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224  structures 636  species 0  interactions 24089  sequences 695  architectures

Family: FERM_M (PF00373)

Summary: FERM central domain

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

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 central domain Provide feedback

This domain is the central 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 IPR019748

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 FERM_M (CL0632), which has the following description:

The clan contains the following 4 members:

ACBP FERM_F1 FERM_F2 FERM_M

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
(54)
Full
(24089)
Representative proteomes UniProt
(42020)
RP15
(3031)
RP35
(8156)
RP55
(20832)
RP75
(28581)
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

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  Seed
(54)
Full
(24089)
Representative proteomes UniProt
(42020)
RP15
(3031)
RP35
(8156)
RP55
(20832)
RP75
(28581)
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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
(54)
Full
(24089)
Representative proteomes UniProt
(42020)
RP15
(3031)
RP35
(8156)
RP55
(20832)
RP75
(28581)
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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: Bateman A
Previous IDs: Band_41;
Type: Domain
Sequence Ontology: SO:0000417
Author: Bateman A
Number in seed: 54
Number in full: 24089
Average length of the domain: 127.20 aa
Average identity of full alignment: 24 %
Average coverage of the sequence by the domain: 12.32 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null --hand HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 23.8 23.8
Trusted cut-off 23.8 23.8
Noise cut-off 23.7 23.7
Model length: 127
Family (HMM) version: 20
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_M domain has been found. There are 224 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
A0A0A1EI90 View 3D Structure Click here
A0A0A1EI90 View 3D Structure Click here
A0A0G2JWC7 View 3D Structure Click here
A0A0G2K161 View 3D Structure Click here
A0A0G2K246 View 3D Structure Click here
A0A0G2K2N0 View 3D Structure Click here
A0A0R4ICT0 View 3D Structure Click here
A0A0R4IDZ8 View 3D Structure Click here
A0A0R4IIA7 View 3D Structure Click here
A0A0R4IM03 View 3D Structure Click here
A0A0R4IPR0 View 3D Structure Click here
A0A140LI67 View 3D Structure Click here
A0A140LIW3 View 3D Structure Click here
A0A1D6DUH0 View 3D Structure Click here
A0A1D6JHE8 View 3D Structure Click here
A0A286Y8Y0 View 3D Structure Click here
A0A286Y9F5 View 3D Structure Click here
A0A286Y9F5 View 3D Structure Click here
A0A286YBL8 View 3D Structure Click here
A0A2R8Q3R0 View 3D Structure Click here
A0A2R8Q5W7 View 3D Structure Click here
A0A2R8QFL6 View 3D Structure Click here
A0A2R8QG39 View 3D Structure Click here
A0A2R8QLR0 View 3D Structure Click here
A0A2R8QRQ3 View 3D Structure Click here
A0A2R8QUR4 View 3D Structure Click here
A0A2R8RR02 View 3D Structure Click here
A0A4V0IJV5 View 3D Structure Click here
A2A2Y4 View 3D Structure Click here
A2AD83 View 3D Structure Click here
A2AFR3 View 3D Structure Click here
A2AKB4 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
B0S541 View 3D Structure Click here
B2GVB9 View 3D Structure Click here
B2RYE5 View 3D Structure Click here
B3DGL5 View 3D Structure Click here
B8JJL6 View 3D Structure Click here
D3ZA84 View 3D Structure Click here
D3ZDI6 View 3D Structure Click here
D3ZFK8 View 3D Structure Click here
D3ZJP6 View 3D Structure Click here
D3ZM69 View 3D Structure Click here
D3ZR47 View 3D Structure Click here
D3ZTV0 View 3D Structure Click here
D3ZUF0 View 3D Structure Click here
D3ZW88 View 3D Structure Click here
D4A3K7 View 3D Structure Click here
D4AA54 View 3D Structure Click here
E7EY21 View 3D Structure Click here
E7F106 View 3D Structure Click here
E7F1C5 View 3D Structure Click here
E7F221 View 3D Structure Click here
E7F448 View 3D Structure Click here
E7FE33 View 3D Structure Click here
E7FEE9 View 3D Structure Click here
E7FEY8 View 3D Structure Click here
E9PT65 View 3D Structure Click here
E9QBZ4 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
F1M885 View 3D Structure Click here
F1Q6B3 View 3D Structure Click here
F1Q777 View 3D Structure Click here
F1Q823 View 3D Structure Click here
F1Q8U6 View 3D Structure Click here
F1Q8X5 View 3D Structure Click here
F1QBE0 View 3D Structure Click here
F1QFY3 View 3D Structure Click here
F1QKJ4 View 3D Structure Click here
F1QLL2 View 3D Structure Click here
F1QLN8 View 3D Structure Click here
F1QPN5 View 3D Structure Click here
F1QXP3 View 3D Structure Click here
F1QYX1 View 3D Structure Click here
F1R8Z1 View 3D Structure Click here
F1RAL6 View 3D Structure Click here
F1REH1 View 3D Structure Click here
F1REV3 View 3D Structure Click here
F6NJ58 View 3D Structure Click here
F6NJM7 View 3D Structure Click here
F8VPU2 View 3D Structure Click here
F8VQB6 View 3D Structure Click here
G3V6B9 View 3D Structure Click here
G3V852 View 3D Structure Click here
G3V8Z6 View 3D Structure Click here
G3V9S3 View 3D Structure Click here
G5EBK3 View 3D Structure Click here
G5ECW4 View 3D Structure Click here
G5ED24 View 3D Structure Click here
G5EGK1 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
I1J891 View 3D Structure Click here
I1L4M5 View 3D Structure Click here
I1LIE8 View 3D Structure Click here
I1MMS6 View 3D Structure Click here
I3ITL5 View 3D Structure Click here
I3ITQ9 View 3D Structure Click here
K7DYJ3 View 3D Structure Click here
O00522 View 3D Structure Click here
O17905 View 3D Structure Click here
O35346 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
P0CD60 View 3D Structure Click here
P0CE94 View 3D Structure Click here
P11171 View 3D Structure Click here
P15311 View 3D Structure Click here
P26038 View 3D Structure Click here
P26039 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
P34152 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
P59113 View 3D Structure Click here
P70600 View 3D Structure Click here
P91443 View 3D Structure Click here
P97479 View 3D Structure Click here
Q00IB7 View 3D Structure Click here
Q05397 View 3D Structure Click here
Q05AK5 View 3D Structure Click here
Q07436 View 3D Structure Click here
Q12923 View 3D Structure Click here
Q13402 View 3D Structure Click here
Q14289 View 3D Structure Click here
Q14CM0 View 3D Structure Click here
Q15678 View 3D Structure Click here
Q16825 View 3D Structure Click here
Q18685 View 3D Structure Click here
Q24564 View 3D Structure Click here
Q3B7L1 View 3D Structure Click here
Q3UFK8 View 3D Structure Click here
Q4CNN5 View 3D Structure Click here
Q4CR63 View 3D Structure Click here
Q4CSR2 View 3D Structure Click here
Q4CX93 View 3D Structure Click here
Q503E6 View 3D Structure Click here
Q54EW0 View 3D Structure Click here
Q54EW0 View 3D Structure Click here
Q54K81 View 3D Structure Click here
Q55E74 View 3D Structure Click here
Q5FVG2 View 3D Structure Click here
Q5JV73 View 3D Structure Click here
Q5SYB0 View 3D Structure Click here
Q5TZG5 View 3D Structure Click here
Q5U2R3 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
Q6PIF6 View 3D Structure Click here
Q6Q413 View 3D Structure Click here
Q6S5J6 View 3D Structure Click here
Q6TEM9 View 3D Structure Click here
Q6ZUT3 View 3D Structure Click here
Q71LX4 View 3D Structure Click here
Q7T2P8 View 3D Structure Click here
Q7XPJ0 View 3D Structure Click here
Q7Z6J6 View 3D Structure Click here
Q7Z736 View 3D Structure Click here
Q80TI1 View 3D Structure Click here
Q86UX7 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
Q8C115 View 3D Structure Click here
Q8CIB5 View 3D Structure Click here
Q8CJE3 View 3D Structure Click here
Q8IVE3 View 3D Structure Click here
Q8JG61 View 3D Structure Click here
Q8K1B8 View 3D Structure Click here
Q8MXF0 View 3D Structure Click here
Q8N878 View 3D Structure Click here
Q8VCE9 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
Q96AC1 View 3D Structure Click here
Q96NE9 View 3D Structure Click here
Q99MZ6 View 3D Structure Click here
Q9BQL6 View 3D Structure Click here
Q9BZ67 View 3D Structure Click here
Q9BZ68 View 3D Structure Click here
Q9FHN8 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
Q9HD67 View 3D Structure Click here
Q9JMB3 View 3D Structure Click here
Q9JMC8 View 3D Structure Click here
Q9P2Q2 View 3D Structure Click here
Q9QVP9 View 3D Structure Click here
Q9ULM0 View 3D Structure Click here
Q9V3V3 View 3D Structure Click here
Q9V3Z6 View 3D Structure Click here
Q9V8R9 View 3D Structure Click here
Q9VBX0 View 3D Structure Click here
Q9VFD3 View 3D Structure Click here
Q9VFU8 View 3D Structure Click here
Q9VKY7 View 3D Structure Click here
Q9VVD2 View 3D Structure Click here
Q9VZI3 View 3D Structure Click here
Q9W0R3 View 3D Structure Click here
Q9W5D0 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
Q9Y490 View 3D Structure Click here
Q9Y4F1 View 3D Structure Click here
Q9Y4G6 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