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apoptosis-inducing factor 1, mitochondrial; programmed cell death protein 8 (AIFM1, AIF, PDCD8)
Function:
- probable oxidoreductase that acts as a caspase- independent mitochondrial effector of apoptotic cell death
- AIF is normally in mitochondria, translocates to the nucleus during apoptosis & induces mitochondria to release cytochrome C & caspase 9
- Bcl-2 inhibits mitochondrial release of AIF but otherwise does not affect apoptotis activity
- recombinant AIF causes chromatin condensation & DNA fragmentation in isolated nuclei
- binds to DNA in (sequence-independent)
- effects of AIF are independent of caspases [3]
- AIF is essential for programmed cell death during early morphogenesis, ie. cavitation of embryoid bodies
- interacts with XIAP
Cofactor: FAD
Structure:
- belongs to the FAD-dependent oxidoreductase family
Compartment:
- mitochondria intermembrane space
- nucleus
- translocated to the nucleus upon induction of apoptosis
Alternative splicing:
- named isoforms=3
Related
apoptosis
programmed cell death protein
General
flavoprotein
mitochondrial protein
oxidoreductase
phosphoprotein
pro apoptotic protein
Properties
SIZE: entity length = 613 aa
MW = 67 kD
COMPARTMENT: mitochondria
cell nucleus
MOTIF: Thr phosphorylation site {T105}
FAD-dependent oxidoreductase {134-483}
MOTIF: cofactor-binding site [138-142]
COFACTOR-BOUND: flavin adenine dinucleotide
cofactor-binding site [164-165]
COFACTOR-BOUND: flavin adenine dinucleotide
binding site
SITE: 172-172
FOR-BINDING-OF: flavin adenine dinucleotide
binding site
SITE: 177-177
FOR-BINDING-OF: flavin adenine dinucleotide
binding site
SITE: 233-233
FOR-BINDING-OF: flavin adenine dinucleotide
Ser phosphorylation site {S268}
cofactor-binding site [285-285]
FOR-BINDING-OF: flavin adenine dinucleotide
cofactor-binding site [438-438]
FOR-BINDING-OF: flavin adenine dinucleotide
nuclear translocation signal {446-451}
cofactor-binding site [454-455]
COFACTOR-BOUND: flavin adenine dinucleotide
binding site
SITE: 483-483
FOR-BINDING-OF: flavin adenine dinucleotide
Database Correlations
OMIM 300169
UniProt O95831
PFAM correlations
LOCUS-LINK correlations
Kegg hsa:51060
References
- UniProt :accession O95831
- Atlas of Genetics & Cytogenetics in Oncology & Haematology
http://atlasgeneticsoncology.org/genes/AIFM1ID44053chXq25.html
- Susin SA et al
Molecular characterization of mitochondrial apoptosis-inducing factor.
Nature 397:441-7 1999
PMID: 9989411
- Joza N et al
Essential role of the mitochondrial apoptosis-inducing factor
in programmed cell death.
Nature 410:549-54, 2001
PMID: 11279485
- Daugas E et al
Mitochondrio-nuclear translocation of AIF in apoptosis and
necrosis.
FASEB J 14:729, 2000
PMID: 10744629