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Q9JM53

- AIFM1_RAT

UniProt

Q9JM53 - AIFM1_RAT

Protein

Apoptosis-inducing factor 1, mitochondrial

Gene

Aifm1

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 110 (01 Oct 2014)
      Sequence version 1 (01 Oct 2000)
      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.By similarity

    Sites

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

    Regions

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

    GO - Molecular functioni

    1. DNA binding Source: UniProtKB-KW
    2. flavin adenine dinucleotide binding Source: InterPro
    3. oxidoreductase activity, acting on NAD(P)H Source: Ensembl

    GO - Biological processi

    1. activation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
    2. apoptotic DNA fragmentation Source: Ensembl
    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: Ensembl
    7. neuron differentiation Source: Ensembl

    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
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Chromosome X

    Organism-specific databases

    RGDi620817. Aifm1.

    Subcellular locationi

    Mitochondrion intermembrane space. Mitochondrion inner membrane By similarity. Cytoplasm By similarity. Cytoplasmperinuclear region By similarity. Nucleus By similarity
    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. cytosol Source: UniProtKB
    2. mitochondrial inner membrane Source: UniProtKB-SubCell
    3. mitochondrial intermembrane space Source: UniProtKB
    4. mitochondrion Source: RGD
    5. nucleus Source: RGD
    6. perinuclear region of cytoplasm Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm, Membrane, Mitochondrion, Mitochondrion inner membrane, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transit peptidei1 – 5454MitochondrionBy similarityAdd
    BLAST
    Propeptidei55 – 10147Removed in mature formBy similarityPRO_0000401937Add
    BLAST
    Chaini102 – 612511Apoptosis-inducing factor 1, mitochondrialPRO_0000022032Add
    BLAST

    Amino acid modifications

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

    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

    PaxDbiQ9JM53.
    PRIDEiQ9JM53.

    PTM databases

    PhosphoSiteiQ9JM53.

    Expressioni

    Gene expression databases

    GenevestigatoriQ9JM53.

    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

    Structurei

    3D structure databases

    ProteinModelPortaliQ9JM53.
    SMRiQ9JM53. Positions 121-610.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni133 – 482350FAD-dependent oxidoreductaseBy similarityAdd
    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.
    InParanoidiQ9JM53.
    KOiK04727.
    OMAiKDGEEHA.
    OrthoDBiEOG7C2R0V.
    PhylomeDBiQ9JM53.
    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.

    Q9JM53-1 [UniParc]FASTAAdd to Basket

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    MFRCGGLAGA FKQKLVPLVR SVCVQRPKQR NRLPGNLFQQ WRVPLELQMA    50
    RQMASSGPSG GKMDNSVLVL IVGLSTIGAG AYAYKTIKED QKRYNERIMG 100
    LGLSPEEKQR RAIASAAEGG SVPPIRVPSH VPFLLIGGGT AAFAAARSIR 150
    ARDPGARVLI VSEDPELPYM RPPLSKELWF SDDPNVTKTL QFRQWNGKER 200
    SIYFQPPSFY VSAQDLPHIE NGGVAVLTGK KVVHLDVRGN MVKLNDGSQI 250
    TFEKCLIATG GTPRSLSAID RAGAEVKSRT TLFRKIGDFR ALEKISREVK 300
    SITVIGGGFL GSELACALGR KSQASGIEVI QLFPEKGNMG KILPEYLSNW 350
    TMEKVKREGV KVMPNAIVQS VGVSGGKLLI KLKDGRKVET DHIVTAVGLE 400
    PNVELAKTGG LEIDSDFGGF RVNAELQARS NIWVAGDAAC FYDIKLGRRR 450
    VEHHDHAVVS GRLAGENMTG AAKPYWHQSM FWSDLGPDVG YEAIGLVDSS 500
    LPTVGVFAKA TAQDNPKSAT EQSGTGIRSE SETESEASEI TIPPSDPAVP 550
    QVPVEGEDYG KGVIFYLRDK VVVGIVLWNV FNRMPIARKI IKDGEQHEDL 600
    NEVAKLFNIH ED 612
    Length:612
    Mass (Da):66,723
    Last modified:October 1, 2000 - v1
    Checksum:i02ECF24FA7400A86
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB041723 mRNA. Translation: BAA94745.1.
    AF375656 mRNA. Translation: AAM46094.1.
    BC072697 mRNA. Translation: AAH72697.1.
    RefSeqiNP_112646.1. NM_031356.1.
    UniGeneiRn.203165.

    Genome annotation databases

    EnsembliENSRNOT00000008503; ENSRNOP00000008503; ENSRNOG00000006067.
    GeneIDi83533.
    KEGGirno:83533.
    UCSCiRGD:620817. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB041723 mRNA. Translation: BAA94745.1 .
    AF375656 mRNA. Translation: AAM46094.1 .
    BC072697 mRNA. Translation: AAH72697.1 .
    RefSeqi NP_112646.1. NM_031356.1.
    UniGenei Rn.203165.

    3D structure databases

    ProteinModelPortali Q9JM53.
    SMRi Q9JM53. Positions 121-610.
    ModBasei Search...
    MobiDBi Search...

    PTM databases

    PhosphoSitei Q9JM53.

    Proteomic databases

    PaxDbi Q9JM53.
    PRIDEi Q9JM53.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSRNOT00000008503 ; ENSRNOP00000008503 ; ENSRNOG00000006067 .
    GeneIDi 83533.
    KEGGi rno:83533.
    UCSCi RGD:620817. rat.

    Organism-specific databases

    CTDi 9131.
    RGDi 620817. Aifm1.

    Phylogenomic databases

    eggNOGi COG0446.
    GeneTreei ENSGT00530000063416.
    HOGENOMi HOG000264253.
    HOVERGENi HBG053538.
    InParanoidi Q9JM53.
    KOi K04727.
    OMAi KDGEEHA.
    OrthoDBi EOG7C2R0V.
    PhylomeDBi Q9JM53.
    TreeFami TF314028.

    Miscellaneous databases

    NextBioi 616033.
    PROi Q9JM53.

    Gene expression databases

    Genevestigatori Q9JM53.

    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. "Molecular cloning of rat apoptosis-inducing factor (AIF)."
      Ohsakaya S., Mihara K.
      Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Liver.
    2. "Cloning and characterization of rat apoptosis-inducing factor: implications for DNA fragmentation in cerebral ischemia."
      Cao G., Sheng L., Pei W., Chen J.
      Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: Sprague-Dawley.
      Tissue: Cerebellum.
    3. "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].
      Tissue: Heart.
    4. Lubec G., Kang S.U., Lubec S.
      Submitted (SEP-2007) to UniProtKB
      Cited for: PROTEIN SEQUENCE OF 378-386, IDENTIFICATION BY MASS SPECTROMETRY.
      Strain: Sprague-Dawley.
      Tissue: Brain.

    Entry informationi

    Entry nameiAIFM1_RAT
    AccessioniPrimary (citable) accession number: Q9JM53
    Secondary accession number(s): Q548E3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 27, 2001
    Last sequence update: October 1, 2000
    Last modified: October 1, 2014
    This is version 110 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

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3