FXN

This nuclear gene encodes a mitochondrial protein which belongs to the FRATAXIN family. The protein functions in regulating mitochondrial iron transport and respiration. The expansion of intronic trinucleotide repeat GAA from 8-33 repeats to>90 repeats results in Friedreich ataxia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016]

Frataxin

Promotes the biosynthesis of heme and assembly and repair of iron-sulfur clusters by delivering Fe2+ to proteins involved in these pathways. May play a role in the protection against iron-catalyzed oxidative stress through its ability to catalyze the oxidation of Fe2+ to Fe3+; 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. Modulates the RNA-binding activity of ACO1.

Adult walking behavior Source: Ensembl
Cellular iron ion homeostasis Source: BHF-UCL
Cellular response to hydrogen peroxide Source: UniProtKB
Embryo development ending in birth or egg hatching Source: Ensembl
Heme biosynthetic process Source: BHF-UCL
Ion transport Source: UniProtKB-KW
Iron incorporation into metallo-sulfur cluster Source: BHF-UCL
Iron-sulfur cluster assembly Source: FlyBase
Mitochondrion organization Source: Ensembl
Negative regulation of apoptotic process Source: UniProtKB
Negative regulation of multicellular organism growth Source: Ensembl
Negative regulation of organ growth Source: Ensembl
Negative regulation of release of cytochrome c from mitochondria Source: UniProtKB
Oxidative phosphorylation Source: Ensembl
Positive regulation of aconitate hydratase activity Source: BHF-UCL
Positive regulation of catalytic activity Source: BHF-UCL
Positive regulation of cell growth Source: BHF-UCL
Positive regulation of cell population proliferation Source: BHF-UCL
Positive regulation of lyase activity Source: UniProtKB
Positive regulation of succinate dehydrogenase activity Source: BHF-UCL
Proprioception Source: Ensembl
Protein autoprocessing Source: BHF-UCL
Regulation of ferrochelatase activity Source: BHF-UCL
Response to iron ion Source: BHF-UCL

Mitochondrion; Cytosol. PubMed:18725397 reports localization exclusively in mitochondria.

Friedreich ataxia (FRDA):
Autosomal recessive, progressive degenerative disease characterized by neurodegeneration and cardiomyopathy it is the most common inherited ataxia. The disorder is usually manifest before adolescence and is generally characterized by incoordination of limb movements, dysarthria, nystagmus, diminished or absent tendon reflexes, Babinski sign, impairment of position and vibratory senses, scoliosis, pes cavus, and hammer toe. In most patients, FRDA is due to GAA triplet repeat expansions in the first intron of the frataxin gene. But in some cases the disease is due to mutations in the coding region.

Processed in two steps by mitochondrial processing peptidase (MPP). MPP first cleaves the precursor to intermediate form and subsequently converts the intermediate to yield frataxin mature form (frataxin(81-210)) which is the predominant form. The additional forms, frataxin(56-210) and frataxin(78-210), seem to be produced when the normal maturation process is impaired; their physiological relevance is unsure.