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

• Pyr_redox_2 (PF07992)
• AIF_C (PF14721)

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

Resource	Link
UniProtKB ID	O95831
UniProtKB Entry Name	AIFM1_HUMAN
GenBank Protein ID	4323587
GenBank Gene ID	AF100928
GenAtlas ID	AIFM1
HGNC ID	HGNC: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. [Article]
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. [Article]
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. [Article]
4. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
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7. Otera H, Ohsakaya S, Nagaura Z, Ishihara N, Mihara K: Export of mitochondrial AIF in response to proapoptotic stimuli depends on processing at the intermembrane space. EMBO J. 2005 Apr 6;24(7):1375-86. Epub 2005 Mar 17. [Article]
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10. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [Article]
11. Wilkinson JC, Wilkinson AS, Galban S, Csomos RA, Duckett CS: Apoptosis-inducing factor is a target for ubiquitination through interaction with XIAP. Mol Cell Biol. 2008 Jan;28(1):237-47. Epub 2007 Oct 29. [Article]
12. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [Article]
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18. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
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20. Ye H, Cande C, Stephanou NC, Jiang S, Gurbuxani S, Larochette N, Daugas E, Garrido C, Kroemer G, Wu H: DNA binding is required for the apoptogenic action of apoptosis inducing factor. Nat Struct Biol. 2002 Sep;9(9):680-4. [Article]
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. [Article]
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. [Article]
23. Berger I, Ben-Neriah Z, Dor-Wolman T, Shaag A, Saada A, Zenvirt S, Raas-Rothschild A, Nadjari M, Kaestner KH, Elpeleg O: Early prenatal ventriculomegaly due to an AIFM1 mutation identified by linkage analysis and whole exome sequencing. Mol Genet Metab. 2011 Dec;104(4):517-20. doi: 10.1016/j.ymgme.2011.09.020. Epub 2011 Sep 24. [Article]
24. Kettwig M, Schubach M, Zimmermann FA, Klinge L, Mayr JA, Biskup S, Sperl W, Gartner J, Huppke P: From ventriculomegaly to severe muscular atrophy: expansion of the clinical spectrum related to mutations in AIFM1. Mitochondrion. 2015 Mar;21:12-8. doi: 10.1016/j.mito.2015.01.001. Epub 2015 Jan 10. [Article]

Drug Relations

Drug Relations

DrugBank ID	Name	Drug group	Pharmacological action?	Actions	Details
DB03147	Flavin adenine dinucleotide	approved	unknown		Details
DB05282	MCC	investigational	unknown		Details