Names & Taxonomy
- Uniprot ID:
- O95831
- Entry Name:
- AIFM1_HUMAN
- Status:
- reviewed
- Protein Names:
- Apoptosis-inducing factor 1, mitochondrial (EC 1.1.1.-) (Programmed cell death protein 8)
- Gene Names:
- AIFM1 AIF PDCD8
- Gene Names Primary:
- AIFM1
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 613
- Sequence:
- MFRCGGLAAGALKQKLVPLVRTVCVRSPRQRNRLPGNLFQRWHVPLELQMTRQMASSGASGGKIDNSVLVLIVGLSTVGAGAYAYKTMKEDEKRYNERISGLGLTPEQKQKKAALSASEGEEVPQDKAPSHVPFLLIGGGTAAFAAARSIRARDPGARVLIVSEDPELPYMRPPLSKELWFSDDPNVTKTLRFKQWNGKERSIYFQPPSFYVSAQDLPHIENGGVAVLTGKKVVQLDVRDNMVKLNDGSQITYEKCLIATGGTPRSLSAIDRAGAEVKSRTTLFRKIGDFRSLEKISREVKSITIIGGGFLGSELACALGRKARALGTEVIQLFPEKGNMGKILPEYLSNWTMEKVRREGVKVMPNAIVQSVGVSSGKLLIKLKDGRKVETDHIVAAVGLEPNVELAKTGGLEIDSDFGGFRVNAELQARSNIWVAGDAACFYDIKLGRRRVEHHDHAVVSGRLAGENMTGAAKPYWHQSMFWSDLGPDVGYEAIGLVDSSLPTVGVFAKATAQDNPKSATEQSGTGIRSESETESEASEITIPPSTPAVPQAPVQGEDYGKGVIFYLRDKVVVGIVLWNIFNRMPIARKIIKDGEQHEDLNEVAKLFNIHED
- Proteomes:
- UP000005640
Subcellular location
- Subcellular Location:
- Mitochondrion intermembrane space. Mitochondrion inner membrane. Cytoplasm. Nucleus. Cytoplasm, perinuclear region. Note=Proteolytic cleavage during or just after translocation into the mitochondrial intermembrane space (IMS) results in the formation of an inner-membrane-anchored mature form (AIFmit). During apoptosis, further proteolytic processing leads to a mature form, which is confined to the mitochondrial IMS in a soluble form (AIFsol). AIFsol is released to the cytoplasm in response to specific death signals, and translocated to the nucleus, where it induces nuclear apoptosis. Colocalizes with EIF3G in the nucleus and perinuclear region.; Isoform 3: Mitochondrion intermembrane space
Function
- Function:
- Functions both as NADH oxidoreductase and as regulator of apoptosis. In response to apoptotic stimuli, it is released from the mitochondrion intermembrane space into the cytosol and to the nucleus, where it functions as a proapoptotic factor in a caspase-independent pathway. In contrast, functions as an antiapoptotic factor in normal mitochondria via its NADH oxidoreductase activity. The soluble form (AIFsol) found in the nucleus induces 'parthanatos' i.e. caspase-independent fragmentation of chromosomal DNA. Interacts with EIF3G,and thereby inhibits the EIF3 machinery and protein synthesis, and activates casapse-7 to amplify apoptosis. Plays a critical role in caspase-independent, pyknotic cell death in hydrogen peroxide-exposed cells. Binds to DNA in a sequence-independent manner.
- Cofactor:
- COFACTOR: Name=FAD; Xref=ChEBI:CHEBI:57692;
- Kinetics:
- BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=1.53 mM for NADH
- Cross Reference Drug Bank:
- DB03147
- Gene Ontology Go:
- cytosol
mitochondrial inner membrane
mitochondrial intermembrane space
mitochondrion
nucleus
perinuclear region of cytoplasm
DNA binding
electron carrier activity
FAD binding
NAD(P)H oxidase activity
oxidoreductase activity, acting on NAD(P)H
activation of cysteine-type endopeptidase activity involved in apoptotic process
apoptotic process
cell redox homeostasis
cellular response to aldosterone
cellular response to estradiol stimulus
cellular response to hydrogen peroxide
cellular response to nitric oxide
cellular response to oxygen-glucose deprivation
chromosome condensation
DNA catabolic process
intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
mitochondrial respiratory chain complex I assembly
neuron apoptotic process
neuron differentiation
positive regulation of apoptotic process
positive regulation of neuron apoptotic process
regulation of apoptotic DNA fragmentation
response to ischemia
response to L-glutamate
response to toxic substance - Gene Ontology Biological Process:
- activation of cysteine-type endopeptidase activity involved in apoptotic process
apoptotic process
cell redox homeostasis
cellular response to aldosterone
cellular response to estradiol stimulus
cellular response to hydrogen peroxide
cellular response to nitric oxide
cellular response to oxygen-glucose deprivation
chromosome condensation
DNA catabolic process
intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
mitochondrial respiratory chain complex I assembly
neuron apoptotic process
neuron differentiation
positive regulation of apoptotic process
positive regulation of neuron apoptotic process
regulation of apoptotic DNA fragmentation
response to ischemia
response to L-glutamate
response to toxic substance - Gene Ontology Molecular Function:
- DNA binding
electron carrier activity
FAD binding
NAD(P)H oxidase activity
oxidoreductase activity, acting on NAD(P)H - Gene Ontology Cellular Component:
- cytosol
mitochondrial inner membrane
mitochondrial intermembrane space
mitochondrion
nucleus
perinuclear region of cytoplasm - Keywords:
- 3D-structure
Acetylation
Alternative splicing
Apoptosis
Charcot-Marie-Tooth disease
Complete proteome
Cytoplasm
DNA-binding
Deafness
Direct protein sequencing
Disease mutation
FAD
Flavoprotein
Isopeptide bond
Membrane
Mental retardation
Mitochondrion
Mitochondrion inner membrane
NAD
Neurodegeneration
Neuropathy
Nucleus
Oxidoreductase
Phosphoprotein
Reference proteome
Transit peptide
Ubl conjugation - Interacts With:
- O75821; Q63ZY3; Q63ZY3-2; Q9Y3Q8