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

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 Structure: belongs to the peptidase C50 family Compartment: cytoplasm, nucleus Alternative splicing: named isoforms=2

General

cysteine proteinase; thiol proteinase phosphoprotein

Properties

SIZE: entity length = 2120 aa MW = 233 kD COMPARTMENT: cytoplasm cell nucleus MOTIF: Ser phosphorylation site {S1126} Ser phosphorylation site {S1396} Ser phosphorylation site {S1399} proteolytic site {1506-1507} Ser phosphorylation site {S1508} proteolytic site {1535-1536} cysteine residue {C2029}

Database Correlations

OMIM 604143 UniProt Q14674 Pfam PF03568 Entrez Gene 9700 Kegg hsa:9700 ENZYME 3.4.22.49

References

UniProt :accession Q14674