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Available structures
PDB Ortholog search: PDBe RCSB
Aliases APAF1, APAF-1, CED4, apoptotic peptidase activating factor 1
External IDs MGI: 1306796 HomoloGene: 7626 GeneCards: APAF1
Gene location (Human)
Human chromosome 12
Chr. Chromosome 12 (human)[1]
Human chromosome 12
Genomic location for APAF1
Genomic location for APAF1
Band No data available Start 98,645,141 bp[1]
End 98,735,433 bp[1]
RNA expression pattern
PBB GE APAF1 211553 x at fs.png

PBB GE APAF1 211554 s at fs.png

PBB GE APAF1 204859 s at fs.png
More reference expression data
Species Human Mouse
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC) Chr 12: 98.65 – 98.74 Mb Chr 10: 90.99 – 91.08 Mb
PubMed search [3] [4]
View/Edit Human View/Edit Mouse

Apoptotic protease activating factor 1, also known as APAF1, is a human homolog of C. elegans CED-4 gene.[5][6][7]


This gene encodes a cytoplasmic protein that forms one of the central hubs in the apoptosis regulatory network. This protein contains (from the N terminal) a caspase recruitment domain (CARD), an ATPase domain (NB-ARC), few short helical domains and then several copies of the WD40 repeat domain. Upon binding cytochrome c and dATP, this protein forms an oligomeric apoptosome. The apoptosome binds and cleaves Procaspase 9 protein, releasing its mature, activated form. The precise mechanism for this reaction is still debated though work published by Guy Salvesen suggests that the apoptosome may induce caspase 9 dimerization and subsequent autocatalysis.[8] Activated caspase 9 stimulates the subsequent caspase cascade that commits the cell to apoptosis.

Alternative splicing results in several transcript variants encoding different isoforms.[5]


APAF1 contains a CARD domain with a Greek key motif composed of six helices, a Rossman fold nucleotide binding domains, a short helical motif and a winged-helix domain.[9]


APAF1 has been shown to interact with:


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000120868 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000019979 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  5. ^ a b "Entrez Gene: APAF1 apoptotic peptidase activating factor 1". 
  6. ^ Zou H, Henzel WJ, Liu X, Lutschg A, Wang X (Aug 1997). "Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3". Cell. 90 (3): 405–13. PMID 9267021. doi:10.1016/S0092-8674(00)80501-2. 
  7. ^ Kim H, Jung YK, Kwon YK, Park SH (1999). "Assignment of apoptotic protease activating factor-1 gene (APAF1) to human chromosome band 12q23 by fluorescence in situ hybridization". Cytogenetics and Cell Genetics. 87 (3–4): 252–3. PMID 10702682. doi:10.1159/000015436. 
  8. ^ Pop C, Timmer J, Sperandio S, Salvesen GS (Apr 2006). "The apoptosome activates caspase-9 by dimerization". Molecular Cell. 22 (2): 269–75. PMID 16630894. doi:10.1016/j.molcel.2006.03.009. 
  9. ^ Riedl SJ, Li W, Chao Y, Schwarzenbacher R, Shi Y (Apr 2005). "Structure of the apoptotic protease-activating factor 1 bound to ADP". Nature. 434 (7035): 926–33. PMID 15829969. doi:10.1038/nature03465. 
  10. ^ a b Cho DH, Hong YM, Lee HJ, Woo HN, Pyo JO, Mak TW, Jung YK (Sep 2004). "Induced inhibition of ischemic/hypoxic injury by APIP, a novel Apaf-1-interacting protein". The Journal of Biological Chemistry. 279 (38): 39942–50. PMID 15262985. doi:10.1074/jbc.M405747200. 
  11. ^ a b Hu Y, Benedict MA, Wu D, Inohara N, Núñez G (Apr 1998). "Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 activation". Proceedings of the National Academy of Sciences of the United States of America. 95 (8): 4386–91. PMC 22498Freely accessible. PMID 9539746. doi:10.1073/pnas.95.8.4386. 
  12. ^ a b Pan G, O'Rourke K, Dixit VM (Mar 1998). "Caspase-9, Bcl-XL, and Apaf-1 form a ternary complex". The Journal of Biological Chemistry. 273 (10): 5841–5. PMID 9488720. doi:10.1074/jbc.273.10.5841. 
  13. ^ a b Chu ZL, Pio F, Xie Z, Welsh K, Krajewska M, Krajewski S, Godzik A, Reed JC (Mar 2001). "A novel enhancer of the Apaf1 apoptosome involved in cytochrome c-dependent caspase activation and apoptosis". The Journal of Biological Chemistry. 276 (12): 9239–45. PMID 11113115. doi:10.1074/jbc.M006309200. 
  14. ^ Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, Wang X (Nov 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. 
  15. ^ Saleh A, Srinivasula SM, Balkir L, Robbins PD, Alnemri ES (Aug 2000). "Negative regulation of the Apaf-1 apoptosome by Hsp70". Nature Cell Biology. 2 (8): 476–83. PMID 10934467. doi:10.1038/35019510. 

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