PROSITE documentation PDOC51232Rho GTPase-binding/formin homology 3 (GBD/FH3) domain profile
Formins are multidomain proteins conserved from plants to fungi and vertebrates. Due to their pivotal role in the organization 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 signaling 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 [1]. 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 <PDOC51231>) 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) [2].
The GBD/FH3 domain 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 localization 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 localization 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 [2]. The GBD/FH3 domain is exclusively α-helical and is comprised of the N-terminal part of the GBD, an armadillo repeat region (ARR) and dimerization subdomains (see <PDB:1Z2C>) [3].
The profile we developed covers the entire GBD/FH3 domain.
Last update:August 2006 / First entry.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Petersen J. Nielsen O. Egel R. Hagan I.M. |
| Title | FH3, a domain found in formins, targets the fission yeast formin Fus1 to the projection tip during conjugation. | |
| Source | J. Cell Biol. 141:1217-1228(1998). | |
| PubMed ID | 9606213 |
| 2 | Authors | Rivero F. Muramoto T. Meyer A.-K. Urushihara H. Uyeda T.Q.P. Kitayama C. |
| Title | A comparative sequence analysis reveals a common GBD/FH3-FH1-FH2-DAD architecture in formins from Dictyostelium, fungi and metazoa. | |
| Source | BMC Genomics 6:28-28(2005). | |
| PubMed ID | 15740615 | |
| DOI | 10.1186/1471-2164-6-28 |
| 3 | Authors | Rose R. Weyand M. Lammers M. Ishizaki T. Ahmadian M.R. Wittinghofer A. |
| Title | Structural and mechanistic insights into the interaction between Rho and mammalian Dia. | |
| Source | Nature 435:513-518(2005). | |
| PubMed ID | 15864301 | |
| DOI | 10.1038/nature03604 |
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