2dl8

Structural highlights

Disease

[SRGP2_HUMAN] A chromosomal aberration disrupting SRGAP2 has been found in a patient with early infantile epileptic encephalopathy. Balanced translocation t(1;9)(q32;q13).

Function

[SRGP2_HUMAN] RAC1 GTPase activating protein (GAP) that binds and deforms membranes, and regulates actin dynamics to regulate cell migration and differentiation. Plays an important role in different aspects of neuronal morphogenesis and migration mainly during development of the cerebral cortex. This includes the biogenesis of neurites, where it is required for both axons and dendrites outgrowth, and the maturation of the dendritic spines. Also stimulates the branching of the leading process and negatively regulates neuron radial migration in the cerebral cortex. Its interaction and inhibition by SRGAP2C reduces the rate of spine maturation, alters dendritic spine morphology and density and indirectly increases neuronal migration. It may have implications for cognition, learning and memory. In non-neuronal cells, it may also play a role in cell migration by regulating the formation of lamellipodia and filopodia.^{[1] [2] [3]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

• Rho GTPase activating protein 3D structures

References

1. ↑ Guo S, Bao S. srGAP2 arginine methylation regulates cell migration and cell spreading through promoting dimerization. J Biol Chem. 2010 Nov 5;285(45):35133-41. doi: 10.1074/jbc.M110.153429. Epub 2010, Sep 1. PMID:20810653 doi:10.1074/jbc.M110.153429
2. ↑ Mason FM, Heimsath EG, Higgs HN, Soderling SH. Bi-modal regulation of a formin by srGAP2. J Biol Chem. 2011 Feb 25;286(8):6577-86. doi: 10.1074/jbc.M110.190397. Epub 2010 , Dec 9. PMID:21148482 doi:10.1074/jbc.M110.190397
3. ↑ Charrier C, Joshi K, Coutinho-Budd J, Kim JE, Lambert N, de Marchena J, Jin WL, Vanderhaeghen P, Ghosh A, Sassa T, Polleux F. Inhibition of SRGAP2 function by its human-specific paralogs induces neoteny during spine maturation. Cell. 2012 May 11;149(4):923-35. doi: 10.1016/j.cell.2012.03.034. Epub 2012 May, 3. PMID:22559944 doi:10.1016/j.cell.2012.03.034