DHR-2 domain (IPR027357)

Short name: DHR-2

Overlapping homologous superfamilies


Domain relationships



Rho guanosine triphosphatases (GTPases) are critical regulators of cell motility, polarity, adhesion, cytoskeletal organisation, proliferation, gene expression, and apoptosis. Conversion of these biomolecular switches to the activated GTP-bound state is controlled by two families of guanine nucleotide exchanges factors (GEFs). DH-PH proteins are a large group of Rho GEFs comprising a catalytic Dbl homology (DH) domain with an adjacent pleckstrin homology (PH) domain within the context of functionally diverse signalling modules. The evolutionarily distinct and smaller family of DOCK (dedicator of cytokinesis) or CDM (CED-5, DOCK1180, Myoblast city) proteins activate either Rac or Cdc42 to control cell migration, morphogenesis, and phagocytosis. DOCK proteins share the DOCK- homology region (DHR)-1 or CDM-zizimin homology 1 (CZH1) domain and the DHR-2 domain (also termed the CZH2 or DOCKER domain) [PMID: 12172552, PMID: 12432077, PMID: 20167601, PMID: 19745154, PMID: 21613211].

The DHR-1 domain is located toward the N terminus[PMID: 20167601]. The DHR-2 domain is a GEF catalytic domain of ~400 residues situated within the C terminus. The structure of the DHR2 domain differs from that of other GEF 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 centre generated entirely from lobes B and C. Lobe A is formed from an antiparallel array of alpha helices. Through extensive contacts with lobe B, lobe A stabilises the DHR2 domain. Lobe B adopts an unusal architecture of two antiparallel beta sheets disposed in a loosely packed orthogonal arrangement, whereas lobe C comprises a four-helix bundle [PMID: 19745154, PMID: 21613211].

This entry represents the DHR-2 domain.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PROSITE profiles