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 lab of
Xiaodong Wang as an activator of caspase-3 in the presense of cytochromeC and dATP.
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
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 togeth ...
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. It is classified as a purine nucleoside triphosphate, with its chemical structure consisting of a deoxyribose s ...
, this protein forms an oligomeric
apoptosome
The apoptosome is a large quaternary protein structure formed in the process of apoptosis. Its formation is triggered by the release of cytochrome c from the mitochondria in response to an internal (intrinsic) or external (extrinsic) cell death st ...
. 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, such ...
dimerization and subsequent
autocatalysis
A single chemical reaction is said to be autocatalytic if one of the reaction products is also a catalyst for the same or a coupled reaction.Steinfeld J.I., Francisco J.S. and Hase W.L. ''Chemical Kinetics and Dynamics'' (2nd ed., Prentice-Hall 199 ...
.
Activated caspase-9 stimulates the subsequent caspase cascade that commits the cell to apoptosis.
Alternative splicing 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.
Interactions
APAF1 has been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
with:
*
APIP
APAF1-interacting protein is a protein that in humans is encoded by the ''APIP'' gene. It is an enzyme with Methylthioribulose 1-phosphate dehydratase activity which is involved in the methionine salvage pathway.
APIP deficiency is associated wi ...
,
[
* 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, such ...
,
* HSPA4
Heat shock 70 kDa protein 4 is a protein that in humans is encoded by the ''HSPA4'' gene.
The protein encoded by this gene was originally suggested to be a member of the heat shock protein 70 family. However it is now known that human HSPA4 is a ...
, 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 4. ...
.
References
External links
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{{DEFAULTSORT:Apaf1
Programmed cell death
Apoptosis