Stable Identifier
Homo sapiens
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Rab GTPases are peripheral membrane proteins involved in membrane trafficking. Often through their indirect interactions with coat components, motors, tethering factors and SNAREs, the Rab GTPases serve as multifaceted organizers of almost all membrane trafficking processes in eukaryotic cells. To perform these diverse processes, Rab GTPases interconvert between an active GTP-bound form and an inactive, GDP-bound form. The GTP-bound activated form mediates membrane transport through specific interaction with multiple effector molecules (Zerial & McBride 2001, Stenmark 2009, Zhen & Stenmark 2015, Cherfils & Zeghouf 2013). Conversion from the GTP- to the GDP-bound form occurs through GTP hydrolysis, which is not only driven by the intrinsic GTPase activity of the Rab protein but is also catalysed by GTPase-activating proteins (GAPs). GAPs not only increase the rate of GTP hydrolysis, but they are also involved in the inactivation of RABs, making sure they are inactivated at the correct membrane. Human cells contain as many as 70 Rabs and at least 51 putative Rab GAPs (Pfeffer 2005). Only a few of these GAPs have been matched to a specific Rab substrate. The Tre-2/Bub2/Cdc16 (TBC) domain-containing RAB-specific GAPs (TBC/RABGAPs) are a key family of RAB regulators, where the TBC domain facilitates the inactivation of RABs by facilitating activation of GTPase activity of the RAB (Pan et al. 2006, Frasa et al. 2012, Stenmark 2009). Studies suggest that TBC/RABGAPs are more than just negative regulators of RABs and can integrate signalling between RABs and other small GTPases, thereby regulating numerous cellular processes like intracellular trafficking (Frasa et al. 2012).
Literature References
PubMed ID Title Journal Year
16855591 TBC-domain GAPs for Rab GTPases accelerate GTP hydrolysis by a dual-finger mechanism

Lambright, DG, Pan, X, Munson, M, Eathiraj, S

Nature 2006
22251903 Illuminating the functional and structural repertoire of human TBC/RABGAPs

Frasa, MA, Braga, VM, Ahmadian, MR, Koessmeier, KT

Nat. Rev. Mol. Cell Biol. 2012
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