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Protein

Apoptosis-inducing factor 1, mitochondrial

Gene

Aifm1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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).By similarity1 Publication

Cofactori

FAD1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei171FAD1 Publication1
Binding sitei176FAD1 Publication1
Binding sitei232FAD; via amide nitrogen and carbonyl oxygen1 Publication1
Binding sitei284FAD1 Publication1
Binding sitei437FAD1 Publication1
Binding sitei482FAD; via carbonyl oxygen1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi137 – 141FAD1 Publication5
Nucleotide bindingi163 – 164FAD1 Publication2
Nucleotide bindingi453 – 454FAD1 Publication2

GO - Molecular functioni

  • DNA binding Source: UniProtKB
  • electron-transferring-flavoprotein dehydrogenase activity Source: MGI
  • FAD binding Source: UniProtKB
  • NAD(P)H oxidase activity Source: UniProtKB
  • oxidoreductase activity, acting on NAD(P)H Source: MGI

GO - Biological processi

  • activation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
  • apoptotic mitochondrial changes Source: MGI
  • apoptotic process Source: MGI
  • cell redox homeostasis Source: InterPro
  • cellular response to aldosterone Source: Ensembl
  • cellular response to estradiol stimulus Source: Ensembl
  • cellular response to hydrogen peroxide Source: Ensembl
  • cellular response to nitric oxide Source: Ensembl
  • cellular response to oxygen-glucose deprivation Source: Ensembl
  • intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress Source: UniProtKB
  • neuron apoptotic process Source: MGI
  • positive regulation of apoptotic process Source: UniProtKB
  • positive regulation of cell death Source: UniProtKB
  • positive regulation of neuron apoptotic process Source: Ensembl
  • regulation of apoptotic DNA fragmentation Source: MGI
  • response to ischemia Source: Ensembl
  • response to L-glutamate Source: Ensembl
  • response to oxidative stress Source: UniProtKB
  • response to toxic substance Source: Ensembl
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
Proteomesi
  • UP000000589 Componenti: Chromosome X

Organism-specific databases

MGIiMGI:1349419. Aifm1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: MGI
  • cytosol Source: UniProtKB
  • mitochondrial inner membrane Source: UniProtKB-SubCell
  • mitochondrial intermembrane space Source: UniProtKB
  • mitochondrial outer membrane Source: MGI
  • mitochondrion Source: UniProtKB
  • nucleus Source: UniProtKB
  • 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)DescriptionActionsGraphical viewLength
Mutagenesisi176K → A: Increases catalytic efficiency. 1 Publication1
Mutagenesisi313E → A: Increases catalytic efficiency 30-fold. Increases affinity for NADH 20-fold. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 54MitochondrionBy similarityAdd BLAST54
PropeptideiPRO_000040193655 – 101Removed in mature form1 PublicationAdd BLAST47
ChainiPRO_0000022031102 – 612Apoptosis-inducing factor 1, mitochondrialAdd BLAST511

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei108N6-succinyllysineCombined sources1
Modified residuei115PhosphoserineBy similarity1
Cross-linki254Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei267PhosphoserineBy similarity1
Modified residuei370PhosphoserineBy similarity1
Modified residuei387N6-acetyllysineCombined sources1
Modified residuei520PhosphothreonineBy similarity1
Modified residuei523PhosphoserineBy similarity1
Modified residuei529PhosphoserineBy similarity1
Modified residuei592N6-acetyllysineCombined sources1

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

EPDiQ9Z0X1.
MaxQBiQ9Z0X1.
PaxDbiQ9Z0X1.
PeptideAtlasiQ9Z0X1.
PRIDEiQ9Z0X1.

PTM databases

iPTMnetiQ9Z0X1.
PhosphoSitePlusiQ9Z0X1.
SwissPalmiQ9Z0X1.

Expressioni

Gene expression databases

BgeeiENSMUSG00000036932.
ExpressionAtlasiQ9Z0X1. baseline and differential.
GenevisibleiQ9Z0X1. MM.

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. 17 interactors.
IntActiQ9Z0X1. 26 interactors.
MINTiMINT-1862023.
STRINGi10090.ENSMUSP00000041104.

Structurei

Secondary structure

1612
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi129 – 137Combined sources9
Helixi140 – 152Combined sources13
Beta strandi157 – 166Combined sources10
Helixi172 – 175Combined sources4
Helixi177 – 179Combined sources3
Helixi186 – 189Combined sources4
Beta strandi191 – 193Combined sources3
Beta strandi199 – 205Combined sources7
Helixi207 – 209Combined sources3
Helixi213 – 218Combined sources6
Beta strandi223 – 229Combined sources7
Beta strandi232 – 236Combined sources5
Turni237 – 240Combined sources4
Beta strandi241 – 244Combined sources4
Beta strandi249 – 257Combined sources9
Beta strandi261 – 263Combined sources3
Helixi267 – 270Combined sources4
Helixi274 – 277Combined sources4
Beta strandi280 – 282Combined sources3
Helixi286 – 296Combined sources11
Beta strandi300 – 305Combined sources6
Helixi309 – 325Combined sources17
Beta strandi328 – 332Combined sources5
Beta strandi334 – 337Combined sources4
Turni338 – 342Combined sources5
Helixi345 – 356Combined sources12
Turni357 – 359Combined sources3
Beta strandi361 – 363Combined sources3
Beta strandi368 – 374Combined sources7
Beta strandi377 – 382Combined sources6
Beta strandi387 – 395Combined sources9
Beta strandi399 – 401Combined sources3
Helixi404 – 406Combined sources3
Turni407 – 410Combined sources4
Turni415 – 417Combined sources3
Beta strandi419 – 421Combined sources3
Beta strandi426 – 429Combined sources4
Beta strandi432 – 434Combined sources3
Helixi436 – 438Combined sources3
Beta strandi439 – 443Combined sources5
Turni444 – 446Combined sources3
Beta strandi447 – 449Combined sources3
Helixi454 – 468Combined sources15
Turni469 – 471Combined sources3
Beta strandi480 – 486Combined sources7
Beta strandi490 – 495Combined sources6
Beta strandi503 – 508Combined sources6
Helixi516 – 523Combined sources8
Helixi528 – 532Combined sources5
Beta strandi539 – 542Combined sources4
Helixi556 – 558Combined sources3
Beta strandi561 – 579Combined sources19
Helixi584 – 593Combined sources10
Helixi600 – 604Combined sources5
Helixi605 – 607Combined sources3

3D structure databases

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

Miscellaneous databases

EvolutionaryTraceiQ9Z0X1.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni133 – 482FAD-dependent oxidoreductaseAdd BLAST350

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi445 – 450Nuclear localization signalSequence analysis6

Sequence similaritiesi

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG1346. Eukaryota.
COG0446. LUCA.
GeneTreeiENSGT00530000063416.
HOGENOMiHOG000264253.
HOVERGENiHBG053538.
InParanoidiQ9Z0X1.
KOiK04727.
OMAiWYTPNPN.
OrthoDBiEOG091G05ST.
PhylomeDBiQ9Z0X1.
TreeFamiTF314028.

Family and domain databases

Gene3Di3.30.390.30. 1 hit.
3.50.50.60. 3 hits.
InterProiIPR029324. AIF_C.
IPR023753. FAD/NAD-binding_dom.
IPR016156. FAD/NAD-linked_Rdtase_dimer.
IPR004099. Pyr_nucl-diS_OxRdtase_dimer.
[Graphical view]
PfamiPF14721. AIF_C. 1 hit.
PF07992. Pyr_redox_2. 1 hit.
[Graphical view]
SUPFAMiSSF51905. SSF51905. 2 hits.
SSF55424. 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

« Hide

        10         20         30         40         50
MFRCGGLAGA FKQKLVPLVR TVYVQRPKQR NRLPGNLFQQ WRVPLELQMA
60 70 80 90 100
RQMASSGSSG GKMDNSVLVL IVGLSTIGAG AYAYKTIKED QKRYNERVMG
110 120 130 140 150
LGLSPEEKQR RAIASATEGG SVPQIRAPSH VPFLLIGGGT AAFAAARSIR
160 170 180 190 200
ARDPGARVLI VSEDPELPYM RPPLSKELWF SDDPNVTKTL QFRQWNGKER
210 220 230 240 250
SIYFQPPSFY VSAQDLPNIE NGGVAVLTGK KVVHLDVRGN MVKLNDGSQI
260 270 280 290 300
TFEKCLIATG GTPRSLSAID RAGAEVKSRT TLFRKIGDFR ALEKISREVK
310 320 330 340 350
SITVIGGGFL GSELACALGR KSQASGIEVI QLFPEKGNMG KILPQYLSNW
360 370 380 390 400
TMEKVKREGV KVMPNAIVQS VGVSGGRLLI KLKDGRKVET DHIVTAVGLE
410 420 430 440 450
PNVELAKTGG LEIDSDFGGF RVNAELQARS NIWVAGDAAC FYDIKLGRRR
460 470 480 490 500
VEHHDHAVVS GRLAGENMTG AAKPYWHQSM FWSDLGPDVG YEAIGLVDSS
510 520 530 540 550
LPTVGVFAKA TAQDNPKSAT EQSGTGIRSE SETESEASEI TIPPSAPAVP
560 570 580 590 600
QVPVEGEDYG KGVIFYLRDK VVVGIVLWNV FNRMPIARKI IKDGEQHEDL
610
NEVAKLFNIH ED
Length:612
Mass (Da):66,765
Last modified:May 1, 1999 - v1
Checksum:iA17EDFD5CF77BB85
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

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

Protein-protein interaction databases

BioGridi205067. 17 interactors.
IntActiQ9Z0X1. 26 interactors.
MINTiMINT-1862023.
STRINGi10090.ENSMUSP00000041104.

PTM databases

iPTMnetiQ9Z0X1.
PhosphoSitePlusiQ9Z0X1.
SwissPalmiQ9Z0X1.

Proteomic databases

EPDiQ9Z0X1.
MaxQBiQ9Z0X1.
PaxDbiQ9Z0X1.
PeptideAtlasiQ9Z0X1.
PRIDEiQ9Z0X1.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi9131.
MGIiMGI:1349419. Aifm1.

Phylogenomic databases

eggNOGiKOG1346. Eukaryota.
COG0446. LUCA.
GeneTreeiENSGT00530000063416.
HOGENOMiHOG000264253.
HOVERGENiHBG053538.
InParanoidiQ9Z0X1.
KOiK04727.
OMAiWYTPNPN.
OrthoDBiEOG091G05ST.
PhylomeDBiQ9Z0X1.
TreeFamiTF314028.

Miscellaneous databases

ChiTaRSiAifm1. mouse.
EvolutionaryTraceiQ9Z0X1.
PROiQ9Z0X1.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000036932.
ExpressionAtlasiQ9Z0X1. baseline and differential.
GenevisibleiQ9Z0X1. MM.

Family and domain databases

Gene3Di3.30.390.30. 1 hit.
3.50.50.60. 3 hits.
InterProiIPR029324. AIF_C.
IPR023753. FAD/NAD-binding_dom.
IPR016156. FAD/NAD-linked_Rdtase_dimer.
IPR004099. Pyr_nucl-diS_OxRdtase_dimer.
[Graphical view]
PfamiPF14721. AIF_C. 1 hit.
PF07992. Pyr_redox_2. 1 hit.
[Graphical view]
SUPFAMiSSF51905. SSF51905. 2 hits.
SSF55424. SSF55424. 1 hit.
ProtoNetiSearch...

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: November 2, 2016
This is version 154 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.