Figure 1. Domain composition of members of a new family of modulators of G protein that share an evolutionary conserved GEF motif as a common functional domain.

Upper part of the figure displays bar diagrams drawn to scale showing the various functional domains of GIV, Daple, Calnuc/NUCB1 and NUCB2 (from top to bottom). The single domain that is shared by them all is the GEF motif shown in dark blue. The alignment of the sequences of GEF motifs with the sequences in synthetic peptides with demonstrated GEF activity towards Giα proteins is shown (lower left). The structural basis for interaction with Giα proteins has been solved for the synthetic KB-752 peptide (lower right), and homology modeling and extensive mutational analyses have confirmed that each member of the GEF family share these structural basis and molecular mechanisms of interaction with Giα.