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Literature summary for 3.4.22.62 extracted from
- The central role of initiator caspase-9 in apoptosis signal transduction and the regulation of its activation and activity on the apoptosome (2012), Exp. Cell Res., 318, 1213-1220.
Activating Compound
| Activating Compound | Comment | Organism | Structure |
|---|---|---|---|
| additional information | caspase-9 is activated on the apoptosome complex. Through its higher affinity, procaspase-9 displaces processed caspase-9 from the apoptosome, thereby closing the proteolytic timer cycle. Dimerisation of caspase-9 results in rapid autocatalytic cleavage, yielding caspase-9 (p35/p12) | Homo sapiens |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| additional information | caspase-3 can bind to the nucleotide binding domain of Apaf-1 on the apoptosome backbone. Binding eliminates the close association of caspase-9 with the nucleotide binding domain of Apaf-1, resulting in its inactivation | Homo sapiens | |
| XIAP | can antagonise caspase-9 activity and stabilises its interaction with the apoptosome. Caspase-3 cleaves XIAP into fragments that retain their inhibitory potential towards caspases-3 or -9, thereby eliminating sterical hindrance that may prevent parallel inhibition of caspases-3 and -9 by XIAP | Homo sapiens |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| cytosol | - |
Homo sapiens | 5829 | - |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| additional information | Homo sapiens | the linker between the large and small subunits contains the caspase-9 auto-cleavage site (D315). Cleavage at this site generates the p35/p12 form of caspase-9. The p35/p12 form can be further processed by caspase-3 by cleavage at site D330, generating caspase-9 | ? | - |
? |  |
| pro-caspase-3 + H2O | Homo sapiens | - |
caspase-3 + caspase-3 propeptide | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | - |
- |
- |
Posttranslational Modification
| Posttranslational Modification | Comment | Organism |
|---|---|---|
| proteolytic modification | initiator pro-caspases exist as monomers and possess long pro-domains. These pro-domains contain specific protein-protein interaction sites that are crucial for initiator caspase activation. The pro-domain of caspases-9 contain a caspase activation recruitment domain (CARD) motif. Release of cytochrome-c and other proapoptotic proteins into the cytosol results in the formation of the apoptosome, the activation platform for initiator caspase-9. Flexible linkers connect the caspase activation recruitment domain (CARD) with the large subunit and the large subunit with the small subunit. The linker between the large and small subunits contains the caspase-9 auto-cleavage site (D315). Cleavage at this site generates the p35/p12 form of caspase-9. The p35/p12 form can be further processed by caspase-3 by cleavage at site D330, generating caspase-9 | Homo sapiens |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| additional information | the linker between the large and small subunits contains the caspase-9 auto-cleavage site (D315). Cleavage at this site generates the p35/p12 form of caspase-9. The p35/p12 form can be further processed by caspase-3 by cleavage at site D330, generating caspase-9 | Homo sapiens | ? | - |
? | |
| pro-caspase-3 + H2O | - |
Homo sapiens | caspase-3 + caspase-3 propeptide | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| dimer | dimerisation of caspase-9 results in rapid autocatalytic cleavage, yielding caspase-9 (p35/p12) | Homo sapiens |
General Information
| General Information | Comment | Organism |
|---|---|---|
| evolution | key structural and catalytic features are conserved across the entire family of cysteine-dependent aspartate-specific proteases (caspases) | Homo sapiens |
| metabolism | of the caspases involved in apoptosis signal transduction, the initiator caspases-2, -8 and -9 are activated at multi-protein activation platforms, and activation is thought to involve homo-dimerisation of the monomeric zymogens. Modeling of caspase-9 signalling dynamics on the apoptosome, overview | Homo sapiens |
| additional information | modeling of the regulation of caspase-9 activation and activity that arise from the complexity of multi-protein interactions at the apoptosome | Homo sapiens |
| physiological function | caspase-9 is the essential initiator caspase required for apoptosis signalling through the mitochondrial pathway, dynamics of caspase-9 signalling on the apoptosome, detailed overview | Homo sapiens |
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