AIFM1
entrez
9131
canonical
uniprot
O95831
canonical
ensembl
ENSG00000156709
resolver
ensp
ENSP00000287295
resolver
ensp
ENSP00000431222
resolver
ensp
ENSP00000446113
resolver
ensp
ENSP00000502184
resolver
enst
ENST00000460436
resolver
genesymbol
AIFM1
resolver
genesymbol_syn
AIF
resolver
genesymbol_syn
PDCD8
resolver
hgnc
HGNC:8768
resolver
uniprot
A4QPB4
resolver
uniprot
B1ALN1
resolver
uniprot
B2RB08
resolver
uniprot
D3DTE9
resolver
uniprot
E9PMA0
resolver
uniprot
E9PRR0
resolver
uniprot
Q1L6K4
resolver
uniprot
Q1L6K6
resolver
uniprot
Q2QKE4
resolver
uniprot
Q5JUZ7
resolver
uniprot
Q6I9X6
resolver
uniprot
Q9Y3I3
resolver
uniprot
Q9Y3I4
resolver
uniprot_entry
AIFM1_HUMAN
resolver
uniprot_entry
E9PMA0_HUMAN
resolver
uniprot_sec
A4QPB4
resolver
uniprot_sec
B1ALN1
resolver
uniprot_sec
B2RB08
resolver
uniprot_sec
D3DTE9
resolver
uniprot_sec
E9PRR0
resolver
uniprot_sec
Q1L6K4
resolver
uniprot_sec
Q1L6K6
resolver
uniprot_sec
Q2QKE4
resolver
uniprot_sec
Q5JUZ7
resolver
uniprot_sec
Q6I9X6
resolver
uniprot_sec
Q9Y3I3
resolver
uniprot_sec
Q9Y3I4
resolver
amino_acid_sequence
MFRCGGLAAGALKQKLVPLVRTVCVRSPRQRNRLPGNLFQRWHVPLELQMTRQMASSGASGGKIDNSVLVLIVGLSTVGAGAYAYKTMKEDEKRYNERISGLGLTPEQKQKKAALSASEGEEVPQDKAPSHVPFLLIGGGTAAFAAARSIRARDPGARVLIVSEDPELPYMRPPLSKELWFSDDPNVTKTLRFKQWNGKERSIYFQPPSFYVSAQDLPHIENGGVAVLTGKKVVQLDVRDNMVKLNDGSQITYEKCLIATGGTPRSLSAIDRAGAEVKSRTTLFRKIGDFRSLEKISREVKSITIIGGGFLGSELACALGRKARALGTEVIQLFPEKGNMGKILPEYLSNWTMEKVRREGVKVMPNAIVQSVGVSSGKLLIKLKDGRKVETDHIVAAVGLEPNVELAKTGGLEIDSDFGGFRVNAELQARSNIWVAGDAACFYDIKLGRRRVEHHDHAVVSGRLAGENMTGAAKPYWHQSMFWSDLGPDVGYEAIGLVDSSLPTVGVFAKATAQDNPKSATEQSGTGIRSESETESEASEITIPPSTPAVPQAPVQGEDYGKGVIFYLRDKVVVGIVLWNIFNRMPIARKIIKDGEQHEDLNEVAKLFNIHED
uniprot
proteins
disease_involvement
DISEASE: 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:0000269|PubMed:20362274, ECO:0000269|PubMed:22019070, ECO:0000269|PubMed:25583628, ECO:0000269|PubMed:26004228, ECO:0000269|PubMed:26173962, ECO:0000269|PubMed:27178839}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Charcot-Marie-Tooth disease, X-linked recessive, 4, with or without cerebellar ataxia (CMTX4) [MIM:310490]: A neuromuscular disorder characterized by progressive sensorimotor axonal neuropathy, distal sensory impairment, difficulty walking due to peripheral neuropathy and/or cerebellar ataxia, and deafness due to auditory neuropathy. Additional features include cognitive impairment, cerebellar atrophy, dysarthria, abnormal extraocular movements, tremor, dysmetria and spasticity. The age at onset ranges from infancy to young adulthood. {ECO:0000269|PubMed:23217327, ECO:0000269|PubMed:26004228}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Deafness, X-linked, 5, with peripheral neuropathy (DFNX5) [MIM:300614]: A form of hearing loss characterized by absent or severely abnormal auditory brainstem response, abnormal middle ear reflexes, abnormal speech discrimination, loss of outer hair cell function, and cochlear nerve hypoplasia. DFNX5 patients manifest auditory neuropathy with childhood onset, associated with distal sensory impairment affecting the peripheral nervous system. {ECO:0000269|PubMed:25986071}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Spondyloepimetaphyseal dysplasia, X-linked, with hypomyelinating leukodystrophy (SEMDHL) [MIM:300232]: An X-linked recessive developmental disorder characterized by slowly progressive skeletal and neurologic abnormalities, including short stature, large and deformed joints, significant motor impairment, visual defects, and sometimes cognitive deficits. Affected individuals typically have normal early development in the first year or so of life, followed by development regression and the development of symptoms. Brain imaging shows white matter abnormalities consistent with hypomyelinating leukodystrophy. {ECO:0000269|PubMed:28842795}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
1.6.99.-
uniprot
proteins
function
FUNCTION: Functions both as NADH oxidoreductase and as regulator of apoptosis (PubMed:17094969, PubMed:20362274, PubMed:23217327, PubMed:33168626). 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:20362274). Release into the cytoplasm is mediated upon binding to poly-ADP-ribose chains (By similarity). The soluble form (AIFsol) found in the nucleus induces 'parthanatos' i.e. caspase-independent fragmentation of chromosomal DNA (PubMed:20362274). Binds to DNA in a sequence-independent manner (PubMed:27178839). Interacts with EIF3G, and thereby inhibits the EIF3 machinery and protein synthesis, and activates caspase-7 to amplify apoptosis (PubMed:17094969). Plays a critical role in caspase-independent, pyknotic cell death in hydrogen peroxide-exposed cells (PubMed:19418225). 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:26004228). {ECO:0000250|UniProtKB:Q9Z0X1, ECO:0000269|PubMed:17094969, ECO:0000269|PubMed:19418225, ECO:0000269|PubMed:20362274, ECO:0000269|PubMed:23217327, ECO:0000269|PubMed:26004228, ECO:0000269|PubMed:27178839, ECO:0000269|PubMed:33168626}.; FUNCTION: [Isoform 4]: Has NADH oxidoreductase activity. Does not induce nuclear apoptosis. {ECO:0000269|PubMed:16644725}.; FUNCTION: [Isoform 5]: Pro-apoptotic isoform. {ECO:0000269|PubMed:16365034}.
uniprot
proteins
mass_dalton
66901
uniprot
proteins
mutagenesis
MUTAGEN 196; /note="W->A: Increases protein dimerization at lower NADH levels."; /evidence="ECO:0000269|PubMed:27818101"; MUTAGEN 413..430; /note="EIDSDFGGFRVNAELQAR->AIDSDFGGFAVNAELQAA: Disrupts dimerization. Lower efficiency in stabilizing charge-transfer complexes upon coenzyme reduction."; /evidence="ECO:0000269|PubMed:24914854"; MUTAGEN 443..445; /note="YDI->ADA: Disrupts dimerization. Disrupts dimerization; when associated with A-477."; /evidence="ECO:0000269|PubMed:27818101"; MUTAGEN 454; /note="H->A: Allows dimerization in absence of NADH."; /evidence="ECO:0000269|PubMed:27818101"; MUTAGEN 477; /note="W->A: Disrupts dimerization; when associated with A-443--445-A."; /evidence="ECO:0000269|PubMed:27818101"; MUTAGEN 480; /note="S->A: Allows dimerization in absence of NADH."; /evidence="ECO:0000269|PubMed:27818101"; MUTAGEN 485; /note="D->A: Increases protein dimerization at lower NADH levels."; /evidence="ECO:0000269|PubMed:27818101"; MUTAGEN 529; /note="R->A: Increases protein dimerization at lower NADH levels."; /evidence="ECO:0000269|PubMed:27818101"; MUTAGEN 531; /note="E->A: Increases protein dimerization at lower NADH levels."; /evidence="ECO:0000269|PubMed:27818101"; MUTAGEN 533; /note="E->A: Increases protein dimerization at lower NADH levels."; /evidence="ECO:0000269|PubMed:27818101"; MUTAGEN 535; /note="E->A: Increases protein dimerization at lower NADH levels."; /evidence="ECO:0000269|PubMed:27818101
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:0000269|PubMed:15775970}.; PTM: Ubiquitination by XIAP/BIRC4 does not lead to proteasomal degradation. Ubiquitination at Lys-255 by XIAP/BIRC4 blocks its ability to bind DNA and induce chromatin degradation, thereby inhibiting its ability to induce cell death. {ECO:0000269|PubMed:17967870, ECO:0000269|PubMed:22103349}.
uniprot
proteins
protein_family
FAD-dependent oxidoreductase family
uniprot
proteins
pubmed
10913597
uniprot
proteins
pubmed
12198487
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15772651
uniprot
proteins
pubmed
15775970
uniprot
proteins
pubmed
16365034
uniprot
proteins
pubmed
16644725
uniprot
proteins
pubmed
17094969
uniprot
proteins
pubmed
17967870
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
19418225
uniprot
proteins
pubmed
20111043
uniprot
proteins
pubmed
20362274
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21364629
uniprot
proteins
pubmed
22019070
uniprot
proteins
pubmed
22103349
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23217327
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24914854
uniprot
proteins
pubmed
25583628
uniprot
proteins
pubmed
25934856
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
25986071
uniprot
proteins
pubmed
26004228
uniprot
proteins
pubmed
26173962
uniprot
proteins
pubmed
27178839
uniprot
proteins
pubmed
27818101
uniprot
proteins
pubmed
28842795
uniprot
proteins
pubmed
33168626
uniprot
proteins
pubmed
9989411
uniprot
proteins
sequence_length
613
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Mitochondrion intermembrane space {ECO:0000269|PubMed:15775970, ECO:0000269|PubMed:24914854, ECO:0000269|PubMed:26004228}. Mitochondrion inner membrane. Cytoplasm {ECO:0000269|PubMed:15775970, ECO:0000269|PubMed:33168626}. Nucleus {ECO:0000269|PubMed:15775970, ECO:0000269|PubMed:17094969, ECO:0000269|PubMed:33168626}. Cytoplasm, perinuclear region {ECO:0000269|PubMed:17094969}. 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 (PubMed:15775970). Release into the cytoplasm is mediated upon binding to poly-ADP-ribose chains (By similarity). Translocation into the nucleus is promoted by interaction with (auto-poly-ADP-ribosylated) processed form of PARP1 (PubMed:33168626). Colocalizes with EIF3G in the nucleus and perinuclear region (PubMed:17094969). {ECO:0000250|UniProtKB:Q9Z0X1, ECO:0000269|PubMed:15775970, ECO:0000269|PubMed:17094969, ECO:0000269|PubMed:33168626}.; SUBCELLULAR LOCATION: [Isoform 3]: Mitochondrion intermembrane space {ECO:0000269|PubMed:20111043}. Mitochondrion inner membrane {ECO:0000269|PubMed:20111043}. Note=Has a stronger membrane anchorage than isoform 1. {ECO:0000269|PubMed:20111043}.; SUBCELLULAR LOCATION: [Isoform 4]: Mitochondrion {ECO:0000269|PubMed:16644725}. Cytoplasm, cytosol {ECO:0000269|PubMed:16644725}. Note=In pro-apoptotic conditions, is released from mitochondria to cytosol in a calpain/cathepsin-dependent manner. {ECO:0000269|PubMed:16644725}.; SUBCELLULAR LOCATION: [Isoform 5]: Cytoplasm {ECO:0000269|PubMed:16365034}.
uniprot
proteins