SH3BP1
Domain
The BAR domain mediates interaction with the exocyst components EXOC4 and EXOC8 and is required for the function in cell migration (PubMed:21658605). It also mediates the interaction with PLXND1 (PubMed:24841563).
Function
GTPase activating protein (GAP) which specifically converts GTP-bound Rho-type GTPases including RAC1 and CDC42 in their inactive GDP-bound form. By specifically inactivating RAC1 at the leading edge of migrating cells, it regulates the spatiotemporal organization of cell protrusions which is important for proper cell migration (PubMed:21658605). Also negatively regulates CDC42 in the process of actin remodeling and the formation of epithelial cell junctions (PubMed:22891260). Through its GAP activity toward RAC1 and/or CDC42 plays a specific role in phagocytosis of large particles. Specifically recruited by a PI3 kinase/PI3K-dependent mechanism to sites of large particles engagement, inactivates RAC1 and/or CDC42 allowing the reorganization of the underlying actin cytoskeleton required for engulfment (PubMed:26465210). It also plays a role in angiogenesis and the process of repulsive guidance as part of a semaphorin-plexin signaling pathway. Following the binding of PLXND1 to extracellular SEMA3E it dissociates from PLXND1 and inactivates RAC1, inducing the intracellular reorganization of the actin cytoskeleton and the collapse of cells (PubMed:24841563).
Cellular localization
- Cell projection
- Cell junction
- Tight junction
- Cell junction
- Adherens junction
- Cell projection
- Phagocytic cup
- Nucleus
- Cytoplasm
- Cytosol
- Localizes at the leading edge of migrating cells (PubMed:21658605, PubMed:24841563). Accumulation at forming phagocytic cups is PI3 kinase/PI3K-dependent and is specific for sites of large particles engagement and their phosphatidylinositol 3,4,5-triphosphate membrane content (PubMed:26465210).
Alternative names
SH3 domain-binding protein 1, SH3BP1