Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol EZR contributors: mct - updated : 30-03-2020
HGNC name ezrin
HGNC id 12691
Location 6q25.3      Physical location : 159.186.773 - 159.240.456
Synonym name
  • cytovillin 2
  • villin 2 (ezrin)
  • epididymis secretory protein Li 105
  • Synonym symbol(s) CVIL, CVL, FLJ26216, MGC1584, VIL2, p81, DKFZp762H157
    DNA
    TYPE functioning gene
    STRUCTURE 53.68 kb     13 Exon(s)
    MAPPING cloned Y linked N status confirmed
    Map cen - D6S442 - D6S1581 - SOD2 - EZR - D6S1579 - D6S281 - qter
    RNA
    TRANSCRIPTS type messenger
    text variants 1 and 2 encode the same protein
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    14 - 3138 69 586 - 2019 30804430
    13 - 3172 69 586 - 2019 30804430
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon highly
     mouth   highly
    Nervousbrain     Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  highly
    Nervouscentralwhite matter  
    Nervousperipherous   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Cardiovascularendothelial cell
    NervousSchawnn cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo
    Text radial glia and migrating cells in the intermediate zone in the cerebrum
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N terminal FERM (EPB41, ezrin, radixin, moesin) domain cysteine-rich
  • basic charged globular module
  • phosphatidylinositol-4,5 biphosphate binding motif
  • consensus motif PPVY(477) present in ezrin C-terminus
  • HOMOLOGY
    Homologene
    FAMILY
  • ezrin/radixin/ moesin (ERM) family member
  • CATEGORY structural protein
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule
    intracellular,nucleus,nucleolus
    text
  • microvillus specific
  • coexpression of EZR with EPS8 promotes the formation of membrane ruffles and tufts of microvilli, whereas expression of EZR and EPS8L1A induces the clustering of actin-containing structures at the cell surface
  • basic FUNCTION
  • membrane associated protein, responding and participating in reorganization of membrane-cytoplasm interactions
  • cross-linker between the actin cytoskeleton and the membrane
  • allows the local activation of RHOG at the apical pole of epithelial cells by recruiting upstream and downstream regulators of RHOG and both PLEKHG6 and ezrin are required for efficient macropinocytosis
  • involved in microvilli formation and breakdown
  • clustering in an endothelial actin rich docking structure with ICAM1, MSN, VCAM1
  • membrane-cytoskeletal linker, binding to L1CAM
  • regulating SLC9A3 translocation and activation after Na=-glucose cotransport (when is activated by MAPK14)
  • playing a key role in cell surface structure adhesion, migration, and organization
  • acts as a link between the cell membrane and actin cytoskeleton to integrate cell adhesion-mediated signaling
  • essential roles of SLC9A3R1 and ezrin in intracellular trafficking in epithelial cells (long-range allosteric regulation of SLC9A3R1 by ezrin enables the membrane-cytoskeleton to assemble protein complexes that control cross-talk and regulate the strength and duration of signaling)
  • with moesin function together to promote T cell activation
  • in the vagina, as in other tissues, likely modulates vaginal cell-cell interactions including the changing vaginal cellular interface with the external environment, the regulation of the elasticity of the vagina, and the regulation of microbial and chemical traffic that determine the pH and microbial environment of the vagina
  • is a negative regulator of death receptor-induced apoptosis
  • ezrin and microtubules are important to down-regulate signalling events leading to Erk1/2 activation
  • a crucial function for ezrin, DLG1 and microtubules in the organization of the immune synapse and TCR signal down-regulation
  • cytoskeleton linker protein that is actively involved in the metastatic capacity of cancer cells
  • ERM proteins (Ezrin, Radixin, Moesin) have the ability to organize multiprotein complexes in specific cellular compartments
  • necessary for RAP-induced cell spreading, but not RAP-induced cell adhesion or basal adhesion processes
  • novel function for Ezrin in TERF2IP-induced cell spreading and evidence of a non-redundant role of an ERM family member
  • its function in building and maintaining the apical domain is essential not only for intestinal morphogenesis but also for homeostasis in the mature intestine
  • function in RAP1A-induced cell spreading and evidence of a non-redundant role of an ERM family member
  • is potentially required for the structural plasticity of peripheral astrocyte process
  • regulate cellular survival, adhesion, migration, and invasion and has been identified as 1 of the key components of tumor progression and metastasis
  • ezrin, radixin and moesin are adaptor proteins that link plasma membrane receptors to the actin cytoskeleton
  • membrane cytoskeleton linker, that participates in several functions downstream of the receptor Met in response to HGF stimulation
  • role for EZR in Met receptor stability and activity through its association with the E3 ubiquitin ligase WWP1
  • EZR and IQGAP1 colocalize in the submembraneous cytoskeleton and in cellular protrusions of human epithelial cells
  • importance of the EZR-mediated connection between plasma membrane and cortex for cellular mechanics and cell morphology
  • BCAR1 and EZR are structural proteins with an important role in signaling pathways and have been shown to promote cancer dissemination
  • in Ovarian cancer, the role of EZR in disease progression is more pronounced than that of BCAR1
  • supportive role of EZR, RDX, MSN in cortical activities during cytokinesis
  • EZR and MSN play mutually exclusive roles in modulating SELL signalling and shedding to control protrusion dynamics and polarity during monocyte Leukocyte transendothelial migration (TEM)
  • S100P and EZR promote trans-endothelial migration of triple negative breast cancer cells
  • modulates cancer stem cells (CSC) properties in pancreatic cancer
  • cytoskeleton linker protein, is closely linked with the metastatic progression of cancer
  • ERM proteins, EZR, radixin and moesin, assist in the formation and maintenance of specialized plasma membrane structures and membrane vesicle structures
  • CELLULAR PROCESS cell organization/biogenesis
    cell communication
    PHYSIOLOGICAL PROCESS
    text downstream effector of trafficking PRKC-integrin complex involved in the control of cell motility
    PATHWAY
    metabolism
    signaling
    a component
  • forms a complex with RHOG
  • significant role for the multiprotein complex CFTR-SLC9A3R1-EZR-actin in maintaining tight junctions organisation and barrier function, suggesting that the RHOA/ROCK pathway is involved
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • colocalizing and interacting with ICAM1 and ICAM2 in microvillar projections
  • interacting with SLC9A3
  • interacting with DAG1 for regulation of actin cytoskeleton
  • interacts with MPP5 (binds to MPP5 via its N terminus and is co-localized with MPP5 to the apical membrane of gastric parietal cells, and essential role of ezrin-MPP5 interaction in the apical membrane remodeling associated with parietal cell secretion)
  • interaction between ezrin and PLEKHG6 (ezrin recruits PLEKHG6 to the apical pole of epithelial cells where PLEKHG6 induces the formation of microvilli and membrane ruffles)
  • ezrin differentially modulates the actin-capping and -bundling activities of EPS8 and EPS8L1a during microvillus assembly
  • coordinating the assembly of an obligate ternary complex with SLC34A1 and the PKA-anchoring protein EZR to facilitate PTH-responsive cAMP signaling events
  • binds to the WW domains of WWP1 via the consensus motif PPVY(477) present in ezrin C-terminus
  • EZR interacts with P2RX7
  • P2RX7 stimulation triggers the phosphorylation of EZR/RDX/MSN, which translocate to the plasma membrane where they associate with P2RX7
  • SLC9A3R1 is involved in PKA-dependent activation of CFTR by interacting with CFTR via its PDZ domains and with ezrin via its C-terminal domain
  • STK10 and SLK are functionally the major relevant kinases involved in the steady-state phosphorylation of EZR in Jeg-3 cells
  • RDX, EZR, MSN exert a redundant control on PDGFA-induced vascular smooth muscle cells (VSMC) migration by regulating focal adhesion turn-over and cell adhesion to substrate
  • ALCAM stably interacts with actin by binding to SDCBP and EZR, and interaction with the ligand CD6 further enhances these multiple interactions
  • inhibition of cell adhesion by phosphorylated EZR/RDX/MSN
  • EZR through STK10 is only phosphorylated at the plasma membrane, and with high specificity by the apically localized kinase STK10
  • through direct interaction with AQP2, EZR facilitates AQP2 endocytosis, thus linking the dynamic actin cytoskeleton network with AQP2 trafficking
  • RICTOR positively regulates B cell receptor signaling by modulating actin reorganization via EZR
  • is recruited to the cleavage furrow through its membrane-associated domain in a cholesterol-dependent but largely RHO-independent manner
  • EZR-anchored PRKACA phosphorylates serine 369 and 373 on GJA1 to enhance gap junction assembly, communication, and cell fusion
  • PODXL promotes extravasation through direct interaction of its intracellular domain with the cytoskeletal linker protein EZR
  • promotes breast cancer progression by modulating AKT1 signals
  • cell & other
  • membrane associated
  • REGULATION
    activated by a MAPK14 -dependent mechanism (phosphorylation of EZR)
    Other under phosphatidylinositol 4,5 biphosphate regulation
    phosphorylated by tyrosine-protein kinases
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in metastatic rhabdomyosarcoma
    tumoral     --over  
    frequently overexpressed in gastrointestinal stromal tumors, especially those arising from the non-gastric sites
    tumoral     --over  
    in highly metastatic cancers is probably due to a direct interaction between S100P-ezrin )
    tumoral     --over  
    contributed to non-small-cell lung cancer progression (
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker might be a potential prognostic marker of non-small-cell lung cancer progression
    Therapy target
    SystemTypeDisorderPubmed
    cancerendocrinepancreas
    may represent a novel target for the treatment of Pancreatic Ductal Adenocarcinoma
    cancerreproductiveuterus
    represents a promising target for the development of novel and effective strategies aimed at preventing the progression of cervical cancer
    ANIMAL & CELL MODELS