|PROSITE documentation PDOC00566 [for PROSITE entry PS00660]|
FERM domains (F for 4.1 protein, E for ezrin, R for radixin and M for moesin) are widespread protein modules of ~300 amino-acids in length that are involved in localizing proteins to the plasma membrane. They are found in a number of cytoskeletal-associated proteins that associate with various proteins at the interface between the plasma membrane and the cytoskeleton. The FERM domain is located at the N-terminus of the majority of FERM-containing proteins [1,2,3,4,5]. The FERM domain defines members of the band 4.1 superfamily, which includes :
Ezrin, moesin, and radixin are highly related proteins (ERM protein family), but the other proteins in which this domain is found do not share any region of similarity outside of the domain. ERM proteins are made of three domains, the FERM domain, a central helical domain and a C-terminal tail domain, which binds F-actin. The amino-acid sequence of the FERM domain is highly conserved among ERM proteins and is responsible for membrane association by direct binding to the cytoplasmic domain or tail of integral membrane proteins. ERM proteins are regulated by an intramolecular association of the FERM and C-terminal tail domains that masks their binding sites for other molecules. For cytoskeleton-membrane crosslinking, the dormant molecules becomes activated and the FERM domain attaches to the membrane by binding specific membrane proteins, while the last 34 residues of the tail bind actin filaments. Aside from binding to membranes, the activated FERM domain of ERM proteins can also bind the guanine nucleotide dissociation inhibitor of Rho GTPase (RhoDGI), which suggest that in addition to functioning as a crosslinker, ERM proteins may influence Rho signalling pathways. The crystal structure of the FERM domain reveals that it is composed of three structural modules (F1, F2, and F3) that together form a compact clover-shaped structure (see <PDB:1EF1>). F1 folds into an α+β structure with one long α-helix and a five-stranded mixed β-sheet. F2 is an all-α structure with four longer α-helices and one short helix. F3 consists of a sandwich of two orthogonal antiparallel β-sheets followed by a long helix [5,7].
The FERM domain has also been called the amino-terminal domain, the 30-kDa domain, 4.1N30, the membrane-cytoskeletal-linking domain, the ERM-like domain, the ezrin-like domain of the band 4.1 superfamily, the conserved N-terminal region, and the membrane attachment domain .
We have developed two signature patterns for this domain, one is based on the conserved positions found at the N-terminal extremity of the domain, the second is located in the C-terminal section.
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December 2004 / Pattern and text revised.
PROSITE methods (with tools and information) covered by this documentation:
|1||Authors||Rees D.J.G. Ades S.E. Singer S.J. Hynes R.O.|
|Title||Sequence and domain structure of talin.|
|2||Authors||Funayama N. Nagafuchi A. Sato N. Tsukita S. Tsukita S.|
|Title||Radixin is a novel member of the band 4.1 family.|
|Source||J. Cell Biol. 115:1039-1048(1991).|
|3||Authors||Takeuchi K. Kawashima A. Nagafuchi A. Tsukita S.|
|Title||Structural diversity of band 4.1 superfamily members.|
|Source||J. Cell Sci. 107:1921-1928(1994).|
|4||Authors||Chishti A.H. Kim A.C. Marfatia S.M. Lutchman M. Hanspal M. Jindal H. Liu S.-C. Low P.S. Rouleau G.A. Mohandas N. Chasis J.A. Conboy J.G. Gascard P. Takakuwa Y. Huang S.-C. Benz E.J. Jr. Bretscher A. Fehon R.G. Gusella J.F. Ramesh V. Solomon F. Marchesi V.T. Tsukita S. Tsukita S. Hoover K.B.|
|Title||The FERM domain: a unique module involved in the linkage of cytoplasmic proteins to the membrane.|
|Source||Trends Biochem. Sci. 23:281-282(1998).|
|5||Authors||Pearson M.A. Reczek D. Bretscher A. Karplus P.A.|
|Title||Structure of the ERM protein moesin reveals the FERM domain fold masked by an extended actin binding tail domain.|
|6||Authors||Girault J.-A. Labesse G. Mornon J.-P. Callebaut I.|
|Title||The N-termini of FAK and JAKs contain divergent band 4.1 domains.|
|Source||Trends Biochem. Sci. 24:54-57(1999).|
|7||Authors||Hamada K. Shimizu T. Matsui T. Tsukita S. Hakoshima T.|
|Title||Structural basis of the membrane-targeting and unmasking mechanisms of the radixin FERM domain.|
|Source||EMBO J. 19:4449-4462(2000).|