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Protein

Apoptosis-inducing factor 1, mitochondrial

Gene

Aifm1

Organism
Rattus norvegicus (Rat)
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 similarity

Cofactori

FADBy similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei171FADBy similarity1
Binding sitei176FADBy similarity1
Binding sitei232FAD; via amide nitrogen and carbonyl oxygenBy similarity1
Binding sitei284FADBy similarity1
Binding sitei437FADBy similarity1
Binding sitei482FAD; via carbonyl oxygenBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi137 – 141FADBy similarity5
Nucleotide bindingi163 – 164FADBy similarity2
Nucleotide bindingi453 – 454FADBy similarity2

GO - Molecular functioni

GO - Biological processi

  • activation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
  • cell redox homeostasis Source: InterPro
  • cellular response to aldosterone Source: RGD
  • cellular response to estradiol stimulus Source: RGD
  • cellular response to hydrogen peroxide Source: RGD
  • cellular response to nitric oxide Source: RGD
  • cellular response to oxygen-glucose deprivation Source: RGD
  • intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress Source: UniProtKB
  • neuron apoptotic process Source: Ensembl
  • positive regulation of neuron apoptotic process Source: RGD
  • regulation of apoptotic DNA fragmentation Source: Ensembl
  • response to ischemia Source: RGD
  • response to L-glutamate Source: RGD
  • response to toxic substance Source: RGD
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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: 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

  • cytoplasm Source: RGD
  • cytosol Source: UniProtKB
  • mitochondrial inner membrane Source: UniProtKB-SubCell
  • mitochondrial intermembrane space Source: UniProtKB
  • mitochondrion Source: RGD
  • nucleus Source: RGD
  • perinuclear region of cytoplasm Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Mitochondrion, Mitochondrion inner membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 54MitochondrionBy similarityAdd BLAST54
PropeptideiPRO_000040193755 – 101Removed in mature formBy similarityAdd BLAST47
ChainiPRO_0000022032102 – 612Apoptosis-inducing factor 1, mitochondrialAdd BLAST511

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei108N6-succinyllysineBy similarity1
Modified residuei115PhosphoserineBy similarity1
Cross-linki254Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei267PhosphoserineCombined sources1
Modified residuei370PhosphoserineBy similarity1
Modified residuei387N6-acetyllysineBy similarity1
Modified residuei520PhosphothreonineBy similarity1
Modified residuei523PhosphoserineBy similarity1
Modified residuei529PhosphoserineBy similarity1
Modified residuei592N6-acetyllysineBy similarity1

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

iPTMnetiQ9JM53.
PhosphoSitePlusiQ9JM53.

Expressioni

Gene expression databases

BgeeiENSRNOG00000006067.
ExpressionAtlasiQ9JM53. baseline and differential.
GenevisibleiQ9JM53. RN.

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

Protein-protein interaction databases

BioGridi249749. 1 interactor.
STRINGi10116.ENSRNOP00000008503.

Structurei

3D structure databases

ProteinModelPortaliQ9JM53.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni133 – 482FAD-dependent oxidoreductaseBy similarityAdd 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.
InParanoidiQ9JM53.
KOiK04727.
OMAiWYTPNPN.
OrthoDBiEOG091G05ST.
PhylomeDBiQ9JM53.
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.

Q9JM53-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MFRCGGLAGA FKQKLVPLVR SVCVQRPKQR NRLPGNLFQQ WRVPLELQMA
60 70 80 90 100
RQMASSGPSG GKMDNSVLVL IVGLSTIGAG AYAYKTIKED QKRYNERIMG
110 120 130 140 150
LGLSPEEKQR RAIASAAEGG SVPPIRVPSH VPFLLIGGGT AAFAAARSIR
160 170 180 190 200
ARDPGARVLI VSEDPELPYM RPPLSKELWF SDDPNVTKTL QFRQWNGKER
210 220 230 240 250
SIYFQPPSFY VSAQDLPHIE NGGVAVLTGK KVVHLDVRGN MVKLNDGSQI
260 270 280 290 300
TFEKCLIATG GTPRSLSAID RAGAEVKSRT TLFRKIGDFR ALEKISREVK
310 320 330 340 350
SITVIGGGFL GSELACALGR KSQASGIEVI QLFPEKGNMG KILPEYLSNW
360 370 380 390 400
TMEKVKREGV KVMPNAIVQS VGVSGGKLLI 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 TIPPSDPAVP
560 570 580 590 600
QVPVEGEDYG KGVIFYLRDK VVVGIVLWNV FNRMPIARKI IKDGEQHEDL
610
NEVAKLFNIH ED
Length:612
Mass (Da):66,723
Last modified:October 1, 2000 - v1
Checksum:i02ECF24FA7400A86
GO

Sequence databases

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

3D structure databases

ProteinModelPortaliQ9JM53.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi249749. 1 interactor.
STRINGi10116.ENSRNOP00000008503.

PTM databases

iPTMnetiQ9JM53.
PhosphoSitePlusiQ9JM53.

Proteomic databases

PaxDbiQ9JM53.
PRIDEiQ9JM53.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi9131.
RGDi620817. Aifm1.

Phylogenomic databases

eggNOGiKOG1346. Eukaryota.
COG0446. LUCA.
GeneTreeiENSGT00530000063416.
HOGENOMiHOG000264253.
HOVERGENiHBG053538.
InParanoidiQ9JM53.
KOiK04727.
OMAiWYTPNPN.
OrthoDBiEOG091G05ST.
PhylomeDBiQ9JM53.
TreeFamiTF314028.

Miscellaneous databases

PROiQ9JM53.

Gene expression databases

BgeeiENSRNOG00000006067.
ExpressionAtlasiQ9JM53. baseline and differential.
GenevisibleiQ9JM53. RN.

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_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: November 2, 2016
This is version 127 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

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.