InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Aifm1

Summary

InnateDB Protein

IDBP-143632.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Aifm1

Protein Name

apoptosis-inducing factor, mitochondrion-associated 1

Synonyms

AIF; AIFsh2; Hq; Pdcd8;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000041104

InnateDB Gene

IDBG-143630 (Aifm1)

Protein Structure

UniProt Annotation

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). {ECO:0000250}.

Subcellular Localization

Mitochondrion intermembrane space {ECO:0000269PubMed:9989411}. Mitochondrion inner membrane {ECO:0000250}. Cytoplasm {ECO:0000250}. Cytoplasm, perinuclear region {ECO:0000250}. Nucleus {ECO:0000269PubMed:9989411}. 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). {ECO:0000250}.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 25 experimentally validated interaction(s) in this database.
They are also associated with 49 interaction(s) predicted by orthology.

Experimentally validated
Total	25 [view]
Protein-Protein	25 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	49 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003677	DNA binding
GO:0004174	electron-transferring-flavoprotein dehydrogenase activity
GO:0005515	protein binding
GO:0016174	NAD(P)H oxidase activity
GO:0016491	oxidoreductase activity
GO:0016651	oxidoreductase activity, acting on NAD(P)H
GO:0046983	protein dimerization activity
GO:0050660	flavin adenine dinucleotide binding
GO:0071949	FAD binding

Biological Process

GO:0006915	apoptotic process
GO:0006919	activation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0006979	response to oxidative stress
GO:0008637	apoptotic mitochondrial changes
GO:0010942	positive regulation of cell death
GO:0030182	neuron differentiation
GO:0032981	mitochondrial respiratory chain complex I assembly
GO:0043065	positive regulation of apoptotic process
GO:0045454	cell redox homeostasis
GO:0051402	neuron apoptotic process
GO:0055114	oxidation-reduction process
GO:0070059	intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
GO:1902510	regulation of apoptotic DNA fragmentation

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005739	mitochondrion
GO:0005741	mitochondrial outer membrane
GO:0005743	mitochondrial inner membrane
GO:0005758	mitochondrial intermembrane space
GO:0005829	cytosol
GO:0048471	perinuclear region of cytoplasm

Protein Structure and Domains

PDB ID

MGI:1349419

InterPro

IPR001327 Pyridine nucleotide-disulphide oxidoreductase, NAD-binding domain
IPR013027 FAD-dependent pyridine nucleotide-disulphide oxidoreductase
IPR016156 FAD/NAD-linked reductase, dimerisation domain
IPR023753 Pyridine nucleotide-disulphide oxidoreductase, FAD/NAD(P)-binding domain

PFAM

PF00070
PF07992

PRINTS

PR00368

PIRSF

SMART

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

Q9Z0X1