Summary: FERM N-terminal domain
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FERM domain Edit Wikipedia article
| FERM N-terminal domain | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 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 | ||||||||
| SCOPe | 1gc7 / SUPFAM | ||||||||
| OPM superfamily | 49 | ||||||||
| OPM protein | 1gc6 | ||||||||
| Membranome | 161 | ||||||||
| |||||||||
| FERM central domain | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 crystal structure of the protein 4.1r membrane binding domain | |||||||||
| Identifiers | |||||||||
| Symbol | FERM_M | ||||||||
| Pfam | PF00373 | ||||||||
| InterPro | IPR019748 | ||||||||
| SCOPe | 1gc7 / SUPFAM | ||||||||
| CDD | cd14473 | ||||||||
| |||||||||
| FERM C-terminal PH-like domain | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 crystal structure of the radixin ferm domain complexed with the nep cytoplasmic tail | |||||||||
| Identifiers | |||||||||
| Symbol | FERM_C | ||||||||
| Pfam | PF09380 | ||||||||
| Pfam clan | CL0266 | ||||||||
| InterPro | IPR018980 | ||||||||
| SCOPe | 1ef1 / SUPFAM | ||||||||
| CDD | cd00836 | ||||||||
| |||||||||
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]
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 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]
Examples
FERM domain containing proteins include:
- 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 mould 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, enzymes 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.
References
- ^ 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.
- ^ 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.
- ^ 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.
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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
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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
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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
| SCOOP: | FERM_M |
| Similarity to PfamA using HHSearch: | TUG-UBL1 |
External database links
| SCOP: | 1gc7 |
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
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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Pfam Clan
This family is a member of clan Ubiquitin (CL0072), which has the following description:
This family includes proteins that share the ubiquitin fold. It currently unites four SCOP superfamilies.
The clan contains the following 76 members:
APG12 APG5 Atg8 AUX_IAA B1 BILBO1_N Blt1 Caps_synth_GfcC CHIPS CIDE-N Cobl CRIM DCX DIX DUF2407 DUF348 DUF4430 DWNN FERM_f0 FERM_N FERM_N_2 Flg_new Flg_new_2 Formin_GBD_N GABP-alpha IgG_binding_B Kindlin_2_N Lambda_tail_I Mub_B2 MucBP MucBP_2 Multi_ubiq NLE NQRA_SLBB Oxidored_molyb Par3_HAL_N_term PB1 Phenol_monoox PI3K_p85B PI3K_rbd Prok_Ub RA Rad60-SLD Rad60-SLD_2 Ras_bdg_2 RAWUL RBD SAP18 Sde2_N_Ubi SHIRT SLBB SSSPR-51 Staphylokinase TBK1_ULD TGS ThiS ThiS-like TmoB TUG-UBL1 Tugs Ub-Mut7C Ub-RnfH ubiquitin Ubiquitin_2 Ubiquitin_3 Ubiquitin_4 Ubiquitin_5 UBX Ufm1 ULD UN_NPL4 Urm1 USP7_C2 USP7_ICP0_bdg YchF-GTPase_C YukDAlignments
We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...
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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.
| Seed (22) |
Full (10539) |
Representative proteomes | UniProt (16677) |
NCBI (35694) |
Meta (1) |
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|---|---|---|---|---|---|---|---|---|---|
| RP15 (1269) |
RP35 (2882) |
RP55 (6581) |
RP75 (10702) |
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| HTML | |||||||||
| PP/heatmap | 1 | ||||||||
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
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| Seed (22) |
Full (10539) |
Representative proteomes | UniProt (16677) |
NCBI (35694) |
Meta (1) |
||||
|---|---|---|---|---|---|---|---|---|---|
| RP15 (1269) |
RP35 (2882) |
RP55 (6581) |
RP75 (10702) |
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| Raw Stockholm | |||||||||
| Gzipped | |||||||||
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
HMM logo
HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
Trees
This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
Note: You can also download the data file for the tree.
Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
Curation
| Seed source: | Bateman A |
| Previous IDs: | none |
| Type: | Domain |
| Sequence Ontology: | SO:0000417 |
| Author: |
Bateman A 
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| Number in seed: | 22 |
| Number in full: | 10539 |
| Average length of the domain: | 62.40 aa |
| Average identity of full alignment: | 35 % |
| Average coverage of the sequence by the domain: | 7.08 % |
HMM information
| HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 47079205 -E 1000 --cpu 4 HMM pfamseq
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| Model details: |
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| Model length: | 64 | ||||||||||||
| Family (HMM) version: | 11 | ||||||||||||
| Download: | download the raw HMM for this family |
Species distribution
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Interactions
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 70 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 sequence.
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