This gene encodes a flavoprotein oxidoreductase that binds single stranded DNA and is thought to contribute to apoptosis in the presence of bacterial and viral DNA. The expression of this gene is also found to be induced by tumor suppressor protein p53 in colon cancer cells. [provided by RefSeq, Nov 2010] See more...

Aliases for AIFM2 Gene

Aliases for AIFM2 Gene

  • Apoptosis Inducing Factor Mitochondria Associated 2 2 3 5
  • PRG3 2 3 4
  • Apoptosis-Inducing Factor (AIF)-Like Mitochondrion-Associated Inducer Of Death 2 3
  • Apoptosis-Inducing Factor, Mitochondrion-Associated, 2 2 3
  • Ferroptosis Suppressor Protein 1 3 4
  • P53-Responsive Gene 3 Protein 3 4
  • AMID 3 4
  • FSP1 3 4
  • Apoptosis-Inducing Factor (AIF)-Homologous Mitochondrion-Associated Inducer Of Death 3
  • Apoptosis-Inducing Factor Homologous Mitochondrion-Associated Inducer Of Death 4
  • Apoptosis-Inducing Factor 2 3
  • EC 1.6.5.- 4
  • FLJ14497 2
  • AIFM2 5

External Ids for AIFM2 Gene

Previous HGNC Symbols for AIFM2 Gene

  • AMID

Previous GeneCards Identifiers for AIFM2 Gene

  • GC10M071528
  • GC10M071857
  • GC10M065864

Summaries for AIFM2 Gene

Entrez Gene Summary for AIFM2 Gene

  • This gene encodes a flavoprotein oxidoreductase that binds single stranded DNA and is thought to contribute to apoptosis in the presence of bacterial and viral DNA. The expression of this gene is also found to be induced by tumor suppressor protein p53 in colon cancer cells. [provided by RefSeq, Nov 2010]

GeneCards Summary for AIFM2 Gene

AIFM2 (Apoptosis Inducing Factor Mitochondria Associated 2) is a Protein Coding gene. Diseases associated with AIFM2 include Febrile Seizures, Familial, 9. Among its related pathways are TP53 Regulates Transcription of Cell Death Genes and Gene Expression. Gene Ontology (GO) annotations related to this gene include oxidoreductase activity and NADH dehydrogenase (ubiquinone) activity.

UniProtKB/Swiss-Prot Summary for AIFM2 Gene

  • 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).

Gene Wiki entry for AIFM2 Gene

Additional gene information for AIFM2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for AIFM2 Gene

Genomics for AIFM2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for AIFM2 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH10J070144 Promoter/Enhancer 2.4 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 618.1 -13.4 -13379 3.3 SP1 CREB1 CTCF TEAD4 PRDM10 ZNF629 TFE3 NFKBIZ POLR2A ZNF692 AIFM2 TYSND1 HSALNG0078627 lnc-TYSND1-1 piR-49846 piR-45079 PPA1 SAR1A
GH10J070168 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas 629.1 -37.8 -37767 4.2 BRCA1 SP1 CREB1 PRDM10 REST ZNF629 IKZF1 ZNF692 POLR2A BACH1 AIFM2 SAR1A PPA1 TYSND1 lnc-PPA1-2
GH10J070130 Promoter/Enhancer 1.9 EPDnew Ensembl ENCODE dbSUPER 606.1 +1.0 989 3.4 GATAD2A PRDM10 TFE3 ZNF512 IKZF1 NFKBIZ RCOR2 ZNF7 BACH1 LARP7 AIFM2 SAR1A PPA1 TYSND1 RF00017-686 MACROH2A2
GH10J070231 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas 14 -100.5 -100456 4.8 CREB1 GATAD2A CTCF HNRNPL ATF7 PRDM10 REST ZNF629 TFE3 ZNF512 PPA1 lnc-H2AFY2-4 lnc-PPA1-1 AIFM2 SAR1A LRRC20 CEP57L1P1 NPFFR1 lnc-NPFFR1-1
GH10J070173 Enhancer 0.9 ENCODE 29.1 -41.4 -41425 1.4 GATAD2A TFE3 SOX13 RCOR2 RBFOX2 RXRB NR2C1 IRF2 GABPA ETV6 AIFM2 TYSND1 SAR1A lnc-PPA1-2 PPA1
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around AIFM2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for AIFM2

Top Transcription factor binding sites by QIAGEN in the AIFM2 gene promoter:
  • AhR
  • AP-1
  • Arnt
  • ATF-2
  • c-Jun
  • CREB
  • FOXL1
  • FOXO4
  • GATA-1
  • Pax-5

Genomic Locations for AIFM2 Gene

Genomic Locations for AIFM2 Gene
chr10:70,098,223-70,132,934
(GRCh38/hg38)
Size:
34,712 bases
Orientation:
Minus strand
chr10:71,857,979-71,892,690
(GRCh37/hg19)
Size:
34,712 bases
Orientation:
Minus strand

Genomic View for AIFM2 Gene

Genes around AIFM2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
AIFM2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for AIFM2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for AIFM2 Gene

Proteins for AIFM2 Gene

  • Protein details for AIFM2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9BRQ8-FSP1_HUMAN
    Recommended name:
    Ferroptosis suppressor protein 1
    Protein Accession:
    Q9BRQ8
    Secondary Accessions:
    • B3KXI0
    • Q63Z39

    Protein attributes for AIFM2 Gene

    Size:
    373 amino acids
    Molecular mass:
    40527 Da
    Cofactor:
    Name=6-hydroxy-FAD; Xref=ChEBI:CHEBI:60470;
    Quaternary structure:
    • Interacts with importin subunits KPNA2 and IPO5; this interaction likely mediates the translocation into the nucleus upon oxidative stress.

    Alternative splice isoforms for AIFM2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for AIFM2 Gene

Post-translational modifications for AIFM2 Gene

  • N-myristoylation at Gly-2 mediates the recruitment to lipid droplets and plasma membrane.
  • Ubiquitination at Lys193
  • Modification sites at PhosphoSitePlus

Other Protein References for AIFM2 Gene

No data available for DME Specific Peptides for AIFM2 Gene

Domains & Families for AIFM2 Gene

Gene Families for AIFM2 Gene

Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for AIFM2 Gene

InterPro:
Blocks:
  • Pyridine nucleotide-disulphide oxidoreductase, NAD-binding region
  • Pyridine nucleotide-disulphide oxidoreductase, class-II
ProtoNet:

Suggested Antigen Peptide Sequences for AIFM2 Gene

GenScript: Design optimal peptide antigens:
  • p53-responsive gene 3 protein (AIFM2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9BRQ8

UniProtKB/Swiss-Prot:

FSP1_HUMAN :
  • Belongs to the FAD-dependent oxidoreductase family.
Family:
  • Belongs to the FAD-dependent oxidoreductase family.
genes like me logo Genes that share domains with AIFM2: view

Function for AIFM2 Gene

Molecular function for AIFM2 Gene

UniProtKB/Swiss-Prot Function:
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).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=H(+) + NADH + ubiquinone-10 = NAD(+) + ubiquinol-10; Xref=Rhea:RHEA:61984, ChEBI:CHEBI:15378, ChEBI:CHEBI:46245, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:64183; Evidence={ECO:0000305|PubMed:31634899, ECO:0000305|PubMed:31634900};.
UniProtKB/Swiss-Prot Induction:
Expression detected at 4 hours after induction by p53/TP53. Down-regulated in a wide range of human tumors.
UniProtKB/Swiss-Prot EnzymeRegulation:
The modification by 4-hydroxy-2-nonenal (HNE) adduction in mitochondria results in loss of the oxidoreductase activity and activation of a novel function in mitochondrial oxidative stress signaling.

Enzyme Numbers (IUBMB) for AIFM2 Gene

Phenotypes From GWAS Catalog for AIFM2 Gene

Gene Ontology (GO) - Molecular Function for AIFM2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003677 DNA binding IEA,IDA 15958387
GO:0004174 electron-transferring-flavoprotein dehydrogenase activity IBA,IDA 15958387
GO:0016491 oxidoreductase activity IEA --
GO:0016655 oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor IDA 31634899
GO:0050660 flavin adenine dinucleotide binding IBA,IDA 15958387
genes like me logo Genes that share ontologies with AIFM2: view
genes like me logo Genes that share phenotypes with AIFM2: view

Animal Models for AIFM2 Gene

MGI Knock Outs for AIFM2:

Animal Model Products

  • Taconic Biosciences Mouse Models for AIFM2

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for AIFM2

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for AIFM2 Gene

Localization for AIFM2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for AIFM2 Gene

Lipid droplet. Cell membrane. Lipid-anchor. Cytoplasm. Mitochondrion membrane. Nucleus.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for AIFM2 gene
Compartment Confidence
plasma membrane 5
mitochondrion 5
cytosol 5
extracellular 4
nucleus 4
cytoskeleton 1
peroxisome 1
endoplasmic reticulum 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (3)
  • Vesicles (3)
  • Plasma membrane (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for AIFM2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005615 extracellular space HDA 22664934
GO:0005634 nucleus ISS --
GO:0005737 cytoplasm IDA 12135761
GO:0005739 mitochondrion IDA 11980907
GO:0005741 mitochondrial outer membrane TAS --
genes like me logo Genes that share ontologies with AIFM2: view

Pathways & Interactions for AIFM2 Gene

genes like me logo Genes that share pathways with AIFM2: view

Gene Ontology (GO) - Biological Process for AIFM2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006743 ubiquinone metabolic process IDA 31634899
GO:0008637 apoptotic mitochondrial changes IDA 11980907
GO:0022904 respiratory electron transport chain IEA --
GO:0042981 regulation of apoptotic process TAS --
GO:0043065 positive regulation of apoptotic process IBA,IDA 11980907
genes like me logo Genes that share ontologies with AIFM2: view

No data available for SIGNOR curated interactions for AIFM2 Gene

Drugs & Compounds for AIFM2 Gene

(1) Drugs for AIFM2 Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
FAD Approved Pharma 0
genes like me logo Genes that share compounds with AIFM2: view

Transcripts for AIFM2 Gene

mRNA/cDNA for AIFM2 Gene

2 REFSEQ mRNAs :
10 NCBI additional mRNA sequence :
4 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for AIFM2

Alternative Splicing Database (ASD) splice patterns (SP) for AIFM2 Gene

No ASD Table

Relevant External Links for AIFM2 Gene

GeneLoc Exon Structure for
AIFM2

Expression for AIFM2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for AIFM2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for AIFM2 Gene

This gene is overexpressed in Adipose - Visceral (Omentum) (x4.4) and Adipose - Subcutaneous (x4.1).

Protein differential expression in normal tissues from HIPED for AIFM2 Gene

This gene is overexpressed in Nasal epithelium (20.3), Nasopharynx (16.7), and Breast (9.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for AIFM2 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for AIFM2

SOURCE GeneReport for Unigene cluster for AIFM2 Gene:

Hs.650680

mRNA Expression by UniProt/SwissProt for AIFM2 Gene:

Q9BRQ8-FSP1_HUMAN
Tissue specificity: Detected in most normal tissues as two transcripts of 1.8 and 4.0 kb in length, respectively. Highly expressed in heart, moderately in liver and skeletal muscles, and expressed at low levels in placenta, lung, kidney, and pancreas. Both transcripts expressed following p53/TP53 induction. The shorter 1.8 kb transcript seems to be the major transcript in EB1 colon cancer cells.

Evidence on tissue expression from TISSUES for AIFM2 Gene

  • Nervous system(4.3)
  • Lung(2.4)
  • Liver(2.1)
genes like me logo Genes that share expression patterns with AIFM2: view

No data available for Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for AIFM2 Gene

Orthologs for AIFM2 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for AIFM2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia AIFM2 30 31
  • 99.11 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia AIFM2 30 31
  • 87.04 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Aifm2 30
  • 86.77 (n)
Mouse
(Mus musculus)
Mammalia Aifm2 30 17 31
  • 86.68 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia AIFM2 30 31
  • 86.33 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia AIFM2 31
  • 76 (a)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia AIFM2 31
  • 71 (a)
OneToOne
Chicken
(Gallus gallus)
Aves AIFM2 30 31
  • 69.27 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia AIFM2 31
  • 69 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia aifm2 30
  • 61.11 (n)
Str.15881 30
Zebrafish
(Danio rerio)
Actinopterygii LOC557507 30
  • 58.42 (n)
AIFM2 31
  • 56 (a)
OneToOne
Rainbow Trout
(Oncorhynchus mykiss)
Actinopterygii Omy.2755 30
Thale Cress
(Arabidopsis thaliana)
eudicotyledons AT3G44190 30
  • 45.1 (n)
Rice
(Oryza sativa)
Liliopsida Os02g0150300 30
  • 44.26 (n)
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 40 (a)
OneToMany
CSA.9377 31
  • 38 (a)
OneToMany
-- 31
  • 38 (a)
OneToMany
-- 31
  • 33 (a)
OneToMany
-- 31
  • 33 (a)
OneToMany
-- 31
  • 28 (a)
OneToMany
Species where no ortholog for AIFM2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for AIFM2 Gene

ENSEMBL:
Gene Tree for AIFM2 (if available)
TreeFam:
Gene Tree for AIFM2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for AIFM2: view image

Paralogs for AIFM2 Gene

No data available for Paralogs for AIFM2 Gene

Variants for AIFM2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for AIFM2 Gene

SNP ID Clinical significance and condition Chr 10 pos Variation AA Info Type
rs10999147 - p.Met135Thr
rs2271694 - p.Asp288Asn

Additional dbSNP identifiers (rs#s) for AIFM2 Gene

Structural Variations from Database of Genomic Variants (DGV) for AIFM2 Gene

Variant ID Type Subtype PubMed ID
esv32737 CNV gain+loss 17666407
nsv551479 CNV loss 21841781
nsv7054 CNV insertion 18451855

Variation tolerance for AIFM2 Gene

Residual Variation Intolerance Score: 85.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 6.34; 76.78% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for AIFM2 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
AIFM2

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for AIFM2 Gene

Disorders for AIFM2 Gene

MalaCards: The human disease database

(1) MalaCards diseases for AIFM2 Gene - From: DISEASES

Disorder Aliases PubMed IDs
febrile seizures, familial, 9
  • feb9
- elite association - COSMIC cancer census association via MalaCards
Search AIFM2 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for AIFM2

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with AIFM2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for AIFM2 Gene

Publications for AIFM2 Gene

  1. The human apoptosis-inducing protein AMID is an oxidoreductase with a modified flavin cofactor and DNA binding activity. (PMID: 15958387) Marshall KR … Munro AW (The Journal of biological chemistry 2005) 2 3 4 23
  2. AMID, an apoptosis-inducing factor-homologous mitochondrion-associated protein, induces caspase-independent apoptosis. (PMID: 11980907) Wu M … Shu HB (The Journal of biological chemistry 2002) 2 3 4
  3. A novel p53-inducible apoptogenic gene, PRG3, encodes a homologue of the apoptosis-inducing factor (AIF). (PMID: 12135761) Ohiro Y … Horikoshi N (FEBS letters 2002) 2 3 4
  4. The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis. (PMID: 31634900) Bersuker K … Olzmann JA (Nature 2019) 3 4
  5. FSP1 is a glutathione-independent ferroptosis suppressor. (PMID: 31634899) Doll S … Conrad M (Nature 2019) 3 4

Products for AIFM2 Gene

Sources for AIFM2 Gene