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Protein

GTP-binding protein Rheb

Gene

Rheb

Organism
Rattus norvegicus (Rat)
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.1 Publication1 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 (By similarity).By similarity

Sites

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

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

  1. GDP binding Source: RGD
  2. GTPase activity Source: RGD
  3. GTP binding Source: RGD
  4. metal ion binding Source: UniProtKB-KW

GO - Biological processi

  1. GTP catabolic process Source: InterPro
  2. positive regulation of TOR signaling Source: UniProtKB
  3. regulation of neuronal synaptic plasticity Source: RGD
  4. small GTPase mediated signal transduction Source: RGD
Complete GO annotation...

Keywords - Ligandi

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

Enzyme and pathway databases

ReactomeiREACT_231506. Release of eIF4E.
REACT_232838. Regulation of Rheb GTPase activity by AMPK.
REACT_239343. mTOR signalling.
REACT_242748. S6K1-mediated signalling.

Names & Taxonomyi

Protein namesi
Recommended name:
GTP-binding protein Rheb
Alternative name(s):
Ras homolog enriched in brain
Gene namesi
Name:Rheb
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Unplaced

Organism-specific databases

RGDi621840. 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

  1. cytosol Source: UniProtKB-SubCell
  2. dendrite Source: RGD
  3. endoplasmic reticulum membrane Source: UniProtKB-SubCell
  4. extracellular vesicular exosome Source: Ensembl
  5. Golgi membrane Source: UniProtKB-SubCell
  6. neuronal cell body Source: RGD
  7. spliceosomal complex Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Golgi apparatus, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 181181GTP-binding protein RhebPRO_0000082710Add
BLAST
Propeptidei182 – 1843Removed in mature formBy similarityPRO_0000281367

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei130 – 1301Phosphoserine; by MAPKAPK5By similarity
Modified residuei181 – 1811Cysteine methyl esterBy similarity
Lipidationi181 – 1811S-farnesyl cysteineBy similarity

Post-translational modificationi

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

Keywords - PTMi

Lipoprotein, Methylation, Phosphoprotein, Prenylation

Proteomic databases

PRIDEiQ62639.

PTM databases

PhosphoSiteiQ62639.

Expressioni

Tissue specificityi

Expressed at high levels in normal adult cortex as well as a number of peripheral tissues, including lung and intestine.

Gene expression databases

ExpressionAtlasiQ62639. baseline.
GenevestigatoriQ62639.

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

Structurei

Secondary structure

1
184
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi7 – 137Combined sources
Helixi19 – 279Combined sources
Beta strandi41 – 499Combined sources
Beta strandi52 – 609Combined sources
Beta strandi63 – 675Combined sources
Beta strandi69 – 735Combined sources
Beta strandi79 – 8810Combined sources
Helixi90 – 10718Combined sources
Beta strandi114 – 1196Combined sources
Helixi121 – 1233Combined sources
Turni124 – 1263Combined sources
Helixi131 – 14111Combined sources
Beta strandi144 – 1474Combined sources
Helixi153 – 17321Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2L0XNMR-A6-174[»]
ProteinModelPortaliQ62639.
SMRiQ62639. Positions 2-171.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ62639.

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

HOVERGENiHBG009351.
InParanoidiQ62639.
KOiK07208.
PhylomeDBiQ62639.

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.

Q62639-1 [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 RRIILEAEKI DGAASQGKSS CSVM
Length:184
Mass (Da):20,479
Last modified:November 1, 1996 - v1
Checksum:i8F4C8080BDF92DE9
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U08227 mRNA. Translation: AAA21380.1.
BC088857 mRNA. Translation: AAH88857.1.
PIRiI55401.
RefSeqiNP_037348.1. NM_013216.1.
UniGeneiRn.859.

Genome annotation databases

GeneIDi26954.
KEGGirno:26954.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U08227 mRNA. Translation: AAA21380.1.
BC088857 mRNA. Translation: AAH88857.1.
PIRiI55401.
RefSeqiNP_037348.1. NM_013216.1.
UniGeneiRn.859.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2L0XNMR-A6-174[»]
ProteinModelPortaliQ62639.
SMRiQ62639. Positions 2-171.
ModBaseiSearch...
MobiDBiSearch...

PTM databases

PhosphoSiteiQ62639.

Proteomic databases

PRIDEiQ62639.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi26954.
KEGGirno:26954.

Organism-specific databases

CTDi6009.
RGDi621840. Rheb.

Phylogenomic databases

HOVERGENiHBG009351.
InParanoidiQ62639.
KOiK07208.
PhylomeDBiQ62639.

Enzyme and pathway databases

ReactomeiREACT_231506. Release of eIF4E.
REACT_232838. Regulation of Rheb GTPase activity by AMPK.
REACT_239343. mTOR signalling.
REACT_242748. S6K1-mediated signalling.

Miscellaneous databases

EvolutionaryTraceiQ62639.
NextBioi608022.
PROiQ62639.

Gene expression databases

ExpressionAtlasiQ62639. baseline.
GenevestigatoriQ62639.

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. "Rheb, a growth factor- and synaptic activity-regulated gene, encodes a novel Ras-related protein."
    Yamagata K., Sanders L.K., Kaufmann W.E., Yee W., Barnes C.A., Nathans D., Worley P.F.
    J. Biol. Chem. 269:16333-16339(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Sprague-Dawley.
    Tissue: Hippocampus.
  2. "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].
    Tissue: Ovary.
  3. Cited for: STRUCTURE BY NMR OF 6-174 IN COMPLEX WITH GTP, FUNCTION, ISOPRENYLATION.

Entry informationi

Entry nameiRHEB_RAT
AccessioniPrimary (citable) accession number: Q62639
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: November 1, 1996
Last modified: March 4, 2015
This is version 114 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. 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.