Alpha-actinin-4 (ACTN4)

Alpha-actinin–4 is a non-muscle isoform of the alpha-actinin family, encoded by the ACTN4 gene. It is a member of the spectrin superfamily and functions as an antiparallel homodimer that crosslinks filamentous actin (F-actin) in the cytoplasm. The protein contains an N-terminal actin-binding domain with calponin homology domains, a central rod domain for dimerization, and a C-terminal calmodulin-like domain with EF-hand motifs. Alpha-actinin–4 plays essential roles in organizing the actin cytoskeleton, maintaining cell shape, facilitating focal adhesion dynamics through interactions with integrins at the plasma membrane, and regulating cell motility. It is ubiquitously expressed in non-muscle cells but can also be found in neoplastic tissues. Mutations in alpha-actinin–4 are associated with autosomal dominant forms of kidney disease such as focal segmental glomerulosclerosis; these mutations often increase its affinity for F-actin or disrupt normal regulation by calcium ions[1][2][3][5]. In cancer biology, altered expression or function has been linked to increased metastatic potential due to changes in cellular adhesion and migration properties. No approved drugs are known to directly target alpha-actinin–4; it is not currently considered a direct therapeutic target such as receptors or enzymes but rather serves critical structural roles within cells[6].

Other names

Alpha actinin 4ACTN4Non-muscle alpha-actinin 4