Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

Q16595

- FRDA_HUMAN

UniProt

Q16595 - FRDA_HUMAN

(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Protein

Frataxin, mitochondrial

Gene

FXN

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

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

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
Complete GO annotation...

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
Complete GO annotation...

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). 1 Publication
Mutagenesisi53 – 542RR → GG: No effect on processing of wild-type FXN. 2 Publications
Mutagenesisi78 – 792LR → GG: Abolishes cleavage to yield frataxin mature form and allows accumulation of frataxin(56-210) and frataxin(78-210). 1 Publication
Mutagenesisi79 – 802RK → GG: Abolishes cleavage to yield frataxin mature form and allows the accumulation of frataxin(56-210). 2 Publications

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

BgeeiQ16595.
CleanExiHS_FXN.
ExpressionAtlasiQ16595. baseline and differential.
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 – 11423Combined sources
Beta strandi124 – 1285Combined sources
Beta strandi131 – 1355Combined sources
Turni138 – 1403Combined sources
Beta strandi142 – 1487Combined sources
Turni149 – 1524Combined sources
Beta strandi153 – 1575Combined sources
Beta strandi159 – 1613Combined sources
Beta strandi164 – 1685Combined sources
Beta strandi170 – 1756Combined sources
Turni176 – 1783Combined sources
Helixi182 – 19413Combined sources
Beta strandi206 – 2083Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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.
GeneTreeiENSGT00390000005811.
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

        10         20         30         40         50
MWTLGRRAVA GLLASPSPAQ AQTLTRVPRP AELAPLCGRR GLRTDIDATC
60 70 80 90 100
TPRRASSNQR GLNQIWNVKK QSVYLMNLRK SGTLGHPGSL DETTYERLAE
110 120 130 140 150
ETLDSLAEFF EDLADKPYTF EDYDVSFGSG VLTVKLGGDL GTYVINKQTP
160 170 180 190 200
NKQIWLSSPS SGPKRYDWTG KNWVYSHDGV SLHELLAAEL TKALKTKLDL
210
SSLAYSGKDA
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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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:
PDBei
RCSB PDBi
PDBji
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.
GeneTreei ENSGT00390000005811.
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

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

Gene expression databases

Bgeei Q16595.
CleanExi HS_FXN.
ExpressionAtlasi Q16595. baseline and differential.
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

« Hide 'large scale' publications
  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: November 26, 2014
This is version 158 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