RAB39B Human

RAB39B is a member of the Ras oncogene family, which is a group of small GTPases involved in the regulation of vesicular trafficking between membrane compartments. This protein is encoded by the RAB39B gene, located on the X chromosome at position Xq28 .

The RAB39B gene consists of two exons spanning approximately 3.8 kilobases of human genomic DNA . The gene encodes a protein of 213 amino acids with a calculated molecular mass of 24 kilodaltons . The protein contains four domains involved in GTP/GDP binding, five RabF domains predicted to interact with regulatory proteins, and a C-terminal prenylation motif (xxCxC) .

RAB39B plays a crucial role in intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes . The protein cycles between an inactive GDP-bound form and an active GTP-bound form, which recruits different sets of downstream effectors responsible for vesicle formation, movement, tethering, and fusion . RAB39B is particularly involved in the homeostasis of alpha-synuclein (SNCA) and the regulation of AMPA receptor composition at post-synapses, thus influencing synaptic transmission .

RAB39B is expressed in multiple human tissues, with the highest expression observed in neuronal precursors and neurons in the hippocampus . The protein is localized to the Golgi apparatus and colocalizes with markers that cycle from the cell surface to the trans-Golgi network via sorting and recycling endosomes . This suggests a role in vesicular transport and synaptic function.

Mutations in the RAB39B gene are associated with several disorders, including Waisman Syndrome and Intellectual Developmental Disorder, X-Linked 72 . These conditions are characterized by cognitive impairments and developmental delays. Studies have shown that downregulation of RAB39B in mouse primary hippocampal neurons results in decreased numbers of growth cones at neurite terminals and decreased numbers of neuronal branches, indicating disorganized growth . Overexpression of RAB39B, on the other hand, leads to decreased neuronal branching and synapse formation, suggesting that proper regulation of RAB39B is essential for normal neuronal development .