Calpainlike

Calpainlike proteins are a family of calcium-dependent, non-lysosomal cysteine proteases that share structural and functional similarities with the classical calpains. These enzymes play critical roles in various cellular processes, including signal transduction, cytoskeletal remodeling, apoptosis, and muscle development. Unlike the canonical calpains, which are heterodimeric enzymes composed of a large catalytic subunit and a smaller regulatory subunit, calpainlike proteins often exist as single-chain enzymes or lack the auxiliary subunit.

The calpainlike family includes several members such as calpain-11 (CAPN11), calpain-14 (CAPN14), and calpain-15 (CAPN15), which are primarily expressed in specific tissues like the brain, heart, and skeletal muscle. These enzymes are activated by elevated intracellular calcium levels, similar to classical calpains, but their substrate specificity and regulatory mechanisms can differ. Some calpainlike proteins are involved in specialized functions, such as CAPN11, which has been implicated in insulin secretion and glucose metabolism, suggesting a role in diabetes regulation.

Structurally, calpainlike proteins contain a conserved protease domain with a cysteine residue in the active site, along with a calmodulin-like domain that mediates calcium binding. However, they often lack the N-terminal domain found in classical calpains, which is essential for their autolytic activation. The lack of this domain may influence their regulation and substrate accessibility.

Research on calpainlike proteins is still evolving, with ongoing studies exploring their physiological roles and potential involvement in diseases such as neurodegenerative disorders, cardiovascular conditions, and metabolic syndromes. Their unique properties make them promising targets for therapeutic intervention in conditions where calcium-dependent proteolysis is dysregulated.