FSP1_XENTR
ID FSP1_XENTR Reviewed; 374 AA.
AC B4F6I3;
DT 24-MAR-2009, integrated into UniProtKB/Swiss-Prot.
DT 23-SEP-2008, sequence version 1.
DT 03-AUG-2022, entry version 74.
DE RecName: Full=Ferroptosis suppressor protein 1 {ECO:0000250|UniProtKB:Q9BRQ8};
DE Short=FSP1 {ECO:0000250|UniProtKB:Q9BRQ8};
DE EC=1.6.5.- {ECO:0000250|UniProtKB:Q9BRQ8};
DE AltName: Full=Apoptosis-inducing factor homologous mitochondrion-associated inducer of death;
DE Short=AMID;
DE AltName: Full=p53-responsive gene 3 protein;
GN Name=aifm2;
OS Xenopus tropicalis (Western clawed frog) (Silurana tropicalis).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Silurana.
OX NCBI_TaxID=8364;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (JUL-2008) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: A NAD(P)H-dependent oxidoreductase involved in cellular
CC oxidative stress response. At the plasma membrane, catalyzes reduction
CC of coenzyme Q/ubiquinone-10 to ubiquinol-10, a lipophilic radical-
CC trapping antioxidant that prevents lipid oxidative damage and
CC consequently ferroptosis. Cooperates with GPX4 to suppress phospholipid
CC peroxidation and ferroptosis. This anti-ferroptotic function is
CC independent of cellular glutathione levels. May play a role in
CC mitochondrial stress signaling. Upon oxidative stress, associates with
CC the lipid peroxidation end product 4-hydroxy-2-nonenal (HNE) forming a
CC lipid adduct devoid of oxidoreductase activity, which then translocates
CC from mitochondria into the nucleus triggering DNA damage and cell
CC death. Capable of DNA binding in a non-sequence specific way.
CC {ECO:0000250|UniProtKB:Q9BRQ8}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + NADH + ubiquinone-10 = NAD(+) + ubiquinol-10;
CC Xref=Rhea:RHEA:61984, ChEBI:CHEBI:15378, ChEBI:CHEBI:46245,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:64183;
CC Evidence={ECO:0000250|UniProtKB:Q9BRQ8};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61985;
CC Evidence={ECO:0000250|UniProtKB:Q9BRQ8};
CC -!- COFACTOR:
CC Name=6-hydroxy-FAD; Xref=ChEBI:CHEBI:60470;
CC Evidence={ECO:0000250|UniProtKB:Q9BRQ8};
CC Note=Binds 6-hydroxy-FAD non-covalently.
CC {ECO:0000250|UniProtKB:Q9BRQ8};
CC -!- ACTIVITY REGULATION: The modification by 4-hydroxy-2-nonenal (HNE)
CC adduction in mitochondria results in loss of the oxidoreductase
CC activity and activation of a novel function in mitochondrial oxidative
CC stress signaling. {ECO:0000250|UniProtKB:Q8BUE4}.
CC -!- SUBCELLULAR LOCATION: Lipid droplet {ECO:0000250|UniProtKB:Q9BRQ8}.
CC Cell membrane {ECO:0000250|UniProtKB:Q9BRQ8}; Lipid-anchor
CC {ECO:0000305}. Cytoplasm {ECO:0000250|UniProtKB:Q9BRQ8}. Mitochondrion
CC membrane {ECO:0000250|UniProtKB:Q9BRQ8}. Nucleus
CC {ECO:0000250|UniProtKB:Q9BRQ8}.
CC -!- PTM: N-myristoylation at Gly-2 mediates the recruitment to lipid
CC droplets and plasma membrane. {ECO:0000250|UniProtKB:Q9BRQ8}.
CC -!- SIMILARITY: Belongs to the FAD-dependent oxidoreductase family.
CC {ECO:0000305}.
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DR EMBL; BC167890; AAI67890.1; -; mRNA.
DR RefSeq; NP_001135491.1; NM_001142019.1.
DR RefSeq; XP_017950783.1; XM_018095294.1.
DR AlphaFoldDB; B4F6I3; -.
DR SMR; B4F6I3; -.
DR STRING; 8364.ENSXETP00000037399; -.
DR PaxDb; B4F6I3; -.
DR GeneID; 100216030; -.
DR KEGG; xtr:100216030; -.
DR CTD; 84883; -.
DR Xenbase; XB-GENE-1003376; aifm2.
DR eggNOG; KOG1336; Eukaryota.
DR HOGENOM; CLU_019845_2_1_1; -.
DR InParanoid; B4F6I3; -.
DR OMA; PIPFKQS; -.
DR OrthoDB; 1463391at2759; -.
DR PhylomeDB; B4F6I3; -.
DR TreeFam; TF329369; -.
DR Proteomes; UP000008143; Chromosome 7.
DR Proteomes; UP000790000; Unplaced.
DR Bgee; ENSXETG00000017152; Expressed in embryo and 11 other tissues.
DR ExpressionAtlas; B4F6I3; baseline.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005811; C:lipid droplet; IEA:UniProtKB-SubCell.
DR GO; GO:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0004174; F:electron-transferring-flavoprotein dehydrogenase activity; IBA:GO_Central.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IBA:GO_Central.
DR GO; GO:0008637; P:apoptotic mitochondrial changes; IBA:GO_Central.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IBA:GO_Central.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR023753; FAD/NAD-binding_dom.
DR Pfam; PF07992; Pyr_redox_2; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 2: Evidence at transcript level;
KW Apoptosis; Cell membrane; Cytoplasm; DNA-binding; FAD; Flavoprotein;
KW Lipid droplet; Lipoprotein; Membrane; Mitochondrion; Myristate; Nucleus;
KW Oxidoreductase; Reference proteome; Transmembrane; Transmembrane helix.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q9BRQ8"
FT CHAIN 2..374
FT /note="Ferroptosis suppressor protein 1"
FT /id="PRO_0000366946"
FT TRANSMEM 13..35
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 17..21
FT /ligand="6-hydroxy-FAD"
FT /ligand_id="ChEBI:CHEBI:60470"
FT /evidence="ECO:0000255"
FT BINDING 53
FT /ligand="6-hydroxy-FAD"
FT /ligand_id="ChEBI:CHEBI:60470"
FT /evidence="ECO:0000255"
FT BINDING 81
FT /ligand="6-hydroxy-FAD"
FT /ligand_id="ChEBI:CHEBI:60470"
FT /evidence="ECO:0000255"
FT BINDING 285
FT /ligand="6-hydroxy-FAD"
FT /ligand_id="ChEBI:CHEBI:60470"
FT /evidence="ECO:0000255"
FT SITE 173
FT /note="4-hydroxy-2-nonenal adduction"
FT /evidence="ECO:0000250|UniProtKB:Q8BUE4"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000250|UniProtKB:Q9BRQ8"
SQ SEQUENCE 374 AA; 40580 MW; FC8D517B1B3B4687 CRC64;
MGSKVSVEES VRVVIVGGGF AGIAAATQLK SFGIPFVLVD LKDAFHHNVA ALRASVESGF
ARKTFISYKD TFQDNFIQGK VVGINLQTQR VILESNEELQ FSHLIIATGS NGPFPGKINN
VISKDQAIQV YEDLVKEIQK AKHVVVVGGG SAGVEMAAEV KTDYPEKEVT LVHSKVALAD
VQLQPKVRRT VKEILLSKGV RLILAQKVTN LDQVTSNVAQ ENTVLQLDKN SEVVTCDLVL
CCTGYKISSS SYSSAFGDKL AEDGALIVND YLQVQGHANV YAVGDCAYIN EPKMAYYAGI
HARVAATNVR NSLIGKSLKT YKPGALSMLL SMGRNDGVGQ FNGCYLGRFF VTMAKSRDIF
VSKSWKEMGQ TMPR
