TBC domain family, member 15 is a novel mammalian Rab GTPase-activating protein with substrate preference for Rab7

Biochem Biophys Res Commun. 2005 Sep 16;335(1):154-61. doi: 10.1016/j.bbrc.2005.07.070.

Abstract

Ypt/Rabs are Ras-related GTPases that function as key regulators of intracellular vesicular trafficking. Their slow intrinsic rates of GTP hydrolysis are catalyzed by GTPase-activating proteins (GAPs). Ypt/Rab-GAPs constitute a family of proteins that contain a TBC (Tre-2/Bub2/Cdc16) domain. Only three of the 51 family members predicted in the human genome are confirmed Ypt/Rab-GAPs. Here, we report the identification and characterization of a novel mammalian Ypt/Rab-GAP, TBC domain family, member 15 (TBC1D15). TBC1D15 is ubiquitously expressed and localized predominantly to the cytosol. The TBC domain of TBC1D15 exhibits relatively high homology with that of Gyp7p, a yeast Ypt/Rab-GAP. Furthermore, TBC1D15 stimulates the intrinsic GTPase activity of Rab7, and to a lesser extent Rab11, but is essentially inactive towards Rab4 or Rab6. These data increase the number of mammalian TBC domain family members with demonstrated Rab-GAP activity to four, and suggest that TBC1D15 may be involved in Rab7-mediated late endosomal trafficking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Chlorocebus aethiops
  • GTPase-Activating Proteins / chemistry*
  • GTPase-Activating Proteins / genetics
  • GTPase-Activating Proteins / metabolism*
  • Gene Expression Profiling
  • Humans
  • Mice
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • Sequence Alignment
  • Substrate Specificity
  • rab GTP-Binding Proteins / metabolism*

Substances

  • GTPase-Activating Proteins
  • TBC1D15 protein, mouse
  • rab7 protein
  • rab GTP-Binding Proteins