UniProtKB - Q15382 (RHEB_HUMAN)
Protein
GTP-binding protein Rheb
Gene
RHEB
Organism
Homo sapiens (Human)
Status
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
Miscellaneous
The conserved catalytic Gln-64 found in other Ras-like GTPases seems not to be involved in GTP hydrolysis in RHEB.Curated
Activity 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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 20 | Magnesium1 Publication | 1 | |
Metal bindingi | 38 | Magnesium1 Publication | 1 | |
Binding sitei | 63 | GTP; via amide nitrogenBy similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 16 – 21 | GTP2 Publications | 6 | |
Nucleotide bindingi | 32 – 38 | GTP2 Publications | 7 | |
Nucleotide bindingi | 119 – 122 | GTP2 Publications | 4 | |
Nucleotide bindingi | 149 – 150 | GTP2 Publications | 2 |
GO - Molecular functioni
- GDP binding Source: CAFA
- GTPase activity Source: GO_Central
- GTP binding Source: CAFA
- magnesium ion binding Source: CAFA
- protein kinase binding Source: Ensembl
GO - Biological processi
- cell cycle arrest Source: Reactome
- negative regulation of cold-induced thermogenesis Source: YuBioLab
- positive regulation of oligodendrocyte differentiation Source: Ensembl
- positive regulation of TOR signaling Source: UniProtKB
- regulation of macroautophagy Source: Reactome
- regulation of type B pancreatic cell development Source: CACAO
- signal transduction Source: ProtInc
- small GTPase mediated signal transduction Source: GO_Central
Keywordsi
Ligand | GTP-binding, Magnesium, Metal-binding, Nucleotide-binding |
Enzyme and pathway databases
PathwayCommonsi | Q15382 |
Reactomei | R-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 R-HSA-8943724, Regulation of PTEN gene transcription R-HSA-9639288, Amino acids regulate mTORC1 |
SABIO-RKi | Q15382 |
SignaLinki | Q15382 |
SIGNORi | Q15382 |
Names & Taxonomyi
Protein namesi | Recommended name: GTP-binding protein RhebAlternative name(s): Ras homolog enriched in brain |
Gene namesi | Name:RHEB Synonyms:RHEB2 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000106615.9 |
HGNCi | HGNC:10011, RHEB |
MIMi | 601293, gene |
neXtProti | NX_Q15382 |
Subcellular locationi
Endoplasmic reticulum
- Endoplasmic reticulum membrane 1 Publication; Lipid-anchor 1 Publication; Cytoplasmic side 1 Publication
Golgi apparatus
- Golgi apparatus membrane 1 Publication; Lipid-anchor 1 Publication; Cytoplasmic side 1 Publication
Cytosol
- cytosol 1 Publication
Other locations
- Endomembrane system Curated1 Publication; Lipid-anchor Curated1 Publication; Cytoplasmic side Curated1 Publication
Cytosol
- cytosol Source: UniProtKB-SubCell
Endoplasmic reticulum
- endoplasmic reticulum membrane Source: UniProtKB-SubCell
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
Golgi apparatus
- Golgi membrane Source: UniProtKB-SubCell
Lysosome
- lysosomal membrane Source: Reactome
Nucleus
- spliceosomal complex Source: Ensembl
Plasma Membrane
- plasma membrane Source: GO_Central
Other locations
- membrane Source: ProtInc
Keywords - Cellular componenti
Cytoplasm, Endoplasmic reticulum, Golgi apparatus, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 15 | R → G: Partially resistant to inactivation by TSC1-TSC2. 1 Publication | 1 | |
Mutagenesisi | 20 | S → N: Deficient in guanine nucleotide binding. Unable to rescue S6K1 from inactivation by amino-acid withdrawal. 2 Publications | 1 | |
Mutagenesisi | 38 | T → M: Slightly impairs signaling through mTORC1, but still binds guanine nucleotides normally. 2 Publications | 1 | |
Mutagenesisi | 39 | I → K: Impairs S6K1 activation, but still binds guanine nucleotides normally. 1 Publication | 1 | |
Mutagenesisi | 40 | E → G: No effect. 1 Publication | 1 | |
Mutagenesisi | 41 | N → A: Impairs interaction with MTOR. Impairs signaling through mTORC1, but still binds guanine nucleotides normally. 2 Publications | 1 | |
Mutagenesisi | 43 | F → C: No effect. 1 Publication | 1 | |
Mutagenesisi | 46 | L → A: Causes slight reduction in S6K1 activation. 1 Publication | 1 | |
Mutagenesisi | 48 | T → A: Causes slightly reduced phosphorylation of EIF4EBP1. 1 Publication | 1 | |
Mutagenesisi | 49 | V → A: Causes slightly reduced phosphorylation of EIF4EBP1. 1 Publication | 1 | |
Mutagenesisi | 53 | E → A: Causes slightly reduced phosphorylation of EIF4EBP1. 1 Publication | 1 | |
Mutagenesisi | 54 | Y → A: Partially deficient in guanine nucleotide binding. Fully impairs EIF4EBP1 phosphorylation and S6K1 activation. 1 Publication | 1 | |
Mutagenesisi | 56 | L → A: Partially deficient in guanine nucleotide binding. Fully impairs EIF4EBP1 phosphorylation and S6K1 activation. 1 Publication | 1 | |
Mutagenesisi | 60 | D → I: Deficient in guanine nucleotide binding. Unable to rescue S6K1 from inactivation by amino-acid withdrawal. 1 Publication | 1 | |
Mutagenesisi | 64 | Q → L: Has a higher basal GTPase level, however, is still sensitive to TSC2 GAP activity. 1 Publication | 1 | |
Mutagenesisi | 181 | C → S: Reduces the ability to rescue S6K1 from inactivation by amino-acid withdrawal. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 6009 |
OpenTargetsi | ENSG00000106615 |
PharmGKBi | PA34389 |
Miscellaneous databases
Pharosi | Q15382, Tbio |
Chemistry databases
ChEMBLi | CHEMBL3108656 |
DrugBanki | DB04315, Guanosine-5'-Diphosphate DB04137, Guanosine-5'-Triphosphate |
Polymorphism and mutation databases
BioMutai | RHEB |
DMDMi | 6919957 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000082708 | 1 – 181 | GTP-binding protein RhebAdd BLAST | 181 | |
PropeptideiPRO_0000281365 | 182 – 184 | Removed in mature form | 3 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 130 | Phosphoserine; by MAPKAPK5By similarity | 1 | |
Modified residuei | 181 | Cysteine methyl esterCombined sources2 Publications | 1 | |
Lipidationi | 181 | S-farnesyl cysteineCombined sources2 Publications | 1 |
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, PrenylationProteomic databases
EPDi | Q15382 |
jPOSTi | Q15382 |
MassIVEi | Q15382 |
MaxQBi | Q15382 |
PaxDbi | Q15382 |
PeptideAtlasi | Q15382 |
PRIDEi | Q15382 |
ProteomicsDBi | 60554 |
TopDownProteomicsi | Q15382 |
PTM databases
iPTMneti | Q15382 |
MetOSitei | Q15382 |
PhosphoSitePlusi | Q15382 |
SwissPalmi | Q15382 |
Expressioni
Tissue specificityi
Ubiquitous. Highest levels observed in skeletal and cardiac muscle.1 Publication
Gene expression databases
Bgeei | ENSG00000106615, Expressed in caudate nucleus and 192 other tissues |
ExpressionAtlasi | Q15382, baseline and differential |
Genevisiblei | Q15382, HS |
Organism-specific databases
HPAi | ENSG00000106615, Low tissue specificity |
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 PublicationsBinary interactionsi
Hide detailsQ15382
With | #Exp. | IntAct |
---|---|---|
APPBP2 [Q92624] | 3 | EBI-1055287,EBI-743771 |
MTOR [P42345] | 2 | EBI-1055287,EBI-359260 |
PLD1 [Q13393] | 2 | EBI-1055287,EBI-2827556 |
TPT1 [P13693] | 2 | EBI-1055287,EBI-1783169 |
GTP-binding protein Rheb (PRO_0000082708)
With | #Exp. | IntAct |
---|---|---|
PDE6D [O43924] | 5 | EBI-6860739,EBI-712685 |
GO - Molecular functioni
- protein kinase binding Source: Ensembl
Protein-protein interaction databases
BioGRIDi | 111941, 59 interactors |
DIPi | DIP-42816N |
IntActi | Q15382, 39 interactors |
MINTi | Q15382 |
STRINGi | 9606.ENSP00000262187 |
Chemistry databases
BindingDBi | Q15382 |
Miscellaneous databases
RNActi | Q15382, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
BMRBi | Q15382 |
SMRi | Q15382 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q15382 |
Family & Domainsi
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 35 – 43 | Effector regionCurated | 9 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG0395, Eukaryota |
GeneTreei | ENSGT00940000159945 |
HOGENOMi | CLU_041217_9_8_1 |
InParanoidi | Q15382 |
OMAi | FIENHFV |
OrthoDBi | 1320427at2759 |
PhylomeDBi | Q15382 |
TreeFami | TF314986 |
Family and domain databases
DisProti | DP00364 |
InterProi | View protein in InterPro IPR027417, P-loop_NTPase IPR037586, RHEB IPR005225, Small_GTP-bd_dom IPR001806, Small_GTPase IPR020849, Small_GTPase_Ras-type |
PANTHERi | PTHR24070, PTHR24070, 1 hit PTHR24070:SF264, PTHR24070:SF264, 1 hit |
Pfami | View protein in Pfam PF00071, Ras, 1 hit |
SUPFAMi | SSF52540, SSF52540, 1 hit |
TIGRFAMsi | TIGR00231, small_GTP, 1 hit |
PROSITEi | View protein in PROSITE PS51421, RAS, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All
Q15382-1 [UniParc]FASTAAdd to basket
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
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketC9J931 | C9J931_HUMAN | GTP-binding protein Rheb | RHEB | 79 | Annotation score: | ||
C9J469 | C9J469_HUMAN | GTP-binding protein Rheb | RHEB | 19 | Annotation score: | ||
F8WBL3 | F8WBL3_HUMAN | GTP-binding protein Rheb | RHEB | 47 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 118 | G → W in BAA11211 (PubMed:8661031).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_036310 | 139 | E → K in a colorectal cancer sample; somatic mutation. 1 Publication | 1 |
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 |
CCDSi | CCDS5927.1 |
PIRi | S68419, S41960 |
RefSeqi | NP_005605.1, NM_005614.3 |
Genome annotation databases
Ensembli | ENST00000262187; ENSP00000262187; ENSG00000106615 |
GeneIDi | 6009 |
KEGGi | hsa:6009 |
UCSCi | uc003wkh.1, human |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
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 |
CCDSi | CCDS5927.1 |
PIRi | S68419, S41960 |
RefSeqi | NP_005605.1, NM_005614.3 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1XTQ | X-ray | 2.00 | A | 1-169 | [»] | |
1XTR | X-ray | 2.65 | A | 1-169 | [»] | |
1XTS | X-ray | 2.80 | A | 1-169 | [»] | |
3SEA | X-ray | 2.00 | A/B | 3-169 | [»] | |
3T5G | X-ray | 1.70 | A | 1-181 | [»] | |
5YXH | X-ray | 2.04 | A/B/C/D | 2-169 | [»] | |
6BCU | electron microscopy | 3.43 | R/S | 1-184 | [»] | |
6BSX | X-ray | 1.65 | A/B/C/D | 1-169 | [»] | |
6BT0 | X-ray | 2.60 | A/B/C/D | 1-169 | [»] | |
7BTA | X-ray | 2.60 | A/B | 1-169 | [»] | |
7BTC | X-ray | 2.10 | A/B/C/D | 1-169 | [»] | |
7BTD | X-ray | 2.00 | A | 1-169 | [»] | |
BMRBi | Q15382 | |||||
SMRi | Q15382 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 111941, 59 interactors |
DIPi | DIP-42816N |
IntActi | Q15382, 39 interactors |
MINTi | Q15382 |
STRINGi | 9606.ENSP00000262187 |
Chemistry databases
BindingDBi | Q15382 |
ChEMBLi | CHEMBL3108656 |
DrugBanki | DB04315, Guanosine-5'-Diphosphate DB04137, Guanosine-5'-Triphosphate |
PTM databases
iPTMneti | Q15382 |
MetOSitei | Q15382 |
PhosphoSitePlusi | Q15382 |
SwissPalmi | Q15382 |
Polymorphism and mutation databases
BioMutai | RHEB |
DMDMi | 6919957 |
Proteomic databases
EPDi | Q15382 |
jPOSTi | Q15382 |
MassIVEi | Q15382 |
MaxQBi | Q15382 |
PaxDbi | Q15382 |
PeptideAtlasi | Q15382 |
PRIDEi | Q15382 |
ProteomicsDBi | 60554 |
TopDownProteomicsi | Q15382 |
Protocols and materials databases
Antibodypediai | 18765, 461 antibodies |
DNASUi | 6009 |
Genome annotation databases
Ensembli | ENST00000262187; ENSP00000262187; ENSG00000106615 |
GeneIDi | 6009 |
KEGGi | hsa:6009 |
UCSCi | uc003wkh.1, human |
Organism-specific databases
CTDi | 6009 |
DisGeNETi | 6009 |
EuPathDBi | HostDB:ENSG00000106615.9 |
GeneCardsi | RHEB |
HGNCi | HGNC:10011, RHEB |
HPAi | ENSG00000106615, Low tissue specificity |
MIMi | 601293, gene |
neXtProti | NX_Q15382 |
OpenTargetsi | ENSG00000106615 |
PharmGKBi | PA34389 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0395, Eukaryota |
GeneTreei | ENSGT00940000159945 |
HOGENOMi | CLU_041217_9_8_1 |
InParanoidi | Q15382 |
OMAi | FIENHFV |
OrthoDBi | 1320427at2759 |
PhylomeDBi | Q15382 |
TreeFami | TF314986 |
Enzyme and pathway databases
PathwayCommonsi | Q15382 |
Reactomei | R-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 R-HSA-8943724, Regulation of PTEN gene transcription R-HSA-9639288, Amino acids regulate mTORC1 |
SABIO-RKi | Q15382 |
SignaLinki | Q15382 |
SIGNORi | Q15382 |
Miscellaneous databases
BioGRID-ORCSi | 6009, 480 hits in 829 CRISPR screens |
ChiTaRSi | RHEB, human |
EvolutionaryTracei | Q15382 |
GeneWikii | RHEB |
GenomeRNAii | 6009 |
Pharosi | Q15382, Tbio |
PROi | PR:Q15382 |
RNActi | Q15382, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000106615, Expressed in caudate nucleus and 192 other tissues |
ExpressionAtlasi | Q15382, baseline and differential |
Genevisiblei | Q15382, HS |
Family and domain databases
DisProti | DP00364 |
InterProi | View protein in InterPro IPR027417, P-loop_NTPase IPR037586, RHEB IPR005225, Small_GTP-bd_dom IPR001806, Small_GTPase IPR020849, Small_GTPase_Ras-type |
PANTHERi | PTHR24070, PTHR24070, 1 hit PTHR24070:SF264, PTHR24070:SF264, 1 hit |
Pfami | View protein in Pfam PF00071, Ras, 1 hit |
SUPFAMi | SSF52540, SSF52540, 1 hit |
TIGRFAMsi | TIGR00231, small_GTP, 1 hit |
PROSITEi | View protein in PROSITE PS51421, RAS, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | RHEB_HUMAN | |
Accessioni | Q15382Primary (citable) accession number: Q15382 Secondary accession number(s): B3KWN6 Q99444 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 30, 2000 |
Last sequence update: | November 1, 1996 | |
Last modified: | December 2, 2020 | |
This is version 218 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 7
Human chromosome 7: entries, gene names and cross-references to MIM - Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations