RHEB
entrez
6009
canonical
uniprot
Q15382
canonical
ensembl
ENSG00000106615
resolver
ensp
ENSP00000262187
resolver
enst
ENST00000262187
resolver
genesymbol
RHEB
resolver
genesymbol_syn
RHEB2
resolver
hgnc
HGNC:10011
resolver
uniprot
B3KWN6
resolver
uniprot
D3DX13
resolver
uniprot
Q53Y56
resolver
uniprot
Q99444
resolver
uniprot_entry
RHEB_HUMAN
resolver
uniprot_sec
B3KWN6
resolver
uniprot_sec
D3DX13
resolver
uniprot_sec
Q53Y56
resolver
uniprot_sec
Q99444
resolver
activity_regulation
ACTIVITY REGULATION: Alternates between an inactive form bound to GDP and an active form bound to GTP (PubMed:12271141, PubMed:12842888, PubMed:12869586, PubMed:12906785, PubMed:15340059, PubMed:22819219, PubMed:24529379). Inactivated by the TSC-TBC complex via the GTPase activating protein (GAP) domain of TSC2 (PubMed:12271141, PubMed:12842888, PubMed:12869586, PubMed:12906785, PubMed:15340059, PubMed:22819219, PubMed:24529379). Autoinhibited by Tyr-35, which constrains the active site conformation, restricting the access of the catalytic Asp-65 to the nucleotide-binding pocket (PubMed:22819219). Specifically inhibited by NR1 (4-bromo-6-(3,4-dichlorophenylthio)-1-(4-(dimethylcarbamoyl)benzyl)-1H-indole-2-carboxylic acid) (PubMed:29416044). {ECO:0000269|PubMed:12271141, ECO:0000269|PubMed:12842888, ECO:0000269|PubMed:12869586, ECO:0000269|PubMed:12906785, ECO:0000269|PubMed:15340059, ECO:0000269|PubMed:22819219, ECO:0000269|PubMed:24529379, ECO:0000269|PubMed:29416044}.
uniprot
proteins
amino_acid_sequence
MPQSKSRKIAILGYRSVGKSSLTIQFVEGQFVDSYDPTIENTFTKLITVNGQEYHLQLVDTAGQDEYSIFPQTYSIDINGYILVYSVTSIKSFEVIKVIHGKLLDMVGKVQIPIMLVGNKKDLHMERVISYEEGKALAESWNAAFLESSAKENQTAVDVFRRIILEAEKMDGAASQGKSSCSVM
uniprot
proteins
ec_number
3.6.5.-
uniprot
proteins
function
FUNCTION: Small GTPase that acts as an allosteric activator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule biosynthesis to promote cellular biomass generation and growth (PubMed:12172553, PubMed:12271141, PubMed:12842888, PubMed:12869586, PubMed:12906785, PubMed:15340059, PubMed:15854902, PubMed:16098514, PubMed:20381137, PubMed:22819219, PubMed:24529379, PubMed:29416044, PubMed:32470140, PubMed:33157014, PubMed:25816988). In response to nutrients, growth factors or amino acids, specifically activates the protein kinase activity of MTOR, the catalytic component of the mTORC1 complex: acts by causing a conformational change that allows the alignment of residues in the active site of MTOR, thereby enhancing the phosphorylation of ribosomal protein S6 kinase (RPS6KB1 and RPS6KB2) and EIF4EBP1 (4E-BP1) (PubMed:29236692, PubMed:33157014). RHEB is also required for localization of the TSC-TBC complex to lysosomal membranes (PubMed:24529379). In response to starvation, RHEB is inactivated by the TSC-TBC complex, preventing activation of mTORC1 (PubMed:24529379, PubMed:33157014). Has low intrinsic GTPase activity (PubMed:15340059). {ECO:0000269|PubMed:12172553, ECO:0000269|PubMed:12271141, ECO:0000269|PubMed:12842888, ECO:0000269|PubMed:12869586, ECO:0000269|PubMed:12906785, ECO:0000269|PubMed:15340059, ECO:0000269|PubMed:15854902, ECO:0000269|PubMed:16098514, ECO:0000269|PubMed:20381137, ECO:0000269|PubMed:22819219, ECO:0000269|PubMed:24529379, ECO:0000269|PubMed:25816988, ECO:0000269|PubMed:29236692, ECO:0000269|PubMed:29416044, ECO:0000269|PubMed:32470140, ECO:0000269|PubMed:33157014}.
uniprot
proteins
mass_dalton
20497
uniprot
proteins
mutagenesis
MUTAGEN 8; /note="K->R: Decreased ubiquitination by RNF152. Does not affect polyubiquitination in response to amino acids."; /evidence="ECO:0000269|PubMed:33157014"; MUTAGEN 15; /note="R->G: Partially resistant to inactivation by TSC1-TSC2."; /evidence="ECO:0000269|PubMed:15340059"; MUTAGEN 20; /note="S->N: Deficient in guanine nucleotide binding. Unable to rescue RPS6KB1 from inactivation by amino-acid withdrawal. Reduces affinity for MCRS1."; /evidence="ECO:0000269|PubMed:15340059, ECO:0000269|PubMed:15854902, ECO:0000269|PubMed:25816988"; MUTAGEN 35; /note="Y->A: Increased GTPase activity; insensitive to TSC2 regulation, leading to impaired regulation of mTORC1 signaling."; /evidence="ECO:0000269|PubMed:22819219"; MUTAGEN 35; /note="Y->N: Dominant mutant, which can activate mTORC1 in both GDP- and GTP-bound forms."; /evidence="ECO:0000269|PubMed:32470140"; MUTAGEN 38; /note="T->M: Slightly impairs signaling through mTORC1, but still binds guanine nucleotides normally."; /evidence="ECO:0000269|PubMed:15854902, ECO:0000269|PubMed:16098514"; MUTAGEN 39; /note="I->K: Impairs RPS6KB1 activation, but still binds guanine nucleotides normally. Slightly reduces interaction with MCRS1."; /evidence="ECO:0000269|PubMed:15854902, ECO:0000269|PubMed:25816988"; MUTAGEN 40; /note="E->G: No effect."; /evidence="ECO:0000269|PubMed:16098514"; MUTAGEN 41; /note="N->A: Impairs interaction with MTOR. Impairs signaling through mTORC1, but still binds guanine nucleotides normally."; /evidence="ECO:0000269|PubMed:15854902, ECO:0000269|PubMed:16098514"; MUTAGEN 43; /note="F->C: No effect."; /evidence="ECO:0000269|PubMed:16098514"; MUTAGEN 46; /note="L->A: Causes slight reduction in RPS6KB1 activation."; /evidence="ECO:0000269|PubMed:16098514"; MUTAGEN 48; /note="T->A: Causes slightly reduced phosphorylation of EIF4EBP1."; /evidence="ECO:0000269|PubMed:16098514"; MUTAGEN 49; /note="V->A: Causes slightly reduced phosphorylation of EIF4EBP1."; /evidence="ECO:0000269|PubMed:16098514"; MUTAGEN 53; /note="E->A: Causes slightly reduced phosphorylation of EIF4EBP1."; /evidence="ECO:0000269|PubMed:16098514"; MUTAGEN 54; /note="Y->A: Partially deficient in guanine nucleotide binding. Fully impairs EIF4EBP1 phosphorylation and RPS6KB1 activation."; /evidence="ECO:0000269|PubMed:16098514"; MUTAGEN 56; /note="L->A: Partially deficient in guanine nucleotide binding. Fully impairs EIF4EBP1 phosphorylation and RPS6KB1 activation."; /evidence="ECO:0000269|PubMed:16098514"; MUTAGEN 60; /note="D->A: Unstable protein, which cannot load GTP."; /evidence="ECO:0000269|PubMed:22819219"; MUTAGEN 60; /note="D->I: Deficient in guanine nucleotide binding. Unable to rescue RPS6KB1 from inactivation by amino-acid withdrawal. Significantly reduces interaction with MCRS1."; /evidence="ECO:0000269|PubMed:15340059, ECO:0000269|PubMed:25816988"; MUTAGEN 60; /note="D->K: Unable to bind Mg(2+), preventing nucleotide-binding."; /evidence="ECO:0000269|PubMed:32470140"; MUTAGEN 64; /note="Q->L: Has a higher basal GTPase level, however, is still sensitive to TSC2 GAP activity. Increases affinity for MCRS1."; /evidence="ECO:0000269|PubMed:12842888, ECO:0000269|PubMed:15340059, ECO:0000269|PubMed:25816988"; MUTAGEN 65; /note="D->A,E,N: Renders RHEB insensitive to TSC2 regulation, leading to impaired regulation of mTORC1 signaling."; /evidence="ECO:0000269|PubMed:22819219"; MUTAGEN 109; /note="K->R: Decreased ubiquitination in response to amino acids; when associated with R-135, R-151 and R-178."; /evidence="ECO:0000269|PubMed:33157014"; MUTAGEN 135; /note="K->R: Decreased ubiquitination in response to amino acids; when associated with R-109, R-151 and R-178."; /evidence="ECO:0000269|PubMed:33157014"; MUTAGEN 151; /note="K->R: Decreased ubiquitination in response to amino acids; when associated with R-109, R-135 and R-178."; /evidence="ECO:0000269|PubMed:33157014"; MUTAGEN 178; /note="K->R: Decreased ubiquitination in response to amino acids; when associated with R-109, R-135 and R-151."; /evidence="ECO:0000269|PubMed:33157014"; MUTAGEN 181; /note="C->S: Reduces the ability to rescue RPS6KB1 from inactivation by amino-acid withdrawal. Significantly reduces interaction with MCRS1."; /evidence="ECO:0000269|PubMed:12906785, ECO:0000269|PubMed:15340059, ECO:0000269|PubMed:25816988
uniprot
proteins
post_translational_modification
PTM: Farnesylation is important for efficiently activating mTORC1-mediated signaling. {ECO:0000269|PubMed:12842888, ECO:0000269|PubMed:12906785, ECO:0000269|PubMed:22002721}.; PTM: Polyubiquitinated in response to amino acid, promoting its interaction with MTOR and mTORC1 activation (PubMed:33157014). Deubiquitination by ATXN3 promotes recruitment of the TSC-TBC complex and RHEB inactivation by TSC2 (PubMed:33157014). Monoubiquitinated at Lys-8 by RNF152, promoting its association with the TSC-TBC complex (PubMed:30514904). Deubiquitinated at Lys-8 by USP4, promoting mTORC1 activation (PubMed:30514904). {ECO:0000269|PubMed:30514904, ECO:0000269|PubMed:33157014}.; PTM: Phosphorylation by MAPKAPK5 impairs GTP-binding and inactivation. {ECO:0000250|UniProtKB:Q921J2}.
uniprot
proteins
protein_family
Rheb family
uniprot
proteins
protein_family
Small GTPase superfamily
uniprot
proteins
pubmed
12172553
uniprot
proteins
pubmed
12271141
uniprot
proteins
pubmed
12842888
uniprot
proteins
pubmed
12853948
uniprot
proteins
pubmed
12869586
uniprot
proteins
pubmed
12906785
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15308774
uniprot
proteins
pubmed
15340059
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15728574
uniprot
proteins
pubmed
15854902
uniprot
proteins
pubmed
16098514
uniprot
proteins
pubmed
16959974
uniprot
proteins
pubmed
20381137
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
22002721
uniprot
proteins
pubmed
22819219
uniprot
proteins
pubmed
24529379
uniprot
proteins
pubmed
25816988
uniprot
proteins
pubmed
29236692
uniprot
proteins
pubmed
29416044
uniprot
proteins
pubmed
30514904
uniprot
proteins
pubmed
32470140
uniprot
proteins
pubmed
33157014
uniprot
proteins
pubmed
8543055
uniprot
proteins
pubmed
8661031
uniprot
proteins
sequence_length
184
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Endomembrane system {ECO:0000269|PubMed:22002721}; Lipid-anchor {ECO:0000269|PubMed:22002721}; Cytoplasmic side {ECO:0000269|PubMed:15489334}. Lysosome membrane {ECO:0000269|PubMed:24529379, ECO:0000269|PubMed:25816988, ECO:0000269|PubMed:33157014}; Lipid-anchor {ECO:0000269|PubMed:22002721}; Cytoplasmic side {ECO:0000269|PubMed:15489334}. Golgi apparatus membrane {ECO:0000269|PubMed:22002721}; Lipid-anchor {ECO:0000305|PubMed:22002721}; Cytoplasmic side {ECO:0000305|PubMed:22002721}. Endoplasmic reticulum membrane {ECO:0000269|PubMed:22002721}; Lipid-anchor {ECO:0000269|PubMed:22002721}; Cytoplasmic side {ECO:0000269|PubMed:22002721}. Cytoplasm, cytosol {ECO:0000269|PubMed:22002721}. Note=Farnesylation is required for recruitment to lysosomal membranes, where it activates the mTORC1 complex. {ECO:0000269|PubMed:24529379}.
uniprot
proteins