Home  |  Contact
PROSITE documentation PDOC51232 [for PROSITE entry PS51232]

Rho GTPase-binding/formin homology 3 (GBD/FH3) domain profile





Description

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.

Technical section

PROSITE method (with tools and information) covered by this documentation:

GBD_FH3, PS51232; Rho GTPase-binding/formin homology 3 (GBD/FH3) domain profile  (MATRIX)


References

1AuthorsPetersen J. Nielsen O. Egel R. Hagan I.M.
TitleFH3, a domain found in formins, targets the fission yeast formin Fus1 to the projection tip during conjugation.
SourceJ. Cell Biol. 141:1217-1228(1998).
PubMed ID9606213

2AuthorsRivero F. Muramoto T. Meyer A.-K. Urushihara H. Uyeda T.Q.P. Kitayama C.
TitleA comparative sequence analysis reveals a common GBD/FH3-FH1-FH2-DAD architecture in formins from Dictyostelium, fungi and metazoa.
SourceBMC Genomics 6:28-28(2005).
PubMed ID15740615
DOI10.1186/1471-2164-6-28

3AuthorsRose R. Weyand M. Lammers M. Ishizaki T. Ahmadian M.R. Wittinghofer A.
TitleStructural and mechanistic insights into the interaction between Rho and mammalian Dia.
SourceNature 435:513-518(2005).
PubMed ID15864301
DOI10.1038/nature03604



PROSITE is copyright. It is produced by the SIB Swiss Institute Bioinformatics. There are no restrictions on its use by non-profit institutions as long as its content is in no way modified. Usage by and for commercial entities requires a license agreement. For information about the licensing scheme send an email to
Prosite License or see: prosite_license.html.

Miscellaneous

View entry in original PROSITE document format
View entry in raw text format (no links)