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Q9JM53 (AIFM1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 108. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Apoptosis-inducing factor 1, mitochondrial

EC=1.1.1.-
Alternative name(s):
Programmed cell death protein 8
Gene names
Name:Aifm1
Synonyms:Aif, Pdcd8
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length612 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Cofactor

FAD By similarity.

Subunit structure

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

Subcellular location

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.

Post-translational modification

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.

Sequence similarities

Belongs to the FAD-dependent oxidoreductase family.

Ontologies

Keywords
   Biological processApoptosis
   Cellular componentCytoplasm
Membrane
Mitochondrion
Mitochondrion inner membrane
Nucleus
   DomainTransit peptide
   LigandDNA-binding
FAD
Flavoprotein
NAD
   Molecular functionOxidoreductase
   PTMAcetylation
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

apoptotic DNA fragmentation

Inferred from electronic annotation. Source: Ensembl

cell redox homeostasis

Inferred from electronic annotation. Source: InterPro

intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress

Inferred from sequence or structural similarity. Source: UniProtKB

mitochondrial respiratory chain complex I assembly

Inferred from electronic annotation. Source: Ensembl

neuron apoptotic process

Inferred from electronic annotation. Source: Ensembl

neuron differentiation

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytosol

Inferred from sequence or structural similarity. Source: UniProtKB

mitochondrial inner membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

mitochondrial intermembrane space

Inferred from sequence or structural similarity. Source: UniProtKB

mitochondrion

Inferred from direct assay PubMed 12453066. Source: RGD

nucleus

Inferred from direct assay PubMed 12453066. Source: RGD

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionDNA binding

Inferred from electronic annotation. Source: UniProtKB-KW

flavin adenine dinucleotide binding

Inferred from electronic annotation. Source: InterPro

oxidoreductase activity, acting on NAD(P)H

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 5454Mitochondrion By similarity
Propeptide55 – 10147Removed in mature form By similarity
PRO_0000401937
Chain102 – 612511Apoptosis-inducing factor 1, mitochondrial
PRO_0000022032

Regions

Nucleotide binding137 – 1415FAD By similarity
Nucleotide binding163 – 1642FAD By similarity
Nucleotide binding453 – 4542FAD By similarity
Region133 – 482350FAD-dependent oxidoreductase By similarity
Motif445 – 4506Nuclear localization signal Potential

Sites

Binding site1711FAD By similarity
Binding site1761FAD By similarity
Binding site2321FAD; via amide nitrogen and carbonyl oxygen By similarity
Binding site2841FAD By similarity
Binding site4371FAD By similarity
Binding site4821FAD; via carbonyl oxygen By similarity

Amino acid modifications

Modified residue1081N6-succinyllysine By similarity
Modified residue2671Phosphoserine By similarity
Modified residue3871N6-acetyllysine By similarity
Modified residue5921N6-acetyllysine By similarity
Cross-link254Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Sequences

Sequence LengthMass (Da)Tools
Q9JM53 [UniParc].

Last modified October 1, 2000. Version 1.
Checksum: 02ECF24FA7400A86

FASTA61266,723
        10         20         30         40         50         60 
MFRCGGLAGA FKQKLVPLVR SVCVQRPKQR NRLPGNLFQQ WRVPLELQMA RQMASSGPSG 

        70         80         90        100        110        120 
GKMDNSVLVL IVGLSTIGAG AYAYKTIKED QKRYNERIMG LGLSPEEKQR RAIASAAEGG 

       130        140        150        160        170        180 
SVPPIRVPSH VPFLLIGGGT AAFAAARSIR ARDPGARVLI VSEDPELPYM RPPLSKELWF 

       190        200        210        220        230        240 
SDDPNVTKTL QFRQWNGKER SIYFQPPSFY VSAQDLPHIE NGGVAVLTGK KVVHLDVRGN 

       250        260        270        280        290        300 
MVKLNDGSQI TFEKCLIATG GTPRSLSAID RAGAEVKSRT TLFRKIGDFR ALEKISREVK 

       310        320        330        340        350        360 
SITVIGGGFL GSELACALGR KSQASGIEVI QLFPEKGNMG KILPEYLSNW TMEKVKREGV 

       370        380        390        400        410        420 
KVMPNAIVQS VGVSGGKLLI KLKDGRKVET DHIVTAVGLE PNVELAKTGG LEIDSDFGGF 

       430        440        450        460        470        480 
RVNAELQARS NIWVAGDAAC FYDIKLGRRR VEHHDHAVVS GRLAGENMTG AAKPYWHQSM 

       490        500        510        520        530        540 
FWSDLGPDVG YEAIGLVDSS LPTVGVFAKA TAQDNPKSAT EQSGTGIRSE SETESEASEI 

       550        560        570        580        590        600 
TIPPSDPAVP QVPVEGEDYG KGVIFYLRDK VVVGIVLWNV FNRMPIARKI IKDGEQHEDL 

       610 
NEVAKLFNIH ED 

« Hide

References

« Hide 'large scale' references
[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB041723 mRNA. Translation: BAA94745.1.
AF375656 mRNA. Translation: AAM46094.1.
BC072697 mRNA. Translation: AAH72697.1.
RefSeqNP_112646.1. NM_031356.1.
UniGeneRn.203165.

3D structure databases

ProteinModelPortalQ9JM53.
SMRQ9JM53. Positions 121-610.
ModBaseSearch...
MobiDBSearch...

PTM databases

PhosphoSiteQ9JM53.

Proteomic databases

PaxDbQ9JM53.
PRIDEQ9JM53.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000008503; ENSRNOP00000008503; ENSRNOG00000006067.
GeneID83533.
KEGGrno:83533.
UCSCRGD:620817. rat.

Organism-specific databases

CTD9131.
RGD620817. Aifm1.

Phylogenomic databases

eggNOGCOG0446.
GeneTreeENSGT00530000063416.
HOGENOMHOG000264253.
HOVERGENHBG053538.
InParanoidQ9JM53.
KOK04727.
OMAKDGEEHA.
OrthoDBEOG7C2R0V.
PhylomeDBQ9JM53.
TreeFamTF314028.

Gene expression databases

GenevestigatorQ9JM53.

Family and domain databases

Gene3D3.30.390.30. 1 hit.
InterProIPR016156. 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]
PfamPF00070. Pyr_redox. 1 hit.
PF07992. Pyr_redox_2. 1 hit.
[Graphical view]
PRINTSPR00368. FADPNR.
SUPFAMSSF55424. SSF55424. 1 hit.
ProtoNetSearch...

Other

NextBio616033.
PROQ9JM53.

Entry information

Entry nameAIFM1_RAT
AccessionPrimary (citable) accession number: Q9JM53
Secondary accession number(s): Q548E3
Entry history
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: October 1, 2000
Last modified: April 16, 2014
This is version 108 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families