General Information of the Ferroptosis Regulator (ID: REG10228)
Regulator Name Frataxin, mitochondrial (FXN)
Synonyms
FRDA, X25; Friedreich ataxia protein
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Gene Name FXN
Gene ID 2395
Regulator Type Protein coding
Uniprot ID Q16595
Sequence
MWTLGRRAVAGLLASPSPAQAQTLTRVPRPAELAPLCGRRGLRTDIDATCTPRRASSNQR
GLNQIWNVKKQSVYLMNLRKSGTLGHPGSLDETTYERLAEETLDSLAEFFEDLADKPYTF
EDYDVSFGSGVLTVKLGGDLGTYVINKQTPNKQIWLSSPSSGPKRYDWTGKNWVYSHDGV
SLHELLAAELTKALKTKLDLSSLAYSGKDA

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Family Frataxin family
Function
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.

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HGNC ID
HGNC:3951
KEGG ID hsa:2395
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
FXN can regulate the following target(s), and cause disease/drug response(s). You can browse detail information of target(s) or disease/drug response(s).
Browse Target
Browse Disease
Unspecific Target [Unspecific Target]
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Responsed Disease Diabetes mellitus ICD-11: 5A10
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
INS-1 cells Insulinoma Rattus norvegicus CVCL_0352
Response regulation FXN, amitochondrial proteininvolved iniron metabolismandROSregulation, was shown by other studies reduced in diabetic islets than nondiabetic and impaired insulin secretion after disruption in mice pancreatic -cells.
Diabetes mellitus [ICD-11: 5A10]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Frataxin, mitochondrial (FXN) Protein coding
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
INS-1 cells Insulinoma Rattus norvegicus CVCL_0352
Response regulation FXN, amitochondrial proteininvolved iniron metabolismandROSregulation, was shown by other studies reduced in diabetic islets than nondiabetic and impaired insulin secretion after disruption in mice pancreatic -cells.
References
Ref 1 Oxidative stress-dependent frataxin inhibition mediated alcoholic hepatocytotoxicity through ferroptosis. Toxicology. 2020 Dec 1;445:152584. doi: 10.1016/j.tox.2020.152584. Epub 2020 Oct 2.