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Q16595

- FRDA_HUMAN

UniProt

Q16595 - FRDA_HUMAN

Protein

Frataxin, mitochondrial

Gene

FXN

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 156 (01 Oct 2014)
      Sequence version 2 (15 Jul 1999)
      Previous versions | rss
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    Functioni

    Promotes the biosynthesis of heme and assembly and repair of iron-sulfur clusters by delivering Fe2+ to proteins involved in these pathways. 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. Modulates the RNA-binding activity of ACO1.6 Publications

    Catalytic activityi

    4 Fe2+ + 4 H+ + O2 = 4 Fe3+ + 2 H2O.1 Publication

    GO - Molecular functioni

    1. 2 iron, 2 sulfur cluster binding Source: BHF-UCL
    2. ferric iron binding Source: BHF-UCL
    3. ferrous iron binding Source: BHF-UCL
    4. ferroxidase activity Source: UniProtKB
    5. iron chaperone activity Source: BHF-UCL
    6. iron-sulfur cluster binding Source: BHF-UCL
    7. protein binding Source: UniProtKB

    GO - Biological processi

    1. adult walking behavior Source: Ensembl
    2. aerobic respiration Source: Ensembl
    3. cellular iron ion homeostasis Source: BHF-UCL
    4. cellular response to hydrogen peroxide Source: UniProtKB
    5. embryo development ending in birth or egg hatching Source: Ensembl
    6. heme biosynthetic process Source: BHF-UCL
    7. ion transport Source: UniProtKB-KW
    8. iron incorporation into metallo-sulfur cluster Source: BHF-UCL
    9. mitochondrion organization Source: Ensembl
    10. negative regulation of apoptotic process Source: UniProtKB
    11. negative regulation of multicellular organism growth Source: Ensembl
    12. negative regulation of organ growth Source: Ensembl
    13. negative regulation of release of cytochrome c from mitochondria Source: UniProtKB
    14. oxidative phosphorylation Source: Ensembl
    15. positive regulation of cell growth Source: BHF-UCL
    16. positive regulation of cell proliferation Source: BHF-UCL
    17. positive regulation of lyase activity Source: UniProtKB
    18. positive regulation of metalloenzyme activity Source: BHF-UCL
    19. positive regulation of oxidoreductase activity Source: BHF-UCL
    20. positive regulation of transferase activity Source: BHF-UCL
    21. proprioception Source: Ensembl
    22. protein autoprocessing Source: BHF-UCL
    23. regulation of ferrochelatase activity Source: BHF-UCL
    24. response to iron ion Source: BHF-UCL
    25. small molecule metabolic process Source: Reactome

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Biological processi

    Heme biosynthesis, Ion transport, Iron storage, Iron transport, Transport

    Keywords - Ligandi

    Iron, Metal-binding

    Enzyme and pathway databases

    ReactomeiREACT_118595. Mitochondrial protein import.
    REACT_150353. Mitochondrial iron-sulfur cluster biogenesis.

    Protein family/group databases

    TCDBi9.B.21.1.1. the frataxin (frataxin) family.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Frataxin, mitochondrial (EC:1.16.3.1)
    Alternative name(s):
    Friedreich ataxia protein
    Short name:
    Fxn
    Cleaved into the following 4 chains:
    Alternative name(s):
    m56-FXN
    Alternative name(s):
    d-FXN
    m78-FXN
    Alternative name(s):
    Frataxin(81-210)
    m81-FXN
    Gene namesi
    Name:FXN
    Synonyms:FRDA, X25
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 9

    Organism-specific databases

    HGNCiHGNC:3951. FXN.

    Subcellular locationi

    Cytoplasm. Mitochondrion
    Note: PubMed:18725397 reports localization exclusively in mitochondria.

    GO - Cellular componenti

    1. cytosol Source: BHF-UCL
    2. mitochondrial matrix Source: BHF-UCL
    3. mitochondrion Source: BHF-UCL

    Keywords - Cellular componenti

    Cytoplasm, Mitochondrion

    Pathology & Biotechi

    Involvement in diseasei

    Friedreich ataxia (FRDA) [MIM:229300]: Autosomal recessive, progressive degenerative disease characterized by neurodegeneration and cardiomyopathy it is the most common inherited ataxia. The disorder is usually manifest before adolescence and is generally characterized by incoordination of limb movements, dysarthria, nystagmus, diminished or absent tendon reflexes, Babinski sign, impairment of position and vibratory senses, scoliosis, pes cavus, and hammer toe. In most patients, FRDA is due to GAA triplet repeat expansions in the first intron of the frataxin gene. But in some cases the disease is due to mutations in the coding region.8 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti106 – 1061L → S in FRDA. 1 Publication
    VAR_016065
    Natural varianti122 – 1221D → Y in FRDA. 3 Publications
    VAR_002428
    Natural varianti130 – 1301G → V in FRDA. 3 Publications
    VAR_002429
    Natural varianti154 – 1541I → F in FRDA; reduces interaction with LYRM4; the interaction is rescued by nickel. Defects in mitochondrial structure, mitochondrial iron deposits, decreased enzymatic activity of some mitochondrial and cytoplasmic iron-sulfur cluster-containing enzymes, increased RNA-binding activity of ACO1 and increased sensitivity to oxidative stress. 2 Publications
    VAR_002430
    Natural varianti155 – 1551W → R in FRDA; reduces interaction with LYRM4; the interaction is rescued by nickel. 1 Publication
    VAR_002431
    Natural varianti165 – 1651R → C in FRDA; mild form. 1 Publication
    VAR_008139
    Natural varianti182 – 1821L → F in FRDA. 1 Publication
    VAR_008140
    Natural varianti198 – 1981L → R in FRDA. 1 Publication
    VAR_016066

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi39 – 402RR → GG: Abolishes cleavage to yield frataxin intermediate form and allows accumulation of frataxin(56-210) and frataxin(78-210).
    Mutagenesisi53 – 542RR → GG: No effect on processing of wild-type FXN.
    Mutagenesisi78 – 792LR → GG: Abolishes cleavage to yield frataxin mature form and allows accumulation of frataxin(56-210) and frataxin(78-210).
    Mutagenesisi79 – 802RK → GG: Abolishes cleavage to yield frataxin mature form and allows the accumulation of frataxin(56-210).

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi229300. phenotype.
    Orphaneti95. Friedreich ataxia.
    PharmGKBiPA28369.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transit peptidei1 – 4141MitochondrionAdd
    BLAST
    Chaini42 – 210169Frataxin intermediate formPRO_0000010129Add
    BLAST
    Chaini56 – 210155Frataxin(56-210)PRO_0000010130Add
    BLAST
    Chaini78 – 210133Frataxin(78-210)PRO_0000399388Add
    BLAST
    Chaini81 – 210130Frataxin mature formPRO_0000289331Add
    BLAST

    Post-translational modificationi

    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.5 Publications

    Proteomic databases

    MaxQBiQ16595.
    PaxDbiQ16595.
    PeptideAtlasiQ16595.
    PRIDEiQ16595.

    2D gel databases

    OGPiQ16595.

    PTM databases

    PhosphoSiteiQ16595.

    Expressioni

    Tissue specificityi

    Expressed in the heart, peripheral blood lymphocytes and dermal fibroblasts.1 Publication

    Gene expression databases

    ArrayExpressiQ16595.
    BgeeiQ16595.
    CleanExiHS_FXN.
    GenevestigatoriQ16595.

    Organism-specific databases

    HPAiCAB022164.

    Interactioni

    Subunit structurei

    Monomer (probable predominant form). Oligomer. Monomers and polymeric aggregates of >1 MDa have been isolated from mitochondria. A small fraction of heterologous overexpressed recombinant frataxin forms high-molecular wight aggregates that incoroprate iron. Interacts with LYRM4 AND HSPA9. Interacts with ACO1. Interacts with ISCU isoform 1 and isoform 2. Interacts with FECH; one iron-bound FXN monomer seems to interact with a FECH homodimer. Interacts with SDHA and SDHB. Interacts with ACO2; the interaction is dependent on citrate By similarity.By similarity

    Protein-protein interaction databases

    BioGridi108677. 5 interactions.
    IntActiQ16595. 5 interactions.
    MINTiMINT-2856590.
    STRINGi9606.ENSP00000366482.

    Structurei

    Secondary structure

    1
    210
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi92 – 11423
    Beta strandi124 – 1285
    Beta strandi131 – 1355
    Turni138 – 1403
    Beta strandi142 – 1487
    Turni149 – 1524
    Beta strandi153 – 1575
    Beta strandi159 – 1613
    Beta strandi164 – 1685
    Beta strandi170 – 1756
    Turni176 – 1783
    Helixi182 – 19413
    Beta strandi206 – 2083

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1EKGX-ray1.80A86-210[»]
    1LY7NMR-A91-210[»]
    3S4MX-ray1.30A82-210[»]
    3S5DX-ray1.50A82-210[»]
    3S5EX-ray1.31A82-210[»]
    3S5FX-ray1.50A/B82-210[»]
    3T3JX-ray1.70A82-210[»]
    3T3KX-ray1.24A82-210[»]
    3T3LX-ray1.15A82-210[»]
    3T3TX-ray1.38A/B/C/D82-210[»]
    3T3XX-ray1.57A/B82-210[»]
    DisProtiDP00607.
    ProteinModelPortaliQ16595.
    SMRiQ16595. Positions 89-209.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ16595.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the frataxin family.Curated

    Keywords - Domaini

    Transit peptide

    Phylogenomic databases

    eggNOGiCOG1965.
    HOGENOMiHOG000190729.
    HOVERGENiHBG005745.
    InParanoidiQ16595.
    OMAiKQSVCLM.
    OrthoDBiEOG7HHWVD.
    PhylomeDBiQ16595.
    TreeFamiTF318958.

    Family and domain databases

    Gene3Di3.30.920.10. 1 hit.
    InterProiIPR017789. Frataxin.
    IPR002908. Frataxin/CyaY.
    IPR020895. Frataxin_CS.
    [Graphical view]
    PANTHERiPTHR16821. PTHR16821. 1 hit.
    PfamiPF01491. Frataxin_Cyay. 1 hit.
    [Graphical view]
    PRINTSiPR00904. FRATAXIN.
    SUPFAMiSSF55387. SSF55387. 1 hit.
    TIGRFAMsiTIGR03421. FeS_CyaY. 1 hit.
    TIGR03422. mito_frataxin. 1 hit.
    PROSITEiPS01344. FRATAXIN_1. 1 hit.
    PS50810. FRATAXIN_2. 1 hit.
    [Graphical view]

    Sequences (3)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 3 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q16595-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MWTLGRRAVA GLLASPSPAQ AQTLTRVPRP AELAPLCGRR GLRTDIDATC    50
    TPRRASSNQR GLNQIWNVKK QSVYLMNLRK SGTLGHPGSL DETTYERLAE 100
    ETLDSLAEFF EDLADKPYTF EDYDVSFGSG VLTVKLGGDL GTYVINKQTP 150
    NKQIWLSSPS SGPKRYDWTG KNWVYSHDGV SLHELLAAEL TKALKTKLDL 200
    SSLAYSGKDA 210
    Length:210
    Mass (Da):23,135
    Last modified:July 15, 1999 - v2
    Checksum:iECC81738779308CF
    GO
    Isoform 2 (identifier: Q16595-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         161-210: SGPKRYDWTGKNWVYSHDGVSLHELLAAELTKALKTKLDLSSLAYSGKDA → RLTWLLWLFHP

    Note: Not highly expressed and may be artifactual.

    Show »
    Length:171
    Mass (Da):19,095
    Checksum:i54BDD6A74B2D22C9
    GO
    Isoform 3 (identifier: Q16595-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         161-210: SGPKRYDWTG...SSLAYSGKDA → RYVVDLSVMT...SCWPQSSLKP

    Note: No experimental confirmation available. Gene prediction based on EST data.

    Show »
    Length:196
    Mass (Da):21,416
    Checksum:i306DDDE81A26C788
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti175 – 1751Y → F in AAA98508. (PubMed:8596916)Curated
    Sequence conflicti175 – 1751Y → F in AAA98510. (PubMed:8596916)Curated
    Sequence conflicti202 – 2021S → W in AAA98508. (PubMed:8596916)Curated
    Sequence conflicti202 – 2021S → W in AAA98510. (PubMed:8596916)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti106 – 1061L → S in FRDA. 1 Publication
    VAR_016065
    Natural varianti122 – 1221D → Y in FRDA. 3 Publications
    VAR_002428
    Natural varianti130 – 1301G → V in FRDA. 3 Publications
    VAR_002429
    Natural varianti154 – 1541I → F in FRDA; reduces interaction with LYRM4; the interaction is rescued by nickel. Defects in mitochondrial structure, mitochondrial iron deposits, decreased enzymatic activity of some mitochondrial and cytoplasmic iron-sulfur cluster-containing enzymes, increased RNA-binding activity of ACO1 and increased sensitivity to oxidative stress. 2 Publications
    VAR_002430
    Natural varianti155 – 1551W → R in FRDA; reduces interaction with LYRM4; the interaction is rescued by nickel. 1 Publication
    VAR_002431
    Natural varianti165 – 1651R → C in FRDA; mild form. 1 Publication
    VAR_008139
    Natural varianti182 – 1821L → F in FRDA. 1 Publication
    VAR_008140
    Natural varianti198 – 1981L → R in FRDA. 1 Publication
    VAR_016066
    Natural varianti202 – 2021S → C.
    Corresponds to variant rs1052195 [ dbSNP | Ensembl ].
    VAR_049100

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei161 – 21050SGPKR…SGKDA → RLTWLLWLFHP in isoform 2. 1 PublicationVSP_001576Add
    BLAST
    Alternative sequencei161 – 21050SGPKR…SGKDA → RYVVDLSVMTGLGKTGCTPT TACPSMSCWPQSSLKP in isoform 3. CuratedVSP_047282Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U43747 mRNA. Translation: AAA98510.1.
    U43752
    , U43748, U43749, U43750, U43751 Genomic DNA. Translation: AAA98508.1.
    U43753
    , U43748, U43749, U43750, U43751 Genomic DNA. Translation: AAA98509.1.
    AL162730 Genomic DNA. Translation: CAH71829.1.
    BC023633 mRNA. Translation: AAH23633.1.
    BC048097 mRNA. Translation: AAH48097.1.
    Y13751 Genomic DNA. Translation: CAA74077.1.
    AF028240 Genomic DNA. Translation: AAB84047.1.
    U93173 Genomic DNA. Translation: AAD00734.1.
    CCDSiCCDS43834.1. [Q16595-3]
    CCDS55313.1. [Q16595-2]
    CCDS6626.1. [Q16595-1]
    RefSeqiNP_000135.2. NM_000144.4. [Q16595-1]
    NP_001155178.1. NM_001161706.1. [Q16595-2]
    NP_852090.1. NM_181425.2. [Q16595-3]
    UniGeneiHs.20685.

    Genome annotation databases

    EnsembliENST00000377270; ENSP00000366482; ENSG00000165060. [Q16595-1]
    ENST00000396364; ENSP00000379650; ENSG00000165060. [Q16595-2]
    ENST00000396366; ENSP00000379652; ENSG00000165060. [Q16595-3]
    GeneIDi2395.
    KEGGihsa:2395.
    UCSCiuc004aha.2. human. [Q16595-1]
    uc011lrr.1. human. [Q16595-2]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism, Triplet repeat expansion

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U43747 mRNA. Translation: AAA98510.1 .
    U43752
    , U43748 , U43749 , U43750 , U43751 Genomic DNA. Translation: AAA98508.1 .
    U43753
    , U43748 , U43749 , U43750 , U43751 Genomic DNA. Translation: AAA98509.1 .
    AL162730 Genomic DNA. Translation: CAH71829.1 .
    BC023633 mRNA. Translation: AAH23633.1 .
    BC048097 mRNA. Translation: AAH48097.1 .
    Y13751 Genomic DNA. Translation: CAA74077.1 .
    AF028240 Genomic DNA. Translation: AAB84047.1 .
    U93173 Genomic DNA. Translation: AAD00734.1 .
    CCDSi CCDS43834.1. [Q16595-3 ]
    CCDS55313.1. [Q16595-2 ]
    CCDS6626.1. [Q16595-1 ]
    RefSeqi NP_000135.2. NM_000144.4. [Q16595-1 ]
    NP_001155178.1. NM_001161706.1. [Q16595-2 ]
    NP_852090.1. NM_181425.2. [Q16595-3 ]
    UniGenei Hs.20685.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1EKG X-ray 1.80 A 86-210 [» ]
    1LY7 NMR - A 91-210 [» ]
    3S4M X-ray 1.30 A 82-210 [» ]
    3S5D X-ray 1.50 A 82-210 [» ]
    3S5E X-ray 1.31 A 82-210 [» ]
    3S5F X-ray 1.50 A/B 82-210 [» ]
    3T3J X-ray 1.70 A 82-210 [» ]
    3T3K X-ray 1.24 A 82-210 [» ]
    3T3L X-ray 1.15 A 82-210 [» ]
    3T3T X-ray 1.38 A/B/C/D 82-210 [» ]
    3T3X X-ray 1.57 A/B 82-210 [» ]
    DisProti DP00607.
    ProteinModelPortali Q16595.
    SMRi Q16595. Positions 89-209.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 108677. 5 interactions.
    IntActi Q16595. 5 interactions.
    MINTi MINT-2856590.
    STRINGi 9606.ENSP00000366482.

    Chemistry

    ChEMBLi CHEMBL2321640.

    Protein family/group databases

    TCDBi 9.B.21.1.1. the frataxin (frataxin) family.

    PTM databases

    PhosphoSitei Q16595.

    2D gel databases

    OGPi Q16595.

    Proteomic databases

    MaxQBi Q16595.
    PaxDbi Q16595.
    PeptideAtlasi Q16595.
    PRIDEi Q16595.

    Protocols and materials databases

    DNASUi 2395.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000377270 ; ENSP00000366482 ; ENSG00000165060 . [Q16595-1 ]
    ENST00000396364 ; ENSP00000379650 ; ENSG00000165060 . [Q16595-2 ]
    ENST00000396366 ; ENSP00000379652 ; ENSG00000165060 . [Q16595-3 ]
    GeneIDi 2395.
    KEGGi hsa:2395.
    UCSCi uc004aha.2. human. [Q16595-1 ]
    uc011lrr.1. human. [Q16595-2 ]

    Organism-specific databases

    CTDi 2395.
    GeneCardsi GC09P071650.
    GeneReviewsi FXN.
    HGNCi HGNC:3951. FXN.
    HPAi CAB022164.
    MIMi 229300. phenotype.
    606829. gene.
    neXtProti NX_Q16595.
    Orphaneti 95. Friedreich ataxia.
    PharmGKBi PA28369.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG1965.
    HOGENOMi HOG000190729.
    HOVERGENi HBG005745.
    InParanoidi Q16595.
    OMAi KQSVCLM.
    OrthoDBi EOG7HHWVD.
    PhylomeDBi Q16595.
    TreeFami TF318958.

    Enzyme and pathway databases

    Reactomei REACT_118595. Mitochondrial protein import.
    REACT_150353. Mitochondrial iron-sulfur cluster biogenesis.

    Miscellaneous databases

    EvolutionaryTracei Q16595.
    GeneWikii Frataxin.
    GenomeRNAii 2395.
    NextBioi 9641.
    PROi Q16595.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q16595.
    Bgeei Q16595.
    CleanExi HS_FXN.
    Genevestigatori Q16595.

    Family and domain databases

    Gene3Di 3.30.920.10. 1 hit.
    InterProi IPR017789. Frataxin.
    IPR002908. Frataxin/CyaY.
    IPR020895. Frataxin_CS.
    [Graphical view ]
    PANTHERi PTHR16821. PTHR16821. 1 hit.
    Pfami PF01491. Frataxin_Cyay. 1 hit.
    [Graphical view ]
    PRINTSi PR00904. FRATAXIN.
    SUPFAMi SSF55387. SSF55387. 1 hit.
    TIGRFAMsi TIGR03421. FeS_CyaY. 1 hit.
    TIGR03422. mito_frataxin. 1 hit.
    PROSITEi PS01344. FRATAXIN_1. 1 hit.
    PS50810. FRATAXIN_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), ALTERNATIVE SPLICING, VARIANT PHE-154.
    2. "DNA sequence and analysis of human chromosome 9."
      Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L.
      , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
      Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Brain and Eye.
    4. "The in vivo mitochondrial two-step maturation of human frataxin."
      Schmucker S., Argentini M., Carelle-Calmels N., Martelli A., Puccio H.
      Hum. Mol. Genet. 17:3521-3531(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 81-90, PROTEOLYTIC PROCESSING, SUBCELLULAR LOCATION, MUTAGENESIS OF 39-ARG-ARG-40; 53-ARG-ARG-54; 78-LEU-ARG-79 AND 79-ARG-LYS-80.
    5. Cited for: PROTEIN SEQUENCE OF 81-86, PROTEOLYTIC PROCESSING, MUTAGENESIS OF 53-ARG-ARG-54 AND 79-ARG-LYS-80, TISSUE SPECIFICITY.
    6. "Molecular control of the cytosolic aconitase/IRP1 switch by extramitochondrial frataxin."
      Condo I., Malisan F., Guccini I., Serio D., Rufini A., Testi R.
      Hum. Mol. Genet. 19:1221-1229(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 81-86, FUNCTION, INTERACTION WITH ACO1, SUBCELLULAR LOCATION.
    7. Kostrzewa M.
      Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 89-128, VARIANT FRDA TYR-122.
    8. "A novel splice site mutation (384+1G-A) in the Friedreich's ataxia gene."
      Doudney J.D., Pook M.A., Al-Mahdawi S., Carvajal J.J., Hillerman R., Chamberlain S.
      Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 89-128, VARIANT FRDA TYR-122.
    9. "Correct sequence in exon 5a of x25: human frataxin (FRDA), F175(TTC)-->Y175(TAC) and W202(TGG)-->S202(TCC)."
      Laccone F., Schloesser M.
      Submitted (MAR-1997) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 162-210.
    10. Cited for: SUBCELLULAR LOCATION.
    11. "Studies of human, mouse and yeast homologues indicate a mitochondrial function for frataxin."
      Koutnikova H., Campuzano V., Foury F., Dolle P., Cazzalini O., Koenig M.
      Nat. Genet. 16:345-351(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.
    12. "Maturation of frataxin within mammalian and yeast mitochondria: one-step processing by matrix processing peptidase."
      Gordon D.M., Shi Q., Dancis A., Pain D.
      Hum. Mol. Genet. 8:2255-2262(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEOLYTIC PROCESSING.
    13. "Yeast and human frataxin are processed to mature form in two sequential steps by the mitochondrial processing peptidase."
      Branda S.S., Cavadini P., Adamec J., Kalousek F., Taroni F., Isaya G.
      J. Biol. Chem. 274:22763-22769(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEOLYTIC PROCESSING.
    14. "Two-step processing of human frataxin by mitochondrial processing peptidase. Precursor and intermediate forms are cleaved at different rates."
      Cavadini P., Adamec J., Taroni F., Gakh O., Isaya G.
      J. Biol. Chem. 275:41469-41475(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEOLYTIC PROCESSING.
    15. "Assembly and iron-binding properties of human frataxin, the protein deficient in Friedreich ataxia."
      Cavadini P., O'Neill H.A., Benada O., Isaya G.
      Hum. Mol. Genet. 11:217-227(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: POSSIBLE FUNCTION IN IRON STORAGE, SUBUNIT.
    16. "Structure of frataxin iron cores: an X-ray absorption spectroscopic study."
      Nichol H., Gakh O., O'Neill H.A., Pickering I.J., Isaya G., George G.N.
      Biochemistry 42:5971-5976(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: POSSIBLE FUNCTION IN IRON STORAGE, SUBUNIT.
    17. "Iron-sulfur cluster biosynthesis. Characterization of frataxin as an iron donor for assembly of [2Fe-2S] clusters in ISU-type proteins."
      Yoon T., Cowan J.A.
      J. Am. Chem. Soc. 125:6078-6084(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN IRON-SULFUR CLUSTER BIOSYNTHESIS, INTERACTION WITH ISCU.
    18. "Frataxin-mediated iron delivery to ferrochelatase in the final step of heme biosynthesis."
      Yoon T., Cowan J.A.
      J. Biol. Chem. 279:25943-25946(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: POSSIBLE FUNCTION IN HEME BIOSYNTHESIS, INTERACTION WITH FECH.
    19. "Frataxin acts as an iron chaperone protein to modulate mitochondrial aconitase activity."
      Bulteau A.L., O'Neill H.A., Kennedy M.C., Ikeda-Saito M., Isaya G., Szweda L.I.
      Science 305:242-245(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    20. "Assembly of human frataxin is a mechanism for detoxifying redox-active iron."
      O'Neill H.A., Gakh O., Park S., Cui J., Mooney S.M., Sampson M., Ferreira G.C., Isaya G.
      Biochemistry 44:537-545(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN OXIDATIVE STRESS, SUBUNIT, CATALYTIC ACTIVITY.
    21. "Frataxin interacts functionally with mitochondrial electron transport chain proteins."
      Gonzalez-Cabo P., Vazquez-Manrique R.P., Garcia-Gimeno M.A., Sanz P., Palau F.
      Hum. Mol. Genet. 14:2091-2098(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SDHA AND SDHB.
    22. "Frataxin deficiency alters heme pathway transcripts and decreases mitochondrial heme metabolites in mammalian cells."
      Schoenfeld R.A., Napoli E., Wong A., Zhan S., Reutenauer L., Morin D., Buckpitt A.R., Taroni F., Lonnerdal B., Ristow M., Puccio H., Cortopassi G.A.
      Hum. Mol. Genet. 14:3787-3799(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INVOLVEMENT IN HEME BIOSYNTHESIS.
    23. "Extra-mitochondrial localisation of frataxin and its association with IscU1 during enterocyte-like differentiation of the human colon adenocarcinoma cell line Caco-2."
      Acquaviva F., De Biase I., Nezi L., Ruggiero G., Tatangelo F., Pisano C., Monticelli A., Garbi C., Acquaviva A.M., Cocozza S.
      J. Cell Sci. 118:3917-3924(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ISCU, SUBCELLULAR LOCATION.
    24. "Supramolecular assemblies of human frataxin are formed via subunit-subunit interactions mediated by a non-conserved amino-terminal region."
      O'Neill H.A., Gakh O., Isaya G.
      J. Mol. Biol. 345:433-439(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBUNIT, SUBCELLULAR LOCATION.
    25. "A pool of extramitochondrial frataxin that promotes cell survival."
      Condo I., Ventura N., Malisan F., Tomassini B., Testi R.
      J. Biol. Chem. 281:16750-16756(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN CELL SURVIVAL, SUBCELLULAR LOCATION.
    26. "Mitochondrial frataxin interacts with ISD11 of the NFS1/ISCU complex and multiple mitochondrial chaperones."
      Shan Y., Napoli E., Cortopassi G.
      Hum. Mol. Genet. 16:929-941(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH LYRM4 AND HSPA9, CHARACTERIZATION OF VARIANTS PHE-154 AND ARG-155.
    27. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    28. Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 88-210.
    29. "Towards a structural understanding of Friedreich's ataxia: the solution structure of frataxin."
      Musco G., Stier G., Kolmerer B., Adinolfi S., Martin S., Frenkiel T., Gibson T., Pastore A.
      Structure 8:695-707(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 91-210.
    30. "Atypical Friedreich ataxia caused by compound heterozygosity for a novel missense mutation and the GAA triplet-repeat expansion."
      Bidichandani S.I., Ashizawa T., Patel P.I.
      Am. J. Hum. Genet. 60:1251-1256(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS FRDA VAL-130 AND PHE-154.
    31. "Identification of a missense mutation in a Friedreich's ataxia patient: implications for diagnosis and carrier studies."
      Bartolo C., Mendell J.R., Prior T.W.
      Am. J. Med. Genet. 79:396-399(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT FRDA SER-106.
    32. "The correlation of clinical phenotype in Friedreich ataxia with the site of point mutations in the FRDA gene."
      Forrest S.M., Knight M., Delatycki M.B., Paris D., Williamson R., King J., Yeung L., Nassif N., Nicholson G.A.
      Neurogenetics 1:253-257(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS FRDA VAL-130; CYS-165 AND PHE-182.
    33. Cited for: VARIANTS FRDA TYR-122 AND VAL-130.
    34. "A missense mutation (W155R) in an American patient with Friedreich's ataxia."
      Labuda M., Poirier J., Pandolfo M.
      Hum. Mutat. 13:506-506(1999)
      Cited for: VARIANT FRDA ARG-155.
    35. "A novel missense mutation (L198R) in the Friedreich's ataxia gene."
      Al-Mahdawi S., Pook M., Chamberlain S.
      Hum. Mutat. 16:95-95(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT FRDA ARG-198.
    36. "The first cellular models based on frataxin missense mutations that reproduce spontaneously the defects associated with Friedreich ataxia."
      Calmels N., Schmucker S., Wattenhofer-Donze M., Martelli A., Vaucamps N., Reutenauer L., Messaddeq N., Bouton C., Koenig M., Puccio H.
      PLoS ONE 4:E6379-E6379(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHARACTERIZATION OF VARIANT FRDA PHE-154.

    Entry informationi

    Entry nameiFRDA_HUMAN
    AccessioniPrimary (citable) accession number: Q16595
    Secondary accession number(s): A8MXJ6
    , C9JJ89, O15545, O95656, Q15294, Q5VZ01
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1999
    Last sequence update: July 15, 1999
    Last modified: October 1, 2014
    This is version 156 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Miscellaneous

    The unusual migration profile of mature frataxin on SDS-PAGE due to its acidic N-terminus most likely contributed to conflicting reports for the N-terminus of the mature protein. Unlike prokaryotic and yeast frataxin homologs, which self-assemble at high iron concentrations, oligomerization of human frataxin is not induced by iron. The existence of a specialized mitochondrial ferritin in mammalia (FTMT) is suggesting that iron storage would be redundant function, at least in mammalian mitochondria.

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 9
      Human chromosome 9: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3