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Q9Z0X1

- AIFM1_MOUSE

UniProt

Q9Z0X1 - AIFM1_MOUSE

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Protein
Apoptosis-inducing factor 1, mitochondrial
Gene
Aifm1, Aif, Pdcd8
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

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.1 Publication

Cofactori

FAD.1 Publication

Sites

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

Regions

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

GO - Molecular functioni

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

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. 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.1 Publication

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
Complete GO annotation...

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 – 5454Mitochondrion By similarity
Add
BLAST
Propeptidei55 – 10147Removed in mature form
PRO_0000401936Add
BLAST
Chaini102 – 612511Apoptosis-inducing factor 1, mitochondrial
PRO_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 – 2671Phosphoserine By 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.
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.

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.

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

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.

Miscellaneous databases

EvolutionaryTraceiQ9Z0X1.

Family & Domainsi

Region

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

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi445 – 4506Nuclear localization signal Reviewed prediction

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

« Hide 'large scale' publications
  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: July 9, 2014
This is version 133 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

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