On 2013 Nov 15, Lillian Kenner commented:

The cytohesin family of of GEFs have been well established as having homologous structural organization. Here, the GRAB2 GEF clearly shows a divergence from the typical GEF. GRAB2, though comprised of the same domains as other GEFs, has a unique conformationally static native state. Variance in this GEF structure have caused markedly different downstream regulation. The lack of specificity in cellular membranes observed here allow BRAG2 to be readily available for signaling in cells. This allows it to regulate signaling from many cellular membranes, such as the plasma membrane, and endosomes. This does lead to the question of how the GRAB2 activity is modulated as there appears to be no auto-inhibition.

On 2013 Nov 15, Lillian Kenner commented:

The cytohesin family of of GEFs have been well established as having homologous structural organization. Here, the GRAB2 GEF clearly shows a divergence from the typical GEF. GRAB2, though comprised of the same domains as other GEFs, has a unique conformationally static native state. Variance in this GEF structure have caused markedly different downstream regulation. The lack of specificity in cellular membranes observed here allow BRAG2 to be readily available for signaling in cells. This allows it to regulate signaling from many cellular membranes, such as the plasma membrane, and endosomes. This does lead to the question of how the GRAB2 activity is modulated as there appears to be no auto-inhibition.