GTP-binding protein Rhes (RASD2)

GTP-binding protein Rhes (RASD2) is a member of the Ras superfamily of small GTPases, preferentially enriched in the striatum of the brain. It acts as a signal transduction protein affecting multiple G-protein–coupled receptor pathways, modulating cAMP/PKA and calcium channel activities critical for synaptic plasticity and neurotransmitter signaling. Rhes also has SUMO E3 ligase activity, facilitating sumoylation of mutant huntingtin protein and contributing to neurodegeneration observed in Huntington's disease, as well as playing a role in Parkinson’s disease and tauopathies. Beyond central nervous system functions, evidence suggests RASD2 participates in cellular homeostasis, iron uptake, and may impact pancreatic β-cell activity. Its central role in neuronal function and its association with disease has made it a subject of therapeutic research, especially in targeting striatal neurodegeneration and psychiatric disorders.

Other names

RhesTumor endothelial marker 2 (TEM2)Ras homolog enriched in striatumGTP-binding protein RhesMGC:4834RASD2

Modulation of dopamine and opioid signaling (affecting behavioral responses); Regulation of cAMP/PKA and Akt pathways (neurotransmission, psychiatric effects); Influences mTOR signaling (affecting neuronal growth, regeneration, protein synthesis); SUMOylation of huntingtin (affecting neurodegenerative progression).