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MT000103

UniProt Annotations

Entry Information

Gene Name	caspase 3, apoptosis-related cysteine peptidase
Protein Entry	CASP3_HUMAN
UniProt ID	P42574
Species	Human

Comments

Comment type	Description
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. Triggers cell adhesion in sympathetic neurons through RET cleavage. {ECO:0000269\|PubMed:21357690, ECO:0000269\|PubMed:7596430}.
Interaction	Q9Y243:AKT3; NbExp=2; IntAct=EBI-524064, EBI-296115; Q00987:MDM2; NbExp=2; IntAct=EBI-524064, EBI-389668; Q9BYP7:WNK3; NbExp=2; IntAct=EBI-524064, EBI-1182602; P98170:XIAP; NbExp=2; IntAct=EBI-524064, EBI-517127;
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. {ECO:0000269\|PubMed:10213689}.
Similarity	Belongs to the peptidase C14A family. {ECO:0000305}.
Subcellular Location	Cytoplasm.
Subunit	Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 17 kDa (p17) and a 12 kDa (p12) subunit. Interacts with BIRC6/bruce. {ECO:0000269\|PubMed:15200957}.
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.
Web Resource	Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/casp3/";