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

Biochem J. 2000 Apr 1;347 Pt 1(Pt 1):223-31.

Abstract

Here we report the molecular cloning and biochemical characterization of Rem2 (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 of Ras-related small GTP-binding proteins. Rem2 mRNA was detected in rat brain 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 significantly different than the majority of the Ras-related GTPases, displaying 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 members did not affect the cellular distribution of the GFP fusion protein, whereas 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 possessing a novel cellular localization signal, consistent with its having a unique role in cell physiology.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Brain / enzymology*
  • Cloning, Molecular
  • Expressed Sequence Tags
  • GTP Phosphohydrolases / chemistry
  • GTP Phosphohydrolases / genetics*
  • GTP Phosphohydrolases / metabolism*
  • Gene Library
  • Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
  • Guanosine Triphosphate / metabolism
  • Humans
  • Immediate-Early Proteins / genetics
  • Kidney / metabolism
  • Kinetics
  • Molecular Sequence Data
  • Monomeric GTP-Binding Proteins / chemistry
  • Monomeric GTP-Binding Proteins / genetics*
  • Monomeric GTP-Binding Proteins / metabolism*
  • Neurons / enzymology*
  • Open Reading Frames
  • Rats
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Transcription, Genetic
  • ras Proteins / genetics

Substances

  • Immediate-Early Proteins
  • RRAD protein, human
  • Rrad protein, mouse
  • Rrad protein, rat
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Guanosine Triphosphate
  • GTP Phosphohydrolases
  • GEM protein, human
  • Monomeric GTP-Binding Proteins
  • Rem2 protein, rat
  • ras Proteins

Associated data

  • GENBANK/AF084464