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GTP-binding protein Rheb; Ras homolog enriched in brain; Rheb GTPase (RHEB, RHEB2)
Function:
- stimulates phosphorylation of S6K1 & EIF4EBP1 via activation of mTORC1 signaling
- activates protein kinase activity of mTORC1
- has low intrinsic GTPase activity
- alternates between an inactive form bound to GDP & an active form bound to GTP
- inactivated by TSC1-TSC2 via GTPase-activating protein (GAP) domain of TSC2
- farnesylation is important for efficiently activating mTORC1-mediated signaling
- binds to mTORC1 (GDP/GTP-independent)
- interacts directly with FRAP1, MLST8 & RPTOR
- interacts with TSC2
Structure:
- belongs to the small GTPase superfamily, Rheb family
- conserved catalytic Gln-64 found in other Ras-like GTPases does not seem to be involved in GTP hydrolysis in RHEB
Compartment:
- cell membrane, lipid-anchor, cytoplasmic side (putative)
Expression:
- ubiquitous
- highest levels observed in skeletal & cardiac muscle
Comparative biology:
- regulates memory functions in mice [2]
- selective depletion of Rheb in mouse forebrain results in:
- spontaneous signs of spatial memory deficits (T-maze, Morris water maze) [2]
- no affect on locomotion (open-field test), anxiety (elevated plus maze), or contextual fear conditioning
General
guanine nucleotide regulatory protein (GNRP)
prenyl protein
Properties
SIZE: entity length = 184 aa
MW = 20 kD
COMPARTMENT: cytoplasm
MOTIF: GTP-binding site
SITE: 16-21
MOTIF: Mg+2-binding site
SITE: 20-20
GTP-binding site
SITE: 32-38
Effector region {35-43}
MOTIF: Mg+2-binding site
SITE: 38-38
GTP-binding site
SITE: 119-122
GTP-binding site
SITE: 149-150
CaaX motif
SITE: C-TERMINUS
QUALITIES: AAX-TRUNCATED
CARBOXYMETHYLATED
EFFECTOR-BOUND: farnesyl
BOUND-VIA: cysteine residue
Database Correlations
OMIM 601293
UniProt Q15382
Pfam PF00071
Entrez Gene 6009
Kegg hsa:6009
References
- UniProt :accession Q15382
- Shahani N, Huang WC, Varnum M et al
Forebrain depletion of Rheb GTPase elicits spatial memory
deficits in mice.
Neurobiol Aging. 2016 Nov 21;50:134-143
PMID: 2796010
http://www.neurobiologyofaging.org/article/S0197-4580(16)30293-7/abstract