DENND5A,B exchange GTP for GDP on RAB39

Stable Identifier
R-HSA-8877813
Type
Reaction
Species
Homo sapiens
Compartment
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Summation

RAB39 proteins are involved in endolysosomal trafficking and are localized to the Golgi membrane where they interact with the multisubunit tethering complex COG (Chen et al, 2003; Giannandrea et al, 2010; Miller et al, 2013; reviewed in Willet et al, 2013). Although RAB proteins are known to play key roles in trafficking and Golgi structure and function, the significance of some of these interactions is not yet clear (reviewed in Liu and Storrie, 2015). Loss-of-function mutations of RAB39B cause X-linked metal retardation, likely as a result of altered trafficking during growth cone and synapse formation (Giannandrea et al, 2010). Activation of RAB39 at the Golgi is dependent on the GEF activity of DENND5A and DENND5B (Yoshimura et al, 2010). Interaction of RAB39:GDP with its GEFs promotes release of GDP, allowing GTP to bind, and precludes the interaction of RAB39 with GDI and CHM proteins.

Literature References
PubMed ID Title Journal Year
20937701 Family-wide characterization of the DENN domain Rab GDP-GTP exchange factors

Yoshimura, S, Gerondopoulos, A, Linford, A, Rigden, DJ, Barr, FA

J. Cell Biol. 2010
12684051 Rab39, a novel Golgi-associated Rab GTPase from human dendritic cells involved in cellular endocytosis

Chen, T, Han, Y, Yang, M, Zhang, W, Li, N, Wan, T, Guo, J, Cao, X

Biochem. Biophys. Res. Commun. 2003
23239882 Molecular insights into vesicle tethering at the Golgi by the conserved oligomeric Golgi (COG) complex and the golgin TATA element modulatory factor (TMF)

Miller, VJ, Sharma, P, Kudlyk, TA, Frost, L, Rofe, AP, Watson, IJ, Duden, R, Lowe, M, Lupashin, VV, Ungar, D

J. Biol. Chem. 2013
22581368 Are Rab proteins the link between Golgi organization and membrane trafficking?

Liu, S, Storrie, B

Cell. Mol. Life Sci. 2012
20159109 Mutations in the small GTPase gene RAB39B are responsible for X-linked mental retardation associated with autism, epilepsy, and macrocephaly

Giannandrea, M, Bianchi, V, Mignogna, ML, Sirri, A, Carrabino, S, D'Elia, E, Vecellio, M, Russo, S, Cogliati, F, Larizza, L, Ropers, HH, Tzschach, A, Kalscheuer, V, Oehl-Jaschkowitz, B, Skinner, C, Schwartz, CE, Gecz, J, Van Esch, H, Raynaud, M, Chelly, J, de Brouwer, AP, Toniolo, D, D'Adamo, P

Am. J. Hum. Genet. 2010
23839779 The Golgi puppet master: COG complex at center stage of membrane trafficking interactions

Willett, R, Ungar, D, Lupashin, V

Histochem. Cell Biol. 2013
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
Rab guanyl-nucleotide exchange factor activity of DENND5A,B [cytosol]
Physical Entity
Activity
Orthologous Events
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Reviewed