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.

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]

• Human APAF1 genome location and APAF1 gene details page in the UCSC Genome Browser.
• Overview of all the structural information available in the PDB for UniProt: O14727 (Apoptotic protease-activating factor 1) at the PDBe-KB.