Frataxin, mitochondrial

Details

Name
Frataxin, mitochondrial
Synonyms
  • 1.16.3.1
  • FRDA
  • Friedreich ataxia protein
  • Fxn
  • X25
Gene Name
FXN
UniProtKB Entry
Q16595Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0049696|Frataxin, mitochondrial
MWTLGRRAVAGLLASPSPAQAQTLTRVPRPAELAPLCGRRGLRTDIDATCTPRRASSNQR
GLNQIWNVKKQSVYLMNLRKSGTLGHPGSLDETTYERLAEETLDSLAEFFEDLADKPYTF
EDYDVSFGSGVLTVKLGGDLGTYVINKQTPNKQIWLSSPSSGPKRYDWTGKNWVYSHDGV
SLHELLAAELTKALKTKLDLSSLAYSGKDA
Number of residues
210
Molecular Weight
23134.895
Theoretical pI
Not Available
GO Classification
Processes
[2Fe-2S] cluster assembly / [4Fe-4S] cluster assembly / intracellular iron ion homeostasis / iron ion transport / iron-sulfur cluster assembly / muscle cell cellular homeostasis / organ growth / positive regulation of cell population proliferation
Components
iron-sulfur cluster assembly complex / L-cysteine desulfurase complex / mitochondrial iron-sulfur cluster assembly complex
General 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 (PubMed:12785837, PubMed:24971490). 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:24971490). Binds ferrous ion and is released from FXN upon the addition of both L-cysteine and reduced FDX2 during [2Fe-2S] cluster assembly (PubMed:29576242). 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 Fe(2+) to Fe(3+); the oligomeric form but not the monomeric form has in vitro ferroxidase activity (PubMed:15641778). 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 (PubMed:11823441, PubMed:12755598). May function as an iron chaperone protein that protects the aconitase [4Fe-4S]2+ cluster from disassembly and promotes enzyme reactivation (PubMed:15247478). 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 (PubMed:15123683, PubMed:16239244)
Specific Function
2 iron, 2 sulfur cluster binding
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Mitochondrion
Gene sequence
>lcl|BSEQ0049697|Frataxin, mitochondrial (FXN)
ATGTGGACTCTCGGGCGCCGCGCAGTAGCCGGCCTCCTGGCGTCACCCAGCCCAGCCCAG
GCCCAGACCCTCACCCGGGTCCCGCGGCCGGCAGAGTTGGCCCCACTCTGCGGCCGCCGT
GGCCTGCGCACCGACATCGATGCGACCTGCACGCCCCGCCGCGCAAGTTCGAACCAACGT
GGCCTCAACCAGATTTGGAATGTCAAAAAGCAGAGTGTCTATTTGATGAATTTGAGGAAA
TCTGGAACTTTGGGCCACCCAGGCTCTCTAGATGAGACCACCTATGAAAGACTAGCAGAG
GAAACGCTGGACTCTTTAGCAGAGTTTTTTGAAGACCTTGCAGACAAGCCATACACGTTT
GAGGACTATGATGTCTCCTTTGGGAGTGGTGTCTTAACTGTCAAACTGGGTGGAGATCTA
GGAACCTATGTGATCAACAAGCAGACGCCAAACAAGCAAATCTGGCTATCTTCTCCATCC
AGTGGACCTAAGCGTTATGACTGGACTGGGAAAAACTGGGTGTACTCCCACGACGGCGTG
TCCCTCCATGAGCTGCTGGCCGCAGAGCTCACTAAAGCCTTAAAAACCAAACTGGACTTG
TCTTCCTTGGCCTATTCCGGAAAAGATGCTTGA
Chromosome Location
9
Locus
9q21.11
External Identifiers
ResourceLink
UniProtKB IDQ16595
UniProtKB Entry NameFRDA_HUMAN
GeneCard IDFXN
HGNC IDHGNC:3951
PDB ID(s)1EKG, 1LY7, 3S4M, 3S5D, 3S5E, 3S5F, 3T3J, 3T3K, 3T3L, 3T3T, 3T3X, 5KZ5, 6NZU
KEGG IDhsa:2395
NCBI Gene ID2395
General References
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  5. Condo I, Ventura N, Malisan F, Rufini A, Tomassini B, Testi R: In vivo maturation of human frataxin. Hum Mol Genet. 2007 Jul 1;16(13):1534-40. Epub 2007 Apr 27. [Article]
  6. Condo I, Malisan F, Guccini I, Serio D, Rufini A, Testi R: Molecular control of the cytosolic aconitase/IRP1 switch by extramitochondrial frataxin. Hum Mol Genet. 2010 Apr 1;19(7):1221-9. doi: 10.1093/hmg/ddp592. Epub 2010 Jan 6. [Article]
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  8. Koutnikova H, Campuzano V, Foury F, Dolle P, Cazzalini O, Koenig M: Studies of human, mouse and yeast homologues indicate a mitochondrial function for frataxin. Nat Genet. 1997 Aug;16(4):345-51. [Article]
  9. Gordon DM, Shi Q, Dancis A, Pain D: Maturation of frataxin within mammalian and yeast mitochondria: one-step processing by matrix processing peptidase. Hum Mol Genet. 1999 Nov;8(12):2255-62. [Article]
  10. Branda SS, Cavadini P, Adamec J, Kalousek F, Taroni F, Isaya G: Yeast and human frataxin are processed to mature form in two sequential steps by the mitochondrial processing peptidase. J Biol Chem. 1999 Aug 6;274(32):22763-9. [Article]
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Associated Data

Bio-Entities
Bio-EntityType
Frataxin, mitochondrial (Humans)protein
primary
Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
IronapprovedunknowntargetDetails
Ferrous gluconateapprovedunknowntargetDetails
Ferrous succinateapprovedunknowntargetDetails
Ferrous ascorbateapprovedunknowntargetDetails
Ferrous fumarateapprovedunknowntargetDetails
Ferrous glycine sulfateapprovedunknowntargetDetails