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Protein FXN PDB 1ekg.png
PDB rendering based on 1ekg.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols FXN ; CyaY; FA; FARR; FRDA; X25
External IDs OMIM606829 MGI1096879 HomoloGene47908 GeneCards: FXN Gene
EC number
RNA expression pattern
PBB GE FXN 205565 s at tn.png
More reference expression data
Species Human Mouse
Entrez 2395 14297
Ensembl ENSG00000165060 ENSMUSG00000059363
UniProt Q16595 O35943
RefSeq (mRNA) NM_000144 NM_008044
RefSeq (protein) NP_000135 NP_032070
Location (UCSC) Chr 9:
69.04 – 69.1 Mb
Chr 19:
24.26 – 24.28 Mb
PubMed search [1] [2]

Frataxin is a protein that in humans is encoded by the FXN gene.[1][2]

Frataxin is localized to the mitochondrion. The function of frataxin is not entirely clear, but it seems to be involved in assembly of iron-sulfur clusters. It has been proposed to act as either an iron chaperone or an iron storage protein.[3]

Frataxin mRNA is predominantly expressed in tissues with a high metabolic rate (including liver, kidney, brown fat and heart). Mouse and yeast frataxin homologues contain a potential N-terminal mitochondrial targeting sequence, and human frataxin has been observed to co-localise with a mitochondrial protein. Furthermore, disruption of the yeast gene has been shown to result in mitochondrial dysfunction. Friedreich's ataxia is thus believed to be a mitochondrial disease caused by a mutation in the nuclear genome (specifically, expansion of an intronic GAA triplet repeat in the FXN gene, which encodes the protein frataxin.).[1][4][5]

Clinical significance[edit]

Reduced expression of frataxin is the cause of Friedreich's ataxia (FRDA), a lethal neurodegenerative disease. The reduction in frataxin gene expression may be attributable from either the silencing of transcription of the frataxin gene because of epigenetic modifciations in the chromosomal entity[6] or from the inability of splicing the expanded GAA repeats in the first intron of the pre-mRNA as seen in Bacteria[7] and Human cells[8] or both. The expansion of intronic trinucleotide repeat GAA results in Friedreich's ataxia.[9]

An overexpression of frataxin in Drosophila has shown an increase in antioxidant capability, resistance to oxidative stress insults and longevity.[10]


Frataxin has been shown to biologically interact with the enzyme PMPCB.[11]


  1. ^ a b Campuzano V, Montermini L, Moltò MD, Pianese L, Cossée M, Cavalcanti F, Monros E, Rodius F, Duclos F, Monticelli A, Zara F, Cañizares J, Koutnikova H, Bidichandani SI, Gellera C, Brice A, Trouillas P, De Michele G, Filla A, De Frutos R, Palau F, Patel PI, Di Donato S, Mandel JL, Cocozza S, Koenig M, Pandolfo M (March 1996). "Friedreich's ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion". Science 271 (5254): 1423–7. doi:10.1126/science.271.5254.1423. PMID 8596916. 
  2. ^ Carvajal JJ, Pook MA, dos Santos M, Doudney K, Hillermann R, Minogue S, Williamson R, Hsuan JJ, Chamberlain S (October 1996). "The Friedreich's ataxia gene encodes a novel phosphatidylinositol-4- phosphate 5-kinase". Nat. Genet. 14 (2): 157–62. doi:10.1038/ng1096-157. PMID 8841185. 
  3. ^ Adinolfi S, Iannuzzi C, Prischi F, Pastore C, Iametti S, Martin SR, Bonomi F, Pastore A (April 2009). "Bacterial frataxin CyaY is the gatekeeper of iron-sulfur cluster formation catalyzed by IscS". Nat. Struct. Mol. Biol. 16 (4): 390–6. doi:10.1038/nsmb.1579. PMID 19305405. 
  4. ^ Durr A, Cossee M, Agid Y, Campuzano V, Mignard C, Penet C, Mandel JL, Brice A, Koenig M (October 1996). "Clinical and genetic abnormalities in patients with Friedreich's ataxia". N. Engl. J. Med. 335 (16): 1169–75. doi:10.1056/NEJM199610173351601. PMID 8815938. 
  5. ^ Koutnikova H, Campuzano V, Foury F, Dollé P, Cazzalini O, Koenig M (August 1997). "Studies of human, mouse and yeast homologues indicate a mitochondrial function for frataxin". Nat. Genet. 16 (4): 345–51. doi:10.1038/ng0897-345. PMID 9241270. 
  6. ^ Kim E, Napierala M, Dent SY (July 2011). "Hyperexpansion of GAA repeats affects post-initiation steps of FXN transcription in Friedreich's ataxia". Nucleic Acids Res. 39 (4): 1–12. doi:10.1093/nar/gkr542. PMC 3201871. PMID 21745819. 
  7. ^ Pan X, Ding Y, Shi L (November 2009). "The roles of SbcCD and RNaseE in the transcription of GAA · TTC repeats in Escherichia coli". DNA Repair (Amst). 8 (11): 1321–7. doi:10.1016/j.dnarep.2009.08.001. PMID 19733517. 
  8. ^ Baralle M, Pastor T, Bussani E, Pagani F (July 2008). "Influence of Friedreich Ataxia GAA Noncoding Repeat Expansions on Pre-mRNA Processing". Am J Hum Genet. 83 (1): 77–88. doi:10.1016/j.ajhg.2008.06.018. PMC 2443835. PMID 18597733. 
  9. ^ "Entrez Gene: FXN frataxin". 
  10. ^ Runko AP, Griswold AJ, Min KT (March 2008). "Overexpression of frataxin in the mitochondria increases resistance to oxidative stress and extends lifespan in Drosophila". FEBS Lett. 582 (5): 715–9. doi:10.1016/j.febslet.2008.01.046. PMID 18258192. 
  11. ^ Koutnikova, H; Campuzano V; Koenig M (Sep 1998). "Maturation of wild-type and mutated frataxin by the mitochondrial processing peptidase". Hum. Mol. Genet. (ENGLAND) 7 (9): 1485–9. doi:10.1093/hmg/7.9.1485. ISSN 0964-6906. PMID 9700204. 

Further reading[edit]

External links[edit]