Aifm2
entrez
71361
canonical
uniprot
Q8BUE4
canonical
ensembl
ENSMUSG00000020085
resolver
ensp
ENSMUSP00000070054
resolver
ensp
ENSMUSP00000078998
resolver
ensp
ENSMUSP00000097297
resolver
ensp
ENSMUSP00000101095
resolver
ensp
ENSMUSP00000215693
resolver
ensp
ENSMUSP00000215694
resolver
ensp
ENSMUSP00000215705
resolver
ensp
ENSMUSP00000215753
resolver
ensp
ENSMUSP00000215754
resolver
genesymbol
Aifm2
resolver
genesymbol_syn
Amid
resolver
uniprot
Q8CHZ2
resolver
uniprot_entry
FSP1_MOUSE
resolver
uniprot_sec
Q8CHZ2
resolver
activity_regulation
ACTIVITY REGULATION: The modification by 4-hydroxy-2-nonenal (HNE) adduction in mitochondria results in loss of the oxidoreductase activity and activation of a novel function in mitochondrial oxidative stress signaling (PubMed:26689472). NADH-dependent oxidoreductase activity in response to ferroptotic stress is supported by ALDH7A1, which generates membrane NADH required for AIFM2/FSP1 activity (By similarity). Inhibited by viFSP1, which targets the NAD(P)H-binding pocket (PubMed:37957306). {ECO:0000250|UniProtKB:Q9BRQ8, ECO:0000269|PubMed:26689472, ECO:0000269|PubMed:37957306}.
uniprot
proteins
amino_acid_sequence
MGSQVSVDTGAVHVVIVGGGFGGIAAASQLQALNVPFMLVDMKDSFHHNVAALRASVESGFAKKTFISYSATFKDNFRQGKVIGIDLKNRMVLLQGGEALPFSHLILATGSTGPFPGKFNEVSCQQAAIQAYEDMVKQIQRSQFIVVVGGGSAGVEMAAEIKTEYPEKEVTLIHSRVPLADKELLPCVRQEVKEILLRKGVQLLLSERVSNLEELPRNEYREYIKVETDKGTEVATNMVIVCNGIKINSSAYRSAFESRLASNGALKVNEFLQVEGYSNIYAIGDCADTKEPKMAYHAGLHANVAVANIVNSMKQRPLKAYKPGALTFLLSMGRNDGVGQISGFYVGRLMVRLAKSRDLLISTSWKTMRQSPP
uniprot
proteins
ec_number
1.6.5.-
uniprot
proteins
function
FUNCTION: A NAD(P)H-dependent oxidoreductase that acts as a key inhibitor of ferroptosis (PubMed:37957306). At the plasma membrane, catalyzes reduction of coenzyme Q/ubiquinone-10 to ubiquinol-10, a lipophilic radical-trapping antioxidant that prevents lipid oxidative damage and consequently ferroptosis (By similarity). Acts in parallel to GPX4 to suppress phospholipid peroxidation and ferroptosis (By similarity). This anti-ferroptotic function is independent of cellular glutathione levels (By similarity). Also acts as a potent radical-trapping antioxidant by mediating warfarin-resistant vitamin K reduction in the canonical vitamin K cycle: catalyzes NAD(P)H-dependent reduction of vitamin K (phylloquinone, menaquinone-4 and menadione) to hydroquinone forms (PubMed:35922516). Hydroquinones act as potent radical-trapping antioxidants inhibitor of phospholipid peroxidation and ferroptosis (PubMed:26689472). May play a role in mitochondrial stress signaling (PubMed:26689472). Upon oxidative stress, associates with the lipid peroxidation end product 4-hydroxy-2-nonenal (HNE) forming a lipid adduct devoid of oxidoreductase activity, which then translocates from mitochondria into the nucleus triggering DNA damage and cell death (PubMed:26689472). {ECO:0000250|UniProtKB:Q9BRQ8, ECO:0000269|PubMed:26689472, ECO:0000269|PubMed:35922516, ECO:0000269|PubMed:37957306}.
uniprot
proteins
mass_dalton
40635
uniprot
proteins
mutagenesis
MUTAGEN 174; /note="H->R: Impairs the NADH oxidoreductase activity. Impairs mitochondria to nucleus translocation. Confers protection to doxorubicin-induced cytotoxicity."; /evidence="ECO:0000269|PubMed:26689472"; MUTAGEN 187; /note="C->T: Decreases the NADH oxidoreductase activity. Has not effect on mitochondria to nucleus translocation."; /evidence="ECO:0000269|PubMed:26689472
uniprot
proteins
post_translational_modification
PTM: N-myristoylation at Gly-2 mediates the recruitment to lipid droplets and plasma membrane. {ECO:0000250|UniProtKB:Q9BRQ8}.; PTM: Acetylation at Lys-168 prevents AIFM2 ubiquitination and degradation, thereby inhibiting ferroptosis. KAT2B mediates acetylation at Lys-168, while HDAC3 removes it. {ECO:0000250|UniProtKB:Q9BRQ8}.; PTM: Ubiquitinated. AIFM2 undergoes 'Lys-29'-ubiquitination and proteasomal degradation, which is inhibited by acetylation at Lys-168. {ECO:0000250|UniProtKB:Q9BRQ8}.
uniprot
proteins
protein_family
FAD-dependent oxidoreductase family
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
16186796
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
26689472
uniprot
proteins
pubmed
35922516
uniprot
proteins
pubmed
37957306
uniprot
proteins
sequence_length
373
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Lipid droplet {ECO:0000250|UniProtKB:Q9BRQ8}. Cell membrane {ECO:0000250|UniProtKB:Q9BRQ8}; Lipid-anchor {ECO:0000305}. Cytoplasm {ECO:0000269|PubMed:26689472}. Mitochondrion membrane {ECO:0000269|PubMed:26689472}. Nucleus {ECO:0000269|PubMed:26689472}.
uniprot
proteins
transmembrane_region
TRANSMEM 7..27; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins