O35943 · FRDA_MOUSE
- ProteinFrataxin, mitochondrial
- GeneFxn
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids207 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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 (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 (By similarity).
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. 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).
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 (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 (By similarity).
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. 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.
Catalytic activity
Frataxin mature form
4 Fe2+ + 4 H+ + O2 = 4 Fe3+ + 2 H2O
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameFrataxin, mitochondrial
- EC number
- Short namesFxn
- Cleaved into 3 chains
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionO35943
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Frataxin mature form
Extramitochondrial frataxin
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Loss of cell division and lethal in fibroblasts.
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 13 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for transit peptide, chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transit peptide | 1-40 | Mitochondrion | ||||
Sequence: MWAFGGRAAVGLLPRTASRASAWVGNPRWREPIVTCGRRG | ||||||
Chain | PRO_0000010132 | 41-207 | Frataxin intermediate form | |||
Sequence: LHVTVNAGATRHAHLNLHYLQILNIKKQSVCVVHLRNLGTLDNPSSLDETAYERLAEETLDSLAEFFEDLADKPYTLEDYDVSFGDGVLTIKLGGDLGTYVINKQTPNKQIWLSSPSSGPKRYDWTGKNWVYSHDGVSLHELLARELTKALNTKLDLSSLAYSGKGT | ||||||
Chain | PRO_0000456949 | 78-207 | Extramitochondrial frataxin | |||
Sequence: LGTLDNPSSLDETAYERLAEETLDSLAEFFEDLADKPYTLEDYDVSFGDGVLTIKLGGDLGTYVINKQTPNKQIWLSSPSSGPKRYDWTGKNWVYSHDGVSLHELLARELTKALNTKLDLSSLAYSGKGT | ||||||
Chain | PRO_0000399390 | 78-207 | Frataxin mature form | |||
Sequence: LGTLDNPSSLDETAYERLAEETLDSLAEFFEDLADKPYTLEDYDVSFGDGVLTIKLGGDLGTYVINKQTPNKQIWLSSPSSGPKRYDWTGKNWVYSHDGVSLHELLARELTKALNTKLDLSSLAYSGKGT |
Post-translational modification
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.
Proteomic databases
PTM databases
Expression
Tissue specificity
Heart, liver, skeletal muscle, kidney, spleen and thymus. Weakly expressed in the brain and lung.
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.
Gene expression databases
Interaction
Subunit
Frataxin mature form
Component of the mitochondrial core iron-sulfur cluster (ISC) complex composed of NFS1, LYRM4, NDUFAB1, ISCU, FXN, and FDX2; this complex is a heterohexamer containing two copies of each monomer (By similarity).
Homodimer. Monomer (probable predominant form). Oligomer (PubMed:11823441).
Monomers and polymeric aggregates of >1 MDa have been isolated from mitochondria. A small fraction of heterologous overexpressed recombinant frataxin forms high-molecular weight aggregates that incorporate iron. Interacts with LYRM4. Interacts (via ferrous form) with ISCU; the interaction is possible when both are bound to the dimeric form of the cysteine desulfurase complex (NFS1:LYRM4) and the interaction enhances FXN interaction to the dimeric form of the cysteine desulfurase complex (NFS1:LYRM4) (By similarity).
Interacts with FECH; one iron-bound FXN monomer seems to interact with a FECH homodimer. Interacts with SDHA and SDHB (By similarity).
Interacts with ACO2; the interaction is dependent on citrate (By similarity).
Interacts with HSPA9 (By similarity).
Component of a complex composed of FXN, NFS1, LYRM4 and ISCU (PubMed:21298097, PubMed:25597503).
Homodimer. Monomer (probable predominant form). Oligomer (PubMed:11823441).
Monomers and polymeric aggregates of >1 MDa have been isolated from mitochondria. A small fraction of heterologous overexpressed recombinant frataxin forms high-molecular weight aggregates that incorporate iron. Interacts with LYRM4. Interacts (via ferrous form) with ISCU; the interaction is possible when both are bound to the dimeric form of the cysteine desulfurase complex (NFS1:LYRM4) and the interaction enhances FXN interaction to the dimeric form of the cysteine desulfurase complex (NFS1:LYRM4) (By similarity).
Interacts with FECH; one iron-bound FXN monomer seems to interact with a FECH homodimer. Interacts with SDHA and SDHB (By similarity).
Interacts with ACO2; the interaction is dependent on citrate (By similarity).
Interacts with HSPA9 (By similarity).
Component of a complex composed of FXN, NFS1, LYRM4 and ISCU (PubMed:21298097, PubMed:25597503).
Extramitochondrial frataxin
Interacts with ACO1. Interacts with ISCU (cytoplasmic form).
Protein-protein interaction databases
Miscellaneous
Structure
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length207
- Mass (Da)22,924
- Last updated1998-01-01 v1
- ChecksumC46FD21B44FB26A2
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
E9Q2P9 | E9Q2P9_MOUSE | Fxn | 145 |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U95736 EMBL· GenBank· DDBJ | AAB67778.1 EMBL· GenBank· DDBJ | mRNA |