Rho GTPase-activating protein 24 (Rho-type GTPase-activating protein 24, filamin-A-associated RhoGAP, FilGAP, p73RhoGAP, RhoGAP of 73 kD, RAC1 & CDC42-specific GTPase-activating protein of 72 kD, RC-GAP72, sarcoma antigen NY-SAR-88, ARHGAP24, FILGAP)
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Function
- Rho GTPase-activating protein
- role in cell polarity, cell morphology & cytoskeletal organization
- GTPase activator for Rac-type GTPase by converting it to an inactive GDP-bound state
- controls actin-remodelling by inactivating Rac downstream of Rho leading to suppress leading edge protrusion & promotes cell retraction to achieve cellular polarity
- suppresses RAC1 & CDC42 activity in vitro
- overexpression induces cell rounding with partial or complete disruption of actin stress fibers & formation of membrane ruffles, lamellipodia, & filopodia
- isoform 2 is a vascular cell-specific GAP involved in modulation of angiogenesis
- interacts with FLNA
- phosphorylated by ROCK, leading to activate the RacGAP activity
Structure
- contains 1 PH domain
- contains 1 Rho-GAP domain
Compartment
- cytoplasm, cell junction, adherens junction, focal adhesion
- localizes to actin stress fibers
- in migrating cells, localizes to membrane lamellae & protusions
Alternative splicing
named isoforms=5
Expression
- isoform 1 is widely expressed with a higher level in kidney
- isoform 2 is mainly expressed in endothelial cells
- isoform 2 is up-regulated during capillary tube formation in umbilical vein endothelial cells
- coiled coil domain mediates interaction with FLNA leading to its recruitment to lamellae