Ezrin (EZR)

The protein contains 586 amino acids for an estimated molecular weight of 69413 Da.

 

Probably involved in connections of major cytoskeletal structures to the plasma membrane. In epithelial cells, required for the formation of microvilli and membrane ruffles on the apical pole. Along with PLEKHG6, required for normal macropinocytosis. (updated: March 4, 2015)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  6. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  7. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.


Interpro domains
Total structural coverage: 97%
Model score: 0

(right-click above to access to more options from the contextual menu)

VariantDescription
dbSNP:rs3103004
dbSNP:rs2230143
empty

Biological Process

Actin cytoskeleton reorganization GO Logo
Actin filament bundle assembly GO Logo
Astral microtubule organization GO Logo
Axon guidance GO Logo
Cellular protein-containing complex localization GO Logo
Cellular response to cAMP GO Logo
Cortical microtubule organization GO Logo
Establishment of centrosome localization GO Logo
Establishment of endothelial barrier GO Logo
Establishment or maintenance of apical/basal cell polarity GO Logo
Filopodium assembly GO Logo
Intestinal D-glucose absorption GO Logo
Leukocyte cell-cell adhesion GO Logo
Membrane to membrane docking GO Logo
Microvillus assembly GO Logo
Negative regulation of ERK1 and ERK2 cascade GO Logo
Negative regulation of interleukin-2 production GO Logo
Negative regulation of interleukin-2 secretion GO Logo
Negative regulation of p38MAPK cascade GO Logo
Negative regulation of T cell receptor signaling pathway GO Logo
Negative regulation of transcription by RNA polymerase II GO Logo
Obsolete cytoskeletal anchoring at plasma membrane GO Logo
Phosphatidylinositol-mediated signaling GO Logo
Positive regulation of cellular protein catabolic process GO Logo
Positive regulation of early endosome to late endosome transport GO Logo
Positive regulation of gene expression GO Logo
Positive regulation of multicellular organism growth GO Logo
Positive regulation of protein localization to early endosome GO Logo
Positive regulation of protein localization to plasma membrane GO Logo
Positive regulation of protein secretion GO Logo
Protein kinase A signaling GO Logo
Protein localization to cell cortex GO Logo
Protein localization to plasma membrane GO Logo
Receptor internalization GO Logo
Regulation of cell shape GO Logo
Regulation of microvillus length GO Logo
Regulation of organelle assembly GO Logo
Sphingosine-1-phosphate receptor signaling pathway GO Logo
Terminal web assembly GO Logo

The reference OMIM entry for this protein is 123900

Ezrin; ezr
Villin 2; vil2
Cytovillin; cvil; cvl

DESCRIPTION

Cytovillin is a microvillar cytoplasmic peripheral membrane protein that is expressed strongly in placental syncytiotrophoblasts and in certain human tumors. It is the same as ezrin, a component of the microvilli of intestinal epithelial cells that serves as a major cytoplasmic substrate for certain protein-tyrosine kinases. Ezrin, radixin (RDX; 179410), and moesin (MSN; 309845), the so-called ERM proteins, act as linkers between the plasma membrane and the actin cytoskeleton. They are involved in a variety of cellular functions, such as cell adhesion, migration, and the organization of cell surface structures. They are highly homologous, both in protein structure and in functional activity, with merlin/schwannomin, the NF2 tumor suppressor protein (607379).

CLONING

Winqvist et al. (1989) cloned cytovillin cDNA from a human placental lambda gt11 library using affinity-purified antibodies. Gould et al. (1989) cloned and sequenced a human ezrin cDNA. The deduced protein sequence indicated that ezrin is a highly charged protein with an overall pI of 6.1 and a calculated molecular mass of 69,000. Using the cDNA clone to survey the distribution of the ezrin transcript, Pakkanen and Vaheri (1989) showed that purified cytovillin reacts with antibodies raised against ezrin. Gould et al. (1989) found the 3.2-kb ezrin mRNA in the same tissues that are known to express the protein and at the same relative levels. Highest expression was found in intestine, kidney, and lung. The cDNA clone hybridized to DNAs from widely divergent organisms, indicating that the sequence is highly conserved throughout evolution. Within its N-terminal domain, ezrin showed a high degree of similarity of amino acid sequence to the erythrocyte cytoskeletal protein band 4.1 (130500).

GENE FUNCTION

The immunologic synapse is the T cell-APC (antigen-presenting cell) contact site where T-cell receptors, coreceptors, signaling molecules, and adhesion receptors polarize upon antigen recognition. The formation of the immunologic synapse is thought to be important for receptor signal transduction and full T-lymphocyte activation. Using superantigen-stimulated Jurkat cells and confocal microscopy, Roumier et al. (2001) demonstrated that ezrin, F-actin (see ACTA1; 102610), and CD43 (182160) relocalize to the sides, not the center, of the T cell-APC contact area after T-cell activation, suggesting that ezrin may contribute to setting the scaffold between the actin cytoskeleton and transmembrane proteins facilitating cell-cell interactions and receptor retention. Using mouse helper T cell lines and confocal microscopy, Allenspach et al. (2001) determined that the cytoplasmic tail of CD43 is necessary and sufficient for CD43 removal from the immunologic synapse. In at least some cells, CD43 is located at the distal pole of the T cell together with ezrin and moesin. No differences in the behavior of ezrin and moesin were noted throughout the study. Using cells from Cd43 -/- mice, Allenspach et al. (2001) observed that ERM proteins move independently of the large CD43 mucin. Overexpression of a dominant-negative ERM mutant containing the N-terminal 320 amino acids of ezrin inhibited the activation-induced movement of CD43 without affecting conjugate formation. The dominant-negative mutant reduced cytokine production but not the expression of T-cell activation markers. Bonilha and Rodriguez-Boulan (2001) identified EBP50 (604990) and SAP97 (60 ... More on the omim web site

Subscribe to this protein entry history

May 12, 2019: Protein entry updated
Automatic update: model status changed

Nov. 17, 2018: Protein entry updated
Automatic update: model status changed

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

Oct. 27, 2017: Protein entry updated
Automatic update: model status changed

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 123900 was added.

Jan. 24, 2016: Protein entry updated
Automatic update: model status changed