RabGGT

RabGGT, or Rab geranylgeranyltransferase, is a eukaryotic enzyme that catalyzes the transfer of geranylgeranyl groups from geranylgeranyl pyrophosphate (GGPP) to Rab family GTPases. This post-translational modification, known as Rab prenylation, enables Rab proteins to associate with membranes and is essential for their role in regulating vesicular trafficking.

In humans, RabGGT is a heteromeric enzyme composed of alpha and beta subunits encoded by RABGGTA and RABGGTB. Rab escort proteins, encoded by RABEP1 and RABEP2, deliver Rab substrates to the enzyme. The reaction typically modifies Rab proteins at C-terminal cysteine residues within CC or CXC motifs, yielding di-geranylgeranylated Rab proteins that can anchor to membranes.

The activity of RabGGT is coordinated with other components of the Rab prenylation pathway and is crucial for proper intracellular transport. Disruption of Rab geranylgeranylation can lead to mislocalization of Rab proteins and defects in vesicle trafficking, with implications for development and neuronal function in model systems; in humans, defects in Rab prenylation pathways have been linked to various disorders in some studies.

RabGGT is categorized among prenyltransferases and shares mechanistic features with other protein-modifying enzymes, while maintaining substrate specificity for Rab GTPases and GGPP.

See also Rab GTPases, geranylgeranyltransferase, prenylation, Rab escort protein.