Reviewed,
UniProtKB/Swiss-Prot Q16595 (FRDA_HUMAN)
Last modified
February 9, 2010.
Version 110.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
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Names and origin
| Protein names | Recommended name: Frataxin, mitochondrial Alternative name(s): Friedreich ataxia protein Short name=Fxn Cleaved into the following 3 chains: 1- Recommended name: Frataxin intermediate form 2- Recommended name: Frataxin(56-210) 3- Recommended name: Frataxin(81-210) | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) [Complete proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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 | Probably involved in iron homeostasis. Anti-apoptotic protein which prevents mitochondrial damage and reactive oxygen species (ROS) production. Ref.13 |
| Subunit structure | Monomer. Interacts with LYRM4 AND HSPA9. Ref.14 |
| Subcellular location | Mitochondrion. Note: Mitochondrial and extramitochondrial. Ref.13 Ref.8 Ref.9 |
| Tissue specificity | Frataxin(81-210) is expressed in the heart, peripheral blood lymphocytes and dermal fibroblasts. Ref.4 |
| 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 mature size protein. Two forms exist, frataxin(56-210) and frataxin(81-210) which is the main form of mature frataxin. |
| Involvement in disease | Defects in FXN are the cause of Friedreich ataxia (FA) [MIM:229300]. FA is an 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, FA 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. Ref.6 Ref.7 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 |
| Sequence similarities | Belongs to the frataxin family. |
Ontologies
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 | 81 – 210 | 130 | Frataxin(81-210) | PRO_0000289331 | ||||||||||||||||||||||
Natural variations | ||||||||||||||||||||||||||
| Alternative sequence | 161 – 210 | 50 | SGPKR…SGKDA → RLTWLLWLFHP in isoform 2. | VSP_001576 | ||||||||||||||||||||||
| Natural variant | 106 | 1 | L → S in FA. Ref.19 | VAR_016065 | ||||||||||||||||||||||
| Natural variant | 122 | 1 | D → Y in FA. Ref.6 Ref.7 Ref.21 | VAR_002428 | ||||||||||||||||||||||
| Natural variant | 130 | 1 | G → V in FA. Ref.18 Ref.20 Ref.21 | VAR_002429 | ||||||||||||||||||||||
| Natural variant | 154 | 1 | I → F in FA; reduces interaction with LYRM4. Interaction is rescued by nickel. Ref.14 Ref.18 Ref.1 | VAR_002430 | ||||||||||||||||||||||
| Natural variant | 155 | 1 | W → R in FA; reduces interaction with LYRM4. Interaction is rescued by nickel. Ref.14 Ref.22 | VAR_002431 | ||||||||||||||||||||||
| Natural variant | 165 | 1 | R → C in FA; mild form. Ref.20 | VAR_008139 | ||||||||||||||||||||||
| Natural variant | 182 | 1 | L → F in FA. Ref.20 | VAR_008140 | ||||||||||||||||||||||
| Natural variant | 198 | 1 | L → R in FA. Ref.23 | VAR_016066 | ||||||||||||||||||||||
| Natural variant | 202 | 1 | S → C: dbSNP rs1052195. | VAR_049100 | ||||||||||||||||||||||
Experimental info | ||||||||||||||||||||||||||
| Mutagenesis | 53 | 1 | R → G: Abolished cleavage of frataxin(81-210); when associated with G-54. Ref.4 | |||||||||||||||||||||||
| Mutagenesis | 54 | 1 | R → G: Abolished cleavage of frataxin(81-210) and allows the accumulation of frataxin(56-210); when associated with G-53. Ref.4 | |||||||||||||||||||||||
| Mutagenesis | 79 | 1 | R → G: Abolished cleavage of frataxin(81-210) and allows the accumulation of frataxin(56-210); when associated with G-80. Ref.4 | |||||||||||||||||||||||
| Mutagenesis | 80 | 1 | K → G: Abolished cleavage of frataxin(81-210); when associated with G-79. Ref.4 | |||||||||||||||||||||||
| 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 | ||||||||||||||||||||||||||
Helix Strand Turn | ||||||||||||||||||||||||||
| Helix | 92 – 113 | 22 | ||||||||||||||||||||||||
| Beta strand | 124 – 128 | 5 | ||||||||||||||||||||||||
| Beta strand | 131 – 135 | 5 | ||||||||||||||||||||||||
| Beta strand | 142 – 148 | 7 | ||||||||||||||||||||||||
| Turn | 149 – 152 | 4 | ||||||||||||||||||||||||
| Beta strand | 153 – 158 | 6 | ||||||||||||||||||||||||
| Turn | 159 – 161 | 3 | ||||||||||||||||||||||||
| Beta strand | 162 – 168 | 7 | ||||||||||||||||||||||||
| Beta strand | 170 – 175 | 6 | ||||||||||||||||||||||||
| Turn | 176 – 178 | 3 | ||||||||||||||||||||||||
| Helix | 182 – 194 | 13 | ||||||||||||||||||||||||
Sequences
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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. Pandolfo M.Science 271:1423-1427(1996) [PubMed: 8596916] [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. Dunham I.Nature 429:369-374(2004) [PubMed: 15164053] [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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain and Eye. |
| [4] | "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: 17468497] [Abstract] Cited for: PROTEIN SEQUENCE OF 81-86, PROTEOLYTIC PROCESSING, MUTAGENESIS OF ARG-53; ARG-54; ARG-79 AND LYS-80, TISSUE SPECIFICITY. |
| [5] | "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. |
| [6] | "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 FA TYR-122. |
| [7] | Kostrzewa M. Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 89-128, VARIANT FA TYR-122. |
| [8] | "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: 9302253] [Abstract] Cited for: SUBCELLULAR LOCATION. |
| [9] | "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: 9241270] [Abstract] Cited for: SUBCELLULAR LOCATION. |
| [10] | "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: 10545606] [Abstract] Cited for: PROTEOLYTIC PROCESSING. |
| [11] | "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: 10428860] [Abstract] Cited for: PROTEOLYTIC PROCESSING. |
| [12] | "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: 11020385] [Abstract] Cited for: PROTEOLYTIC PROCESSING. |
| [13] | "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: 16608849] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION. |
| [14] | "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: 17331979] [Abstract] Cited for: INTERACTION WITH LYRM4 AND HSPA9, CHARACTERIZATION OF VARIANTS PHE-154 AND ARG-155. |
| [15] | Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. |
| [16] | "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: 10900192] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 88-210. |
| [17] | "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: 10903947] [Abstract] Cited for: STRUCTURE BY NMR OF 91-210. |
| [18] | "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: 9150176] [Abstract] Cited for: VARIANTS FA VAL-130 AND PHE-154. |
| [19] | "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: 9779809] [Abstract] Cited for: VARIANT FA SER-106. |
| [20] | "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: 10732799] [Abstract] Cited for: VARIANTS FA VAL-130; CYS-165 AND PHE-182. |
| [21] | "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. Pandolfo M.Ann. Neurol. 45:200-206(1999) [PubMed: 9989622] [Abstract] Cited for: VARIANTS FA TYR-122 AND VAL-130. |
| [22] | "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 FA ARG-155. |
| [23] | "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: 10874325] [Abstract] Cited for: VARIANT FA ARG-198. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| EMBL GenBank DDBJ | U43747 mRNA. Translation: AAA98510.1. U43752 U43751 Genomic DNA. Translation: AAA98508.1. U43753 U43751 Genomic DNA. Translation: AAA98509.1. AL162730 Genomic DNA. Translation: CAH71829.1. BC023633 mRNA. Translation: AAH23633.1. BC048097 mRNA. Translation: AAH48097.1. U93173 Genomic DNA. Translation: AAD00734.1. AF028240 Genomic DNA. Translation: AAB84047.1. Y13751 Genomic DNA. Translation: CAA74077.1. | ||||||||||||||||||
| IPI | IPI00217745. IPI00293425. | ||||||||||||||||||
| RefSeq | NP_000135.2. NP_001155178.1. NP_852090.1. | ||||||||||||||||||
| UniGene | Hs.20685 | ||||||||||||||||||
3D structure databases | |||||||||||||||||||
| PDBe RCSB PDB PDBj |
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| ModBase | Search... | ||||||||||||||||||
Protein-protein interaction databases | |||||||||||||||||||
| IntAct | Q16595. 2 interactions. | ||||||||||||||||||
| STRING | Q16595. | ||||||||||||||||||
Protein family/group databases | |||||||||||||||||||
| TCDB | 9.B.21.1.1. frataxin family. | ||||||||||||||||||
2-D gel databases | |||||||||||||||||||
| OGP | Q16595. | ||||||||||||||||||
Proteomic databases | |||||||||||||||||||
| PeptideAtlas | Q16595. | ||||||||||||||||||
| PRIDE | Q16595. | ||||||||||||||||||
Genome annotation databases | |||||||||||||||||||
| Ensembl | ENST00000377270; ENSP00000366482; ENSG00000165060; Homo sapiens. [Genome view] | ||||||||||||||||||
| GeneID | 2395. | ||||||||||||||||||
| KEGG | hsa:2395. | ||||||||||||||||||
| NMPDR | fig|9606.3.peg.31391. | ||||||||||||||||||
| UCSC | uc004aha.1. human. | ||||||||||||||||||
Organism-specific databases | |||||||||||||||||||
| CTD | 2395. | ||||||||||||||||||
| GeneCards | GC09P070840. | ||||||||||||||||||
| H-InvDB | HIX0025740. | ||||||||||||||||||
| HGNC | HGNC:3951. FXN. | ||||||||||||||||||
| HPA | CAB022164. | ||||||||||||||||||
| MIM | 229300. phenotype. 606829. gene. | ||||||||||||||||||
| Orphanet | 95. Friedreich ataxia. | ||||||||||||||||||
| PharmGKB | PA28369. | ||||||||||||||||||
| GenAtlas | Search... | ||||||||||||||||||
Phylogenomic databases | |||||||||||||||||||
| eggNOG | prNOG11242. | ||||||||||||||||||
| HOGENOM | HBG125781. | ||||||||||||||||||
| HOVERGEN | Q16595. | ||||||||||||||||||
| InParanoid | Q16595. | ||||||||||||||||||
| OMA | DETAYER. | ||||||||||||||||||
| OrthoDB | EOG9C5G4B. | ||||||||||||||||||
| PhylomeDB | Q16595. | ||||||||||||||||||
Gene expression databases | |||||||||||||||||||
| ArrayExpress | Q16595. | ||||||||||||||||||
| Bgee | Q16595. | ||||||||||||||||||
| CleanEx | HS_FXN. | ||||||||||||||||||
| Genevestigator | Q16595. | ||||||||||||||||||
| GermOnline | ENSG00000165060. Homo sapiens. | ||||||||||||||||||
Family and domain databases | |||||||||||||||||||
| InterPro | IPR017789. Frataxin. IPR002908. Frataxin-like. IPR020895. Frataxin_CS. IPR001794. Frataxin_sub. [Graphical view] | ||||||||||||||||||
| Gene3D | G3DSA:3.30.920.10. Frataxin_like. 1 hit. | ||||||||||||||||||
| Pfam | PF01491. Frataxin_Cyay. 1 hit. [Graphical view] | ||||||||||||||||||
| PRINTS | PR00904. FRATAXIN. | ||||||||||||||||||
| 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 Resources | |||||||||||||||||||
| NextBio | 9641. | ||||||||||||||||||
| SOURCE | Search... | ||||||||||||||||||
Entry information
| Entry name | FRDA_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q16595 Secondary accession number(s): O15545 Q5VZ01 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
| 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. | ||||||||
Relevant documents
| Human chromosome 9 Human chromosome 9: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| SIMILARITY comments Index of protein domains and families |

Clusters with


