FRDA_MOUSE
ID FRDA_MOUSE Reviewed; 207 AA.
AC O35943;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Frataxin, mitochondrial;
DE Short=Fxn;
DE EC=1.16.3.1;
DE Contains:
DE RecName: Full=Frataxin intermediate form;
DE Contains:
DE RecName: Full=Frataxin mature form;
DE Flags: Precursor;
GN Name=Fxn; Synonyms=Frda;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RC TISSUE=Embryo;
RX PubMed=9241270; DOI=10.1038/ng0897-345;
RA Koutnikova H., Campuzano V., Foury F., Dolle P., Cazzalini O., Koenig M.;
RT "Studies of human, mouse and yeast homologues indicate a mitochondrial
RT function for frataxin.";
RL Nat. Genet. 16:345-351(1997).
RN [2]
RP SUBUNIT.
RX PubMed=11823441; DOI=10.1093/hmg/11.3.217;
RA Cavadini P., O'Neill H.A., Benada O., Isaya G.;
RT "Assembly and iron-binding properties of human frataxin, the protein
RT deficient in Friedreich ataxia.";
RL Hum. Mol. Genet. 11:217-227(2002).
RN [3]
RP SUBCELLULAR LOCATION.
RX PubMed=17597094; DOI=10.1093/hmg/ddm163;
RA Martelli A., Wattenhofer-Donze M., Schmucker S., Bouvet S., Reutenauer L.,
RA Puccio H.;
RT "Frataxin is essential for extramitochondrial Fe-S cluster proteins in
RT mammalian tissues.";
RL Hum. Mol. Genet. 16:2651-2658(2007).
RN [4]
RP PROTEOLYTIC PROCESSING.
RX PubMed=18725397; DOI=10.1093/hmg/ddn244;
RA Schmucker S., Argentini M., Carelle-Calmels N., Martelli A., Puccio H.;
RT "The in vivo mitochondrial two-step maturation of human frataxin.";
RL Hum. Mol. Genet. 17:3521-3531(2008).
RN [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=19629184; DOI=10.1371/journal.pone.0006379;
RA Calmels N., Schmucker S., Wattenhofer-Donze M., Martelli A., Vaucamps N.,
RA Reutenauer L., Messaddeq N., Bouton C., Koenig M., Puccio H.;
RT "The first cellular models based on frataxin missense mutations that
RT reproduce spontaneously the defects associated with Friedreich ataxia.";
RL PLoS ONE 4:E6379-E6379(2009).
RN [6]
RP FUNCTION.
RX PubMed=19805308; DOI=10.1073/pnas.0906784106;
RA Huang M.L., Becker E.M., Whitnall M., Rahmanto Y.S., Ponka P.,
RA Richardson D.R.;
RT "Elucidation of the mechanism of mitochondrial iron loading in Friedreich's
RT ataxia by analysis of a mouse mutant.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:16381-16386(2009).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Pancreas, Spleen,
RC and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Promotes the biosynthesis of heme and assembly and repair of
CC iron-sulfur clusters by delivering Fe(2+) to proteins involved in these
CC pathways. May play a role in the protection against iron-catalyzed
CC oxidative stress through its ability to catalyze the oxidation of
CC Fe(2+) to Fe(3+); the oligomeric form but not the monomeric form has in
CC vitro ferroxidase activity. May be able to store large amounts of iron
CC in the form of a ferrihydrite mineral by oligomerization. Modulates the
CC RNA-binding activity of ACO1 (By similarity). {ECO:0000250,
CC ECO:0000269|PubMed:19805308}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4 Fe(2+) + 4 H(+) + O2 = 4 Fe(3+) + 2 H2O;
CC Xref=Rhea:RHEA:11148, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034; EC=1.16.3.1;
CC -!- SUBUNIT: Monomer (probable predominant form). Oligomer
CC (PubMed:11823441). Interacts with LYRM4 and HSPA9. Interacts with ACO1.
CC Interacts with ISCU. Interacts with FECH; one iron-bound FXN monomer
CC seems to interact with a FECH homodimer. Interacts with SDHA and SDHB.
CC Interacts with ACO2; the interaction is dependent on citrate (By
CC similarity). {ECO:0000250|UniProtKB:D3ZYW7,
CC ECO:0000250|UniProtKB:Q16595, ECO:0000269|PubMed:11823441}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q16595}. Mitochondrion
CC {ECO:0000269|PubMed:17597094, ECO:0000269|PubMed:9241270}.
CC Note=PubMed:17597094 describes localization exclusively in
CC mitochondria.
CC -!- TISSUE SPECIFICITY: Heart, liver, skeletal muscle, kidney, spleen and
CC thymus. Weakly expressed in the brain and lung.
CC {ECO:0000269|PubMed:9241270}.
CC -!- DEVELOPMENTAL STAGE: Expression in the ventricular zone which
CC corresponds to dividing neuronal precursors begins at day 12.5,
CC increases during embryonic development and persists at postnatal day 7
CC (P7) in the ependymal layer, which is the remnant of the ventricular
CC zone. Weak expression seen in the spinal cord and medulla oblongata,
CC starting at 14.5 dpc and expression also observed in dorsal root
CC ganglia, starting at 14.5 dpc. At P14, expression in the dorsal root
CC ganglia is restricted to the cortical region where the sensory neuron
CC cell bodies are located. In non-neural tissues strong expression seen
CC in the developing liver from 10.5 dpc. Expression detected in the heart
CC and in the cortex of the developing kidney at 12.5 dpc and later. Very
CC high expression observed in the brown adipose tissue. Expression seen
CC in small islands around the neck and back at 14.5 dpc, then in large
CC masses at 16.5 dpc and 18.5 dpc and at P14 is absent in brown adipose
CC tissue. Expression also seen in the thymus and developing gut at 14.5
CC dpc and until postnatal life. At P14, expression in thymus is
CC restricted to the proliferating cells in the cortical zone and is also
CC prominent in the spleen. Found in the lung at 14.5 dpc.
CC {ECO:0000269|PubMed:9241270}.
CC -!- PTM: Processed in two steps by mitochondrial processing peptidase
CC (MPP). MPP first cleaves the precursor to intermediate form and
CC subsequently converts the intermediate to yield frataxin mature form
CC (By similarity). {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Loss of cell division and lethal in fibroblasts.
CC {ECO:0000269|PubMed:19629184}.
CC -!- SIMILARITY: Belongs to the frataxin family. {ECO:0000305}.
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DR EMBL; U95736; AAB67778.1; -; mRNA.
DR CCDS; CCDS29711.1; -.
DR RefSeq; NP_032070.1; NM_008044.2.
DR AlphaFoldDB; O35943; -.
DR SMR; O35943; -.
DR BioGRID; 199741; 5.
DR ComplexPortal; CPX-5823; Mitochondrial NIAUFX iron-sulfur cluster assembly complex.
DR STRING; 10090.ENSMUSP00000080081; -.
DR iPTMnet; O35943; -.
DR PhosphoSitePlus; O35943; -.
DR EPD; O35943; -.
DR jPOST; O35943; -.
DR PaxDb; O35943; -.
DR PeptideAtlas; O35943; -.
DR PRIDE; O35943; -.
DR ProteomicsDB; 267517; -.
DR ABCD; O35943; 1 sequenced antibody.
DR Antibodypedia; 26793; 649 antibodies from 35 providers.
DR DNASU; 14297; -.
DR Ensembl; ENSMUST00000081333; ENSMUSP00000080081; ENSMUSG00000059363.
DR GeneID; 14297; -.
DR KEGG; mmu:14297; -.
DR UCSC; uc008hao.1; mouse.
DR CTD; 2395; -.
DR MGI; MGI:1096879; Fxn.
DR VEuPathDB; HostDB:ENSMUSG00000059363; -.
DR eggNOG; KOG3413; Eukaryota.
DR GeneTree; ENSGT00390000005811; -.
DR HOGENOM; CLU_080880_1_0_1; -.
DR InParanoid; O35943; -.
DR OMA; CWINLRT; -.
DR OrthoDB; 1372185at2759; -.
DR PhylomeDB; O35943; -.
DR TreeFam; TF318958; -.
DR Reactome; R-MMU-1268020; Mitochondrial protein import.
DR Reactome; R-MMU-1362409; Mitochondrial iron-sulfur cluster biogenesis.
DR BioGRID-ORCS; 14297; 26 hits in 72 CRISPR screens.
DR ChiTaRS; Fxn; mouse.
DR PRO; PR:O35943; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; O35943; protein.
DR Bgee; ENSMUSG00000059363; Expressed in bone marrow and 129 other tissues.
DR ExpressionAtlas; O35943; baseline and differential.
DR Genevisible; O35943; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:1990229; C:iron-sulfur cluster assembly complex; IC:ComplexPortal.
DR GO; GO:1990221; C:L-cysteine desulfurase complex; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0051537; F:2 iron, 2 sulfur cluster binding; ISO:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0008199; F:ferric iron binding; ISO:MGI.
DR GO; GO:0008198; F:ferrous iron binding; ISO:MGI.
DR GO; GO:0004322; F:ferroxidase activity; ISO:MGI.
DR GO; GO:0034986; F:iron chaperone activity; ISO:MGI.
DR GO; GO:0007628; P:adult walking behavior; IMP:MGI.
DR GO; GO:0009060; P:aerobic respiration; IMP:MGI.
DR GO; GO:0006879; P:cellular iron ion homeostasis; IMP:MGI.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; ISO:MGI.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; IMP:MGI.
DR GO; GO:0006783; P:heme biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0006811; P:ion transport; IEA:UniProtKB-KW.
DR GO; GO:0018283; P:iron incorporation into metallo-sulfur cluster; ISO:MGI.
DR GO; GO:0016226; P:iron-sulfur cluster assembly; IMP:MGI.
DR GO; GO:0007005; P:mitochondrion organization; IMP:MGI.
DR GO; GO:0046716; P:muscle cell cellular homeostasis; IMP:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:0040015; P:negative regulation of multicellular organism growth; IMP:MGI.
DR GO; GO:0046621; P:negative regulation of organ growth; IMP:MGI.
DR GO; GO:0090201; P:negative regulation of release of cytochrome c from mitochondria; ISO:MGI.
DR GO; GO:0035265; P:organ growth; IMP:MGI.
DR GO; GO:0006119; P:oxidative phosphorylation; IMP:MGI.
DR GO; GO:1904234; P:positive regulation of aconitate hydratase activity; ISO:MGI.
DR GO; GO:0045773; P:positive regulation of axon extension; ISO:MGI.
DR GO; GO:0043085; P:positive regulation of catalytic activity; ISO:MGI.
DR GO; GO:0030307; P:positive regulation of cell growth; ISO:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0051349; P:positive regulation of lyase activity; ISO:MGI.
DR GO; GO:1904231; P:positive regulation of succinate dehydrogenase activity; ISO:MGI.
DR GO; GO:0019230; P:proprioception; IMP:MGI.
DR GO; GO:0016540; P:protein autoprocessing; ISO:MGI.
DR GO; GO:0010722; P:regulation of ferrochelatase activity; ISO:MGI.
DR GO; GO:0010039; P:response to iron ion; ISO:MGI.
DR Gene3D; 3.30.920.10; -; 1.
DR InterPro; IPR017789; Frataxin.
DR InterPro; IPR002908; Frataxin/CyaY.
DR InterPro; IPR036524; Frataxin/CyaY_sf.
DR InterPro; IPR020895; Frataxin_CS.
DR PANTHER; PTHR16821; PTHR16821; 1.
DR Pfam; PF01491; Frataxin_Cyay; 1.
DR PRINTS; PR00904; FRATAXIN.
DR SMART; SM01219; Frataxin_Cyay; 1.
DR SUPFAM; SSF55387; SSF55387; 1.
DR TIGRFAMs; TIGR03421; FeS_CyaY; 1.
DR TIGRFAMs; TIGR03422; mito_frataxin; 1.
DR PROSITE; PS01344; FRATAXIN_1; 1.
DR PROSITE; PS50810; FRATAXIN_2; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Heme biosynthesis; Ion transport; Iron; Iron storage;
KW Iron transport; Metal-binding; Mitochondrion; Oxidoreductase;
KW Reference proteome; Transit peptide; Transport.
FT TRANSIT 1..40
FT /note="Mitochondrion"
FT /evidence="ECO:0000250"
FT CHAIN 41..207
FT /note="Frataxin intermediate form"
FT /id="PRO_0000010132"
FT CHAIN 78..207
FT /note="Frataxin mature form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000399390"
SQ SEQUENCE 207 AA; 22924 MW; C46FD21B44FB26A2 CRC64;
MWAFGGRAAV GLLPRTASRA SAWVGNPRWR EPIVTCGRRG LHVTVNAGAT RHAHLNLHYL
QILNIKKQSV CVVHLRNLGT LDNPSSLDET AYERLAEETL DSLAEFFEDL ADKPYTLEDY
DVSFGDGVLT IKLGGDLGTY VINKQTPNKQ IWLSSPSSGP KRYDWTGKNW VYSHDGVSLH
ELLARELTKA LNTKLDLSSL AYSGKGT
