Homo sapiens Protein: AIFM1 | |||||||||||||||||||||||
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Summary | |||||||||||||||||||||||
InnateDB Protein | IDBP-85976.7 | ||||||||||||||||||||||
Last Modified | 2014-10-13 [Report errors or provide feedback] | ||||||||||||||||||||||
Gene Symbol | AIFM1 | ||||||||||||||||||||||
Protein Name | apoptosis-inducing factor, mitochondrion-associated, 1 | ||||||||||||||||||||||
Synonyms | AIF; CMT2D; CMTX4; COWCK; COXPD6; NADMR; NAMSD; PDCD8; | ||||||||||||||||||||||
Species | Homo sapiens | ||||||||||||||||||||||
Ensembl Protein | ENSP00000315122 | ||||||||||||||||||||||
InnateDB Gene | IDBG-85972 (AIFM1) | ||||||||||||||||||||||
Protein Structure | |||||||||||||||||||||||
UniProt Annotation | |||||||||||||||||||||||
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:0000269PubMed:17094969, ECO:0000269PubMed:19418225, ECO:0000269PubMed:20362274, ECO:0000269PubMed:23217327}. | ||||||||||||||||||||||
Subcellular Localization | 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 {ECO:0000269PubMed:20111043}. Mitochondrion inner membrane {ECO:0000269PubMed:20111043}. Note=Has a stronger membrane anchorage than isoform 1.Isoform 5: Cytoplasm {ECO:0000269PubMed:16365034}. | ||||||||||||||||||||||
Disease Associations | 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:0000269PubMed:20362274, ECO:0000269PubMed:22019070}. Note=The disease is caused by mutations affecting the gene represented in this entry.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:0000269PubMed:23217327}. Note=The disease is caused by mutations affecting the gene represented in this entry. | ||||||||||||||||||||||
Tissue Specificity | Detected in muscle and skin fibroblasts (at protein level). Isoform 5 is frequently down-regulated in human cancers. {ECO:0000269PubMed:16365034, ECO:0000269PubMed:23217327}. | ||||||||||||||||||||||
Comments | |||||||||||||||||||||||
Interactions | |||||||||||||||||||||||
Number of Interactions |
This gene and/or its encoded proteins are associated with 72 experimentally validated interaction(s) in this database.
They are also associated with 5 interaction(s) predicted by orthology.
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Gene Ontology | |||||||||||||||||||||||
Molecular Function |
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Biological Process |
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Cellular Component |
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Protein Structure and Domains | |||||||||||||||||||||||
PDB ID | |||||||||||||||||||||||
InterPro |
IPR001327
Pyridine nucleotide-disulphide oxidoreductase, NAD-binding domain IPR013027 FAD-dependent pyridine nucleotide-disulphide oxidoreductase IPR016156 FAD/NAD-linked reductase, dimerisation domain IPR023753 Pyridine nucleotide-disulphide oxidoreductase, FAD/NAD(P)-binding domain |
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PFAM |
PF00070
PF07992 |
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PRINTS |
PR00368
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PIRSF | |||||||||||||||||||||||
SMART | |||||||||||||||||||||||
TIGRFAMs | |||||||||||||||||||||||
Post-translational Modifications | |||||||||||||||||||||||
Modification | |||||||||||||||||||||||
Cross-References | |||||||||||||||||||||||
SwissProt | O95831 | ||||||||||||||||||||||
PhosphoSite | PhosphoSite-O95831 | ||||||||||||||||||||||
TrEMBL | E9PMA0 | ||||||||||||||||||||||
UniProt Splice Variant | |||||||||||||||||||||||
Entrez Gene | 9131 | ||||||||||||||||||||||
UniGene | Hs.56294 | ||||||||||||||||||||||
RefSeq | NP_665811 | ||||||||||||||||||||||
HUGO | HGNC:8768 | ||||||||||||||||||||||
OMIM | 300169 | ||||||||||||||||||||||
CCDS | CCDS14619 | ||||||||||||||||||||||
HPRD | 02161 | ||||||||||||||||||||||
IMGT | |||||||||||||||||||||||
EMBL | AF100928 AF131759 AK314446 AL049703 AL049704 AL139234 BC111065 BC139738 CH471107 CR457379 DQ016496 DQ016498 DQ016500 | ||||||||||||||||||||||
GenPept | AAD16436 AAD20036 AAI11066 AAI39739 AAY84737 AAY84739 AAY84741 BAG37055 CAB41267 CAB41268 CAG33660 CAI42778 CAI42779 CAI42780 EAX11810 EAX11811 EAX11812 | ||||||||||||||||||||||