In molecular biology, the FERM domain (F for 4.1 protein, E for ezrin, R for radixin and M for moesin) is a widespread protein module involved in localising to the plasma membrane.
Structure and function
Ezrin, moesin, and radixin are highly related proteins (ERM protein family), but the other proteins in which the FERM domain is found do not share any region of similarity outside of this domain. ERM proteins are made of three domains, the FERM domain, a central
Helix 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
cell 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
protein domains that masks their
for other
. For cytoskeleton-membrane cross-linking, 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 (RhoGDI), which suggests that in addition to functioning as a cross-linker, 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.
The N-terminal module is
ubiquitin-like. The C-terminal module is a
PH domain-like domain.
The FERM domain has also been called the amino-terminal domain, the 30kDa 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.
Examples
FERM domain containing proteins include:
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Band 4.1, which links the spectrin-actin cytoskeleton of to the plasma membrane.
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Ezrin, a component of the undercoat of the microvilli plasma membrane.
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Moesin, which is probably involved in binding major cytoskeleton to the plasma membrane.
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Radixin, which is involved in the binding of the barbed end of actin filaments to the plasma membrane in the undercoat of the cell-to-cell Adherens junction.
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Talin, a cytoskeletal protein concentrated in regions of cell-substratum contact and, in lymphocytes, of cell-cell contacts.
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Filopodin, a slime mould protein that binds actin and which is involved in the control of cell motility and chemotaxis.
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Merlin (or schwannomin).
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Protein NBL4.
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Unconventional X, Myosin VIIA and XV, which are mutation in congenital deafness.
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Focal-adhesion kinases (FAKs), protein tyrosine kinases involved in signalling through integrins.
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Janus tyrosine kinases (JAKs), cytoplasmic tyrosine that are non-covalently associated with the cytoplasmic tails of receptors for or polypeptidic hormones.
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Non-receptor tyrosine-protein kinase TYK2.
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Protein-tyrosine phosphatases PTPN3 and PTPN4, enzymes that appear to act at junctions between the membrane and the cytoskeleton.
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Protein-tyrosine phosphatases PTPN14 and PTP-D1, PTP-RL10 and PTP2E.
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Caenorhabditis elegans protein phosphatase ptp-1.
