RHEB_RAT
ID RHEB_RAT Reviewed; 184 AA.
AC Q62639;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=GTP-binding protein Rheb;
DE AltName: Full=Ras homolog enriched in brain;
DE Flags: Precursor;
GN Name=Rheb;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Hippocampus;
RX PubMed=8206940; DOI=10.1016/s0021-9258(17)34012-7;
RA Yamagata K., Sanders L.K., Kaufmann W.E., Yee W., Barnes C.A., Nathans D.,
RA Worley P.F.;
RT "Rheb, a growth factor- and synaptic activity-regulated gene, encodes a
RT novel Ras-related protein.";
RL J. Biol. Chem. 269:16333-16339(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
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 [3]
RP STRUCTURE BY NMR OF 6-174 IN COMPLEX WITH GTP, FUNCTION, AND
RP ISOPRENYLATION.
RX PubMed=20685651; DOI=10.1074/jbc.m109.095968;
RA Karassek S., Berghaus C., Schwarten M., Goemans C.G., Ohse N., Kock G.,
RA Jockers K., Neumann S., Gottfried S., Herrmann C., Heumann R., Stoll R.;
RT "Ras homolog enriched in brain (Rheb) enhances apoptotic signaling.";
RL J. Biol. Chem. 285:33979-33991(2010).
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:20685651, ECO:0000305|PubMed:20685651}.
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 (By similarity).
CC {ECO:0000250|UniProtKB:Q15382}.
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 -!- TISSUE SPECIFICITY: Expressed at high levels in normal adult cortex as
CC well as a number of peripheral tissues, including lung and intestine.
CC -!- PTM: Farnesylation is important for efficiently activating mTORC1-
CC mediated signaling. {ECO:0000269|PubMed:20685651}.
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:0000250}.
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; U08227; AAA21380.1; -; mRNA.
DR EMBL; BC088857; AAH88857.1; -; mRNA.
DR PIR; I55401; I55401.
DR RefSeq; NP_037348.1; NM_013216.1.
DR PDB; 2L0X; NMR; -; A=6-174.
DR PDBsum; 2L0X; -.
DR AlphaFoldDB; Q62639; -.
DR BMRB; Q62639; -.
DR SMR; Q62639; -.
DR BioGRID; 247802; 2.
DR STRING; 10116.ENSRNOP00000063915; -.
DR iPTMnet; Q62639; -.
DR PhosphoSitePlus; Q62639; -.
DR jPOST; Q62639; -.
DR PaxDb; Q62639; -.
DR PRIDE; Q62639; -.
DR DNASU; 26954; -.
DR Ensembl; ENSRNOT00000071737; ENSRNOP00000063915; ENSRNOG00000050578.
DR GeneID; 26954; -.
DR KEGG; rno:26954; -.
DR CTD; 6009; -.
DR RGD; 621840; Rheb.
DR eggNOG; KOG0395; Eukaryota.
DR GeneTree; ENSGT00940000159945; -.
DR InParanoid; Q62639; -.
DR OrthoDB; 1320427at2759; -.
DR PhylomeDB; Q62639; -.
DR Reactome; R-RNO-1632852; Macroautophagy.
DR Reactome; R-RNO-165159; MTOR signalling.
DR Reactome; R-RNO-166208; mTORC1-mediated signalling.
DR Reactome; R-RNO-380972; Energy dependent regulation of mTOR by LKB1-AMPK.
DR Reactome; R-RNO-5628897; TP53 Regulates Metabolic Genes.
DR Reactome; R-RNO-8943724; Regulation of PTEN gene transcription.
DR Reactome; R-RNO-9639288; Amino acids regulate mTORC1.
DR EvolutionaryTrace; Q62639; -.
DR PRO; PR:Q62639; -.
DR Proteomes; UP000002494; Chromosome 4.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0014069; C:postsynaptic density; ISO:RGD.
DR GO; GO:0005681; C:spliceosomal complex; ISO:RGD.
DR GO; GO:0019003; F:GDP binding; IDA:RGD.
DR GO; GO:0005525; F:GTP binding; IDA:RGD.
DR GO; GO:0003924; F:GTPase activity; IDA:RGD.
DR GO; GO:0000287; F:magnesium ion binding; ISO:RGD.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR GO; GO:0120163; P:negative regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0048714; P:positive regulation of oligodendrocyte differentiation; ISO:RGD.
DR GO; GO:0032008; P:positive regulation of TOR signaling; ISS:UniProtKB.
DR GO; GO:0048168; P:regulation of neuronal synaptic plasticity; NAS:RGD.
DR GO; GO:0099175; P:regulation of postsynapse organization; IDA:SynGO.
DR GO; GO:0032006; P:regulation of TOR signaling; ISO:RGD.
DR GO; GO:2000074; P:regulation of type B pancreatic cell development; ISO:RGD.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IDA:RGD.
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_0000082710"
FT PROPEP 182..184
FT /note="Removed in mature form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000281367"
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:20685651"
FT BINDING 20
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q15382"
FT BINDING 32..38
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:20685651"
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 /evidence="ECO:0000250|UniProtKB:Q8TAI7"
FT BINDING 119..122
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:20685651"
FT BINDING 149..150
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:20685651"
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:0000250"
FT LIPID 181
FT /note="S-farnesyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q15382"
FT STRAND 7..13
FT /evidence="ECO:0007829|PDB:2L0X"
FT HELIX 19..27
FT /evidence="ECO:0007829|PDB:2L0X"
FT STRAND 41..49
FT /evidence="ECO:0007829|PDB:2L0X"
FT STRAND 52..60
FT /evidence="ECO:0007829|PDB:2L0X"
FT STRAND 63..67
FT /evidence="ECO:0007829|PDB:2L0X"
FT STRAND 69..73
FT /evidence="ECO:0007829|PDB:2L0X"
FT STRAND 79..88
FT /evidence="ECO:0007829|PDB:2L0X"
FT HELIX 90..107
FT /evidence="ECO:0007829|PDB:2L0X"
FT STRAND 114..119
FT /evidence="ECO:0007829|PDB:2L0X"
FT HELIX 121..123
FT /evidence="ECO:0007829|PDB:2L0X"
FT TURN 124..126
FT /evidence="ECO:0007829|PDB:2L0X"
FT HELIX 131..141
FT /evidence="ECO:0007829|PDB:2L0X"
FT STRAND 144..147
FT /evidence="ECO:0007829|PDB:2L0X"
FT HELIX 153..173
FT /evidence="ECO:0007829|PDB:2L0X"
SQ SEQUENCE 184 AA; 20479 MW; 8F4C8080BDF92DE9 CRC64;
MPQSKSRKIA ILGYRSVGKS SLTIQFVEGQ FVDSYDPTIE NTFTKLITVN GQEYHLQLVD
TAGQDEYSIF PQTYSIDING YILVYSVTSI KSFEVIKVIH GKLLDMVGKV QIPIMLVGNK
KDLHMERVIS YEEGKALAES WNAAFLESSA KENQTAVDVF RRIILEAEKI DGAASQGKSS
CSVM
