Frataxin

Frataxin
PDB rendering based on 1ekg.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1EKG, 1LY7, 3S4M, 3S5D, 3S5E, 3S5F, 3T3J, 3T3K, 3T3L, 3T3T, 3T3X
Identifiers
Symbols	FXN ; CyaY; FA; FARR; FRDA; X25
External IDs	OMIM: 606829 MGI: 1096879 HomoloGene: 47908 GeneCards: FXN Gene
EC number	1.16.3.1
Gene ontology Molecular function • ferroxidase activity • protein binding • ferrous iron binding • ferric iron binding • iron chaperone activity • iron-sulfur cluster binding • 2 iron, 2 sulfur cluster binding Cellular component • mitochondrion • mitochondrial matrix • cytosol Biological process • oxidative phosphorylation • heme biosynthetic process • ion transport • cellular iron ion homeostasis • mitochondrion organization • adult walking behavior • positive regulation of cell proliferation • aerobic respiration • embryo development ending in birth or egg hatching • response to iron ion • regulation of ferrochelatase activity • protein autoprocessing • iron incorporation into metallo-sulfur cluster • proprioception • positive regulation of cell growth • negative regulation of multicellular organism growth • negative regulation of apoptotic process • small molecule metabolic process • negative regulation of organ growth • positive regulation of metalloenzyme activity • positive regulation of lyase activity • cellular response to hydrogen peroxide • negative regulation of release of cytochrome c from mitochondria • positive regulation of succinate dehydrogenase activity • positive regulation of aconitate hydratase activity Sources: Amigo / QuickGO
RNA expression pattern
File:PBB GE FXN 205565 s at tn.png
More reference expression data
Orthologs
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.

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.

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.).

Clinical significance

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 or from the inability of splicing the expanded GAA repeats in the first intron of the pre-mRNA as seen in Bacteria and Human cells or both. The expansion of intronic trinucleotide repeat GAA results in Friedreich's ataxia.

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

Interactions

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

External links

• GeneReviews/NCBI/NIH/UW entry on Friedreich Ataxia
• frataxin at the US National Library of Medicine Medical Subject Headings (MeSH)