InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: AIFM1

Summary

InnateDB Protein

IDBP-380906.5

Last Modified

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

Gene Symbol

AIFM1

Protein Name

apoptosis-inducing factor, mitochondrion-associated, 1

Synonyms

AIF; CMT2D; CMTX4; COWCK; COXPD6; NADMR; NAMSD; PDCD8;

Species

Homo sapiens

Ensembl Protein

ENSP00000402535

InnateDB Gene

IDBG-85972 (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. {ECO:0000269PubMed:17094969, ECO:0000269PubMed:19418225, ECO:0000269PubMed:20362274, ECO:0000269PubMed:23217327}.

Subcellular Localization

Mitochondrion intermembrane space. Mitochondrion inner membrane. Cytoplasm. Nucleus. Cytoplasm, perinuclear region. 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.Isoform 3: Mitochondrion intermembrane space {ECO:0000269PubMed:20111043}. Mitochondrion inner membrane {ECO:0000269PubMed:20111043}. Note=Has a stronger membrane anchorage than isoform 1.Isoform 5: Cytoplasm {ECO:0000269PubMed:16365034}.

Disease Associations

Combined oxidative phosphorylation deficiency 6 (COXPD6) [MIM:300816]: A mitochondrial disease resulting in a neurodegenerative disorder characterized by psychomotor delay, hypotonia, areflexia, muscle weakness and wasting. Some patients manifest prenatal ventriculomegaly and severe postnatal encephalomyopathy. {ECO:0000269PubMed:20362274, ECO:0000269PubMed:22019070}. Note=The disease is caused by mutations affecting the gene represented in this entry.Cowchock syndrome (COWCK) [MIM:310490]: An X-linked recessive neuromuscular disorder characterized by early childhood onset of a slowly progressive axonal sensorimotor neuropathy associated in some patients with sensorineural deafness and cognitive impairment. {ECO:0000269PubMed:23217327}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Detected in muscle and skin fibroblasts (at protein level). Isoform 5 is frequently down-regulated in human cancers. {ECO:0000269PubMed:16365034, ECO:0000269PubMed:23217327}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 72 experimentally validated interaction(s) in this database.
They are also associated with 5 interaction(s) predicted by orthology.

Experimentally validated
Total	72 [view]
Protein-Protein	70 [view]
Protein-DNA	2 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	5 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003677	DNA binding
GO:0005515	protein binding
GO:0009055	electron carrier activity
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

Biological Process

GO:0006308	DNA catabolic process
GO:0006915	apoptotic process
GO:0006919	activation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0030182	neuron differentiation
GO:0030261	chromosome condensation
GO:0032981	mitochondrial respiratory chain complex I assembly
GO:0043065	positive regulation of apoptotic process
GO:0045454	cell redox homeostasis
GO:0055114	oxidation-reduction process
GO:0070059	intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress

Cellular Component

GO:0005634	nucleus
GO:0005739	mitochondrion
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

InterPro

IPR013027 FAD-dependent pyridine nucleotide-disulphide oxidoreductase
IPR023753 Pyridine nucleotide-disulphide oxidoreductase, FAD/NAD(P)-binding domain

PFAM

PF07992

PRINTS

PR00368

PIRSF

SMART

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

O95831