| Type: | Domain | Name: | Rho GTPase-binding/formin homology 3 (GBD/FH3) domain |
| Description: | Formins are multidomain proteins conserved from plants to fungi and vertebrates. Due to their pivotal role in the organisation of the actin cytoskeleton formins are involved in processes as diverse as formation of filopodia, microspikes and lamellipodia, establishment and maintenance of cell polarity, vesicular trafficking, formation of adherens junctions, cytokinesis, embryonic development and signalling to the nucleus. Formins are defined by a conserved formin homology 2 (FH2) domain with actin nucleation activity preceded by a proline-rich formin homology 1 (FH1) domain. In most fungal and metazoan formins the FH1-FH2 core is accompanied by a less conserved N-terminal formin homology 3 (FH3) domain involved in targeting []. The Diaphanous-related formins are able to interact with activated Rho GTPases through a poorly defined N-terminal Rho GTPase binding domain (GBD) that overlaps with the formin homology 3 (FH3) domain. This binding releases the intramolecular inhibitory interaction between the GBD and a C-terminal Diaphanous autoregulatory domain (DAD) (see ) and renders the protein active. It has been proposed that the GBD and FH3 domains constitute a single domain also found in Dictyostelium guanine nucleotide exchange factors (RasGEFs) [].This entry represents the GBD/FH3 domain that is approximately 380 residues in length. Its role appears to be twofold. On one hand the N-terminal region of formins is involved in subcellular localisation through interaction with diverse targets. The low degree of sequence conservation of this region might correlate with the diversity of binding partners, not only Rho GTPases, and subcellular localisation patterns. On the other hand the GBD/FH3 domain is involved in regulation of activation by releasing of an intramolecular interaction between the DAD and the N terminus []. The GBD/FH3 domain is exclusively alpha-helical and is comprised of the N-terminal part of the GBD, an armadillo repeat region (ARR) and dimerisation subdomains []. | Short Name: | GBD/FH3_dom |
