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3.4.22.49: separase

This is an abbreviated version!
For detailed information about separase, go to the full flat file.

Word Map on EC 3.4.22.49

Reaction

all bonds known to be hydrolysed by this endopeptidase have arginine in P1 and an acidic residue in P4. P6 is often occupied by an acidic residue or by an hydroxy-amino-acid residue, the phosphorylation of which enhances cleavage =

Synonyms

AESP, AtESP, Cut1, Cut1/separase, ESP, Esp1, ESPL1, sep-1, separase, separin, SSE, TbSep

ECTree

     3 Hydrolases
         3.4 Acting on peptide bonds (peptidases)
             3.4.22 Cysteine endopeptidases
                3.4.22.49 separase

Engineering

Engineering on EC 3.4.22.49 - separase

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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C1129S
-
inactive
C2029A
E1483R/R1486E
-
autoproteolytically cleaved like wild-type
E1503R/R1506E
-
autoproteolytically cleaved like wild-type
E1532R/R1535E
-
autoproteolytically cleaved like wild-type
R1486A
-
mutation fails to block autocatalytical cleavage
R1506A
-
mutation at autocatalytical cleavage site, mutant enzyme is still cleaved indicating the existence of a second cleavage site
R1506A/R1486A
-
mutation fails to block autocatalytical cleavage
S1126A
S1126A/T1346A
-
active mutant
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