ID   FRDA_RAT                Reviewed;         208 AA.
AC   D3ZYW7;
DT   05-OCT-2010, integrated into UniProtKB/Swiss-Prot.
DT   20-APR-2010, sequence version 1.
DT   03-AUG-2022, entry version 59.
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;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Brown Norway;
RX   PubMed=15057822; DOI=10.1038/nature02426;
RA   Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA   Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA   Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA   Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA   Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA   Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA   Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA   Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA   Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA   Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA   Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA   Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA   Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA   Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA   Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA   Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA   Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA   Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA   Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA   Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA   Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA   Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA   Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA   Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA   Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA   Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA   Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA   Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA   Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA   Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA   Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA   Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA   Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA   Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA   Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA   Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA   Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA   Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA   Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA   Mockrin S., Collins F.S.;
RT   "Genome sequence of the Brown Norway rat yields insights into mammalian
RT   evolution.";
RL   Nature 428:493-521(2004).
RN   [2]
RP   FUNCTION AS IRON CHAPERONE, AND INTERACTION WITH ACO2.
RX   PubMed=15247478; DOI=10.1126/science.1098991;
RA   Bulteau A.L., O'Neill H.A., Kennedy M.C., Ikeda-Saito M., Isaya G.,
RA   Szweda L.I.;
RT   "Frataxin acts as an iron chaperone protein to modulate mitochondrial
RT   aconitase activity.";
RL   Science 305:242-245(2004).
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:15247478}.
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. Interacts with
CC       LYRM4 and HSPA9. Interacts with ACO1. Interacts with ISCU. Interacts
CC       with FECH; one iron-bound FXN monomer seems to interact with a FECH
CC       homodimer. Interacts with SDHA and SDHB (By similarity). Interacts with
CC       ACO2; the interaction is dependent on citrate (PubMed:15247478).
CC       {ECO:0000250|UniProtKB:Q16595, ECO:0000269|PubMed:15247478}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC       {ECO:0000250|UniProtKB:Q16595}. Mitochondrion
CC       {ECO:0000250|UniProtKB:Q16595}.
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   -!- SIMILARITY: Belongs to the frataxin family. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AABR03005338; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AABR03006217; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AABR03009513; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   AlphaFoldDB; D3ZYW7; -.
DR   SMR; D3ZYW7; -.
DR   STRING; 10116.ENSRNOP00000020412; -.
DR   iPTMnet; D3ZYW7; -.
DR   PhosphoSitePlus; D3ZYW7; -.
DR   PeptideAtlas; D3ZYW7; -.
DR   PRIDE; D3ZYW7; -.
DR   UCSC; RGD:1565754; rat.
DR   RGD; 1565754; Fxn.
DR   eggNOG; KOG3413; Eukaryota.
DR   InParanoid; D3ZYW7; -.
DR   PhylomeDB; D3ZYW7; -.
DR   TreeFam; TF318958; -.
DR   Reactome; R-RNO-1268020; Mitochondrial protein import.
DR   Reactome; R-RNO-1362409; Mitochondrial iron-sulfur cluster biogenesis.
DR   PRO; PR:D3ZYW7; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0005829; C:cytosol; ISO:RGD.
DR   GO; GO:1990221; C:L-cysteine desulfurase complex; ISO:RGD.
DR   GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR   GO; GO:0051537; F:2 iron, 2 sulfur cluster binding; ISO:RGD.
DR   GO; GO:0019899; F:enzyme binding; IPI:RGD.
DR   GO; GO:0008199; F:ferric iron binding; ISO:RGD.
DR   GO; GO:0008198; F:ferrous iron binding; ISO:RGD.
DR   GO; GO:0004322; F:ferroxidase activity; ISO:RGD.
DR   GO; GO:0034986; F:iron chaperone activity; ISO:RGD.
DR   GO; GO:0016530; F:metallochaperone activity; NAS:RGD.
DR   GO; GO:0007628; P:adult walking behavior; ISO:RGD.
DR   GO; GO:0009060; P:aerobic respiration; ISO:RGD.
DR   GO; GO:0006879; P:cellular iron ion homeostasis; ISO:RGD.
DR   GO; GO:0070301; P:cellular response to hydrogen peroxide; ISO:RGD.
DR   GO; GO:0009792; P:embryo development ending in birth or egg hatching; ISO:RGD.
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:RGD.
DR   GO; GO:0016226; P:iron-sulfur cluster assembly; ISO:RGD.
DR   GO; GO:0007005; P:mitochondrion organization; ISO:RGD.
DR   GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD.
DR   GO; GO:0040015; P:negative regulation of multicellular organism growth; ISO:RGD.
DR   GO; GO:0046621; P:negative regulation of organ growth; ISO:RGD.
DR   GO; GO:0090201; P:negative regulation of release of cytochrome c from mitochondria; ISO:RGD.
DR   GO; GO:0006119; P:oxidative phosphorylation; ISO:RGD.
DR   GO; GO:1904234; P:positive regulation of aconitate hydratase activity; ISO:RGD.
DR   GO; GO:0045773; P:positive regulation of axon extension; IMP:RGD.
DR   GO; GO:0043085; P:positive regulation of catalytic activity; ISO:RGD.
DR   GO; GO:0030307; P:positive regulation of cell growth; ISO:RGD.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:RGD.
DR   GO; GO:0051349; P:positive regulation of lyase activity; ISO:RGD.
DR   GO; GO:1904231; P:positive regulation of succinate dehydrogenase activity; ISO:RGD.
DR   GO; GO:0019230; P:proprioception; ISO:RGD.
DR   GO; GO:0016540; P:protein autoprocessing; ISO:RGD.
DR   GO; GO:0010722; P:regulation of ferrochelatase activity; ISO:RGD.
DR   GO; GO:0010039; P:response to iron ion; ISO:RGD.
DR   GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR   GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR   Gene3D; 3.30.920.10; -; 1.
DR   InterPro; IPR017789; Frataxin.
DR   InterPro; IPR002908; Frataxin/CyaY.
DR   InterPro; IPR036524; Frataxin/CyaY_sf.
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; PS50810; FRATAXIN_2; 1.
PE   1: Evidence at protein level;
KW   Cytoplasm; Heme biosynthesis; Ion transport; Iron; Iron storage;
KW   Iron transport; Mitochondrion; Oxidoreductase; Reference proteome;
KW   Transit peptide; Transport.
FT   TRANSIT         1..40
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000250"
FT   CHAIN           41..208
FT                   /note="Frataxin intermediate form"
FT                   /id="PRO_0000399465"
FT   CHAIN           79..208
FT                   /note="Frataxin mature form"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000399391"
SQ   SEQUENCE   208 AA;  23066 MW;  401B8210F5CEDD35 CRC64;
     MWTFGRRAAA GLLPRTASRA SAWVRNPRGR ERIGTCGRRG LHVTANADAI RHSHLNLHYL
     GQILNIKKQS VCVVHLRNSG TLGNPSSLDE TAYERLAEET LDALAEFFED LADKPYTLKD
     YDVSFGDGVL TIKLGGDLGT YVINKQTPLL YLWFSGPCSG PKRYDWTGKN WVYSHDGVSL
     HELLARELTE ALNTKLDLSS LAYSGKGT