Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Cdc14 + H2O
?
-
separase regulates INCENP-Aurora B anaphase spindle function through activation of Cdc14
-
-
?
cohesin + H2O
cleaved cohesin
cohesin + H2O
fragments of cohesin
Rec8 + H2O
fragments of Rac8
Rec8 + H2O
fragments of Rec8
-
phosphorylation either of separase or cohesin is necessary for Rec8 cleavage
-
-
?
Scc1 + H2O
fragments of Scc1
Slk19 + H2O
?
-
a protein implicated in the mitotic exit via its role in the stabilization of spindle in budding yeast
-
-
?
Slk19 + H2O
cleaved Slk19
Slk19 + H2O
fragments of Slk19
-
separase cleaves the kinetochore-associated protein Slk19 in anaphase
-
?
additional information
?
-
cohesin + H2O
?
-
-
-
?
cohesin + H2O
?
-
-
-
-
?
cohesin + H2O
?
cohesin Is cleaved with similar kinetics and timing near the centromere and telomere. Separase inhibition of PP2ACdc55 is necessary for robust cleavage of cohesin
-
-
?
cohesin + H2O
?
-
-
-
-
?
cohesin + H2O
?
-
separase selectively cleaves only the chromosome-associated cohesin with the cofactor chromosomal DNA
-
-
?
cohesin + H2O
cleaved cohesin
-
-
-
-
?
cohesin + H2O
cleaved cohesin
-
separase, i.e. Esp1, is implicated in the removal of cohesin which links sister chromatids in the S-phase and is postulated to be a specific protease or a positive regulator of protease against cohesin
-
-
?
cohesin + H2O
cleaved cohesin
-
separase triggers anaphase by cohesin cleavage, and triggers the release and activation of the phosphatase Cdc14 independently of its protease activity
-
-
?
cohesin + H2O
fragments of cohesin
-
-
-
?
cohesin + H2O
fragments of cohesin
-
-
-
?
cohesin + H2O
fragments of cohesin
-
-
-
-
?
cohesin + H2O
fragments of cohesin
-
separase Esp1 is implicated in the removal of cohesin which links sister chromatids in the S-phase and is postulated to be a specific protease or a positive regulator of protease against cohesin
-
?
Rec8 + H2O
cleaved Rac8
-
-
-
-
?
Rec8 + H2O
cleaved Rac8
-
cleavage of meiosis-specific Scc1 variant Rec8 is required for chromosome segregation during meiosis
-
-
?
Rec8 + H2O
fragments of Rac8
-
-
-
?
Rec8 + H2O
fragments of Rac8
-
cleavage of meiosis-specific Scc1 variant Rec8 is required for chromosome segregation during meiosis
-
?
Scc1 + H2O
cleaved Scc1
-
-
-
-
?
Scc1 + H2O
cleaved Scc1
-
Esp1 cleaves Scc1, the central subunit of the chromosomal cohesin complex during mitosis
-
-
?
Scc1 + H2O
cleaved Scc1
-
cleavage at 2 defined sites results in rapid destabilization of Scc1 and its dissociation from chromosomes
-
-
?
Scc1 + H2O
fragments of Scc1
-
-
-
?
Scc1 + H2O
fragments of Scc1
-
separase Esp1 cleaves Scc1, the central subunit of the chromosomal cohesin complex during mitosis
-
?
Slk19 + H2O
cleaved Slk19
-
-
-
-
?
Slk19 + H2O
cleaved Slk19
-
separase cleaves the kinetochore-associated protein Slk19 in metaphase-to-anaphase transition
-
-
?
additional information
?
-
the enzyme interacts with Ty1-IN and does not affect the processing of the TyA-TyB polypeptide
-
-
?
additional information
?
-
-
the enzyme interacts with Ty1-IN and does not affect the processing of the TyA-TyB polypeptide
-
-
?
additional information
?
-
-
downregulation of PP2A(Cdc55) phosphatase by separase initiates mitotic exit. At anaphase onset, PP2A(Cdc55) activity is downregulated in a separase-dependent manner, triggering a first wave of Cdk-dependent Net1 phosphorylation and Cdc14 release. Separase is the essential trigger for Cdc14 activation in anaphase
-
-
?
additional information
?
-
-
separase recognizes both, a cleavage site consensus sequence as well as features outside the cleavage site
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
evolution
in-depth bioinformatical analysis of separase and generation of structural models of the two conserved domains that comprise the C-terminal region: a caspase-like domain and a putative death domain. This analysis provides insights into substrate recognition and identifies potential sites of protein-protein interactions. Both the death domain and caspase-like domain are well-conserved in separases, which suggests an evolutionary pressure to keep these two domains together, perhaps to enable separase activity and/or provide stability
evolution
-
separases belong to CD clan of cysteine proteases. Unlike other members of this clan, separases are large multidomain proteins with more than 1000 amino acid residues. The catalytic domain of Arabidopsis thaliana separase exhibits 31 and 32% identity to the corresponding domains of human and budding yeast homologues, respectively. The sequence identity drops dramatically for the N-termini of separases. Mode of action in vivo and mechanistic differences in mitosis between organisms, overview
physiological function
separase acts directly on Scc1 and also indirectly, through inhibition of PP2ACdc55, to stimulate cohesin cleavage, providing a feedforward loop that may contribute to a robust and timely anaphase. PP2A activity is inhibited by separase during anaphase, triggering activation of the Cdc14 mitotic phosphatase
physiological function
separase is required at the onset of anaphase to cleave cohesin and thereby enable sister chromatid separation. The enzyme also promotes release of the Cdc14 phosphatase from the nucleolus to enable mitotic exit. The enzyme serves two roles to mediate Ty1 transposition, one to remove cohesin and the second to target Ty1-IN to chromatin
physiological function
chiasmata resolution and segregation of homologous chromosome pair. Role in DNA repair. Assembly and elongation of spindle at mitotic anaphase. Spindle formation in meiosis. Karyokinesis (division of nucleus). Spindle midzone assembly. Apoptosis promotion. Cleavage of Slk19. Cdc14 activation and release of Cdc14 from nucleolus
physiological function
separase cleaves the proteins that maintain the cohesion between sister chromatids
malfunction
-
cells that do not express both Cdc55 and securin prematurely separate their sister chromatids, leading to cell death
malfunction
-
in the cells lacking securin Pds1, Esp1 distribution is largely restricted to the cytoplasm
physiological function
-
function of separases in metaphase to anaphase transition, overview. Separase cleaves and removes the remaining centromeric cohesin. In yeasts, separase is responsible for the removal of both arm and centromeric cohesin after its phosphorylation by Cdc5 or other Plks. Esp1 action is not limited to this stage. When securin is depleted in yeast cells, the proteolytic activity of Esp1 is no longer cell cycle regulated, while Scc1 is cleaved on schedule suggesting the existence of additional regulatory elements
physiological function
-
separase Esp1 is a protease specialized in the cleavage of sister chromatid cohesion. When inhibitor securin Pds1 is degraded, Esp1 is activated, and cells transit into anaphase. Esp1, together with Clb2- and Polo-kinases, promotes Cdc14 activation through the FEAR network. Separase also leads to the activation of Cdc14 phosphatase. The phosphatase is kept inactive in the nucleolus by Net1 throughout the cell cycle until anaphase. The proteolytic function of separase causes spindle elongation by cohesin cleavage, which activates mitotic exit network, MEN, by bringing Tem1 together with its activator Lte1
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
additional information
-
dynamics of the mitotic exit control system in budding yeast, Queralt's model, modifications, overview. Queralt's model centres around the non-proteolytic function of separase Esp1, which triggers a positive feedback in the activation of MEN by FEAR-induced release of Cdc14
additional information
-
securin, in addition to its inhibitory role, can act as a molecular chaperone of separase, essential for its proper folding. Securin is dispensable for the growth of normal human cells. The first 156 amino acids of Esp1 seem imperative for the binding of securin Pds1, it interacts with other parts of Esp1 as well. Securin is not only a guardian of separase, but is also responsible for its translocation to the nucleus in the budding yeast
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Yanagida, M.
Cell cycle mechanisms of sister chromatid separation; roles of Cut1/separin and Cut2/securin
Genes Cells
5
1-8
2000
Saccharomyces cerevisiae, Homo sapiens, Schizosaccharomyces pombe
brenda
Sullivan, M.; Lehane, C.; Uhlmann, F.
Orchestrating anaphase and mitotic exit: separase cleavage and localization of Slk19
Nat. Cell Biol.
3
771-777
2001
Saccharomyces cerevisiae
brenda
Amon, A.
Together until separin do us part
Nat. Cell Biol.
3
E12-14
2001
Saccharomyces cerevisiae, Homo sapiens, Schizosaccharomyces pombe
brenda
Siomos, M.F.; Badrinath, A.; Pasierbek, P.; Livingstone, D.; White, J.; Glotzer, M.; Nasmyth, K.
Separase is required for chromosome segregation during meiosis I in Caenorhabditis elegans
Curr. Biol.
11
1825-1835
2001
Saccharomyces cerevisiae, Caenorhabditis elegans
brenda
Ross, K.E.; Cohen-Fix, O.
Separase: a conserved protease separating more than just sisters
Trends Cell Biol.
12
1-3
2002
Saccharomyces cerevisiae, Drosophila melanogaster, Homo sapiens, Schizosaccharomyces pombe, Xenopus laevis
brenda
Hornig, N.C.; Knowles, P.P.; McDonald, N.Q.; Uhlmann, F.
The dual mechanism of separase regulation by securin
Curr. Biol.
12
973-982
2002
Saccharomyces cerevisiae
brenda
Stegmeier, F.; Visintin, R.; Amon, A.
Separase, polo kinase, the kinetochore protein Slk19, and Spo12 function in a network that controls Cdc14 localization during early anaphase
Cell
108
207-220
2002
Saccharomyces cerevisiae
brenda
Buonomo, S.B.C.; Rabitsch, K.P.; Fuchs, J.; Gruber, S.; Sullivan, M.; Uhlmann, F.; Petronczki, M.; Toth, A.; Nasmyth, K.
Division of the nucleolus and its release of CDC14 during anaphase of meiosis I depends on separase, SPO12, and SLK19
Dev. Cell
4
727-739
2003
Saccharomyces cerevisiae
brenda
Sullivan, M.; Uhlmann, F.
A non-proteolytic function of separase links the onset of anaphase to mitotic exit
Nat. Cell Biol.
5
249-254
2003
Saccharomyces cerevisiae
brenda
Queralt, E.; Lehane, C.; Novak, B.; Uhlmann, F.
Downregulation of PP2A(Cdc55) phosphatase by separase initiates mitotic exit in budding yeast
Cell
125
719-732
2006
Saccharomyces cerevisiae
brenda
Sullivan, M.; Hornig, N.C.; Porstmann, T.; Uhlmann, F.
Studies on substrate recognition by the budding yeast separase
J. Biol. Chem.
279
1191-1196
2004
Saccharomyces cerevisiae
brenda
Pereira, G.; Schiebel, E.
Separase regulates INCENP-Aurora B anaphase spindle function through Cdc14
Science
302
2120-2124
2003
Saccharomyces cerevisiae
brenda
Terret, M.; Jallepalli, P.V.
Meiosis: separase strikes twice
Nat. Cell Biol.
8
910-911
2006
Saccharomyces cerevisiae, Mus musculus
brenda
Baskerville, C.; Segal, M.; Reed, S.I.
The protease activity of yeast separase (esp1) is required for anaphase spindle elongation independently of its role in cleavage of cohesin
Genetics
178
2361-2372
2008
Saccharomyces cerevisiae
brenda
Queralt, E.; Uhlmann, F.
Separase cooperates with Zds1 and Zds2 to activate Cdc14 phosphatase in early anaphase
J. Cell Biol.
182
873-883
2008
Saccharomyces cerevisiae
brenda
Lu, Y.; Cross, F.
Mitotic exit in the absence of separase activity
Mol. Biol. Cell
20
1576-1591
2009
Saccharomyces cerevisiae (Q03018), Saccharomyces cerevisiae
brenda
Katis, V.L.; Lipp, J.J.; Imre, R.; Bogdanova, A.; Okaz, E.; Habermann, B.; Mechtler, K.; Nasmyth, K.; Zachariae, W.
Rec8 phosphorylation by casein kinase 1 and Cdc7-Dbf4 kinase regulates cohesin cleavage by separase during meiosis
Dev. Cell
18
397-409
2010
Saccharomyces cerevisiae, Saccharomyces cerevisiae SK1
brenda
Vinod, P.K.; Freire, P.; Rattani, A.; Ciliberto, A.; Uhlmann, F.; Novak, B.
Computational modelling of mitotic exit in budding yeast: the role of separase and Cdc14 endocycles
J. R. Soc. Interface
8
1128-1141
2011
Saccharomyces cerevisiae
brenda
Kucej, M.; Zou, H.
DNA-dependent cohesin cleavage by separase
Nucleus
1
4-7
2011
Saccharomyces cerevisiae, Homo sapiens, Mus musculus
brenda
Moschou, P.N.; Bozhkov, P.V.
Separases: biochemistry and function
Physiol. Plant.
145
67-76
2012
Saccharomyces cerevisiae, Caenorhabditis elegans, Ricinus communis, Chlamydomonas reinhardtii, Drosophila melanogaster, Homo sapiens, Oryza sativa, Schizosaccharomyces pombe, Sorghum bicolor, Vitis vinifera, Cryptosporidium muris, Arabidopsis thaliana (Q5IBC5)
brenda
Yaakov, G.; Thorn, K.; Morgan, D.O.
Separase biosensor reveals that cohesin cleavage timing depends on phosphatase PP2A(Cdc55) regulation
Dev. Cell
23
124-136
2012
Saccharomyces cerevisiae (Q03018), Saccharomyces cerevisiae
brenda
Han, X.; Poon, R.Y.
Critical differences between isoforms of securin reveal mechanisms of separase regulation
Mol. Cell. Biol.
33
3400-3415
2013
Saccharomyces cerevisiae (Q03018)
brenda
Ho, K.L.; Ma, L.; Cheung, S.; Manhas, S.; Fang, N.; Wang, K.; Young, B.; Loewen, C.; Mayor, T.; Measday, V.
A role for the budding yeast separase, Esp1, in Ty1 element retrotransposition
PLoS Genet.
11
e1005109
2015
Saccharomyces cerevisiae (Q03018), Saccharomyces cerevisiae
brenda
Luo, S.; Tong, L.
Structural biology of the separase-securin complex with crucial roles in chromosome segregation
Curr. Opin. Struct. Biol.
49
114-122
2018
Caenorhabditis elegans (G5ED39), Caenorhabditis elegans, Saccharomyces cerevisiae, Thermochaetoides thermophila (G0SHM3), Thermochaetoides thermophila DSM 1495 (G0SHM3)
brenda
Kumar, R.
Separase Function beyond cohesion cleavage and an emerging oncogene
J. Cell. Biochem.
118
1283-1299
2017
Caenorhabditis elegans, Arabidopsis thaliana (A0A1P8B3N4), Schizosaccharomyces pombe (P18296), Saccharomyces cerevisiae (Q03018), Drosophila melanogaster (Q9VRN6), Picea abies (R4XPW1), Schizosaccharomyces pombe ATCC 24843 (P18296)
brenda
Winter, A.; Schmid, R.; Bayliss, R.
Structural insights into separase architecture and substrate recognition through computational modelling of caspase-like and death domains
PLoS Comput. Biol.
11
e1004548
2015
Arabidopsis thaliana (Q5IBC5), Caenorhabditis elegans (G5ED39), Caenorhabditis elegans, Homo sapiens (Q14674), Saccharomyces cerevisiae (Q03018), Saccharomyces cerevisiae ATCC 204508 (Q03018)
brenda