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apoptotic protease-activating factor 1; APAF-1 (APAF1, KIAA0413)
Function:
- oligomeric Apaf-1 mediates the cytochrome c-dependent autocatalytic activation of pro-caspase-9 (Apaf-3), leading to the activation of caspase-3 & apoptosis (activation requires ATP)
- isoform 6 is less effective in inducing apoptosis
- oligomerizes upon binding of cytochrome C & dATP
- oligomeric Apaf-1 & pro-caspase-9 bind to each other via their respective NH2-terminal CARD domains & consecutively mature caspase-9 is released from the complex
- pro-caspase-3 is recruited into the Apaf-1-pro-caspase-9 complex via interaction with pro-caspase-9
- interacts with APIP
Structure:
- monomer
- homologous to C. elegans CED-4.
- the CARD domain mediates interaction with APIP
- contains 1 CARD domain
- contains 1 NB-ARC domain
- contains 13 WD repeats
Compartment: cytoplasm
Alternative splicing: named isoforms=6
Expression:
- ubiquitous
- highest levels of expression in adult spleen & peripheral blood leukocytes, & in fetal brain, kidney & lung
- isoform 1 is expressed in heart, kidney & liver
- induced by E2F & p53 in apoptotic neurons
Interactions
molecular events
Related
nucleotide-binding oligomerization domain-containing protein 1; caspase recruitment domain-containing protein 4 (NOD1, CARD4)
General
phosphoprotein
pro apoptotic protein
WD repeat protein family
Properties
SIZE: entity length = 1248 aa
MW = 142 kD
COMPARTMENT: cytoplasm
MOTIF: CARD domain {1-90}
serine-rich region {95-98}
MOTIF: serine residue (SEVERAL)
NB-ARC {104-415}
MOTIF: ATP-binding site
NAME: ATP-binding site
SITE: 154-161
Thr phosphorylation site {T204}
Ser phosphorylation site {S238}
Ser phosphorylation site {S248}
WD repeat {613-652}
WD repeat {655-694}
WD repeat {697-738}
WD repeat {741-780}
WD repeat {796-836}
WD repeat {838-877}
WD repeat {880-919}
WD repeat {959-998}
WD repeat {1001-1040}
WD repeat {1042-1080}
WD repeat {1083-1122}
WD repeat {1125-1164}
WD repeat {1175-1212}
References
- Zou H, Henzel WJ, Liu X, Lutschg A, Wang X.
Apaf-1, a human protein homologous to C. elegans CED-4,
participates in cytochrome c-dependent activation of caspase-3.
Cell. 1997 Aug 8;90(3):405-13.
PMID: 9267021
- UniProt :accession O14727
- Atlas of Genetics & Cytogenetics in Oncology & Haematology
http://atlasgeneticsoncology.org/genes/APAF1ID422.html
Component-of
molecular complex
Databases & Figures
OMIM 602233
UniProt O14727
PFAM correlations
Entrez Gene 317
KEGG correlations
signaling pathways: caspases