Catalytic activity:Strict requirement for an Asp residue at positions P1 and P4. It has a preferred cleavage sequence of Asp-Xaa-Xaa-Asp-|- with a hydrophobic amino-acid residue at P2 and a hydrophilic amino-acid residue at P3 , although Val or Ala are also accepted at this position. ,enzyme regulation:Inhibited by isatin sulfonamides. ,Function:Involved in the activation cascade of caspases responsible for apoptosis execution. At the onset of apoptosis it proteolytically cleaves poly (ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' bond. Cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain. Cleaves and activates caspase-6 , -7 and -9. Involved in the cleavage of huntingtin. ,PTM:Cleavage by granzyme B , caspase-6 , caspase-8 and caspase-10 generates the two active subunits. 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. ,PTM: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. ,similarity:Belongs to the peptidase C14A family. ,subunit:Heterotetramer that consists of two anti-parallel arranged heterodimers , each one formed by a 17 kDa (p17) and a 12 kDa (p12) subunit. ,tissue specificity:Highly expressed in lung , spleen , heart , liver and kidney. Moderate levels in brain and skeletal muscle , and low in testis. Also found in many cell lines , highest expression in cells of the immune system. ,
展开内容