Rem2, a new member of the Rem/Rad/Gem/Kir family of Ras-related GTPases

Here we report the molecular cloning and biochemical characterization of Re m2 (for Rem, Rad and Gem-related 2), a novel GTP-binding protein identified on the basis of its homology with the Rem, Rad, Gem and Kir (RGK) family o f Ras-related small GTP-binding proteins. Rem2 mRNA was detected in rat bra in and kidney, making it the first member of the RGK family to be expressed at relatively high levels in neuronal tissues. Recombinant Rem2 binds GTP saturably and exhibits a low intrinsic rate of GTP hydrolysis. Surprisingly , the guanine nucleotide dissociation constants for both Rem2 and Rem are s ignificantly different than the majority of the Ras-related GTPases, displa ying higher dissociation rates for GTP than GDP. Localization studies with green fluorescent protein (GFP)-tagged recombinant protein fusions indicate that Rem2 has a punctate, plasma membrane localization. Deletion of the C- terminal seven amino acid residues that are conserved in all RGK family mem bers did not affect the cellular distribution of the GFP fusion protein, wh ereas a larger deletion, including much of the polybasic region of the Rem2 C-terminus, resulted in its redistribution to the cytosol. Thus Rem2 is a GTPase of the RGK family with distinctive biochemical properties and posses sing a novel cellular localization signal, consistent with its having a uni que role in cell physiology.