCELLULAR LOCATION: Endomembrane system
CC {ECO:0000250|UniProtKB:Q15382}; Lipid-anchor
CC {ECO:0000250|UniProtKB:Q15382}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:Q15382}. Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:Q15382}; Lipid-anchor
CC {ECO:0000250|UniProtKB:Q15382}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:Q15382}. Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q15382}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q15382}; Lipid-anchor
CC {ECO:0000250|UniProtKB:Q15382}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:Q15382}.
CC -!- PTM: Farnesylation is important for efficiently activating mTORC1-
CC mediated signaling. {ECO:0000250|UniProtKB:Q62639}.
CC -!- PTM: Phosphorylation by MAPKAPK5 impairs GTP-binding and inactivation.
CC {ECO:0000269|PubMed:21336308}.
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:0000250}.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rheb family.
CC {ECO:0000305}.
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DR EMBL; BC012273; AAH12273.1; -; mRNA.
DR CCDS; CCDS39032.1; -.
DR RefSeq; NP_444305.2; NM_053075.3.
DR PDB; 4O25; X-ray; 2.20 A; A/B=1-169.
DR PDB; 4O2L; X-ray; 2.40 A; A/B=1-169.
DR PDB; 4O2R; X-ray; 2.25 A; A/B=1-169.
DR PDBsum; 4O25; -.
DR PDBsum; 4O2L; -.
DR PDBsum; 4O2R; -.
DR AlphaFoldDB; Q921J2; -.
DR BMRB; Q921J2; -.
DR SMR; Q921J2; -.
DR BioGRID; 202889; 18.
DR IntAct; Q921J2; 5.
DR MINT; Q921J2; -.
DR STRING; 10090.ENSMUSP00000030787; -.
DR iPTMnet; Q921J2; -.
DR PhosphoSitePlus; Q921J2; -.
DR EPD; Q921J2; -.
DR MaxQB; Q921J2; -.
DR PaxDb; Q921J2; -.
DR PRIDE; Q921J2; -.
DR ProteomicsDB; 255328; -.
DR Antibodypedia; 18765; 495 antibodies from 40 providers.
DR DNASU; 19744; -.
DR Ensembl; ENSMUST00000030787; ENSMUSP00000030787; ENSMUSG00000028945.
DR GeneID; 19744; -.
DR KEGG; mmu:19744; -.
DR UCSC; uc008wsj.1; mouse.
DR CTD; 6009; -.
DR MGI; MGI:97912; Rheb.
DR VEuPathDB; HostDB:ENSMUSG00000028945; -.
DR eggNOG; KOG0395; Eukaryota.
DR GeneTree; ENSGT00940000159945; -.
DR HOGENOM; CLU_041217_9_8_1; -.
DR InParanoid; Q921J2; -.
DR OMA; MPIHTEL; -.
DR OrthoDB; 1320427at2759; -.
DR PhylomeDB; Q921J2; -.
DR TreeFam; TF314986; -.
DR Reactome; R-MMU-1632852; Macroautophagy.
DR Reactome; R-MMU-165159; MTOR signalling.
DR Reactome; R-MMU-166208; mTORC1-mediated signalling.
DR Reactome; R-MMU-380972; Energy dependent regulation of mTOR by LKB1-AMPK.
DR Reactome; R-MMU-5628897; TP53 Regulates Metabolic Genes.
DR Reactome; R-MMU-8943724; Regulation of PTEN gene transcription.
DR Reactome; R-MMU-9639288; Amino acids regulate mTORC1.
DR BioGRID-ORCS; 19744; 16 hits in 75 CRISPR screens.
DR ChiTaRS; Rheb; mouse.
DR PRO; PR:Q921J2; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q921J2; protein.
DR Bgee; ENSMUSG00000028945; Expressed in ear vesicle and 249 other tissues.
DR ExpressionAtlas; Q921J2; baseline and differential.
DR Genevisible; Q921J2; MM.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0014069; C:postsynaptic density; ISO:MGI.
DR GO; GO:0005681; C:spliceosomal complex; IDA:MGI.
DR GO; GO:0019003; F:GDP binding; ISO:MGI.
DR GO; GO:0005525; F:GTP binding; IDA:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; ISO:MGI.
DR GO; GO:0000287; F:magnesium ion binding; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0120163; P:negative regulation of cold-induced thermogenesis; IMP:YuBioLab.
DR GO; GO:0048709; P:oligodendrocyte differentiation; IMP:MGI.
DR GO; GO:0048714; P:positive regulation of oligodendrocyte differentiation; IMP:MGI.
DR GO; GO:0032008; P:positive regulation of TOR signaling; IDA:UniProtKB.
DR GO; GO:0099175; P:regulation of postsynapse organization; ISO:MGI.
DR GO; GO:0032006; P:regulation of TOR signaling; IMP:CACAO.
DR GO; GO:2000074; P:regulation of type B pancreatic cell development; ISO:MGI.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; ISO:MGI.
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_0000082709"
FT PROPEP 182..184
FT /note="Removed in mature form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000281366"
FT MOTIF 35..43
FT /note="Effector region"
FT BINDING 16..21
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:24648513"
FT BINDING 20
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:24648513"
FT BINDING 32..38
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:24648513"
FT BINDING 38
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q15382"
FT BINDING 63
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT BINDING 119..122
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:24648513"
FT BINDING 149..150
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:24648513"
FT MOD_RES 130
FT /note="Phosphoserine; by MAPKAPK5"
FT /evidence="ECO:0000269|PubMed:21336308"
FT MOD_RES 181
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000250"
FT LIPID 181
FT /note="S-farnesyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q15382"
FT MUTAGEN 63
FT /note="G->A: Impairs GTPase activity and increases
FT stimulation of the protein kinase activity of mTORC1."
FT /evidence="ECO:0000269|PubMed:24648513"
FT MUTAGEN 130
FT /note="S->A: Abolishes phosphorylation by MAPKAPK5 and
FT impairs GTP-binding."
FT /evidence="ECO:0000269|PubMed:21336308"
FT STRAND 5..14
FT /evidence="ECO:0007829|PDB:4O25"
FT HELIX 19..28
FT /evidence="ECO:0007829|PDB:4O25"
FT STRAND 41..49
FT /evidence="ECO:0007829|PDB:4O25"
FT STRAND 52..60
FT /evidence="ECO:0007829|PDB:4O25"
FT STRAND 80..86
FT /evidence="ECO:0007829|PDB:4O25"
FT HELIX 90..107
FT /evidence="ECO:0007829|PDB:4O25"
FT STRAND 114..119
FT /evidence="ECO:0007829|PDB:4O25"
FT HELIX 124..126
FT /evidence="ECO:0007829|PDB:4O25"
FT HELIX 131..140
FT /evidence="ECO:0007829|PDB:4O25"
FT STRAND 145..147
FT /evidence="ECO:0007829|PDB:4O25"
FT HELIX 153..167
FT /evidence="ECO:0007829|PDB:4O25"
SQ SEQUENCE 184 AA; 20451 MW; 7EC58080BDF92DFB CRC64;
MPQSKSRKIA ILGYRSVGKS SLTIQFVEGQ FVDSYDPTIE NTFTKLITVN GQEYHLQLVD
TAGQDEYSIF PQTYSIDING YILVYSVTSI KSFEVIKVIH GKLLDMVGKV QIPIMLVGNK
KDLHMERVIS YEEGKALAES WNAAFLESSA KENQTAVDVF KRIILEAEKI DGAASQGKSS
CSVM
