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Q16595 (FRDA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 151. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Frataxin, mitochondrial

EC=1.16.3.1
Alternative name(s):
Friedreich ataxia protein
Short name=Fxn

Cleaved into the following 4 chains:

  1. Frataxin intermediate form
    Short name=i-FXN
  2. Frataxin(56-210)
    Alternative name(s):
    m56-FXN
  3. Frataxin(78-210)
    Alternative name(s):
    d-FXN
    m78-FXN
  4. Frataxin mature form
    Alternative name(s):
    Frataxin(81-210)
    m81-FXN
Gene names
Name:FXN
Synonyms:FRDA, X25
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length210 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.6 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.22 Ref.25

Catalytic activity

4 Fe2+ + 4 H+ + O2 = 4 Fe3+ + 2 H2O. Ref.20

Subunit structure

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. Ref.6 Ref.15 Ref.16 Ref.17 Ref.18 Ref.20 Ref.21 Ref.23 Ref.24 Ref.26

Subcellular location

Cytoplasm. Mitochondrion. Note: Ref.4 reports localization exclusively in mitochondria. Ref.4 Ref.6 Ref.10 Ref.11 Ref.23 Ref.24 Ref.25

Tissue specificity

Expressed in the heart, peripheral blood lymphocytes and dermal fibroblasts. Ref.5

Post-translational modification

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.

Involvement in disease

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Ref.8 Ref.30 Ref.31 Ref.32 Ref.33 Ref.34 Ref.35 Ref.36

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.

Sequence similarities

Belongs to the frataxin family.

Ontologies

Keywords
   Biological processHeme biosynthesis
Ion transport
Iron storage
Iron transport
Transport
   Cellular componentCytoplasm
Mitochondrion
   Coding sequence diversityAlternative splicing
Polymorphism
Triplet repeat expansion
   DiseaseDisease mutation
   DomainTransit peptide
   LigandIron
Metal-binding
   Molecular functionOxidoreductase
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processadult walking behavior

Inferred from electronic annotation. Source: Ensembl

aerobic respiration

Inferred from electronic annotation. Source: Ensembl

cellular iron ion homeostasis

Inferred from mutant phenotype PubMed 18160053. Source: BHF-UCL

cellular response to hydrogen peroxide

Inferred from direct assay Ref.20. Source: UniProtKB

embryo development ending in birth or egg hatching

Inferred from electronic annotation. Source: Ensembl

heme biosynthetic process

Non-traceable author statement Ref.18. Source: BHF-UCL

ion transport

Inferred from electronic annotation. Source: UniProtKB-KW

iron incorporation into metallo-sulfur cluster

Inferred from direct assay Ref.17. Source: BHF-UCL

mitochondrion organization

Inferred from electronic annotation. Source: Ensembl

negative regulation of apoptotic process

Inferred from mutant phenotype Ref.25. Source: UniProtKB

negative regulation of multicellular organism growth

Inferred from electronic annotation. Source: Ensembl

negative regulation of organ growth

Inferred from electronic annotation. Source: Ensembl

negative regulation of release of cytochrome c from mitochondria

Inferred from mutant phenotype Ref.25. Source: UniProtKB

oxidative phosphorylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell growth

Inferred from mutant phenotype PubMed 15509595. Source: BHF-UCL

positive regulation of cell proliferation

Inferred from mutant phenotype PubMed 18160053. Source: BHF-UCL

positive regulation of lyase activity

Inferred from direct assay Ref.6. Source: UniProtKB

positive regulation of metalloenzyme activity

Inferred from mutant phenotype PubMed 15509595. Source: BHF-UCL

positive regulation of oxidoreductase activity

Inferred from mutant phenotype PubMed 18160053. Source: BHF-UCL

positive regulation of transferase activity

Inferred from mutant phenotype PubMed 18160053. Source: BHF-UCL

proprioception

Inferred from electronic annotation. Source: Ensembl

protein autoprocessing

Inferred from direct assay Ref.17. Source: BHF-UCL

regulation of ferrochelatase activity

Inferred from direct assay Ref.18. Source: BHF-UCL

response to iron ion

Inferred from mutant phenotype PubMed 18424449. Source: BHF-UCL

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentcytosol

Inferred from direct assay Ref.5. Source: BHF-UCL

mitochondrial matrix

Inferred from sequence or structural similarity. Source: BHF-UCL

mitochondrion

Inferred from direct assay Ref.5. Source: BHF-UCL

   Molecular_function2 iron, 2 sulfur cluster binding

Inferred from direct assay Ref.17. Source: BHF-UCL

ferric iron binding

Inferred from direct assay Ref.17PubMed 18537827. Source: BHF-UCL

ferrous iron binding

Inferred from direct assay Ref.17Ref.18PubMed 17285345. Source: BHF-UCL

ferroxidase activity

Inferred from direct assay Ref.20. Source: UniProtKB

iron chaperone activity

Inferred from direct assay Ref.18. Source: BHF-UCL

iron-sulfur cluster binding

Inferred from direct assay PubMed 17285345. Source: BHF-UCL

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q16595-1)

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.
Isoform 2 (identifier: Q16595-2)

The sequence of this isoform differs from the canonical sequence as follows:
     161-210: SGPKRYDWTGKNWVYSHDGVSLHELLAAELTKALKTKLDLSSLAYSGKDA → RLTWLLWLFHP
Note: Not highly expressed and may be artifactual.
Isoform 3 (identifier: Q16595-3)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 4141Mitochondrion
Chain42 – 210169Frataxin intermediate form
PRO_0000010129
Chain56 – 210155Frataxin(56-210)
PRO_0000010130
Chain78 – 210133Frataxin(78-210)
PRO_0000399388
Chain81 – 210130Frataxin mature form
PRO_0000289331

Natural variations

Alternative sequence161 – 21050SGPKR…SGKDA → RLTWLLWLFHP in isoform 2.
VSP_001576
Alternative sequence161 – 21050SGPKR…SGKDA → RYVVDLSVMTGLGKTGCTPT TACPSMSCWPQSSLKP in isoform 3.
VSP_047282
Natural variant1061L → S in FRDA. Ref.31
VAR_016065
Natural variant1221D → Y in FRDA. Ref.7 Ref.8 Ref.33
VAR_002428
Natural variant1301G → V in FRDA. Ref.30 Ref.32 Ref.33
VAR_002429
Natural variant1541I → 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. Ref.1 Ref.26 Ref.30 Ref.36
VAR_002430
Natural variant1551W → R in FRDA; reduces interaction with LYRM4; the interaction is rescued by nickel. Ref.26 Ref.34
VAR_002431
Natural variant1651R → C in FRDA; mild form. Ref.32
VAR_008139
Natural variant1821L → F in FRDA. Ref.32
VAR_008140
Natural variant1981L → R in FRDA. Ref.35
VAR_016066
Natural variant2021S → C.
Corresponds to variant rs1052195 [ dbSNP | Ensembl ].
VAR_049100

Experimental info

Mutagenesis39 – 402RR → GG: Abolishes cleavage to yield frataxin intermediate form and allows accumulation of frataxin(56-210) and frataxin(78-210). Ref.4 Ref.5
Mutagenesis53 – 542RR → GG: No effect on processing of wild-type FXN. Ref.4 Ref.5
Mutagenesis78 – 792LR → GG: Abolishes cleavage to yield frataxin mature form and allows accumulation of frataxin(56-210) and frataxin(78-210). Ref.4 Ref.5
Mutagenesis79 – 802RK → GG: Abolishes cleavage to yield frataxin mature form and allows the accumulation of frataxin(56-210). Ref.4 Ref.5
Sequence conflict1751Y → F in AAA98508. Ref.1
Sequence conflict1751Y → F in AAA98510. Ref.1
Sequence conflict2021S → W in AAA98508. Ref.1
Sequence conflict2021S → W in AAA98510. Ref.1

Secondary structure

........................ 210
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified July 15, 1999. Version 2.
Checksum: ECC81738779308CF

FASTA21023,135
        10         20         30         40         50         60 
MWTLGRRAVA GLLASPSPAQ AQTLTRVPRP AELAPLCGRR GLRTDIDATC TPRRASSNQR 

        70         80         90        100        110        120 
GLNQIWNVKK QSVYLMNLRK SGTLGHPGSL DETTYERLAE ETLDSLAEFF EDLADKPYTF 

       130        140        150        160        170        180 
EDYDVSFGSG VLTVKLGGDL GTYVINKQTP NKQIWLSSPS SGPKRYDWTG KNWVYSHDGV 

       190        200        210 
SLHELLAAEL TKALKTKLDL SSLAYSGKDA 

« Hide

Isoform 2 [UniParc].

Checksum: 54BDD6A74B2D22C9
Show »

FASTA17119,095
Isoform 3 [UniParc].

Checksum: 306DDDE81A26C788
Show »

FASTA19621,416

References

« Hide 'large scale' references
[1]"Friedreich's ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion."
Campuzano V., Montermini L., Molto M.D., Pianese L., Cossee M., Cavalcanti F., Monros E., Rodius F., Duclos F., Monticelli A., Zara F., Canizares J., Koutnikova H., Bidichandani S., Gellera C., Brice A., Trouillas P., de Michele G. expand/collapse author list , Filla A., de Frutos R., Palau F., Patel P.I., di Donato S., Mandel J.-L., Cocozza S., Koenig M., Pandolfo M.
Science 271:1423-1427(1996) [PubMed] [Europe PMC] [Abstract]
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. expand/collapse author list , 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]"In vivo maturation of human frataxin."
Condo I., Ventura N., Malisan F., Rufini A., Tomassini B., Testi R.
Hum. Mol. Genet. 16:1534-1540(2007) [PubMed] [Europe PMC] [Abstract]
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]"Frataxin is reduced in Friedreich ataxia patients and is associated with mitochondrial membranes."
Campuzano V., Montermini L., Lutz Y., Cova L., Hindelang C., Jiralerspong S., Trottier Y., Kish S.J., Faucheux B., Trouillas P., Authier F.J., Duerr A., Mandel J.-L., Vescovi A., Pandolfo M., Koenig M.
Hum. Mol. Genet. 6:1771-1780(1997) [PubMed] [Europe PMC] [Abstract]
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]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[28]"Crystal structure of human frataxin."
Dhe-Paganon S., Shigeta R., Chi Y.-I., Ristow M., Shoelson S.E.
J. Biol. Chem. 275:30753-30756(2000) [PubMed] [Europe PMC] [Abstract]
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]"Friedreich's ataxia: point mutations and clinical presentation of compound heterozygotes."
Cossee M., Duerr A., Schmitt M., Dahl N., Trouillas P., Allinson P., Kostrzewa M., Nivelon-Chevallier A., Gustavson K.-H., Kohlschuetter A., Mueller U., Mandel J.-L., Brice A., Koenig M., Cavalcanti F., Tammaro A., de Michele G., Filla A. expand/collapse author list , Cocozza S., Labuda M., Montermini L., Poirier J., Pandolfo M.
Ann. Neurol. 45:200-206(1999) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U43747 mRNA. Translation: AAA98510.1.
U43752 expand/collapse EMBL AC list , U43748, U43749, U43750, U43751 Genomic DNA. Translation: AAA98508.1.
U43753 expand/collapse EMBL AC list , 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.
RefSeqNP_000135.2. NM_000144.4.
NP_001155178.1. NM_001161706.1.
NP_852090.1. NM_181425.2.
UniGeneHs.20685.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1EKGX-ray1.80A88-210[»]
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[»]
DisProtDP00607.
ProteinModelPortalQ16595.
SMRQ16595. Positions 89-209.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108677. 5 interactions.
IntActQ16595. 5 interactions.
MINTMINT-2856590.
STRING9606.ENSP00000366482.

Chemistry

ChEMBLCHEMBL2321640.

Protein family/group databases

TCDB9.B.21.1.1. the frataxin (frataxin) family.

PTM databases

PhosphoSiteQ16595.

2D gel databases

OGPQ16595.

Proteomic databases

PaxDbQ16595.
PeptideAtlasQ16595.
PRIDEQ16595.

Protocols and materials databases

DNASU2395.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000377270; ENSP00000366482; ENSG00000165060. [Q16595-1]
ENST00000396364; ENSP00000379650; ENSG00000165060. [Q16595-2]
ENST00000396366; ENSP00000379652; ENSG00000165060. [Q16595-3]
GeneID2395.
KEGGhsa:2395.
UCSCuc004aha.2. human. [Q16595-1]
uc011lrr.1. human. [Q16595-2]

Organism-specific databases

CTD2395.
GeneCardsGC09P071650.
HGNCHGNC:3951. FXN.
HPACAB022164.
MIM229300. phenotype.
606829. gene.
neXtProtNX_Q16595.
Orphanet95. Friedreich ataxia.
PharmGKBPA28369.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1965.
HOGENOMHOG000190729.
HOVERGENHBG005745.
InParanoidQ16595.
OMAKQSVCLM.
OrthoDBEOG7HHWVD.
PhylomeDBQ16595.
TreeFamTF318958.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
REACT_17015. Metabolism of proteins.

Gene expression databases

ArrayExpressQ16595.
BgeeQ16595.
CleanExHS_FXN.
GenevestigatorQ16595.

Family and domain databases

Gene3D3.30.920.10. 1 hit.
InterProIPR017789. Frataxin.
IPR002908. Frataxin/CyaY.
IPR020895. Frataxin_CS.
[Graphical view]
PANTHERPTHR16821. PTHR16821. 1 hit.
PfamPF01491. Frataxin_Cyay. 1 hit.
[Graphical view]
PRINTSPR00904. FRATAXIN.
SUPFAMSSF55387. SSF55387. 1 hit.
TIGRFAMsTIGR03421. FeS_CyaY. 1 hit.
TIGR03422. mito_frataxin. 1 hit.
PROSITEPS01344. FRATAXIN_1. 1 hit.
PS50810. FRATAXIN_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ16595.
GeneWikiFrataxin.
GenomeRNAi2395.
NextBio9641.
PROQ16595.
SOURCESearch...

Entry information

Entry nameFRDA_HUMAN
AccessionPrimary (citable) accession number: Q16595
Secondary accession number(s): A8MXJ6 expand/collapse secondary AC list , C9JJ89, O15545, O95656, Q15294, Q5VZ01
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: July 15, 1999
Last modified: April 16, 2014
This is version 151 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM