Any feedback?
No. of entries
Information on EC 3.4.22.49 - separase
for references in articles please use BRENDA:EC3.4.22.49
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree 3 Hydrolases
3.4 Acting on peptide bonds (peptidases)
3.4.22 Cysteine endopeptidases
3.4.22.49 separase
IUBMB Comments
In both budding yeast and human cells, cleavage of the cohesin subunit Scc1 by separase is required for sister chromatid separation in mitosis. Budding yeast separase is also known to cleave the Rec8 subunit of a meiotic cohesin complex and the kinetochore protein Slk19. Type example of peptidase family C50.
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
- 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
-
cyclosome
-
kleisin
-
meiosis-specific
-
chiasmata
- pds1
-
condensins
- medicine
- diagnostics
-
nondisjunction
- molecular biology
-
cdk1-dependent
-
pp2acdc55
-
kinetochore-microtubule
Reaction Schemes
showall 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
topPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Cut1
Esp1
ESPL1
sep-1
separase
separin
-
-
-
-
Esp1
-
Saccharomyces cerevisiae separase homolog, N-terminal region comprises approximately the first 850 amino acids of the 1630 amino acids open reading frame
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
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
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
-
-
-
-
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
cohesin cleavage by human separase requires DNA in a sequence-nonspecific manner (in vitro). Autocleavage of separase is not stimulated by DNA. Cleavage of the chromosome-associated cohesins is sensitive to nuclease treatment.
-
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
unphosphorylatable form of cohesin subunit Rad21 is less efficiently cleaved by Separase
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
hydrolysis of peptide bond
-
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
CAS REGISTRY NUMBER
COMMENTARY
351527-77-0
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
acetyl-Asp-Arg-Glu-Ile-Nle-Arg-7-amido-4-methylcoumarin + H2O
acetyl-Asp-Arg-Glu-Ile-Nle-Arg + 7-amino-4-methylcoumarin
-
Substrates: acetyl-Asp-Arg-Glu-Ile-Nle-Arg is the Rad21-peptidyl
Products: -
Products: -
?
Cdc14 + H2O
?
-
Substrates: separase regulates INCENP-Aurora B anaphase spindle function through activation of Cdc14
Products: -
Products: -
?
Rad21 + H2O
cleaved Rad21
-
Substrates: Rad21 is cleaved by Cut1 at the metaphase-anaphase transition
Products: -
Products: -
?
Slk19 + H2O
fragments of Slk19
-
Substrates: separase cleaves the kinetochore-associated protein Slk19 in anaphase
Products: -
Products: -
?
SYN1 + H2O
?
Substrates: the enzyme plays an essential role in embryo development. The enzyme is required for the removal of cohesin from meiotic chromosomes. The cleavage of SYN1 by separase is responsible for the release of sister chromatid cohesion during meiosis
Products: -
Products: -
?
[Cy5-D-R-E-I-M-R]2-rhodamine-110 + H2O
2 [Cy5-D-R-E-I-M-R] + rhodamine-110
Substrates: -
Products: -
Products: -
?
[Cy5-DREIMR]2-rhodamine 110 + H2O
[Cy5-DREIMR]2 + rhodamine 110
Substrates: -
Products: -
Products: -
?
Bcl-xL + H2O
?
Substrates: the enzyme cleaves BCL-XL after Arg34. Cleavage of the substrate by the enzyme essentially requires phosphorylation by NEK2A
Products: -
Products: -
?
BCL-XL protein + H2O
?
Substrates: -
Products: -
Products: -
?
cohesin + H2O
?
-
Substrates: cohesin cleavage by human separase requires DNA in a sequence-nonspecific manner
Products: -
Products: -
?
cohesin + H2O
?
-
Substrates: separase selectively cleaves only the chromosome-associated cohesin with the cofactor chromosomal DNA, chromosome-associated cohesin is cleaved preferentially by separase, mechanism
Products: -
Products: -
?
cohesin + H2O
?
-
Substrates: separase selectively cleaves only the chromosome-associated cohesin with the cofactor chromosomal DNA
Products: -
Products: -
?
cohesin + H2O
?
Substrates: chromatin-bound cohesion is the preferential substrate
Products: -
Products: -
?
cohesin + H2O
?
-
Substrates: separase selectively cleaves only the chromosome-associated cohesin with the cofactor chromosomal DNA
Products: -
Products: -
?
cohesin + H2O
?
Substrates: cohesin Is cleaved with similar kinetics and timing near the centromere and telomere. Separase inhibition of PP2ACdc55 is necessary for robust cleavage of cohesin
Products: -
Products: -
?
cohesin + H2O
?
-
Substrates: separase-mediated cleavage of cohesin at interphase is required for DNA repair. It is proposed that the securin-separase complex might aid DNA repair by removing local cohesin in interphase cells
Products: -
Products: -
?
cohesin + H2O
?
Substrates: the enzyme cleaves the kleisin subunit of cohesin and opens the cohesin ring to allow chromosome segregation
Products: -
Products: -
?
cohesin + H2O
?
Substrates: the enzyme cleaves the kleisin subunit of cohesin and opens the cohesin ring to allow chromosome segregation
Products: -
Products: -
?
cohesin + H2O
cleaved cohesin
-
Substrates: separase is required for sister chromatid separation during mitosis
Products: -
Products: -
?
cohesin + H2O
cleaved cohesin
-
Substrates: 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
Products: -
Products: -
?
cohesin + H2O
cleaved cohesin
-
Substrates: separase triggers anaphase by cohesin cleavage, and triggers the release and activation of the phosphatase Cdc14 independently of its protease activity
Products: -
Products: -
?
cohesin + H2O
fragments of cohesin
-
Substrates: -
Products: -
Products: -
?
cohesin + H2O
fragments of cohesin
-
Substrates: 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
Products: -
Products: -
?
cohesin + H2O
fragments of cohesin
-
Substrates: -
Products: -
Products: -
?
cohesin + H2O
fragments of cohesin
-
Substrates: -
Products: -
Products: -
?
CPAR-1 protein + H2O
?
Substrates: separase cleaves the N-tail of the CENP-A related protein CPAR-1 at the meiosis I metaphase-anaphase transition
Products: -
Products: -
?
kendrin + H2O
?
Substrates: kendrin, also named pericentrin and specifically cleaved at a consensus site (R2231), is a crucial substrate for separase at the centrosome, protecting the engaged centrioles from premature disengagement and thereby blocking reduplication until the cell passes through mitosis
Products: -
Products: -
?
kleisin subunit of cohesin + H2O
?
Substrates: cleavage triggers chromosome segregation during cell division
Products: -
Products: -
?
kleisin subunit of cohesin + H2O
?
Substrates: -
Products: -
Products: -
?
kleisin subunit of cohesin + H2O
?
Substrates: cleavage triggers chromosome segregation during cell division
Products: -
Products: -
?
kleisin subunit of cohesin + H2O
?
Substrates: -
Products: -
Products: -
?
MCL-1 protein + H2O
?
Substrates: cleavage triggers apoptosis
Products: -
Products: -
?
MCL-1 protein + H2O
?
Substrates: cleavage triggers apoptosis
Products: -
Products: -
?
MCL1 + H2O
?
Substrates: the enzyme cleaves MCL1 after Arg176. Cleavage of the substrate by the enzyme essentially requires phosphorylation by NEK2A
Products: -
Products: -
?
Meikin + H2O
?
Substrates: separase cleaves the kinetochore protein Meikin at the meiosis I/II transition
Products: -
Products: -
?
Rad21 + H2O
fragments of Rad21
-
Substrates: Rad21 is cleaved by the separase Cut1 at the metaphase-anaphase transition
Products: -
Products: -
?
Rec8 + H2O
?
Substrates: Rec8 is a subunit of the cohesin complex constituting the physical connection between sister chromatids. Rec8 is cleaved on chromosome arms in meiosis I and in the centromere region in meiosis II
Products: -
Products: -
?
Rec8 + H2O
?
Substrates: 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
Products: -
Products: -
?
Rec8 + H2O
?
-
Substrates: cleavage is required for meiotic nuclear divisions in fission yeast
Products: -
Products: -
?
Rec8 + H2O
cleaved Rac8
-
Substrates: cleavage of meiosis-specific Scc1 variant Rec8 is required for chromosome segregation during meiosis
Products: -
Products: -
?
Rec8 + H2O
fragments of Rac8
-
Substrates: cleavage of meiosis-specific Scc1 variant Rec8 is required for chromosome segregation during meiosis
Products: -
Products: -
?
Rec8 + H2O
fragments of Rec8
-
Substrates: the phosphorylations of Rec8 at S412 and the surrounding sites, which are most probably dependent on CK1, are essential for the cleavability of Rec8 by separase
Products: -
Products: -
?
Rec8 + H2O
fragments of Rec8
-
Substrates: Rec8 is a meiosis-specific alpha-kleisin subunit of cohesion, phosphorylation by polo-like kinase 1 of either Rec8 or separase, or both, promotes Rec8 cleavage. Separase prefers to cleave at R454
Products: -
Products: -
?
Rec8 + H2O
fragments of Rec8
-
Substrates: phosphorylation either of separase or cohesin is necessary for Rec8 cleavage
Products: -
Products: -
?
Rec8 + H2O
fragments of Rec8
-
Substrates: phosphorylation either of separase or cohesin is necessary for Rec8 cleavage
Products: -
Products: -
?
Scc1 + H2O
?
Substrates: an LPE motif is identified on the Scc1 substrate that is distinct from the cleavage site and is required for rapid and specific substrate cleavage
Products: -
Products: -
?
Scc1 + H2O
cleaved Scc1
-
Substrates: Scc1 contains 2 separase cleavage sites
Products: -
Products: -
?
Scc1 + H2O
cleaved Scc1
-
Substrates: Esp1 cleaves Scc1, the central subunit of the chromosomal cohesin complex during mitosis
Products: -
Products: -
?
Scc1 + H2O
cleaved Scc1
-
Substrates: cleavage at 2 defined sites results in rapid destabilization of Scc1 and its dissociation from chromosomes
Products: -
Products: -
?
Scc1 + H2O
fragments of Scc1
-
Substrates: Scc1 is a subunit of cohesion, centrosomal Scc1 is cleaved by separase coincidentally with chromatin Scc1
Products: -
Products: -
?
Scc1 + H2O
fragments of Scc1
-
Substrates: Scc1 is an alpha-kleisin subunit of cohesin
Products: -
Products: -
?
Scc1 + H2O
fragments of Scc1
-
Substrates: separase Esp1 cleaves Scc1, the central subunit of the chromosomal cohesin complex during mitosis
Products: -
Products: -
?
Slk19 + H2O
?
Substrates: the cleavage product of Slk19 stabilizes the anaphase spindle
Products: -
Products: -
?
Slk19 + H2O
?
-
Substrates: a protein implicated in the mitotic exit via its role in the stabilization of spindle in budding yeast
Products: -
Products: -
?
Slk19 + H2O
cleaved Slk19
-
Substrates: separase cleaves the kinetochore-associated protein Slk19 in metaphase-to-anaphase transition
Products: -
Products: -
?
additional information
?
-
-
Substrates: separase is primarily required for sister chromatid separation during mitotic and meiotic division, by cleavage of a subunit of the cohesin complex. Separase is also and perhaps indirectly important for epithelial integrity
Products: -
Products: -
?
additional information
?
-
-
Substrates: separase auto-cleavage coordinates multiple aspects of the G2/M programme in human cells, thus contributing to the timing and efficiency of chromosome segregation
Products: -
Products: -
?
additional information
?
-
-
Substrates: Hela cells lacking separase are delayed or arrested at the G2-M phase transition. Without separase, cells also have a prolonged prometaphase. Separase is required at multiple cell cycle stages including the interphase. Its role in promoting loss of sister chromatid cohesion might be important preferentially at arms but not centromers
Products: -
Products: -
?
additional information
?
-
-
Substrates: auto-cleavage of separase coordinates multiple aspects of the G2/M programme in human cells, thus contributing to the timing and efficiency of chromosome segregation
Products: -
Products: -
?
additional information
?
-
-
Substrates: does not cleave Leu-Glu-His-Asp-CHO-7-amido-4-methylcoumarin
Products: -
Products: -
?
additional information
?
-
-
Substrates: autocleavage of human separase is to be essential and results in conformational changes
Products: -
Products: -
?
additional information
?
-
-
Substrates: the meiosis I-to-meiosis II transition in mouse oocytes requires separase activity
Products: -
Products: -
?
additional information
?
-
-
Substrates: deletion of separase specifically blocks sister chromatid separation but not other aspects of mitosis, mitotic exit, cytokinesis, or even chromosome replication
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: separase recognizes both, a cleavage site consensus sequence as well as features outside the cleavage site
Products: -
Products: -
?
additional information
?
-
Substrates: the enzyme interacts with Ty1-IN and does not affect the processing of the TyA-TyB polypeptide
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme interacts with Ty1-IN and does not affect the processing of the TyA-TyB polypeptide
Products: -
Products: -
?
additional information
?
-
Substrates: identification of a novel substrate motif of yeast separase and deciphering the recognition specificity using AlphaFold2 and molecular dynamics simulation
Products: -
Products: -
-
additional information
?
-
-
Substrates: MAP kinase is required for the increased securin-separase interaction that rescues separase mutants under stresses
Products: -
Products: -
?
additional information
?
-
-
Substrates: Cdc48 is required for the stability of Cut1/separase in mitotic anaphase
Products: -
Products: -
?
additional information
?
-
-
Substrates: TbSep is essential for the segregation of both large and minichromosomes (RNAi experiment)
Products: -
Products: -
?
additional information
?
-
-
Substrates: separase shows self-cleavage upon activation. Separase is auto-cleaved between meiosis I and II in oocytes
Products: -
Products: -
?
additional information
?
-
-
Substrates: separase is a stoichiometric inhibitor of cyclin-dependent kinase 1. This function of separase is independent of proteolytic activity
Products: -
Products: -
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
Cdc14 + H2O
?
-
Substrates: separase regulates INCENP-Aurora B anaphase spindle function through activation of Cdc14
Products: -
Products: -
?
CPAR-1 protein + H2O
?
Substrates: separase cleaves the N-tail of the CENP-A related protein CPAR-1 at the meiosis I metaphase-anaphase transition
Products: -
Products: -
?
Rad21 + H2O
cleaved Rad21
-
Substrates: Rad21 is cleaved by Cut1 at the metaphase-anaphase transition
Products: -
Products: -
?
Scc1 + H2O
fragments of Scc1
-
Substrates: Scc1 is a subunit of cohesion, centrosomal Scc1 is cleaved by separase coincidentally with chromatin Scc1
Products: -
Products: -
?
SYN1 + H2O
?
Substrates: the enzyme plays an essential role in embryo development. The enzyme is required for the removal of cohesin from meiotic chromosomes. The cleavage of SYN1 by separase is responsible for the release of sister chromatid cohesion during meiosis
Products: -
Products: -
?
Bcl-xL + H2O
?
Substrates: the enzyme cleaves BCL-XL after Arg34. Cleavage of the substrate by the enzyme essentially requires phosphorylation by NEK2A
Products: -
Products: -
?
BCL-XL protein + H2O
?
Substrates: -
Products: -
Products: -
?
cohesin + H2O
?
-
Substrates: cohesin cleavage by human separase requires DNA in a sequence-nonspecific manner
Products: -
Products: -
?
cohesin + H2O
?
-
Substrates: separase selectively cleaves only the chromosome-associated cohesin with the cofactor chromosomal DNA, chromosome-associated cohesin is cleaved preferentially by separase, mechanism
Products: -
Products: -
?
cohesin + H2O
?
-
Substrates: separase selectively cleaves only the chromosome-associated cohesin with the cofactor chromosomal DNA
Products: -
Products: -
?
cohesin + H2O
?
Substrates: chromatin-bound cohesion is the preferential substrate
Products: -
Products: -
?
cohesin + H2O
?
-
Substrates: separase selectively cleaves only the chromosome-associated cohesin with the cofactor chromosomal DNA
Products: -
Products: -
?
cohesin + H2O
?
Substrates: cohesin Is cleaved with similar kinetics and timing near the centromere and telomere. Separase inhibition of PP2ACdc55 is necessary for robust cleavage of cohesin
Products: -
Products: -
?
cohesin + H2O
?
-
Substrates: separase-mediated cleavage of cohesin at interphase is required for DNA repair. It is proposed that the securin-separase complex might aid DNA repair by removing local cohesin in interphase cells
Products: -
Products: -
?
cohesin + H2O
?
Substrates: the enzyme cleaves the kleisin subunit of cohesin and opens the cohesin ring to allow chromosome segregation
Products: -
Products: -
?
cohesin + H2O
?
Substrates: the enzyme cleaves the kleisin subunit of cohesin and opens the cohesin ring to allow chromosome segregation
Products: -
Products: -
?
cohesin + H2O
cleaved cohesin
-
Substrates: separase is required for sister chromatid separation during mitosis
Products: -
Products: -
?
cohesin + H2O
cleaved cohesin
-
Substrates: 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
Products: -
Products: -
?
cohesin + H2O
cleaved cohesin
-
Substrates: separase triggers anaphase by cohesin cleavage, and triggers the release and activation of the phosphatase Cdc14 independently of its protease activity
Products: -
Products: -
?
cohesin + H2O
fragments of cohesin
-
Substrates: -
Products: -
Products: -
?
kendrin + H2O
?
Substrates: kendrin, also named pericentrin and specifically cleaved at a consensus site (R2231), is a crucial substrate for separase at the centrosome, protecting the engaged centrioles from premature disengagement and thereby blocking reduplication until the cell passes through mitosis
Products: -
Products: -
?
kleisin subunit of cohesin + H2O
?
Substrates: cleavage triggers chromosome segregation during cell division
Products: -
Products: -
?
kleisin subunit of cohesin + H2O
?
Substrates: -
Products: -
Products: -
?
kleisin subunit of cohesin + H2O
?
Substrates: cleavage triggers chromosome segregation during cell division
Products: -
Products: -
?
kleisin subunit of cohesin + H2O
?
Substrates: -
Products: -
Products: -
?
MCL-1 protein + H2O
?
Substrates: cleavage triggers apoptosis
Products: -
Products: -
?
MCL-1 protein + H2O
?
Substrates: cleavage triggers apoptosis
Products: -
Products: -
?
MCL1 + H2O
?
Substrates: the enzyme cleaves MCL1 after Arg176. Cleavage of the substrate by the enzyme essentially requires phosphorylation by NEK2A
Products: -
Products: -
?
Rec8 + H2O
?
Substrates: Rec8 is a subunit of the cohesin complex constituting the physical connection between sister chromatids. Rec8 is cleaved on chromosome arms in meiosis I and in the centromere region in meiosis II
Products: -
Products: -
?
Rec8 + H2O
?
Substrates: 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
Products: -
Products: -
?
Rec8 + H2O
?
-
Substrates: cleavage is required for meiotic nuclear divisions in fission yeast
Products: -
Products: -
?
Rec8 + H2O
cleaved Rac8
-
Substrates: cleavage of meiosis-specific Scc1 variant Rec8 is required for chromosome segregation during meiosis
Products: -
Products: -
?
Rec8 + H2O
fragments of Rec8
-
Substrates: the phosphorylations of Rec8 at S412 and the surrounding sites, which are most probably dependent on CK1, are essential for the cleavability of Rec8 by separase
Products: -
Products: -
?
Rec8 + H2O
fragments of Rec8
-
Substrates: phosphorylation either of separase or cohesin is necessary for Rec8 cleavage
Products: -
Products: -
?
Rec8 + H2O
fragments of Rec8
-
Substrates: phosphorylation either of separase or cohesin is necessary for Rec8 cleavage
Products: -
Products: -
?
Scc1 + H2O
cleaved Scc1
-
Substrates: Scc1 contains 2 separase cleavage sites
Products: -
Products: -
?
Scc1 + H2O
cleaved Scc1
-
Substrates: Esp1 cleaves Scc1, the central subunit of the chromosomal cohesin complex during mitosis
Products: -
Products: -
?
Scc1 + H2O
cleaved Scc1
-
Substrates: cleavage at 2 defined sites results in rapid destabilization of Scc1 and its dissociation from chromosomes
Products: -
Products: -
?
Slk19 + H2O
?
Substrates: the cleavage product of Slk19 stabilizes the anaphase spindle
Products: -
Products: -
?
Slk19 + H2O
?
-
Substrates: a protein implicated in the mitotic exit via its role in the stabilization of spindle in budding yeast
Products: -
Products: -
?
Slk19 + H2O
cleaved Slk19
-
Substrates: separase cleaves the kinetochore-associated protein Slk19 in metaphase-to-anaphase transition
Products: -
Products: -
?
additional information
?
-
-
Substrates: separase is primarily required for sister chromatid separation during mitotic and meiotic division, by cleavage of a subunit of the cohesin complex. Separase is also and perhaps indirectly important for epithelial integrity
Products: -
Products: -
?
additional information
?
-
-
Substrates: separase auto-cleavage coordinates multiple aspects of the G2/M programme in human cells, thus contributing to the timing and efficiency of chromosome segregation
Products: -
Products: -
?
additional information
?
-
-
Substrates: Hela cells lacking separase are delayed or arrested at the G2-M phase transition. Without separase, cells also have a prolonged prometaphase. Separase is required at multiple cell cycle stages including the interphase. Its role in promoting loss of sister chromatid cohesion might be important preferentially at arms but not centromers
Products: -
Products: -
?
additional information
?
-
-
Substrates: auto-cleavage of separase coordinates multiple aspects of the G2/M programme in human cells, thus contributing to the timing and efficiency of chromosome segregation
Products: -
Products: -
?
additional information
?
-
-
Substrates: autocleavage of human separase is to be essential and results in conformational changes
Products: -
Products: -
?
additional information
?
-
-
Substrates: the meiosis I-to-meiosis II transition in mouse oocytes requires separase activity
Products: -
Products: -
?
additional information
?
-
-
Substrates: deletion of separase specifically blocks sister chromatid separation but not other aspects of mitosis, mitotic exit, cytokinesis, or even chromosome replication
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
Substrates: the enzyme interacts with Ty1-IN and does not affect the processing of the TyA-TyB polypeptide
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme interacts with Ty1-IN and does not affect the processing of the TyA-TyB polypeptide
Products: -
Products: -
?
additional information
?
-
-
Substrates: MAP kinase is required for the increased securin-separase interaction that rescues separase mutants under stresses
Products: -
Products: -
?
additional information
?
-
-
Substrates: TbSep is essential for the segregation of both large and minichromosomes (RNAi experiment)
Products: -
Products: -
?
additional information
?
-
-
Substrates: separase shows self-cleavage upon activation. Separase is auto-cleaved between meiosis I and II in oocytes
Products: -
Products: -
?
additional information
?
-
-
Substrates: separase is a stoichiometric inhibitor of cyclin-dependent kinase 1. This function of separase is independent of proteolytic activity
Products: -
Products: -
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Ca2+
the enzyme contains a Ca2+-binding EF-hand motif, which can possibly affect separase interaction with the spindle, similar to the budding yeast Esp1, or alternatively Ca2+ might be a critical component for (auto-)catalysis
Ca2+
-
Ca2+-levels affect separase function, C-terminal region contains a Ca2+-binding motif
Ca2+
-
Ca2+-levels affect separase function, C-terminal region contains a Ca2+-binding motif
Ca2+
-
Ca2+-levels affect separase function, C-terminal region contains a Ca2+-binding motif
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2E)-2-([4-[4-(furan-2-carbonyl)piperazine-1-carbonyl]phenyl]methylidene)-4-[(3-methylphenyl)methyl]-2H-1,4-benzothiazin-3(4H)-one
-
1,3-dihydroxy-2,2-dimethyl-5-(trifluoromethyl)-2H-benzimidazole-1,3-diium
0.1 mM, 8.0% inhibition
1,3-dihydroxy-2,2-dimethyl-5-nitro-2H-benzimidazole-1,3-diium
0.1 mM, 95.9% inhibition
1,3-dihydroxy-2,2-dimethyl-5-[(trifluoromethoxy)sulfinyl]-2H-benzimidazole-1,3-diium
0.1 mM, 64.6% inhibition
1,3-dihydroxy-5-nitrospiro[benzimidazole-1,3-diium-2,1'-cyclohexane]
0.1 mM, 99.5% inhibition
1,3-dihydroxy-5-nitrospiro[benzimidazole-1,3-diium-2,1'-cyclopentane]
0.1 mM, 96.2% inhibition
1,3-dihydroxy-5-[hydroxy(methoxy)methyl]-2,2-dimethyl-2H-benzimidazole-1,3-diium
0.1 mM, 14.6% inhibition
2-(4-carboxyphenyl)-1,3-dihydroxy-2-methyl-5-nitro-2H-benzimidazole-1,3-diium
0.1 mM, 84.1% inhibition
2-butyl-1,3-dihydroxy-2-methyl-5-nitro-2H-benzimidazole-1,3-diium
0.1 mM, 99.8% inhibition
2-ethyl-1,3-dihydroxy-2-methyl-5-nitro-2H-benzimidazole-1,3-diium
0.1 mM, 99.6% inhibition
2-ethyl-1,3-dihydroxy-5-nitro-2-propyl-2H-benzimidazole-1,3-diium
0.1 mM, 99.2% inhibition
3-(1-((4-fluorophenyl)sulfonyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole
-
4-bromo-1,3-dihydroxy-2,2-dimethyl-6-nitro-2H-benzimidazole-1,3-diium
0.1 mM, 100% inhibition
5-(butylamino)-1,3-dihydroxy-2,2-dimethyl-2H-benzimidazole-1,3-diium
0.1 mM, 40.9% inhibition
5-bromo-1,3-dihydroxy-2,2-dimethyl-2H-benzimidazole-1,3-diium
0.1 mM, 24.6% inhibition
5-carboxy-1,3-dihydroxy-2,2-dimethyl-2H-benzimidazole-1,3-diium
0.1 mM, 24.4% inhibition
5-ethoxy-1,3-dihydroxy-2,2-dimethyl-2H-benzimidazole-1,3-diium
0.1 mM, 21.2% inhibition
5-ethoxy-6-fluoro-1,3-dihydroxy-2,2-dimethyl-2H-benzimidazole-1,3-diium
0.1 mM, 25.2% inhibition
5-fluoro-1,3-dihydroxy-2,2-dimethyl-2H-benzimidazole-1,3-diium
0.1 mM, 35.4% inhibition
5-fluoro-1,3-dihydroxy-2,2-dimethyl-6-nitro-2H-benzimidazole-1,3-diium
0.1 mM, 60.1% inhibition
5-hexyl-1,3-dihydroxy-2,2-dimethyl-2H-benzimidazole-1,3-diium
0.1 mM, 39.3% inhibition
7-(4-chlorophenyl)-10-(4-hydroxyphenyl)-3,4a,5,5a,8a,9,9a,10-octahydro-5,9-methano[1,3]thiazolo[5',4':5,6]thiopyrano[2,3-f]isoindole-2,6,8(7H)-trione
-
7-(4-chlorophenyl)-11-(4-hydroxyphenyl)-4a,5,5a,8a,9,10,10a,11-octahydro-2H-5,10-methanopyrrolo[3'',4'':4',5']cyclohepta[1',2':5,6]thiopyrano[2,3-d][1,3]thiazole-2,6,8(3H,7H)-trione
-
Cdc55
-
results suggest that Cdc55 acts as inhibitor downstream from shugoshin
-
Cdk1 kinase
-
phosphorylation-dependent binding of the cyclin B1 subunit of Cdk1 kinase to a Cdc6-like domain of separase inhibits separase
-
cyclin-dependent kinase 1-cyclin B1
Cdk1-cyclin B1 triggers precipitation of separase by phosphorylation but stabilizes it by inhibitory binding. Only separase that is first complexed by Cdk1-cyclin B1 can later be activated by cyclin B1 degradation
-
cyclinB-CDK1 complex
separase activity is highly regulated by binding with securin and cyclinB-CDK1 complex. These bindings prevent the proteolytic activity of separase until the onset of anaphase
-
PATRONUS1
prevents chromosome separation by antagonizing separase
-
Pds1
Pds1 is a chaperone, inhibition of Esp1 by overexpression of undegradable Pds1 blocks mitotic exit via blockage of cohesin cleavage
-
peptide
-
acyloxymethyl ketone derivative of human SCC1 cleavage site peptide, chloromethyl ketone derivatives of the yeast Scc1 cleavage site
securin Pds1
-
an inhibitor of separase Esp1 in budding yeast. As Pds1 is degraded, Esp1 is activated, and cells transit into anaphase
sercurin
securin persistently binds and inhibits separase during much of metaphase
-
shugoshin
-
prevents separase activation independently of securin, protein phosphatase 2A coupled to regulatory subunit Cdc55 is essential for Shugoshin-mediated inhibition
-
Cdk1-cyclin B1
suppresses separase activity by activating autoinhibitory sequences in loops of separase itself
-
securin
-
destruction of securin occurs only upon the correct attachment of chromosomes to the spindle
securin
in addition to its inhibitory role, can act as a molecular chaperone of separase, essential for its proper folding
securin
-
in addition to its inhibitory role, can act as a molecular chaperone of separase, essential for its proper folding
securin
-
in addition to its inhibitory role, can act as a molecular chaperone of separase, essential for its proper folding
securin
-
in addition to its inhibitory role, can act as a molecular chaperone of separase, essential for its proper folding
securin
-
securin homolog pimples, i.e. PIM, binds and inhibits separase
securin
-
in addition to its inhibitory role, can act as a molecular chaperone of separase, essential for its proper folding
securin
-
small protein that binds to and inhibits separase until all pairs of chromatids have established bipolar spindle attachments
securin
-
securin inhibits separase by blocking the access of substrates to the active site
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, in contrast to cancer cells, where depletion of PTTG1 leads to chromosome instability. The human separase-securin complex shows a whale-type distinct elongated pattern. In this complex, securin is thought to interact with the N-part of separase spanned by the ARM repeats. The N- to C-terminus intramolecular interaction in separase molecules is considered to be necessary for their catalytic activation, and this interaction is abolished by securin binding
securin
separase is initially inhibited by securin that binds to separase co-translationally and acts as a chaperone to promote separase folding
securin
separase activity is highly regulated by binding with securin and cyclinB-CDK1 complex. These bindings prevent the proteolytic activity of separase until the onset of anaphase
securin
rapid cohesin cleavage by separase requires a substrate docking interaction outside the active site. This interaction is blocked by securin, providing a second mechanism by which securin inhibits cohesin cleavage
securin
acts as an extended pseudosubstrate that blocks substrate binding at the catalytic site and at nearby docking sites
securin
securin forms a tight complex with separase and potently inhibits its catalytic activity. Recent structures of the separase-securin complex have revealed the molecular mechanism for the inhibitory activity of securin. A segment of securin is bound in the active site of separase, thereby blocking substrate binding. Securin itself is not cleaved by separase as its binding mode is not compatible with catalysis. Securin has extensive interactions with separase outside the active site, consistent with its function as a chaperone to stabilize this enzyme
securin
-
in addition to its inhibitory role, can act as a molecular chaperone of separase, essential for its proper folding
securin
-
in addition to its inhibitory role, can act as a molecular chaperone of separase, essential for its proper folding
securin
-
small protein that binds to and inhibits separase until all pairs of chromatids have established bipolar spindle attachments
securin
-
securin regulates both the proteolytic and non-proteolytic activities of separase
securin
-
in addition to its inhibitory role, can act as a molecular chaperone of separase, essential for its proper folding. 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
-
small protein that binds to and inhibits separase until all pairs of chromatids have established bipolar spindle attachments
securin
-
in addition to its inhibitory role, can act as a molecular chaperone of separase, essential for its proper folding. Interaction takes place between the N-terminus of separase and the C-terminus of securin
securin
-
in addition to its inhibitory role, can act as a molecular chaperone of separase, essential for its proper folding
securin
inhibits separase by binding as a pseudo substrate
securin
-
in addition to its inhibitory role, can act as a molecular chaperone of separase, essential for its proper folding
securing
the motif containing H134 in securing isoform PTTG1 has a strong affinity for separase and is involved in inhibiting it, while another domain(s) in isoform is involved in activating separase and has a weaker affinity for it. Isoform PTTG2 does not interact with separase
-
additional information
-
nuclear exclusion of separase might provide the means to preclude cohesin cleavage at telophase and G1 stage of the cell cycle
-
additional information
-
separase is kept inactive in human cells by Cdk(Cdc2)-dependent phosphorylation even when securin is degraded
-
additional information
the proteolytic activity of separase is tightly controlled through binding partners (securin and cyclin B) that inhibit enzyme activity by blocking substrate binding. Vertebrate separase is kept in check by the action of two complexes whose inhibitory mechanisms fundamentally differ from each other
-
additional information
-
the activity of separase is tightly controlled at many levels, through direct binding of inhibitory proteins as well as posttranslational modification
-
additional information
the activity of separase is tightly controlled at many levels, through direct binding of inhibitory proteins as well as posttranslational modification
-
additional information
-
nuclear exclusion of separase might provide the means to preclude cohesin cleavage at telophase and G1 stage of the cell cycle
-
additional information
-
cohesin cleavage is inhibited by a PP2ACdc55-dependent mechanism
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
cell division cycle 6
-
Cdc6, a mitotic substrate of polo-like kinase. Cleavage of chesin/Rad21 is much greater in wild-type Cdc6 expressing cells than in GFP and Cdc6-T37V mutant expressing cells
-
imatinib
activation of separase proteolytic activity occurs exclusively in BCR-ABL-positive cells during imatinib treatment (0.00025-0.01 mM for 24 h)
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
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
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
securin
-
securin is required to support separase activity in anaphase
securin
-
the central domain of securin has a functionally essential specific sequence that may directly interact with the catalytic region of separase. This central securin domain is unrelated to destruction by polyubiquitination, but essential for the activation of separase
securing
the motif containing H134 in securing isoform PTTG1 has a strong affinity for separase and is involved in inhibiting it, while another domain(s) in isoform PTTG2 is involved in activating separase and has a weaker affinity for it. Isoform PTTG2 does not interact with separase
-
additional information
-
separase can be activated by incubating immunoglobulin G-Sepharose 6 containing ZZ TEV4-separase with anaphase-initiated Xenopus cytostatic factor to degrade its inhibitor securin at room temperature for 1 h
-
additional information
-
Cdc20 is essential for mitotic progression
-
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
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0178
1,3-dihydroxy-2,2-dimethyl-5-nitro-2H-benzimidazole-1,3-diium
Homo sapiens
pH and temperature not specified in the publication
0.0501
1,3-dihydroxy-2,2-dimethyl-5-[(trifluoromethoxy)sulfinyl]-2H-benzimidazole-1,3-diium
Homo sapiens
pH and temperature not specified in the publication
0.0162
1,3-dihydroxy-5-nitrospiro[benzimidazole-1,3-diium-2,1'-cyclohexane]
Homo sapiens
pH and temperature not specified in the publication
0.0171
1,3-dihydroxy-5-nitrospiro[benzimidazole-1,3-diium-2,1'-cyclopentane]
Homo sapiens
pH and temperature not specified in the publication
0.0292
2-(4-carboxyphenyl)-1,3-dihydroxy-2-methyl-5-nitro-2H-benzimidazole-1,3-diium
Homo sapiens
pH and temperature not specified in the publication
0.0146
2-butyl-1,3-dihydroxy-2-methyl-5-nitro-2H-benzimidazole-1,3-diium
Homo sapiens
pH and temperature not specified in the publication
0.0127
2-ethyl-1,3-dihydroxy-2-methyl-5-nitro-2H-benzimidazole-1,3-diium
Homo sapiens
pH and temperature not specified in the publication
0.0141
2-ethyl-1,3-dihydroxy-5-nitro-2-propyl-2H-benzimidazole-1,3-diium
Homo sapiens
pH and temperature not specified in the publication
0.0121
4-bromo-1,3-dihydroxy-2,2-dimethyl-6-nitro-2H-benzimidazole-1,3-diium
Homo sapiens
pH and temperature not specified in the publication
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
The protease activity of Esp1 is required for anaphase spindle elongation in Mcd1-depleted cells (Mcd1 is a subunit of cohesin)
additional information
Esp1 contributes to mitotic exit kinetics mainly through cohesin cleavage. Absence of Esp1 activity: only a minor mitotic exit delay observed which is consistent with a Cdc14 early anaphase release defect. Esp1 overexpression drives mitotic exit in Cdc20-depleted cells arrested in metaphase. Activity of overexpressed Esp1 depends on spindle integrity and the mitotic exit network.
additional information
-
Esp1 contributes to mitotic exit kinetics mainly through cohesin cleavage. Absence of Esp1 activity: only a minor mitotic exit delay observed which is consistent with a Cdc14 early anaphase release defect. Esp1 overexpression drives mitotic exit in Cdc20-depleted cells arrested in metaphase. Activity of overexpressed Esp1 depends on spindle integrity and the mitotic exit network.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
gene Sse/THR, Drosophila separase is encoded by two different genes: (1) Sse-encoding separase-like protein with protease domain and (2) THR (three rows) for the protein interacting with PIM (pimples), a securin homologue of Drosophila
-
-
brenda
separase is required for sister chromatid separation in mitosis
-
-
brenda
-
638856, 638858, 638861, 638862, 638863, 638865, 638869, 664551, 666418, 680926, 681015, 681037, 697184, 697240, 697382, 700945, 707105, 708281, 709217, 709220, 710036, 718177, 718320, 718433
-
-
brenda
-
SwissProt
brenda
-
-
-
brenda
separase is part of the so called Cdc fourteen anaphase release network, that promotes Cdc14 release from the nucleolus during early anaphase
-
-
brenda
separase mediates Cdc14 release from nucleoli during meiosis through a mechanism that is indepenent of its protease activity
-
-
brenda
-
-
-
brenda
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
overexpressed in numerous human cancers including breast, bone, brain, and prostate
brenda
-
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
brenda
overexpressed in numerous human cancers including breast, bone, brain, and prostate
brenda
-
highly expressed in human fetal cerebral cortex compared with adult
brenda
-
separase expression is very high in both normal nonneoplastic and neoplastic colons
brenda
-
separase localizes to the ingressing furrow and midbody during cytokinesis in the Caenorhabditis elegans embryo
brenda
-
diploid FSK3 mouse mammary epithelial cells
brenda
overexpressed in numerous human cancers including breast, bone, brain, and prostate
brenda
additional information
-
human separase is present in cells as a part of very large protein complex, which in addition to securin contains also Cdk and cyclin B1, both able to inhibit separase
brenda
-
Separase is significantly overexpressed in human breast tumors compared with matched normal tissue (Western blot)
brenda
overexpressed in numerous human cancers including breast, bone, brain, and prostate
brenda
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
the spatial localization of separase varies with the progression of the cell cycle. In interphase cells, separase is localized in the cytoplasm, but during mitosis it accumulates in the nucleus and associates with chromosomes
brenda
-
in nondividing cells in healthy tissue, immunofluorescence microscopy
brenda
-
separase is abundantly expressed within the cytoplasm of a broad range of human tumor cell lines, including MDA-MB-231 breast carcinoma cells
brenda
the spatial localization of separase varies with the progression of the cell cycle. In interphase cells, separase is localized in the cytoplasm, but during mitosis it accumulates in the nucleus and associates with chromosomes
brenda
-
Cut1 seems to be localized in the cytoplasm
brenda
-
tumor cells significantly more abundant, immunofluorescence microscopy
brenda
the spatial localization of separase varies with the progression of the cell cycle. In interphase cells, separase is localized in the cytoplasm, but during mitosis it accumulates in the nucleus and associates with chromosomes
brenda
-
while inhibiting separase, securin is able to promote nuclear accumulation of separase
brenda
-
possibly localized in the nucleus, in the mitotic stage Cut1 is mobilized to the spindle poles and the spindle microtubules
brenda
additional information
-
separase localizes to cortically located filamentous structures in prometaphase I upon oocyte maturation. After fertilization, separase disappears from these structures and appears on cortical granules by anaphase I
-
brenda
additional information
-
separase binds terminin proteins and HP1, and that it is enriched at telomeres
-
brenda
additional information
-
human separase is associated with centrosomes but not with spindle before anaphase, featuring predominantly cytoplasmic localization in non-dividing cells
-
brenda
additional information
-
budding yeast Esp1 is localized to the centrosomes and spindle before anaphase
-
brenda
additional information
-
in fission yeast Cut1 features similar localization in the beginning of anaphase onset persisting on the spindle until mid-anaphase
-
brenda
additional information
-
Separase is present in the cell during the entire cell cycle, but excluded from the nucleus until the metaphase-anaphase transition
-
brenda
Highest Expressing Human Cell Lines
Cell Line LinksPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug target
evolution
malfunction
metabolism
physiological function
additional information
drug target
separase is highly overexpressed in many solid cancers, making it an attractive chemotherapeutic target. As shown by our RNAi experiments, minimal amounts of separase are sufficient to ensure the proper segregation of chromosomes implicating that inhibitors of separase have to be extraordinarily potent in order to inhibit the growth of cancer cells
drug target
dysregulation of separase activity is linked to cancer and genome instability, making it a target for drug discovery
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 separase exhibits 31 and 32% identity to the corresponding domains of human and budding yeast homologues, respectively, while the identity exceeds 50% within plant kingdom showing that the proteolytic domain of separases is the most conserved one. The sequence identity drops dramatically for the N-termini of separases. For example, the identity of the first 600 amino acid residues between Arabidopsis and Vitis vinifera separases does not exceed 39%, and it is only 30% between Arabidopsis and rice. Mode of action in vivo and mechanistic differences in mitosis between organisms, overview
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 sequence identity exceeds 50% within plant kingdom showing that the proteolytic domain of separases is the most conserved one. The sequence identity drops dramatically for the N-termini of separases. For example, the identity of the first 600 amino acid residues between Arabidopsis thaliana and Vitis vinifera separases does not exceed 39%. Mode of action in vivo and mechanistic differences in mitosis between organisms, overview
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. Mode of action in vivo and mechanistic differences in mitosis between organisms, overview
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
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. Mode of action in vivo and mechanistic differences in mitosis between organisms, overview
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. Mode of action in vivo and mechanistic differences in mitosis between organisms, overview
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. Mode of action in vivo and mechanistic differences in mitosis between organisms, overview
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
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. Mode of action in vivo and mechanistic differences in mitosis between organisms, overview
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. Mode of action in vivo and mechanistic differences in mitosis between organisms, overview
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 sequence identity exceeds 50% within plant kingdom showing that the proteolytic domain of separases is the most conserved one. The sequence identity drops dramatically for the N-termini of separases. For example, the identity of the first 600 amino acid residues between Arabidopsis thaliana and Oryza sativa is only 30%. Mode of action in vivo and mechanistic differences in mitosis between organisms, overview
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. Mode of action in vivo and mechanistic differences in mitosis between organisms, overview
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 identifis 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
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
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
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
while caspases and separases have evolved different substrate specificities associated with their specialized functions in apoptosis and cell division respectively, they appear to have retained the residual ability to participate in both processes, supporting the view that co-option of components in cell division may have led to the innovation of programmed cell suicide early in metazoan evolution
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
-
malfunction
-
loss of separase function during the early mitotic divisions causes cytokinesis failure, depletion of separase causes the accumulation of RAB-11-positive vesicles at the cleavage furrow and midbody
malfunction
-
loss of separase blocks centriole disengagement during mitotic exit and delays assembly of new centrioles during the following S phase
malfunction
-
Arabidopsis thaliana radially swollen 4 (rsw4), a temperature-sensitive mutant, harbors a mutation in At4g22970, the separase. Loss of separase function in rsw4 at the restrictive temperature is indicated by the widespread failure of replicated chromosomes to disjoin. rsw4 has neither pronounced cell cycle arrest nor anomalous spindle formation, rsw4 roots have disorganized cortical microtubules and accumulate the mitosis-specific cyclin, cyclin B1,1
malfunction
-
meiotic expression of ESP RNA interference blocks the removal of cohesin during both meiosis I and II, results in alterations in nonhomologous centromere association, disrupts the radial microtubule system after telophase II, and affects the proper establishment of nuclear cytoplasmic domains, resulting in the formation of multinucleate microspores
malfunction
knocking down AtESP in meiocytes using RNAi unexpectedly converts the symmetric radial microtubule systems that form after telophase II into asymmetric structures partially resembling phragmoplasts
malfunction
-
cells depleted of securin or separase display defective acidification of early endosomes and increased membrane recruitment of vacuolar ATPase complexes, mimicking the effect of the specific V-ATPase inhibitor Bafilomycin A1. Securin and separase depletion causes trans-Golgi network and endosome swelling independent of cell cycle. Endosome-mediated receptor degradation and recycling are also significantly impaired by securin and separase depletion, although not receptor internalization or Rab5 activity and autophagy
malfunction
-
cells that do not express both Cdc55 and securin prematurely separate their sister chromatids, leading to cell death
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
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
malfunction
-
human cells with one hESP allele-encoding uncleavable protein and another allele harboring a single cleavage site grow slowly owing to cell cycle delay, in particular during G2/M transition, but not when it was expected, i.e. during anaphase
malfunction
-
loss of either APC or separase results in a failure of the transduction of the presumed polarity signal from the centrosome cortex
malfunction
-
mutations in the Drosophila Separase encoding gene Sse lead not only to endoreduplication but also telomeric fusions, suggesting a role for Sse in telomere capping
malfunction
overexpression and deregulated proteolytic activity of Separase as frequently observed in human cancers is associated with the occurrence of supernumerary centrosomes, chromosomal missegregation and aneuploidy
malfunction
deregulated separase activity is associated with aneuploidy, a hallmark of most human cancers
malfunction
mutations that prevent Meikin cleavage or that conditionally inactivate Meikin at anaphase I result in defective meiosis II chromosome alignment in mouse oocytes
malfunction
-
enzyme depletion results in growth inhibition, bud enlargement, and filamentation
malfunction
aberrant expression and/or altered separase proteolytic activity are associated with aneuploidy, tumorigenesis, and disease progression
malfunction
enzyme loss results in extra surviving cells in a weak ced-3(-) mutant, and suppresses the embryonic lethality of a mutant defective for the apoptotic suppressor ced-9/Bcl-2 implicating the enzyme in execution of apoptosis
malfunction
dysregulation of the enzyme activity is linked to cancer, aneuploidy and genome instability
metabolism
-
Plk1-mediated phosphorylation of Cdc6 on residue T37 promotes the interaction of Cdc6 and Cdk1, leading to the attenuation of Cdk1 activity, release of separase, and subsequent anaphase progression
metabolism
human cells that enter mitosis with already active separase rapidly undergo death in mitosis owing to direct cleavage of anti-apoptotic MCL1 and BCL-XL by separase. Cleavage not only prevents MCL1 and BCL-XL from sequestering pro-apoptotic BAK, but also converts them into active promoters of death in mitosis. The deadliest cleavage fragment, the C-terminal half of MCL1, forms BAK/BAX-like pores in the mitochondrial outer membrane. MCL1 and BCL-XL are turned into separase substrates only upon phosphorylation by NEK2A. Early mitotic degradation of this kinase is therefore crucial for preventing apoptosis upon scheduled activation of separase in metaphase. Speeding up mitosis by abrogation of the spindle assembly checkpoint results in a temporal overlap of the enzymatic activities of NEK2A and separase and consequently in cell death
physiological function
-
separase plays a pivotal role in the separation of sister chromatids at anaphase by cleaving its substrate cohesin Rad21
physiological function
-
separase is required for cytokinesis by regulating the incorporation of RAB-11-positive vesicles into the plasma membrane at the cleavage furrow and midbody
physiological function
-
separase acts during M phase to license centrosome duplication
physiological function
-
plant separase, in addition to cleaving cohesin, regulates cyclin B1,1, with profound ramifications for morphogenesis
physiological function
-
sister chromatid separation at anaphase is triggered by cleavage of the cohesin subunit Scc1, which is mediated by separase
physiological function
-
Separase is essential for sister chromatid separation during anaphase II. Separase-mediated proteolytic cleavage of the alpha-kleisin subunit of the cohesin complex at the metaphase-to-anaphase transition is essential for the proper segregation of chromosomes. Separase is also involved in mitotic and meiotic anaphase spindle assembly and elongation, interphase spindle pole body positioning, and epithelial cell reorganization
physiological function
function of separases in metaphase to anaphase transition, overview. Separase cleaves and removes the remaining centromeric cohesin. In plants, the molecular mechanisms regulating sister chromatid separation remain largely elusive. AtESP plays a role in microtubule organization or cell polarity, and an additional role for AtESP beyond cohesin cleavage
physiological function
-
function of separases in metaphase to anaphase transition, overview. Separase cleaves and removes the remaining centromeric cohesin. In plants, the molecular mechanisms regulating sister chromatid separation remain largely elusive
physiological function
-
function of separases in metaphase to anaphase transition, overview. Separase cleaves and removes the remaining centromeric cohesin. In plants, the molecular mechanisms regulating sister chromatid separation remain largely elusive
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
-
chromosomal segregation is mediated by cyclin-dependent kinase 1 and separase, which is regulated by cell division cycle 6, Cdc6, a mitotic substrate of polo-like kinase 1. The phosphorylation of Cdc6 by Plk1 regulates the activity of separase through the association with Cdk1
physiological function
-
functional role of securin and separase in the modulation of membrane traffic and protein secretion implicating regulation of V-ATPase assembly and function. Separase activity is controlled by securin, i.e. pituitary tumor transforming gene 1, PTTG1, a member of a divergent class of anaphase inhibitors whose proteosomal degradation by the anaphase promoting complex, APC, is required to release separase and allow its activation
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
-
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
-
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
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
-
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. Separase can target both centromeric cohesin and cohesin of chromosomal arms. Cohesin is implicated in transcriptional regulation in Schizosaccharomyces pombe. 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
-
function of separases in metaphase to anaphase transition, overview
physiological function
-
function of separases in metaphase to anaphase transition, overview
physiological function
-
function of separases in metaphase to anaphase transition, overview. Human separase is a potential oncogene and hESP transcripts are accumulated in a large number of tumors
physiological function
-
function of separases in metaphase to anaphase transition, overview. The activated APCCdc20/separase pathway plays a fundamental role in the establishment of the anterior-posterior axis
physiological function
-
function of separases in metaphase to anaphase transition, overview
physiological function
-
function of separases in metaphase to anaphase transition, overview. Separase cleaves and removes the remaining centromeric cohesin. In plants, the molecular mechanisms regulating sister chromatid separation remain largely elusive
physiological function
-
function of separases in metaphase to anaphase transition, overview. Separase cleaves and removes the remaining centromeric cohesin. In plants, the molecular mechanisms regulating sister chromatid separation remain largely elusive
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
separase is required for the separation of sister-chromatides in mitotic anaphase, triggers centriole disengagement during centrosome duplication. In cancer, separase is frequently overexpressed, pointing to a functional role as an aneuploidy promoter associated with centrosomal amplification and genomic instability
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
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 cleaves the Scc1/Rad21 subunit of cohesin, thereby triggering chromosome segregation
physiological function
-
Separase plays an evolutionarily conserved role in telomere protection
physiological function
separase cleaves the proteins that maintain the cohesion between sister chromatids
physiological function
separase is required for homolog and sister disjunction during Drosophila melanogaster male meiosis, but not for biorientation of sister centromeres
physiological function
the enzyme is required for centrosome duplication and separation of sister-chromatides in anaphase of mitosis
physiological function
separase cleaves the N-tail of the CENP-A related protein CPAR-1 at the meiosis I metaphase-anaphase transition
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. In addition to its canonical role in the dissolution of chromosomal cohesin during metaphase to anaphase transition, separase is also implicated in centrosome cycle, membrane trafficking and DNA-damage repair
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
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
physiological function
separase cleaves the proteins that maintain the cohesion between sister chromatids
physiological function
separase cleaves the proteins that maintain the cohesion between sister chromatids
physiological function
separase cleaves the proteins that maintain the cohesion between sister chromatids
physiological function
role in DNA repair. Involved in positioning of spindle pole body
physiological function
-
involved in proper positioning of the centrosomes during the first asymmetric mitotic division, in the development of egg shell and in membrane trafficking
physiological function
the enzyme is involved in reorganization and dynamics in epithelial cells, in telomere capping and in inactivation of alternative conjunction at anaphase I onset
physiological function
the enzyme is involved in establishment of cell polarity and cytokinesis, in microtubule polymerization and Kin7 activation
physiological function
the enzyme triggers chromosome segregation during mitosis by cleaving the cohesin ring entrapping the two sister chromatids
physiological function
cleavage of the kleisin subunit of cohesin triggers chromosome segregation during cell division. Separase also cleaves MCL-1 or BCL-XL proteins to trigger apoptosis
physiological function
separase is a key cysteine protease in the separation of sister chromatids through the digestion of the cohesin ring that inhibits chromosome segregation as a trigger of the metaphase-anaphase transition in eukaryotes. Its activity is highly regulated by binding with securin and cyclinB-CDK1 complex
physiological function
equal distribution of the duplicated genetic material during mitosis is key for the genesis of healthy eukaryotic cells. Separase-mediated sister chromatid separation is a key step in this processtion
physiological function
separase cleaves the kinetochore protein Meikin at the meiosis I/II transition
physiological function
it is proposed that NEK2A and separase jointly check on spindle assembly checkpoint integrity and eliminate cells that are prone to chromosome missegregation owing to accelerated progression through early mitosis
physiological function
-
the enzyme is essential for chromosome segregation and important for spindle elongation
physiological function
essential activity of separase in cell division and cortical granule exocytosis
physiological function
role of separase in developmentally programmed cell death when the predominant pro-apoptotic caspase CED-3 is compromised
physiological function
the enzyme has crucial roles in many cellular processes, especially chromosome segregation during mitosis and meiosis, DNA damage repair, centrosome disengagement and duplication, spindle stabilization and elongation. It dissolves the cohesion between sister chromatids by cleaving one of the subunits of the cohesin ring for chromosome segregation
physiological function
the enzyme is a key player in mitotic sister chromatid separation, replication fork dynamics, and DNA repair
physiological function
NEK2A and separase jointly check on spindle assembly checkpoint integrity and eliminate cells that are prone to chromosome missegregation owing to accelerated progression through early mitosis
physiological function
separase is essential for cohesion release and chromosome segregation at both meiosis and mitosis
physiological function
the enzyme has essential activity in cell division and cortical granule exocytosis, and plays a role in developmentally programmed cell death when the predominant pro-apoptotic caspase CED-3 is compromised
physiological function
the enzyme cleaves the cohesin protein ring that links the sister chromatids and thus facilitates their separation and segregation to the opposite poles of the dividing cell
physiological function
the enzyme cleaves the cohesin protein ring that links the sister chromatids and thus facilitates their separation and segregation to the opposite poles of the dividing cell
physiological function
the enzyme disintegrates the cohesion between sister chromatids by cleaving one of the subunits Scc1/Rad21/Mcd1 from the cohesin ring for chromosomal segregation
physiological function
in meiosis, the enzyme has to be activated twice: once in meiosis I, to remove cohesion from chromosome arms and immediately afterward in meiosis II, to cleave pericentromeric cohesin
physiological function
-
the enzyme rewires key cell division processes at the meiosis I/II transition by cleaving the meiosis-specific protein Meikin. Enzyme proteolysis does not inactivate Meikin but instead alters its function to create a distinct activity state. Full-length Meikin and the C-terminal Meikin enzyme-cleavage product both localize to kinetochores, bind to Plk1 kinase, and promote Rec8 cleavage
physiological function
-
the enzyme rewires key cell division processes at the meiosis I/II transition by cleaving the meiosis-specific protein Meikin. Enzyme proteolysis does not inactivate Meikin but instead alters its function to create a distinct activity state. Full-length Meikin and the C-terminal Meikin enzyme-cleavage product both localize to kinetochores, bind to Plk1 kinase, and promote Rec8 cleavage
physiological function
-
role in DNA repair. Involved in positioning of spindle pole body
-
physiological function
-
separase cleaves the proteins that maintain the cohesion between sister chromatids
-
physiological function
-
cleavage of the kleisin subunit of cohesin triggers chromosome segregation during cell division. Separase also cleaves MCL-1 or BCL-XL proteins to trigger apoptosis
-
additional information
securin, in addition to its inhibitory role, can act as a molecular chaperone of separase, essential for its proper folding
additional information
-
securin, in addition to its inhibitory role, can act as a molecular chaperone of separase, essential for its proper folding
additional information
-
securin, in addition to its inhibitory role, can act as a molecular chaperone of separase, essential for its proper folding
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
-
cells expressing wild-type Cdc6 display lower Cdk1 activity and higher separase activity than cells expressing Cdc6 mutant T37V
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
additional information
-
securin, in addition to its inhibitory role, can act as a molecular chaperone of separase, essential for its proper folding. Interaction takes place between the N-terminus of separase and the C-terminus of securin
additional information
-
securin, in addition to its inhibitory role, can act as a molecular chaperone of separase, essential for its proper folding
additional information
-
securin, in addition to its inhibitory role, can act as a molecular chaperone of separase, essential for its proper folding
additional information
-
human separase is present in cells as a part of very large protein complex, which in addition to securin contains also Cdk and cyclin B1, both able to inhibit separase. Securin, in addition to its inhibitory role, can act as a molecular chaperone of separase, essential for its proper folding. The human separase-securin complex shows a whale-type distinct elongated pattern. In this complex, securin is thought to interact with the N-part of separase spanned by the ARM repeats. The N- to C-terminus intramolecular interaction in separase molecules is considered to be necessary for their catalytic activation, and this interaction is abolished by securin binding
additional information
-
securin, in addition to its inhibitory role, can act as a molecular chaperone of separase, essential for its proper folding
additional information
-
securin, in addition to its inhibitory role, can act as a molecular chaperone of separase, essential for its proper folding
additional information
-
securin, in addition to its inhibitory role, can act as a molecular chaperone of separase, essential for its proper folding
additional information
-
securin, in addition to its inhibitory role, can act as a molecular chaperone of separase, essential for its proper folding
additional information
-
a biosensor to assess meiotic cohesin subunit Rec8 cleavage in mouse oocytes is described
additional information
a biosensor to assess meiotic cohesin subunit Rec8 cleavage in mouse oocytes is described
Show AA Sequence and Transmembrane Helices (3831 entries)
Please use the AA Sequence and Transmembrane Helices Search for a specific query.
Please use the AA Sequence and Transmembrane Helices Search for a specific query.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PDB
SCOP
CATH
UNIPROT
ORGANISM
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
233000
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
the human separase is composed of three domains: the tail, the trunk, and the head, structure modeling. The first two domains are spanned by Armadillo, ARM, repeats, which are composed of multiple 42 amino acid repeats and are present in the proteomes of all eukaryotic organisms. The ARM repeat domain is highly conserved right-handed super helix of ?-helices, which serves as molecular scaffold for protein-protein interactions. Phosphorylation and potential autocleavage sites span the region of the last ARM repeats and the central unstructured region. Human separase has an N-terminal region spanned by 26 ARM repeats and separated from the
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
proteolytic modification
additional information
phosphoprotein
-
three phoshorylation sites within the the Cdc6-like domain of separase are identified which are critical for Cdk1 binding: Thr 1346, Thr 1363 and Ser 1399
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
phosphoprotein
-
phosphorylation sites span the region of the last ARM repeats and the central unstructured region
phosphoprotein
mitosis-specific phosphorylation of Ser-1126 decreases the solubility of separase by cyclin-dependent kinase 1-cyclin B1
phosphoprotein
the enzyme is phosphorylated by Cdk1 on Ser1126 and Ser1399
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
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
proteolytic modification
during metaphase, separase is kept inactive through its binding to the chaperone securin. During anaphase, APCcdc20 cleaves securin releasing separase. Active separase cleaves itself, and the resulting N- and C-terminal fragments associate, mechanism of separase maturation during metaphase to anaphase transition
proteolytic modification
-
during metaphase, separase is kept inactive through its binding to the chaperone securin. During anaphase, APCcdc20 cleaves securin releasing separase. Active separase cleaves itself, and the resulting N- and C-terminal fragments associate, mechanism of separase maturation during metaphase to anaphase transition
proteolytic modification
-
during metaphase, separase is kept inactive through its binding to the chaperone securin. During anaphase, APCcdc20 cleaves securin releasing separase. Active separase cleaves itself, and the resulting N- and C-terminal fragments associate, mechanism of separase maturation during metaphase to anaphase transition
proteolytic modification
-
during metaphase, separase is kept inactive through its binding to the chaperone securin. During anaphase, APCcdc20 cleaves securin releasing separase. Active separase cleaves itself, and the resulting N- and C-terminal fragments associate, mechanism of separase maturation during metaphase to anaphase transition
proteolytic modification
-
during metaphase, separase is kept inactive through its binding to the chaperone securin. During anaphase, APCcdc20 cleaves securin releasing separase. Active separase cleaves itself, and the resulting N- and C-terminal fragments associate, mechanism of separase maturation during metaphase to anaphase transition
proteolytic modification
-
separase is subjected to auto-catalytic proteolytic cleavage at 3 adjacent sites, cleavage occurs specifically at anaphase coincident with separase activation, cleavage has no effect on in vitro activity
proteolytic modification
-
during metaphase, separase is kept inactive through its binding to the chaperone securin. During anaphase, APCcdc20 cleaves securin releasing separase. Active separase cleaves itself, and the resulting N- and C-terminal fragments associate, mechanism of separase maturation during metaphase to anaphase transition. Autocleavage of human separase is to be essential and results in conformational changes. The C-terminal fragment of human separase, which results from autocleavage, is more unstable than the N-terminal one. The C-terminal fragment, which possesses the catalytic domain of separase, is subjected to the N-end rule pathway of protein degradation. Consequently, catalytic activity of separase can persist only for a short period of time facilitating switch off of its proteolytic function upon entering anaphase
proteolytic modification
-
during metaphase, separase is kept inactive through its binding to the chaperone securin. During anaphase, APCcdc20 cleaves securin releasing separase. Active separase cleaves itself, and the resulting N- and C-terminal fragments associate, mechanism of separase maturation during metaphase to anaphase transition
proteolytic modification
-
during metaphase, separase is kept inactive through its binding to the chaperone securin. During anaphase, APCcdc20 cleaves securin releasing separase. Active separase cleaves itself, and the resulting N- and C-terminal fragments associate, mechanism of separase maturation during metaphase to anaphase transition
proteolytic modification
-
during metaphase, separase is kept inactive through its binding to the chaperone securin. During anaphase, APCcdc20 cleaves securin releasing separase. Active separase cleaves itself, and the resulting N- and C-terminal fragments associate, mechanism of separase maturation during metaphase to anaphase transition
proteolytic modification
-
during metaphase, separase is kept inactive through its binding to the chaperone securin. During anaphase, APCcdc20 cleaves securin releasing separase. Active separase cleaves itself, and the resulting N- and C-terminal fragments associate, mechanism of separase maturation during metaphase to anaphase transition
proteolytic modification
-
during metaphase, separase is kept inactive through its binding to the chaperone securin. During anaphase, APCcdc20 cleaves securin releasing separase. Active separase cleaves itself, and the resulting N- and C-terminal fragments associate, mechanism of separase maturation during metaphase to anaphase transition
proteolytic modification
-
during metaphase, separase is kept inactive through its binding to the chaperone securin. During anaphase, APCcdc20 cleaves securin releasing separase. Active separase cleaves itself, and the resulting N- and C-terminal fragments associate, mechanism of separase maturation during metaphase to anaphase transition
additional information
-
phosphorylation and potential autocleavage sites span the region of the last ARM repeats and the central unstructured region. Human separase has an N-terminal region spanned by 26 ARM repeats and separated from the two caspase-like domains, one of which is active, by the unstructured region
additional information
-
the activity of separase is tightly controlled at many levels, through direct binding of inhibitory proteins as well as posttranslational modification
additional information
the activity of separase is tightly controlled at many levels, through direct binding of inhibitory proteins as well as posttranslational modification
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystal structure of full-length separase in complex with securin
crystal structures of the active protease segment of Chaetomium thermophilum separase in complex with a substrate-mimic inhibitor at up to 1.85 A resolution
crystal structures of the separase protease domain from the thermophilic fungus Chaetomium thermophilum, alone or covalently bound to unphosphorylated and phosphorylated inhibitory peptides derived from a cohesin cleavage site
crystal structure of full-length separase in complex with securin
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C2029A
R1506A
-
mutation at autocatalytical cleavage site, mutant enzyme is still cleaved indicating the existence of a second cleavage site
S1126A
T1346A/T1363A/S1399A
-
this triple mutant binds relatively more Cdk1 than S1126A but its Cdk1 binding capacity is much decreased compared to wildtype. A doxycycline-induced overexpression of the triple mutant in HEK-293 cells leads to an increase of the G2/M cell population from 24 to 37% within 24 h compared to wild-type. Giemsa-stained prometaphase-chromosomes from triple mutant expressing cells are mostly separated (61%), whereas those from wild-type or T1346E/T1363E/S1399D expressing cells are almost always paired (78 and 83%, respectively)
T1346A/T1363A/S1399D
-
the mitotic arrest phenotype caused by the T1346A/T1363A/S1399A triple mutant is largely abrogated when just residue 1399 is changed to aspartate. Thus among the phosphorylation sites within the Cdc6-like domain serine 1399 is sufficient to support Cdk1-dependent inhibition of separase
T1346E/T1363E/S1399D
-
changing the phosphorylation sites within the Cdc6-like domain to acidic residues results in a separase that can still be inhibited by Cdk1 in vivo
T1346E/T1363E/S1399S
-
the mitotic arrest phenotype caused by the T1346A/T1363A/S1399A triple mutant is largely abrogated when just residue 1399 is changed to serine. Thus among the phosphorylation sites within the Cdc6-like domain serine 1399 is sufficient to support Cdk1-dependent inhibition of separase
S1121A
S1126A
-
specifically abolished separase hyperphosphorylation in Smad3-deficient cells
H1531A
-
active site point mutation prevents Scc1 from being cleaved after binding
S1138A
-
mutant containing phosphorylation site mutation compromises Cdk1-inhibitory ability
S1139A
-
mutant containing phosphorylation site mutation compromises Cdk1-inhibitory ability
additional information
S1126A
-
cleaved autoproteolytically to the same degree as wild-type, shows similar SCC1 cleavage activity as wild-type
S1126A
-
a doxycycline-induced overexpression of S1126A mutant in HEK-293 cells leads to an increase of the G2/M cell population from 24 to 49% within 24 h compared to wild-type. Giemsa-stained prometaphase-chromosomes from S1126A expressing cells are mostly separated (61%), whereas those from wild-type or T1346E/T1363E/S1399D expressing cells are almost always paired (78 and 83%, respectively)
S1126A
the mutation prevents the conformational change of the enzyme caused by phosphorylation, thereby rendering separase resistant to precipitation in mitosis
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
additional information
-
RNAi of sep-1 inhibits degranulation in addition to causing extensive chromosomal segregation failures. Temperature-sensitive sep-1(e2406) allele exhibits similar inhibition of degranulation, but has minimal effects on chromosome segregation
additional information
-
analysis of the homozygous zebrafish mutant cds (cease&desist), bearing a mutation in the separase gene, reveals high levels of polyploidy and aneuploidy, spindle defects, and a mitotic exit delay in mutant embryos. Carcinogenesis studies demonstrate that cds heterozygous adults have an eightfold increase in the percentage of fish bearing epithelial tumors
additional information
-
in cells lacking separase or expressing noncleavable Scc1, arm cohesion is not efficiently removed during nocodazole arrest
additional information
-
generation of human cells with one hESP allele-encoding uncleavable protein and another allele harboring a single cleavage site, the cells grow slowly owing to cell cycle delay, in particular during G2/M transition, but not when it was expected, i.e. during anaphase
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
additional information
-
the loss-of-function of Esp1 activity in yeast cells could be complemented by the tobacco etch virus, TEV, protease, which is also able to cleave Scc1 thus promoting segregation of sister chromatids
additional information
-
it is shown that separase acts as a direct inhibitor of cyclin-dependent kinase 1 on liberation from the inhibitory protein securin. Blocking separase-cyclin-dependent kinase 1 complex formation by microinjection of anti-separase antibodies prevents polar-body extrusion in vertebrate oocytes
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
Cdc48 is required for the stability of Cut1/separase in mitotic anaphase
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
separase is expressed as a GST- or myc-tagged fusion protein in Escherichia coli BL-21 and HEK-293 cells
-
StrepTactin column chromatography, HisTrap column chromatography, and Superose 6 column chromatography
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
analysis of correlation between overexpression of separase and aneuploidy in tetracycline-inducible diploid FSK3 mouse mammary epithelial cells
-
depletion of endogenous separase with siRNA in NSCLCs shows that separase affects progression through the G2 phase of mitosis. Analysis of the effect of separase depletion on irradiated cells (cell cycle progression, M-phase fraction, late mitotic-linked cell death and clonogenic survival)
-
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
-
expressed in HEK-293T cells
expressed in HeLa cells
investigation of the expression level of separase across a wide range of human tumors. Overexpression of separase transcripts strongly correlates with high incidence of relapse, metastasis and lower 5-year overall survival rate in breast and prostate cancer patients.
-
mutations introducing substitutions throughout the Esp1 polypeptide prevent loss of sister chromatid cohesion and cause mitotic failure. Generation of esp1-temperature sensitive mutant for functional analysis of further enzymes
-
the active (S1126A/T1346A) and the inactive (C1129S) separase mutants are coexpressed in HEK-293T cells with human securin
-
Zds1 is required for Separase-induced Cdc14 activation. Analysing the role of proteins Zds1 and Zds2 in mitotic exit machinery
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
decreased separase protein levels are observed in BCR-ABL-positive and -negative cells treated with imatinib in a dose dependent manner
separase is overexpressed and mislocalized in a wide range of human cancers, including breast, prostate, and osteosarcoma
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
diagnostics
medicine
molecular biology
diagnostics
measurement of separase proteolytic activity in single living cells by a fluorogenic flow cytometry assay. The assay is used to quantify Separase proteolytic activity in leukemic cell lines and peripheral blood samples from leukemia patients
diagnostics
a live cell monitoring systems is established for separase activity through microscopic observation and flow cytometric analysis that could allow quantitative assay for separase activation profiles during cell cycle with spatiotemporal resolution. The assay will be applicable as a clinical diagnostic and prognostic tool to monitor separase proteolytic activity combined with other cellular events in human malignancies, and as a therapeutic mechanism in future studies
diagnostics
separase activity distribution can be a marker of major molecular response and proliferation of CD34+ cells in TKI-treated chronic myeloid leukemia patients
medicine
due to the oncogenic activity of cohesin protease, separase in human cancer cells, modulation of separase enzymatic activity could constitute a new therapeutic strategy for targeting resistant, separase-overexpressing aneuploid tumors
medicine
enzyme distribution can be a marker of major molecular response and proliferation of CD34+ cells in tyrosine kinase inhibitor-treated chronic myeloid leukemia patients
molecular biology
-
separase is identified as a key cell cycle component that is required for degranulation
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
molecular biology
-
data suggest that the co-ordinated expression of separase, securin and Rad21 is fundamental for the developing brain
molecular biology
-
data suggest that the co-ordinated expression of separase, securin and Rad21 is fundamental for the developing brain
molecular biology
-
the results show that a fraction of arm cohesin is protected by Sgo1, which prevents cohesin from being removed by the prophase pathway, and that separase is partly activated in nocodazole-arrested cells and removes the arm cohesion protected by Sgo1
molecular biology
-
in Saccharomyces cerevisiae separase it is shown that separase is implicated in a second non-proteolytic pathway: separsae is essential for the activation of Cdc14 phosphatase and thus a broad programme of late mitotic events culminating in mitotic exit and cell division
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Yanagida, M.
Cell cycle mechanisms of sister chromatid separation; roles of Cut1/separin and Cut2/securin
Genes Cells
5
1-8
2000
Saccharomyces cerevisiae, Schizosaccharomyces pombe, Homo sapiens
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, Schizosaccharomyces pombe, Homo sapiens
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
Jager, H.; Herzig, A.; Lehner, C.F.; Heidmann, S.
Drosophila separase is required for sister chromatid separation and binds to PIM and THR
Genes Dev.
15
2572-2584
2001
Drosophila melanogaster
brenda
Hauf, S.; Waizenegger, I.C.; Peters, J.M.
Cohesin cleavage by separase required for anaphase and cytokinesis in human cells
Science
293
1320-1323
2001
Homo sapiens
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, Schizosaccharomyces pombe, Homo sapiens, Drosophila melanogaster, Xenopus laevis
brenda
Zou, H.; Stemman, O.; Anderson, J.S.; Mann, M.; Kirschner, M.W.
Anaphase specific auto-cleavage of separase
FEBS Lett.
528
246-250
2002
Homo sapiens
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
Waizenegger, I.C.; Gimenez-Abian, J.F.; Wernic, D.; Peters, J.M.
Regulation of human separase by securin binding and autocleavage
Curr. Biol.
12
1368-1378
2002
Homo sapiens
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
Chestukhin, A.; Pfeffer, C.; Milligan, S.; DeCaprio, J.A.; Pellman, D.
Processing, localization, and requirement of human separase for normal anaphase progression
Proc. Natl. Acad. Sci. USA
100
4574-4579
2003
Homo sapiens
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
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
brenda
Gimenez-Abian, J.F.; Diaz-Martinez, L.A.; Waizenegger, I.C.; Gimenez-Martin, G.; Clarke, D.J.
Separase is required at multiple pre-anaphase cell cycle stages in human cells
Cell Cycle
4
1576-1584
2005
Homo sapiens
brenda
Kawasaki, Y.; Nagao, K.; Nakamura, T.; Yanagida, M.
Fission yeast MAP kinase is required for the increased securin-separase interaction that rescues separase mutants under stresses
Cell Cycle
5
1831-1839
2006
Schizosaccharomyces pombe
brenda
Fan, H.Y.; Sun, Q.Y.; Zou, H.
Regulation of Separase in meiosis: Separase is activated at the metaphase I-II transition in Xenopus oocytes during meiosis
Cell Cycle
5
198-204
2006
Xenopus sp.
brenda
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
brenda
Kitajima, T.S.; Miyazaki, Y.; Yamamoto, M.; Watanabe, Y.
Rec8 cleavage by separase is required for meiotic nuclear divisions in fission yeast
EMBO J.
22
5643-5653
2003
Schizosaccharomyces pombe
brenda
Nagao, K.; Yanagida, M.
Securin can have a separase cleavage site by substitution mutations in the domain required for stabilization and inhibition of separase
Genes Cells
11
247-260
2006
Schizosaccharomyces pombe
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
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
brenda
Pandey, R.; Heidmann, S.; Lehner, C.F.
Epithelial re-organization and dynamics of progression through mitosis in Drosophila separase complex mutants
J. Cell Sci.
118
733-742
2005
Drosophila sp. (in: flies)
brenda
Ikai, N.; Yanagida, M.
Cdc48 is required for the stability of Cut1/separase in mitotic anaphase
J. Struct. Biol.
156
50-61
2006
Schizosaccharomyces pombe
brenda
Gorr, I.H.; Boos, D.; Stemmann, O.
Mutual inhibition of separase and Cdk1 by two-step complex formation
Mol. Cell
19
135-141
2005
Xenopus sp.
brenda
Papi, M.; Berdougo, E.; Randall, C.L.; Ganguly, S.; Jallepalli, P.V.
Multiple roles for separase auto-cleavage during the G2/M transition
Nat. Cell Biol.
7
1029-1035
2005
Homo sapiens
brenda
Nagao, K.; Adachi, Y.; Yanagida, M.
Separase-mediated cleavage of cohesin at interphase is required for DNA repair
Nature
430
1044-1048
2004
Schizosaccharomyces pombe
brenda
Liu, Z.; Makaroff, C.A.
Arabidopsis separase AESP is essential for embryo development and the release of cohesin during meiosis
Plant Cell
18
1213-1225
2006
Arabidopsis thaliana (Q5IBC5), Arabidopsis thaliana
brenda
Pereira, G.; Schiebel, E.
Separase regulates INCENP-Aurora B anaphase spindle function through Cdc14
Science
302
2120-2124
2003
Saccharomyces cerevisiae
brenda
Bembenek, J.N.; Richie, C.T.; Squirrell, J.M.; Campbell, J.M.; Eliceiri, K.W.; Poteryaev, D.; Spang, A.; Golden, A.; White, J.G.
Cortical granule exocytosis in C. elegans is regulated by cell cycle components including separase
Development
134
3837-3848
2007
Caenorhabditis elegans
brenda
Shepard, J.L.; Amatruda, J.F.; Finkelstein, D.; Ziai, J.; Finley, K.R.; Stern, H.M.; Chiang, K.; Hersey, C.; Barut, B.; Freeman, J.L.; Lee, C.; Glickman, J.N.; Kutok, J.L.; Aster, J.C.; Zon, L.I.
A mutation in separase causes genome instability and increased susceptibility to epithelial cancer
Genes Dev.
21
55-59
2007
Danio rerio
brenda
Boos, D.; Kuffer, C.; Lenobel, R.; Koerner, R.; Stemmann, O.
Phosphorylation-dependent binding of cyclin B1 to a Cdc6-like domain of human separase
J. Biol. Chem.
283
816-823
2008
Homo sapiens
brenda
Nakajima, M.; Kumada, K.; Hatakeyama, K.; Noda, T.; Peters, J.M.; Hirota, T.
The complete removal of cohesin from chromosome arms depends on separase
J. Cell Sci.
120
4188-4196
2007
Homo sapiens
brenda
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
brenda
Gorr, I.H.; Reis, A.; Boos, D.; Wuehr, M.; Madgwick, S.; Jones, K.T.; Stemmann, O.
Essential CDK1-inhibitory role for separase during meiosis I in vertebrate oocytes
Nat. Cell Biol.
8
1035-1037
2006
Xenopus laevis
brenda
Terret, M.; Jallepalli, P.V.
Meiosis: separase strikes twice
Nat. Cell Biol.
8
910-911
2006
Mus musculus, Saccharomyces cerevisiae
brenda
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
brenda
Adachi, Y.; Kokubu, A.; Ebe, M.; Nagao, K.; Yanagida, M.
Cut1/separase-dependent roles of multiple phosphorylation of fission yeast cohesion subunit Rad21 in post-replicative damage repair and mitosis
Cell Cycle
7
765-776
2008
Schizosaccharomyces pombe
brenda
Sak, A.; Fegers, I.; Groneberg, M.; Stuschke, M.
Effect of separase depletion on ionizing radiation-induced cell cycle checkpoints and survival in human lung cancer cell lines
Cell Prolif.
41
660-670
2008
Homo sapiens
brenda
Sun, Y.; Kucej, M.; Fan, H.Y.; Yu, H.; Sun, Q.Y.; Zou, H.
Separase is recruited to mitotic chromosomes to dissolve sister chromatid cohesion in a DNA-dependent manner
Cell
137
123-132
2009
Homo sapiens
brenda
Meyer, R.; Fofanov, V.; Panigrahi, A.; Merchant, F.; Zhang, N.; Pati, D.
Overexpression and mislocalization of the chromosomal segregation protein separase in multiple human cancers
Clin. Cancer Res.
15
2703-2710
2009
Homo sapiens
brenda
Clift, D.; Bizzari, F.; Marston, A.L.
Shugoshin prevents cohesin cleavage by PP2A(Cdc55)-dependent inhibition of separase
Genes Dev.
23
766-780
2009
Anaplasma marginale
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
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
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
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
brenda
Bessat, M.; Ersfeld, K.
Functional characterization of cohesin SMC3 and separase and their roles in the segregation of large and minichromosomes in Trypanosoma brucei
Mol. Microbiol.
71
1371-1385
2009
Trypanosoma brucei
brenda
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
Mus musculus, Homo sapiens
brenda
Basu, D.; Zhang, N.; Panigrahi, A.K.; Horton, T.M.; Pati, D.
Development and validation of a fluorogenic assay to measure separase enzyme activity
Anal. Biochem.
392
133-138
2009
Homo sapiens
brenda
Bembenek, J.N.; White, J.G.; Zheng, Y.
A role for separase in the regulation of RAB-11-positive vesicles at the cleavage furrow and midbody
Curr. Biol.
20
259-264
2010
Caenorhabditis elegans
brenda
Tsou, M.F.; Wang, W.J.; George, K.A.; Uryu, K.; Stearns, T.; Jallepalli, P.V.
Polo kinase and separase regulate the mitotic licensing of centriole duplication in human cells
Dev. Cell
17
344-354
2009
Homo sapiens
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
Wu, S.; Scheible, W.R.; Schindelasch, D.; Van Den Daele, H.; De Veylder, L.; Baskin, T.I.
A conditional mutation in Arabidopsis thaliana separase induces chromosome non-disjunction, aberrant morphogenesis and cyclin B1,1 stability
Development
137
953-961
2010
Arabidopsis thaliana
brenda
Nakamura, A.; Arai, H.; Fujita, N.
Centrosomal Aki1 and cohesin function in separase-regulated centriole disengagement
J. Cell Biol.
187
607-614
2009
Homo sapiens
brenda
Kudo, N.R.; Anger, M.; Peters, A.H.; Stemmann, O.; Theussl, H.C.; Helmhart, W.; Kudo, H.; Heyting, C.; Nasmyth, K.
Role of cleavage by separase of the Rec8 kleisin subunit of cohesin during mammalian meiosis I
J. Cell Sci.
122
2686-2698
2009
Homo sapiens
brenda
Ishiguro, T.; Tanaka, K.; Sakuno, T.; Watanabe, Y.
Shugoshin-PP2A counteracts casein-kinase-1-dependent cleavage of Rec8 by separase
Nat. Cell Biol.
12
500-506
2010
Homo sapiens
brenda
Yang, X.; Boateng, K.A.; Strittmatter, L.; Burgess, R.; Makaroff, C.A.
Arabidopsis separase functions beyond the removal of sister chromatid cohesion during meiosis
Plant Physiol.
151
323-333
2009
Arabidopsis thaliana
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
Homo sapiens, Mus musculus, Saccharomyces cerevisiae
brenda
Moschou, P.N.; Bozhkov, P.V.
Separases: biochemistry and function
Physiol. Plant.
145
67-76
2012
Arabidopsis thaliana (Q5IBC5), Vitis vinifera, Ricinus communis, Saccharomyces cerevisiae, Schizosaccharomyces pombe, Cryptosporidium muris, Caenorhabditis elegans, Homo sapiens, Drosophila melanogaster, Chlamydomonas reinhardtii, Oryza sativa, Sorghum bicolor
brenda
Yim, H.; Erikson, R.L.
Cell division cycle 6, a mitotic substrate of polo-like kinase 1, regulates chromosomal segregation mediated by cyclin-dependent kinase 1 and separase
Proc. Natl. Acad. Sci. USA
107
19742-19747
2010
Homo sapiens
brenda
Bacac, M.; Fusco, C.; Planche, A.; Santodomingo, J.; Demaurex, N.; Leemann-Zakaryan, R.; Provero, P.; Stamenkovic, I.
Securin and separase modulate membrane traffic by affecting endosomal acidification
Traffic
12
615-626
2011
Homo sapiens
brenda
Matsuo, K.; Ohsumi, K.; Iwabuchi, M.; Kawamata, T.; Ono, Y.; Takahashi, M.
Kendrin is a novel substrate for separase involved in the licensing of centriole duplication
Curr. Biol.
22
915-921
2012
Homo sapiens (Q14674)
brenda
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)
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
Hellmuth, S.; Poehlmann, C.; Brown, A.; Boettger, F.; Sprinzl, M.; Stemmann, O.
Positive and negative regulation of vertebrate separase by cdk1-cyclin b1 may explain why securin is dispensable
J. Biol. Chem.
290
8002-8010
2015
Homo sapiens (Q14674)
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
Agircan, F.G.; Schiebel, E.
Sensors at centrosomes reveal determinants of local separase activity
PLoS Genet.
10
e1004672
2014
Homo sapiens (Q14674)
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
Haass, W.; Stehle, M.; Nittka, S.; Giehl, M.; Schrotz-King, P.; Fabarius, A.; Hofmann, W.K.; Seifarth, W.
The proteolytic activity of separase in BCR-ABL-positive cells is increased by imatinib
PLoS ONE
7
e42863
2012
Homo sapiens (Q14674), Homo sapiens
brenda
Zhang, N.; Pati, D.
Biology and insights into the role of cohesin protease separase in human malignancies
Biol. Rev. Camb. Philos. Soc.
92
2070-2083
2017
Homo sapiens (Q14674), Homo sapiens, Mus musculus (P60330), Mus musculus
brenda
Do, H.T.; Zhang, N.; Pati, D.; Gilbertson, S.R.
Synthesis and activity of benzimidazole-1,3-dioxide inhibitors of separase
Bioorg. Med. Chem. Lett.
26
4446-4450
2016
Homo sapiens (Q14674), Homo sapiens
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
Saccharomyces cerevisiae (Q03018), Schizosaccharomyces pombe (P18296), Drosophila melanogaster (Q9VRN6), Arabidopsis thaliana (A0A1P8B3N4), Picea abies (R4XPW1), Caenorhabditis elegans, Schizosaccharomyces pombe ATCC 24843 (P18296)
brenda
Cipressa, F.; Morciano, P.; Bosso, G.; Mannini, L.; Galati, A.; Raffa, G.D.; Cacchione, S.; Musio, A.; Cenci, G.
A role for Separase in telomere protection
Nat. Commun.
7
10405
2016
Drosophila sp. (in: flies)
brenda
Lin, Z.; Luo, X.; Yu, H.
Structural basis of cohesin cleavage by separase
Nature
532
131-134
2016
Thermochaetoides thermophila (G0SHM3), Thermochaetoides thermophila DSM 1495 (G0SHM3)
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
Blattner, A.C.; Chaurasia, S.; McKee, B.D.; Lehner, C.F.
Separase is required for homolog and sister disjunction during Drosophila melanogaster male meiosis, but not for biorientation of sister centromeres
PLoS Genet.
12
e1005996
2016
Drosophila melanogaster (Q9VRN6), Drosophila melanogaster
brenda
Monen, J.; Hattersley, N.; Muroyama, A.; Stevens, D.; Oegema, K.; Desai, A.
Separase cleaves the N-tail of the CENP-A related protein CPAR-1 at the meiosis I metaphase-anaphase transition in C. elegans
PLoS ONE
10
e0125382
2015
Caenorhabditis elegans (G5ED39), Caenorhabditis elegans
brenda
Haass, W.; Kleiner, H.; Mueller, M.C.; Hofmann, W.K.; Fabarius, A.; Seifarth, W.
Measurement of separase proteolytic activity in single living cells by a fluorogenic flow cytometry assay
PLoS ONE
10
e0133769
2015
Homo sapiens (Q14674), Homo sapiens
brenda
Henschke, L.; Frese, M.; Hellmuth, S.; Marx, A.; Stemmann, O.; Mayer, T.U.
Identification of bioactive small molecule inhibitors of separase
ACS Chem. Biol.
14
2155-2159
2019
Homo sapiens, Homo sapiens (Q14674)
brenda
Spiess, B.; Kleiner, H.; Flach, J.; Fabarius, A.; Saussele, S.; Hofmann, W.K.; Seifarth, W.
Separase activity distribution can be a marker of major molecular response and proliferation of CD34+ cells in TKI-treated chronic myeloid leukemia patients
Ann. Hematol.
99
991-1006
2020
Homo sapiens, Homo sapiens (Q14674)
brenda
Liang, M.; Chen, X.; Zhu, C.; Liang, X.; Gao, Z.; Luo, S.
Identification of a novel substrate motif of yeast separase and deciphering the recognition specificity using AlphaFold2 and molecular dynamics simulation
Biochem. Biophys. Res. Commun.
620
173-179
2022
Saccharomyces cerevisiae (Q03018), Saccharomyces cerevisiae ATCC 204508 (Q03018)
brenda
Yu, J.; Morgan, D.O.; Boland, A.
The molecular mechanisms of human separase regulation
Biochem. Soc. Trans.
51
1225-1233
2023
Homo sapiens (Q14674), Saccharomyces cerevisiae (Q03018)
brenda
Rahman, M.S.; Shindo, Y.; Oka, K.; Ikeda, W.; Suzuki, M.
Live cell monitoring of separase activity, a key enzymatic reaction for chromosome segregation, with chimeric FRET-based molecular sensor upon cell cycle progression
Biosensors
14
192
2024
Homo sapiens, Homo sapiens (Q14674)
brenda
Wassmann, K.
Separase control and cohesin cleavage in oocytes should I stay or should I go?
Cells
11
3399
2022
Homo sapiens, Homo sapiens (Q14674)
brenda
Maier, N.K.; Ma, J.; Lampson, M.A.; Cheeseman, I.M.
Separase cleaves the kinetochore protein Meikin at the meiosis I/II transition
Dev. Cell
56
2192-2206.e8
2021
Mus musculus (P60330)
brenda
Maier, N.K.; Ma, J.; Lampson, M.A.; Cheeseman, I.M.
Separase cleaves the kinetochore protein Meikin at the meiosis I/II transition
Dev. Cell
56
2192-2206
2021
Mus musculus, Homo sapiens
brenda
Sparapani, S.; Bachewich, C.
Characterization of a novel separase-interacting protein and candidate new securin, Eip1p, in the fungal pathogen Candida albicans
Mol. Biol. Cell
30
2469-2489
2019
Candida albicans
brenda
Rosen, L.E.; Klebba, J.E.; Asfaha, J.B.; Ghent, C.M.; Campbell, M.G.; Cheng, Y.; Morgan, D.O.
Cohesin cleavage by separase is enhanced by a substrate motif distinct from the cleavage site
Nat. Commun.
10
5189
2019
Homo sapiens, Homo sapiens (Q14674)
brenda
Hellmuth, S.; Stemmann, O.
Separase-triggered apoptosis enforces minimal length of mitosis
Nature
580
542-547
2020
Homo sapiens, Homo sapiens (Q14674)
brenda
Yu, J.; Raia, P.; Ghent, C.M.; Raisch, T.; Sadian, Y.; Cavadini, S.; Sabale, P.M.; Barford, D.; Raunser, S.; Morgan, D.O.; Boland, A.
Structural basis of human separase regulation by securin and CDK1-cyclin B1
Nature
596
138-142
2021
Homo sapiens (Q14674)
brenda
Cromer, L.; Jolivet, S.; Singh, D.K.; Berthier, F.; De Winne, N.; De Jaeger, G.; Komaki, S.; Prusicki, M.A.; Schnittger, A.; Guerois, R.; Mercier, R.
Patronus is the elusive plant securin, preventing chromosome separation by antagonizing separase
Proc. Natl. Acad. Sci. USA
116
16018-16027
2019
Arabidopsis thaliana, Arabidopsis thaliana (Q5IBC5)
brenda
Jeong, P.Y.; Kumar, A.; Joshi, P.M.; Rothman, J.H.
Intertwined functions of separase and caspase in cell division and programmed cell death
Sci. Rep.
10
6159
2020
Caenorhabditis elegans, Caenorhabditis elegans (G5ED39)
brenda
Nikalayevich, E.; Wassmann, K.
Protocol to measure cleavage efficiency of the meiotic cohesin subunit Rec8 by separase in mouse oocytes using a biosensor
STAR Protoc.
3
101714
2022
Mus musculus, Mus musculus (P60330)
brenda
Luo, S.; Tong, L.
Structure and function of the Separase-securin complex
Subcell. Biochem.
96
217-232
2021
Homo sapiens, Homo sapiens (Q14674)
brenda
EXTERNAL LINKS (specific for EC-Number 3.4.22.49)
html completed
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2026.1 (March 2026)
About BRENDA
Social media
Help
Survey
Download
Contribution
Legal
Curated at
Member of
![DSMZ Digital Diversity]()
![Global Core Biodata Resource]()
![ELIXIR Core Data Resource]()
![German Network for Bioinformatics Infrastructure]()
