General Information of Target

Target ID LDTP06569
Target Name Frataxin, mitochondrial (FXN)
Gene Name FXN
Gene ID 2395
Synonyms
FRDA; X25; Frataxin, mitochondrial; EC 1.16.3.1; Friedreich ataxia protein; Fxn) [Cleaved into: Frataxin intermediate form; i-FXN; Frataxin(56-210; m56-FXN; Frataxin(78-210; d-FXN; m78-FXN; Frataxin mature form; Frataxin(81-210); m81-FXN; Extramitochondrial frataxin]
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Sequence
MWTLGRRAVAGLLASPSPAQAQTLTRVPRPAELAPLCGRRGLRTDIDATCTPRRASSNQR
GLNQIWNVKKQSVYLMNLRKSGTLGHPGSLDETTYERLAEETLDSLAEFFEDLADKPYTF
EDYDVSFGSGVLTVKLGGDLGTYVINKQTPNKQIWLSSPSSGPKRYDWTGKNWVYSHDGV
SLHELLAAELTKALKTKLDLSSLAYSGKDA
Target Bioclass
Enzyme
Family
Frataxin family
Subcellular location
Cytoplasm, cytosol; Mitochondrion
Function
[Frataxin mature form]: Functions as an activator of persulfide transfer to the scaffoding protein ISCU as component of the core iron-sulfur cluster (ISC) assembly complex and participates to the [2Fe-2S] cluster assembly. Accelerates sulfur transfer from NFS1 persulfide intermediate to ISCU and to small thiols such as L-cysteine and glutathione leading to persulfuration of these thiols and ultimately sulfide release. Binds ferrous ion and is released from FXN upon the addition of both L-cysteine and reduced FDX2 during [2Fe-2S] cluster assembly. The core iron-sulfur cluster (ISC) assembly complex is involved in the de novo synthesis of a [2Fe-2S] cluster, the first step of the mitochondrial iron-sulfur protein biogenesis. This process is initiated by the cysteine desulfurase complex (NFS1:LYRM4:NDUFAB1) that produces persulfide which is delivered on the scaffold protein ISCU in a FXN-dependent manner. Then this complex is stabilized by FDX2 which provides reducing equivalents to accomplish the [2Fe-2S] cluster assembly. Finally, the [2Fe-2S] cluster is transferred from ISCU to chaperone proteins, including HSCB, HSPA9 and GLRX5. May play a role in the protection against iron-catalyzed oxidative stress through its ability to catalyze the oxidation of Fe(2+) to Fe(3+); the oligomeric form but not the monomeric form has in vitro ferroxidase activity. May be able to store large amounts of iron in the form of a ferrihydrite mineral by oligomerization; however, the physiological relevance is unsure as reports are conflicting and the function has only been shown using heterologous overexpression systems. May function as an iron chaperone protein that protects the aconitase [4Fe-4S]2+ cluster from disassembly and promotes enzyme reactivation. May play a role as a high affinity iron binding partner for FECH that is capable of both delivering iron to ferrochelatase and mediating the terminal step in mitochondrial heme biosynthesis.; [Extramitochondrial frataxin]: Modulates the RNA-binding activity of ACO1. May be involved in the cytoplasmic iron-sulfur protein biogenesis. May contribute to oxidative stress resistance and overall cell survival.
Uniprot ID
Q16595
Ensemble ID
ENST00000396366.6
HGNC ID
HGNC:3951
ChEMBL ID
CHEMBL2321640

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
MCC13 SNV: p.E108K .
NCIH1975 SNV: p.L98I .
OVISE SNV: p.R54C .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 4 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
5E-2FA
 Probe Info 
H177(0.00); H86(0.00)  LDD2235  [1]
m-APA
 Probe Info 
N.A.  LDD2231  [1]
2PCA
 Probe Info 
N.A.  LDD0034  [2]
WYneN
 Probe Info 
N.A.  LDD0021  [3]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 4 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Calpain-10 (CAPN10) Peptidase C2 family Q9HC96
E3 SUMO-protein ligase PIAS1 (PIAS1) PIAS family O75925
E3 ubiquitin-protein ligase RNF138 (RNF138) . Q8WVD3
E3 ubiquitin-protein ligase RNF183 (RNF183) . Q96D59
Other
Click To Hide/Show 4 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Golgin subfamily A member 6-like protein 9 (GOLGA6L9) GOLGA6 family A6NEM1
Coronin-2A (CORO2A) WD repeat coronin family Q92828
Dual adapter for phosphotyrosine and 3-phosphotyrosine and 3-phosphoinositide (DAPP1) . Q9UN19
Superkiller complex protein 8 (SKIC8) . Q9GZS3

The Drug(s) Related To This Target

Approved
Click To Hide/Show 6 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Iron Small molecular drug DB01592
Ferrous Ascorbate . DB14490
Ferrous Fumarate . DB14491
Ferrous Gluconate . DB14488
Ferrous Glycine Sulfate . DB14501
Ferrous Succinate . DB14489

References

1 Global profiling of functional histidines in live cells using small-molecule photosensitizer and chemical probe relay labelling. Nat Chem. 2024 Jun 4. doi: 10.1038/s41557-024-01545-6. Online ahead of print.
Mass spectrometry data entry: PXD042377
2 Unveiling the Multifaceted Capabilities of Endophytic Aspergillus flavus Isolated from Annona squamosa Fruit Peels against Staphylococcus Isolates and HCoV 229E-In Vitro and In Silico Investigations. Pharmaceuticals (Basel). 2024 May 19;17(5):656. doi: 10.3390/ph17050656.
Mass spectrometry data entry: PXD013019
3 A modification-centric assessment tool for the performance of chemoproteomic probes. Nat Chem Biol. 2022 Aug;18(8):904-912. doi: 10.1038/s41589-022-01074-8. Epub 2022 Jul 21.
Mass spectrometry data entry: PXD027758 , PXD027755 , PXD027760 , PXD027762 , PXD027756 , PXD027591 , PXD007149 , PXD030064 , PXD032392 , PXD027789 , PXD027767 , PXD027764