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

More general terms

• caspase

More specific terms

• caspase-9, p10 subunit
• caspase-9, p35 subunit
• procaspase-9

Database

• UniProt: http://www.uniprot.org/uniprot/P55211.html
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:842
• OMIM: https://mirror.omim.org/entry/602234
• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=842
• Kegg: http://www.genome.jp/dbget-bin/www_bget?