General Information of Target

Target ID LDTP11124
Target Name Ferroptosis suppressor protein 1 (AIFM2)
Gene Name AIFM2
Gene ID 84883
Synonyms
AMID; PRG3; Ferroptosis suppressor protein 1; FSP1; EC 1.6.5.-; Apoptosis-inducing factor homologous mitochondrion-associated inducer of death; AMID; p53-responsive gene 3 protein
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MGSTESSEGRRVSFGVDEEERVRVLQGVRLSENVVNRMKEPSSPPPAPTSSTFGLQDGNL
RAPHKESTLPRSGSSGGQQPSGMKEGVKRYEQEHAAIQDKLFQVAKREREAATKHSKASL
PTGEGSISHEEQKSVRLARELESREAELRRRDTFYKEQLERIERKNAEMYKLSSEQFHEA
ASKMESTIKPRRVEPVCSGLQAQILHCYRDRPHEVLLCSDLVKAYQRCVSAAHKG
Target Bioclass
Enzyme
Family
FAD-dependent oxidoreductase family
Subcellular location
Lipid droplet
Function
A NAD(P)H-dependent oxidoreductase that acts as a key inhibitor of ferroptosis. 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. Acts in parallel to GPX4 to suppress phospholipid peroxidation and ferroptosis. This anti-ferroptotic function is independent of cellular glutathione levels. Also acts as a potent radical-trapping antioxidant by mediating warfarin-resistant vitamin K reduction in the canonical vitamin K cycle: catalyzes NAD(P)H-dependent reduction of vitamin K (phylloquinone, menaquinone-4 and menadione) to hydroquinone forms. Hydroquinones act as potent radical-trapping antioxidants inhibitor of phospholipid peroxidation and ferroptosis. 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. Capable of DNA binding in a non-sequence specific way.
Uniprot ID
Q9BRQ8
Ensemble ID
ENST00000307864.3
HGNC ID
HGNC:21411

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
MCC13 SNV: p.R267I DBIA    Probe Info 
NCIH716 SNV: p.A261D .
SKOV3 SNV: p.G337D .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 6 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
FBP2
 Probe Info 
2.80  LDD0323  [1]
STPyne
 Probe Info 
K254(7.30)  LDD0277  [2]
m-APA
 Probe Info 
9.03  LDD0403  [3]
DBIA
 Probe Info 
C242(2.64)  LDD3314  [4]
IPM
 Probe Info 
C286(2.27)  LDD1701  [5]
NAIA_4
 Probe Info 
C242(0.00); C286(0.00)  LDD2226  [6]
PAL-AfBPP Probe
Click To Hide/Show 1 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
A-DA
 Probe Info 
16.14  LDD0143  [7]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0156  Aniline NCI-H1299 9.03  LDD0403  [3]
 LDCM0083  Avasimibe A-549 16.14  LDD0143  [7]
 LDCM0022  KB02 42-MG-BA C242(1.97)  LDD2244  [4]
 LDCM0023  KB03 MDA-MB-231 C286(2.27)  LDD1701  [5]
 LDCM0024  KB05 IGR37 C242(2.64)  LDD3314  [4]
 LDCM0084  Ro 48-8071 A-549 2.20  LDD0144  [7]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Tripartite motif-containing protein 54 (TRIM54) . Q9BYV2
Other
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Protein canopy homolog 4 (CNPY4) Canopy family Q8N129

References

1 Tranylcypromine specificity for monoamine oxidase is limited by promiscuous protein labelling and lysosomal trapping. RSC Chem Biol. 2020 Aug 12;1(4):209-213. doi: 10.1039/d0cb00048e. eCollection 2020 Oct 1.
Mass spectrometry data entry: PXD018580
2 A Paal-Knorr agent for chemoproteomic profiling of targets of isoketals in cells. Chem Sci. 2021 Oct 15;12(43):14557-14563. doi: 10.1039/d1sc02230j. eCollection 2021 Nov 10.
Mass spectrometry data entry: PXD028270
3 Quantitative and Site-Specific Chemoproteomic Profiling of Targets of Acrolein. Chem Res Toxicol. 2019 Mar 18;32(3):467-473. doi: 10.1021/acs.chemrestox.8b00343. Epub 2019 Jan 15.
4 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840
5 Nucleophilic covalent ligand discovery for the cysteine redoxome. Nat Chem Biol. 2023 Nov;19(11):1309-1319. doi: 10.1038/s41589-023-01330-5. Epub 2023 May 29.
Mass spectrometry data entry: PXD039908 , PXD029761
6 N-Acryloylindole-alkyne (NAIA) enables imaging and profiling new ligandable cysteines and oxidized thiols by chemoproteomics. Nat Commun. 2023 Jun 15;14(1):3564. doi: 10.1038/s41467-023-39268-w.
Mass spectrometry data entry: PXD041264
7 A Global Map of Lipid-Binding Proteins and Their Ligandability in Cells. Cell. 2015 Jun 18;161(7):1668-80. doi: 10.1016/j.cell.2015.05.045.