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Beschreibung

Rab5 GDP/GTP exchange factor (UniProt: Q9UJ41, also known as RAP1, Rabaptin-5-associated exchange factor for Rab5, Rabex-5) is encoded by the RABGEF1 (also known as RABEX5) gene (Gene ID: 27342) in human. Rabex-5 is a guanine nucleotide exchange factor that catalyzes the exchange of GTP for GDP on the Rab5 subfamily of low molecular weight GTPases. It forms a tight complex with Rabaptin-5 that augments its exchange activity and generates GTP-bound, membrane-associated Rab5, which in turn binds Rabaptin-5 and stabilizes the Rabex-5- Rabaptin-5 complex on endosomes. It is involved in endocytic membrane fusion and membrane trafficking of recycling endosomes. It can also act as a ubiquitin ligase. It binds to ubiquitin (Ub) through two independent ubiquitin-binding domains (UBDs). These UBDs determine a number of properties of Rabex-5, including its coupled monoubiquitination and interaction in vivo with ubiquitinated epidermal growth factor receptors. The first Ub binding region is localized in amino acids 2-49 and is named as RUZ domain (Rabex-5 ubiquitin binding zinc finger). The second Ub binding region is highly conserved and is localized in amino acids 48-74. In this domain Ala58 is shown to be critical for Ub binding and A58G mutagenesis causes significant reduction in its binding to Ub. (Ref., Penengo, L., et al. (2006). Cell. 124. 1183-1195, Mattera, R., et al. (2006). J. Biol. Chem. 281(10), 6874-6883).