Q16595 (FRDA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	210 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 process	Heme biosynthesis Ion transport Iron storage Iron transport Transport
Cellular component	Cytoplasm Mitochondrion
Coding sequence diversity	Alternative splicing Polymorphism Triplet repeat expansion
Disease	Disease mutation
Domain	Transit peptide
Ligand	Iron Metal-binding
Molecular function	Oxidoreductase
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	adult walking behavior Inferred from electronic annotation. Source: Compara aerobic respiration Inferred from electronic annotation. Source: Compara 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: Compara 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: Compara negative regulation of apoptotic process Inferred from mutant phenotype Ref.25. Source: UniProtKB negative regulation of multicellular organism growth Inferred from electronic annotation. Source: Compara negative regulation of organ growth Inferred from electronic annotation. Source: Compara negative regulation of release of cytochrome c from mitochondria Inferred from mutant phenotype Ref.25. Source: UniProtKB oxidative phosphorylation Inferred from electronic annotation. Source: Compara positive regulation of axon extension Inferred from electronic annotation. Source: Compara 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: Compara 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 drug Inferred from electronic annotation. Source: Compara response to iron ion Inferred from mutant phenotype PubMed 18424449. Source: BHF-UCL response to organic cyclic compound Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Inferred from direct assay Ref.5. Source: BHF-UCL mitochondrial matrix Inferred from sequence or structural similarity. Source: BHF-UCL
Molecular_function	2 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
Complete GO annotation...

Alternative products

This entry describes 2 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.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 41

41

Mitochondrion

Chain

42 – 210

169

Frataxin intermediate form

PRO_0000010129

Chain

56 – 210

155

Frataxin(56-210)

PRO_0000010130

Chain

78 – 210

133

Frataxin(78-210)

PRO_0000399388

Chain

81 – 210

130

Frataxin mature form

PRO_0000289331

Natural variations

Alternative sequence

161 – 210

50

SGPKR…SGKDA → RLTWLLWLFHP in isoform 2.

VSP_001576

Natural variant

106

1

L → S in FRDA. Ref.31

VAR_016065

Natural variant

122

1

D → Y in FRDA. Ref.7 Ref.8 Ref.33

VAR_002428

Natural variant

130

1

G → V in FRDA. Ref.30 Ref.32 Ref.33

VAR_002429

Natural variant

154

1

I → 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 variant

155

1

W → R in FRDA; reduces interaction with LYRM4; the interaction is rescued by nickel. Ref.26 Ref.34

VAR_002431

Natural variant

165

1

R → C in FRDA; mild form. Ref.32

VAR_008139

Natural variant

182

1

L → F in FRDA. Ref.32

VAR_008140

Natural variant

198

1

L → R in FRDA. Ref.35

VAR_016066

Natural variant

202

1

S → C.
Corresponds to variant rs1052195 [ dbSNP | Ensembl ].

VAR_049100

Experimental info

Mutagenesis

39 – 40

2

RR → GG: Abolishes cleavage to yield frataxin intermediate form and allows accumulation of frataxin(56-210) and frataxin(78-210). Ref.4 Ref.5

Mutagenesis

53 – 54

2

RR → GG: No effect on processing of wild-type FXN. Ref.4 Ref.5

Mutagenesis

78 – 79

2

LR → GG: Abolishes cleavage to yield frataxin mature form and allows accumulation of frataxin(56-210) and frataxin(78-210). Ref.4 Ref.5

Mutagenesis

79 – 80

2

RK → GG: Abolishes cleavage to yield frataxin mature form and allows the accumulation of frataxin(56-210). Ref.4 Ref.5

Sequence conflict

175

1

Y → F in AAA98508. Ref.1

Sequence conflict

175

1

Y → F in AAA98510. Ref.1

Sequence conflict

202

1

S → W in AAA98508. Ref.1

Sequence conflict

202

1

S → W in AAA98510. Ref.1

Secondary structure

1

.

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210

Helix Strand Turn

Details...

Helix

92 – 114

23

Beta strand

124 – 128

5

Beta strand

131 – 135

5

Turn

138 – 140

3

Beta strand

142 – 148

7

Turn

149 – 152

4

Beta strand

153 – 157

5

Beta strand

159 – 161

3

Beta strand

164 – 168

5

Beta strand

170 – 175

6

Turn

176 – 178

3

Helix

182 – 194

13

Beta strand

206 – 208

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 15, 1999. Version 2. Checksum: ECC81738779308CF	FASTA	210	23,135
	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
	Isoform 2 [UniParc]. Checksum: 54BDD6A74B2D22C9	FASTA	171	19,095
	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 EDYDVSFGSG VLTVKLGGDL GTYVINKQTP NKQIWLSSPS RLTWLLWLFH P

References

	« Hide 'large scale' referencesShow '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. , 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], 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]	"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. , 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

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00217745.
IPI00293425.

RefSeq

NP_000135.2. NM_000144.4.
NP_001155178.1. NM_001161706.1.
NP_852090.1. NM_181425.2.

UniGene

Hs.20685.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1EKG	X-ray	1.80	A	88-210	[»]
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	[»]

ProteinModelPortal

Q16595.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q16595. 4 interactions.

MINT

MINT-2856590.

STRING

9606.ENSP00000366482.

Protein family/group databases

TCDB

9.B.21.1.1. frataxin family.

PTM databases

PhosphoSite

Q16595.

Polymorphism databases

DMDM

6166193.

2D gel databases

OGP

Q16595.

Proteomic databases

PaxDb

Q16595.

PeptideAtlas

Q16595.

PRIDE

Q16595.

Protocols and materials databases

DNASU

2395.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000377270; ENSP00000366482; ENSG00000165060.
ENST00000396364; ENSP00000379650; ENSG00000165060.

GeneID

2395.

KEGG

hsa:2395.

UCSC

uc004aha.2. human.
uc011lrr.1. human.

Organism-specific databases

CTD

2395.

GeneCards

GC09P071650.

HGNC

HGNC:3951. FXN.

HPA

CAB022164.

MIM

229300. phenotype.
606829. gene.

neXtProt

NX_Q16595.

Orphanet

95. Friedreich ataxia.

PharmGKB

PA28369.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1965.

HOGENOM

HOG000190729.

HOVERGEN

HBG005745.

InParanoid

Q16595.

OMA

KQSVCLM.

OrthoDB

EOG4ZCT5S.

PhylomeDB

Q16595.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.
REACT_17015. Metabolism of proteins.

Gene expression databases

ArrayExpress

Q16595.

Bgee

Q16595.

CleanEx

HS_FXN.

Genevestigator

Q16595.

GermOnline

ENSG00000165060. Homo sapiens.

Family and domain databases

Gene3D

3.30.920.10. 1 hit.

InterPro

IPR017789. Frataxin.
IPR002908. Frataxin/CyaY.
IPR020895. Frataxin_CS.
[Graphical view]

PANTHER

PTHR16821. PTHR16821. 1 hit.

Pfam

PF01491. Frataxin_Cyay. 1 hit.
[Graphical view]

PRINTS

PR00904. FRATAXIN.

SUPFAM

SSF55387. Frataxin_like. 1 hit.

TIGRFAMs

TIGR03421. FeS_CyaY. 1 hit.
TIGR03422. mito_frataxin. 1 hit.

PROSITE

PS01344. FRATAXIN_1. 1 hit.
PS50810. FRATAXIN_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q16595.

GenomeRNAi

2395.

NextBio

9641.

SOURCE

Search...

Entry information

Entry name

FRDA_HUMAN

Accession

Primary (citable) accession number: Q16595
Secondary accession number(s): O15545 , O95656, Q15294, Q5VZ01

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	July 15, 1999
Last modified:	May 1, 2013
This is version 141 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.