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Protein

GTP-binding protein Rheb

Gene

Rheb

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.Curated1 Publication

Enzyme regulationi

Alternates between an inactive form bound to GDP and an active form bound to GTP. Inactivated by TSC1-TSC2 via the GTPase activating protein (GAP) domain of TSC2.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi20 – 201Magnesium1 Publication
Metal bindingi38 – 381MagnesiumBy similarity
Binding sitei63 – 631GTP; via amide nitrogen

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi16 – 216GTP1 Publication
Nucleotide bindingi32 – 387GTP1 Publication
Nucleotide bindingi119 – 1224GTP1 Publication
Nucleotide bindingi149 – 1502GTP1 Publication

GO - Molecular functioni

  • GTP binding Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • protein kinase binding Source: UniProtKB

GO - Biological processi

  • positive regulation of TOR signaling Source: UniProtKB
  • regulation of TOR signaling Source: CACAO
  • regulation of type B pancreatic cell development Source: MGI
  • small GTPase mediated signal transduction Source: InterPro
Complete GO annotation...

Keywords - Ligandi

GTP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiREACT_288513. Regulation of AMPK activity via LKB1.
REACT_290209. Release of eIF4E.
REACT_303124. mTOR signalling.
REACT_307891. Regulation of Rheb GTPase activity by AMPK.
REACT_333210. S6K1-mediated signalling.
REACT_360191. TP53 Regulates Metabolic Genes.

Names & Taxonomyi

Protein namesi
Recommended name:
GTP-binding protein Rheb
Alternative name(s):
Ras homolog enriched in brain
Gene namesi
Name:Rheb
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:97912. Rheb.

Subcellular locationi

  • Endomembrane system By similarity; Lipid-anchor By similarity; Cytoplasmic side By similarity
  • Golgi apparatus membrane By similarity; Lipid-anchor By similarity; Cytoplasmic side By similarity
  • Cytoplasmcytosol By similarity
  • Endoplasmic reticulum membrane By similarity; Lipid-anchor By similarity; Cytoplasmic side By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Golgi apparatus, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi63 – 631G → A: Impairs GTPase activity and increases stimulation of the protein kinase activity of mTORC1. 1 Publication
Mutagenesisi130 – 1301S → A: Abolishes phosphorylation by MAPKAPK5 and impairs GTP-binding. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 181181GTP-binding protein RhebPRO_0000082709Add
BLAST
Propeptidei182 – 1843Removed in mature formBy similarityPRO_0000281366

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei130 – 1301Phosphoserine; by MAPKAPK51 Publication
Modified residuei181 – 1811Cysteine methyl esterBy similarity
Lipidationi181 – 1811S-farnesyl cysteineBy similarity

Post-translational modificationi

Farnesylation is important for efficiently activating mTORC1-mediated signaling.By similarity
Phosphorylation by MAPKAPK5 impairs GTP-binding and inactivation.1 Publication

Keywords - PTMi

Lipoprotein, Methylation, Phosphoprotein, Prenylation

Proteomic databases

MaxQBiQ921J2.
PaxDbiQ921J2.
PRIDEiQ921J2.

PTM databases

PhosphoSiteiQ921J2.

Expressioni

Gene expression databases

BgeeiQ921J2.
CleanExiMM_RHEB.
ExpressionAtlasiQ921J2. baseline and differential.
GenevisibleiQ921J2. MM.

Interactioni

Subunit structurei

Binds to mTORC1 in a guanyl nucleotide-independent manner. Interacts directly with MTOR, MLST8 and RPTOR. Interacts with TSC2 (By similarity). Interacts (when prenylated) with PDE6D; this promotes release from membranes (By similarity).By similarity

Protein-protein interaction databases

BioGridi202889. 5 interactions.
IntActiQ921J2. 2 interactions.
MINTiMINT-4611176.
STRINGi10090.ENSMUSP00000030787.

Structurei

Secondary structure

1
184
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi5 – 1410Combined sources
Helixi19 – 2810Combined sources
Beta strandi41 – 499Combined sources
Beta strandi52 – 609Combined sources
Beta strandi80 – 867Combined sources
Helixi90 – 10718Combined sources
Beta strandi114 – 1196Combined sources
Helixi124 – 1263Combined sources
Helixi131 – 14010Combined sources
Beta strandi145 – 1473Combined sources
Helixi153 – 16715Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4O25X-ray2.20A/B1-169[»]
4O2LX-ray2.40A/B1-169[»]
4O2RX-ray2.25A/B1-169[»]
ProteinModelPortaliQ921J2.
SMRiQ921J2. Positions 3-169.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi35 – 439Effector region

Sequence similaritiesi

Belongs to the small GTPase superfamily. Rheb family.Curated

Phylogenomic databases

eggNOGiCOG1100.
GeneTreeiENSGT00780000121877.
HOGENOMiHOG000233973.
HOVERGENiHBG009351.
InParanoidiQ921J2.
KOiK07208.
OMAiTILNSKH.
OrthoDBiEOG7Q2N6K.
PhylomeDBiQ921J2.
TreeFamiTF314986.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR027417. P-loop_NTPase.
IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
IPR020849. Small_GTPase_Ras.
[Graphical view]
PANTHERiPTHR24070. PTHR24070. 1 hit.
PfamiPF00071. Ras. 1 hit.
[Graphical view]
PRINTSiPR00449. RASTRNSFRMNG.
SMARTiSM00173. RAS. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR00231. small_GTP. 1 hit.
PROSITEiPS51421. RAS. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q921J2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPQSKSRKIA ILGYRSVGKS SLTIQFVEGQ FVDSYDPTIE NTFTKLITVN
60 70 80 90 100
GQEYHLQLVD TAGQDEYSIF PQTYSIDING YILVYSVTSI KSFEVIKVIH
110 120 130 140 150
GKLLDMVGKV QIPIMLVGNK KDLHMERVIS YEEGKALAES WNAAFLESSA
160 170 180
KENQTAVDVF KRIILEAEKI DGAASQGKSS CSVM
Length:184
Mass (Da):20,451
Last modified:December 1, 2001 - v1
Checksum:i7EC58080BDF92DFB
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC012273 mRNA. Translation: AAH12273.1.
CCDSiCCDS39032.1.
RefSeqiNP_444305.2. NM_053075.3.
UniGeneiMm.319175.

Genome annotation databases

EnsembliENSMUST00000030787; ENSMUSP00000030787; ENSMUSG00000028945.
GeneIDi19744.
KEGGimmu:19744.
UCSCiuc008wsj.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC012273 mRNA. Translation: AAH12273.1.
CCDSiCCDS39032.1.
RefSeqiNP_444305.2. NM_053075.3.
UniGeneiMm.319175.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4O25X-ray2.20A/B1-169[»]
4O2LX-ray2.40A/B1-169[»]
4O2RX-ray2.25A/B1-169[»]
ProteinModelPortaliQ921J2.
SMRiQ921J2. Positions 3-169.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202889. 5 interactions.
IntActiQ921J2. 2 interactions.
MINTiMINT-4611176.
STRINGi10090.ENSMUSP00000030787.

PTM databases

PhosphoSiteiQ921J2.

Proteomic databases

MaxQBiQ921J2.
PaxDbiQ921J2.
PRIDEiQ921J2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000030787; ENSMUSP00000030787; ENSMUSG00000028945.
GeneIDi19744.
KEGGimmu:19744.
UCSCiuc008wsj.1. mouse.

Organism-specific databases

CTDi6009.
MGIiMGI:97912. Rheb.

Phylogenomic databases

eggNOGiCOG1100.
GeneTreeiENSGT00780000121877.
HOGENOMiHOG000233973.
HOVERGENiHBG009351.
InParanoidiQ921J2.
KOiK07208.
OMAiTILNSKH.
OrthoDBiEOG7Q2N6K.
PhylomeDBiQ921J2.
TreeFamiTF314986.

Enzyme and pathway databases

ReactomeiREACT_288513. Regulation of AMPK activity via LKB1.
REACT_290209. Release of eIF4E.
REACT_303124. mTOR signalling.
REACT_307891. Regulation of Rheb GTPase activity by AMPK.
REACT_333210. S6K1-mediated signalling.
REACT_360191. TP53 Regulates Metabolic Genes.

Miscellaneous databases

ChiTaRSiRheb. mouse.
NextBioi297194.
PROiQ921J2.
SOURCEiSearch...

Gene expression databases

BgeeiQ921J2.
CleanExiMM_RHEB.
ExpressionAtlasiQ921J2. baseline and differential.
GenevisibleiQ921J2. MM.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR027417. P-loop_NTPase.
IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
IPR020849. Small_GTPase_Ras.
[Graphical view]
PANTHERiPTHR24070. PTHR24070. 1 hit.
PfamiPF00071. Ras. 1 hit.
[Graphical view]
PRINTSiPR00449. RASTRNSFRMNG.
SMARTiSM00173. RAS. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR00231. small_GTP. 1 hit.
PROSITEiPS51421. RAS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  2. "Inactivation of Rheb by PRAK-mediated phosphorylation is essential for energy-depletion-induced suppression of mTORC1."
    Zheng M., Wang Y.H., Wu X.N., Wu S.Q., Lu B.J., Dong M.Q., Zhang H., Sun P., Lin S.C., Guan K.L., Han J.
    Nat. Cell Biol. 13:263-272(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-130, MUTAGENESIS OF SER-130.
  3. "Structure-guided mutation of the conserved G3-box glycine in Rheb generates a constitutively activated regulator of mammalian target of rapamycin (mTOR)."
    Mazhab-Jafari M.T., Marshall C.B., Ho J., Ishiyama N., Stambolic V., Ikura M.
    J. Biol. Chem. 289:12195-12201(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 1-169 IN COMPLEX WITH GTP AND MAGNESIUM, FUNCTION, ENZYME REGULATION, MUTAGENESIS OF GLY-63.

Entry informationi

Entry nameiRHEB_MOUSE
AccessioniPrimary (citable) accession number: Q921J2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 10, 2003
Last sequence update: December 1, 2001
Last modified: July 22, 2015
This is version 120 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

The conserved catalytic Gln-64 found in other Ras-like GTPases seems not to be involved in GTP hydrolysis in RHEB.By similarity

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.