Description: Homo sapiens apoptosis-inducing factor, mitochondrion-associated, 1 (AIFM1), nuclear gene encoding mitochondrial protein, transcript variant 1, mRNA. RefSeq Summary (NM_004208): This gene encodes a flavoprotein essential for nuclear disassembly in apoptotic cells, and it is found in the mitochondrial intermembrane space in healthy cells. Induction of apoptosis results in the translocation of this protein to the nucleus where it affects chromosome condensation and fragmentation. In addition, this gene product induces mitochondria to release the apoptogenic proteins cytochrome c and caspase-9. Mutations in this gene cause combined oxidative phosphorylation deficiency 6 (COXPD6), a severe mitochondrial encephalomyopathy, as well as Cowchock syndrome, also known as X-linked recessive Charcot-Marie-Tooth disease-4 (CMTX-4), a disorder resulting in neuropathy, and axonal and motor-sensory defects with deafness and cognitive disability. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 10. [provided by RefSeq, Aug 2015]. Transcript (Including UTRs) Position: hg19 chrX:129,263,338-129,299,861 Size: 36,524 Total Exon Count: 16 Strand: - Coding Region Position: hg19 chrX:129,263,532-129,299,630 Size: 36,099 Coding Exon Count: 16
ID:AIFM1_HUMAN DESCRIPTION: RecName: Full=Apoptosis-inducing factor 1, mitochondrial; EC=1.-.-.-; AltName: Full=Programmed cell death protein 8; Flags: Precursor; FUNCTION: Probable oxidoreductase that has a dual role in controlling cellular life and death; during apoptosis, it is translocated from the mitochondria to the nucleus to function as a proapoptotic factor in a caspase-independent pathway, while in normal mitochondria, it functions as an antiapoptotic factor via its 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: FAD. SUBUNIT: Interacts with XIAP/BIRC4. Interacts (via N-terminus) with EIF3G (via C-terminus). INTERACTION: 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; 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. 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. 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. DISEASE: Defects in AIFM1 are the cause of combined oxidative phosphorylation deficiency type 6 (COXPD6) [MIM:300816]. It is a mitochondrial disease resulting in a neurodegenerative disorder characterized by psychomotor delay, hypotonia, areflexia, muscle weakness and wasting. SIMILARITY: Belongs to the FAD-dependent oxidoreductase family. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/AIFM1ID44053chXq25.html";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on O95831
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0002931 response to ischemia GO:0006915 apoptotic process GO:0006919 activation of cysteine-type endopeptidase activity involved in apoptotic process GO:0009636 response to toxic substance GO:0010942 positive regulation of cell death GO:0030182 neuron differentiation GO:0030261 chromosome condensation GO:0032981 mitochondrial respiratory chain complex I assembly GO:0043065 positive regulation of apoptotic process GO:0043525 positive regulation of neuron apoptotic process GO:0051402 neuron apoptotic process GO:0055114 oxidation-reduction process GO:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress GO:0070301 cellular response to hydrogen peroxide GO:0071392 cellular response to estradiol stimulus GO:0071732 cellular response to nitric oxide GO:0090650 cellular response to oxygen-glucose deprivation GO:1902065 response to L-glutamate GO:1902510 regulation of apoptotic DNA fragmentation GO:1904045 cellular response to aldosterone
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa04210 - Apoptosis
BioCarta from NCI Cancer Genome Anatomy Project h_aifPathway - Opposing roles of AIF in Apoptosis and Cell Survival h_mitochondriaPathway - Role of Mitochondria in Apoptotic Signaling h_ceramidePathway - Ceramide Signaling Pathway
US Server
