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Developmental stage

Very strong staining is detected in the Purkinje cell layer and in part of the molecular layer of the infant brain compared to adult brain.

Domain

Has three main structural domains: an N-terminal FERM domain, a central alpha-helical domain and a C-terminal actin-binding domain.

The FERM domain is organized in a clover-shaped structure that comprises three subdomains identified as F1 (residues 2-82), F2 (residues 96-198), and F3 (residues 204-296). In the active form, the subdomain F3 adopts two mutually exclusive conformational isomers where a row of four phenylalanine side chains (Phe250, Phe255, Phe267 and Phe269) must point in the same direction. In the autoinhibited form, the F3 subdomain interacts with the C-terminal domain (residues 516-586) and stabilizes the structure, selecting only one possible arrangement of phenylalanine side chains. The FERM domain mediates binding to membrane lipids and signaling molecules.

The central alpha-helical domain is composed of two alpha helices (residues 326-406 and 417-466) connected by a linker. It protrudes from the FERM domain forming a coiled coil structure where the linker can have either a loop or a helix conformation. The monomer is predicted to form an intra-molecular helix-loop-helix coiled coil structure. Whereas the dimer adopts an elongated dumbbell-shaped configuration where continuous alpha helices from each protomer are organized in a antiparallel coiled coil structure that connect FERM:C-terminal domain swapped complex at each end. The dimer is predicted to link actin filaments parallel to the plasma membrane.

The [IL]-x-C-x-x-[DE] motif is a proposed target motif for cysteine S-nitrosylation mediated by the iNOS-S100A8/A9 transnitrosylase complex.

Function

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.

Post-translational modifications

Phosphorylated by tyrosine-protein kinases. Phosphorylation by ROCK2 suppresses the head-to-tail association of the N-terminal and C-terminal halves resulting in an opened conformation which is capable of actin and membrane-binding (By similarity).

S-nitrosylation is induced by interferon-gamma and oxidatively-modified low-densitity lipoprotein (LDL(ox)) possibly implicating the iNOS-S100A8/9 transnitrosylase complex.

Tissue specificity

Expressed in cerebral cortex, basal ganglia, hippocampus, hypophysis, and optic nerve. Weakly expressed in brain stem and diencephalon. Stronger expression was detected in gray matter of frontal lobe compared to white matter (at protein level). Component of the microvilli of intestinal epithelial cells. Preferentially expressed in astrocytes of hippocampus, frontal cortex, thalamus, parahippocampal cortex, amygdala, insula, and corpus callosum. Not detected in neurons in most tissues studied.

Cellular localization

  • Apical cell membrane
  • Peripheral membrane protein
  • Cytoplasmic side
  • Cell projection
  • Cell projection
  • Microvillus membrane
  • Peripheral membrane protein
  • Cytoplasmic side
  • Cell projection
  • Ruffle membrane
  • Peripheral membrane protein
  • Cytoplasmic side
  • Cytoplasm
  • Cell cortex
  • Cytoplasm
  • Cytoskeleton
  • Cell projection
  • Microvillus
  • Localization to the apical membrane of parietal cells depends on the interaction with PALS1. Localizes to cell extensions and peripheral processes of astrocytes (By similarity). Microvillar peripheral membrane protein (cytoplasmic side).

Alternative names

VIL2, EZR, Ezrin, Cytovillin, Villin-2, p81

Target type

Proteins

Primary research area

Oncology

Molecular weight

69413Da

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