FSP1_TAEGU
ID FSP1_TAEGU Reviewed; 373 AA.
AC B5FXE5;
DT 24-MAR-2009, integrated into UniProtKB/Swiss-Prot.
DT 14-OCT-2008, sequence version 1.
DT 03-AUG-2022, entry version 54.
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 Taeniopygia guttata (Zebra finch) (Poephila guttata).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Passeriformes; Passeroidea; Estrildidae;
OC Estrildinae; Taeniopygia.
OX NCBI_TaxID=59729;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=17018643; DOI=10.1073/pnas.0607098103;
RA Wada K., Howard J.T., McConnell P., Whitney O., Lints T., Rivas M.V.,
RA Horita H., Patterson M.A., White S.A., Scharff C., Haesler S., Zhao S.,
RA Sakaguchi H., Hagiwara M., Shiraki T., Hirozane-Kishikawa T., Skene P.,
RA Hayashizaki Y., Carninci P., Jarvis E.D.;
RT "A molecular neuroethological approach for identifying and characterizing a
RT cascade of behaviorally regulated genes.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:15212-15217(2006).
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; DQ213309; ACH43706.1; -; mRNA.
DR RefSeq; NP_001232472.1; NM_001245543.1.
DR AlphaFoldDB; B5FXE5; -.
DR SMR; B5FXE5; -.
DR STRING; 59729.ENSTGUP00000004247; -.
DR GeneID; 100190613; -.
DR KEGG; tgu:100190613; -.
DR CTD; 84883; -.
DR InParanoid; B5FXE5; -.
DR OrthoDB; 1463391at2759; -.
DR Proteomes; UP000007754; Unplaced.
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: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:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
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_0000366944"
FT TRANSMEM 13..29
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 284
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 373 AA; 40394 MW; CC8BEBD12060C5EB CRC64;
MGSRLSLDGS VRVVVVGGGF GGTAAASLLK SWAVPFVLVD VRDAFHHNVA ALRAAVESGF
AKKTFISYSV TFGDSFRQGK VVAIDPGRQQ VVLSDGEELH YSHLILATGS DGPFPGKFNQ
VIDMESAIQT YEDMVKEIEK SQRILVVGGG AAGVEMAAEI KTEYPGKEII LIHSKTALAD
VELLPSVRQV VKEILLRKGV RLLLSEKVSD IENLRPNQFQ KDMVVRTEKG TEVVVDMVVL
CTGIKINSSA YAAAFGDKMA SDGALKVNKH LQLEGYENIY AIGDCADLKE PKMAYHAGLH
ANVVVTNIIN SLTQKPLKTY EPGSLTFLLS MGRNDGVGQV NGYYVGRLLV TIAKSRDLFV
SKSWRTMGQT MPS
