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Q9Z0X1

- AIFM1_MOUSE

UniProt

Q9Z0X1 - AIFM1_MOUSE

Protein

Apoptosis-inducing factor 1, mitochondrial

Gene

Aifm1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 134 (01 Oct 2014)
      Sequence version 1 (01 May 1999)
      Previous versions | rss
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    Functioni

    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.By similarity

    Cofactori

    FAD.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei171 – 1711FAD1 Publication
    Binding sitei176 – 1761FAD1 Publication
    Binding sitei232 – 2321FAD; via amide nitrogen and carbonyl oxygen1 Publication
    Binding sitei284 – 2841FAD1 Publication
    Binding sitei437 – 4371FAD1 Publication
    Binding sitei482 – 4821FAD; via carbonyl oxygen1 Publication

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi137 – 1415FAD1 Publication
    Nucleotide bindingi163 – 1642FAD1 Publication
    Nucleotide bindingi453 – 4542FAD1 Publication

    GO - Molecular functioni

    1. DNA binding Source: UniProtKB
    2. electron-transferring-flavoprotein dehydrogenase activity Source: MGI
    3. FAD binding Source: UniProtKB
    4. NAD(P)H oxidase activity Source: UniProtKB
    5. protein binding Source: IntAct

    GO - Biological processi

    1. activation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
    2. apoptotic mitochondrial changes Source: MGI
    3. cell redox homeostasis Source: InterPro
    4. intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress Source: UniProtKB
    5. mitochondrial respiratory chain complex I assembly Source: Ensembl
    6. neuron apoptotic process Source: MGI
    7. neuron differentiation Source: Ensembl
    8. positive regulation of apoptotic process Source: UniProtKB
    9. positive regulation of cell death Source: UniProtKB
    10. regulation of apoptotic DNA fragmentation Source: MGI
    11. response to oxidative stress Source: UniProtKB

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Biological processi

    Apoptosis

    Keywords - Ligandi

    DNA-binding, FAD, Flavoprotein, NAD

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Apoptosis-inducing factor 1, mitochondrial (EC:1.1.1.-)
    Alternative name(s):
    Programmed cell death protein 8
    Gene namesi
    Name:Aifm1
    Synonyms:Aif, Pdcd8
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome X

    Organism-specific databases

    MGIiMGI:1349419. Aifm1.

    Subcellular locationi

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

    GO - Cellular componenti

    1. cytoplasm Source: MGI
    2. cytosol Source: UniProtKB
    3. mitochondrial inner membrane Source: UniProtKB-SubCell
    4. mitochondrial intermembrane space Source: UniProtKB
    5. mitochondrial outer membrane Source: MGI
    6. mitochondrion Source: UniProtKB
    7. nucleus Source: UniProtKB
    8. perinuclear region of cytoplasm Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm, Membrane, Mitochondrion, Mitochondrion inner membrane, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi176 – 1761K → A: Increases catalytic efficiency. 1 Publication
    Mutagenesisi313 – 3131E → A: Increases catalytic efficiency 30-fold. Increases affinity for NADH 20-fold. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transit peptidei1 – 5454MitochondrionBy similarityAdd
    BLAST
    Propeptidei55 – 10147Removed in mature form1 PublicationPRO_0000401936Add
    BLAST
    Chaini102 – 612511Apoptosis-inducing factor 1, mitochondrialPRO_0000022031Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei108 – 1081N6-succinyllysine1 Publication
    Cross-linki254 – 254Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
    Modified residuei267 – 2671PhosphoserineBy similarity
    Modified residuei387 – 3871N6-acetyllysine1 Publication
    Modified residuei592 – 5921N6-acetyllysine1 Publication

    Post-translational modificationi

    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.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.By similarity

    Keywords - PTMi

    Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiQ9Z0X1.
    PaxDbiQ9Z0X1.
    PRIDEiQ9Z0X1.

    PTM databases

    PhosphoSiteiQ9Z0X1.

    Expressioni

    Gene expression databases

    ArrayExpressiQ9Z0X1.
    BgeeiQ9Z0X1.
    GenevestigatoriQ9Z0X1.

    Interactioni

    Subunit structurei

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

    Binary interactionsi

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

    Protein-protein interaction databases

    BioGridi205067. 3 interactions.
    IntActiQ9Z0X1. 13 interactions.
    MINTiMINT-1862023.
    STRINGi10090.ENSMUSP00000041104.

    Structurei

    Secondary structure

    1
    612
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi129 – 1379
    Helixi140 – 15213
    Beta strandi157 – 16610
    Helixi172 – 1754
    Helixi177 – 1793
    Helixi186 – 1894
    Beta strandi191 – 1933
    Beta strandi199 – 2057
    Helixi207 – 2093
    Helixi213 – 2186
    Beta strandi223 – 2297
    Beta strandi232 – 2365
    Turni237 – 2404
    Beta strandi241 – 2444
    Beta strandi249 – 2579
    Beta strandi261 – 2633
    Helixi267 – 2704
    Helixi274 – 2774
    Beta strandi280 – 2823
    Helixi286 – 29611
    Beta strandi300 – 3056
    Helixi309 – 32517
    Beta strandi328 – 3325
    Beta strandi334 – 3374
    Turni338 – 3425
    Helixi345 – 35612
    Turni357 – 3593
    Beta strandi361 – 3633
    Beta strandi368 – 3747
    Beta strandi377 – 3826
    Beta strandi387 – 3959
    Beta strandi399 – 4013
    Helixi404 – 4063
    Turni407 – 4104
    Turni415 – 4173
    Beta strandi419 – 4213
    Beta strandi426 – 4294
    Beta strandi432 – 4343
    Helixi436 – 4383
    Beta strandi439 – 4435
    Turni444 – 4463
    Beta strandi447 – 4493
    Helixi454 – 46815
    Turni469 – 4713
    Beta strandi480 – 4867
    Beta strandi490 – 4956
    Beta strandi503 – 5086
    Helixi516 – 5238
    Helixi528 – 5325
    Beta strandi539 – 5424
    Helixi556 – 5583
    Beta strandi561 – 57919
    Helixi584 – 59310
    Helixi600 – 6045
    Helixi605 – 6073

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1GV4X-ray2.00A/B122-610[»]
    3GD3X-ray2.95A/B/C/D78-612[»]
    3GD4X-ray2.24A/B102-612[»]
    ProteinModelPortaliQ9Z0X1.
    SMRiQ9Z0X1. Positions 121-610.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ9Z0X1.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni133 – 482350FAD-dependent oxidoreductaseAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi445 – 4506Nuclear localization signalSequence Analysis

    Sequence similaritiesi

    Keywords - Domaini

    Transit peptide

    Phylogenomic databases

    eggNOGiCOG0446.
    GeneTreeiENSGT00530000063416.
    HOGENOMiHOG000264253.
    HOVERGENiHBG053538.
    InParanoidiQ9Z0X1.
    KOiK04727.
    OMAiKDGEEHA.
    PhylomeDBiQ9Z0X1.
    TreeFamiTF314028.

    Family and domain databases

    Gene3Di3.30.390.30. 1 hit.
    InterProiIPR029324. 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]
    PfamiPF14721. AIF_C. 1 hit.
    PF00070. Pyr_redox. 1 hit.
    PF07992. Pyr_redox_2. 1 hit.
    [Graphical view]
    PRINTSiPR00368. FADPNR.
    SUPFAMiSSF55424. SSF55424. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q9Z0X1-1 [UniParc]FASTAAdd to Basket

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    MFRCGGLAGA FKQKLVPLVR TVYVQRPKQR NRLPGNLFQQ WRVPLELQMA    50
    RQMASSGSSG GKMDNSVLVL IVGLSTIGAG AYAYKTIKED QKRYNERVMG 100
    LGLSPEEKQR RAIASATEGG SVPQIRAPSH VPFLLIGGGT AAFAAARSIR 150
    ARDPGARVLI VSEDPELPYM RPPLSKELWF SDDPNVTKTL QFRQWNGKER 200
    SIYFQPPSFY VSAQDLPNIE NGGVAVLTGK KVVHLDVRGN MVKLNDGSQI 250
    TFEKCLIATG GTPRSLSAID RAGAEVKSRT TLFRKIGDFR ALEKISREVK 300
    SITVIGGGFL GSELACALGR KSQASGIEVI QLFPEKGNMG KILPQYLSNW 350
    TMEKVKREGV KVMPNAIVQS VGVSGGRLLI KLKDGRKVET DHIVTAVGLE 400
    PNVELAKTGG LEIDSDFGGF RVNAELQARS NIWVAGDAAC FYDIKLGRRR 450
    VEHHDHAVVS GRLAGENMTG AAKPYWHQSM FWSDLGPDVG YEAIGLVDSS 500
    LPTVGVFAKA TAQDNPKSAT EQSGTGIRSE SETESEASEI TIPPSAPAVP 550
    QVPVEGEDYG KGVIFYLRDK VVVGIVLWNV FNRMPIARKI IKDGEQHEDL 600
    NEVAKLFNIH ED 612
    Length:612
    Mass (Da):66,765
    Last modified:May 1, 1999 - v1
    Checksum:iA17EDFD5CF77BB85
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF100927 mRNA. Translation: AAD16435.1.
    BC003292 mRNA. Translation: AAH03292.1.
    CCDSiCCDS30109.1.
    RefSeqiNP_001277293.1. NM_001290364.1.
    NP_036149.1. NM_012019.3.
    UniGeneiMm.240434.

    Genome annotation databases

    EnsembliENSMUST00000037349; ENSMUSP00000041104; ENSMUSG00000036932.
    GeneIDi26926.
    KEGGimmu:26926.
    UCSCiuc009tcg.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF100927 mRNA. Translation: AAD16435.1 .
    BC003292 mRNA. Translation: AAH03292.1 .
    CCDSi CCDS30109.1.
    RefSeqi NP_001277293.1. NM_001290364.1.
    NP_036149.1. NM_012019.3.
    UniGenei Mm.240434.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1GV4 X-ray 2.00 A/B 122-610 [» ]
    3GD3 X-ray 2.95 A/B/C/D 78-612 [» ]
    3GD4 X-ray 2.24 A/B 102-612 [» ]
    ProteinModelPortali Q9Z0X1.
    SMRi Q9Z0X1. Positions 121-610.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 205067. 3 interactions.
    IntActi Q9Z0X1. 13 interactions.
    MINTi MINT-1862023.
    STRINGi 10090.ENSMUSP00000041104.

    PTM databases

    PhosphoSitei Q9Z0X1.

    Proteomic databases

    MaxQBi Q9Z0X1.
    PaxDbi Q9Z0X1.
    PRIDEi Q9Z0X1.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000037349 ; ENSMUSP00000041104 ; ENSMUSG00000036932 .
    GeneIDi 26926.
    KEGGi mmu:26926.
    UCSCi uc009tcg.1. mouse.

    Organism-specific databases

    CTDi 9131.
    MGIi MGI:1349419. Aifm1.

    Phylogenomic databases

    eggNOGi COG0446.
    GeneTreei ENSGT00530000063416.
    HOGENOMi HOG000264253.
    HOVERGENi HBG053538.
    InParanoidi Q9Z0X1.
    KOi K04727.
    OMAi KDGEEHA.
    PhylomeDBi Q9Z0X1.
    TreeFami TF314028.

    Miscellaneous databases

    ChiTaRSi AIFM1. mouse.
    EvolutionaryTracei Q9Z0X1.
    NextBioi 304817.
    PROi Q9Z0X1.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9Z0X1.
    Bgeei Q9Z0X1.
    Genevestigatori Q9Z0X1.

    Family and domain databases

    Gene3Di 3.30.390.30. 1 hit.
    InterProi IPR029324. 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 ]
    Pfami PF14721. AIF_C. 1 hit.
    PF00070. Pyr_redox. 1 hit.
    PF07992. Pyr_redox_2. 1 hit.
    [Graphical view ]
    PRINTSi PR00368. FADPNR.
    SUPFAMi SSF55424. SSF55424. 1 hit.
    ProtoNeti Search...

    Publicationsi

    1. 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. Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 108-610 IN COMPLEX WITH FAD, NAD-BINDING, MUTAGENESIS OF LYS-176 AND GLU-313.

    Entry informationi

    Entry nameiAIFM1_MOUSE
    AccessioniPrimary (citable) accession number: Q9Z0X1
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 27, 2001
    Last sequence update: May 1, 1999
    Last modified: October 1, 2014
    This is version 134 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3