APAF1

Apoptotic protease activating factor 1, also known as APAF1, is a human homolog of C. elegans CED-4 gene. APAF-1 and CED-4 homologs have been found in all currently sequenced animal genomes.

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

is_associated_with::Alternative splicing results in several transcript variants encoding different isoforms.

Structure
The first is_associated_with::crystal structure of the first two (CARD and NB-ARC) domains of the Apaf-1 protein was solved in the laboratory of is_associated_with::Yigong Shi. It contains a is_associated_with::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.

Discovery
The Apaf-1 protein was identified by is_associated_with::.

Interactions
APAF1 has been shown to interact with is_associated_with::NLRP1, is_associated_with::Caspase-9,   is_associated_with::APIP, BCL2-like 1  and is_associated_with::HSPA4.