ID:CASP9_HUMAN DESCRIPTION: RecName: Full=Caspase-9; Short=CASP-9; EC=3.4.22.62; AltName: Full=Apoptotic protease Mch-6; AltName: Full=Apoptotic protease-activating factor 3; Short=APAF-3; AltName: Full=ICE-like apoptotic protease 6; Short=ICE-LAP6; Contains: RecName: Full=Caspase-9 subunit p35; Contains: RecName: Full=Caspase-9 subunit p10; Flags: Precursor; FUNCTION: Involved in the activation cascade of caspases responsible for apoptosis execution. Binding of caspase-9 to Apaf- 1 leads to activation of the protease which then cleaves and activates caspase-3. Proteolytically cleaves poly(ADP-ribose) polymerase (PARP). FUNCTION: Isoform 2 lacks activity is an dominant-negative inhibitor of caspase-9. CATALYTIC ACTIVITY: Strict requirement for an Asp residue at position P1 and with a marked preference for His at position P2. It has a preferred cleavage sequence of Leu-Gly-His-Asp-|-Xaa. SUBUNIT: Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 35 kDa (p35) and a 10 kDa (p10) subunit. Caspase-9 and APAF1 bind to each other via their respective NH2-terminal CED-3 homologous domains in the presence of cytochrome C and ATP. Interacts (inactive form) with EFHD2. Interacts with HAX1. Interacts with BIRC2/c-IAP1, XIAP/BIRC4, BIRC5/survivin, BIRC6/bruce and BIRC7/livin. INTERACTION: O14727:APAF1; NbExp=17; IntAct=EBI-516799, EBI-446492; Q96CA5:BIRC7; NbExp=5; IntAct=EBI-516799, EBI-517623; Q13418:ILK; NbExp=2; IntAct=EBI-516799, EBI-747644; P98170:XIAP; NbExp=5; IntAct=EBI-516799, EBI-517127; TISSUE SPECIFICITY: Ubiquitous, with highest expression in the heart, moderate expression in liver, skeletal muscle, and pancreas. Low levels in all other tissues. Within the heart, specifically expressed in myocytes. DEVELOPMENTAL STAGE: Expressed at low levels in fetal heart, at moderate levels in neonate heart, and at high levels in adult heart. PTM: Cleavages at Asp-315 by granzyme B and at Asp-330 by caspase- 3 generate the two active subunits. Caspase-8 and -10 can also be involved in these processing events. PTM: Phosphorylated at Thr-125 by MAPK1/ERK2. Phosphorylation at Thr-125 is sufficient to block caspase-9 processing and subsequent caspase-3 activation. SIMILARITY: Belongs to the peptidase C14A family. SIMILARITY: Contains 1 CARD domain. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/CASP9ID423ch1p36.html"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/casp9/"; WEB RESOURCE: Name=Wikipedia; Note=Caspase-9 entry; URL="http://en.wikipedia.org/wiki/Caspase-9";
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 P55211
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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:0004197 cysteine-type endopeptidase activity GO:0005515 protein binding GO:0008047 enzyme activator activity GO:0008233 peptidase activity GO:0008234 cysteine-type peptidase activity GO:0016787 hydrolase activity GO:0017124 SH3 domain binding GO:0019901 protein kinase binding GO:0042802 identical protein binding GO:0097200 cysteine-type endopeptidase activity involved in execution phase of apoptosis
Biological Process: 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:0007568 aging GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage GO:0008635 activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c GO:0009411 response to UV GO:0014070 response to organic cyclic compound GO:0030220 platelet formation GO:0032025 response to cobalt ion GO:0032355 response to estradiol GO:0032496 response to lipopolysaccharide GO:0034349 glial cell apoptotic process GO:0034644 cellular response to UV GO:0042770 signal transduction in response to DNA damage GO:0042981 regulation of apoptotic process GO:0043065 positive regulation of apoptotic process GO:0043525 positive regulation of neuron apoptotic process GO:0046677 response to antibiotic GO:0071407 cellular response to organic cyclic compound GO:0071549 cellular response to dexamethasone stimulus GO:0097192 extrinsic apoptotic signaling pathway in absence of ligand GO:0097194 execution phase of apoptosis GO:2001020 regulation of response to DNA damage stimulus