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127  structures 420  species 0  interactions 15327  sequences 297  architectures

Family: FERM_C (PF09380)

Summary: FERM C-terminal PH-like domain

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This is the Wikipedia entry entitled "FERM domain". More...

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
SymbolFERM_N
PfamPF09379
Pfam clanCL0072
InterProIPR018979
SCOPe1gc7 / SUPFAM
OPM superfamily49
OPM protein1gc6
Membranome161
FERM central domain
PDB 1gg3 EBI.jpg
crystal structure of the protein 4.1r membrane binding domain
Identifiers
SymbolFERM_M
PfamPF00373
InterProIPR019748
SCOPe1gc7 / SUPFAM
CDDcd14473
FERM C-terminal PH-like domain
PDB 2yvc EBI.jpg
crystal structure of the radixin ferm domain complexed with the nep cytoplasmic tail
Identifiers
SymbolFERM_C
PfamPF09380
Pfam clanCL0266
InterProIPR018980
SCOPe1ef1 / SUPFAM
CDDcd00836

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:

References

  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 C-terminal PH-like domain Provide feedback

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Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR018980

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 ].

This entry represents the PH-like domain found at the C terminus of the FERM domain.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Alignments

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 and the UniProtKB 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
(45)
Full
(15327)
Representative proteomes UniProt
(26584)
RP15
(1774)
RP35
(4844)
RP55
(13078)
RP75
(18240)
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PP/heatmap 1            

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

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  Seed
(45)
Full
(15327)
Representative proteomes UniProt
(26584)
RP15
(1774)
RP35
(4844)
RP55
(13078)
RP75
(18240)
Alignment:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(45)
Full
(15327)
Representative proteomes UniProt
(26584)
RP15
(1774)
RP35
(4844)
RP55
(13078)
RP75
(18240)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download  

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 View help on the curation process

Seed source: Pfam-B_851 (release 2.1)
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Bateman A
Number in seed: 45
Number in full: 15327
Average length of the domain: 90.70 aa
Average identity of full alignment: 30 %
Average coverage of the sequence by the domain: 10.44 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.5 20.5
Trusted cut-off 20.5 20.5
Noise cut-off 20.4 20.4
Model length: 94
Family (HMM) version: 12
Download: download the raw HMM for this family

Species distribution

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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_C domain has been found. There are 127 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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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A0G2K161 View 3D Structure Click here
A0A0G2K2N0 View 3D Structure Click here
A0A0R4IM03 View 3D Structure Click here
A0A0R4IPR0 View 3D Structure Click here
A0A140LI67 View 3D Structure Click here
A0A286Y8Y0 View 3D Structure Click here
A0A286YBL8 View 3D Structure Click here
A0A2R8QLR0 View 3D Structure Click here
A0A4V0IJV5 View 3D Structure Click here
A2A2Y4 View 3D Structure Click here
A2AD83 View 3D Structure Click here
A2ALK8 View 3D Structure Click here
A2CGB3 View 3D Structure Click here
A8JPC8 View 3D Structure Click here
A9JRC9 View 3D Structure Click here
B2RYE5 View 3D Structure Click here
B3DGL5 View 3D Structure Click here
B5DEZ0 View 3D Structure Click here
B8JJL6 View 3D Structure Click here
D3ZDI6 View 3D Structure Click here
D3ZFK8 View 3D Structure Click here
D3ZM69 View 3D Structure Click here
D3ZU85 View 3D Structure Click here
E7EY21 View 3D Structure Click here
E7F1C5 View 3D Structure Click here
E7FE33 View 3D Structure Click here
E7FEE9 View 3D Structure Click here
E9PT65 View 3D Structure Click here
E9QIC8 View 3D Structure Click here
F1LQQ5 View 3D Structure Click here
F1LT14 View 3D Structure Click here
F1LVM9 View 3D Structure Click here
F1LYQ8 View 3D Structure Click here
F1LZB7 View 3D Structure Click here
F1M1Y3 View 3D Structure Click here
F1Q8U6 View 3D Structure Click here
F1QBE0 View 3D Structure Click here
F1QFY3 View 3D Structure Click here
F1QLN8 View 3D Structure Click here
F1RAL6 View 3D Structure Click here
F1RD94 View 3D Structure Click here
F1REH1 View 3D Structure Click here
F6NJ58 View 3D Structure Click here
F8VPU2 View 3D Structure Click here
G3V6B9 View 3D Structure Click here
G3V9S3 View 3D Structure Click here
G5EBK3 View 3D Structure Click here
G5ECW4 View 3D Structure Click here
H2KYX3 View 3D Structure Click here
H2KYZ7 View 3D Structure Click here
H2KZV9 View 3D Structure Click here
H8W3Y2 View 3D Structure Click here
O17905 View 3D Structure Click here
O35763 View 3D Structure Click here
O43491 View 3D Structure Click here
O57457 View 3D Structure Click here
O70318 View 3D Structure Click here
O94887 View 3D Structure Click here
P11171 View 3D Structure Click here
P15311 View 3D Structure Click here
P26038 View 3D Structure Click here
P26040 View 3D Structure Click here
P26041 View 3D Structure Click here
P26043 View 3D Structure Click here
P26045 View 3D Structure Click here
P28191 View 3D Structure Click here
P29074 View 3D Structure Click here
P31977 View 3D Structure Click here
P35240 View 3D Structure Click here
P35241 View 3D Structure Click here
P46150 View 3D Structure Click here
P46662 View 3D Structure Click here
P48193 View 3D Structure Click here
P52963 View 3D Structure Click here
Q07436 View 3D Structure Click here
Q12923 View 3D Structure Click here
Q15678 View 3D Structure Click here
Q16825 View 3D Structure Click here
Q24564 View 3D Structure Click here
Q503E6 View 3D Structure Click here
Q5FVG2 View 3D Structure Click here
Q5TZG5 View 3D Structure Click here
Q62130 View 3D Structure Click here
Q62136 View 3D Structure Click here
Q62728 View 3D Structure Click here
Q63648 View 3D Structure Click here
Q64512 View 3D Structure Click here
Q66I42 View 3D Structure Click here
Q68DX3 View 3D Structure Click here
Q68EI5 View 3D Structure Click here
Q6P5H6 View 3D Structure Click here
Q6Q413 View 3D Structure Click here
Q6ZUT3 View 3D Structure Click here
Q7Z6J6 View 3D Structure Click here
Q8BGS1 View 3D Structure Click here
Q8BHD4 View 3D Structure Click here
Q8BIE6 View 3D Structure Click here
Q8BM54 View 3D Structure Click here
Q8C0V9 View 3D Structure Click here
Q8JG61 View 3D Structure Click here
Q8VII0 View 3D Structure Click here
Q8WY64 View 3D Structure Click here
Q91VS8 View 3D Structure Click here
Q920B0 View 3D Structure Click here
Q96NE9 View 3D Structure Click here
Q9H329 View 3D Structure Click here
Q9H4G0 View 3D Structure Click here
Q9HCM4 View 3D Structure Click here
Q9HCS5 View 3D Structure Click here
Q9JMB3 View 3D Structure Click here
Q9JMC8 View 3D Structure Click here
Q9P2Q2 View 3D Structure Click here
Q9V3V3 View 3D Structure Click here
Q9V8R9 View 3D Structure Click here
Q9VFU8 View 3D Structure Click here
Q9VKY7 View 3D Structure Click here
Q9W0R3 View 3D Structure Click here
Q9WTP0 View 3D Structure Click here
Q9WU22 View 3D Structure Click here
Q9WV92 View 3D Structure Click here
Q9XXK4 View 3D Structure Click here
Q9Y2J2 View 3D Structure Click here
Q9Y2L6 View 3D Structure Click here
Q9Y4F1 View 3D Structure Click here
Q9Z2H5 View 3D Structure Click here
R4GDY5 View 3D Structure Click here
U3JAK2 View 3D Structure Click here
X1WBG6 View 3D Structure Click here