Summary: Ezrin/radixin/moesin family
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This is the Wikipedia entry entitled "ERM protein family". More...
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ERM protein family Edit Wikipedia article
The ERM protein family consists of three closely related proteins, ezrin, radixin and moesin. The three paralogs, ezrin, radixin and moesin, are present in vertebrates, whereas other species have only one ERM gene. Therefore, in vertebrates these paralogs likely arose by gene duplication.
ERM proteins are highly conserved throughout evolution . More than 75% identity is observed in the N-terminal and the C-terminal of vertebrates (ezrin, radixin, moesin), Drosophila (dmoesin) and C. elegans (ERM-1) homologs.
- N-terminal globular domain, also called FERM domain (Band 4.1, ezrin, radixin, moesin). The FERM domain allows ERM proteins to interact with integral proteins of the plasma membrane, or scaffolding proteins localized beneath the plasma membrane. The FERM domain is composed of three subdomains (F1, F2, F3) that are arranged as a cloverleaf.
- extended alpha-helical domain.
- charged C-terminal domain. This domain mediates the interaction with F-actin.
ERM proteins crosslink actin filaments with plasma membranes. They co-localize with CD44 at actin filament-plasma membrane interaction sites, associating with CD44 via their N-terminal domains and with actin filaments via their C-terminal domains.
ERM proteins Moesin directly binds to microtubules via its N-terminal FERM domain in vitro and stabilizes microtubules at the cell cortex in vivo. This interaction is required for specific ERM-dependent functions in mitosis.
- the FERM domain is able to interact with the F-actin binding site and this head-to-tail interaction maintains ERM proteins into a folded form; in this state, ERM proteins are inactive for the folding prevents either integral protein binding, or actin-binding.
- if this head-to-tail interaction is disrupted, ERM proteins unfold, leading to an open and active conformation.
In culture cells, ERM proteins mainly exhibit the folded conformation (about 80-85%).
The current model for ERM proteins activation is a two-steps mechanism:
- First, phosphatidylinositol 4,5-bisphosphate interaction at the plasma membrane induces a pre-opening of ERM molecule
- Then, a not yet identified kinase phosphorylates a Threonine localized in a highly conserved region of the C-terminal domain. The phosphate will stabilize the opening of the molecule.
- PDB 1E5W; Edwards SD, Keep NH (June 2001). "The 2.7 Ã… crystal structure of the activated FERM domain of moesin: an analysis of structural changes on activation". Biochemistry 40 (24): 7061â€“8. doi:10.1021/bi010419h. PMID 11401550.
- Bretscher A (August 1983). "Purification of an 80,000-dalton protein that is a component of the isolated microvillus cytoskeleton, and its localization in nonmuscle cells". J. Cell Biol. 97 (2): 425â€“32. doi:10.1083/jcb.97.2.425. PMC 2112519. PMID 6885906.
- Tsukita S, Hieda Y, Tsukita S (June 1989). "A new 82-kD barbed end-capping protein (radixin) localized in the cell- to-cell adherens junction: purification and characterization". J. Cell Biol. 108 (6): 2369â€“82. doi:10.1083/jcb.108.6.2369. PMC 2115614. PMID 2500445.
- Lankes W, Griesmacher A, GrÃ¼nwald J, Schwartz-Albiez R, Keller R (May 1988). "A heparin-binding protein involved in inhibition of smooth-muscle cell proliferation". Biochem. J. 251 (3): 831â€“42. PMC 1149078. PMID 3046603.
- Tsukita S, Yonemura S, Tsukita S (February 1997). "ERM proteins: head-to-tail regulation of actin-plasma membrane interaction". Trends Biochem. Sci. 22 (2): 53â€“8. doi:10.1016/S0968-0004(96)10071-2. PMID 9048483.
- Bretscher A, Edwards K, Fehon RG (August 2002). "ERM proteins and merlin: integrators at the cell cortex". Nat Rev Mol Cell Biol. 8 (8): 586â€“99. doi:10.1038/nrm882. PMID 12154370.
- FiÃ©vet B, Louvard D, Arpin M (May 2007). "ERM proteins in epithelial cell organization and functions". Biochim Biophys Acta. 1773 (5): 653â€“60. doi:10.1016/j.bbamcr.2006.06.013. PMID 16904765.
- Yonemura S, Hirao M, Doi Y, Takahashi N, Kondo T, Tsukita S, Tsukita S (February 1998). "Ezrin/Radixin/Moesin (ERM) Proteins Bind to a Positively Charged Amino Acid Cluster in the Juxta-Membrane Cytoplasmic Domain of CD44, CD43, and ICAM-2". J. Cell Biol. 140 (4): 885â€“95. doi:10.1083/jcb.140.4.885. PMC 2141743. PMID 9472040.
- Solinet S, Mahmud K, Stewman SF, Ben El Kadhi K, Decelle B, Talje L, Ma A, Kwok BH, Carreno S (July 2013). "The actin-binding ERM protein Moesin binds to and stabilizes microtubules at the cell cortex". J. Cell Biol. 202 (2): 251â€“60. doi:10.1083/jcb.201304052. PMID 23857773.
- Gautreau A, Louvard D, Arpin M (July 2000). "Morphogenic Effects of Ezrin Require a Phosphorylation-Induced Transition from Oligomers to Monomers at the Plasma Membrane". J Cell Biol. 150 (1): 193â€“203. doi:10.1083/jcb.150.1.193. PMC 2185562. PMID 10893267.
- Fievet BT, Gautreau A, Roy C, Del Maestro L, Mangeat P, Louvard D, Arpin M (March 2004). "Phosphoinositide binding and phosphorylation act sequentially in the activation mechanism of ezrin". J Cell Biol. 164 (5): 653â€“9. doi:10.1083/jcb.200307032. PMC 2172172. PMID 14993232.
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.
Ezrin/radixin/moesin family Provide feedback
This family of proteins contain a band 4.1 domain (PF00373), at their amino terminus. This family represents the rest of these proteins.
Yonemura S, Hirao M, Doi Y, Takahashi N, Kondo T, Tsukita S; , J Cell Biol 1998;140:885-895.: Ezrin/radixin/moesin (ERM) proteins bind to a positively charged amino acid cluster in the juxta-membrane cytoplasmic domain of CD44, CD43, and ICAM-2. PUBMED:9472040 EPMC:9472040
Internal database links
|SCOOP:||Phage_mat-A MAD USP8_interact DUF3166 DUF4200 DUF4686|
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR011259The ERM family consists of three closely-related proteins, ezrin, radixin and moesin [PUBMED:9048483]. Ezrin was first identified as a constituent of microvilli [PUBMED:6885906], radixin as a barbed, end-capping actin-modulating protein from isolated junctional fractions [PUBMED:2500445], and moesin as a heparin binding protein [PUBMED:3046603]. A tumour suppressor molecule responsible for neurofibromatosis type 2 (NF2) is highly similar to ERM proteins and has been designated merlin (moesin-ezrin-radixin-like protein). ERM molecules contain 3 domains, an N-terminal globular domain; an extended alpha-helical domain; and a charged C-terminal domain [PUBMED:9048483]. Ezrin, radixin and merlin also contain a polyproline region between the helical and C-terminal domains. The N-terminal domain is highly conserved, and is also found in merlin, band 4.1 proteins and members of the band 4.1 superfamily. ERM proteins crosslink actin filaments with plasma membranes. They co-localise with CD44 at actin filament-plasma membrane interaction sites, associating with CD44 via their N-terminal domains and with actin filaments via their C-terminal domains [PUBMED:9048483].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Cellular component||extrinsic component of membrane (GO:0019898)|
|Molecular function||cytoskeletal protein binding (GO:0008092)|
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
The graphic that is shown by default represents the longest sequence with a given architecture. Each row contains the following information:
- the number of sequences which exhibit this architecture
a textual description of the architecture, e.g. Gla, EGF x 2, Trypsin.
This example describes an architecture with one
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EGFdomains, and finally a single
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Note that you can see the family page for a particular domain by clicking on the graphic. You can also choose to see all sequences which have a given architecture by clicking on the Show link in each row.
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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 using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...
There are various ways to view or download the sequence alignments that we store. We provide several sequence viewers and a plain-text Stockholm-format file for download.
We make a range of alignments for each Pfam-A family:
- the curated alignment from which the HMM for the family is built
- the alignment generated by searching the sequence database using the HMM
- Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
- alignment generated by searching the NCBI sequence database using the family HMM
- alignment generated by searching the metagenomics sequence database using the family HMM
You can see the alignments as HTML or in three different sequence viewers:
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You can download (or view in your browser) a text representation of a Pfam alignment in various formats:
You can also change the order in which sequences are listed in the alignment, change how insertions are represented, alter the characters that are used to represent gaps in sequences and, finally, choose whether to download the alignment or to view it in your browser directly.
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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.
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
Format an alignment
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.
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.
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...
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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.
|Seed source:||Pfam-B_851 (release 2.1)|
|Number in seed:||72|
|Number in full:||729|
|Average length of the domain:||227.80 aa|
|Average identity of full alignment:||33 %|
|Average coverage of the sequence by the domain:||43.21 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 80369284 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||15|
|Download:||download the raw HMM for this family|
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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the More....
This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.
How the sunburst is generated
The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.
In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:
Colouring and labels
Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.
As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.
Anomalies in the taxonomy tree
There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.
Missing taxonomic levels
Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.
Unmapped species names
The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".
Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.
Too many species/sequences
For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.
The tree shows the occurrence of this domain across different species. More...
We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.
Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.
If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.
For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.
Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.
We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.
You can use the tree controls to manipulate how the interactive tree is displayed:
- show/hide the summary boxes
- highlight species that are represented in the seed alignment
- expand/collapse the tree or expand it to a given depth
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Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.
There are 5 interactions for this family. More...
We determine these interactions using iPfam, which considers the interactions between residues in three-dimensional protein structures and maps those interactions back to Pfam families. You can find more information about the iPfam algorithm in the journal article that accompanies the website.
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 ERM domain has been found. There are 5 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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