FSP1_BOVIN
ID FSP1_BOVIN Reviewed; 373 AA.
AC A5PJM4;
DT 24-MAR-2009, integrated into UniProtKB/Swiss-Prot.
DT 10-JUL-2007, sequence version 1.
DT 03-AUG-2022, entry version 89.
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 Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Ascending colon;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (JUN-2007) 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 -!- SUBUNIT: Interacts with importin subunits KPNA2 and IPO5; this
CC interaction likely mediates the translocation into the nucleus upon
CC oxidative stress. {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; BC142171; AAI42172.1; -; mRNA.
DR RefSeq; NP_001300960.1; NM_001314031.1.
DR RefSeq; XP_005226544.1; XM_005226487.3.
DR RefSeq; XP_005226545.1; XM_005226488.3.
DR RefSeq; XP_010818955.1; XM_010820653.2.
DR RefSeq; XP_010818956.1; XM_010820654.2.
DR AlphaFoldDB; A5PJM4; -.
DR SMR; A5PJM4; -.
DR STRING; 9913.ENSBTAP00000001550; -.
DR PaxDb; A5PJM4; -.
DR Ensembl; ENSBTAT00000001550; ENSBTAP00000001550; ENSBTAG00000001165.
DR Ensembl; ENSBTAT00000067758; ENSBTAP00000070646; ENSBTAG00000001165.
DR GeneID; 534217; -.
DR KEGG; bta:534217; -.
DR CTD; 84883; -.
DR VEuPathDB; HostDB:ENSBTAG00000001165; -.
DR VGNC; VGNC:25762; AIFM2.
DR eggNOG; KOG1336; Eukaryota.
DR GeneTree; ENSGT00390000004582; -.
DR HOGENOM; CLU_019845_2_1_1; -.
DR InParanoid; A5PJM4; -.
DR OMA; GDSFRQG; -.
DR OrthoDB; 1463391at2759; -.
DR TreeFam; TF329369; -.
DR Proteomes; UP000009136; Chromosome 28.
DR Bgee; ENSBTAG00000001165; Expressed in bone marrow and 105 other tissues.
DR ExpressionAtlas; A5PJM4; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
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; ISS:UniProtKB.
DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:Ensembl.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
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:0016655; F:oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor; IEA:Ensembl.
DR GO; GO:0008637; P:apoptotic mitochondrial changes; IBA:GO_Central.
DR GO; GO:0110076; P:negative regulation of ferroptosis; IEA:Ensembl.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IBA:GO_Central.
DR GO; GO:1900407; P:regulation of cellular response to oxidative stress; ISS:UniProtKB.
DR GO; GO:0006743; P:ubiquinone metabolic process; IEA:Ensembl.
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..373
FT /note="Ferroptosis suppressor protein 1"
FT /id="PRO_0000366943"
FT TRANSMEM 7..27
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 18..22
FT /ligand="6-hydroxy-FAD"
FT /ligand_id="ChEBI:CHEBI:60470"
FT /evidence="ECO:0000255"
FT BINDING 54
FT /ligand="6-hydroxy-FAD"
FT /ligand_id="ChEBI:CHEBI:60470"
FT /evidence="ECO:0000255"
FT BINDING 82
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 174
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 373 AA; 40477 MW; D74BCC97D3EC6FBE CRC64;
MGSQVSMDAG AVHVVIVGGG FGGIAAASQL QALNIPFVLV DMKDSFHHNV AALRASVESG
FAKKTFISYS VTFKENFRQG LVVEIDLKNQ TVLLEDGQAL PFSHLILATG STGLFPGKFN
QVSSQQMAIQ AYEDMVTQVQ RSQSIVVVGG GSAGVEMAAE IKTEYPEKEV TLIHSKMALA
DTELLPCVRQ EVKEILLRKG VQLLLSERVS NLEALPVNER RECIKVQTDK GTEVDANLVI
VCNGIKINSA AYRSAFGDRL ASNGALRVNE YLQVEGYSHI YAIGDCADVR EPKMAYHASL
HANVAVANIV NSMKQRPLKT YKPGSLTFLL AMGRNDGVGQ ISGFYVGRLM VRLAKSRDLL
VSTSWKTMKQ SPP
