InterPro domain: IPR042201

Formin homology (FH) proteins play a crucial role in the reorganisation of the actin cytoskeleton, which mediates various functions of the cell cortex including motility, adhesion, and cytokinesis [ 1 ]. Formins are multidomain proteins that interact with diverse signalling molecules and cytoskeletal proteins, although some formins have been assigned functions within the nucleus. Formins are characterised by the presence of three FH domains (FH1, FH2 and FH3), although members of the formin family do not necessarily contain all three domains [ 2 ]. The proline-rich FH1 domain mediates interactions with a variety of proteins, including the actin-binding protein profilin, SH3 (Src homology 3) domain proteins, and WW domain proteins. The FH2 domain is required for the self-association of formin proteins through the ability of FH2 domains to directly bind each other [ 3 ], and may also act to inhibit actin polymerisation [ 4 ]. The FH3 domain ( IPR010472 ) is less well conserved and may be important for determining intracellular localisation of formin family proteins. In addition, some formins can contain a GTPase-binding domain (GBD) ( IPR010473 ) required for binding to Rho small GTPases, and a C-terminal conserved Dia-autoregulatory domain (DAD).

This superfamily represents the FH2 domain, which was shown by X-ray crystallography to have an elongated, crescent shape containing three helical subdomains [ 5 ].

1. Formin family proteins in cytoskeletal control. Biochem. Biophys. Res. Commun. 267, 479-81
2. ForC, a novel type of formin family protein lacking an FH1 domain, is involved in multicellular development in Dictyostelium discoideum. J. Cell. Sci. 116, 711-23
3. Fhos, a mammalian formin, directly binds to F-actin via a region N-terminal to the FH1 domain and forms a homotypic complex via the FH2 domain to promote actin fiber formation. J. Cell. Sci. 116, 4567-75
4. The core FH2 domain of diaphanous-related formins is an elongated actin binding protein that inhibits polymerization. Mol. Cell 13, 511-22
5. Crystal structures of a Formin Homology-2 domain reveal a tethered dimer architecture. Cell 116, 711-23