CLIC5 belongs to a family of six vertebrate chloride intracellular channel (CLIC) proteins, all sharing a conserved C-terminal CLIC module []. CLIC5 associates with the cortical actin cytoskeleton [, ]. It is strongly and reversibly inhibited by cytosolic F-actin []. The isoform CLIC5A is required for the development and/or maintenance of the proper glomerular endothelial cell and podocyte architecture [].
This entry represents the C-terminal glutathione S-transferase (GST) domain found in chloride intracellular channel 5 (CLIC5) protein. CLIC5 exists in two alternatively-spliced isoforms, CLIC5A or CLIC5B (also called p64) []. It is expressed at high levels in hair cell stereocilia and is associated with the actin cytoskeleton and ezrin []. A recessive mutation in the CLIC5 gene in mice led to the lack of coordination and deafness, due to a defect in the basal region of the hair bundle causing stereocilia to degrade. CLIC5 is therefore essential for normal inner ear function []. CLIC5 is also highly expressed in podocytes where it is colocalized with the ezrin/radixin/moesin (ERM) complex. It is essential for foot process integrity, and for podocyte morphology and function [, ].CLICs are auto-inserting, self-assembling intracellular anion channels involved in a wide variety of functions including regulated secretion, cell division, and apoptosis. They can exist in both water-soluble and membrane-bound states and are found in various vesicles and membranes, and they may play roles in the maintenance of these intracellular membranes. The membrane localization domain is present in the N-terminal part of the protein. Structures of soluble CLICs reveal that they adopt a fold similar to GSTs, containing an N-terminal domain with a thioredoxin fold and a C-terminal alpha helical domain [, , ].
