Ezrin (EZR)

Ezrin is a membrane-cytoskeletal linker protein encoded by the EZR gene, and is the best studied member of the ERM (Ezrin-Radixin-Moesin) protein family[1][3][5]. It is characterized structurally by an N-terminal FERM domain, a helical linker, and a C-terminal actin-binding (ERM) domain[1][3][6]. Ezrin cycles between an inactive closed conformation and an active open conformation upon phosphorylation (notably at T567), enabling it to bind F-actin with its C-terminus and plasma membrane proteins (e.g., CD44, ICAMs) via its N-terminus[3][5][6]. It plays a crucial role in the spatial organization of microvilli and other cell surface structures, cell adhesion, migration, signal transduction, and is implicated in tumor metastasis and invasion[3][5][7]. Ezrin is a potential therapeutic target in cancers because its dysregulation is associated with increased metastatic potential and poor prognosis[3]. Experimental small-molecule inhibitors of ezrin act principally by blocking phosphorylation at key residues, thereby preventing the structural activation necessary for cytoskeleton-membrane linkage and cancer cell invasion[3].

Other names

CytovillinVillin-2VIL2p81cytovillin 2CVILCVLHEL-S-105epididymis secretory protein Li 105

Direct inhibition of Ezrin phosphorylation (at T567), Disruption of actin binding, Inhibition of conformational activation