Caspase-9

Title: Caspase-9
CAS Registry Number: 180189-96-2
CAS Name: ICE-LAP6
Additional Names: Mch6
Literature References: Central initiator caspase. Synthesized as an inactive 46 kDa precursor protein, procaspase-9, which consists of three domains: an N-terminal pro-domain, a 20 kDa large subunit, and a 10 kDa small subunit. Activated in the cytoplasm by cleavage of the prodomain, in response to mitochondrial damage. Activation occurs by binding to an Apaf-1/cytochrome c complex known as the apoptosome, in the presence of dATP. Isoln and characterization: H. Duan et al., J. Biol. Chem. 271, 16720 (1996); S. M. Srinivasula et al., ibid. 27099. Purification, binding to Apaf-1, and activation of caspase-3, q.v.: P. Li et al., Cell 91, 479 (1997). Role in initiation of the caspase cascade: E. A. Slee et al., J. Cell Biol. 144, 281 (1999). Crystal structure of the prodomain in complex with the prodomain of Apaf-1: H. Qin et al., Nature 399, 549 (1999). Human gene structure and chromosomal location: S. Hadano et al., Mammal. Genome 10, 757 (1999). Activation mechanism: J. Rodriguez, Y. Lazebnik, Genes Dev. 13, 3179 (1999); E. N. Shiozaki et al., Proc. Natl. Acad. Sci. USA 99, 4197 (2002). Review of structure and function: K. Kuida, Int. J. Biochem. Cell Biol. 32, 121-124 (2000); of activation mechanism: Y. Shi, Structure 10, 285-288 (2002).
Caspofungin Cassaidine Cassaine Cassamine Castanea

Caspase 9, apoptosis-related cysteine peptidase

PDB rendering based on 1jxq.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols CASP9 (; APAF-3; APAF3; CASPASE-9c; ICE-LAP6; MCH6; PPP1R56)
External IDs OMIM: 602234 MGI: 1277950 HomoloGene: 31024 ChEMBL: 2273 GeneCards: CASP9 Gene
EC number 3.4.22.62
RNA expression pattern
PBB GE CASP9 203984 s at tn.png
PBB GE CASP9 210775 x at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 842 12371
Ensembl ENSG00000132906 ENSMUSG00000028914
UniProt P55211 Q8C3Q9
RefSeq (mRNA) NM_001229 NM_001277932
RefSeq (protein) NP_001220 NP_001264861
Location (UCSC) Chr 1:
15.82 – 15.85 Mb
Chr 4:
141.79 – 141.82 Mb
PubMed search [1] [2]

Caspase-9 is an initiator caspase,[1] encoded by the CASP9 gene. CASP9 orthologs [2] have been identified in all mammals for which complete genome data are available. Unique orthologs are also present in lizards, lissamphibians, and teleosts.

The aspartic acid specific protease caspase-9 has been linked to the mitochondrial death pathway. It is activated during programmed cell death (apoptosis). Induction of stress signaling pathways JNK/SAPK causes release of cytochrome c from mitochondria and activation of apaf-1 (apoptosome), which in turn cleaves the pro-enzyme of caspase-9 into the active form.

Once initiated caspase-9 goes on to cleave procaspase-3 & procaspase-7, which cleave several cellular targets, including poly ADP ribose polymerase.