JavaScript is disabled in your browser. Please enable JavaScript to view this website.

Fxn

Developmental stage

Expression in the ventricular zone which corresponds to dividing neuronal precursors begins at day 12.5, increases during embryonic development and persists at postnatal day 7 (P7) in the ependymal layer, which is the remnant of the ventricular zone. Weak expression seen in the spinal cord and medulla oblongata, starting at 14.5 dpc and expression also observed in dorsal root ganglia, starting at 14.5 dpc. At P14, expression in the dorsal root ganglia is restricted to the cortical region where the sensory neuron cell bodies are located. In non-neural tissues strong expression seen in the developing liver from 10.5 dpc. Expression detected in the heart and in the cortex of the developing kidney at 12.5 dpc and later. Very high expression observed in the brown adipose tissue. Expression seen in small islands around the neck and back at 14.5 dpc, then in large masses at 16.5 dpc and 18.5 dpc and at P14 is absent in brown adipose tissue. Expression also seen in the thymus and developing gut at 14.5 dpc and until postnatal life. At P14, expression in thymus is restricted to the proliferating cells in the cortical zone and is also prominent in the spleen. Found in the lung at 14.5 dpc.

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 (PubMed:19805308, PubMed:25597503). 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 (PubMed:25597503). Binds ferrous ion and is released from FXN upon the addition of both L-cysteine and reduced FDX2 during [2Fe-2S] cluster assembly (By similarity). 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 (NFS1NDUFAB1) 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 (By similarity). 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 (By similarity).

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.

Post-translational modifications

Frataxin mature form

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.

Sequence Similarities

Belongs to the frataxin family.

Tissue Specificity

Heart, liver, skeletal muscle, kidney, spleen and thymus. Weakly expressed in the brain and lung.

Cellular localization

Alternative names

Frda, Fxn

swissprot:O35943 entrezGene:14297

Other research areas