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
• selective depletion of Rheb in mouse forebrain results in:
  • spontaneous signs of spatial memory deficits (T-maze, Morris water maze)
  • no affect on locomotion (open-field test), anxiety (elevated plus maze), or contextual fear conditioning

More general terms

• guanine nucleotide regulatory protein (GNRP)
• prenyl protein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=6009
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:6009
• OMIM: https://mirror.omim.org/entry/601293
• UniProt: http://www.uniprot.org/uniprot/Q15382.html