ID   FRDA_DROME              Reviewed;         190 AA.
AC   Q9W385; Q9GQQ7;
DT   01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   03-AUG-2022, entry version 156.
DE   RecName: Full=Frataxin homolog, mitochondrial;
DE            Short=Dfh {ECO:0000303|PubMed:25628335, ECO:0000312|FlyBase:FBgn0030092};
DE            EC=1.16.3.1 {ECO:0000269|PubMed:18540637};
DE   Flags: Precursor;
GN   Name=fh {ECO:0000312|FlyBase:FBgn0030092};
GN   ORFNames=CG8971 {ECO:0000312|FlyBase:FBgn0030092};
OS   Drosophila melanogaster (Fruit fly).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC   Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC   Drosophilidae; Drosophila; Sophophora.
OX   NCBI_TaxID=7227;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND DEVELOPMENTAL STAGE.
RX   PubMed=11054533; DOI=10.1016/s0378-1119(00)00343-7;
RA   Canizares-Sales J., Blanca-Postigo J.M., Navarro J.A., Monros E.,
RA   Palau-Martinez F., Molto-Ruiz M.D.;
RT   "dfh is a Drosophila homolog of the Friedreich's ataxia disease gene.";
RL   Gene 256:35-42(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Berkeley;
RX   PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA   Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA   Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA   George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA   Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA   Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA   Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA   An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA   Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA   Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA   Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA   Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA   Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA   Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA   Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA   Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA   Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA   Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA   Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA   Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA   Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA   Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA   McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA   Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA   Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA   Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA   Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA   Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA   Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA   Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA   Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA   Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA   Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA   Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA   Venter J.C.;
RT   "The genome sequence of Drosophila melanogaster.";
RL   Science 287:2185-2195(2000).
RN   [3]
RP   GENOME REANNOTATION.
RC   STRAIN=Berkeley;
RX   PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA   Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA   Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA   Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA   Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA   Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA   Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT   "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT   review.";
RL   Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Berkeley; TISSUE=Testis;
RX   PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA   Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA   Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA   Celniker S.E.;
RT   "A Drosophila full-length cDNA resource.";
RL   Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN   [5]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=18540637; DOI=10.1021/bi800366d;
RA   Kondapalli K.C., Kok N.M., Dancis A., Stemmler T.L.;
RT   "Drosophila frataxin: an iron chaperone during cellular Fe-S cluster
RT   bioassembly.";
RL   Biochemistry 47:6917-6927(2008).
RN   [6]
RP   FUNCTION, DISRUPTION PHENOTYPE, AND SUBUNIT.
RX   PubMed=25628335; DOI=10.1093/hmg/ddv024;
RA   Palandri A., L'hote D., Cohen-Tannoudji J., Tricoire H., Monnier V.;
RT   "Frataxin inactivation leads to steroid deficiency in flies and human
RT   ovarian cells.";
RL   Hum. Mol. Genet. 24:2615-2626(2015).
RN   [7]
RP   INTERACTION WITH BCN92; ISCU AND NSF1.
RX   PubMed=29491838; DOI=10.3389/fphys.2018.00050;
RA   Marelja Z., Leimkuehler S., Missirlis F.;
RT   "Iron Sulfur and Molybdenum Cofactor Enzymes Regulate the Drosophila Life
RT   Cycle by Controlling Cell Metabolism.";
RL   Front. Physiol. 9:50-50(2018).
CC   -!- FUNCTION: Promotes the biosynthesis of heme as well as the assembly and
CC       repair of iron-sulfur clusters by delivering Fe(2+) to proteins
CC       involved in these pathways (PubMed:18540637). May play a role in the
CC       protection against iron-catalyzed oxidative stress through its ability
CC       to catalyze the oxidation of Fe(2+) to Fe(3+) (PubMed:18540637). May be
CC       able to store large amounts of the metal in the form of a ferrihydrite
CC       mineral by oligomerization (PubMed:18540637). Required for
CC       ecdysteroidogenesis in the prothoracic gland which is necessary for
CC       larval to pupal transition (PubMed:25628335).
CC       {ECO:0000269|PubMed:18540637, ECO:0000269|PubMed:25628335}.
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         Evidence={ECO:0000269|PubMed:18540637};
CC   -!- SUBUNIT: Monomer (probable predominant form) (PubMed:18540637).
CC       Oligomer (PubMed:18540637). Might form a complex with bcn92, IscU and
CC       Nsf1 (Probable). Interacts with IscU (By similarity).
CC       {ECO:0000250|UniProtKB:Q16595, ECO:0000269|PubMed:18540637,
CC       ECO:0000305|PubMed:29491838}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:Q16595}.
CC   -!- DEVELOPMENTAL STAGE: Expressed throughout development, levels are high
CC       during embryogenesis but low in following stages.
CC       {ECO:0000269|PubMed:11054533}.
CC   -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown results in nearly absent
CC       pupariation and reduced ecdysteroid peak level required to proceed to
CC       pupal stage (PubMed:25628335). RNAi-mediated knockdown in the
CC       prothoracic gland results in delayed or absent pupariation
CC       (PubMed:25628335). {ECO:0000269|PubMed:25628335}.
CC   -!- SIMILARITY: Belongs to the frataxin family. {ECO:0000305}.
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DR   EMBL; AJ002208; CAC20098.1; -; mRNA.
DR   EMBL; AF208491; AAG35732.1; -; mRNA.
DR   EMBL; AF208492; AAG35733.1; -; Genomic_DNA.
DR   EMBL; AE014298; AAF46449.1; -; Genomic_DNA.
DR   EMBL; AY094649; AAM11002.1; -; mRNA.
DR   RefSeq; NP_511094.1; NM_078539.3.
DR   AlphaFoldDB; Q9W385; -.
DR   BMRB; Q9W385; -.
DR   SMR; Q9W385; -.
DR   BioGRID; 58300; 9.
DR   IntAct; Q9W385; 6.
DR   STRING; 7227.FBpp0071283; -.
DR   PaxDb; Q9W385; -.
DR   DNASU; 31845; -.
DR   EnsemblMetazoa; FBtr0071348; FBpp0071283; FBgn0030092.
DR   GeneID; 31845; -.
DR   KEGG; dme:Dmel_CG8971; -.
DR   CTD; 2271; -.
DR   FlyBase; FBgn0030092; fh.
DR   VEuPathDB; VectorBase:FBgn0030092; -.
DR   eggNOG; KOG3413; Eukaryota.
DR   GeneTree; ENSGT00390000005811; -.
DR   HOGENOM; CLU_080880_2_1_1; -.
DR   InParanoid; Q9W385; -.
DR   OMA; WIYKHSG; -.
DR   PhylomeDB; Q9W385; -.
DR   Reactome; R-DME-1362409; Mitochondrial iron-sulfur cluster biogenesis.
DR   BioGRID-ORCS; 31845; 0 hits in 1 CRISPR screen.
DR   GenomeRNAi; 31845; -.
DR   PRO; PR:Q9W385; -.
DR   Proteomes; UP000000803; Chromosome X.
DR   Bgee; FBgn0030092; Expressed in secondary oocyte and 20 other tissues.
DR   Genevisible; Q9W385; DM.
DR   GO; GO:1904115; C:axon cytoplasm; IEA:GOC.
DR   GO; GO:1990221; C:L-cysteine desulfurase complex; ISS:FlyBase.
DR   GO; GO:0005739; C:mitochondrion; IMP:FlyBase.
DR   GO; GO:0051537; F:2 iron, 2 sulfur cluster binding; IBA:GO_Central.
DR   GO; GO:0008199; F:ferric iron binding; IBA:GO_Central.
DR   GO; GO:0008198; F:ferrous iron binding; IBA:GO_Central.
DR   GO; GO:0004322; F:ferroxidase activity; ISS:FlyBase.
DR   GO; GO:0034986; F:iron chaperone activity; IDA:FlyBase.
DR   GO; GO:0008344; P:adult locomotory behavior; IMP:FlyBase.
DR   GO; GO:0019896; P:axonal transport of mitochondrion; IDA:FlyBase.
DR   GO; GO:0006879; P:cellular iron ion homeostasis; IBA:GO_Central.
DR   GO; GO:0008340; P:determination of adult lifespan; IMP:FlyBase.
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; IBA:GO_Central.
DR   GO; GO:0016226; P:iron-sulfur cluster assembly; ISS:FlyBase.
DR   GO; GO:0016042; P:lipid catabolic process; IMP:FlyBase.
DR   GO; GO:0045998; P:positive regulation of ecdysteroid biosynthetic process; IMP:FlyBase.
DR   GO; GO:0045823; P:positive regulation of heart contraction; IMP:FlyBase.
DR   GO; GO:1903862; P:positive regulation of oxidative phosphorylation; IDA:FlyBase.
DR   GO; GO:0051881; P:regulation of mitochondrial membrane potential; IDA:FlyBase.
DR   GO; GO:0042542; P:response to hydrogen peroxide; IMP:FlyBase.
DR   GO; GO:0010039; P:response to iron ion; IMP:FlyBase.
DR   GO; GO:0006979; P:response to oxidative stress; IMP:FlyBase.
DR   GO; GO:0006694; P:steroid biosynthetic process; IEA:UniProtKB-KW.
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   Heme biosynthesis; Ion transport; Iron; Iron storage; Iron transport;
KW   Lipid metabolism; Mitochondrion; Oxidoreductase; Reference proteome;
KW   Steroid metabolism; Steroidogenesis; Transit peptide; Transport.
FT   TRANSIT         1..?
FT                   /note="Mitochondrion"
FT   CHAIN           ?..190
FT                   /note="Frataxin homolog, mitochondrial"
FT                   /id="PRO_0000010133"
SQ   SEQUENCE   190 AA;  20922 MW;  8C48332C239F3036 CRC64;
     MFAGRLMVRS IVGRACLATM GRWSKPQAHA SQVILPSTPA IAAVAIQCEE FTANRRLFSS
     QIETESTLDG ATYERVCSDT LDALCDYFEE LTENASELQG TDVAYSDGVL TVNLGGQHGT
     YVINRQTPNK QIWLSSPTSG PKRYDFVGTV AAGRWIYKHS GQSLHELLQQ EIPGILKSQS
     VDFLRLPYCS