SRGAP2
Domain
The F-BAR domain mediates oligomerization, binds membranes, and induces plasma membrane protrusions.
Function
Postsynaptic RAC1 GTPase activating protein (GAP) that plays a key role in neuronal morphogenesis and migration mainly during development of the cerebral cortex (PubMed:20810653, PubMed:27373832, PubMed:28333212). Regulates excitatory and inhibitory synapse maturation and density in cortical pyramidal neurons (PubMed:22559944, PubMed:27373832). SRGAP2/SRGAP2A limits excitatory and inhibitory synapse density through its RAC1-specific GTPase activating activity, while it promotes maturation of both excitatory and inhibitory synapses through its ability to bind to the postsynaptic scaffolding protein HOMER1 at excitatory synapses, and the postsynaptic protein GPHN at inhibitory synapses (By similarity). Mechanistically, acts by binding and deforming membranes, thereby regulating actin dynamics to regulate cell migration and differentiation (PubMed:27373832). Promotes cell repulsion and contact inhibition of locomotion: localizes to protrusions with curved edges and controls the duration of RAC1 activity in contact protrusions (By similarity). In non-neuronal cells, may also play a role in cell migration by regulating the formation of lamellipodia and filopodia (PubMed:20810653, PubMed:21148482).
Involvement in disease
A chromosomal aberration disrupting SRGAP2 has been found in a patient with early infantile epileptic encephalopathy. Balanced translocation t(1;9)(q32;q13) (PubMed:22106086).
Post-translational modifications
Methylation at Arg-927 is required for the stimulation of cell migration, dimerization and localization at the plasma membrane protrusions.
Cellular localization
- Cell membrane
- Cell projection
- Dendritic spine
- Postsynaptic density
- Postsynaptic cell membrane
- Cell projection
- Lamellipodium
- Cytoplasmic vesicle
- Phagosome
- Nucleus
- Cytoplasm
- Cytosol
- Recruited to actin-rich phagosomes during phagocytosis (By similarity). Translocates from nucleus to cytoplasm during development (By similarity).
Alternative names
ARHGAP34, FNBP2, KIAA0456, SRGAP2A, SRGAP2, SLIT-ROBO Rho GTPase-activating protein 2, srGAP2, Formin-binding protein 2, Rho GTPase-activating protein 34