FSP1_HUMAN
ID FSP1_HUMAN Reviewed; 373 AA.
AC Q9BRQ8; B3KXI0; Q63Z39;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Ferroptosis suppressor protein 1 {ECO:0000303|PubMed:31634899, ECO:0000303|PubMed:31634900};
DE Short=FSP1 {ECO:0000303|PubMed:31634899, ECO:0000303|PubMed:31634900};
DE EC=1.6.5.- {ECO:0000269|PubMed:31634899, ECO:0000269|PubMed:31634900};
DE AltName: Full=Apoptosis-inducing factor homologous mitochondrion-associated inducer of death {ECO:0000303|PubMed:11980907};
DE Short=AMID {ECO:0000303|PubMed:11980907};
DE AltName: Full=p53-responsive gene 3 protein {ECO:0000303|PubMed:12135761};
GN Name=AIFM2 {ECO:0000312|HGNC:HGNC:21411};
GN Synonyms=AMID, PRG3 {ECO:0000303|PubMed:12135761};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAL73229.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, INDUCTION, AND CAUTION.
RX PubMed=12135761; DOI=10.1016/s0014-5793(02)03049-1;
RA Ohiro Y., Garkavtsev I., Kobayashi S., Sreekumar K.R., Nantz R.,
RA Higashikubo B.T., Duffy S.L., Higashikubo R., Usheva A., Gius D., Kley N.,
RA Horikoshi N.;
RT "A novel p53-inducible apoptogenic gene, PRG3, encodes a homologue of the
RT apoptosis-inducing factor (AIF).";
RL FEBS Lett. 524:163-171(2002).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAM77596.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, AND CAUTION.
RX PubMed=11980907; DOI=10.1074/jbc.m202285200;
RA Wu M., Xu L.-G., Li X., Zhai Z., Shu H.-B.;
RT "AMID, an apoptosis-inducing factor-homologous mitochondrion-associated
RT protein, induces caspase-independent apoptosis.";
RL J. Biol. Chem. 277:25617-25623(2002).
RN [3] {ECO:0000305, ECO:0000312|EMBL:BAB55089.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Hippocampus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4] {ECO:0000305, ECO:0000312|EMBL:AL731540}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [5] {ECO:0000305, ECO:0000312|EMBL:CAH56481.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6] {ECO:0000305, ECO:0000312|EMBL:AAH06121.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Kidney {ECO:0000312|EMBL:AAH06121.1}, and
RC Lung {ECO:0000312|EMBL:AAH23601.1};
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 23-373 (ISOFORM 2).
RC TISSUE=Esophageal carcinoma;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [8] {ECO:0000305}
RP INDUCTION.
RX PubMed=15273740; DOI=10.1038/sj.onc.1207909;
RA Wu M., Xu L.-G., Su T., Tian Y., Zhai Z., Shu H.-B.;
RT "AMID is a p53-inducible gene downregulated in tumors.";
RL Oncogene 23:6815-6819(2004).
RN [9] {ECO:0000305}
RP FUNCTION, COFACTOR, AND CAUTION.
RX PubMed=15958387; DOI=10.1074/jbc.m414018200;
RA Marshall K.R., Gong M., Wodke L., Lamb J.H., Jones D.J., Farmer P.B.,
RA Scrutton N.S., Munro A.W.;
RT "The human apoptosis-inducing protein AMID is an oxidoreductase with a
RT modified flavin cofactor and DNA binding activity.";
RL J. Biol. Chem. 280:30735-30740(2005).
RN [10]
RP MYRISTOYLATION AT GLY-2.
RX PubMed=20213681; DOI=10.1002/pmic.200900783;
RA Suzuki T., Moriya K., Nagatoshi K., Ota Y., Ezure T., Ando E.,
RA Tsunasawa S., Utsumi T.;
RT "Strategy for comprehensive identification of human N-myristoylated
RT proteins using an insect cell-free protein synthesis system.";
RL Proteomics 10:1780-1793(2010).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP MYRISTOYLATION AT GLY-2, CLEAVAGE OF INITIATOR METHIONINE, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=25255805; DOI=10.1038/ncomms5919;
RA Thinon E., Serwa R.A., Broncel M., Brannigan J.A., Brassat U., Wright M.H.,
RA Heal W.P., Wilkinson A.J., Mann D.J., Tate E.W.;
RT "Global profiling of co- and post-translationally N-myristoylated proteomes
RT in human cells.";
RL Nat. Commun. 5:4919-4919(2014).
RN [13]
RP FUNCTION, SUBCELLULAR LOCATION, AND CAUTION.
RX PubMed=26689472; DOI=10.1016/j.freeradbiomed.2015.12.002;
RA Miriyala S., Thippakorn C., Chaiswing L., Xu Y., Noel T., Tovmasyan A.,
RA Batinic-Haberle I., Vander Kooi C.W., Chi W., Latif A.A., Panchatcharam M.,
RA Prachayasittikul V., Butterfield D.A., Vore M., Moscow J., St Clair D.K.;
RT "Novel role of 4-hydroxy-2-nonenal in AIFm2-mediated mitochondrial stress
RT signaling.";
RL Free Radic. Biol. Med. 91:68-80(2016).
RN [14]
RP FUNCTION, CATALYTIC ACTIVITY, MYRISTOYLATION AT GLY-2, MUTAGENESIS OF
RP GLY-2, AND CAUTION.
RX PubMed=31634899; DOI=10.1038/s41586-019-1707-0;
RA Doll S., Freitas F.P., Shah R., Aldrovandi M., da Silva M.C., Ingold I.,
RA Grocin A.G., Xavier da Silva T.N., Panzilius E., Scheel C., Mourao A.,
RA Buday K., Sato M., Wanninger J., Vignane T., Mohana V., Rehberg M.,
RA Flatley A., Schepers A., Kurz A., White D., Sauer M., Sattler M.,
RA Tate E.W., Schmitz W., Schulze A., O'Donnel V., Proneth B., Popowicz G.M.,
RA Pratt D., Angeli J.P.F., Conrad M.;
RT "FSP1 is a glutathione-independent ferroptosis suppressor.";
RL Nature 575:693-698(2019).
RN [15]
RP FUNCTION, CATALYTIC ACTIVITY, MYRISTOYLATION AT GLY-2, SUBCELLULAR
RP LOCATION, MUTAGENESIS OF GLU-156, AND CAUTION.
RX PubMed=31634900; DOI=10.1038/s41586-019-1705-2;
RA Bersuker K., Hendricks J., Li Z., Magtanong L., Ford B., Tang P.H.,
RA Roberts M.A., Tong B., Maimone T.J., Zoncu R., Bassik M.C., Nomura D.K.,
RA Dixon S.J., Olzmann J.A.;
RT "The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit
RT ferroptosis.";
RL Nature 575:688-692(2019).
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 (PubMed:31634899,
CC PubMed:31634900). May play a role in mitochondrial stress signaling.
CC Upon oxidative stress, associates with the lipid peroxidation end
CC product 4-hydroxy-2-nonenal (HNE) forming a lipid adduct devoid of
CC oxidoreductase activity, which then translocates from mitochondria into
CC the nucleus triggering DNA damage and cell death (PubMed:26689472).
CC Capable of DNA binding in a non-sequence specific way
CC (PubMed:15958387). {ECO:0000269|PubMed:15958387,
CC ECO:0000269|PubMed:26689472, ECO:0000269|PubMed:31634899,
CC ECO:0000269|PubMed:31634900}.
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:0000305|PubMed:31634899, ECO:0000305|PubMed:31634900};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61985;
CC Evidence={ECO:0000305|PubMed:31634899, ECO:0000305|PubMed:31634900};
CC -!- COFACTOR:
CC Name=6-hydroxy-FAD; Xref=ChEBI:CHEBI:60470;
CC Evidence={ECO:0000269|PubMed:15958387};
CC Note=Binds 6-hydroxy-FAD non-covalently. {ECO:0000269|PubMed:15958387};
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 -!- INTERACTION:
CC Q9BRQ8; Q8N129: CNPY4; NbExp=3; IntAct=EBI-3956936, EBI-723824;
CC Q9BRQ8; Q9BYV2: TRIM54; NbExp=3; IntAct=EBI-3956936, EBI-2130429;
CC Q9BRQ8; Q86WT6-2: TRIM69; NbExp=3; IntAct=EBI-3956936, EBI-11525489;
CC -!- SUBCELLULAR LOCATION: Lipid droplet {ECO:0000269|PubMed:31634900}. Cell
CC membrane {ECO:0000269|PubMed:31634900}; Lipid-anchor {ECO:0000305}.
CC Cytoplasm {ECO:0000269|PubMed:11980907, ECO:0000269|PubMed:12135761,
CC ECO:0000269|PubMed:26689472}. Mitochondrion membrane
CC {ECO:0000269|PubMed:11980907, ECO:0000269|PubMed:26689472}. Nucleus
CC {ECO:0000269|PubMed:26689472}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1 {ECO:0000269|PubMed:11980907, ECO:0000269|PubMed:12135761};
CC IsoId=Q9BRQ8-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:15489334};
CC IsoId=Q9BRQ8-2; Sequence=VSP_052047, VSP_052048;
CC -!- TISSUE SPECIFICITY: Detected in most normal tissues as two transcripts
CC of 1.8 and 4.0 kb in length, respectively. Highly expressed in heart,
CC moderately in liver and skeletal muscles, and expressed at low levels
CC in placenta, lung, kidney, and pancreas. Both transcripts expressed
CC following p53/TP53 induction. The shorter 1.8 kb transcript seems to be
CC the major transcript in EB1 colon cancer cells.
CC {ECO:0000269|PubMed:12135761}.
CC -!- INDUCTION: Expression detected at 4 hours after induction by p53/TP53.
CC Down-regulated in a wide range of human tumors.
CC {ECO:0000269|PubMed:12135761, ECO:0000269|PubMed:15273740}.
CC -!- PTM: N-myristoylation at Gly-2 mediates the recruitment to lipid
CC droplets and plasma membrane. {ECO:0000269|PubMed:31634900}.
CC -!- SIMILARITY: Belongs to the FAD-dependent oxidoreductase family.
CC {ECO:0000305}.
CC -!- CAUTION: Conflicting data exist on the pro-apoptotic function of the
CC protein. It was initially claimed that overexpression of FSP1 induces
CC caspase-independent apoptosis, but new evidence disputes this function.
CC {ECO:0000269|PubMed:11980907, ECO:0000269|PubMed:12135761,
CC ECO:0000269|PubMed:15958387, ECO:0000269|PubMed:26689472,
CC ECO:0000269|PubMed:31634899, ECO:0000269|PubMed:31634900}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/AIFM2ID41842ch10q22.html";
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DR EMBL; AF337957; AAL73229.1; -; mRNA.
DR EMBL; AF506757; AAM77596.1; -; mRNA.
DR EMBL; AK027403; BAB55089.1; -; mRNA.
DR EMBL; AK127353; BAG54492.1; -; mRNA.
DR EMBL; AL731540; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471083; EAW54376.1; -; Genomic_DNA.
DR EMBL; BC006121; AAH06121.1; -; mRNA.
DR EMBL; BC023601; AAH23601.1; -; mRNA.
DR EMBL; BX537621; CAH56481.1; -; mRNA.
DR CCDS; CCDS7297.1; -. [Q9BRQ8-1]
DR RefSeq; NP_001185625.1; NM_001198696.1. [Q9BRQ8-1]
DR RefSeq; NP_116186.1; NM_032797.5. [Q9BRQ8-1]
DR AlphaFoldDB; Q9BRQ8; -.
DR SMR; Q9BRQ8; -.
DR BioGRID; 124325; 26.
DR ELM; Q9BRQ8; -.
DR IntAct; Q9BRQ8; 9.
DR STRING; 9606.ENSP00000478931; -.
DR iPTMnet; Q9BRQ8; -.
DR PhosphoSitePlus; Q9BRQ8; -.
DR BioMuta; AIFM2; -.
DR DMDM; 74752283; -.
DR EPD; Q9BRQ8; -.
DR jPOST; Q9BRQ8; -.
DR MassIVE; Q9BRQ8; -.
DR MaxQB; Q9BRQ8; -.
DR PaxDb; Q9BRQ8; -.
DR PeptideAtlas; Q9BRQ8; -.
DR PRIDE; Q9BRQ8; -.
DR ProteomicsDB; 78808; -. [Q9BRQ8-1]
DR ProteomicsDB; 78809; -. [Q9BRQ8-2]
DR Antibodypedia; 14832; 295 antibodies from 37 providers.
DR DNASU; 84883; -.
DR Ensembl; ENST00000307864.3; ENSP00000312370.1; ENSG00000042286.15. [Q9BRQ8-1]
DR Ensembl; ENST00000373248.5; ENSP00000362345.1; ENSG00000042286.15. [Q9BRQ8-1]
DR Ensembl; ENST00000613322.4; ENSP00000478931.1; ENSG00000042286.15. [Q9BRQ8-1]
DR GeneID; 84883; -.
DR KEGG; hsa:84883; -.
DR MANE-Select; ENST00000307864.3; ENSP00000312370.1; NM_032797.6; NP_116186.1.
DR UCSC; uc001jqp.3; human. [Q9BRQ8-1]
DR CTD; 84883; -.
DR DisGeNET; 84883; -.
DR GeneCards; AIFM2; -.
DR HGNC; HGNC:21411; AIFM2.
DR HPA; ENSG00000042286; Tissue enhanced (adipose).
DR MIM; 605159; gene.
DR neXtProt; NX_Q9BRQ8; -.
DR OpenTargets; ENSG00000042286; -.
DR PharmGKB; PA162376150; -.
DR VEuPathDB; HostDB:ENSG00000042286; -.
DR eggNOG; KOG1336; Eukaryota.
DR GeneTree; ENSGT00390000004582; -.
DR HOGENOM; CLU_019845_2_1_1; -.
DR InParanoid; Q9BRQ8; -.
DR OMA; GDSFRQG; -.
DR OrthoDB; 1463391at2759; -.
DR PhylomeDB; Q9BRQ8; -.
DR TreeFam; TF329369; -.
DR BRENDA; 7.1.1.2; 2681.
DR PathwayCommons; Q9BRQ8; -.
DR Reactome; R-HSA-6803204; TP53 Regulates Transcription of Genes Involved in Cytochrome C Release.
DR SignaLink; Q9BRQ8; -.
DR SIGNOR; Q9BRQ8; -.
DR BioGRID-ORCS; 84883; 20 hits in 1069 CRISPR screens.
DR ChiTaRS; AIFM2; human.
DR GeneWiki; AIFM2; -.
DR GenomeRNAi; 84883; -.
DR Pharos; Q9BRQ8; Tbio.
DR PRO; PR:Q9BRQ8; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q9BRQ8; protein.
DR Bgee; ENSG00000042286; Expressed in adipose tissue and 146 other tissues.
DR Genevisible; Q9BRQ8; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005811; C:lipid droplet; IDA:UniProtKB.
DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0004174; F:electron-transferring-flavoprotein dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IDA:UniProtKB.
DR GO; GO:0016655; F:oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor; IDA:UniProtKB.
DR GO; GO:0008637; P:apoptotic mitochondrial changes; IDA:MGI.
DR GO; GO:0110076; P:negative regulation of ferroptosis; IMP:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:1900407; P:regulation of cellular response to oxidative stress; ISS:UniProtKB.
DR GO; GO:0006743; P:ubiquinone metabolic process; IDA:UniProtKB.
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 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cytoplasm; DNA-binding; FAD;
KW Flavoprotein; Lipid droplet; Lipoprotein; Membrane; Mitochondrion;
KW Myristate; Nucleus; Oxidoreductase; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:25255805"
FT CHAIN 2..373
FT /note="Ferroptosis suppressor protein 1"
FT /id="PRO_0000238922"
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:0000269|PubMed:20213681,
FT ECO:0000269|PubMed:25255805, ECO:0000269|PubMed:31634899,
FT ECO:0000269|PubMed:31634900"
FT VAR_SEQ 99..138
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:17974005"
FT /id="VSP_052047"
FT VAR_SEQ 206
FT /note="S -> SLLG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:17974005"
FT /id="VSP_052048"
FT VARIANT 135
FT /note="M -> T (in dbSNP:rs10999147)"
FT /id="VAR_050651"
FT VARIANT 288
FT /note="D -> N (in dbSNP:rs2271694)"
FT /id="VAR_050652"
FT MUTAGEN 2
FT /note="G->A: Impairs N-myristoylation and ferroptosis
FT suppression."
FT /evidence="ECO:0000269|PubMed:31634899"
FT MUTAGEN 156
FT /note="E->A: Impairs the reductase activity toward coenzyme
FT Q1/ubiquinone-1. Impairs ferroptosis suppression."
FT /evidence="ECO:0000269|PubMed:31634900"
SQ SEQUENCE 373 AA; 40527 MW; 47F2E6F682D4C060 CRC64;
MGSQVSVESG ALHVVIVGGG FGGIAAASQL QALNVPFMLV DMKDSFHHNV AALRASVETG
FAKKTFISYS VTFKDNFRQG LVVGIDLKNQ MVLLQGGEAL PFSHLILATG STGPFPGKFN
EVSSQQAAIQ AYEDMVRQVQ RSRFIVVVGG GSAGVEMAAE IKTEYPEKEV TLIHSQVALA
DKELLPSVRQ EVKEILLRKG VQLLLSERVS NLEELPLNEY REYIKVQTDK GTEVATNLVI
LCTGIKINSS AYRKAFESRL ASSGALRVNE HLQVEGHSNV YAIGDCADVR TPKMAYLAGL
HANIAVANIV NSVKQRPLQA YKPGALTFLL SMGRNDGVGQ ISGFYVGRLM VRLTKSRDLF
VSTSWKTMRQ SPP
