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Q9Z0X1 (AIFM1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length612 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 By similarity. Ref.1

Cofactor

FAD. Ref.1

Subunit structure

Monomer (oxidized form). Homodimer (reduced form). Interacts with XIAP/BIRC4. Interacts (via N-terminus) with EIF3G (via C-terminus). Interacts with PRELID1 By similarity.

Subcellular location

Mitochondrion intermembrane space. Mitochondrion inner membrane By similarity. Cytoplasm By similarity. Cytoplasmperinuclear region By similarity. Nucleus. 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 By similarity. Ref.1

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 By similarity.

Ubiquitination by XIAP/BIRC4 does not lead to proteasomal degradation. Ubiquitination at Lys-254 by XIAP/BIRC4 blocks its ability to bind DNA and induce chromatin degradation, thereby inhibiting its ability to induce cell death By similarity.

Sequence similarities

Belongs to the FAD-dependent oxidoreductase family.

Ontologies

Keywords
   Biological processApoptosis
   Cellular componentCytoplasm
Membrane
Mitochondrion
Mitochondrion inner membrane
Nucleus
   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_processactivation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

apoptotic mitochondrial changes

Traceable author statement PubMed 10913597. Source: MGI

cell redox homeostasis

Inferred from electronic annotation. Source: InterPro

intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress

Inferred from mutant phenotype PubMed 18056262. Source: UniProtKB

mitochondrial respiratory chain complex I assembly

Inferred from electronic annotation. Source: Ensembl

neuron apoptotic process

Inferred from genetic interaction PubMed 15703386. Source: MGI

neuron differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of apoptotic process

Traceable author statement PubMed 18309324. Source: UniProtKB

positive regulation of cell death

Inferred from mutant phenotype PubMed 21467298. Source: UniProtKB

regulation of apoptotic DNA fragmentation

Inferred from genetic interaction PubMed 15703386. Source: MGI

response to oxidative stress

Traceable author statement PubMed 18309324. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 14707049. Source: MGI

cytosol

Inferred from direct assay PubMed 18056262. Source: UniProtKB

mitochondrial inner membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

mitochondrial intermembrane space

Inferred from sequence or structural similarity. Source: UniProtKB

mitochondrial outer membrane

Traceable author statement PubMed 14561754. Source: MGI

mitochondrion

Inferred from direct assay PubMed 18056262PubMed 20360685. Source: UniProtKB

nucleus

Inferred from direct assay PubMed 18056262PubMed 20360685. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionDNA binding

Inferred from direct assay PubMed 21467298. Source: UniProtKB

FAD binding

Inferred from direct assay PubMed 21467298. Source: UniProtKB

NAD(P)H oxidase activity

Inferred from direct assay PubMed 21467298. Source: UniProtKB

electron-transferring-flavoprotein dehydrogenase activity

Traceable author statement PubMed 10913597. Source: MGI

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

H2AFXP161042EBI-5326677,EBI-494830From a different organism.
H2afxP276613EBI-773597,EBI-495621
Tsc22d4Q9EQN34EBI-773597,EBI-7821198

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 5454Mitochondrion By similarity
Propeptide55 – 10147Removed in mature form
PRO_0000401936
Chain102 – 612511Apoptosis-inducing factor 1, mitochondrial
PRO_0000022031

Regions

Nucleotide binding137 – 1415FAD
Nucleotide binding163 – 1642FAD
Nucleotide binding453 – 4542FAD
Region133 – 482350FAD-dependent oxidoreductase
Motif445 – 4506Nuclear localization signal Potential

Sites

Binding site1711FAD
Binding site1761FAD
Binding site2321FAD; via amide nitrogen and carbonyl oxygen
Binding site2841FAD
Binding site4371FAD
Binding site4821FAD; via carbonyl oxygen

Amino acid modifications

Modified residue1081N6-succinyllysine Ref.4
Modified residue2671Phosphoserine By similarity
Modified residue3871N6-acetyllysine Ref.5
Modified residue5921N6-acetyllysine Ref.5
Cross-link254Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Experimental info

Mutagenesis1761K → A: Increases catalytic efficiency. Ref.6
Mutagenesis3131E → A: Increases catalytic efficiency 30-fold. Increases affinity for NADH 20-fold. Ref.6

Secondary structure

..................................................................................................... 612
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9Z0X1 [UniParc].

Last modified May 1, 1999. Version 1.
Checksum: A17EDFD5CF77BB85

FASTA61266,765
        10         20         30         40         50         60 
MFRCGGLAGA FKQKLVPLVR TVYVQRPKQR NRLPGNLFQQ WRVPLELQMA RQMASSGSSG 

        70         80         90        100        110        120 
GKMDNSVLVL IVGLSTIGAG AYAYKTIKED QKRYNERVMG LGLSPEEKQR RAIASATEGG 

       130        140        150        160        170        180 
SVPQIRAPSH VPFLLIGGGT AAFAAARSIR ARDPGARVLI VSEDPELPYM RPPLSKELWF 

       190        200        210        220        230        240 
SDDPNVTKTL QFRQWNGKER SIYFQPPSFY VSAQDLPNIE NGGVAVLTGK KVVHLDVRGN 

       250        260        270        280        290        300 
MVKLNDGSQI TFEKCLIATG GTPRSLSAID RAGAEVKSRT TLFRKIGDFR ALEKISREVK 

       310        320        330        340        350        360 
SITVIGGGFL GSELACALGR KSQASGIEVI QLFPEKGNMG KILPQYLSNW TMEKVKREGV 

       370        380        390        400        410        420 
KVMPNAIVQS VGVSGGRLLI KLKDGRKVET DHIVTAVGLE PNVELAKTGG LEIDSDFGGF 

       430        440        450        460        470        480 
RVNAELQARS NIWVAGDAAC FYDIKLGRRR VEHHDHAVVS GRLAGENMTG AAKPYWHQSM 

       490        500        510        520        530        540 
FWSDLGPDVG YEAIGLVDSS LPTVGVFAKA TAQDNPKSAT EQSGTGIRSE SETESEASEI 

       550        560        570        580        590        600 
TIPPSAPAVP QVPVEGEDYG KGVIFYLRDK VVVGIVLWNV FNRMPIARKI IKDGEQHEDL 

       610 
NEVAKLFNIH ED 

« Hide

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], PROTEIN SEQUENCE OF N-TERMINUS, PROTEIN SEQUENCE OF 322-336, FUNCTION, COFACTOR, IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION.
[2]"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].
Strain: FVB/N.
Tissue: Mammary gland.
[3]Lubec G., Sunyer B., Chen W.-Q.
Submitted (JAN-2009) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 378-386, IDENTIFICATION BY MASS SPECTROMETRY.
Strain: OF1.
Tissue: Hippocampus.
[4]"SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-108, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[5]"Label-free quantitative proteomics of the lysine acetylome in mitochondria identifies substrates of SIRT3 in metabolic pathways."
Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B., Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.
Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-387 AND LYS-592, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[6]"The crystal structure of the mouse apoptosis-inducing factor AIF."
Mate M.J., Ortiz-Lombardia M., Boitel B., Haouz A., Tello D., Susin S.A., Penninger J., Kroemer G., Alzari P.M.
Nat. Struct. Biol. 9:442-446(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 108-610 IN COMPLEX WITH FAD, NAD-BINDING, MUTAGENESIS OF LYS-176 AND GLU-313.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF100927 mRNA. Translation: AAD16435.1.
BC003292 mRNA. Translation: AAH03292.1.
RefSeqNP_036149.1. NM_012019.2.
UniGeneMm.240434.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1GV4X-ray2.00A/B122-610[»]
3GD3X-ray2.95A/B/C/D78-612[»]
3GD4X-ray2.24A/B102-612[»]
ProteinModelPortalQ9Z0X1.
SMRQ9Z0X1. Positions 121-610.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid205067. 3 interactions.
IntActQ9Z0X1. 13 interactions.
MINTMINT-1862023.
STRING10090.ENSMUSP00000041104.

PTM databases

PhosphoSiteQ9Z0X1.

Proteomic databases

PaxDbQ9Z0X1.
PRIDEQ9Z0X1.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000037349; ENSMUSP00000041104; ENSMUSG00000036932.
GeneID26926.
KEGGmmu:26926.
UCSCuc009tcg.1. mouse.

Organism-specific databases

CTD9131.
MGIMGI:1349419. Aifm1.

Phylogenomic databases

eggNOGCOG0446.
GeneTreeENSGT00530000063416.
HOGENOMHOG000264253.
HOVERGENHBG053538.
InParanoidQ9Z0X1.
KOK04727.
OMAKDGEEHA.
PhylomeDBQ9Z0X1.
TreeFamTF314028.

Gene expression databases

ArrayExpressQ9Z0X1.
BgeeQ9Z0X1.
GenevestigatorQ9Z0X1.

Family and domain databases

Gene3D3.30.390.30. 1 hit.
InterProIPR016156. 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]
PfamPF00070. Pyr_redox. 1 hit.
PF07992. Pyr_redox_2. 1 hit.
[Graphical view]
PRINTSPR00368. FADPNR.
SUPFAMSSF55424. SSF55424. 1 hit.
ProtoNetSearch...

Other

ChiTaRSAIFM1. mouse.
EvolutionaryTraceQ9Z0X1.
NextBio304817.
PROQ9Z0X1.
SOURCESearch...

Entry information

Entry nameAIFM1_MOUSE
AccessionPrimary (citable) accession number: Q9Z0X1
Entry history
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: May 1, 1999
Last modified: April 16, 2014
This is version 130 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot