Apoptosis-inducing factor 1, mitochondrial precursor

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Q9JM53 (AIFM1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 101. History...

Clusters with 100%, 90%, 50% identity |

Documents (1) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Apoptosis-inducing factor 1, mitochondrial
EC=1.-.-.-

Alternative name(s):
Programmed cell death protein 8

Gene names

Name:	Aifm1
Synonyms:	Aif, Pdcd8

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	612 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Probable oxidoreductase that has a dual role in controlling cellular life and death; during apoptosis, it is translocated from the mitochondria to the nucleus to function as a proapoptotic factor in a caspase-independent pathway, while in normal mitochondria, it functions as an antiapoptotic factor via its 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	Interacts with XIAP/BIRC4. Interacts (via N-terminus) with EIF3G (via C-terminus) By similarity.
Subcellular location	Mitochondrion intermembrane space. Mitochondrion inner membrane By similarity. Cytoplasm By similarity. Cytoplasm › perinuclear 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 process	Apoptosis
Cellular component	Cytoplasm Membrane Mitochondrion Mitochondrion inner membrane Nucleus
Domain	Transit peptide
Ligand	DNA-binding FAD Flavoprotein
Molecular function	Oxidoreductase
PTM	Acetylation Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	activation 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: Compara 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: Compara neuron apoptotic process Inferred from electronic annotation. Source: Compara neuron differentiation Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol 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 mitochondrial membrane part Inferred from electronic annotation. Source: Compara nucleus Inferred from direct assay PubMed 12453066. Source: RGD perinuclear region of cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW flavin adenine dinucleotide binding Inferred from electronic annotation. Source: InterPro oxidoreductase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 54

Mitochondrion By similarity

Propeptide

55 – 101

Removed in mature form By similarity

PRO_0000401937

Chain

102 – 612

511

Apoptosis-inducing factor 1, mitochondrial

PRO_0000022032

Regions

Nucleotide binding

137 – 141

FAD By similarity

Nucleotide binding

163 – 164

FAD By similarity

Nucleotide binding

453 – 454

FAD By similarity

Region

133 – 482

350

FAD-dependent oxidoreductase By similarity

Motif

445 – 450

Nuclear localization signal Potential

Sites

Binding site

171

FAD By similarity

Binding site

176

FAD By similarity

Binding site

232

FAD; via amide nitrogen and carbonyl oxygen By similarity

Binding site

284

FAD By similarity

Binding site

437

FAD By similarity

Binding site

482

FAD; via carbonyl oxygen By similarity

Amino acid modifications

Modified residue

267

Phosphoserine By similarity

Modified residue

592

N6-acetyllysine By similarity

Cross-link

254

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Sequences

Sequence

Length

Mass (Da)

Tools

Q9JM53 [UniParc].

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

FASTA

612

66,723

        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' referencesShow '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, 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.
IPI	IPI00204118.
RefSeq	NP_112646.1. NM_031356.1.
UniGene	Rn.203165.
3D structure databases
ProteinModelPortal	Q9JM53.
SMR	Q9JM53. Positions 121-610.
ModBase	Search...
PTM databases
PhosphoSite	Q9JM53.
Proteomic databases
PaxDb	Q9JM53.
PRIDE	Q9JM53.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000008503; ENSRNOP00000008503; ENSRNOG00000006067.
GeneID	83533.
KEGG	rno:83533.
UCSC	RGD:620817. rat.
Organism-specific databases
CTD	9131.
RGD	620817. Aifm1.
Phylogenomic databases
eggNOG	COG0446.
GeneTree	ENSGT00530000063416.
HOGENOM	HOG000264253.
HOVERGEN	HBG053538.
InParanoid	Q9JM53.
KO	K04727.
OMA	KIGDFRT.
OrthoDB	EOG40S0FD.
Gene expression databases
Genevestigator	Q9JM53.
GermOnline	ENSRNOG00000006067. Rattus norvegicus.
Family and domain databases
Gene3D	3.30.390.30. 1 hit.
InterPro	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]
Pfam	PF00070. Pyr_redox. 1 hit. PF07992. Pyr_redox_2. 1 hit. [Graphical view]
PRINTS	PR00368. FADPNR.
SUPFAM	SSF55424. FAD/NAD-linked_reductase_dimer. 1 hit.
ProtoNet	Search...
Other
NextBio	616033.

Entry information

Entry name

AIFM1_RAT

Accession

Primary (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 3, 2013
This is version 101 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Sequences

References

Cross-references

Sequence databases

3D structure databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents