FERM Protein Domain

The FERM domain of mouse Radixin bound to Ins(1,4,5)P₃ (red).

Domain Binding and Function

Previously known as the B4.1 (band 4.1) homology and ERM domain, the FERM domain is named for the four proteins from which this domain was originally described: Band 4.1 (F), Ezrin (E), Radixin (R), and Moesin (M). The FERM domain is approximately 150 amino acids in length and is found in a number of cytoskeletal-associated proteins that are localized to the plasma membrane and cytoskeleton interface. The FERM domain is responsible for the PIP₂ regulated binding of ERM (Ezrin/Radixin/Moesin) proteins to the membrane, which associates the cytoskeleton with the membrane by linking actin filaments to adhesion proteins. The FERM domain containing adaptor protein Merlin has been shown to act as a tumour suppressor. FERM domains contain three lobes, with the N-terminal lobe resembling ubiquitin, the central lobe resembling acyl-CoA binding proteins and the C-terminal lobe having a structure similar to that of PTB domains. The structure of the Radixin FERM domain bound to IP₃ has been solved; phosphoinositide binding is not mediated by the PH-fold subdomain of FERM but occurs at a cleft between two subdomains on a relatively flat face of the module. The FERM domain is also thought to bind to adhesion proteins in a PIP₂-regulated fashion to provide a link between cytoskeletal signals and membrane dynamics.

Structure Reference

1. Hamada, K. et al. (2000) EMBO J. 19(17), 4449–4462.

Examples of Domain Proteins

Binding Examples