separin; caspase-like protein ESPL1; extra spindle poles-like 1 protein; separase (ESPL1, ESP1, KIAA0165)

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Function

caspase-like protease
role in chromosome segregation by cleaving the SCC1/RAD21 subunit of the cohesin complex at the onset of anaphase
during most of the cell cycle, it is inactivated by different mechanisms
all bonds known to be hydrolyzed by this endopeptidase have Arg in P1 & an acidic residue in P4
P6 is often occupied by an acidic residue or by an hydroxy-amino-acid residue (Ser/Thr), phosphorylation of which enhances cleavage
regulated by at least two independent mechanisms
- inactivated via its interaction with securin/PTTG1, which probably covers its active site
  - association with PTTG1 is not only inhibitory, since PTTG1 is also required for activating it, the enzyme being inactive in cells in which PTTG1 is absent
  - PTTG1 degradation at anaphase, liberates it & triggers RAD21 cleavage
- phosphorylation at Ser-1126 inactivates it.
  - phosphorylation during mitosis, is removed when cells undergo anaphase
  - activation of the enzyme at the metaphase-anaphase transition probably requires the removal of both securin & inhibitory phosphate
autocleaves
- not essential for its protease activity
- function unknown
phosphorylated by CDK1
there are 8 Ser/Thr phosphorylation sites
- among them, Ser-1126 phosphorylation is the major site, which is associated with enzyme inactivation
interacts with PTTG1
interacts with RAD21

belongs to the peptidase C50 family