Affinage

FXN

Frataxin, mitochondrial · UniProt Q16595

Length
210 aa
Mass
23.1 kDa
Annotated
2026-06-09
100 papers in source corpus 23 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Frataxin (FXN) is an essential mitochondrial iron-binding protein that functions in iron-sulfur (Fe-S) cluster biogenesis and the protection of mitochondria from iron-mediated oxidative damage (PMID:11590127, PMID:19305405). The protein adopts a conserved fold of a six-stranded antiparallel β-sheet flanked by two α-helices (PMID:10908679), presenting a highly anionic surface that binds both ferrous and ferric iron with weak, chaperone-like affinity and attenuates Fenton-driven hydroxyl radical production (PMID:15276847, PMID:15530368). Through this iron-binding surface, frataxin acts as an iron-dependent regulator of Fe-S cluster assembly: the bacterial ortholog CyaY binds the cysteine desulfurase IscS to slow cluster formation on the IscU scaffold by modulating IscS enzymatic activity, with IscX competing for the same IscS surface to provide iron-concentration-dependent tuning of assembly rate (PMID:19305405, PMID:21799759, PMID:29457004). Restoring frataxin to FRDA-deficient cells reverses mitochondrial iron accumulation, loss of membrane potential, and reduced Fe-S enzyme (aconitase) activity, while delivery of functional frataxin to deficient neurons and mice restores succinate dehydrogenase activity and reduces apoptotic signaling, directly establishing its role in mitochondrial iron homeostasis and oxidative protection (PMID:11590127, PMID:28980774). In Friedreich ataxia, expanded GAA repeats in FXN intron 1 silence the gene through heterochromatin-like histone marks confined to the locus, blocking the transition from initiation to productive transcriptional elongation, with additional promoter-level initiation deficiency, altered 5-hydroxymethylcytosine and reduced CTCF occupancy, and post-transcriptional repression by miRNAs targeting the FXN 3′-UTR (PMID:21745819, PMID:26401053, PMID:24023969, PMID:23382970, PMID:32291635).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1999 Medium

    Established whether the bacterial frataxin ortholog was essential, testing if its structural conservation implied a conserved indispensable iron role.

    Evidence Homologous recombination knockout of cyaY in E. coli with iron content and oxidant sensitivity readouts

    PMID:10452520

    Open questions at the time
    • Negative result under normal conditions did not exclude a redundant or condition-specific role
    • No biochemical mechanism addressed
  2. 2000 High

    Defined the frataxin fold at atomic resolution, providing the structural framework for interpreting disease mutations and iron binding.

    Evidence X-ray crystallography of E. coli CyaY at 1.4 Å

    PMID:10908679

    Open questions at the time
    • Structure alone did not assign function
    • Iron-binding surface not yet mapped
  3. 2001 High

    Placed frataxin causally in mitochondrial iron homeostasis by showing re-expression reverses the deficiency phenotype.

    Evidence Stable frataxin transfection of FRDA lymphoblasts with mitochondrial iron, membrane potential, and aconitase/ICDH assays

    PMID:11590127

    Open questions at the time
    • Did not resolve direct molecular partners
    • Whether the defect is primary in Fe-S assembly vs iron sequestration unresolved
  4. 2004 High

    Characterized the iron-binding biochemistry and antioxidant behavior, supporting an iron chaperone role and mapping iron to a conserved anionic surface.

    Evidence ITC, EPR spin trapping, spectroscopy, ultracentrifugation, and NMR with mutagenesis of CyaY

    PMID:15276847 PMID:15530368

    Open questions at the time
    • Weak affinity left physiological iron donation uncertain
    • Secondary CyaY sites absent in human frataxin limit direct extrapolation
  5. 2003 Medium

    Confirmed mitochondrial targeting from the native locus and demonstrated FXN expression is pharmacologically tunable.

    Evidence BAC FRDA-EGFP fusion in stable cells with fluorescence localization and pharmacological treatment

    PMID:12516053

    Open questions at the time
    • Mechanism of hemin/butyrate upregulation not defined
    • Reporter context may differ from endogenous regulation
  6. 2009 High

    Resolved whether frataxin activates or inhibits Fe-S assembly by showing CyaY is an iron-dependent inhibitor binding IscS through its iron surface.

    Evidence Biochemical/biophysical binding to IscS, cluster formation kinetics, and iron-surface mutagenesis

    PMID:19305405

    Open questions at the time
    • Inhibitory directionality differs from activating models reported for the human system
    • In vivo regulatory relevance not established here
  7. 2011 High

    Independently confirmed the inhibitory mechanism and localized the effect to IscS enzymatic activity, and separately established that GAA repeats block transcriptional elongation rather than initiation.

    Evidence Spectroscopic cluster-formation kinetics on IscU; ChIP-qPCR and GFP reporter with 560 GAA repeats plus pre-mRNA quantification

    PMID:21745819 PMID:21799759

    Open questions at the time
    • Reconciliation of elongation-block vs initiation-block models for the disease locus unresolved
    • Cluster-type ratio unaffected leaves the precise regulatory output unclear
  8. 2015 Medium

    Defined the regulatory logic of frataxin in assembly via IscX competition and refined the chromatin and transcriptional basis of FXN silencing.

    Evidence Genetic cyaY/iscX epistasis; RNA-seq and ChIP confining heterochromatin to the FXN locus; nascent transcript labeling in a humanized mouse model

    PMID:25430730 PMID:26393353 PMID:26401053

    Open questions at the time
    • Initiation-deficiency (YG8sR) vs elongation-block (patient cells) findings not fully reconciled
    • Whether bacterial IscX competition has a eukaryotic equivalent unknown
  9. 2013 Medium

    Identified post-transcriptional and epigenetic layers of FXN repression beyond the GAA chromatin defect.

    Evidence Luciferase 3′-UTR reporters with cohort sequencing (miR-124); MethylScreen and CTCF ChIP in FRDA cerebellum/heart

    PMID:23382970 PMID:24023969

    Open questions at the time
    • Relative contribution of miRNA vs chromatin silencing to total deficit unquantified
    • Functional consequence of 5hmC/CTCF loss on transcription not directly tested
  10. 2017 Medium

    Demonstrated structural basis of iron-driven oligomerization and that exogenous functional frataxin can rescue mitochondrial enzyme and survival defects.

    Evidence DLS/SAXS/EM/cross-linking MS of human FXN81-210 and CyaY; TAT-MTScs-FXN delivery to DRG neurons and FRDA mice with enzyme and apoptosis readouts

    PMID:28980774 PMID:29200434

    Open questions at the time
    • Physiological role of human frataxin oligomers uncertain given low stability
    • Delivery rescue durability and dosing not fully resolved
  11. 2020 Medium

    Extended the miRNA regulatory network controlling FXN levels.

    Evidence miRNAseq/RNAseq, luciferase, qRT-PCR, immunoblot, and ZFN GAA excision for miR-224-5p

    PMID:32291635

    Open questions at the time
    • In vivo relevance to neuronal/cardiac tissue not established
    • Interaction with chromatin-level silencing unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the human frataxin–NFS1/ISCU regulatory interaction (inhibitory vs activating) and the relative weight of transcriptional, chromatin, and miRNA mechanisms combine to determine tissue-specific frataxin deficit remain unresolved.
  • Direct human FXN-NFS1-ISCU mechanism not biochemically resolved in this corpus
  • Quantitative apportioning of silencing mechanisms missing
  • Tissue-selectivity of pathology mechanistically unexplained

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0140313 molecular sequestering activity 3 GO:0016209 antioxidant activity 2
Localization
GO:0005739 mitochondrion 3 GO:0005829 cytosol 1
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-1643685 Disease 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
ISCS/NFS1ISCU/ISCUISCX

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 Bacterial frataxin ortholog CyaY acts as an iron-dependent inhibitor of iron-sulfur (Fe-S) cluster formation by binding to the desulfurase IscS through its iron-binding surface, functioning as an iron sensor/regulator that fine-tunes Fe-S cluster assembly relative to available acceptor concentration. Biochemical and biophysical assays (iron-dependent binding to IscS, kinetic measurements of cluster formation, site-directed analysis of iron-binding surface) Nature structural & molecular biology High 19305405
2000 The crystal structure of E. coli frataxin ortholog CyaY was solved at 1.4 Å resolution, revealing a novel fold consisting of a six-stranded antiparallel β-sheet flanked by two α-helices, predicted to be shared by all frataxin family members and providing a framework for interpreting disease-associated mutations. X-ray crystallography (1.4 Å resolution) Proceedings of the National Academy of Sciences of the United States of America High 10908679
2004 CyaY (bacterial frataxin ortholog) binds at least two ferrous ions per monomer with weak affinity (Kd ~4 µM), consistent with an iron chaperone role; Fe(II) is oxidized rapidly by H2O2 (not O2) with stoichiometry of 2 Fe(II)/H2O2, greatly attenuating hydroxyl radical production from Fenton chemistry; up to ~25–26 Fe(III) ions can bind per monomer, and iron addition induces tetramerization. Isothermal titration calorimetry (ITC), EPR spin trapping, UV-visible/fluorescence spectroscopy, iron analysis, pH-stat titrations, analytical ultracentrifugation Journal of molecular biology High 15276847
2004 The solution structure of CyaY was solved by NMR; iron binding was mapped to a highly anionic surface of the molecule (conserved across frataxin family) that hosts both Fe(2+) and Fe(3+) with defined stoichiometry without requiring aggregation; secondary binding sites on CyaY (absent in human frataxin) may underlie its polymerization mechanism. NMR structure determination, mutagenesis of iron-binding surface, comparative binding studies with wild-type vs. mutant CyaY Structure (London, England : 1993) High 15530368
2011 CyaY slows down Fe-S cluster formation on the IscU scaffold protein and does not alter the relative ratio of [2Fe2S]²⁺ to [4Fe4S]²⁺ clusters but directly affects the enzymatic activity of IscS, independently confirming an inhibitory rather than activating role for the bacterial frataxin ortholog. Spectroscopic characterization of cluster formation kinetics (UV-vis, resonance Raman, EPR, Mössbauer), enzymatic assays PloS one High 21799759
2001 Frataxin expression in Friedreich's ataxia lymphoblasts rescues mitochondrial iron homeostasis and membrane potential defects: FXN-deficient cells showed increased filtrable mitochondrial iron, decreased mitochondrial membrane potential (MMP), and reduced aconitase/ICDH activities, all of which were reversed by transfection of frataxin to near-physiological levels, establishing frataxin's direct role in mitochondrial iron homeostasis and protection from oxidative stress. Stable transfection of frataxin into FRDA compound heterozygote lymphoblasts, mitochondrial iron measurement, MMP measurement, aconitase/ICDH enzyme assays, oxidative stress challenge Human molecular genetics High 11590127
2015 CyaY is a member of the ISC pathway for Fe-S cluster protein maturation in E. coli, requiring iron-rich conditions for its contribution; a genetic interaction was discovered between cyaY and iscX (additive effect on Fe-S cluster maturation when both genes are deleted), establishing IscX as a co-regulator. Genetic knockout/double knockout, in vivo Fe-S cluster protein activity assays, growth phenotype analysis under iron-variable conditions Molecular microbiology Medium 25430730
2018 IscX (YfhJ) competes with CyaY for the same binding surface on IscS; at low iron concentrations IscX rescues the CyaY-inhibited rate of enzymatic Fe-S cluster formation, while at high iron the competition effect is negligible, establishing a dual iron-concentration-dependent regulatory mechanism of Fe-S cluster assembly mediated by the CyaY/IscX competition. NMR, small-angle X-ray scattering (SAXS), biochemical competition assays, kinetic measurements of cluster assembly Frontiers in molecular biosciences High 29457004
1999 Knockout of cyaY in E. coli did not affect cellular iron content or sensitivity to oxidants under normal conditions, suggesting that despite structural similarities CyaY may have a different or redundant function compared to mitochondrial frataxin homologs in eukaryotes. Homologous recombination knockout, iron content measurement, H2O2 sensitivity assay FEBS letters Medium 10452520
2007 CyaY (frataxin ortholog) expressed as a mitochondria-targeted form in S. cerevisiae yfh1Δ complemented loss of Fe-S cluster enzyme activities and heme synthesis, maintaining near-normal respiratory growth and protecting against oxidative damage, demonstrating partial conservation of frataxin function between prokaryotes and eukaryotes. Mitochondria-targeted expression of CyaY in frataxin-null yeast, respiratory growth assays, Fe-S enzyme activity measurements, oxidative stress assays FEMS yeast research Medium 17727661
2007 Deletion of cyaY in E. coli reduces the amount of assembled respiratory complex I (NADH:ubiquinone oxidoreductase) by one third, but the assembled complex retains full activity and all iron-sulfur clusters; live-cell GFP imaging and fractionation showed CyaY localizes to the cytoplasm, not the membrane, establishing a non-essential assembly role rather than structural component role. cyaY deletion mutant analysis, Western blot, live-cell GFP imaging, subcellular fractionation, complex I activity assay BMC biochemistry Medium 17650323
2011 Expanded GAA repeats in FXN intron 1 induce heterochromatin-like histone modifications downstream of the promoter (near the GAA tract) and impede the transition from transcription initiation to productive elongation; pre-mRNA levels upstream of the GAA repeats were similar in FRDA and control cells, establishing that the primary block is at post-initiation/elongation, not initiation. Chromatin immunoprecipitation (ChIP) with quantitative PCR, GFP reporter assay with 560 GAA repeats, pre-mRNA quantification by qPCR Nucleic acids research High 21745819
2015 Expanded GAA repeats impede transcription elongation through the FXN locus without affecting neighboring genes; deep sequencing of FXN pre-mRNA revealed a pronounced elongation defect in FRDA cells; ChIP studies confirmed heterochromatin histone marks are confined to the FXN locus and not spread to flanking genomic regions. Next-generation RNA sequencing of FRDA and control fibroblasts, FXN pre-mRNA deep sequencing, ChIP with histone modification antibodies Human molecular genetics High 26401053
2003 Frataxin-EGFP fusion proteins are targeted to mitochondria when driven by the endogenous FRDA locus regulatory elements; hemin and butyric acid enhance FRDA gene expression from the intact locus, establishing that FXN expression can be pharmacologically upregulated. BAC-based FRDA-EGFP fusion construct in stable cell lines, mitochondrial targeting verified by fluorescence, RT-PCR for expression, pharmacological treatment The journal of gene medicine Medium 12516053
2013 miR-124 (hsa-mir-124-3p) directly binds to the FXN 3'-UTR and downregulates frataxin expression; an FRDA-specific 3'-UTR haplotype confers reduced reporter gene expression compared to an alternative haplotype, establishing post-transcriptional regulation of FXN through miRNA targeting. Luciferase reporter assays with FXN 3'-UTR constructs, sequencing of 3'-UTR in FRDA cohorts, bioinformatic miRNA target prediction validated experimentally PloS one Medium 23382970
2020 miRNA-224-5p directly targets FXN mRNA, resulting in decreases in both FXN mRNA and frataxin protein levels in FRDA cells; validated by luciferase assays and ZFN-mediated GAA repeat excision experiments. miRNAseq and RNAseq of FRDA vs. control cells, luciferase reporter assays, qRT-PCR, immunoblotting, ZFN-mediated GAA repeat excision Molecular neurobiology Medium 32291635
2013 Increased 5-hydroxymethylcytosine (5hmC, not 5mC) is the predominant form of DNA methylation at the FXN upstream GAA region in FRDA cerebellum and heart tissues; decreased CTCF occupancy at the FXN 5' UTR was identified in FRDA cerebellum, implicating chromatin insulator disruption in FXN silencing. MethylScreen restriction enzyme digestion/qPCR distinguishing 5hmC vs 5mC, chromatin immunoprecipitation (ChIP) for CTCF PloS one Medium 24023969
2015 FXN transcriptional deficiency in Friedreich ataxia results primarily from deficient transcriptional initiation (promoter silencing) across multiple cell types and tissues, as shown by metabolic labeling of newly synthesized transcripts in fibroblasts from the YG8sR humanized mouse model. Metabolic labeling of nascent transcripts, transgenic humanized mouse model comparison (YG8sR vs Y47R), multi-tissue qRT-PCR PloS one Medium 26393353
2017 TAT-MTScs-FXN fusion protein (frataxin delivered via TAT cell-penetrating peptide) reaches muscle mitochondria in vivo, restores succinate dehydrogenase activity, increases cell survival, decreases neurite degeneration, reduces apoptotic markers (α-fodrin cleavage, caspase 9 activation), rescues impaired HSP60 processing in frataxin-deficient DRG neurons, and prolongs lifespan in FRDA mouse models. TAT-peptide-frataxin protein delivery to DRG neurons and mice, mitochondrial fractionation, enzyme activity assay (succinate dehydrogenase), immunoblotting for apoptotic markers, lifespan analysis Journal of cellular and molecular medicine Medium 28980774
2017 FXN81-210 (mature human frataxin) forms oligomers in the presence of iron under aerobic conditions; FXN81-210 and CyaY monomers pack in a head-to-tail, ring-shaped fashion with iron-binding sites at monomer interfaces; FXN81-210 oligomers are less stable than CyaY oligomers (dissociate after ~24 h) due to fewer acidic residues at the interface; FXN81-210 oligomerization is primarily driven by ferric iron while CyaY requires both ferric and ferrous iron. Dynamic light scattering, SAXS, electron microscopy, cross-linking mass spectrometry PloS one Medium 29200434
2015 Frataxin deficiency in hiPSC-derived cardiomyocytes leads to iron accumulation, ROS production, mitochondrial network disorganization, reduced respiratory chain proteins (CxII/COXIV), and impaired calcium handling; deferiprone (DFP) modulates iron homeostasis including the IRP-1/ferritin/transferrin receptor regulatory loop, restoring redox conditions and cardiac EC coupling function. hiPSC-derived FRDA cardiomyocytes, ROS assay, iron uptake measurement, immunoblotting for respiratory chain proteins, calcium imaging, drug treatment International journal of cardiology Medium 26625322
2016 Compound heterozygous FRDA patients with mutations in the hydrophobic core of frataxin show reduced stability, while surface residue mutations affect frataxin interactions with iron-sulfur cluster assembly and heme biosynthetic proteins; null mutations (no frataxin) lead to significantly earlier disease onset and increased diabetes compared to those retaining partially functional frataxin. Structural modeling, stability analyses, systematic literature review of mutations, clinical regression analyses Annals of neurology Low 26704351
2015 miRNA-145 directly binds to the 3'-UTR of FXN and negatively regulates its expression; FXN deficiency downstream of miRNA-145 regulation affects apoptosis and mitochondrial function in cardiac cells. TargetScan bioinformatic prediction, real-time PCR of clinical samples, cell line experiments confirming direct 3'-UTR binding and negative regulation, apoptosis and mitochondrial function assays Pediatric cardiology Low 26717909

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 The cannabinoid CB1 receptor antagonist SR141716 increases Acrp30 mRNA expression in adipose tissue of obese fa/fa rats and in cultured adipocyte cells. Molecular pharmacology 472 12644592
2007 Rimonabant reduces obesity-associated hepatic steatosis and features of metabolic syndrome in obese Zucker fa/fa rats. Hepatology (Baltimore, Md.) 247 17526015
2009 Bacterial frataxin CyaY is the gatekeeper of iron-sulfur cluster formation catalyzed by IscS. Nature structural & molecular biology 207 19305405
2018 The roles of free ammonia (FA) in biological wastewater treatment processes: A review. Environment international 196 30481673
1990 Exercise training increases glucose transporter protein GLUT-4 in skeletal muscle of obese Zucker (fa/fa) rats. FEBS letters 149 2200706
2003 Arcuate nucleus-specific leptin receptor gene therapy attenuates the obesity phenotype of Koletsky (fa(k)/fa(k)) rats. Endocrinology 138 12697710
1998 Leptin receptor signal transduction: OBRa and OBRb of fa type. Biochemical and biophysical research communications 127 9618284
2016 Compound heterozygous FXN mutations and clinical outcome in friedreich ataxia. Annals of neurology 119 26704351
2005 Soy protein reduces hepatic lipotoxicity in hyperinsulinemic obese Zucker fa/fa rats. Journal of lipid research 119 15995177
2004 Solution structure of the bacterial frataxin ortholog, CyaY: mapping the iron binding sites. Structure (London, England : 1993) 114 15530368
2000 Topiramate reduces energy and fat gains in lean (Fa/?) and obese (fa/fa) Zucker rats. Obesity research 107 11225714
2004 Iron binding and oxidation kinetics in frataxin CyaY of Escherichia coli. Journal of molecular biology 103 15276847
1999 Altered expression of hepatic CYP2E1 and CYP4A in obese, diabetic ob/ob mice, and fa/fa Zucker rats. Biochemical and biophysical research communications 99 10049703
2000 Crystal structure of Escherichia coli CyaY protein reveals a previously unidentified fold for the evolutionarily conserved frataxin family. Proceedings of the National Academy of Sciences of the United States of America 97 10908679
2009 CHK1 inhibition as a strategy for targeting Fanconi Anemia (FA) DNA repair pathway deficient tumors. Molecular cancer 96 19371427
2012 FXN methylation predicts expression and clinical outcome in Friedreich ataxia. Annals of neurology 93 22522441
2001 Frataxin expression rescues mitochondrial dysfunctions in FRDA cells. Human molecular genetics 74 11590127
2012 FAAP20: a novel ubiquitin-binding FA nuclear core-complex protein required for functional integrity of the FA-BRCA DNA repair pathway. Blood 73 22343915
2007 The Fanconi anemia (FA) pathway confers glioma resistance to DNA alkylating agents. Journal of molecular medicine (Berlin, Germany) 72 17221219
2012 Fanconi anemia (FA) binding protein FAAP20 stabilizes FA complementation group A (FANCA) and participates in interstrand cross-link repair. Proceedings of the National Academy of Sciences of the United States of America 70 22396592
2005 Physiological difference between obese (fa/fa) Zucker rats and lean Zucker rats concerning adiponectin. Metabolism: clinical and experimental 69 16092047
2011 Hyperexpansion of GAA repeats affects post-initiation steps of FXN transcription in Friedreich's ataxia. Nucleic acids research 65 21745819
2015 Expanded GAA repeats impede transcription elongation through the FXN gene and induce transcriptional silencing that is restricted to the FXN locus. Human molecular genetics 64 26401053
1998 Parental gender, age at birth and expansion length influence GAA repeat intergenerational instability in the X25 gene: pedigree studies and analysis of sperm from patients with Friedreich's ataxia. Human molecular genetics 64 9811933
1999 Knock-out of the cyaY gene in Escherichia coli does not affect cellular iron content and sensitivity to oxidants. FEBS letters 61 10452520
2003 FarR regulates the farAB-encoded efflux pump of Neisseria gonorrhoeae via an MtrR regulatory mechanism. Journal of bacteriology 60 14645274
2003 Characterization of bone structure in leptin receptor-deficient Zucker (fa/fa) rats. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 59 12968669
2003 Upregulation of expression from the FRDA genomic locus for the therapy of Friedreich ataxia. The journal of gene medicine 57 12516053
1980 Genetic and physical characterization of lambda transducing phages (lambda frdA) containing the fumarate reductase gene of Escherichia coli K12. Molecular & general genetics : MGG 49 6446651
2011 Both FA- and mPEG-conjugated chitosan nanoparticles for targeted cellular uptake and enhanced tumor tissue distribution. Nanoscale research letters 47 22027239
2006 Anti-dsDNA antibody testing by Farr and ELISA techniques is not equivalent. The Journal of rheumatology 47 16924691
1990 The fumarate reductase operon of Wolinella succinogenes. Sequence and expression of the frdA and frdB genes. Archives of microbiology 47 2244791
2018 Causes and solutions to "globesity": The new fa(s)t alarming global epidemic. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 46 30176311
2011 DHA and EPA reverse cystic fibrosis-related FA abnormalities by suppressing FA desaturase expression and activity. Journal of lipid research 44 22095831
2007 Infectious delivery and expression of a 135 kb human FRDA genomic DNA locus complements Friedreich's ataxia deficiency in human cells. Molecular therapy : the journal of the American Society of Gene Therapy 43 17235301
2012 Exonic deletions of FXN and early-onset Friedreich ataxia. Archives of neurology 39 22409940
1993 Decreased expression of protein kinase-C alpha, beta, and epsilon in soleus muscle of Zucker obese (fa/fa) rats. Endocrinology 39 8404676
2020 FXR-mediated inhibition of autophagy contributes to FA-induced TG accumulation and accordingly reduces FA-induced lipotoxicity. Cell communication and signaling : CCS 38 32192487
2011 The role of CyaY in iron sulfur cluster assembly on the E. coli IscU scaffold protein. PloS one 38 21799759
2003 Phosphotransferase-mediated transport of the osmolyte 2-O-alpha-mannosyl-D-glycerate in Escherichia coli occurs by the product of the mngA (hrsA) gene and is regulated by the mngR (farR) gene product acting as repressor. The Journal of biological chemistry 38 14645248
1997 Differential responsiveness of obese (fa/fa) and lean (Fa/Fa) Zucker rats to cytokine-induced anorexia. Obesity research 38 9061714
1994 Identification of a fatty acyl responsive regulator (FarR) in Escherichia coli. FEBS letters 38 7805834
2020 Degradation of FA reduces Aβ neurotoxicity and Alzheimer-related phenotypes. Molecular psychiatry 36 33328587
2013 Pharmacological screening using an FXN-EGFP cellular genomic reporter assay for the therapy of Friedreich ataxia. PloS one 36 23418481
2006 Assessing the link between BACH1 and BRCA1 in the FA pathway. Cell cycle (Georgetown, Tex.) 36 16357529
1998 An association between NIDDM and a GAA trinucleotide repeat polymorphism in the X25/frataxin (Friedreich's ataxia) gene. Diabetes 36 9588463
2015 The iron-binding CyaY and IscX proteins assist the ISC-catalyzed Fe-S biogenesis in Escherichia coli. Molecular microbiology 35 25430730
2020 Obesity and Age-Related Changes in the Brain of the Zucker Lepr Rats. Nutrients 34 32397542
1999 Analysis of Tyr to Phe and fa/fa leptin receptor mutations in the PC12 cell line. European cytokine network 34 10586122
2014 Distinct roles of the Salmonella enterica serovar Typhimurium CyaY and YggX proteins in the biosynthesis and repair of iron-sulfur clusters. Infection and immunity 33 24421039
2017 FA-SAT Is an Old Satellite DNA Frozen in Several Bilateria Genomes. Genome biology and evolution 32 29608678
2007 Disruption of the FA/BRCA pathway in bladder cancer. Cytogenetic and genome research 32 18000367
2017 Frataxin-deficient neurons and mice models of Friedreich ataxia are improved by TAT-MTScs-FXN treatment. Journal of cellular and molecular medicine 31 28980774
2016 Gene Transfer of Brain-derived Neurotrophic Factor (BDNF) Prevents Neurodegeneration Triggered by FXN Deficiency. Molecular therapy : the journal of the American Society of Gene Therapy 31 26849417
2015 Efficient attenuation of Friedreich's ataxia (FRDA) cardiomyopathy by modulation of iron homeostasis-human induced pluripotent stem cell (hiPSC) as a drug screening platform for FRDA. International journal of cardiology 31 26625322
2017 A never-ending story: the steadily growing family of the FA and FA-like genes. Genetics and molecular biology 30 28558075
2020 SSO and other putative inhibitors of FA transport across membranes by CD36 disrupt intracellular metabolism, but do not affect FA translocation. Journal of lipid research 29 32102800
2016 Infectious Delivery and Expression of a 135 kb Human FRDA Genomic DNA Locus Complements Friedreich's Ataxia Deficiency in Human Cells. Molecular therapy : the journal of the American Society of Gene Therapy 29 28182935
2020 Multiple mechanisms underpin cerebral and cerebellar white matter deficits in Friedreich ataxia: The IMAGE-FRDA study. Human brain mapping 28 31904895
2012 A Boolean network model of the FA/BRCA pathway. Bioinformatics (Oxford, England) 27 22267503
1999 Leptin responsiveness and gene dosage for leptin receptor mutation (fa) in newborn rats. The American journal of physiology 27 10329976
1980 Adipocyte size distribution in fa/fa rats during development. Metabolism: clinical and experimental 27 7374443
2013 Genetic variations creating microRNA target sites in the FXN 3'-UTR affect frataxin expression in Friedreich ataxia. PloS one 26 23382970
2007 Effects of the deletion of the Escherichia coli frataxin homologue CyaY on the respiratory NADH:ubiquinone oxidoreductase. BMC biochemistry 26 17650323
2018 The Molecular Bases of the Dual Regulation of Bacterial Iron Sulfur Cluster Biogenesis by CyaY and IscX. Frontiers in molecular biosciences 25 29457004
2015 MiRNA-145 Regulates the Development of Congenital Heart Disease Through Targeting FXN. Pediatric cardiology 25 26717909
2009 FANCM-FAAP24 and FANCJ: FA proteins that metabolize DNA. Mutation research 25 19379763
2000 Atypical Friedreich ataxia phenotype associated with a novel missense mutation in the X25 gene. Neurology 25 10668723
1981 Serum insulin and lipogenesis in the suckling 'fatty' fa/fa rat. Diabetologia 25 6114892
2016 Defects in homologous recombination repair behind the human diseases: FA and HBOC. Endocrine-related cancer 24 27550963
2014 Epigenetics and development of food allergy (FA) in early childhood. Current allergy and asthma reports 23 25096861
2012 Clinical use of frataxin measurement in a patient with a novel deletion in the FXN gene. Journal of neurology 23 23196337
2007 Partial conservation of functions between eukaryotic frataxin and the Escherichia coli frataxin homolog CyaY. FEMS yeast research 23 17727661
2014 The carboxyl terminus of FANCE recruits FANCD2 to the Fanconi Anemia (FA) E3 ligase complex to promote the FA DNA repair pathway. The Journal of biological chemistry 22 24451376
2013 Friedreich ataxia patient tissues exhibit increased 5-hydroxymethylcytosine modification and decreased CTCF binding at the FXN locus. PloS one 22 24023969
2011 Characterization of E. coli MG1655 and frdA and sdhC mutants at various aerobiosis levels. Journal of biotechnology 22 21458504
2008 Abnormal immune responses in fa/fa Zucker rats and effects of feeding conjugated linoleic acid. Obesity (Silver Spring, Md.) 22 18483478
2015 A case report and literature review of Fanconi Anemia (FA) diagnosed by genetic testing. Italian journal of pediatrics 21 25953249
2010 Remarkable features of ovarian morphology and reproductive hormones in insulin-resistant Zucker fatty (fa/fa) rats. Reproductive biology and endocrinology : RB&E 20 20576113
2008 BRCA-FA pathway as a target for anti-tumor drugs. Anti-cancer agents in medicinal chemistry 20 18473727
2010 A novel role for Fanconi anemia (FA) pathway effector protein FANCD2 in cell cycle progression of untransformed primary human cells. Cell cycle (Georgetown, Tex.) 19 20519958
2000 Heterozygous expansion of the GAA tract of the X25/frataxin gene is associated with insulin resistance in humans. Diabetes 19 10969848
1999 Corticotropin-releasing hormone-binding protein in brain and pituitary of food-deprived obese (fa/fa) Zucker rats. The American journal of physiology 19 10600923
2019 The first biallelic missense mutation in the FXN gene in a consanguineous Turkish family with Charcot-Marie-Tooth-like phenotype. Neurogenetics 18 31673878
2017 Activation of the FA pathway mediated by phosphorylation and ubiquitination. Mutation research 18 28552166
2015 FXN Promoter Silencing in the Humanized Mouse Model of Friedreich Ataxia. PloS one 18 26393353
2002 Identification of a novel transcript of X25, the human gene involved in Friedreich ataxia. Neuroscience letters 18 11852181
2019 The Mechanism FA-Dependent H+ Transport by UCP1. Handbook of experimental pharmacology 17 29797089
2013 Frataxin mRNA isoforms in FRDA patients and normal subjects: effect of tocotrienol supplementation. BioMed research international 17 24175286
2001 Renal and metabolic effects of caffeine in obese (fa/fa(cp)), diabetic, hypertensive ZSF1 rats. Renal failure 17 11417948
2020 A Comprehensive Transcriptome Analysis Identifies FXN and BDNF as Novel Targets of miRNAs in Friedreich's Ataxia Patients. Molecular neurobiology 16 32291635
2018 Oligomerization of the FERM-FA protein Yurt controls epithelial cell polarity. The Journal of cell biology 16 30082297
2015 Analyzing the Effects of a G137V Mutation in the FXN Gene. Frontiers in molecular neuroscience 16 26635519
2002 Intrafamilial phenotypic variability in Friedreich ataxia associated with a G130V mutation in the FRDA gene. Archives of neurology 16 11843702
2017 Iron-induced oligomerization of human FXN81-210 and bacterial CyaY frataxin and the effect of iron chelators. PloS one 14 29200434
2014 Phylogenetic analyses and characterization of RNase X25 from Drosophila melanogaster suggest a conserved housekeeping role and additional functions for RNase T2 enzymes in protostomes. PloS one 14 25133712
2006 Integration Host Factor is required for FarR repression of the farAB-encoded efflux pump of Neisseria gonorrhoeae. Molecular microbiology 14 16796676
2005 Evaluation of an FRDA-EGFP genomic reporter assay in transgenic mice. Mammalian genome : official journal of the International Mammalian Genome Society 14 15965784
1998 Ultrastructural and secretory heterogeneity of fa/fa (Zucker) rat islets. Molecular and cellular endocrinology 14 9548215
1991 Stimulation of FA and casein kinase II by insulin in 3T3-L1 cells. Biochemical and biophysical research communications 14 1647765

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