RanGAP1

Ran GTPase-activating protein 1 (RanGAP1) is a cytoplasmic regulator of the Ran GTPase cycle. In humans it is encoded by the RANGAP1 gene. RanGAP1 catalyzes the hydrolysis of GTP bound to Ran, converting Ran-GTP to Ran-GDP and thereby helping to maintain the nucleocytoplasmic Ran-GTP gradient that drives directional transport through the nuclear pore complex.

A major pool of RanGAP1 is localized to the cytoplasmic filaments of the nuclear pore complex via an interaction with the nucleoporin RanBP2/Nup358. This NPC-associated RanGAP1 is SUMOylated at lysine 526 with SUMO-1; SUMOylation promotes its binding to RanBP2 and NPC tethering. A cytosolic form of RanGAP1 without SUMO-1 modification exists as well.

By hydrolyzing Ran-GTP to Ran-GDP in the cytoplasm, RanGAP1 participates in resetting the Ran gradient after cargo release in the nucleus and cargo loading for export receptors in the cytoplasm. The RanGTP–RanGDP cycle is coordinated with RCC1, the Ran guanine nucleotide exchange factor in the nucleus, to provide directionality for importins and exportins.

Human RanGAP1 is a ~589‑amino-acid protein with a catalytic GAP domain in the N-terminal region; the C-terminal region contains the SUMOylation site at lysine 526 and mediates interaction with RanBP2. The protein is ubiquitously expressed and essential for proper nucleocytoplasmic transport. Disruption of RanGAP1 localization or function can impair transport processes and nuclear envelope dynamics.

See also: Ran, RCC1, RanBP1, RanBP2.