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Information on EC 3.4.22.49 - separase and Organism(s) Mus musculus and UniProt Accession P60330
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3.4.22.49 separaseSpecify your search results
Word Map
- 3.4.22.49
-
chromatid
-
sister
-
anaphase
- cohesin
-
mitosis
- securin
- spindle
-
metaphase
-
meiotic
-
checkpoint
-
centromeres
-
kinetochore
-
anaphase-promoting
- scc1
-
prophase
-
aneuploidy
- rec8
- cdc14
- rad21
-
metaphase-to-anaphase
- centrosome
- shugoshins
- centriole
-
sister-chromatid
-
metaphase-anaphase
-
disjunction
-
medicaid
-
disengagement
-
prometaphase
-
missegregation
-
polo-like
-
biorientation
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cyclosome
-
kleisin
-
meiosis-specific
-
chiasmata
- pds1
-
condensins
- medicine
- diagnostics
-
nondisjunction
- molecular biology
-
cdk1-dependent
-
pp2acdc55
-
kinetochore-microtubule
The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Reaction Schemes
all bonds known to be hydrolysed by this endopeptidase have arginine in P1 and an acidic residue in P4. P6 is often occupied by an acidic residue or by an hydroxy-amino-acid residue, the phosphorylation of which enhances cleavage
Synonyms
separase, sep-1, espl1, separin, atesp, cut1/separase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
separin
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
351527-77-0
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
cohesin + H2O
?
chromatin-bound cohesion is the preferential substrate
-
-
?
Rec8 + H2O
?
resolution of chiasmata in oocytes requires separase-mediated proteolysis. Proteolytic cleavage by separase is essential for Rec8's removal from chromosome arms and for chiasma resolution but not for the first polar body
-
-
?
cohesin + H2O
?
-
separase selectively cleaves only the chromosome-associated cohesin with the cofactor chromosomal DNA
-
-
?
additional information
?
-
-
deletion of separase specifically blocks sister chromatid separation but not other aspects of mitosis, mitotic exit, cytokinesis, or even chromosome replication
-
-
?
additional information
?
-
-
the meiosis I-to-meiosis II transition in mouse oocytes requires separase activity
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
cohesin + H2O
?
chromatin-bound cohesion is the preferential substrate
-
-
?
Rec8 + H2O
?
resolution of chiasmata in oocytes requires separase-mediated proteolysis. Proteolytic cleavage by separase is essential for Rec8's removal from chromosome arms and for chiasma resolution but not for the first polar body
-
-
?
cohesin + H2O
?
-
separase selectively cleaves only the chromosome-associated cohesin with the cofactor chromosomal DNA
-
-
?
additional information
?
-
-
deletion of separase specifically blocks sister chromatid separation but not other aspects of mitosis, mitotic exit, cytokinesis, or even chromosome replication
-
-
?
additional information
?
-
-
the meiosis I-to-meiosis II transition in mouse oocytes requires separase activity
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
sercurin
securin persistently binds and inhibits separase during much of metaphase
-
additional information
-
nuclear exclusion of separase might provide the means to preclude cohesin cleavage at telophase and G1 stage of the cell cycle
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
in a murine model of absent securin expression, the PTTG knock-out mouse, separase and Rad21 are over-expressed in multiple brain regions. Furthermore, Rad21 mRNA expression is highly correlated with that of securin, separase, cyclin C and sestrin 2 in fetal brains
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
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
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
physiological function
binding between separase and cyclin B1 is required for the anaphase movement of unpaired sister chromatids. Separase promotes the reversal of Cdk1-mediated phosphorylation on chromosomes at anaphase onset
physiological function
the enzyme resolves sister chromatid cohesion during the metaphase-to-anaphase transition and plays a pivotal role in chromosomal segregation and cell division. Separase is oncogenic, and its overexpression is sufficient to induce mammary tumours in mice. Either acute or chronic overexpression of separase in mouse mammary glands leads to aneuploidy and tumorigenesis, and inhibition of separase enzymatic activity decreases the growth of human breast tumour xenografts in mice
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). ESPL1_MOUSE
2118
0
233035
Swiss-Prot
other Location (Reliability: 3)
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
phosphoprotein
-
by phosphorylation of serine 1121 separase is negatively regulated
phosphoprotein
-
phosphorylation on Ser1121, mechanism to inhibit activity prior to the onset of the anaphase. Inhibitory phosphorylation of separase is not required for meiosis. Critical role of separase phosphorylation in germ cell development as well as in early embryogenesis
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
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
S1121A
S1126A
-
specifically abolished separase hyperphosphorylation in Smad3-deficient cells
additional information
-
clear evidence for a non-proteolytic function of separase is provided: by separase gene deletion in mouse oocytes it is shown that separase null-oocytes are unable to either destroy chesin along chromosome arms or segregate homologous chromosomes and these oocytes are unable to complete cell division. Microinjection of wild-type separase mRNA in separase null-oocytes restores normal homologue disjunction and polar body extrusion
S1121A
-
a mouse strain is created bearing a S1121A mutation: S1121A mutation causes infertility in mice, germ cells in the mutants are depleted during development. S1121A causes chromosome misalignment during proliferation of the postmigratory primordial germ cells, resulting in mitotic arrest, aneuploidy, and eventual cell death
S1121A
-
mutation causes embryogenesis failure between the 8- and 16-cell stages in mice
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
analysis of correlation between overexpression of separase and aneuploidy in tetracycline-inducible diploid FSK3 mouse mammary epithelial cells
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enhanced cyclin-dependent kinase 1 activity due to deregulation of CDC27-anaphase-promoting complex leads in turn to hyperphosphorylation of Separase, impeding chromatid separation. Regulation of mitotic progression by transforming growth factor-beta in bone marrow stromal cells is through targeting the APC-separase pathway
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
molecular biology
molecular biology
-
data suggest that the co-ordinated expression of separase, securin and Rad21 is fundamental for the developing brain
molecular biology
-
separse is not only required for chromosome segregation but also for meiotic exit
molecular biology
-
the results indicate that inhibitory phosphorylation of separase plays a critical role in the maintenance of sister chromatid cohesion and genome stability in proliferating postmigratory primordial germ cells
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Kudo, N.R.; Wassmann, K.; Anger, M.; Schuh, M.; Wirth, K.G.; Xu, H.; Helmhart, W.; Kudo, H.; McKay, M.; Maro, B.; Ellenberg, J.; de Boer, P.; Nasmyth, K.
Resolution of chiasmata in oocytes requires separase-mediated proteolysis
Cell
126
135-146
2006
Mus musculus (P60330), Mus musculus
Terret, M.E.; Wassmann, K.; Waizenegger, I.; Maro, B.; Peters, J.M.; Verlhac, M.H.
The meiosis I-to-meiosis II transition in mouse oocytes requires separase activity
Curr. Biol.
13
1797-1802
2003
Mus musculus
Wirth, K.G.; Wutz, G.; Kudo, N.R.; Desdouets, C.; Zetterberg, A.; Taghybeeglu, S.; Seznec, J.; Ducos, G.M.; Ricci, R.; Firnberg, N.; Peters, J.M.; Nasmyth, K.
Separase: a universal trigger for sister chromatid disjunction but not chromosome cycle progression
J. Cell Biol.
172
847-860
2006
Mus musculus
Pemberton, H.N.; Franklyn, J.A.; Boelaert, K.; Chan, S.Y.; Kim, D.S.; Kim, C.; Cheng, S.Y.; Kilby, M.D.; McCabe, C.J.
Separase, securin and Rad21 in neural cell growth
J. Cell. Physiol.
213
45-53
2007
Homo sapiens, Mus musculus
Terret, M.; Jallepalli, P.V.
Meiosis: separase strikes twice
Nat. Cell Biol.
8
910-911
2006
Saccharomyces cerevisiae, Mus musculus
Huang, X.; Andreu-Vieyra, C.V.; York, J.P.; Hatcher, R.; Lu, T.; Matzuk, M.M.; Zhang, P.
Inhibitory phosphorylation of separase is essential for genome stability and viability of murine embryonic germ cells
PLoS Biol.
6
e15
2008
Mus musculus
Fujita, T.; Epperly, M.W.; Zou, H.; Greenberger, J.S.; Wan, Y.
Regulation of the anaphase-promoting complex-separase cascade by transforming growth factor-beta modulates mitotic progression in bone marrow stromal cells
Mol. Biol. Cell
19
5446-5455
2008
Mus musculus
Huang, X.; Andreu-Vieyra, C.V.; Wang, M.; Cooney, A.J.; Matzuk, M.M.; Zhang, P.
Preimplantation mouse embryos depend on inhibitory phosphorylation of separase to prevent chromosome missegregation
Mol. Cell. Biol.
29
1498-1505
2009
Mus musculus
Zhang, N.; Ge, G.; Meyer, R.; Sethi, S.; Basu, D.; Pradhan, S.; Zhao, Y.J.; Li, X.N.; Cai, W.W.; El-Naggar, A.K.; Baladandayuthapani, V.; Kittrell, F.S.; Rao, P.H.; Medina, D.; Pati, D.
Overexpression of Separase induces aneuploidy and mammary tumorigenesis
Proc. Natl. Acad. Sci. USA
105
13033-13038
2008
Homo sapiens, Mus musculus
Kucej, M.; Zou, H.
DNA-dependent cohesin cleavage by separase
Nucleus
1
4-7
2011
Saccharomyces cerevisiae, Homo sapiens, Mus musculus
Shindo, N.; Kumada, K.; Hirota, T.
Separase sensor reveals dual roles for separase coordinating cohesin cleavage and cdk1 inhibition
Dev. Cell
23
112-123
2012
Mus musculus (P60330)
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