ID FRDA_YEAST Reviewed; 174 AA. AC Q07540; D6VRN0; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 14-DEC-2011, entry version 112. DE RecName: Full=Frataxin homolog, mitochondrial; DE EC=1.16.3.1; DE Contains: DE RecName: Full=Frataxin homolog intermediate form; DE Flags: Precursor; GN Name=YFH1; OrderedLocusNames=YDL120W; OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast). OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; OC Saccharomycetes; Saccharomycetales; Saccharomycetaceae; Saccharomyces. OX NCBI_TaxID=559292; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX MEDLINE=97313263; PubMed=9169867; RA Jacq C., Alt-Moerbe J., Andre B., Arnold W., Bahr A., Ballesta J.P.G., RA Bargues M., Baron L., Becker A., Biteau N., Bloecker H., Blugeon C., RA Boskovic J., Brandt P., Brueckner M., Buitrago M.J., Coster F., RA Delaveau T., del Rey F., Dujon B., Eide L.G., Garcia-Cantalejo J.M., RA Goffeau A., Gomez-Peris A., Granotier C., Hanemann V., Hankeln T., RA Hoheisel J.D., Jaeger W., Jimenez A., Jonniaux J.-L., Kraemer C., RA Kuester H., Laamanen P., Legros Y., Louis E.J., Moeller-Rieker S., RA Monnet A., Moro M., Mueller-Auer S., Nussbaumer B., Paricio N., RA Paulin L., Perea J., Perez-Alonso M., Perez-Ortin J.E., Pohl T.M., RA Prydz H., Purnelle B., Rasmussen S.W., Remacha M.A., Revuelta J.L., RA Rieger M., Salom D., Saluz H.P., Saiz J.E., Saren A.-M., Schaefer M., RA Scharfe M., Schmidt E.R., Schneider C., Scholler P., Schwarz S., RA Soler-Mira A., Urrestarazu L.A., Verhasselt P., Vissers S., Voet M., RA Volckaert G., Wagner G., Wambutt R., Wedler E., Wedler H., Woelfl S., RA Harris D.E., Bowman S., Brown D., Churcher C.M., Connor R., Dedman K., RA Gentles S., Hamlin N., Hunt S., Jones L., McDonald S., Murphy L.D., RA Niblett D., Odell C., Oliver K., Rajandream M.A., Richards C., RA Shore L., Walsh S.V., Barrell B.G., Dietrich F.S., Mulligan J.T., RA Allen E., Araujo R., Aviles E., Berno A., Carpenter J., Chen E., RA Cherry J.M., Chung E., Duncan M., Hunicke-Smith S., Hyman R.W., RA Komp C., Lashkari D., Lew H., Lin D., Mosedale D., Nakahara K., RA Namath A., Oefner P., Oh C., Petel F.X., Roberts D., Schramm S., RA Schroeder M., Shogren T., Shroff N., Winant A., Yelton M.A., RA Botstein D., Davis R.W., Johnston M., Andrews S., Brinkman R., RA Cooper J., Ding H., Du Z., Favello A., Fulton L., Gattung S., RA Greco T., Hallsworth K., Hawkins J., Hillier L.W., Jier M., RA Johnson D., Johnston L., Kirsten J., Kucaba T., Langston Y., RA Latreille P., Le T., Mardis E., Menezes S., Miller N., Nhan M., RA Pauley A., Peluso D., Rifkin L., Riles L., Taich A., Trevaskis E., RA Vignati D., Wilcox L., Wohldman P., Vaudin M., Wilson R., RA Waterston R., Albermann K., Hani J., Heumann K., Kleine K., RA Mewes H.-W., Zollner A., Zaccaria P.; RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome IV."; RL Nature 387:75-78(1997). RN [2] RP GENOME REANNOTATION. RC STRAIN=ATCC 204508 / S288c; RG Saccharomyces Genome Database; RL Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=17322287; DOI=10.1101/gr.6037607; RA Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F., RA Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., RA Raphael J., Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., RA Williamson J., Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., RA Kolodner R.D., LaBaer J.; RT "Approaching a complete repository of sequence-verified protein- RT encoding clones for Saccharomyces cerevisiae."; RL Genome Res. 17:536-543(2007). RN [4] RP FUNCTION, AND SUBCELLULAR LOCATION. RX MEDLINE=97324273; PubMed=9180083; DOI=10.1126/science.276.5319.1709; RA Babcock M., de Silva D., Oaks R., Davis-Kaplan S., Jiralerspong S., RA Montermini L., Pandolfo M., Kaplan J.; RT "Regulation of mitochondrial iron accumulation by Yfh1p, a putative RT homolog of frataxin."; RL Science 276:1709-1712(1997). RN [5] RP FUNCTION, AND SUBCELLULAR LOCATION. RX MEDLINE=99143100; PubMed=9988680; DOI=10.1074/jbc.274.8.4497; RA Radisky D.C., Babcock M.C., Kaplan J.; RT "The yeast frataxin homologue mediates mitochondrial iron efflux. RT Evidence for a mitochondrial iron cycle."; RL J. Biol. Chem. 274:4497-4499(1999). RN [6] RP PROCESSING. RX MEDLINE=20014717; PubMed=10545606; DOI=10.1093/hmg/8.12.2255; RA Gordon D.M., Shi Q., Dancis A., Pain D.; RT "Maturation of frataxin within mammalian and yeast mitochondria: one- RT step processing by matrix processing peptidase."; RL Hum. Mol. Genet. 8:2255-2262(1999). RN [7] RP PROCESSING. RX MEDLINE=99357816; PubMed=10428860; DOI=10.1074/jbc.274.32.22763; RA Branda S.S., Cavadini P., Adamec J., Kalousek F., Taroni F., Isaya G.; RT "Yeast and human frataxin are processed to mature form in two RT sequential steps by the mitochondrial processing peptidase."; RL J. Biol. Chem. 274:22763-22769(1999). RN [8] RP INTERACTION WITH ISU1. RX PubMed=10588895; DOI=10.1006/jmbi.1999.3294; RA Garland S.A., Hoff K., Vickery L.E., Culotta V.C.; RT "Saccharomyces cerevisiae ISU1 and ISU2: members of a well-conserved RT gene family for iron-sulfur cluster assembly."; RL J. Mol. Biol. 294:897-907(1999). RN [9] RP INTERACTION WITH ISU1. RX PubMed=12947415; DOI=10.1038/sj.embor.embor918; RA Gerber J., Muhlenhoff U., Lill R.; RT "An interaction between frataxin and Isu1/Nfs1 that is crucial for RT Fe/S cluster synthesis on Isu1."; RL EMBO Rep. 4:906-911(2003). RN [10] RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS]. RX MEDLINE=22923965; PubMed=14562106; DOI=10.1038/nature02046; RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., RA Dephoure N., O'Shea E.K., Weissman J.S.; RT "Global analysis of protein expression in yeast."; RL Nature 425:737-741(2003). RN [11] RP FUNCTION, AND INTERACTION WITH YHB1; SDH1; SDH2; AIM45 AND CIR1. RX PubMed=15961414; DOI=10.1093/hmg/ddi214; RA Gonzalez-Cabo P., Vazquez-Manrique R.P., Garcia-Gimeno M.A., Sanz P., RA Palau F.; RT "Frataxin interacts functionally with mitochondrial electron transport RT chain proteins."; RL Hum. Mol. Genet. 14:2091-2098(2005). RN [12] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF ASP-79; ASP-82; RP GLU-93; ASP-97 AND GLU-103. RX PubMed=16371422; DOI=10.1093/hmg/ddi461; RA Gakh O., Park S., Liu G., Macomber L., Imlay J.A., Ferreira G.C., RA Isaya G.; RT "Mitochondrial iron detoxification is a primary function of frataxin RT that limits oxidative damage and preserves cell longevity."; RL Hum. Mol. Genet. 15:467-479(2006). RN [13] RP INTERACTION WITH ISU1, AND MUTAGENESIS OF 122-ASN--GLU-124. RX PubMed=18319250; DOI=10.1074/jbc.M800399200; RA Wang T., Craig E.A.; RT "Binding of yeast frataxin to the scaffold for Fe-S cluster RT biogenesis, Isu."; RL J. Biol. Chem. 283:12674-12679(2008). RN [14] RP FUNCTION IN IRON-SULFUR CLUSTER BIOSYNTHESIS, INTERACTION WITH ISU1, RP AND MUTAGENESIS OF GLN-129; ILE-130; TRP-131 AND ARG-141. RX PubMed=19884169; DOI=10.1093/hmg/ddp495; RA Leidgens S., De Smet S., Foury F.; RT "Frataxin interacts with Isu1 through a conserved tryptophan in its RT beta-sheet."; RL Hum. Mol. Genet. 19:276-286(2010). RN [15] RP X-RAY CRYSTALLOGRAPHY (3.01 ANGSTROMS) OF 52-174 ALONE AND IN COMPLEX RP WITH IRON, ELECTRON MICROSCOPY OF MUTANT ALA-73, FUNCTION, AND RP SUBUNIT. RX PubMed=17027502; DOI=10.1016/j.str.2006.08.010; RA Karlberg T., Schagerlof U., Gakh O., Park S., Ryde U., Lindahl M., RA Leath K., Garman E., Isaya G., Al-Karadaghi S.; RT "The structures of frataxin oligomers reveal the mechanism for the RT delivery and detoxification of iron."; RL Structure 14:1535-1546(2006). RN [16] RP ELECTRON MICROSCOPY OF MUTANT ALA-73 (13 ANGSTROMS), AND SUBUNIT. RX PubMed=18393441; DOI=10.1021/bi800052m; RA Schagerlof U., Elmlund H., Gakh O., Nordlund G., Hebert H., RA Lindahl M., Isaya G., Al-Karadaghi S.; RT "Structural basis of the iron storage function of frataxin from RT single-particle reconstruction of the iron-loaded oligomer."; RL Biochemistry 47:4948-4954(2008). CC -!- FUNCTION: Promotes the biosynthesis of heme as well as the CC assembly and repair of iron-sulfur clusters by delivering Fe(2+) CC to proteins involved in these pathways. Plays a role in the CC protection against iron-catalyzed oxidative stress through its CC ability to catalyze the oxidation of Fe(2+) to Fe(3+). Can store CC large amounts of the metal in the form of a ferrihydrite mineral CC by oligomerization. May be involved in regulation of the CC mitochondrial electron transport chain. CC -!- CATALYTIC ACTIVITY: 4 Fe(2+) + 4 H(+) + O(2) = 4 Fe(3+) + 2 H(2)O. CC -!- SUBUNIT: Monomer; increments in mitochondrial iron uptake induce CC stepwise assembly of species ranging from trimers to 24-mers. CC Interacts with ISU1. Interacts with YHB1, SDH1, SDH2, AIM45 and CC CIR1. CC -!- INTERACTION: CC P39676:YHB1; NbExp=2; IntAct=EBI-2206814, EBI-6905; CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix. 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 mature size protein. CC -!- MISCELLANEOUS: Present with 1560 molecules/cell in log phase SD CC medium. CC -!- SIMILARITY: Belongs to the frataxin family. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; Z74168; CAA98688.1; -; Genomic_DNA. DR EMBL; AY558160; AAS56486.1; -; Genomic_DNA. DR EMBL; BK006938; DAA11740.1; -; Genomic_DNA. DR PIR; S67663; S67663. DR RefSeq; NP_010163.1; NM_001180179.1. DR PDB; 2FQL; X-ray; 3.01 A; A=52-174. DR PDB; 2GA5; NMR; -; A=53-174. DR PDB; 3OEQ; X-ray; 2.96 A; A=52-174. DR PDB; 3OER; X-ray; 3.20 A; A=52-174. DR PDBsum; 2FQL; -. DR PDBsum; 2GA5; -. DR PDBsum; 3OEQ; -. DR PDBsum; 3OER; -. DR ProteinModelPortal; Q07540; -. DR SMR; Q07540; 52-174. DR DIP; DIP-7485N; -. DR IntAct; Q07540; 11. DR MINT; MINT-4300743; -. DR STRING; Q07540; -. DR EnsemblFungi; YDL120W; YDL120W; YDL120W. DR GeneID; 851437; -. DR KEGG; sce:YDL120W; -. DR NMPDR; fig|4932.3.peg.900; -. DR CYGD; YDL120w; -. DR SGD; S000002278; YFH1. DR eggNOG; fuNOG11011; -. DR GeneTree; EFGT00050000006737; -. DR HOGENOM; HBG396998; -. DR OrthoDB; EOG4WHCWJ; -. DR NextBio; 968672; -. DR ArrayExpress; Q07540; -. DR Genevestigator; Q07540; -. DR GermOnline; YDL120W; Saccharomyces cerevisiae. DR GO; GO:0005759; C:mitochondrial matrix; IDA:SGD. DR GO; GO:0008198; F:ferrous iron binding; IDA:SGD. DR GO; GO:0004322; F:ferroxidase activity; IDA:SGD. DR GO; GO:0034986; F:iron chaperone activity; IDA:SGD. DR GO; GO:0005515; F:protein binding; IPI:IntAct. DR GO; GO:0006879; P:cellular iron ion homeostasis; IMP:SGD. DR GO; GO:0006749; P:glutathione metabolic process; IMP:SGD. DR GO; GO:0006783; P:heme biosynthetic process; IEA:UniProtKB-KW. DR GO; GO:0006811; P:ion transport; IEA:UniProtKB-KW. DR GO; GO:0016226; P:iron-sulfur cluster assembly; IMP:SGD. DR GO; GO:0006121; P:mitochondrial electron transport, succinate to ubiquinone; IMP:UniProtKB. DR GO; GO:0010040; P:response to iron(II) ion; IMP:UniProtKB. DR GO; GO:0006979; P:response to oxidative stress; IMP:UniProtKB. DR InterPro; IPR017789; Frataxin. DR InterPro; IPR002908; Frataxin-like. DR InterPro; IPR020895; Frataxin_CS. DR Gene3D; G3DSA:3.30.920.10; Frataxin_like; 1. DR PANTHER; PTHR16821; PTHR16821; 1. DR Pfam; PF01491; Frataxin_Cyay; 1. DR SUPFAM; SSF55387; Frataxin_like; 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 3D-structure; Complete proteome; Heme biosynthesis; Ion transport; KW Iron; Iron storage; Iron transport; Mitochondrion; Oxidoreductase; KW Reference proteome; Transit peptide; Transport. FT TRANSIT 1 21 Mitochondrion (Probable). FT CHAIN 22 174 Frataxin homolog intermediate form. FT /FTId=PRO_0000010135. FT CHAIN 52 174 Frataxin homolog, mitochondrial. FT /FTId=PRO_0000010136. FT MUTAGEN 79 79 D->A: Nearly abolishes ferroxidase FT avtivity, slows down oligomerization, FT impairs resistance to iron-catalyzed FT oxidative stress, no effect on Fe(2+) FT delivery and cell growth; when associated FT with A-82. FT MUTAGEN 82 82 D->A: Nearly abolishes ferroxidase FT avtivity, slows down oligomerization, FT impairs resistance to iron-catalyzed FT oxidative stress, no effect on Fe(2+) FT delivery and cell growth; when associated FT with A-79. FT MUTAGEN 93 93 E->A: Impairs oligomerization and iron FT mineralization. FT MUTAGEN 93 93 E->A: Impairs resistance to iron- FT catalyzed oxidative stress, no effect on FT Fe(2+) delivery and cell growth; when FT associated with A-97 and A-103. FT MUTAGEN 97 97 D->A: Impairs resistance to iron- FT catalyzed oxidative stress, no effect on FT Fe(2+) delivery and cell growth; when FT associated with A-93 and A-103. FT MUTAGEN 103 103 E->A: Impairs resistance to iron- FT catalyzed oxidative stress, no effect on FT Fe(2+) delivery and cell growth; when FT associated with A-93 and A-97. FT MUTAGEN 122 124 NKQ->ATA: Impairs cell growth, lowers FT activity of motochondrial iron-sulfur FT cluster-containing enzymes, no effect on FT iron binding and oligomerization. FT MUTAGEN 129 129 Q->A: Impairs cell growth and lowers FT aconitase activity. FT MUTAGEN 130 130 I->A: Impairs cell growth and lowers FT aconitase activity. FT MUTAGEN 131 131 W->A: Impairs cell growth, lowers FT aconitase activity and strongly decreases FT interaction with ISU1. FT MUTAGEN 131 131 W->F: Lowers aconitase activity and no FT effexct on interaction with ISU1. FT MUTAGEN 141 141 R->A: Impairs cell growth and lowers FT aconitase activity. FT TURN 63 67 FT HELIX 76 89 FT STRAND 92 94 FT STRAND 96 99 FT STRAND 101 103 FT STRAND 106 113 FT TURN 114 116 FT STRAND 117 123 FT STRAND 126 134 FT TURN 135 137 FT STRAND 138 147 FT STRAND 149 151 FT TURN 152 154 FT HELIX 158 171 SQ SEQUENCE 174 AA; 19490 MW; AB1FF7478EF0E5D6 CRC64; MIKRSLASLV RVSSVMGRRY MIAAAGGERA RFCPAVTNKK NHTVNTFQKR FVESSTDGQV VPQEVLNLPL EKYHEEADDY LDHLLDSLEE LSEAHPDCIP DVELSHGVMT LEIPAFGTYV INKQPPNKQI WLASPLSGPN RFDLLNGEWV SLRNGTKLTD ILTEEVEKAI SKSQ //