O35943 (FRDA_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	207 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. 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 process	Heme biosynthesis Ion transport Iron storage Iron transport Transport
Cellular component	Cytoplasm Mitochondrion
Domain	Transit peptide
Ligand	Iron Metal-binding
Molecular function	Oxidoreductase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	adult 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: Compara 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: Compara 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: Compara 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: Compara oxidative phosphorylation Inferred from mutant phenotype PubMed 16278235PubMed 17404227. Source: MGI positive regulation of axon extension Inferred from electronic annotation. Source: Compara positive regulation of cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of lyase activity Inferred from electronic annotation. Source: Compara positive regulation of metalloenzyme activity Inferred from electronic annotation. Source: Compara positive regulation of oxidoreductase activity Inferred from electronic annotation. Source: Compara positive regulation of transferase activity Inferred from electronic annotation. Source: Compara proprioception Inferred from mutant phenotype PubMed 11175786PubMed 14985441. Source: MGI protein autoprocessing Inferred from electronic annotation. Source: Compara regulation of ferrochelatase activity Inferred from electronic annotation. Source: Compara response to drug Inferred from electronic annotation. Source: Compara response to iron ion Inferred from electronic annotation. Source: Compara response to organic cyclic compound Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Inferred from electronic annotation. Source: Compara mitochondrion Inferred from direct assay PubMed 14651853Ref.3PubMed 18614015. Source: MGI
Molecular_function	2 iron, 2 sulfur cluster binding Inferred from electronic annotation. Source: Compara ferric iron binding Inferred from electronic annotation. Source: InterPro ferrous iron binding Inferred from electronic annotation. Source: Compara ferroxidase activity Inferred from electronic annotation. Source: EC iron chaperone activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 40	40	Mitochondrion By similarity
	Chain	41 – 207	167	Frataxin intermediate form		PRO_0000010132
	Chain	78 – 207	130	Frataxin mature form By similarity		PRO_0000399390

Sequences

	Sequence		Length	Mass (Da)
	O35943 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: C46FD21B44FB26A2	FASTA	207	22,924
	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

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.
IPI	IPI00136201.
RefSeq	NP_032070.1. NM_008044.2.
UniGene	Mm.7319.
3D structure databases
ProteinModelPortal	O35943.
SMR	O35943. Positions 86-205.
ModBase	Search...
PTM databases
PhosphoSite	O35943.
Proteomic databases
PaxDb	O35943.
PRIDE	O35943.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000081333; ENSMUSP00000080081; ENSMUSG00000059363.
GeneID	14297.
KEGG	mmu:14297.
Organism-specific databases
CTD	2395.
MGI	MGI:1096879. Fxn.
Phylogenomic databases
eggNOG	COG1965.
HOGENOM	HOG000190729.
HOVERGEN	HBG005745.
InParanoid	O35943.
OMA	KQSVCLM.
OrthoDB	EOG4ZCT5S.
Gene expression databases
ArrayExpress	O35943.
Bgee	O35943.
CleanEx	MM_FXN.
Genevestigator	O35943.
GermOnline	ENSMUSG00000059363. Mus musculus.
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
NextBio	285709.
SOURCE	Search...

Entry information

Entry name

FRDA_MOUSE

Accession

Primary (citable) accession number: O35943

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	January 1, 1998
Last modified:	April 3, 2013
This is version 98 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program