Rabex5

Rabex-5 is a guanine nucleotide exchange factor (GEF) for the small GTPase Rab5, a key regulator of early endosome dynamics in eukaryotic cells. By catalyzing the exchange of GDP for GTP on Rab5, Rabex-5 promotes Rab5 activation and enables Rab5-dependent trafficking events within the endocytic pathway, including endosome fusion and cargo sorting.

In mammalian cells, Rabex-5 functions as part of the Rab5 activation cascade by forming a stable complex with Rabaptin-5, which enhances Rab5 recruitment and activity on early endosomes. The catalytic activity of Rabex-5 centers on the Vps9 domain, a motif shared by Rab5 GEFs. Rabex-5 localizes to early endosomal membranes and coordinates with other regulators of endocytosis to promote vesicle fusion and endosome maturation.

Structural features of Rabex-5 include the Vps9 GEF domain and regions that mediate protein–protein interactions, enabling connections with Rab5, Rabaptin-5, and other partners involved in trafficking. Regulation of Rabex-5 activity is influenced by its localization, interactions, and the broader Rab5 cycle, ensuring appropriate timing and extent of Rab5 activation.

Rabex-5 is conserved across metazoans and occupies a central position in the early endosome network. Given Rab5’s role in endocytic trafficking, Rabex-5 participates in multiple cellular processes, and dysregulation of Rab5 activation involving Rabex-5 has been implicated in alterations of endocytic pathways in various contexts, though the precise mechanisms remain an area of ongoing study.