MitoProteome Database

New search | Record Overview | Ontology/Pathway Information | Domain Information | UniProt Annotations | Related Proteins
MT000696

UniProt Annotations

Entry Information
Gene Nameapoptosis-inducing factor, mitochondrion-associated, 1
Protein EntryAIFM1_HUMAN
UniProt IDO95831
SpeciesHuman
Comments
Comment typeDescription
Alternative Products Event=Alternative splicing; Named isoforms=6; Name=1; Synonyms=AIF; IsoId=O95831-1; Sequence=Displayed; Name=2; IsoId=O95831-2; Sequence=VSP_004357; Name=3; Synonyms=AIF-exB, AIF2; IsoId=O95831-3; Sequence=VSP_022953; Note=Brain-specific.; Name=4; Synonyms=AIFsh2; IsoId=O95831-4; Sequence=VSP_043637, VSP_043638; Note=Does not induce nuclear apoptosis.; Name=5; Synonyms=AIFsh; IsoId=O95831-5; Sequence=VSP_046248; Note=Pro-apoptotic isoform, strongly down-regulated in many tumor cells, up-regulated by gamma-irradiation.; Name=6; IsoId=O95831-6; Sequence=VSP_047646, VSP_043637, VSP_043638;
Biophysicochemical Properties Kinetic parameters: KM=1.53 mM for NADH {ECO:0000269|PubMed:23217327}; KM=26 uM for cytochrome c {ECO:0000269|PubMed:23217327};
Cofactor Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000269|PubMed:23217327};
Disease Combined oxidative phosphorylation deficiency 6 (COXPD6) [MIM:300816]: A mitochondrial disease resulting in a neurodegenerative disorder characterized by psychomotor delay, hypotonia, areflexia, muscle weakness and wasting. Some patients manifest prenatal ventriculomegaly and severe postnatal encephalomyopathy. {ECO:0000269|PubMed:20362274, ECO:0000269|PubMed:22019070}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Disease Cowchock syndrome (COWCK) [MIM:310490]: An X-linked recessive neuromuscular disorder characterized by early childhood onset of a slowly progressive axonal sensorimotor neuropathy associated in some patients with sensorineural deafness and cognitive impairment. {ECO:0000269|PubMed:23217327}. Note=The disease is caused by mutations affecting the gene represented in this entry.
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. {ECO:0000269|PubMed:17094969, ECO:0000269|PubMed:19418225, ECO:0000269|PubMed:20362274, ECO:0000269|PubMed:23217327}.
Interaction O75821:EIF3G; NbExp=9; IntAct=EBI-356440, EBI-366632; Q63ZY3:KANK2; NbExp=2; IntAct=EBI-356440, EBI-2556193; Q63ZY3-2:KANK2; NbExp=4; IntAct=EBI-356440, EBI-6244894; Q9Y3Q8:TSC22D4; NbExp=2; IntAct=EBI-356440, EBI-739485;
Ptm Ubiquitination by XIAP/BIRC4 does not lead to proteasomal degradation. Ubiquitination at Lys-255 by XIAP/BIRC4 blocks its ability to bind DNA and induce chromatin degradation, thereby inhibiting its ability to induce cell death. {ECO:0000269|PubMed:17967870, ECO:0000269|PubMed:22103349}.
Ptm Under normal conditions, a 54-residue N-terminal segment is first proteolytically removed during or just after translocation into the mitochondrial intermembrane space (IMS) by the mitochondrial processing peptidase (MPP) to form the inner- membrane-anchored mature form (AIFmit). During apoptosis, it is further proteolytically processed at amino-acid position 101 leading to the generation of the 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 in a caspase-independent manner. {ECO:0000269|PubMed:15775970}.
Similarity Belongs to the FAD-dependent oxidoreductase family. {ECO:0000305}.
Subcellular Location Isoform 3: Mitochondrion intermembrane space {ECO:0000269|PubMed:20111043}. Mitochondrion inner membrane {ECO:0000269|PubMed:20111043}. Note=Has a stronger membrane anchorage than isoform 1.
Subcellular Location Isoform 5: Cytoplasm {ECO:0000269|PubMed:16365034}.
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.
Subunit Monomer (oxidized form). Homodimer (reduced form). Also dimerizes with isoform 3 preventing its release from mitochondria. Interacts with XIAP/BIRC4. Interacts (via N-terminus) with EIF3G (via C-terminus). Interacts with PRELID1. {ECO:0000269|PubMed:12198487, ECO:0000269|PubMed:17094969, ECO:0000269|PubMed:17967870, ECO:0000269|PubMed:20111043, ECO:0000269|PubMed:21364629, ECO:0000269|PubMed:23217327}.
Tissue Specificity Detected in muscle and skin fibroblasts (at protein level). Isoform 5 is frequently down-regulated in human cancers. {ECO:0000269|PubMed:16365034, ECO:0000269|PubMed:23217327}.
Web Resource Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/AIFM1ID44053chXq25.html";