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GTP-binding protein Rhes; Ras homolog enriched in striatum; tumor endothelial marker 2 (RASD2, TEM2)

Function: 1) binds to GTP 2) intrinsic GTPase activity 3) signal transduction - attenuation of G protein-coupled receptor signalling - binds G-beta-1, G-beta-2 & G-beta-3 [2] - AGS1 & RASD2 trigger nearly identical modulation of N-type Ca+2 channels (CaV2.2) by selectively altering Gi-alpha-dependent signaling - role in cAMP/PKA signalling pathway, proximal to the activation of heterotrimeric G-protein complex [5] - role in dopamine D2 receptor signalling [5] - absence of RASD2 increases expression of Golf protein [5] 4) insulin secretory response to efaroxan Structure: - monomer - sequence homology to AGS1 - belongs to the small GTPase superfamily, RasD family Compartment: membrane, lipid-anchor Expression: - expressed in striatum - RASD2 expression enhanced by dopaminergic input [4] - expressed in pancreatic endocrine cells (islets of Langerhans) Pathology: - RASD2 (Rhes) interacts with huntingtin; [3] RASD2 induces sumoylation of mutant huntingtin, which results in cytotoxicity & cell death - specificity of RASD2 expression for striatum may confer striatal-specific pathology in Huntington's disease [3]

General

guanine nucleotide regulatory protein (GNRP)

Properties

SIZE: entity length = 266 aa MW = 30 kD MOTIF: GTP-binding site SITE: 26-33 Effector region {48-56} GTP-binding site SITE: 73-77 GTP-binding site SITE: 140-143 CaaX motif SITE: C-TERMINUS EFFECTOR-BOUND: farnesyl

Database Correlations

UniProt Q96D21 Pfam PF00071 Entrez Gene 23551 Kegg hsa:23551

References

  1. UniProt :accession Q96D21
  2. Hill C et al The cationic region of Rhes mediates its interactions with specific Gbeta subunits Cell Physiol Biochem. 2009;23(1-3):1-8. Epub 2009 Feb 18. PMID: 19255495
  3. Subramaniam S et al Rhes, a Striatal Specific Protein, Mediates Mutant- Huntingtin Cytotoxicity Science. 2009 Jun 5;324(5932):1327-1330. PMID: 19498170 DOI: 10.1126/science.1172871
  4. Harrison LM et al, Ontogeny and dopaminergic regulation in brain of Ras homolog enriched in striatum (Rhes). Brain Res. 2008 Dec 15;1245:16-25. Epub 2008 Oct 2 PMID: 18929545
  5. Errico F et al The GTP-binding protein Rhes modulates dopamine signalling in striatal medium spiny neurons. Mol Cell Neurosci. 2008 Feb;37(2):335-45. Epub 2007 Oct 23. PMID: 18035555