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Protein

GTP-binding protein Rheb

Gene

RHEB

Organism
Homo sapiens (Human)
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.6 Publications

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.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi20Magnesium1 Publication1
Metal bindingi38Magnesium1 Publication1
Binding sitei63GTP; via amide nitrogenBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi16 – 21GTP2 Publications6
Nucleotide bindingi32 – 38GTP2 Publications7
Nucleotide bindingi119 – 122GTP2 Publications4
Nucleotide bindingi149 – 150GTP2 Publications2

GO - Molecular functioni

GO - Biological processi

  • cell cycle arrest Source: Reactome
  • macroautophagy Source: Reactome
  • positive regulation of oligodendrocyte differentiation Source: Ensembl
  • positive regulation of TOR signaling Source: UniProtKB
  • regulation of type B pancreatic cell development Source: CACAO
  • signal transduction Source: ProtInc
  • small GTPase mediated signal transduction Source: InterPro
Complete GO annotation...

Keywords - Ligandi

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000106615-MONOMER.
ReactomeiR-HSA-1632852. Macroautophagy.
R-HSA-165159. mTOR signalling.
R-HSA-166208. mTORC1-mediated signalling.
R-HSA-380972. Energy dependent regulation of mTOR by LKB1-AMPK.
R-HSA-5628897. TP53 Regulates Metabolic Genes.
SignaLinkiQ15382.
SIGNORiQ15382.

Names & Taxonomyi

Protein namesi
Recommended name:
GTP-binding protein Rheb
Alternative name(s):
Ras homolog enriched in brain
Gene namesi
Name:RHEB
Synonyms:RHEB2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:10011. RHEB.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: UniProtKB-SubCell
  • endoplasmic reticulum membrane Source: UniProtKB-SubCell
  • extracellular exosome Source: UniProtKB
  • Golgi membrane Source: UniProtKB-SubCell
  • lysosomal membrane Source: Reactome
  • membrane Source: ProtInc
  • spliceosomal complex Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Golgi apparatus, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi15R → G: Partially resistant to inactivation by TSC1-TSC2. 1 Publication1
Mutagenesisi20S → N: Deficient in guanine nucleotide binding. Unable to rescue S6K1 from inactivation by amino-acid withdrawal. 2 Publications1
Mutagenesisi38T → M: Slightly impairs signaling through mTORC1, but still binds guanine nucleotides normally. 2 Publications1
Mutagenesisi39I → K: Impairs S6K1 activation, but still binds guanine nucleotides normally. 1 Publication1
Mutagenesisi40E → G: No effect. 1 Publication1
Mutagenesisi41N → A: Impairs interaction with MTOR. Impairs signaling through mTORC1, but still binds guanine nucleotides normally. 2 Publications1
Mutagenesisi43F → C: No effect. 1 Publication1
Mutagenesisi46L → A: Causes slight reduction in S6K1 activation. 1 Publication1
Mutagenesisi48T → A: Causes slightly reduced phosphorylation of EIF4EBP1. 1 Publication1
Mutagenesisi49V → A: Causes slightly reduced phosphorylation of EIF4EBP1. 1 Publication1
Mutagenesisi53E → A: Causes slightly reduced phosphorylation of EIF4EBP1. 1 Publication1
Mutagenesisi54Y → A: Partially deficient in guanine nucleotide binding. Fully impairs EIF4EBP1 phosphorylation and S6K1 activation. 1 Publication1
Mutagenesisi56L → A: Partially deficient in guanine nucleotide binding. Fully impairs EIF4EBP1 phosphorylation and S6K1 activation. 1 Publication1
Mutagenesisi60D → I: Deficient in guanine nucleotide binding. Unable to rescue S6K1 from inactivation by amino-acid withdrawal. 1 Publication1
Mutagenesisi64Q → L: Has a higher basal GTPase level, however, is still sensitive to TSC2 GAP activity. 1 Publication1
Mutagenesisi181C → S: Reduces the ability to rescue S6K1 from inactivation by amino-acid withdrawal. 1 Publication1

Organism-specific databases

DisGeNETi6009.
OpenTargetsiENSG00000106615.
PharmGKBiPA34389.

Chemistry databases

ChEMBLiCHEMBL3108656.

Polymorphism and mutation databases

BioMutaiRHEB.
DMDMi6919957.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000827081 – 181GTP-binding protein RhebAdd BLAST181
PropeptideiPRO_0000281365182 – 184Removed in mature form3

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei130Phosphoserine; by MAPKAPK5By similarity1
Modified residuei181Cysteine methyl esterCurated1
Lipidationi181S-farnesyl cysteine1 Publication1

Post-translational modificationi

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

Keywords - PTMi

Lipoprotein, Methylation, Phosphoprotein, Prenylation

Proteomic databases

EPDiQ15382.
MaxQBiQ15382.
PaxDbiQ15382.
PeptideAtlasiQ15382.
PRIDEiQ15382.
TopDownProteomicsiQ15382.

PTM databases

iPTMnetiQ15382.
PhosphoSitePlusiQ15382.
SwissPalmiQ15382.

Expressioni

Tissue specificityi

Ubiquitous. Highest levels observed in skeletal and cardiac muscle.1 Publication

Gene expression databases

BgeeiENSG00000106615.
CleanExiHS_RHEB.
ExpressionAtlasiQ15382. baseline and differential.
GenevisibleiQ15382. HS.

Organism-specific databases

HPAiCAB019436.
HPA054743.

Interactioni

Subunit structurei

Binds to mTORC1 in a guanyl nucleotide-independent manner. Interacts directly with MTOR, MLST8 and RPTOR. Interacts with TSC2. Interacts (when prenylated) with PDE6D; this promotes release from membranes.4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
PDE6DO439245EBI-6860739,EBI-712685

Protein-protein interaction databases

BioGridi111941. 47 interactors.
DIPiDIP-42816N.
IntActiQ15382. 15 interactors.
MINTiMINT-1365334.
STRINGi9606.ENSP00000262187.

Chemistry databases

BindingDBiQ15382.

Structurei

Secondary structure

1184
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi4 – 14Combined sources11
Helixi19 – 28Combined sources10
Beta strandi41 – 49Combined sources9
Beta strandi52 – 60Combined sources9
Beta strandi66 – 68Combined sources3
Helixi72 – 74Combined sources3
Turni75 – 77Combined sources3
Beta strandi79 – 86Combined sources8
Helixi90 – 106Combined sources17
Beta strandi114 – 119Combined sources6
Turni124 – 126Combined sources3
Helixi131 – 140Combined sources10
Beta strandi144 – 147Combined sources4
Helixi153 – 168Combined sources16

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1XTQX-ray2.00A1-169[»]
1XTRX-ray2.65A1-169[»]
1XTSX-ray2.80A1-169[»]
3SEAX-ray2.00A/B3-169[»]
3T5GX-ray1.70A1-181[»]
DisProtiDP00364.
ProteinModelPortaliQ15382.
SMRiQ15382.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ15382.

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi35 – 43Effector regionCurated9

Sequence similaritiesi

Belongs to the small GTPase superfamily. Rheb family.Curated

Phylogenomic databases

eggNOGiKOG0395. Eukaryota.
COG1100. LUCA.
GeneTreeiENSGT00860000133696.
HOGENOMiHOG000233973.
HOVERGENiHBG009351.
InParanoidiQ15382.
KOiK07208.
OMAiNHLGTES.
OrthoDBiEOG091G0ONO.
PhylomeDBiQ15382.
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]
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.

Q15382-1 [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 RRIILEAEKM DGAASQGKSS CSVM
Length:184
Mass (Da):20,497
Last modified:November 1, 1996 - v1
Checksum:i8F4C8080BDF928FD
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti118G → W in BAA11211 (PubMed:8661031).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_036310139E → K in a colorectal cancer sample; somatic mutation. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z29677 mRNA. Translation: CAA82774.1.
D78132 mRNA. Translation: BAA11211.1.
AF148645 mRNA. Translation: AAF73125.1.
AF493921 mRNA. Translation: AAM12635.1.
AK125446 mRNA. Translation: BAG54198.1.
BT006958 mRNA. Translation: AAP35604.1.
AC005996 Genomic DNA. Translation: AAD15548.1.
CH471173 Genomic DNA. Translation: EAW53989.1.
BC016155 mRNA. Translation: AAH16155.1.
BC107705 mRNA. Translation: AAI07706.1.
CCDSiCCDS5927.1.
PIRiS68419. S41960.
RefSeqiNP_005605.1. NM_005614.3.
UniGeneiHs.283521.
Hs.568850.
Hs.647068.

Genome annotation databases

EnsembliENST00000262187; ENSP00000262187; ENSG00000106615.
GeneIDi6009.
KEGGihsa:6009.
UCSCiuc003wkh.1. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z29677 mRNA. Translation: CAA82774.1.
D78132 mRNA. Translation: BAA11211.1.
AF148645 mRNA. Translation: AAF73125.1.
AF493921 mRNA. Translation: AAM12635.1.
AK125446 mRNA. Translation: BAG54198.1.
BT006958 mRNA. Translation: AAP35604.1.
AC005996 Genomic DNA. Translation: AAD15548.1.
CH471173 Genomic DNA. Translation: EAW53989.1.
BC016155 mRNA. Translation: AAH16155.1.
BC107705 mRNA. Translation: AAI07706.1.
CCDSiCCDS5927.1.
PIRiS68419. S41960.
RefSeqiNP_005605.1. NM_005614.3.
UniGeneiHs.283521.
Hs.568850.
Hs.647068.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1XTQX-ray2.00A1-169[»]
1XTRX-ray2.65A1-169[»]
1XTSX-ray2.80A1-169[»]
3SEAX-ray2.00A/B3-169[»]
3T5GX-ray1.70A1-181[»]
DisProtiDP00364.
ProteinModelPortaliQ15382.
SMRiQ15382.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111941. 47 interactors.
DIPiDIP-42816N.
IntActiQ15382. 15 interactors.
MINTiMINT-1365334.
STRINGi9606.ENSP00000262187.

Chemistry databases

BindingDBiQ15382.
ChEMBLiCHEMBL3108656.

PTM databases

iPTMnetiQ15382.
PhosphoSitePlusiQ15382.
SwissPalmiQ15382.

Polymorphism and mutation databases

BioMutaiRHEB.
DMDMi6919957.

Proteomic databases

EPDiQ15382.
MaxQBiQ15382.
PaxDbiQ15382.
PeptideAtlasiQ15382.
PRIDEiQ15382.
TopDownProteomicsiQ15382.

Protocols and materials databases

DNASUi6009.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000262187; ENSP00000262187; ENSG00000106615.
GeneIDi6009.
KEGGihsa:6009.
UCSCiuc003wkh.1. human.

Organism-specific databases

CTDi6009.
DisGeNETi6009.
GeneCardsiRHEB.
HGNCiHGNC:10011. RHEB.
HPAiCAB019436.
HPA054743.
MIMi601293. gene.
neXtProtiNX_Q15382.
OpenTargetsiENSG00000106615.
PharmGKBiPA34389.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0395. Eukaryota.
COG1100. LUCA.
GeneTreeiENSGT00860000133696.
HOGENOMiHOG000233973.
HOVERGENiHBG009351.
InParanoidiQ15382.
KOiK07208.
OMAiNHLGTES.
OrthoDBiEOG091G0ONO.
PhylomeDBiQ15382.
TreeFamiTF314986.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000106615-MONOMER.
ReactomeiR-HSA-1632852. Macroautophagy.
R-HSA-165159. mTOR signalling.
R-HSA-166208. mTORC1-mediated signalling.
R-HSA-380972. Energy dependent regulation of mTOR by LKB1-AMPK.
R-HSA-5628897. TP53 Regulates Metabolic Genes.
SignaLinkiQ15382.
SIGNORiQ15382.

Miscellaneous databases

ChiTaRSiRHEB. human.
EvolutionaryTraceiQ15382.
GeneWikiiRHEB.
GenomeRNAii6009.
PROiQ15382.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000106615.
CleanExiHS_RHEB.
ExpressionAtlasiQ15382. baseline and differential.
GenevisibleiQ15382. HS.

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]
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR00231. small_GTP. 1 hit.
PROSITEiPS51421. RAS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiRHEB_HUMAN
AccessioniPrimary (citable) accession number: Q15382
Secondary accession number(s): B3KWN6
, D3DX13, Q53Y56, Q99444
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: November 1, 1996
Last modified: November 30, 2016
This is version 184 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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 one 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.