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Literature summary for 3.4.22.49 extracted from
- DNA-dependent cohesin cleavage by separase (2011), Nucleus, 1, 4-7.
Activating Compound
| Activating Compound | Comment | Organism | Structure |
|---|---|---|---|
| DNA | chromosomal DNA is required as a cofactor for the cleavage of cohesin to occur, and allows separase to selectively cleave only the chromosome-associated cohesin | Saccharomyces cerevisiae |  |
| DNA | chromosomal DNA is required as a cofactor for the cleavage of cohesin to occur, and allows separase to selectively cleave only the chromosome-associated cohesin. Separase binds to DNA in a sequence nonspecific manner in vitro and associates with the entire length of the mitotic chromosomes | Mus musculus | |
| DNA | chromosomal DNA is required as a cofactor for the cleavage of cohesin to occur, and allows separase to selectively cleave only the chromosome-associated cohesin. Separase binds to DNA in a sequence nonspecific manner in vitro and associates with the entire length of the mitotic chromosomes | Homo sapiens | |
| additional information | most of the budding yeast cohesin is cleaved in anaphase, and this cleavage is stimulated by phosphorylation of the Scc1 subunit by the Plk1 kinase | Saccharomyces cerevisiae |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| additional information | nuclear exclusion of separase might provide the means to preclude cohesin cleavage at telophase and G1 stage of the cell cycle | Homo sapiens | |
| additional information | nuclear exclusion of separase might provide the means to preclude cohesin cleavage at telophase and G1 stage of the cell cycle | Mus musculus | |
| additional information | cohesin cleavage is inhibited by a PP2ACdc55-dependent mechanism | Saccharomyces cerevisiae | |
| securin | - |
Homo sapiens | |
| securin | - |
Mus musculus | |
| securin | - |
Saccharomyces cerevisiae | |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| cohesin + H2O | Mus musculus | separase selectively cleaves only the chromosome-associated cohesin with the cofactor chromosomal DNA | ? | - |
? | |
| cohesin + H2O | Saccharomyces cerevisiae | separase selectively cleaves only the chromosome-associated cohesin with the cofactor chromosomal DNA | ? | - |
? | |
| cohesin + H2O | Homo sapiens | separase selectively cleaves only the chromosome-associated cohesin with the cofactor chromosomal DNA, chromosome-associated cohesin is cleaved preferentially by separase, mechanism | ? | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | - |
- |
- |
| Mus musculus | - |
- |
- |
| Saccharomyces cerevisiae | - |
- |
- |
Posttranslational Modification
| Posttranslational Modification | Comment | Organism |
|---|---|---|
| phosphoprotein | in vertebrate cells, separase is phosphorylated and inhibited before anaphase by a cyclin B/CDK1. This phosphorylation leads to an inhibitory binding of the cyclin B/CDK1 complex to separase | Mus musculus |
| phosphoprotein | in vertebrate cells, separase is phosphorylated and inhibited before anaphase by a cyclin B/CDK1. This phosphorylation leads to an inhibitory binding of the cyclin B/CDK1 complex to separase | Homo sapiens |
| phosphoprotein | most of the budding yeast cohesin is cleaved in anaphase, and this cleavage is stimulated by phosphorylation of the Scc1 subunit by the Plk1 kinase | Saccharomyces cerevisiae |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| cohesin + H2O | - |
Mus musculus | ? | - |
? | |
| cohesin + H2O | - |
Homo sapiens | ? | - |
? | |
| cohesin + H2O | - |
Saccharomyces cerevisiae | ? | - |
? | |
| cohesin + H2O | separase selectively cleaves only the chromosome-associated cohesin with the cofactor chromosomal DNA | Mus musculus | ? | - |
? | |
| cohesin + H2O | separase selectively cleaves only the chromosome-associated cohesin with the cofactor chromosomal DNA | Saccharomyces cerevisiae | ? | - |
? | |
| cohesin + H2O | separase selectively cleaves only the chromosome-associated cohesin with the cofactor chromosomal DNA, chromosome-associated cohesin is cleaved preferentially by separase, mechanism | Homo sapiens | ? | - |
? | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| malfunction | cells that do not express both Cdc55 and securin prematurely separate their sister chromatids, leading to cell death | Homo sapiens |
| malfunction | cells that do not express both Cdc55 and securin prematurely separate their sister chromatids, leading to cell death | Saccharomyces cerevisiae |
| malfunction | cells that do not express both Cdc55 and securin prematurely separate their sister chromatids, leading to cell death. Mutant mice lacking securin and expressing a non-phosphorylatable separase die in embryonic stage. But mouse embryonic stem cells lacking both these separase regulations can still progress through mitosis in a timely fashion with correct chromosome segregation | Mus musculus |
| physiological function | sister chromatid cohesion depends on the cohesin complex, a proteinaceous ring that entraps the chromatids together. At the metaphase-to-anaphase transition, separase is activated and completely dissolves the cohesion by cleaving SCC1, a subunit of the cohesin complex. As one of the key executors of anaphase, separase is regulated temporally and spatially by often redundant mechanisms. Chromosomal DNA dependent cohesin cleavage by separase is a component of a regulatory pathway that cells utilize to protect the bulk of cohesin. Degradation of securin plays a critical role in the timely activation of separase activity. But securin-independent separase regulation occur, cohesin cleavage is inhibited by a PP2ACdc55-dependent mechanism. Most of the budding yeast cohesin is cleaved in anaphase, and this cleavage is stimulated by phosphorylation of the Scc1 subunit by the Plk1 kinase | Saccharomyces cerevisiae |
| physiological function | sister chromatid cohesion depends on the cohesin complex, a proteinaceous ring that entraps the chromatids together. At the metaphase-to-anaphase transition, separase is activated and completely dissolves the cohesion by cleaving SCC1, a subunit of the cohesin complex. As one of the key executors of anaphase, separase is regulated temporally and spatially by often redundant mechanisms. Chromosomal DNA dependent cohesin cleavage by separase is a component of a regulatory pathway that cells utilize to protect the bulk of cohesin. Degradation of securin plays a critical role in the timely activation of separase activity. In vertebrate cells, separase is phosphorylated and inhibited before anaphase by a cyclin B/CDK1. Nuclear exclusion of separase might provide the means to preclude cohesin cleavage at telophase and G1 stage of the cell cycle | Mus musculus |
| physiological function | sister chromatid cohesion depends on the cohesin complex, a proteinaceous ring that entraps the chromatids together. At the metaphase-to-anaphase transition, separase is activated and completely dissolves the cohesion by cleaving SCC1, a subunit of the cohesin complex. As one of the key executors of anaphase, separase is regulated temporally and spatially by often redundant mechanisms. Chromosomal DNA dependent cohesin cleavage by separase is a component of a regulatory pathway that cells utilize to protect the bulk of cohesin. Degradation of securin plays a critical role in the timely activation of separase activity. In vertebrate cells, separase is phosphorylated and inhibited before anaphase by a cyclin B/CDK1. Nuclear exclusion of separase might provide the means to preclude cohesin cleavage at telophase and G1 stage of the cell cycle | Homo sapiens |
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