Apoptotic protease activating factor 1, also known as APAF1, is a human homolog of ''C. elegans'' CED-4 gene.

Function

The protein was identified in the laboratory of Xiaodong Wang as an activator of caspase-3 in the presence of cytochromeC and dATP. This gene encodes a cytoplasmic protein that forms one of the central hubs in the

apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...

regulatory network. This protein contains (from the N terminal) a caspase recruitment domain (

CARD Card or The Card may refer to: Common uses * Plastic cards of various types: **Bank card **Credit card **Debit card **Payment card * Playing card, used in games * Printed circuit board, or card * Greeting card, given on special occasions Arts an ...

), an

ATPase ATPases (, Adenosine 5'-TriPhosphatase, adenylpyrophosphatase, ATP monophosphatase, triphosphatase, ATP hydrolase, adenosine triphosphatase) are a class of enzymes that catalyze the decomposition of ATP into ADP and a free phosphate ion or ...

domain (NB-ARC), few short helical domains and then several copies of the

WD40 repeat The WD40 repeat (also known as the WD or beta-transducin repeat) is a short structural motif of approximately 40 amino acids, often terminating in a tryptophan-aspartic acid (W-D) dipeptide. Tandem copies of these repeats typically fold togethe ...

domain. Upon binding cytochrome c and

dATP Deoxyadenosine triphosphate (dATP) is a nucleotide used in cells for DNA synthesis (or replication), as a substrate of DNA polymerase. Deoxyadenosine triphosphate is produced from DNA by the action of nuclease P1, adenylate kinase, and pyruvate ...

, 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 Caspase-9 is an enzyme that in humans is encoded by the ''CASP9'' gene. It is an initiator caspase, critical to the apoptotic pathway found in many tissues. Caspase-9 homologs have been identified in all mammals for which they are known to exist, ...

dimerization and subsequent

autocatalysis In chemistry, a chemical reaction is said to be autocatalytic if one of the reaction products is also a catalyst for the same reaction. Many forms of autocatalysis are recognized.Steinfeld J.I., Francisco J.S. and Hase W.L. ''Chemical Kinetics and ...

. Activated caspase-9 stimulates the subsequent caspase cascade that commits the cell to apoptosis.

Alternative splicing Alternative splicing, alternative RNA splicing, or differential splicing, is an alternative RNA splicing, splicing process during gene expression that allows a single gene to produce different splice variants. For example, some exons of a gene ma ...

results in several transcript variants encoding different isoforms.

Structure

APAF1 contains a

CARD domain Caspase recruitment domains, or caspase activation and recruitment domains (CARDs), are interaction motifs found in a wide array of proteins, typically those involved in processes relating to inflammation and apoptosis. These domains mediate th ...

with a Greek key motif composed of six helices, a Rossman fold nucleotide binding domains, a short helical motif and a winged-helix domain. 177-Apoptosomes human apoptosome

Interactions

APAF1 has been shown to interact with: * APIP, * BCL2-like 1 *

Caspase-9 Caspase-9 is an enzyme that in humans is encoded by the ''CASP9'' gene. It is an initiator caspase, critical to the apoptotic pathway found in many tissues. Caspase-9 homologs have been identified in all mammals for which they are known to exist, ...

, *

HSPA4 Heat shock 70 kDa protein 4 is a protein that in humans is encoded by the ''HSPA4'' gene. The protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. ...

, and *

NLRP1 NLRP1 encodes NACHT, LRR, FIIND, CARD domain and PYD domains-containing protein 1 in humans. NLRP1 was the first protein shown to form an inflammasome. Material was copied from this source, which is available under Creative Commons Attribution ...

Function

Structure

Interactions

References

Further reading