||Caspase-2 is an initiator caspase, as are caspase-8 (EC 126.96.36.199), caspase-9 (EC 188.8.131.52) and caspase-10 (EC 184.108.40.206) . Contains a caspase-recruitment domain (CARD) in its N-terminal prodomain, which plays a role in procaspase activation . Two forms of caspase-2 with antagonistic effects exist: caspase-2L induces programmed cell death and caspase-2S suppresses cell death [2,3,5]. Caspase-2 is activated by caspase-3 (EC 220.127.116.11), or by a caspase-3-like protease. Activation involves cleavage of the N-terminal prodomain, followed by self-proteolysis between the large and small subunits of pro-caspase-2 and further proteolysis into smaller fragments . Proteolysis occurs at Asp residues and the preferred substrate for this enzyme is a pentapeptide rather than a tetrapeptide . Apart from itself, the enzyme can cleave golgin-16, which is present in the Golgi complex and has a cleavage site that is unique for caspase-2 [4,5]. αII-Spectrin, a component of the membrane cytoskeleton, is a substrate of the large isoform of pro-caspase-2 (caspase-2L) but not of the short isoform (caspase-2S). Belongs in peptidase family C14.
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