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18  structures 162  species 0  interactions 862  sequences 40  architectures

Family: FERM_F2 (PF18377)

Summary: FERM F2 acyl-CoA binding protein-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 F2 acyl-CoA binding protein-like domain Provide feedback

This is an F2 lobe domain consisting of an acyl-CoA binding protein fold found in FERM region of Jak-family tyrosine kinases [1]. Multidomain JAK molecules interact with receptors through their FERM and SH2-like domains, triggering a series of phosphorylation events, resulting in the activation of their kinase domains [2]. Overall, the FERM region maintains the typical three-lobed architecture, with an F1 lobe consisting of a ubiquitin-like fold, an F2 lobe consisting of an acyl-CoA binding protein fold, and an F3 lobe consisting of a pleckstrin-homology (PH) fold. JAK1 FERM-F2 domain has been shown to act as the interaction site for the IFNLR1 box1 motif (PxxLxF) of class II cytokine receptors which is essential for kinase activation [3].

Literature references

  1. Zhang D, Wlodawer A, Lubkowski J;, J Mol Biol. 2016;428:4651-4668.: Crystal Structure of a Complex of the Intracellular Domain of Interferon lambda Receptor 1 (IFNLR1) and the FERM/SH2 Domains of Human JAK1. PUBMED:27725180 EPMC:27725180

  2. McNally R, Toms AV, Eck MJ;, PLoS One. 2016;11:e0156218.: Crystal Structure of the FERM-SH2 Module of Human Jak2. PUBMED:27227461 EPMC:27227461

  3. Ferrao R, Lupardus PJ;, Front Endocrinol (Lausanne). 2017;8:71.: The Janus Kinase (JAK) FERM and SH2 Domains: Bringing Specificity to JAK-Receptor Interactions. PUBMED:28458652 EPMC:28458652


Internal database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR041046

This is an F2 lobe domain consisting of an acyl-CoA binding protein fold found in FERM region of Jak-family tyrosine kinases [PUBMED:27725180]. Multidomain JAK molecules interact with receptors through their FERM and SH2-like domains, triggering a series of phosphorylation events, resulting in the activation of their kinase domains [PUBMED:27227461]. Overall, the FERM region maintains the typical three-lobed architecture, with an F1 lobe consisting of a ubiquitin-like fold, an F2 lobe consisting of an acyl-CoA binding protein fold, and an F3 lobe consisting of a pleckstrin-homology (PH) fold. JAK1 FERM-F2 domain has been shown to act as the interaction site for the IFNLR1 box1 motif (PxxLxF) of class II cytokine receptors which is essential for kinase activation [PUBMED:28458652].

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

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(49)
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(701)
RP75
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(26)
Full
(862)
Representative proteomes UniProt
(1602)
NCBI
(2323)
Meta
(0)
RP15
(49)
RP35
(218)
RP55
(701)
RP75
(1031)
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  Seed
(26)
Full
(862)
Representative proteomes UniProt
(1602)
NCBI
(2323)
Meta
(0)
RP15
(49)
RP35
(218)
RP55
(701)
RP75
(1031)
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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.

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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: ECOD:EUF05222
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: El-Gebali S
Number in seed: 26
Number in full: 862
Average length of the domain: 121.90 aa
Average identity of full alignment: 44 %
Average coverage of the sequence by the domain: 11.30 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 47079205 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 26.0 26.0
Trusted cut-off 26.1 26.0
Noise cut-off 25.9 25.7
Model length: 131
Family (HMM) version: 2
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_F2 domain has been found. There are 18 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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