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caspase-9; ice-like apoptotic protease 6; ICE-LAP6; apoptotic protease MCH-6 (CASP9, MCH6)
Function:
- role in the activation cascade of caspases responsible for apoptosis execution
- binding of caspase-9 to Apaf-1 leads to activation of the protease which then cleaves & activates caspase-3
- proteolytically cleaves poly(ADP-ribose) polymerase (PARP)
- isoform 2 lacks activity is an dominant-negative inhibitor of caspase-9
- heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 35 kD (p35) & a 10 kD (p10) subunit
- caspase-9 & APAF1 bind to each other via their respective NH2-terminal CED-3 homologous domains in the presence of cytochrome C & ATP
- interacts with the inhibitors BIRC2, BIRC4, BIRC5 & BIRC7
- cleavages at Asp-315 by granzyme B & at Asp-330 by caspase-3 generate the two active subunits
- caspase-8 & caspase-10 can also be involved in these processing events
- strict requirement for an Asp residue at position P1 & with a marked preference for His at position P2
- preferred cleavage sequence of Leu-gly-His-Asp-|-Xaa
Structure:
- belongs to the peptidase C14 family
- contains 1 CARD domain
Alternative splicing: named isoforms=2
Expression:
- ubiquitous
- highest expression in heart, moderate expression in liver, skeletal muscle, & pancreas
- low levels in all other tissues
Interactions
molecular events
Specific
caspase-9, p10 subunit
caspase-9, p35 subunit
procaspase-9
General
caspase; cysteinyl aspartate-specific proteinase; ICE/CED3 family protease
Properties
SIZE: entity length = 416 aa
MW = 46 kD
MOTIF: CARD domain {1-92}
histidine residue {H237}
cysteine residue {C287}
References
- UniProt :accession P55211
- Atlas of genetics & cytogenetics in oncology & haematology
http://atlasgeneticsoncology.org/genes/CASP9ID423ch1p36.html
- Wikipedia; Note: Caspase-9 entry
http://en.wikipedia.org/wiki/Caspase-9
Component-of
molecular complex
Databases & Figures
OMIM 602234
UniProt P55211
PFAM correlations
Entrez Gene 842
KEGG correlations
ENZYME 3.4.22.62
Figures/diagrams/slides/tables related to caspase-9