RHEB
Description
The RHEB (Ras homolog, mTORC1 binding) is a protein-coding gene located on chromosome 7.
RHEB, also known as Ras homolog enriched in brain (RHEB), is a GTP-binding protein that is ubiquitously expressed in humans and other mammals. The protein is largely involved in the mTOR pathway and the regulation of the cell cycle. RHEB is a recently discovered member of the Ras superfamily. Being a relative of Ras, the overexpression of RHEB can be seen in multiple human carcinomas. For this reason, ways to inhibit RHEB to control the mTOR pathway are studied as possible treatments for uncontrollable tumor cell growth in several diseases, especially in tuberous sclerosis.
== Structure ==
Rheb is a 21 kDa protein monomer composed of 184 amino acids. The first 169 amino acids by the N-terminus make up the GTPase domain, and the remaining amino acids are part of a hypervariable region ending at the C-terminus in a CAAX motif (C – cysteine, A – aliphatic amino acid, X – C-terminus amino acid). The protein is a lipid-anchored, cell-membrane protein with five repeats of the RAS-related GTP-binding region. Also present are “switch” regions, I and II, which undergo conformational changes when shuttling between GTP-bound(activated) and GDP-bound(inactive) forms. RHEB is expressed by the RHEB gene in humans.
RHEB is a small GTPase that acts as an allosteric activator of the mTORC1 complex, a key nutrient sensor that controls cell growth. It stimulates anabolic reactions and macromolecule biosynthesis, ultimately driving cellular growth. RHEB activates mTORC1 in response to nutrients, growth factors, and amino acids, triggering the phosphorylation of key proteins like RPS6KB1/2 and EIF4EBP1. This activation is essential for cell growth and involves conformational changes that enhance mTOR's kinase activity. RHEB also influences the localization of the TSC-TBC complex to lysosomal membranes. During starvation, the TSC-TBC complex inactivates RHEB, preventing mTORC1 activation and cell growth. RHEB has low intrinsic GTPase activity.
RHEB is also known as RHEB2.
