P26040
SS
Gene name |
Ezr (Vil2) |
Protein name |
Ezrin |
Names |
Cytovillin , Villin-2 , p81 |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:22350 |
EC number |
|
Protein Class |
|
Descriptions
MSN is a moesin protein and belongs to the ezrin-radixin-moesin (ERM) protein family, directly involved in the cytoskeleton-membrane crosslinking. Functional N-terminal FERM domain of ERM attaches to the membrane by binding specific membrane proteins while the last 34 residues of the C-terminal tail domain bind actin filaments. The autoinhibitory domain is positions at the C-terminal tail domain of ERM, where FERM domain of ERM is bound tightly via phosphotyrosine binding (PTB), pleckstrin homology (PH), and Enabled/VASP Homology 1 (EVH1) domains, thus masking the binding sites for other molecules. ERM is activated through phosphorylation at Thr558 weakening the FERM/tail binding and, unmasks the binding sites of membrane protein and actin filaments in the presence of phospholipids.
Autoinhibitory domains (AIDs)
Target domain |
5-295 (FERM domain) |
Relief mechanism |
PTM |
Assay |
|
Accessory elements
No accessory elements
References
- Yeon JH et al. (2016) "Systems-wide Identification of cis-Regulatory Elements in Proteins", Cell systems, 2, 89-100
- Pearson MA et al. (2000) "Structure of the ERM protein moesin reveals the FERM domain fold masked by an extended actin binding tail domain", Cell, 101, 259-70
- Austermann J et al. (2008) "Characterization of the Ca2+ -regulated ezrin-S100P interaction and its role in tumor cell migration", The Journal of biological chemistry, 283, 29331-40
- Liu J et al. (2014) "Conserved sequence repeats of IQGAP1 mediate binding to Ezrin", Journal of proteome research, 13, 1156-66
Autoinhibited structure
Activated structure
1 structures for P26040
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-P26040-F1 | Predicted | AlphaFoldDB |
31 variants for P26040
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs3389441368 | 78 | F>I | No | EVA | |
| rs3389441453 | 85 | Y>* | No | EVA | |
| rs3389422898 | 115 | I>F | No | EVA | |
| rs3389432191 | 118 | P>L | No | EVA | |
| rs3389447386 | 123 | V>L | No | EVA | |
| rs3389432700 | 159 | D>N | No | EVA | |
| rs3389432200 | 175 | W>C | No | EVA | |
| rs3389441372 | 201 | Y>F | No | EVA | |
| rs3389345517 | 243 | S>N | No | EVA | |
| rs3389437213 | 255 | F>C | No | EVA | |
| rs3389345481 | 269 | F>L | No | EVA | |
| rs3389430820 | 276 | I>F | No | EVA | |
| rs3389400440 | 304 | Q>H | No | EVA | |
| rs3389409790 | 309 | A>D | No | EVA | |
| rs3407371573 | 330 | R>Q | No | EVA | |
| rs3389391857 | 340 | M>V | No | EVA | |
| rs3389432147 | 342 | R>W | No | EVA | |
| rs214114099 | 363 | K>R | No | EVA | |
| rs3389421823 | 373 | L>P | No | EVA | |
| rs3389447408 | 402 | E>K | No | EVA | |
| rs3389430795 | 406 | Q>R | No | EVA | |
| rs3389430798 | 410 | Q>R | No | EVA | |
| rs3389345460 | 412 | K>* | No | EVA | |
| rs3389345460 | 412 | K>E | No | EVA | |
| rs3389345463 | 426 | A>D | No | EVA | |
| rs3389400402 | 448 | R>L | No | EVA | |
| rs3389432691 | 469 | A>V | No | EVA | |
| rs3406454923 | 491 | D>A | No | EVA | |
| rs3410540275 | 521 | A>T | No | EVA | |
| rs3389441415 | 566 | K>R | No | EVA | |
| rs3389432157 | 584 | E>* | No | EVA |
No associated diseases with P26040
10 regional properties for P26040
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | FERM domain | 5 - 295 | IPR000299 |
| domain | Ezrin/radixin/moesin, C-terminal | 511 - 586 | IPR011259 |
| domain | FERM, N-terminal | 9 - 68 | IPR018979 |
| domain | FERM, C-terminal PH-like domain | 210 - 299 | IPR018980 |
| conserved_site | FERM conserved site | 58 - 88 | IPR019747-1 |
| conserved_site | FERM conserved site | 176 - 205 | IPR019747-2 |
| domain | FERM central domain | 91 - 206 | IPR019748 |
| domain | Band 4.1 domain | 1 - 206 | IPR019749 |
| domain | ERM family, FERM domain C-lobe | 200 - 296 | IPR041789 |
| domain | Ezrin/radixin/moesin, alpha-helical domain | 337 - 456 | IPR046810 |
Functions
30 GO annotations of cellular component
| Name | Definition |
|---|---|
| actin cytoskeleton | The part of the cytoskeleton (the internal framework of a cell) composed of actin and associated proteins. Includes actin cytoskeleton-associated complexes. |
| actin filament | A filamentous structure formed of a two-stranded helical polymer of the protein actin and associated proteins. Actin filaments are a major component of the contractile apparatus of skeletal muscle and the microfilaments of the cytoskeleton of eukaryotic cells. The filaments, comprising polymerized globular actin molecules, appear as flexible structures with a diameter of 5-9 nm. They are organized into a variety of linear bundles, two-dimensional networks, and three dimensional gels. In the cytoskeleton they are most highly concentrated in the cortex of the cell just beneath the plasma membrane. |
| adherens junction | A cell-cell junction composed of the epithelial cadherin-catenin complex. The epithelial cadherins, or E-cadherins, of each interacting cell extend through the plasma membrane into the extracellular space and bind to each other. The E-cadherins bind to catenins on the cytoplasmic side of the membrane, where the E-cadherin-catenin complex binds to cytoskeletal components and regulatory and signaling molecules. |
| apical part of cell | The region of a polarized cell that forms a tip or is distal to a base. For example, in a polarized epithelial cell, the apical region has an exposed surface and lies opposite to the basal lamina that separates the epithelium from other tissue. |
| apical plasma membrane | The region of the plasma membrane located at the apical end of the cell. |
| astrocyte projection | A prolongation or process extending from the soma of an astrocyte and wrapping around neurons. |
| basolateral plasma membrane | The region of the plasma membrane that includes the basal end and sides of the cell. Often used in reference to animal polarized epithelial membranes, where the basal membrane is the part attached to the extracellular matrix, or in plant cells, where the basal membrane is defined with respect to the zygotic axis. |
| brush border | The dense covering of microvilli on the apical surface of an epithelial cell in tissues such as the intestine, kidney, and choroid plexus; the microvilli aid absorption by increasing the surface area of the cell. |
| cell body | The portion of a cell bearing surface projections such as axons, dendrites, cilia, or flagella that includes the nucleus, but excludes all cell projections. |
| cell cortex | The region of a cell that lies just beneath the plasma membrane and often, but not always, contains a network of actin filaments and associated proteins. |
| cell tip | The region at the end of the longest axis of a cylindrical or elongated cell. |
| ciliary basal body | A membrane-tethered, short cylindrical array of microtubules and associated proteins found at the base of a eukaryotic cilium (also called flagellum) that is similar in structure to a centriole and derives from it. The cilium basal body is the site of assembly and remodelling of the cilium and serves as a nucleation site for axoneme growth. As well as anchoring the cilium, it is thought to provide a selective gateway regulating the entry of ciliary proteins and vesicles by intraflagellar transport. |
| cytosol | The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. |
| endosome | A vacuole to which materials ingested by endocytosis are delivered. |
| fibrillar center | A structure found most metazoan nucleoli, but not usually found in lower eukaryotes; surrounded by the dense fibrillar component; the zone of transcription from multiple copies of the pre-rRNA genes is in the border region between these two structures. |
| filopodium | Thin, stiff, actin-based protrusion extended by the leading edge of a motile cell such as a crawling fibroblast or amoeba, or an axonal or dendritic growth cone, or a dendritic shaft. |
| focal adhesion | A cell-substrate junction that anchors the cell to the extracellular matrix and that forms a point of termination of actin filaments. In insects focal adhesion has also been referred to as hemi-adherens junction (HAJ). |
| immunological synapse | An area of close contact between a lymphocyte (T-, B-, or natural killer cell) and a target cell formed through the clustering of particular signaling and adhesion molecules and their associated membrane rafts on both the lymphocyte and the target cell and facilitating activation of the lymphocyte, transfer of membrane from the target cell to the lymphocyte, and in some situations killing of the target cell through release of secretory granules and/or death-pathway ligand-receptor interaction. |
| microspike | A dynamic, actin-rich projection extending from the surface of a migrating animal cell. |
| microvillus | Thin cylindrical membrane-covered projections on the surface of an animal cell containing a core bundle of actin filaments. Present in especially large numbers on the absorptive surface of intestinal cells. |
| microvillus membrane | The portion of the plasma membrane surrounding a microvillus. |
| myelin sheath | An electrically insulating fatty layer that surrounds the axons of many neurons. It is an outgrowth of glial cells |
| perinuclear region of cytoplasm | Cytoplasm situated near, or occurring around, the nucleus. |
| plasma membrane | The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. |
| plasma membrane raft | A membrane raft that is part of the plasma membrane. |
| protein-containing complex | A stable assembly of two or more macromolecules, i.e. proteins, nucleic acids, carbohydrates or lipids, in which at least one component is a protein and the constituent parts function together. |
| ruffle membrane | The portion of the plasma membrane surrounding a ruffle. |
| Schwann cell microvillus | Small finger-like extension of a Schwann cell that contacts the nodal membrane. |
| T-tubule | Invagination of the plasma membrane of a muscle cell that extends inward from the cell surface around each myofibril. The ends of T-tubules make contact with the sarcoplasmic reticulum membrane. |
| uropod | A membrane projection with related cytoskeletal components at the trailing edge of a cell in the process of migrating or being activated, found on the opposite side of the cell from the leading edge or immunological synapse, respectively. |
12 GO annotations of molecular function
| Name | Definition |
|---|---|
| actin binding | Binding to monomeric or multimeric forms of actin, including actin filaments. |
| actin filament binding | Binding to an actin filament, also known as F-actin, a helical filamentous polymer of globular G-actin subunits. |
| ATPase binding | Binding to an ATPase, any enzyme that catalyzes the hydrolysis of ATP. |
| cell adhesion molecule binding | Binding to a cell adhesion molecule. |
| disordered domain specific binding | Binding to a disordered domain of a protein. |
| identical protein binding | Binding to an identical protein or proteins. |
| microtubule binding | Binding to a microtubule, a filament composed of tubulin monomers. |
| protein domain specific binding | Binding to a specific domain of a protein. |
| protein kinase A catalytic subunit binding | Binding to one or both of the catalytic subunits of protein kinase A. |
| protein kinase A regulatory subunit binding | Binding to one or both of the regulatory subunits of protein kinase A. |
| protein-containing complex binding | Binding to a macromolecular complex. |
| S100 protein binding | Binding to a S100 protein. S100 is a small calcium and zinc binding protein produced in astrocytes that is implicated in Alzheimer's disease, Down Syndrome and ALS. |
33 GO annotations of biological process
| Name | Definition |
|---|---|
| actin filament bundle assembly | The assembly of actin filament bundles; actin filaments are on the same axis but may be oriented with the same or opposite polarities and may be packed with different levels of tightness. |
| astral microtubule organization | A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of astral microtubules, any of the spindle microtubules that radiate in all directions from the spindle poles. |
| cellular response to cAMP | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a cAMP (cyclic AMP, adenosine 3',5'-cyclophosphate) stimulus. |
| cortical microtubule organization | A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of structures formed of microtubules and associated proteins in the cell cortex, i.e. just beneath the plasma membrane of a cell. |
| establishment of centrosome localization | The directed movement of the centrosome to a specific location. |
| establishment of endothelial barrier | The establishment of a barrier between endothelial cell layers, such as those in the brain, lung or intestine, to exert specific and selective control over the passage of water and solutes, thus allowing formation and maintenance of compartments that differ in fluid and solute composition. |
| establishment or maintenance of apical/basal cell polarity | Any cellular process that results in the specification, formation or maintenance polarization of a cell's architecture along its apical/basal axis so that the apical and basal regions of the cell have different membrane, extracellular matrix and sub-membrane cellular components. |
| filopodium assembly | The assembly of a filopodium, a thin, stiff protrusion extended by the leading edge of a motile cell such as a crawling fibroblast or amoeba, or an axonal growth cone. |
| intestinal D-glucose absorption | Uptake of D-glucose into the blood by absorption from the small intestine. |
| leukocyte cell-cell adhesion | The attachment of a leukocyte to another cell via adhesion molecules. |
| membrane to membrane docking | The initial attachment of a membrane to a target membrane, mediated by proteins protruding from the two membranes. Docking requires only that the membranes come close enough for the proteins to interact and adhere. |
| negative regulation of ERK1 and ERK2 cascade | Any process that stops, prevents, or reduces the frequency, rate or extent of signal transduction mediated by the ERK1 and ERK2 cascade. |
| negative regulation of interleukin-2 production | Any process that stops, prevents, or reduces the frequency, rate, or extent of interleukin-2 production. |
| negative regulation of p38MAPK cascade | Any process that stops, prevents or reduces the frequency, rate or extent of p38MAPK cascade. |
| negative regulation of T cell receptor signaling pathway | Any process that stops, prevents, or reduces the frequency, rate or extent of signaling pathways initiated by the cross-linking of an antigen receptor on a T cell. |
| negative regulation of transcription by RNA polymerase II | Any process that stops, prevents, or reduces the frequency, rate or extent of transcription mediated by RNA polymerase II. |
| positive regulation of early endosome to late endosome transport | Any process that activates or increases the frequency, rate or extent of early endosome to late endosome transport. |
| positive regulation of gene expression | Any process that increases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA). |
| positive regulation of multicellular organism growth | Any process that activates or increases the frequency, rate or extent of growth of an organism to reach its usual body size. |
| positive regulation of protein catabolic process | Any process that activates or increases the frequency, rate or extent of the chemical reactions and pathways resulting in the breakdown of a protein by the destruction of the native, active configuration, with or without the hydrolysis of peptide bonds. |
| positive regulation of protein localization to early endosome | Any process that activates or increases the frequency, rate or extent of protein localization to early endosome. |
| positive regulation of protein localization to plasma membrane | Any process that activates or increases the frequency, rate or extent of protein localization to plasma membrane. |
| postsynaptic actin cytoskeleton organization | A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of cytoskeletal structures comprising actin filaments and their associated proteins in the postsynaptic actin cytoskeleton. |
| protein kinase A signaling | A series of reactions, mediated by the intracellular serine/threonine kinase protein kinase A, which occurs as a result of a single trigger reaction or compound. |
| protein localization to cell cortex | A process in which a protein is transported to, or maintained in, the cell cortex. |
| protein localization to plasma membrane | A process in which a protein is transported to, or maintained in, a specific location in the plasma membrane. |
| protein-containing complex localization | A localization process that acts on a protein complex; the complex is transported to, or maintained in, a specific location. |
| receptor internalization | A receptor-mediated endocytosis process that results in the movement of receptors from the plasma membrane to the inside of the cell. The process begins when cell surface receptors are monoubiquitinated following ligand-induced activation. Receptors are subsequently taken up into endocytic vesicles from where they are either targeted to the lysosome or vacuole for degradation or recycled back to the plasma membrane. |
| regulation of cell shape | Any process that modulates the surface configuration of a cell. |
| regulation of microvillus length | A process that modulates the length of a microvillus. |
| regulation of organelle assembly | Any process that modulates the frequency, rate or extent of organelle assembly. |
| sphingosine-1-phosphate receptor signaling pathway | A G protein-coupled receptor signaling pathway initiated by sphingosine-1-phosphate binding to its receptor on the surface of a cell, and ending with the regulation of a downstream cellular process, e.g. transcription. |
| terminal web assembly | The aggregation, arrangement and bonding together of a set of components to form a terminal web. |
21 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| P31976 | EZR | Ezrin | Bos taurus (Bovine) | PR |
| Q2HJ49 | MSN | Moesin | Bos taurus (Bovine) | PR |
| Q32LP2 | RDX | Radixin | Bos taurus (Bovine) | SS |
| Q9PU45 | RDX | Radixin | Gallus gallus (Chicken) | PR |
| Q24564 | Mer | Moesin/ezrin/radixin homolog 2 | Drosophila melanogaster (Fruit fly) | SS |
| P46150 | Moe | Moesin/ezrin/radixin homolog 1 | Drosophila melanogaster (Fruit fly) | SS |
| Q3KP66 | INAVA | Innate immunity activator protein | Homo sapiens (Human) | PR |
| P35240 | NF2 | Merlin | Homo sapiens (Human) | EV |
| P35241 | RDX | Radixin | Homo sapiens (Human) | SS |
| P15311 | EZR | Ezrin | Homo sapiens (Human) | EV |
| P26038 | MSN | Moesin | Homo sapiens (Human) | EV |
| A2AD83 | Frmd7 | FERM domain-containing protein 7 | Mus musculus (Mouse) | PR |
| P26041 | Msn | Moesin | Mus musculus (Mouse) | SS |
| P26043 | Rdx | Radixin | Mus musculus (Mouse) | SS |
| P46662 | Nf2 | Merlin | Mus musculus (Mouse) | SS |
| P26042 | MSN | Moesin | Sus scrofa (Pig) | PR |
| P26044 | RDX | Radixin | Sus scrofa (Pig) | SS |
| Q63648 | Nf2 | Merlin | Rattus norvegicus (Rat) | SS |
| O35763 | Msn | Moesin | Rattus norvegicus (Rat) | SS |
| P31977 | Ezr | Ezrin | Rattus norvegicus (Rat) | SS |
| Q6Q413 | nf2b | NF2, moesin-ezrin-radixin-like | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MPKPINVRVT | TMDAELEFAI | QPNTTGKQLF | DQVVKTIGLR | EVWYFGLQYV | DNKGFPTWLK |
| 70 | 80 | 90 | 100 | 110 | 120 |
| LDKKVSAQEV | RKENPVQFKF | RAKFYPEDVA | EELIQDITQK | LFFLQVKDGI | LSDEIYCPPE |
| 130 | 140 | 150 | 160 | 170 | 180 |
| TAVLLGSYAV | QAKFGDYNKE | MHKSGYLSSE | RLIPQRVMDQ | HKLSRDQWED | RIQVWHAEHR |
| 190 | 200 | 210 | 220 | 230 | 240 |
| GMLKDSAMLE | YLKIAQDLEM | YGINYFEIKN | KKGTDLWLGV | DALGLNIYEK | DDKLTPKIGF |
| 250 | 260 | 270 | 280 | 290 | 300 |
| PWSEIRNISF | NDKKFVIKPI | DKKAPDFVFY | APRLRINKRI | LQLCMGNHEL | YMRRRKPDTI |
| 310 | 320 | 330 | 340 | 350 | 360 |
| EVQQMKAQAR | EEKHQKQLER | QQLETEKKRR | ETVEREKEQM | LREKEELMLR | LQDYEQKTKR |
| 370 | 380 | 390 | 400 | 410 | 420 |
| AEKELSEQIE | KALQLEEERR | RAQEEAERLE | ADRMAALRAK | EELERQAQDQ | IKSQEQLAAE |
| 430 | 440 | 450 | 460 | 470 | 480 |
| LAEYTAKIAL | LEEARRRKED | EVEEWQHRAK | EAQDDLVKTK | EELHLVMTAP | PPPPPPVYEP |
| 490 | 500 | 510 | 520 | 530 | 540 |
| VNYHVQEGLQ | DEGAEPMGYS | AELSSEGILD | DRNEEKRITE | AEKNERVQRQ | LLTLSNELSQ |
| 550 | 560 | 570 | 580 | ||
| ARDENKRTHN | DIIHNENMRQ | GRDKYKTLRQ | IRQGNTKQRI | DEFEAM |