Apoptosis-inducing factor 1, mitochondrial

Details

Name
Apoptosis-inducing factor 1, mitochondrial
Synonyms
  • 1.1.1.-
  • AIF
  • PDCD8
  • Programmed cell death protein 8
Gene Name
AIFM1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0001921|Apoptosis-inducing factor 1, mitochondrial
MFRCGGLAAGALKQKLVPLVRTVCVRSPRQRNRLPGNLFQRWHVPLELQMTRQMASSGAS
GGKIDNSVLVLIVGLSTVGAGAYAYKTMKEDEKRYNERISGLGLTPEQKQKKAALSASEG
EEVPQDKAPSHVPFLLIGGGTAAFAAARSIRARDPGARVLIVSEDPELPYMRPPLSKELW
FSDDPNVTKTLRFKQWNGKERSIYFQPPSFYVSAQDLPHIENGGVAVLTGKKVVQLDVRD
NMVKLNDGSQITYEKCLIATGGTPRSLSAIDRAGAEVKSRTTLFRKIGDFRSLEKISREV
KSITIIGGGFLGSELACALGRKARALGTEVIQLFPEKGNMGKILPEYLSNWTMEKVRREG
VKVMPNAIVQSVGVSSGKLLIKLKDGRKVETDHIVAAVGLEPNVELAKTGGLEIDSDFGG
FRVNAELQARSNIWVAGDAACFYDIKLGRRRVEHHDHAVVSGRLAGENMTGAAKPYWHQS
MFWSDLGPDVGYEAIGLVDSSLPTVGVFAKATAQDNPKSATEQSGTGIRSESETESEASE
ITIPPSTPAVPQAPVQGEDYGKGVIFYLRDKVVVGIVLWNIFNRMPIARKIIKDGEQHED
LNEVAKLFNIHED
Number of residues
613
Molecular Weight
66900.09
Theoretical pI
9.39
GO Classification
Functions
DNA binding / electron carrier activity / FAD binding / NAD(P)H oxidase activity / oxidoreductase activity, acting on NAD(P)H
Processes
activation of cysteine-type endopeptidase activity involved in apoptotic process / apoptotic process / cell redox homeostasis / 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 / regulation of apoptotic DNA fragmentation
Components
cytosol / mitochondrial inner membrane / mitochondrial intermembrane space / mitochondrion / nucleus / perinuclear region of cytoplasm
General Function
Oxidoreductase activity, acting on nad(p)h
Specific 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.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Mitochondrion intermembrane space
Gene sequence
>lcl|BSEQ0019044|Apoptosis-inducing factor 1, mitochondrial (AIFM1)
ATGGAAAAAGTCAGACGAGAGGGGGTTAAGGTGATGCCCAATGCTATTGTGCAATCCGTT
GGAGTCAGCAGTGGCAAGTTACTTATCAAGCTGAAAGACGGCAGGAAGGTAGAAACTGAC
CACATAGTGGCAGCTGTGGGCCTGGAGCCCAATGTTGAGTTGGCCAAGACTGGTGGCCTG
GAAATAGACTCAGATTTTGGTGGCTTCCGGGTAAATGCAGAGCTACAAGCACGCTCTAAC
ATCTGGGTGGCAGGAGATGCTGCATGCTTCTACGATATAAAGTTGGGAAGGAGGCGGGTA
GAGCACCATGATCACGCTGTTGTGAGTGGAAGATTGGCTGGAGAAAATATGACTGGAGCT
GCTAAGCCGTACTGGCATCAGTCAATGTTCTGGAGTGATTTGGGCCCCGATGTTGGCTAT
GAAGCTATTGGTCTTGTGGACAGTAGTTTGCCCACAGTTGGTGTTTTTGCAAAAGCAACT
GCACAAGACAACCCCAAATCTGCCACAGAGCAGTCAGGAACTGGTATCCGATCAGAGAGT
GAGACAGAGTCCGAGGCCTCAGAAATTACTATTCCTCCCAGCACCCCGGCAGTTCCACAG
GCTCCCGTCCAGGGGGAGGACTACGGCAAAGGTGTCATCTTCTACCTCAGGGACAAAGTG
GTCGTGGGGATTGTGCTATGGAACATCTTTAACCGAATGCCAATAGCAAGGAAGATCATT
AAGGACGGTGAGCAGCATGAAGATCTCAATGAAGTAGCCAAACTATTCAACATTCATGAA
GACTGA
Chromosome Location
X
Locus
Xq25-q26
External Identifiers
ResourceLink
UniProtKB IDO95831
UniProtKB Entry NameAIFM1_HUMAN
GenBank Protein ID4323587
GenBank Gene IDAF100928
GenAtlas IDAIFM1
HGNC IDHGNC:8768
General References
  1. Susin SA, Lorenzo HK, Zamzami N, Marzo I, Snow BE, Brothers GM, Mangion J, Jacotot E, Costantini P, Loeffler M, Larochette N, Goodlett DR, Aebersold R, Siderovski DP, Penninger JM, Kroemer G: Molecular characterization of mitochondrial apoptosis-inducing factor. Nature. 1999 Feb 4;397(6718):441-6. [PubMed:9989411]
  2. Delettre C, Yuste VJ, Moubarak RS, Bras M, Lesbordes-Brion JC, Petres S, Bellalou J, Susin SA: AIFsh, a novel apoptosis-inducing factor (AIF) pro-apoptotic isoform with potential pathological relevance in human cancer. J Biol Chem. 2006 Mar 10;281(10):6413-27. Epub 2005 Dec 19. [PubMed:16365034]
  3. Delettre C, Yuste VJ, Moubarak RS, Bras M, Robert N, Susin SA: Identification and characterization of AIFsh2, a mitochondrial apoptosis-inducing factor (AIF) isoform with NADH oxidase activity. J Biol Chem. 2006 Jul 7;281(27):18507-18. Epub 2006 Apr 27. [PubMed:16644725]
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  21. Rinaldi C, Grunseich C, Sevrioukova IF, Schindler A, Horkayne-Szakaly I, Lamperti C, Landoure G, Kennerson ML, Burnett BG, Bonnemann C, Biesecker LG, Ghezzi D, Zeviani M, Fischbeck KH: Cowchock syndrome is associated with a mutation in apoptosis-inducing factor. Am J Hum Genet. 2012 Dec 7;91(6):1095-102. doi: 10.1016/j.ajhg.2012.10.008. [PubMed:23217327]
  22. Ghezzi D, Sevrioukova I, Invernizzi F, Lamperti C, Mora M, D'Adamo P, Novara F, Zuffardi O, Uziel G, Zeviani M: Severe X-linked mitochondrial encephalomyopathy associated with a mutation in apoptosis-inducing factor. Am J Hum Genet. 2010 Apr 9;86(4):639-49. doi: 10.1016/j.ajhg.2010.03.002. Epub 2010 Apr 1. [PubMed:20362274]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB03147Flavin adenine dinucleotideapprovedunknownDetails
DB05282MCCinvestigationalunknownDetails