ARHGEF12 (also called LARG) is a Rho guanine-nucleotide exchange factor that are RhoA-selective and directly activated by the Galpha12/13 family of heterotrimeric G proteins. LARG contains a regulator of G protein signaling (RGS) homology (RH) domain, the catalytic Dbl homology (DH) domain and the pleckstrin homology (PH) domain. The DH and PH domains bind RhoA and catalyze the exchange of GDP for GTP on RhoA. The active site of RhoA adopts two distinct GDP-excluding conformations among the four unique complexes in the asymmetric unit. The LARG PH domain also contains a potential protein-docking site. LARG forms a homotetramer via its DH domains []. This entry represents the PH domain of ARHGEF12. It has an exposed hydrophobic patch that could interface with other domains of LARG or other regulatory proteins [].
