 FERM Domain | |
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| Class:Phospholipid binding | |
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Structure:
The crystal structure of the radaxin FERM domain shows that the FERM domain consists of three subdomains that interact with one another to form a single module. Subdomain A (residues 1-82) contains one long helix and a five-stranded β-sheet. It resembles a typical ubiquitin fold; however, it has no sequence identity to this fold in other proteins and lacks a short helix between α1-β3 in the ubiquitin loop. Subdomain B (residues 96-195) is composed of four longer α-helices and one shorter helix. Subdomain B is tethered to subdomain A by a 13 residue linker helix and is classified as an acyl-coenzyme A binding protein-like fold. Subdomain C (residues 204-297) consists of a seven-stranded β-sandwich core and a single α-helix. Subdomain C is tethered to subdomain B by an eight-residue linker and is structurally similar to the PTB domain.
Structure Reference:
Hamada, K. et al. (2000) EMBO J. 19(17): 4449-4462. PDB: 1GC6.
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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 in which this domain was originally described: F for Band 4.1, E for Ezrin, R for Radixin, M for Moesin. The FERM domain is approximately 300 amino acids in length and is found in a number of cytoskeletal-associated proteins that are found at the interface between the plasma membrane and the cytoskeleton. The FERM domain is responsible for PIP2 regulated membrane binding of ERM (Ezrin/Radixin/Moesin) proteins that play a role in formation of membrane-associated cytoskeleton by linking actin filaments to adhesion proteins. Merlin, a FERM domain containing adaptor protein has been shown to act as a tumour suppressor. FERM domains contain three lobes with the most N-terminal lobe resembling ubiquitin, the central lobe resembling acyl-CoA binding proteins and the most C-terminal lobe having a related structure to PTB domains. The structure of the Radixin FERM domain bound to IP3 has been solved and, surprisingly, 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 postulated to bind to adhesion proteins, in a PIP2 -regulated fashion, providing a link between cytoskeletal signals and membrane dynamics.
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Examples of Proteins:
| FERM domain protein |
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Binding partner |
Talin
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integrin β subunits2
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| Radixin |  |
IP3, PI(4,5)P2
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| ERM | |
PI(4,5)P2
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Willin
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PI(3)P, PI(4)P, PI(5)P
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Moesin
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PI(3)P, PI(4)P, PI(5)P
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PTLP1
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PI(4,5)P2
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Radixin
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PI(1,4,5)P3
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Referenced in part on Cell Signaling Technology Website, Reference Section on Protein Domains. We gratefully acknowledge the following contributors:
Piers Nash1, Dan Lin3, Kathleen Binns2, Clark Wells2, Rob Ingham2, Terry Kubiseski2, Bernard Liu1, Matt Smith2,3, Ivan Blasutig2,3, Maria Sierra1, Caesar Lim2,3, Michael Arc1, Jim Fawcett2 and Tony Pawson2,3.
1. Ben May Institute for Cancer Research, The University of Chicago, Chicago, Illinois, 60637, USA
2. Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, M5G 1X5, Canada
3. Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, M5S 1A8, Canada
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