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O35943 (FRDA_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 106. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Frataxin, mitochondrial

Short name=Fxn
EC=1.16.3.1

Cleaved into the following 2 chains:

  1. Frataxin intermediate form
  2. Frataxin mature form
Gene names
Name:Fxn
Synonyms:Frda
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length207 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. Modulates the RNA-binding activity of ACO1 By similarity. Ref.6

Catalytic activity

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

Subunit structure

Monomer (probable predominant form). Oligomer. Interacts with LYRM4 AND HSPA9. Interacts with ACO1. Interacts with ISCU. 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.2

Subcellular location

Cytoplasm By similarity. Mitochondrion. Note: Ref.3 describes localization exclusively in mitochondria. Ref.1 Ref.3

Tissue specificity

Heart, liver, skeletal muscle, kidney, spleen and thymus. Weakly expressed in the brain and lung. Ref.1

Developmental stage

Expression in the ventricular zone which corresponds to dividing neuronal precursors begins at day 12.5, increases during embryonic development and persists at postnatal day 7 (P7) in the ependymal layer, which is the remenant of the ventricular zone. Weak expression seen in the spinal cord and medulla oblongata, starting at embryonic day 14.5 (E14.5) and expression also observed in dorsal root ganglia, starting at E14.5. At P14, expression in the dorsal root ganglia is restricted to the cortical region where the sensory neuron cell bodies are located. In non-neural tissues strong expression seen in the developing liver from E10.5. Expression detected in the heart and in the cortex of the developing kidney at E12.5 and later. Very high expression observed in the brown adipose tissue. Expression seen in small islands around the neck and back at E14.5, then in large masses at E16.5 and E18.5 and at P14 is absent in brown adipose tissue. Expression also seen in the thymus and developing gut at E14.5 and until postnatal life. At P14, expression in thymus is restricted to the proliferating cells in the cortical zone and is also prominent in the spleen. Found in the lung at E14.5. Ref.1

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 By similarity.

Disruption phenotype

Loss of cell division and lethal in fibroblasts. Ref.5

Sequence similarities

Belongs to the frataxin family.

Ontologies

Keywords
   Biological processHeme biosynthesis
Ion transport
Iron storage
Iron transport
Transport
   Cellular componentCytoplasm
Mitochondrion
   DomainTransit peptide
   LigandIron
Metal-binding
   Molecular functionOxidoreductase
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processadult walking behavior

Inferred from mutant phenotype PubMed 14985441PubMed 9405681. Source: MGI

aerobic respiration

Inferred from mutant phenotype PubMed 16278235PubMed 9405681. Source: MGI

cellular iron ion homeostasis

Inferred from mutant phenotype PubMed 9405681. Source: MGI

cellular response to hydrogen peroxide

Inferred from electronic annotation. Source: Ensembl

embryo development ending in birth or egg hatching

Inferred from mutant phenotype PubMed 10767347. Source: MGI

heme biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-KW

ion transport

Inferred from electronic annotation. Source: UniProtKB-KW

iron incorporation into metallo-sulfur cluster

Inferred from electronic annotation. Source: Ensembl

iron-sulfur cluster assembly

Inferred from mutant phenotype PubMed 16278235Ref.3. Source: MGI

mitochondrion organization

Inferred from mutant phenotype PubMed 14985441PubMed 9405681. Source: MGI

negative regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of multicellular organism growth

Inferred from mutant phenotype PubMed 17404227. Source: MGI

negative regulation of organ growth

Inferred from mutant phenotype PubMed 9405681. Source: MGI

negative regulation of release of cytochrome c from mitochondria

Inferred from electronic annotation. Source: Ensembl

oxidative phosphorylation

Inferred from mutant phenotype PubMed 16278235PubMed 17404227. Source: MGI

positive regulation of cell growth

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of lyase activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of metalloenzyme activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of oxidoreductase activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of transferase activity

Inferred from electronic annotation. Source: Ensembl

proprioception

Inferred from mutant phenotype PubMed 11175786PubMed 14985441. Source: MGI

protein autoprocessing

Inferred from electronic annotation. Source: Ensembl

regulation of ferrochelatase activity

Inferred from electronic annotation. Source: Ensembl

response to iron ion

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytosol

Inferred from electronic annotation. Source: Ensembl

mitochondrion

Inferred from direct assay PubMed 14651853Ref.3PubMed 18614015. Source: MGI

   Molecular_function2 iron, 2 sulfur cluster binding

Inferred from electronic annotation. Source: Ensembl

ferric iron binding

Inferred from electronic annotation. Source: InterPro

ferrous iron binding

Inferred from electronic annotation. Source: Ensembl

ferroxidase activity

Inferred from electronic annotation. Source: UniProtKB-EC

iron chaperone activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 4040Mitochondrion By similarity
Chain41 – 207167Frataxin intermediate form
PRO_0000010132
Chain78 – 207130Frataxin mature form By similarity
PRO_0000399390

Sequences

Sequence LengthMass (Da)Tools
O35943 [UniParc].

Last modified January 1, 1998. Version 1.
Checksum: C46FD21B44FB26A2

FASTA20722,924
        10         20         30         40         50         60 
MWAFGGRAAV GLLPRTASRA SAWVGNPRWR EPIVTCGRRG LHVTVNAGAT RHAHLNLHYL 

        70         80         90        100        110        120 
QILNIKKQSV CVVHLRNLGT LDNPSSLDET AYERLAEETL DSLAEFFEDL ADKPYTLEDY 

       130        140        150        160        170        180 
DVSFGDGVLT IKLGGDLGTY VINKQTPNKQ IWLSSPSSGP KRYDWTGKNW VYSHDGVSLH 

       190        200 
ELLARELTKA LNTKLDLSSL AYSGKGT 

« Hide

References

[1]"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: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
Tissue: Embryo.
[2]"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: SUBUNIT.
[3]"Frataxin is essential for extramitochondrial Fe-S cluster proteins in mammalian tissues."
Martelli A., Wattenhofer-Donze M., Schmucker S., Bouvet S., Reutenauer L., Puccio H.
Hum. Mol. Genet. 16:2651-2658(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[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: PROTEOLYTIC PROCESSING.
[5]"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: DISRUPTION PHENOTYPE.
[6]"Elucidation of the mechanism of mitochondrial iron loading in Friedreich's ataxia by analysis of a mouse mutant."
Huang M.L., Becker E.M., Whitnall M., Rahmanto Y.S., Ponka P., Richardson D.R.
Proc. Natl. Acad. Sci. U.S.A. 106:16381-16386(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U95736 mRNA. Translation: AAB67778.1.
RefSeqNP_032070.1. NM_008044.2.
UniGeneMm.7319.

3D structure databases

ProteinModelPortalO35943.
SMRO35943. Positions 86-205.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActO35943. 2 interactions.
MINTMINT-1847605.

PTM databases

PhosphoSiteO35943.

Proteomic databases

PaxDbO35943.
PRIDEO35943.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000081333; ENSMUSP00000080081; ENSMUSG00000059363.
GeneID14297.
KEGGmmu:14297.
UCSCuc008hao.1. mouse.

Organism-specific databases

CTD2395.
MGIMGI:1096879. Fxn.

Phylogenomic databases

eggNOGCOG1965.
HOGENOMHOG000190729.
HOVERGENHBG005745.
InParanoidO35943.
OMAKQSVCLM.
OrthoDBEOG7HHWVD.
PhylomeDBO35943.
TreeFamTF318958.

Gene expression databases

ArrayExpressO35943.
BgeeO35943.
CleanExMM_FXN.
GenevestigatorO35943.

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

NextBio285709.
PROO35943.
SOURCESearch...

Entry information

Entry nameFRDA_MOUSE
AccessionPrimary (citable) accession number: O35943
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: January 1, 1998
Last modified: April 16, 2014
This is version 106 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot