Aifm1
entrez
26926
canonical
uniprot
Q9Z0X1
canonical
ensembl
ENSMUSG00000036932
resolver
ensp
ENSMUSP00000041104
resolver
ensp
ENSMUSP00000110595
resolver
enst
ENSMUST00000114945
resolver
genesymbol
Aifm1
resolver
genesymbol_syn
Aif
resolver
genesymbol_syn
Pdcd8
resolver
uniprot
B1AU25
resolver
uniprot
Q1L6K5
resolver
uniprot_entry
AIFM1_MOUSE
resolver
uniprot_entry
B1AU25_MOUSE
resolver
uniprot_sec
Q1L6K5
resolver
amino_acid_sequence
MFRCGGLAGAFKQKLVPLVRTVYVQRPKQRNRLPGNLFQQWRVPLELQMARQMASSGSSGGKMDNSVLVLIVGLSTIGAGAYAYKTIKEDQKRYNERVMGLGLSPEEKQRRAIASATEGGSVPQIRAPSHVPFLLIGGGTAAFAAARSIRARDPGARVLIVSEDPELPYMRPPLSKELWFSDDPNVTKTLQFRQWNGKERSIYFQPPSFYVSAQDLPNIENGGVAVLTGKKVVHLDVRGNMVKLNDGSQITFEKCLIATGGTPRSLSAIDRAGAEVKSRTTLFRKIGDFRALEKISREVKSITVIGGGFLGSELACALGRKSQASGIEVIQLFPEKGNMGKILPQYLSNWTMEKVKREGVKVMPNAIVQSVGVSGGRLLIKLKDGRKVETDHIVTAVGLEPNVELAKTGGLEIDSDFGGFRVNAELQARSNIWVAGDAACFYDIKLGRRRVEHHDHAVVSGRLAGENMTGAAKPYWHQSMFWSDLGPDVGYEAIGLVDSSLPTVGVFAKATAQDNPKSATEQSGTGIRSESETESEASEITIPPSAPAVPQVPVEGEDYGKGVIFYLRDKVVVGIVLWNVFNRMPIARKIIKDGEQHEDLNEVAKLFNIHED
uniprot
proteins
ec_number
1.6.99.-
uniprot
proteins
function
FUNCTION: Functions both as NADH oxidoreductase and as regulator of apoptosis (By similarity). 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 (PubMed:12114629, PubMed:21467298, PubMed:9989411). Release into the cytoplasm is mediated upon binding to poly-ADP-ribose chains (PubMed:21467298). The soluble form (AIFsol) found in the nucleus induces 'parthanatos' i.e. caspase-independent fragmentation of chromosomal DNA (PubMed:12114629, PubMed:21467298, PubMed:9989411). Binds to DNA in a sequence-independent manner (PubMed:21467298). Interacts with EIF3G, and thereby inhibits the EIF3 machinery and protein synthesis, and activates caspase-7 to amplify apoptosis (By similarity). Plays a critical role in caspase-independent, pyknotic cell death in hydrogen peroxide-exposed cells (By similarity). In contrast, participates in normal mitochondrial metabolism. Plays an important role in the regulation of respiratory chain biogenesis by interacting with CHCHD4 and controlling CHCHD4 mitochondrial import (PubMed:19447115). {ECO:0000250|UniProtKB:O95831, ECO:0000269|PubMed:12114629, ECO:0000269|PubMed:19447115, ECO:0000269|PubMed:21467298, ECO:0000269|PubMed:9989411}.
uniprot
proteins
mass_dalton
66765
uniprot
proteins
mutagenesis
MUTAGEN 176; /note="K->A: Increases catalytic efficiency."; /evidence="ECO:0000269|PubMed:11967568"; MUTAGEN 195; /note="W->A: Increases redox potential, reacts faster to NADH and forms two-fold longer-lived CTC."; /evidence="ECO:0000269|PubMed:19447115"; MUTAGEN 254; /note="K->A: Abolished DNA-binding without affecting binding to poly-ADP-ribose chains; when associated with A-264."; /evidence="ECO:0000269|PubMed:21467298"; MUTAGEN 264; /note="R->A: Abolished DNA-binding without affecting binding to poly-ADP-ribose chains; when associated with A-254."; /evidence="ECO:0000269|PubMed:21467298"; MUTAGEN 313; /note="E->A: Increases catalytic efficiency 30-fold. Increases affinity for NADH 20-fold."; /evidence="ECO:0000269|PubMed:11967568"; MUTAGEN 588..592; /note="RKIIK->AAIIA: Abolished binding to poly-ADP-ribose chains, preventing induction of parthanatos."; /evidence="ECO:0000269|PubMed:21467298
uniprot
proteins
post_translational_modification
PTM: 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. {ECO:0000250|UniProtKB:O95831}.; PTM: 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. {ECO:0000250|UniProtKB:O95831}.
uniprot
proteins
protein_family
FAD-dependent oxidoreductase family
uniprot
proteins
pubmed
11967568
uniprot
proteins
pubmed
12114629
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16644725
uniprot
proteins
pubmed
19447115
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
21467298
uniprot
proteins
pubmed
23576753
uniprot
proteins
pubmed
23806337
uniprot
proteins
pubmed
26004228
uniprot
proteins
pubmed
30830864
uniprot
proteins
pubmed
9989411
uniprot
proteins
sequence_length
612
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Mitochondrion intermembrane space {ECO:0000269|PubMed:9989411}. Mitochondrion inner membrane {ECO:0000269|PubMed:30830864}. Cytoplasm {ECO:0000269|PubMed:21467298}. Nucleus {ECO:0000269|PubMed:12114629}. Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:O95831}. 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) (By similarity). During apoptosis, further proteolytic processing leads to a mature form, which is confined to the mitochondrial IMS in a soluble form (AIFsol) (By similarity). AIFsol is released to the cytoplasm in response to specific death signals, and translocated to the nucleus, where it induces nuclear apoptosis (PubMed:12114629). Release into the cytoplasm is mediated upon binding to poly-ADP-ribose chains (PubMed:21467298). Translocation into the nucleus is promoted by interaction with (auto-poly-ADP-ribosylated) processed form of PARP1 (By similarity). Colocalizes with EIF3G in the nucleus and perinuclear region. {ECO:0000250|UniProtKB:O95831, ECO:0000269|PubMed:12114629}.; SUBCELLULAR LOCATION: [Isoform 2]: Mitochondrion {ECO:0000269|PubMed:16644725}. Cytoplasm, cytosol {ECO:0000250|UniProtKB:O95831}. Note=In pro-apoptotic conditions, is released from mitochondria to cytosol in a calpain/cathepsin-dependent manner. {ECO:0000250|UniProtKB:O95831}.
uniprot
proteins