RHEB
RHEB (Ras homolog, mTORC1 binding) is a small GTPase that acts as an allosteric activator of the mTORC1 complex, linking nutrient and growth factor signals to cell growth. It is also known as RHEB2, Ras homolog enriched in brain and GTP-binding protein Rheb. Browse Assay Genie's current range of RHEB research reagents below, or read on for the biology behind the target.
RHEB is a 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. In response to nutrients, growth factors or amino acids, RHEB specifically activates the protein kinase activity of MTOR, the catalytic component of mTORC1. It does so by causing a conformational change that aligns residues in the MTOR active site, enhancing phosphorylation of ribosomal protein S6 kinase (RPS6KB1 and RPS6KB2) and EIF4EBP1 (4E-BP1).
RHEB is also required for localisation of the TSC-TBC complex to lysosomal membranes. In response to starvation, the TSC-TBC complex inactivates RHEB, which prevents activation of mTORC1. The protein has low intrinsic GTPase activity and shuttles between a GDP-bound and a GTP-bound form; farnesylation is required for this activity. UniProt records localisation to the endomembrane system, including lysosome, Golgi apparatus and endoplasmic reticulum membranes, as well as the cytosol.
The human RHEB gene belongs to the small GTPase superfamily and the Rheb family, and is classed by HGNC in the RAS type GTPase family. NCBI describes a lipid-anchored membrane protein with five repeats of the RAS-related GTP-binding region, with a role in growth and cell cycle progression through the insulin/TOR/S6K signalling pathway. Previous names include Ras homolog enriched in brain and Ras homolog enriched in brain 2. Three pseudogenes have been mapped, two on chromosome 10 and one on chromosome 22.
RHEB allosterically activates MTOR kinase activity, making it a central node for studying how nutrients, amino acids and growth factors drive mTORC1.
Inactivation of RHEB by the TSC-TBC complex during starvation prevents mTORC1 activation, offering a route to study nutrient-dependent regulation.
Through the insulin/TOR/S6K pathway, RHEB regulates growth and cell cycle progression, with S6 kinase and 4E-BP1 phosphorylation as downstream readouts.
RHEB is needed for TSC-TBC localisation to lysosomal membranes and is found on endomembranes, supporting work on signalling at organelle surfaces.
RHEB is a small GTPase that activates the kinase activity of MTOR within the mTORC1 complex in response to nutrients, growth factors or amino acids. This enhances phosphorylation of S6 kinases and 4E-BP1. During starvation, the TSC-TBC complex inactivates RHEB and mTORC1 activation is prevented.
The HGNC full name is Ras homolog, mTORC1 binding, and UniProt names the protein GTP-binding protein Rheb. RHEB2 is a listed alias, and earlier names were Ras homolog enriched in brain and Ras homolog enriched in brain 2.
Yes. Mouse and rat both have a Rheb ortholog, and UniProt describes mTORC1 as an evolutionarily conserved nutrient sensor. RHEB belongs to the Rheb family of the small GTPase superfamily. Check the datasheet of any product for its validated reactivity.
A related Rheb-family GTPase with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q15382; product specifications from Assay Genie datasheets.