Rhes: A striatal-specific Ras homolog related to Dexras1

Abstract

We have characterized an apparently full-length cDNA corresponding to a rat mRNA, SE6C, previously identified by subtractive hybridization as being expressed predominantly in the striatal region of the brain. The SE6C mRNA encodes a 266 amino acid protein with significant similarity to members of the Ras-like GTP-binding protein family; thus, we have chosen the name Rhes, for Ras homolog enriched in striatum. The human homolog was found in a genomic sequence from human chromosome 22q13.1 and shares 95% identity with rat Rhes. Among the family of small G-proteins, Rhes shares 62% identity with Dexras1, a mouse dexamethasone-inducible Ras-like protein. Both Rhes and Dexras1 have substantially longer C-termini than other members of the Ras-like small G-protein family. Divergence between the C-terminal sequences of Rhes and Dexras1 suggests that, although their functions are probably similar, they have unique properties. Bacterially expressed Rhes binds GTP, suggesting that the protein indeed has GTPase functionality. Although Rhes was not induced by dexamethasone, its full expression is dependent upon thyroid hormone availability. Its accumulation is postnatal, consistent with the dependence upon thyroid hormone. It is noteworthy that most striatum-"specific" mRNAs characterized to date encode components of signal transduction cascades.