| Type: | Domain | Name: | DHR-2 domain |
| Description: | Rho guanosine triphosphatases (GTPases) are critical regulators of cell motility, polarity, adhesion, cytoskeletal organisation, proliferation, geneexpression, and apoptosis. Conversion of these biomolecular switches to the activated GTP-bound state is controlled by two families of guanine nucleotideexchanges factors (GEFs). DH-PH proteins are a large group of Rho GEFs comprising a catalytic Dbl homology (DH) domain with anadjacent pleckstrin homology (PH) domain within the context of functionally diverse signalling modules. The evolutionarily distinct andsmaller family of DOCK (dedicator of cytokinesis) or CDM (CED-5, DOCK1180, Myoblast city) proteins activate either Rac or Cdc42 to control cellmigration, morphogenesis, and phagocytosis. DOCK proteins share the DOCK- homology region (DHR)-1 or CDM-zizimin homology 1 (CZH1) domain and the DHR-2domain (also termed the CZH2 or DOCKER domain) [, , , , ].The DHR-1 domain is located toward the N terminus[]. The DHR-2 domain is a GEF catalytic domain of ~400 residues situated withinthe C terminus. The structure of the DHR2 domain differs from that of otherGEF catalytic domains. It is organised into three lobes of roughly equal size (lobes A, B, and C), with the Rho-family binding site and catalytic centregenerated entirely from lobes B and C. Lobe A is formed from an antiparallel array of alpha helices. Through extensive contacts with lobeB, lobe A stabilises the DHR2 domain. Lobe B adopts an unusal architecture of two antiparallel beta sheets disposed in a loosely packed orthogonalarrangement, whereas lobe C comprises a four-helix bundle [, ].This entry represents the DHR-2 domain. | Short Name: | DHR-2 |
