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Protein CASP9 PDB 1jxq.png
Available structures
PDB Ortholog search: PDBe RCSB
Aliases CASP9, APAF-3, APAF3, ICE-LAP6, MCH6, PPP1R56, caspase 9
External IDs OMIM: 602234 MGI: 1277950 HomoloGene: 31024 GeneCards: CASP9
Gene location (Human)
Chromosome 1 (human)
Chr. Chromosome 1 (human)[1]
Chromosome 1 (human)
Genomic location for CASP9
Genomic location for CASP9
Band 1p36.21 Start 15,490,832 bp[1]
End 15,526,534 bp[1]
RNA expression pattern
PBB GE CASP9 210775 x at fs.png

PBB GE CASP9 203984 s at fs.png
More reference expression data
Species Human Mouse
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC) Chr 1: 15.49 – 15.53 Mb Chr 1: 141.79 – 141.82 Mb
PubMed search [3] [4]
View/Edit Human View/Edit Mouse

Caspase-9 is an initiator caspase,[5] encoded by the CASP9 gene. CASP9 orthologs [6] 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.


Caspase-9 precursor procaspase-9 is present as an inactive monomer before it undergoes a conformational change to a dimer and associates with the apf-1 and cytochrome c complex to form an apoptosome.[7]


Caspase-9 has been shown to interact with:

Overview of signal transduction pathways involved in apoptosis.

See also[edit]


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000132906 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000028914 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  5. ^ Caspase 9
  6. ^ "OrthoMaM phylogenetic marker: CASP9 coding sequence". 
  7. ^ Bratton, Shawn; Salvesen, Guy (2010). "Regulation of the Apaf-1-caspase-9 apoptosome". Journal of Cell Science. 123: 3209–3214. PMC 2939798Freely accessible. PMID 20844150. doi:10.1242/jcs.073643. Retrieved 27 September 2015. 
  8. ^ a b Chu ZL, Pio F, Xie Z, Welsh K, Krajewska M, Krajewski S, Godzik A, Reed JC (March 2001). "A novel enhancer of the Apaf1 apoptosome involved in cytochrome c-dependent caspase activation and apoptosis". J. Biol. Chem. 276 (12): 9239–45. PMID 11113115. doi:10.1074/jbc.M006309200. 
  9. ^ Cho DH, Hong YM, Lee HJ, Woo HN, Pyo JO, Mak TW, Jung YK (September 2004). "Induced inhibition of ischemic/hypoxic injury by APIP, a novel Apaf-1-interacting protein". J. Biol. Chem. 279 (38): 39942–50. PMID 15262985. doi:10.1074/jbc.M405747200. 
  10. ^ Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, Wang X (November 1997). "Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade". Cell. 91 (4): 479–89. PMID 9390557. doi:10.1016/s0092-8674(00)80434-1. 
  11. ^ Hu Y, Benedict MA, Wu D, Inohara N, Núñez G (April 1998). "Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 activation". Proc. Natl. Acad. Sci. U.S.A. 95 (8): 4386–91. PMC 22498Freely accessible. PMID 9539746. doi:10.1073/pnas.95.8.4386. 
  12. ^ Pan G, O'Rourke K, Dixit VM (March 1998). "Caspase-9, Bcl-XL, and Apaf-1 form a ternary complex". J. Biol. Chem. 273 (10): 5841–5. PMID 9488720. doi:10.1074/jbc.273.10.5841. 
  13. ^ a b c Deveraux QL, Roy N, Stennicke HR, Van Arsdale T, Zhou Q, Srinivasula SM, Alnemri ES, Salvesen GS, Reed JC (April 1998). "IAPs block apoptotic events induced by caspase-8 and cytochrome c by direct inhibition of distinct caspases". EMBO J. 17 (8): 2215–23. PMC 1170566Freely accessible. PMID 9545235. doi:10.1093/emboj/17.8.2215. 
  14. ^ Guo Y, Srinivasula SM, Druilhe A, Fernandes-Alnemri T, Alnemri ES (April 2002). "Caspase-2 induces apoptosis by releasing proapoptotic proteins from mitochondria". J. Biol. Chem. 277 (16): 13430–7. PMID 11832478. doi:10.1074/jbc.M108029200. 
  15. ^ Srinivasula SM, Ahmad M, Fernandes-Alnemri T, Litwack G, Alnemri ES (December 1996). "Molecular ordering of the Fas-apoptotic pathway: the Fas/APO-1 protease Mch5 is a CrmA-inhibitable protease that activates multiple Ced-3/ICE-like cysteine proteases". Proc. Natl. Acad. Sci. U.S.A. 93 (25): 14486–91. PMC 26159Freely accessible. PMID 8962078. doi:10.1073/pnas.93.25.14486. 
  16. ^ Hlaing T, Guo RF, Dilley KA, Loussia JM, Morrish TA, Shi MM, Vincenz C, Ward PA (March 2001). "Molecular cloning and characterization of DEFCAP-L and -S, two isoforms of a novel member of the mammalian Ced-4 family of apoptosis proteins". J. Biol. Chem. 276 (12): 9230–8. PMID 11076957. doi:10.1074/jbc.M009853200. 
  17. ^ Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. PMID 16189514. doi:10.1038/nature04209. 
  18. ^ Davoodi J, Lin L, Kelly J, Liston P, MacKenzie AE (September 2004). "Neuronal apoptosis-inhibitory protein does not interact with Smac and requires ATP to bind caspase-9". J. Biol. Chem. 279 (39): 40622–8. PMID 15280366. doi:10.1074/jbc.M405963200. 
  19. ^ Richter BW, Mir SS, Eiben LJ, Lewis J, Reffey SB, Frattini A, Tian L, Frank S, Youle RJ, Nelson DL, Notarangelo LD, Vezzoni P, Fearnhead HO, Duckett CS (July 2001). "Molecular cloning of ILP-2, a novel member of the inhibitor of apoptosis protein family". Mol. Cell. Biol. 21 (13): 4292–301. PMC 87089Freely accessible. PMID 11390657. doi:10.1128/MCB.21.13.4292-4301.2001. 

Further reading[edit]

External links[edit]

  • The MEROPS online database for peptidases and their inhibitors: C14.010