RAN is a small
GTP-binding protein of the
RAS superfamily. Ran
GTPase is a master regulatory switch, which among other functions, controls the shuttling of proteins between the nuclear and cytoplasm compartments of the cell. Ran GTPase controls a variety of cellular functions through its interactions with other proteins. The
RanBP2 gene encodes a very large RAN-binding protein that localizes to cytoplasmic filaments emanating from the
nuclear pore complex. RanBP2/Nup358 is a giant scaffold and mosaic
cyclophilin-related nucleoporin implicated in controlling selective processes of the
Ran-GTPase cycle. RanBP2 is composed of multiple domains. Each domain of RanBP2 selectively and directly interacts with distinct proteins such as Ran GTPase,
importin-beta,
exportin-1/
CRM1, red
opsin, subunits of the
proteasome, cox11 and the
kinesin-1 isoforms,
KIF5B and
KIF5C. Another partner of RanBP2 is the
E2 enzyme UBC9. RanBP2 strongly enhances
SUMO1 transfer from UBC9 to the SUMO1 target
SP100. Another target for SUMOylation is
RanGAP which is the GTPase activating protein for Ran. SUMO-RanGAP interacts with a domain near the carboxyl terminus of RanBP2. These findings place
sumoylation at the cytoplasmic filaments of the nuclear pore complex and suggest that, for some substrates, modification and nuclear import are linked events. The pleiotropic (multifunctional) role of RanBP2 reflects its interaction with multiple partners, each presenting distinct cellular or molecular functions. This gene is partially duplicated in a gene cluster that lies in a hot spot for recombination on human chromosome 2q. == Clinical significance ==