RAB9 Effector Protein With Kelch Motifs (RABEPK)

RAB9 GTPase is required for the stimulation of mannose 6-phosphate receptor (MPR) transport from endosomes to the trans-Golgi network (TGN).Sequence analysis predicted that the 372-amino acid protein contains six 50-residue kelch repeats that fold p40 into a compact beta barrel. Immunoblot analysis showed expression of a 44-kD, predominantly cytosolic protein (somewhat larger than the predicted 40-kD protein), some of which cofractionated with RAB9 and MPR. Binding analysis indicated that p40 preferentially interacts with the GTP-bound form of RAB9 and interacts poorly with the GDI -complexed form or RAB7 . Functional analysis showed that membrane-associated p40, in concert with RAB9, greatly stimulates the overall extent of endosome-to-TGN transport of MPR.