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Calpastatin is an intracellular calcium-dependent protease that cleaves cytoskeletal and sub-membranous proteins. Calpains are non-lysosomal, calcium-activated intracellular cysteine proteases. Calpains mediate specific Ca2+- dependent processes including cell fusion, mitosis and meiosis. Calpains are heterodimers of a small regulatory subunit and one of three large catalytic subunits, designated Calpastatin, Calpain 2 and Calpain p94. Calpastatin regulates Calpain by inhibiting both the proteolytic activity of Calpain and its binding to membranes. Calpastatin exists in two types, tissue type and erythrocyte type, resulting from both alternative splicing and proteolytic processing. Calpastatin co-localizes with human leukocyte antigen-DR (HLA-DR) on activated microglia in the aging brain. Calpain influences the process of spermatogenesis and the events preceding fertilization, such as the acrosome reaction.
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