UniProtKB - Q9BRQ8 (FSP1_HUMAN)
Ferroptosis suppressor protein 1
AIFM2
Functioni
A NAD(P)H-dependent oxidoreductase involved in cellular oxidative stress response. 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. Cooperates with GPX4 to suppress phospholipid peroxidation and ferroptosis. This anti-ferroptotic function is independent of cellular glutathione levels (PubMed:31634899, PubMed:31634900).
May play a role in mitochondrial stress signaling. 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).
Capable of DNA binding in a non-sequence specific way (PubMed:15958387).
4 PublicationsCaution
Catalytic activityi
- This reaction proceeds in the forward2 Publications direction.
Cofactori
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 54 | 6-hydroxy-FADSequence analysis | 1 | |
Binding sitei | 82 | 6-hydroxy-FAD; via amide nitrogen and carbonyl oxygenSequence analysis | 1 | |
Sitei | 174 | 4-hydroxy-2-nonenal adductionBy similarity | 1 | |
Binding sitei | 285 | 6-hydroxy-FADSequence analysis | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 18 – 22 | 6-hydroxy-FADSequence analysis | 5 |
GO - Molecular functioni
- DNA binding Source: UniProtKB
- electron-transferring-flavoprotein dehydrogenase activity Source: UniProtKB
- flavin adenine dinucleotide binding Source: UniProtKB
- oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor Source: UniProtKB
GO - Biological processi
- apoptotic mitochondrial changes Source: MGI
- negative regulation of ferroptosis Source: UniProtKB
- positive regulation of apoptotic process Source: UniProtKB
- regulation of cellular response to oxidative stress Source: UniProtKB
- ubiquinone metabolic process Source: UniProtKB
Keywordsi
Molecular function | DNA-binding, Oxidoreductase |
Ligand | FAD, Flavoprotein |
Enzyme and pathway databases
BRENDAi | 7.1.1.2, 2681 |
PathwayCommonsi | Q9BRQ8 |
Reactomei | R-HSA-6803204, TP53 Regulates Transcription of Genes Involved in Cytochrome C Release |
SignaLinki | Q9BRQ8 |
SIGNORi | Q9BRQ8 |
Names & Taxonomyi
Protein namesi | Recommended name: Ferroptosis suppressor protein 12 Publications (EC:1.6.5.-2 Publications)Short name: FSP12 Publications Alternative name(s): Apoptosis-inducing factor homologous mitochondrion-associated inducer of death1 Publication Short name: AMID1 Publication p53-responsive gene 3 protein1 Publication |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:21411, AIFM2 |
MIMi | 605159, gene |
neXtProti | NX_Q9BRQ8 |
VEuPathDBi | HostDB:ENSG00000042286 |
Subcellular locationi
Mitochondrion
- Mitochondrion membrane 2 Publications
Plasma membrane
- Cell membrane 1 Publication; Lipid-anchor Curated
Nucleus
- Nucleus 1 Publication
Cytoplasm and Cytosol
- Cytoplasm 3 Publications
Other locations
- Lipid droplet 1 Publication
Cytosol
- cytosol Source: UniProtKB
Extracellular region or secreted
- extracellular space Source: UniProtKB
Mitochondrion
- mitochondrial outer membrane Source: UniProtKB
- mitochondrion Source: MGI
Nucleus
- nucleus Source: UniProtKB
Plasma Membrane
- plasma membrane Source: UniProtKB
Other locations
- cytoplasm Source: MGI
- integral component of membrane Source: UniProtKB-KW
- lipid droplet Source: UniProtKB
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transmembranei | 7 – 27 | HelicalSequence analysisAdd BLAST | 21 |
Keywords - Cellular componenti
Cell membrane, Cytoplasm, Lipid droplet, Membrane, Mitochondrion, NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 2 | G → A: Impairs N-myristoylation and ferroptosis suppression. 1 Publication | 1 | |
Mutagenesisi | 156 | E → A: Impairs the reductase activity toward coenzyme Q1/ubiquinone-1. Impairs ferroptosis suppression. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 84883 |
OpenTargetsi | ENSG00000042286 |
PharmGKBi | PA162376150 |
Miscellaneous databases
Pharosi | Q9BRQ8, Tbio |
Genetic variation databases
BioMutai | AIFM2 |
DMDMi | 74752283 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | Removed1 Publication | |||
ChainiPRO_0000238922 | 2 – 373 | Ferroptosis suppressor protein 1Add BLAST | 372 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Lipidationi | 2 | N-myristoyl glycine4 Publications | 1 |
Post-translational modificationi
Keywords - PTMi
Lipoprotein, MyristateProteomic databases
EPDi | Q9BRQ8 |
jPOSTi | Q9BRQ8 |
MassIVEi | Q9BRQ8 |
MaxQBi | Q9BRQ8 |
PaxDbi | Q9BRQ8 |
PeptideAtlasi | Q9BRQ8 |
PRIDEi | Q9BRQ8 |
ProteomicsDBi | 78808 [Q9BRQ8-1] 78809 [Q9BRQ8-2] |
PTM databases
iPTMneti | Q9BRQ8 |
PhosphoSitePlusi | Q9BRQ8 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSG00000042286, Expressed in adipose tissue of abdominal region and 181 other tissues |
Genevisiblei | Q9BRQ8, HS |
Organism-specific databases
HPAi | ENSG00000042286, Tissue enhanced (adipose) |
Interactioni
Subunit structurei
Interacts with importin subunits KPNA2 and IPO5; this interaction likely mediates the translocation into the nucleus upon oxidative stress.
By similarityBinary interactionsi
Q9BRQ8
With | #Exp. | IntAct |
---|---|---|
CNPY4 [Q8N129] | 3 | EBI-3956936,EBI-723824 |
TRIM54 [Q9BYV2] | 3 | EBI-3956936,EBI-2130429 |
TRIM69 - isoform 2 [Q86WT6-2] | 3 | EBI-3956936,EBI-11525489 |
Protein-protein interaction databases
BioGRIDi | 124325, 25 interactors |
ELMi | Q9BRQ8 |
IntActi | Q9BRQ8, 9 interactors |
STRINGi | 9606.ENSP00000478931 |
Miscellaneous databases
RNActi | Q9BRQ8, protein |
Family & Domainsi
Sequence similaritiesi
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG1336, Eukaryota |
GeneTreei | ENSGT00390000004582 |
HOGENOMi | CLU_019845_2_1_1 |
InParanoidi | Q9BRQ8 |
OMAi | GDSFRQG |
OrthoDBi | 1463391at2759 |
PhylomeDBi | Q9BRQ8 |
TreeFami | TF329369 |
Family and domain databases
InterProi | View protein in InterPro IPR036188, FAD/NAD-bd_sf IPR023753, FAD/NAD-binding_dom |
Pfami | View protein in Pfam PF07992, Pyr_redox_2, 1 hit |
SUPFAMi | SSF51905, SSF51905, 1 hit |
s (2)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MGSQVSVESG ALHVVIVGGG FGGIAAASQL QALNVPFMLV DMKDSFHHNV
60 70 80 90 100
AALRASVETG FAKKTFISYS VTFKDNFRQG LVVGIDLKNQ MVLLQGGEAL
110 120 130 140 150
PFSHLILATG STGPFPGKFN EVSSQQAAIQ AYEDMVRQVQ RSRFIVVVGG
160 170 180 190 200
GSAGVEMAAE IKTEYPEKEV TLIHSQVALA DKELLPSVRQ EVKEILLRKG
210 220 230 240 250
VQLLLSERVS NLEELPLNEY REYIKVQTDK GTEVATNLVI LCTGIKINSS
260 270 280 290 300
AYRKAFESRL ASSGALRVNE HLQVEGHSNV YAIGDCADVR TPKMAYLAGL
310 320 330 340 350
HANIAVANIV NSVKQRPLQA YKPGALTFLL SMGRNDGVGQ ISGFYVGRLM
360 370
VRLTKSRDLF VSTSWKTMRQ SPP
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_050651 | 135 | M → T. Corresponds to variant dbSNP:rs10999147Ensembl. | 1 | |
Natural variantiVAR_050652 | 288 | D → N. Corresponds to variant dbSNP:rs2271694Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_052047 | 99 – 138 | Missing in isoform 2. 2 PublicationsAdd BLAST | 40 | |
Alternative sequenceiVSP_052048 | 206 | S → SLLG in isoform 2. 2 Publications | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF337957 mRNA Translation: AAL73229.1 AF506757 mRNA Translation: AAM77596.1 AK027403 mRNA Translation: BAB55089.1 AK127353 mRNA Translation: BAG54492.1 AL731540 Genomic DNA No translation available. CH471083 Genomic DNA Translation: EAW54376.1 BC006121 mRNA Translation: AAH06121.1 BC023601 mRNA Translation: AAH23601.1 BX537621 mRNA Translation: CAH56481.1 |
CCDSi | CCDS7297.1 [Q9BRQ8-1] |
RefSeqi | NP_001185625.1, NM_001198696.1 [Q9BRQ8-1] NP_116186.1, NM_032797.5 [Q9BRQ8-1] |
Genome annotation databases
Ensembli | ENST00000307864.3; ENSP00000312370.1; ENSG00000042286.15 ENST00000373248.5; ENSP00000362345.1; ENSG00000042286.15 ENST00000613322.4; ENSP00000478931.1; ENSG00000042286.15 |
GeneIDi | 84883 |
KEGGi | hsa:84883 |
MANE-Selecti | ENST00000307864.3; ENSP00000312370.1; NM_032797.6; NP_116186.1 |
UCSCi | uc001jqp.3, human [Q9BRQ8-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
Atlas of Genetics and Cytogenetics in Oncology and Haematology |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF337957 mRNA Translation: AAL73229.1 AF506757 mRNA Translation: AAM77596.1 AK027403 mRNA Translation: BAB55089.1 AK127353 mRNA Translation: BAG54492.1 AL731540 Genomic DNA No translation available. CH471083 Genomic DNA Translation: EAW54376.1 BC006121 mRNA Translation: AAH06121.1 BC023601 mRNA Translation: AAH23601.1 BX537621 mRNA Translation: CAH56481.1 |
CCDSi | CCDS7297.1 [Q9BRQ8-1] |
RefSeqi | NP_001185625.1, NM_001198696.1 [Q9BRQ8-1] NP_116186.1, NM_032797.5 [Q9BRQ8-1] |
3D structure databases
AlphaFoldDBi | Q9BRQ8 |
SMRi | Q9BRQ8 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 124325, 25 interactors |
ELMi | Q9BRQ8 |
IntActi | Q9BRQ8, 9 interactors |
STRINGi | 9606.ENSP00000478931 |
PTM databases
iPTMneti | Q9BRQ8 |
PhosphoSitePlusi | Q9BRQ8 |
Genetic variation databases
BioMutai | AIFM2 |
DMDMi | 74752283 |
Proteomic databases
EPDi | Q9BRQ8 |
jPOSTi | Q9BRQ8 |
MassIVEi | Q9BRQ8 |
MaxQBi | Q9BRQ8 |
PaxDbi | Q9BRQ8 |
PeptideAtlasi | Q9BRQ8 |
PRIDEi | Q9BRQ8 |
ProteomicsDBi | 78808 [Q9BRQ8-1] 78809 [Q9BRQ8-2] |
Protocols and materials databases
Antibodypediai | 14832, 292 antibodies from 37 providers |
DNASUi | 84883 |
Genome annotation databases
Ensembli | ENST00000307864.3; ENSP00000312370.1; ENSG00000042286.15 ENST00000373248.5; ENSP00000362345.1; ENSG00000042286.15 ENST00000613322.4; ENSP00000478931.1; ENSG00000042286.15 |
GeneIDi | 84883 |
KEGGi | hsa:84883 |
MANE-Selecti | ENST00000307864.3; ENSP00000312370.1; NM_032797.6; NP_116186.1 |
UCSCi | uc001jqp.3, human [Q9BRQ8-1] |
Organism-specific databases
CTDi | 84883 |
DisGeNETi | 84883 |
GeneCardsi | AIFM2 |
HGNCi | HGNC:21411, AIFM2 |
HPAi | ENSG00000042286, Tissue enhanced (adipose) |
MIMi | 605159, gene |
neXtProti | NX_Q9BRQ8 |
OpenTargetsi | ENSG00000042286 |
PharmGKBi | PA162376150 |
VEuPathDBi | HostDB:ENSG00000042286 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1336, Eukaryota |
GeneTreei | ENSGT00390000004582 |
HOGENOMi | CLU_019845_2_1_1 |
InParanoidi | Q9BRQ8 |
OMAi | GDSFRQG |
OrthoDBi | 1463391at2759 |
PhylomeDBi | Q9BRQ8 |
TreeFami | TF329369 |
Enzyme and pathway databases
BRENDAi | 7.1.1.2, 2681 |
PathwayCommonsi | Q9BRQ8 |
Reactomei | R-HSA-6803204, TP53 Regulates Transcription of Genes Involved in Cytochrome C Release |
SignaLinki | Q9BRQ8 |
SIGNORi | Q9BRQ8 |
Miscellaneous databases
BioGRID-ORCSi | 84883, 20 hits in 1069 CRISPR screens |
ChiTaRSi | AIFM2, human |
GeneWikii | AIFM2 |
GenomeRNAii | 84883 |
Pharosi | Q9BRQ8, Tbio |
PROi | PR:Q9BRQ8 |
RNActi | Q9BRQ8, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000042286, Expressed in adipose tissue of abdominal region and 181 other tissues |
Genevisiblei | Q9BRQ8, HS |
Family and domain databases
InterProi | View protein in InterPro IPR036188, FAD/NAD-bd_sf IPR023753, FAD/NAD-binding_dom |
Pfami | View protein in Pfam PF07992, Pyr_redox_2, 1 hit |
SUPFAMi | SSF51905, SSF51905, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | FSP1_HUMAN | |
Accessioni | Q9BRQ8Primary (citable) accession number: Q9BRQ8 Secondary accession number(s): B3KXI0, Q63Z39 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 30, 2006 |
Last sequence update: | June 1, 2001 | |
Last modified: | May 25, 2022 | |
This is version 165 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human chromosome 10
Human chromosome 10: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families