SRGAP2

This locus encodes a member of the SLIT-ROBO Rho GTPase activating protein family. The encoded protein stimulates GTPase activity of Rac1, and plays a role in cortical neuron development. This locus has several paralogs on human chromosome 1 resulting from segmental duplication. While this locus itself is conserved among various species, the paralogs are found only in the genus Homo, and not in the genomes of non-human great apes. Alternatively spliced transcript variants have been described for this locus.

Full Name

SLIT-ROBO Rho GTPase Activating Protein 2

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).

Biological Process

Biological Process actin filament severingManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process dendritic spine developmentManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process excitatory synapse assemblyManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process extension of a leading process involved in cell motility in cerebral cortex radial glia guided migrationISS:UniProtKB
Biological Process filopodium assemblyManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process inhibitory synapse assemblyManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process lamellipodium assembly involved in ameboidal cell migrationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process negative regulation of cell migrationManual Assertion Based On ExperimentIBA:GO_Central
Biological Process negative regulation of neuron migrationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process neuron projection morphogenesisISS:UniProtKB
Biological Process positive regulation of GTPase activityManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process regulation of small GTPase mediated signal transductionTAS:Reactome
Biological Process signal transductionIEA:InterPro
Biological Process substrate adhesion-dependent cell spreadingManual Assertion Based On ExperimentIMP:UniProtKB

Cellular Location

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).

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).

PTM

Methylation at Arg-927 is required for the stimulation of cell migration, dimerization and localization at the plasma membrane protrusions.