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46  structures 200  species 3  interactions 3027  sequences 150  architectures

Family: FERM_N (PF09379)

Summary: FERM N-terminal domain

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FERM domain Edit Wikipedia article

FERM N-terminal domain
PDB 1h4r EBI.jpg
crystal structure of the ferm domain of merlin, the neurofibromatosis 2 tumor suppressor protein.
Identifiers
Symbol FERM_N
Pfam PF09379
Pfam clan CL0072
InterPro IPR018979
SCOP 1gc7
SUPERFAMILY 1gc7
FERM central domain
PDB 1gg3 EBI.jpg
crystal structure of the protein 4.1r membrane binding domain
Identifiers
Symbol FERM_M
Pfam PF00373
InterPro IPR019748
SCOP 1gc7
SUPERFAMILY 1gc7
FERM C-terminal PH-like domain
PDB 2yvc EBI.jpg
crystal structure of the radixin ferm domain complexed with the nep cytoplasmic tail
Identifiers
Symbol FERM_C
Pfam PF09380
Pfam clan CL0266
InterPro IPR018980
SCOP 1ef1
SUPERFAMILY 1ef1

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 proteins to the plasma membrane.[1] FERM domains 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 in the majority of proteins in which it is found.[1][2]

FERM domain containing proteins include:

  • Ezrin, a component of the undercoat of the microvilli plasma membrane.
  • Protein NBL4.
  • Non-receptor tyrosine-protein kinase TYK2.
  • Protein-tyrosine phosphatases PTPN14 and PTP-D1, PTP-RL10 and PTP2E.

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 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 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 (RhoDGI), 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.[3] The N-terminal module is ubiquitin-like. The C-terminal module is a PH-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.[1]

References[edit]

  1. ^ a b c Chishti AH, Kim AC, Marfatia SM, Lutchman M, Hanspal M, Jindal H, Liu SC, Low PS, Rouleau GA, Mohandas N, Chasis JA, Conboy JG, Gascard P, Takakuwa Y, Huang SC, Benz EJ, Bretscher A, Fehon RG, Gusella JF, Ramesh V, Solomon F, Marchesi VT, Tsukita S, Tsukita S, Hoover KB (August 1998). "The FERM domain: a unique module involved in the linkage of cytoplasmic proteins to the membrane". Trends Biochem. Sci. 23 (8): 281–2. doi:10.1016/S0968-0004(98)01237-7. PMID 9757824. 
  2. ^ Pearson MA, Reczek D, Bretscher A, Karplus PA (April 2000). "Structure of the ERM protein moesin reveals the FERM domain fold masked by an extended actin binding tail domain". Cell 101 (3): 259–70. doi:10.1016/S0092-8674(00)80836-3. PMID 10847681. 
  3. ^ Hamada K, Shimizu T, Matsui T, Tsukita S, Hakoshima T (September 2000). "Structural basis of the membrane-targeting and unmasking mechanisms of the radixin FERM domain". EMBO J. 19 (17): 4449–62. doi:10.1093/emboj/19.17.4449. PMC 302071. PMID 10970839. 

This article incorporates text from the public domain Pfam and InterPro IPR018980

This article incorporates text from the public domain Pfam and InterPro IPR019748

This article incorporates text from the public domain Pfam and InterPro IPR018979

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

FERM N-terminal domain Provide feedback

This domain is the N-terminal ubiquitin-like structural domain of the FERM domain.

Literature references

  1. Chishti AH, Kim AC, Marfatia SM, Lutchman M, Hanspal M, Jindal H, Liu SC, Low PS, Rouleau GA, Mohandas N, Chasis JA, Conboy JG, Gascard P, Takakuwa Y, Huang SC, Benz EJ Jr, Bretscher A, Fehon RG, Gusella JF, Ramesh V, Solomon F, Marchesi VT, Tsukita S, Ts, Trends Biochem Sci 1998;23:281-282.: The FERM domain: a unique module involved in the linkage of cytoplasmic proteins to the membrane. PUBMED:9757824 EPMC:9757824

  2. Girault JA, Labesse G, Mornon JP, Callebaut I; , Trends Biochem Sci 1999;24:54-57.: The N-termini of FAK and JAKs contain divergent band 4.1 domains. PUBMED:10098398 EPMC:10098398


Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR018979

This domain is the N-terminal ubiquitin-like structural domain of the FERM domain.

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 proteins to the plasma membrane [PUBMED:9757824]. FERM domains 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 [PUBMED:9757824, PUBMED:10847681], which includes:

  • Band 4.1, which links the spectrin-actin cytoskeleton of erythrocytes to the plasma membrane.
  • Ezrin, a component of the undercoat of the microvilli plasma membrane.
  • Moesin, which is probably involved in binding major cytoskeletal structures to the plasma membrane.
  • 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.
  • Talin, a cytoskeletal protein concentrated in regions of cell-substratum contact and, in lymphocytes, of cell-cell contacts.
  • Filopodin, a slime mold protein that binds actin and which is involved in the control of cell motility and chemotaxis.
  • Merlin (or schwannomin).
  • Protein NBL4.
  • Unconventional myosins X, VIIa and XV, which are mutated in congenital deafness.
  • Focal-adhesion kinases (FAKs), cytoplasmic protein tyrosine kinases involved in signalling through integrins.
  • Janus tyrosine kinases (JAKs), cytoplasmic tyrosine kinases that are non-covalently associated with the cytoplasmic tails of receptors for cytokines or polypeptidic hormones.
  • Non-receptor tyrosine-protein kinase TYK2.
  • Protein-tyrosine phosphatases PTPN3 and PTPN4, enzyme that appear to act at junctions between the membrane and the cytoskeleton.
  • Protein-tyrosine phosphatases PTPN14 and PTP-D1, PTP-RL10 and PTP2E.
  • Caenorhabditis elegans protein phosphatase ptp-1.

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 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 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 (RhoDGI), 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 [PUBMED:10970839].

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 [PUBMED:9757824].

Domain organisation

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Alignments

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Representative proteomes NCBI
(2604)
Meta
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RP15
(372)
RP35
(505)
RP55
(936)
RP75
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  Seed
(30)
Full
(3027)
Representative proteomes NCBI
(2604)
Meta
(2)
RP15
(372)
RP35
(505)
RP55
(936)
RP75
(1524)
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External links

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Curation and family details

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Curation View help on the curation process

Seed source: Bateman A
Previous IDs: none
Type: Domain
Author: Bateman A
Number in seed: 30
Number in full: 3027
Average length of the domain: 84.60 aa
Average identity of full alignment: 27 %
Average coverage of the sequence by the domain: 9.05 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.1 21.1
Trusted cut-off 21.1 21.1
Noise cut-off 21.0 21.0
Model length: 80
Family (HMM) version: 5
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Species distribution

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Interactions

There are 3 interactions for this family. More...

FERM_N FERM_C FERM_M

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the FERM_N domain has been found. There are 46 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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