APAF1

The protein was identified in the laboratory of Xiaodong Wang as an activator of caspase-3 in the presence of cytochromeC and dATP.^[8] 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.^[9] Activated caspase-9 stimulates the subsequent caspase cascade that commits the cell to apoptosis.^{[citation needed]}

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.^[10]

APAF1 has been shown to interact with:

• APIP,^[11]
• BCL2-like 1^[12][13]
• Caspase-9,^{[14][11][15][12][13]}
• HSPA4,^[16] and
• NLRP1.^[14]