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O95831 (AIFM1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 149. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Apoptosis-inducing factor 1, mitochondrial

EC=1.1.1.-
Alternative name(s):
Programmed cell death protein 8
Gene names
Name:AIFM1
Synonyms:AIF, PDCD8
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length613 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.13 Ref.17 Ref.23 Ref.24

Cofactor

FAD. Ref.23

Subunit structure

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. Ref.13 Ref.15 Ref.18 Ref.19 Ref.23

Subcellular location

Mitochondrion intermembrane space. Mitochondrion inner membrane. Cytoplasm. Nucleus. Cytoplasmperinuclear 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. Ref.2 Ref.10 Ref.13 Ref.18 Ref.22 Ref.23

Isoform 3: Mitochondrion intermembrane space. Mitochondrion inner membrane. Note: Has a stronger membrane anchorage than isoform 1. Ref.2 Ref.10 Ref.13 Ref.18 Ref.22 Ref.23

Isoform 5: Cytoplasm Ref.2 Ref.10 Ref.13 Ref.18 Ref.22 Ref.23.

Tissue specificity

Detected in muscle and skin fibroblasts (at protein level). Isoform 5 is frequently down-regulated in human cancers. Ref.2 Ref.23

Post-translational modification

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.

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.

Involvement in 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.24 Ref.25

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.23

Sequence similarities

Belongs to the FAD-dependent oxidoreductase family.

Biophysicochemical properties

Kinetic parameters:

KM=1.53 mM for NADH Ref.23

KM=26 µM for cytochrome c

Ontologies

Keywords
   Biological processApoptosis
   Cellular componentCytoplasm
Membrane
Mitochondrion
Mitochondrion inner membrane
Nucleus
   Coding sequence diversityAlternative splicing
   DiseaseCharcot-Marie-Tooth disease
Deafness
Disease mutation
Mental retardation
Neurodegeneration
Neuropathy
   DomainTransit peptide
   LigandDNA-binding
FAD
Flavoprotein
NAD
   Molecular functionOxidoreductase
   PTMAcetylation
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processDNA catabolic process

Traceable author statement PubMed 18309324. Source: UniProtKB

activation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from direct assay Ref.13. Source: UniProtKB

apoptotic DNA fragmentation

Traceable author statement Ref.1. Source: ProtInc

apoptotic process

Inferred from mutant phenotype Ref.23. Source: UniProtKB

cell redox homeostasis

Inferred from electronic annotation. Source: InterPro

chromosome condensation

Traceable author statement PubMed 18309324. Source: UniProtKB

intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress

Inferred from sequence or structural similarity. Source: UniProtKB

mitochondrial respiratory chain complex I assembly

Inferred from mutant phenotype Ref.18. Source: UniProtKB

neuron apoptotic process

Inferred from electronic annotation. Source: Ensembl

neuron differentiation

Inferred from direct assay Ref.18. Source: UniProtKB

positive regulation of apoptotic process

Traceable author statement PubMed 18309324. Source: UniProtKB

   Cellular_componentcytosol

Inferred from sequence or structural similarity. Source: UniProtKB

mitochondrial inner membrane

Traceable author statement PubMed 18309324. Source: UniProtKB

mitochondrial intermembrane space

Inferred from direct assay Ref.10. Source: UniProtKB

mitochondrion

Inferred from direct assay PubMed 20833797. Source: UniProt

nucleus

Inferred from direct assay Ref.23. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionDNA binding

Inferred from electronic annotation. Source: UniProtKB-KW

NAD(P)H oxidase activity

Traceable author statement PubMed 18309324. Source: UniProtKB

electron carrier activity

Traceable author statement Ref.1. Source: ProtInc

flavin adenine dinucleotide binding

Inferred from electronic annotation. Source: InterPro

oxidoreductase activity, acting on NAD(P)H

Inferred from direct assay Ref.23. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.13Ref.19. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 6 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O95831-1)

Also known as: AIF;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: O95831-2)

The sequence of this isoform differs from the canonical sequence as follows:
     36-322: Missing.
Isoform 3 (identifier: O95831-3)

Also known as: AIF-exB; AIF2;

The sequence of this isoform differs from the canonical sequence as follows:
     36-82: GNLFQRWHVP...VGLSTVGAGA → VVQSHHLGSP...GATVTGAGVY
Note: Brain-specific.
Isoform 4 (identifier: O95831-4)

Also known as: AIFsh2;

The sequence of this isoform differs from the canonical sequence as follows:
     323-324: AR → DI
     325-613: Missing.
Note: Does not induce nuclear apoptosis.
Isoform 5 (identifier: O95831-5)

Also known as: AIFsh;

The sequence of this isoform differs from the canonical sequence as follows:
     1-352: Missing.
Note: Pro-apoptotic isoform, strongly down-regulated in many tumor cells, up-regulated by gamma-irradiation.
Isoform 6 (identifier: O95831-6)

The sequence of this isoform differs from the canonical sequence as follows:
     1-87: Missing.
     323-324: AR → DI
     325-613: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 5454Mitochondrion Ref.2 Ref.10
Propeptide55 – 10147Removed in mature form
PRO_0000401935
Chain102 – 613512Apoptosis-inducing factor 1, mitochondrial
PRO_0000022030

Regions

Nucleotide binding138 – 1425FAD
Nucleotide binding164 – 1652FAD
Nucleotide binding454 – 4552FAD
Region134 – 483350FAD-dependent oxidoreductase By similarity
Motif446 – 4516Nuclear localization signal Potential

Sites

Binding site1721FAD
Binding site1771FAD
Binding site2331FAD; via amide nitrogen and carbonyl oxygen
Binding site2851FAD
Binding site4381FAD
Binding site4831FAD; via carbonyl oxygen

Amino acid modifications

Modified residue1051Phosphothreonine Ref.14
Modified residue1091N6-succinyllysine By similarity
Modified residue2681Phosphoserine Ref.16
Modified residue3881N6-acetyllysine By similarity
Modified residue5931N6-acetyllysine By similarity
Cross-link255Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.21

Natural variations

Alternative sequence1 – 352352Missing in isoform 5.
VSP_046248
Alternative sequence1 – 8787Missing in isoform 6.
VSP_047646
Alternative sequence36 – 322287Missing in isoform 2.
VSP_004357
Alternative sequence36 – 8247GNLFQ…VGAGA → VVQSHHLGSPSRSLASTGAS GKDGSNLVYFLIVGATVTGA GVY in isoform 3.
VSP_022953
Alternative sequence323 – 3242AR → DI in isoform 4 and isoform 6.
VSP_043637
Alternative sequence325 – 613289Missing in isoform 4 and isoform 6.
VSP_043638
Natural variant2011Missing in COXPD6; higher DNA binding affinity, partially impaired flavin binding and association with increased parthanatos-linked cell death. Ref.24
VAR_063827
Natural variant3081G → E in COXPD6; with prenatal ventriculomegaly and severe postnatal encephalomyopathy. Ref.25
VAR_067334
Natural variant4931E → V in COWCK; increases affinity for NADH and electron transfer activity. Increases affinity for DNA, resulting in increased apoptosis. Ref.23
VAR_069468

Secondary structure

................................................................................................ 613
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (AIF) [UniParc].

Last modified May 1, 1999. Version 1.
Checksum: A156762BC64E6340

FASTA61366,901
        10         20         30         40         50         60 
MFRCGGLAAG ALKQKLVPLV RTVCVRSPRQ RNRLPGNLFQ RWHVPLELQM TRQMASSGAS 

        70         80         90        100        110        120 
GGKIDNSVLV LIVGLSTVGA GAYAYKTMKE DEKRYNERIS GLGLTPEQKQ KKAALSASEG 

       130        140        150        160        170        180 
EEVPQDKAPS HVPFLLIGGG TAAFAAARSI RARDPGARVL IVSEDPELPY MRPPLSKELW 

       190        200        210        220        230        240 
FSDDPNVTKT LRFKQWNGKE RSIYFQPPSF YVSAQDLPHI ENGGVAVLTG KKVVQLDVRD 

       250        260        270        280        290        300 
NMVKLNDGSQ ITYEKCLIAT GGTPRSLSAI DRAGAEVKSR TTLFRKIGDF RSLEKISREV 

       310        320        330        340        350        360 
KSITIIGGGF LGSELACALG RKARALGTEV IQLFPEKGNM GKILPEYLSN WTMEKVRREG 

       370        380        390        400        410        420 
VKVMPNAIVQ SVGVSSGKLL IKLKDGRKVE TDHIVAAVGL EPNVELAKTG GLEIDSDFGG 

       430        440        450        460        470        480 
FRVNAELQAR SNIWVAGDAA CFYDIKLGRR RVEHHDHAVV SGRLAGENMT GAAKPYWHQS 

       490        500        510        520        530        540 
MFWSDLGPDV GYEAIGLVDS SLPTVGVFAK ATAQDNPKSA TEQSGTGIRS ESETESEASE 

       550        560        570        580        590        600 
ITIPPSTPAV PQAPVQGEDY GKGVIFYLRD KVVVGIVLWN IFNRMPIARK IIKDGEQHED 

       610 
LNEVAKLFNI HED 

« Hide

Isoform 2 [UniParc].

Checksum: A87ACDC0A0556040
Show »

FASTA32635,638
Isoform 3 (AIF-exB) (AIF2) [UniParc].

Checksum: 313ADD6FA4E5D61A
Show »

FASTA60966,295
Isoform 4 (AIFsh2) [UniParc].

Checksum: 259AA55812C2F07E
Show »

FASTA32435,384
Isoform 5 (AIFsh) [UniParc].

Checksum: B05C9E9F3AA3F2E3
Show »

FASTA26128,404
Isoform 6 [UniParc].

Checksum: C1DDF16F42339374
Show »

FASTA23726,033

References

« Hide 'large scale' references
[1]"Molecular characterization of mitochondrial apoptosis-inducing factor."
Susin S.A., Lorenzo H.K., Zamzami N., Marzo I., Snow B.E., Brothers G.M., Mangion J., Jacotot E., Costantini P., Loeffler M., Larochette N., Goodlett D.R., Aebersold R., Siderovski D.P., Penninger J.M., Kroemer G.
Nature 397:441-446(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"AIFsh, a novel apoptosis-inducing factor (AIF) pro-apoptotic isoform with potential pathological relevance in human cancer."
Delettre C., Yuste V.J., Moubarak R.S., Bras M., Lesbordes-Brion J.-C., Petres S., Bellalou J., Susin S.A.
J. Biol. Chem. 281:6413-6427(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), PROTEIN SEQUENCE OF N-TERMINUS, SUBCELLULAR LOCATION (ISOFORM 5), TISSUE SPECIFICITY.
[3]"Identification and characterization of AIFsh2, a mitochondrial apoptosis-inducing factor (AIF) isoform with NADH oxidase activity."
Delettre C., Yuste V.J., Moubarak R.S., Bras M., Robert N., Susin S.A.
J. Biol. Chem. 281:18507-18518(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 4 AND 6), ALTERNATIVE SPLICING.
[4]Rhodes S.
Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3).
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
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. expand/collapse author list , 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 T.-O., 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.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
Tissue: Kidney.
[6]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[7]"The DNA sequence of the human X chromosome."
Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. expand/collapse author list , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R.
Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
Tissue: Brain.
[10]"Export of mitochondrial AIF in response to proapoptotic stimuli depends on processing at the intermembrane space."
Otera H., Ohsakaya S., Nagaura Z., Ishihara N., Mihara K.
EMBO J. 24:1375-1386(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 55-59, SUBCELLULAR LOCATION, PROTEOLYTIC CLEAVAGE.
[11]Mei G., Yu W., Gibbs R.A.
Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 171-613.
Tissue: Brain.
[12]"Apoptosis-inducing factor (AIF): a ubiquitous mitochondrial oxidoreductase involved in apoptosis."
Daugas E., Nochy D., Ravagnan L., Loeffler M., Susin S.A., Zamzami N., Kroemer G.
FEBS Lett. 476:118-123(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[13]"Apoptosis-inducing factor (AIF) inhibits protein synthesis by interacting with the eukaryotic translation initiation factor 3 subunit p44 (eIF3g)."
Kim J.T., Kim K.D., Song E.Y., Lee H.G., Kim J.W., Kim J.W., Chae S.K., Kim E., Lee M.S., Yang Y., Lim J.S.
FEBS Lett. 580:6375-6383(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH EIF3G.
[14]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-105, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[15]"Apoptosis-inducing factor is a target for ubiquitination through interaction with XIAP."
Wilkinson J.C., Wilkinson A.S., Galban S., Csomos R.A., Duckett C.S.
Mol. Cell. Biol. 28:237-247(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION BY XIAP/BIRC4, INTERACTION WITH XIAP/BIRC4.
[16]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-268, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[17]"Apoptosis-inducing factor plays a critical role in caspase-independent, pyknotic cell death in hydrogen peroxide-exposed cells."
Son Y.O., Jang Y.S., Heo J.S., Chung W.T., Choi K.C., Lee J.C.
Apoptosis 14:796-808(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[18]"A brain-specific isoform of mitochondrial apoptosis-inducing factor: AIF2."
Hangen E., De Zio D., Bordi M., Zhu C., Dessen P., Caffin F., Lachkar S., Perfettini J.L., Lazar V., Benard J., Fimia G.M., Piacentini M., Harper F., Pierron G., Vicencio J.M., Benit P., de Andrade A., Hoglinger G. expand/collapse author list , Culmsee C., Rustin P., Blomgren K., Cecconi F., Kroemer G., Modjtahedi N.
Cell Death Differ. 17:1155-1166(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING (ISOFORM 3), SUBCELLULAR LOCATION (ISOFORM 3), SUBUNIT.
[19]"Vital function of PRELI and essential requirement of its LEA motif."
McKeller M.R., Herrera-Rodriguez S., Ma W., Ortiz-Quintero B., Rangel R., Cande C., Sims-Mourtada J.C., Melnikova V., Kashi C., Phan L.M., Chen Z., Huang P., Dunner K. Jr., Kroemer G., Singh K.K., Martinez-Valdez H.
Cell Death Dis. 1:E21-E21(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PRELID1.
[20]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[21]"Nondegradative ubiquitination of apoptosis inducing factor (AIF) by X-linked inhibitor of apoptosis at a residue critical for AIF-mediated chromatin degradation."
Lewis E.M., Wilkinson A.S., Davis N.Y., Horita D.A., Wilkinson J.C.
Biochemistry 50:11084-11096(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION AT LYS-255 BY XIAP/BIRC4.
[22]"DNA binding is required for the apoptogenic action of apoptosis inducing factor."
Ye H., Cande C., Stephanou N.C., Jiang S., Gurbuxani S., Larochette N., Daugas E., Garrido C., Kroemer G., Wu H.
Nat. Struct. Biol. 9:680-684(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 121-613 IN COMPLEX WITH FAD, SUBCELLULAR LOCATION, DNA-BINDING.
[23]"Cowchock syndrome is associated with a mutation in apoptosis-inducing factor."
Rinaldi C., Grunseich C., Sevrioukova I.F., Schindler A., Horkayne-Szakaly I., Lamperti C., Landoure G., Kennerson M.L., Burnett B.G., Boennemann C., Biesecker L.G., Ghezzi D., Zeviani M., Fischbeck K.H.
Am. J. Hum. Genet. 91:1095-1102(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 103-613 IN COMPLEX WITH FAD, FUNCTION, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, DNA-BINDING, SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, VARIANT COWCK VAL-493, CHARACTERIZATION OF VARIANT COWCK VAL-493.
[24]"Severe X-linked mitochondrial encephalomyopathy associated with a mutation in apoptosis-inducing factor."
Ghezzi D., Sevrioukova I., Invernizzi F., Lamperti C., Mora M., D'Adamo P., Novara F., Zuffardi O., Uziel G., Zeviani M.
Am. J. Hum. Genet. 86:639-649(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT COXPD6 ARG-201 DEL, CHARACTERIZATION OF VARIANT COXPD6 ARG-201 DEL, FUNCTION.
[25]"Early prenatal ventriculomegaly due to an AIFM1 mutation identified by linkage analysis and whole exome sequencing."
Berger I., Ben-Neriah Z., Dor-Wolman T., Shaag A., Saada A., Zenvirt S., Raas-Rothschild A., Nadjari M., Kaestner K.H., Elpeleg O.
Mol. Genet. Metab. 104:517-520(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT COXPD6 GLU-308.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF100928 mRNA. Translation: AAD16436.1.
DQ016496 mRNA. Translation: AAY84737.1.
DQ016498 mRNA. Translation: AAY84739.1.
DQ016500 mRNA. Translation: AAY84741.1.
AL049703 mRNA. Translation: CAB41267.1.
AL049704 mRNA. Translation: CAB41268.1.
AK314446 mRNA. Translation: BAG37055.1.
CR457379 mRNA. Translation: CAG33660.1.
AL139234 Genomic DNA. Translation: CAI42778.1.
AL139234 Genomic DNA. Translation: CAI42779.1.
AL139234 Genomic DNA. Translation: CAI42780.1.
CH471107 Genomic DNA. Translation: EAX11811.1.
CH471107 Genomic DNA. Translation: EAX11812.1.
CH471107 Genomic DNA. Translation: EAX11810.1.
BC111065 mRNA. Translation: AAI11066.1.
BC139738 mRNA. Translation: AAI39739.1.
AF131759 mRNA. Translation: AAD20036.1.
CCDSCCDS14618.1. [O95831-1]
CCDS14619.1. [O95831-3]
CCDS48166.1. [O95831-5]
CCDS48167.1. [O95831-4]
RefSeqNP_001124318.1. NM_001130846.2. [O95831-5]
NP_001124319.1. NM_001130847.3. [O95831-4]
NP_004199.1. NM_004208.3. [O95831-1]
NP_665811.1. NM_145812.2. [O95831-3]
NP_665812.1. NM_145813.2. [O95831-2]
UniGeneHs.424932.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1M6IX-ray1.80A121-613[»]
4FDCX-ray2.40B103-613[»]
4LIIX-ray1.88A100-611[»]
ProteinModelPortalO95831.
SMRO95831. Positions 125-611.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114579. 71 interactions.
119252. 6 interactions.
IntActO95831. 28 interactions.
MINTMINT-209209.
STRING9606.ENSP00000287295.

PTM databases

PhosphoSiteO95831.

2D gel databases

REPRODUCTION-2DPAGEIPI00157908.
UCD-2DPAGEO95831.

Proteomic databases

MaxQBO95831.
PaxDbO95831.
PRIDEO95831.

Protocols and materials databases

DNASU51060.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000287295; ENSP00000287295; ENSG00000156709. [O95831-1]
ENST00000319908; ENSP00000315122; ENSG00000156709. [O95831-3]
ENST00000346424; ENSP00000316320; ENSG00000156709. [O95831-2]
ENST00000416073; ENSP00000402535; ENSG00000156709. [O95831-4]
ENST00000440263; ENSP00000405879; ENSG00000156709. [O95831-5]
ENST00000535724; ENSP00000446113; ENSG00000156709. [O95831-6]
GeneID9131.
KEGGhsa:9131.
UCSCuc004evg.3. human. [O95831-1]
uc004evh.3. human. [O95831-3]
uc004evi.3. human. [O95831-2]
uc004evk.3. human.
uc011mus.2. human. [O95831-4]

Organism-specific databases

CTD9131.
GeneCardsGC0XM129263.
HGNCHGNC:8768. AIFM1.
HPACAB003764.
HPA030611.
MIM300169. gene.
300816. phenotype.
310490. phenotype.
neXtProtNX_O95831.
Orphanet238329. Severe X-linked mitochondrial encephalomyopathy.
101078. X-linked Charcot-Marie-Tooth disease type 4.
PharmGKBPA162376129.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0446.
HOGENOMHOG000124580.
HOVERGENHBG053538.
InParanoidO95831.
KOK04727.
OMAKDGEEHA.
OrthoDBEOG7C2R0V.
PhylomeDBO95831.
TreeFamTF314028.

Enzyme and pathway databases

SignaLinkO95831.

Gene expression databases

ArrayExpressO95831.
BgeeO95831.
CleanExHS_AIFM1.
GenevestigatorO95831.

Family and domain databases

Gene3D3.30.390.30. 1 hit.
InterProIPR029324. AIF_C.
IPR016156. FAD/NAD-linked_Rdtase_dimer.
IPR013027. FAD_pyr_nucl-diS_OxRdtase.
IPR004099. Pyr_nucl-diS_OxRdtase_dimer.
IPR023753. Pyr_nucl-diS_OxRdtase_FAD/NAD.
IPR001327. Pyr_OxRdtase_NAD-bd_dom.
[Graphical view]
PfamPF14721. AIF_C. 1 hit.
PF00070. Pyr_redox. 1 hit.
PF07992. Pyr_redox_2. 1 hit.
[Graphical view]
PRINTSPR00368. FADPNR.
SUPFAMSSF55424. SSF55424. 1 hit.
ProtoNetSearch...

Other

ChiTaRSAIFM1. human.
EvolutionaryTraceO95831.
GeneWikiAIFM1.
GenomeRNAi9131.
NextBio34229.
PROO95831.
SOURCESearch...

Entry information

Entry nameAIFM1_HUMAN
AccessionPrimary (citable) accession number: O95831
Secondary accession number(s): A4QPB4 expand/collapse secondary AC list , B1ALN1, B2RB08, D3DTE9, Q1L6K4, Q1L6K6, Q2QKE4, Q5JUZ7, Q6I9X6, Q9Y3I3, Q9Y3I4
Entry history
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: May 1, 1999
Last modified: July 9, 2014
This is version 149 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome X

Human chromosome X: entries, gene names and cross-references to MIM