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Caspase 3
UniProt Number:
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P42574 |
Alternate Names:
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Apopain, Cysteine protease CPP32, Protein Yama, SREBP cleavage activity 1 |
Structure and Function:
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Caspase 3 is a cysteine protease involved in the activation cascade of caspases responsible for apoptosis execution. At the onset of apoptosis caspase 3 proteolytically cleaves poly (ADP-ribose) polymerase (PARP) at Asp216-Gly217 bond. Caspase 3 cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain. Caspase 3 cleaves and activates caspase-6, -7 and -9. Caspase 3 is involved in the cleavage of huntingtin. Caspase 3 is a cytoplasmic protein highly expressed in lung, spleen, heart, liver and kidney. Moderate levels of caspase 3 are in brain and skeletal muscle, and low levels in testis. Also caspase 3 is found in many cell lines, highest expression in cells of the immune system. Caspase 3 is expressed in an inactive pro-form (pro caspase 3). In apoptosis, the pro caspase 3 is activated by proteolytic cleavages at Asp28-Ser29 and Asp175-Ser176 bonds catalyzed by granzyme B, caspase-6, caspase-8, caspase-9 and caspase-10 generating two active subunits. Thus the pro-form and the active form are useful biomarkers of apoptosis. Active caspase 3 is a heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 17 kDa (p17) and a 12 kDa (p12) subunit. Additional processing of the propeptides is likely due to the autocatalytic activity of the activated protease. Active heterodimers between the small subunit of caspase-7 protease and the large subunit of caspase-3 also occur and vice versa. Caspase 3 is S-nitrosylated on its catalytic site cysteine in unstimulated human cell lines and denitrosylated upon activation of the Fas apoptotic pathway, associated with an increase in intracellular caspase activity. Fas therefore activates caspase-3 not only by inducing the cleavage of the caspase zymogen to its active subunits, but also by stimulating the denitrosylation of its active site thiol. |
Disease Associations:
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Protein Quantity Assays
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Related Pathways:
Apoptosis
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