Family C50


Summary Holotypes Alignment Tree Genomes Structure Literature H-seq M-seq Architecture

Summary for family C50

NamePeptidase family C50 (separase family)
Family type peptidaseC50.001 - separase (yeast-type) (Saccharomyces cerevisiae), MEROPS Accession MER0010982 (peptidase unit: 996-1629)
Content of familyPeptidase family C50 contains endopeptidases.
History Identifier created: MEROPS 5.00 (20 April 2000)
Genes encoding separase (C50.001) were originally discovered by genetic analysis of mitosis in fungi (e.g. Baum et al., 1988). These genes encode large proteins with conserved sequences near the C-termini that were recognised as homologous to peptidases in clan CD (Uhlmann et al., 2000). The peptidase was first termed separin and later separase.
Catalytic typeCysteine
Active site residuesH1505 C1531 
Active siteThe active site consists of a His, Cys catalytic dyad. The histidine occurs within a Xaa-Xaa-Xaa-Xaa-Gly-His-Gly motif, and the cysteine within a Xaa-Xaa-Xaa-Gly-Cys-Ser-Ser motif, in which Xaa is a hydrophobic residue (see the Alignment). These motifs are characteristic of clan CD.
Activities and specificitiesRecombinant yeast separase cleaves the protein Scc1 in vitro, and separase purified from human cells is also capable of cleaving human Scc1. All bonds known to be hydrolysed by separase have Arg in P1 and an acidic residue in P4; there is also a preference for an acidic residue in P6 (Peters & Nasmyth, 2004).
InhibitorsThe protein securin provides regulation of the activity of separase in vivo: it is an inhibitor, but also is necessary for the activation of separase and for its correct location in the cell (Hornig et al., 2002).
Molecular structureThe peptidase unit is found at the C-terminus of proteins in the family; the N-terminal parts show little conservation of sequence.
Basis of clan assignmentActive site residues for members of this family and family C14 occur in the same order in the sequence: H, C.
Distribution of family Bacteria details  
Archaea -  
Protozoa details  
Fungi -  
Plants details  
Animals details  
Viruses -  
Biological functionsSeparase has been shown to be required for the separation of sister chromatids during mitosis in a range of organisms from yeasts to man (Peters & Nasmyth, 2004). Cleavage of the cohesin subunit Scc1 is required for sister chromatid separation (Uhlmann et al., 1999; Hauf et al., 2001). Separase also acts during meiosis in Arabidopsis (Liu & Makaroff, 2006).
ReviewsPeters & Nasmyth (2004)
Statistics for family C50Sequences:881
Identifiers with PDB entries:3
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Other databases INTERPRO IPR005314
PFAM PF03568
Peptidases and Homologues MEROPS ID Structure
separase (yeast-type)C50.001Yes
separase (Homo sapiens-type)C50.002-
separase (Drosophila-type)C50.003-
SEP-1 peptidase (Nematoda)C50.004Yes
separase (plant type)C50.005-
ZK430.5 g.p. (Caenorhabditis elegans)C50.A01-
separase-like pseudogeneC50.P01-
Family C50 non-peptidase homologuesnon-peptidase homologue-
Family C50 unassigned peptidasesunassignedYes