ID:CASP3_HUMAN DESCRIPTION: RecName: Full=Caspase-3; Short=CASP-3; EC=3.4.22.56; AltName: Full=Apopain; AltName: Full=Cysteine protease CPP32; Short=CPP-32; AltName: Full=Protein Yama; AltName: Full=SREBP cleavage activity 1; Short=SCA-1; Contains: RecName: Full=Caspase-3 subunit p17; Contains: RecName: Full=Caspase-3 subunit p12; Flags: Precursor; 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. 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. 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. INTERACTION: Q9BYP7:WNK3; NbExp=2; IntAct=EBI-524064, EBI-1182602; SUBCELLULAR LOCATION: Cytoplasm. 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. 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. WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/casp3/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P42574
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0002020 protease binding GO:0004190 aspartic-type endopeptidase activity GO:0004197 cysteine-type endopeptidase activity GO:0004861 cyclin-dependent protein serine/threonine kinase inhibitor activity GO:0005123 death receptor binding GO:0005515 protein binding GO:0008233 peptidase activity GO:0008234 cysteine-type peptidase activity GO:0008656 cysteine-type endopeptidase activator activity involved in apoptotic process GO:0016005 phospholipase A2 activator activity GO:0016787 hydrolase activity GO:0044877 macromolecular complex binding GO:0097153 cysteine-type endopeptidase activity involved in apoptotic process GO:0097200 cysteine-type endopeptidase activity involved in execution phase of apoptosis
Biological Process: GO:0001666 response to hypoxia GO:0001782 B cell homeostasis GO:0006309 apoptotic DNA fragmentation GO:0006508 proteolysis GO:0006915 apoptotic process GO:0006919 activation of cysteine-type endopeptidase activity involved in apoptotic process GO:0006974 cellular response to DNA damage stimulus GO:0007507 heart development GO:0007605 sensory perception of sound GO:0007611 learning or memory GO:0008627 intrinsic apoptotic signaling pathway in response to osmotic stress GO:0009411 response to UV GO:0009611 response to wounding GO:0009749 response to glucose GO:0010033 response to organic substance GO:0010038 response to metal ion GO:0010165 response to X-ray GO:0014070 response to organic cyclic compound GO:0016241 regulation of macroautophagy GO:0016485 protein processing GO:0019221 cytokine-mediated signaling pathway GO:0021766 hippocampus development GO:0030182 neuron differentiation GO:0030216 keratinocyte differentiation GO:0030218 erythrocyte differentiation GO:0030220 platelet formation GO:0030889 negative regulation of B cell proliferation GO:0032025 response to cobalt ion GO:0032355 response to estradiol GO:0032496 response to lipopolysaccharide GO:0034349 glial cell apoptotic process GO:0034612 response to tumor necrosis factor GO:0035094 response to nicotine GO:0035329 hippo signaling GO:0035556 intracellular signal transduction GO:0042060 wound healing GO:0042493 response to drug GO:0042542 response to hydrogen peroxide GO:0043029 T cell homeostasis GO:0043065 positive regulation of apoptotic process GO:0043066 negative regulation of apoptotic process GO:0043085 positive regulation of catalytic activity GO:0043200 response to amino acid GO:0043525 positive regulation of neuron apoptotic process GO:0045165 cell fate commitment GO:0045736 negative regulation of cyclin-dependent protein serine/threonine kinase activity GO:0045786 negative regulation of cell cycle GO:0046007 negative regulation of activated T cell proliferation GO:0046677 response to antibiotic GO:0048011 neurotrophin TRK receptor signaling pathway GO:0051384 response to glucocorticoid GO:0051402 neuron apoptotic process GO:0071310 cellular response to organic substance GO:0071407 cellular response to organic cyclic compound GO:0072734 cellular response to staurosporine GO:0097190 apoptotic signaling pathway GO:0097192 extrinsic apoptotic signaling pathway in absence of ligand GO:0097194 execution phase of apoptosis
Protein P42574 (Reactome details) participates in the following event(s):
R-HSA-114252 Cleavage of Procaspase-3 by the apoptosome R-HSA-418845 Activation of caspase-3 R-HSA-205117 p75NTR:NADE promotes caspase2/3 activation R-HSA-211219 Translocation of caspase-3 to the nucleus R-HSA-114419 Dissociation of Caspase-3 from SMAC:XIAP:Caspase-3 R-HSA-114306 SMAC binds XIAP:Caspase-3 R-HSA-201595 Caspase-mediated cleavage of plakophilin-1 R-HSA-201603 Caspase-mediated cleavage of PKC theta R-HSA-201608 Caspase-mediated cleavage of alpha adducin R-HSA-201611 Caspase-mediated cleavage of Rock-1 R-HSA-201622 Caspase-mediated cleavage of gelsolin R-HSA-201629 Caspase-mediated cleavage of Tau R-HSA-201630 Caspase-mediated cleavage of Acinus R-HSA-201631 Caspase-mediated cleavage of Desmoglein 3 R-HSA-201636 Caspase-mediated cleavage of Desmoplakin R-HSA-201640 Caspase-mediated cleavage of farnesyltransferase/geranyl- geranyltransferase subunit alpha R-HSA-202917 Caspase-mediated cleavage of Desmoglein 1 R-HSA-202939 Caspase-mediated cleavage of E-Cadherin R-HSA-202947 Caspase mediated cleavage of APC R-HSA-202960 Caspase mediated cleavage of C-IAP1 R-HSA-202966 Caspase mediated cleavage of HIP-55 R-HSA-202967 Caspase mediated cleavage of alpha-II-Fodrin R-HSA-202969 Caspase mediated cleavage of beta-catenin R-NUL-211643 Cleavage of PAK-2 at 212 R-HSA-211651 Cleavage of PAK-2 at 212 R-HSA-212552 Caspase 3-mediated cleavage of PKC delta R-HSA-350651 Caspase-mediated cleavage of MASK R-HSA-351849 Caspase-mediated cleavage of Etk R-HSA-351871 Caspase-mediated cleavage of Z0-2 R-HSA-351876 Caspase-mediated cleavage of occludin R-HSA-351877 Caspase-mediated cleavage of Desmoglein 2 R-HSA-351913 Caspase-mediated cleavage of TJP1 R-HSA-418846 Caspase cleavage of UNC5A R-HSA-418852 Caspase cleavage of UNC5B R-HSA-2028692 Cleavage of p-STK4 (p-MST1) by caspase 3 R-HSA-2028697 Cleavage of p-STK3 (p-MST2) by caspase 3 R-HSA-449073 Caspase-3 cleaves pro-interleukin-16 R-HSA-373705 Caspase cleavage of DCC R-HSA-211186 Cleavage of DFF45 (224) by caspase-3 R-HSA-211190 Caspase 3-mediated cleavage of DFF45 (117) R-HSA-201628 Caspase-mediated cleavage of vimentin at DSVD (85) R-HSA-201639 Caspase-mediated cleavage of GAS2 R-HSA-351901 Caspase-mediated cleavage of MST3 R-HSA-2534260 E-cadherin degradation by caspase-3 and calpain-1 R-HSA-111459 Activation of caspases through apoptosome-mediated cleavage R-HSA-418889 Ligand-independent caspase activation via DCC R-HSA-205025 NADE modulates death signalling R-HSA-111461 Cytochrome c-mediated apoptotic response R-HSA-5357769 Caspase activation via extrinsic apoptotic signalling pathway R-HSA-204998 Cell death signalling via NRAGE, NRIF and NADE R-HSA-211227 Activation of DNA fragmentation factor R-HSA-111464 SMAC-mediated dissociation of IAP:caspase complexes R-HSA-111471 Apoptotic factor-mediated response R-HSA-109581 Apoptosis R-HSA-193704 p75 NTR receptor-mediated signalling R-HSA-111463 SMAC binds to IAPs R-HSA-140342 Apoptosis induced DNA fragmentation R-HSA-111469 SMAC-mediated apoptotic response R-HSA-351906 Apoptotic cleavage of cell adhesion proteins R-HSA-111465 Apoptotic cleavage of cellular proteins R-HSA-264870 Caspase-mediated cleavage of cytoskeletal proteins R-HSA-211736 Stimulation of the cell death response by PAK-2p34 R-HSA-2028269 Signaling by Hippo R-HSA-449836 Other interleukin signaling R-HSA-109606 Intrinsic Pathway for Apoptosis R-HSA-5357801 Programmed Cell Death R-HSA-73887 Death Receptor Signalling R-HSA-1474228 Degradation of the extracellular matrix R-HSA-75153 Apoptotic execution phase R-HSA-162582 Signal Transduction R-HSA-449147 Signaling by Interleukins R-HSA-1474244 Extracellular matrix organization R-HSA-1280215 Cytokine Signaling in Immune system R-HSA-168256 Immune System
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
