Q07540 (FRDA_YEAST) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Frataxin homolog, mitochondrial
EC=1.16.3.1

Cleaved into the following chain:

1. Frataxin homolog intermediate form

Gene names

Name:	YFH1
Ordered Locus Names:	YDL120W

Organism

Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) [Reference proteome]

Taxonomic identifier

559292 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Fungi › Dikarya › Ascomycota › saccharomyceta › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces › Saccharomyces cerevisiae

Protein attributes

Sequence length	174 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 as well as the assembly and repair of iron-sulfur clusters by delivering Fe2+ to proteins involved in these pathways. Plays a role in the protection against iron-catalyzed oxidative stress through its ability to catalyze the oxidation of Fe2+ to Fe3+. Can store large amounts of the metal in the form of a ferrihydrite mineral by oligomerization. May be involved in regulation of the mitochondrial electron transport chain. Ref.4 Ref.5 Ref.11 Ref.12 Ref.14 Ref.15
Catalytic activity	4 Fe2+ + 4 H+ + O2 = 4 Fe3+ + 2 H2O. Ref.12
Subunit structure	Monomer; increments in mitochondrial iron uptake induce stepwise assembly of species ranging from trimers to 24-mers. Interacts with ISU1. Interacts with YHB1, SDH1, SDH2, AIM45 and CIR1. Ref.8 Ref.9 Ref.11 Ref.13 Ref.14 Ref.15 Ref.16
Subcellular location	Mitochondrion matrix Ref.4 Ref.5.
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 mature size protein.
Miscellaneous	Present with 1560 molecules/cell in log phase SD medium.
Sequence similarities	Belongs to the frataxin family.

Ontologies

Keywords
Biological process	Heme biosynthesis Ion transport Iron storage Iron transport Transport
Cellular component	Mitochondrion
Domain	Transit peptide
Ligand	Iron
Molecular function	Oxidoreductase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular iron ion homeostasis Inferred from mutant phenotype Ref.4. Source: SGD glutathione metabolic process Inferred from mutant phenotype PubMed 18562474. Source: SGD heme biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW ion transport Inferred from electronic annotation. Source: UniProtKB-KW iron-sulfur cluster assembly Inferred from mutant phenotype PubMed 12221295Ref.9PubMed 12970193. Source: SGD mitochondrial electron transport, succinate to ubiquinone Inferred from mutant phenotype Ref.11. Source: UniProtKB response to iron(II) ion Inferred from mutant phenotype Ref.12. Source: UniProtKB response to oxidative stress Inferred from mutant phenotype Ref.12. Source: UniProtKB
Cellular_component	mitochondrial inner membrane Traceable author statement. Source: Reactome mitochondrial intermembrane space Traceable author statement. Source: Reactome mitochondrial matrix Inferred from direct assay Ref.7. Source: SGD
Molecular_function	ferric iron binding Inferred from electronic annotation. Source: InterPro ferrous iron binding Inferred from direct assay PubMed 10930361PubMed 16784228. Source: SGD ferroxidase activity Inferred from direct assay PubMed 12149269PubMed 12732649. Source: SGD iron chaperone activity Inferred from direct assay PubMed 12732649. Source: SGD
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
YHB1	P39676	2	EBI-2206814,EBI-6905

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 21

21

Mitochondrion Probable

Chain

22 – 174

153

Frataxin homolog intermediate form

PRO_0000010135

Chain

52 – 174

123

Frataxin homolog, mitochondrial

PRO_0000010136

Experimental info

Mutagenesis

79

1

D → A: Nearly abolishes ferroxidase avtivity, slows down oligomerization, impairs resistance to iron-catalyzed oxidative stress, no effect on Fe(2+) delivery and cell growth; when associated with A-82. Ref.12

Mutagenesis

82

1

D → A: Nearly abolishes ferroxidase avtivity, slows down oligomerization, impairs resistance to iron-catalyzed oxidative stress, no effect on Fe(2+) delivery and cell growth; when associated with A-79. Ref.12

Mutagenesis

93

1

E → A: Impairs oligomerization and iron mineralization. Ref.12

Mutagenesis

93

1

E → A: Impairs resistance to iron-catalyzed oxidative stress, no effect on Fe(2+) delivery and cell growth; when associated with A-97 and A-103. Ref.12

Mutagenesis

97

1

D → A: Impairs resistance to iron-catalyzed oxidative stress, no effect on Fe(2+) delivery and cell growth; when associated with A-93 and A-103. Ref.12

Mutagenesis

103

1

E → A: Impairs resistance to iron-catalyzed oxidative stress, no effect on Fe(2+) delivery and cell growth; when associated with A-93 and A-97. Ref.12

Mutagenesis

122 – 124

3

NKQ → ATA: Impairs cell growth, lowers activity of motochondrial iron-sulfur cluster-containing enzymes, no effect on iron binding and oligomerization. Ref.13

Mutagenesis

129

1

Q → A: Impairs cell growth and lowers aconitase activity. Ref.14

Mutagenesis

130

1

I → A: Impairs cell growth and lowers aconitase activity. Ref.14

Mutagenesis

131

1

W → A: Impairs cell growth, lowers aconitase activity and strongly decreases interaction with ISU1. Ref.14

Mutagenesis

131

1

W → F: Lowers aconitase activity and no effexct on interaction with ISU1. Ref.14

Mutagenesis

141

1

R → A: Impairs cell growth and lowers aconitase activity. Ref.14

Secondary structure

1

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174

Helix Strand Turn

Details...

Turn

64 – 67

4

Helix

76 – 88

13

Turn

89 – 91

3

Beta strand

92 – 94

3

Beta strand

96 – 99

4

Beta strand

101 – 104

4

Beta strand

106 – 112

7

Turn

114 – 116

3

Beta strand

119 – 122

4

Beta strand

126 – 128

3

Beta strand

131 – 134

4

Turn

135 – 137

3

Beta strand

138 – 151

14

Turn

152 – 154

3

Helix

158 – 171

14

Sequences

	Sequence		Length	Mass (Da)
	Q07540 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: AB1FF7478EF0E5D6	FASTA	174	19,490
	10 20 30 40 50 60 MIKRSLASLV RVSSVMGRRY MIAAAGGERA RFCPAVTNKK NHTVNTFQKR FVESSTDGQV 70 80 90 100 110 120 VPQEVLNLPL EKYHEEADDY LDHLLDSLEE LSEAHPDCIP DVELSHGVMT LEIPAFGTYV 130 140 150 160 170 INKQPPNKQI WLASPLSGPN RFDLLNGEWV SLRNGTKLTD ILTEEVEKAI SKSQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The nucleotide sequence of Saccharomyces cerevisiae chromosome IV." Jacq C., Alt-Moerbe J., Andre B., Arnold W., Bahr A., Ballesta J.P.G., Bargues M., Baron L., Becker A., Biteau N., Bloecker H., Blugeon C., Boskovic J., Brandt P., Brueckner M., Buitrago M.J., Coster F., Delaveau T. , del Rey F., Dujon B., Eide L.G., Garcia-Cantalejo J.M., Goffeau A., Gomez-Peris A., Granotier C., Hanemann V., Hankeln T., Hoheisel J.D., Jaeger W., Jimenez A., Jonniaux J.-L., Kraemer C., Kuester H., Laamanen P., Legros Y., Louis E.J., Moeller-Rieker S., Monnet A., Moro M., Mueller-Auer S., Nussbaumer B., Paricio N., Paulin L., Perea J., Perez-Alonso M., Perez-Ortin J.E., Pohl T.M., Prydz H., Purnelle B., Rasmussen S.W., Remacha M.A., Revuelta J.L., Rieger M., Salom D., Saluz H.P., Saiz J.E., Saren A.-M., Schaefer M., Scharfe M., Schmidt E.R., Schneider C., Scholler P., Schwarz S., Soler-Mira A., Urrestarazu L.A., Verhasselt P., Vissers S., Voet M., Volckaert G., Wagner G., Wambutt R., Wedler E., Wedler H., Woelfl S., Harris D.E., Bowman S., Brown D., Churcher C.M., Connor R., Dedman K., Gentles S., Hamlin N., Hunt S., Jones L., McDonald S., Murphy L.D., Niblett D., Odell C., Oliver K., Rajandream M.A., Richards C., Shore L., Walsh S.V., Barrell B.G., Dietrich F.S., Mulligan J.T., Allen E., Araujo R., Aviles E., Berno A., Carpenter J., Chen E., Cherry J.M., Chung E., Duncan M., Hunicke-Smith S., Hyman R.W., Komp C., Lashkari D., Lew H., Lin D., Mosedale D., Nakahara K., Namath A., Oefner P., Oh C., Petel F.X., Roberts D., Schramm S., Schroeder M., Shogren T., Shroff N., Winant A., Yelton M.A., Botstein D., Davis R.W., Johnston M., Andrews S., Brinkman R., Cooper J., Ding H., Du Z., Favello A., Fulton L., Gattung S., Greco T., Hallsworth K., Hawkins J., Hillier L.W., Jier M., Johnson D., Johnston L., Kirsten J., Kucaba T., Langston Y., Latreille P., Le T., Mardis E., Menezes S., Miller N., Nhan M., Pauley A., Peluso D., Rifkin L., Riles L., Taich A., Trevaskis E., Vignati D., Wilcox L., Wohldman P., Vaudin M., Wilson R., Waterston R., Albermann K., Hani J., Heumann K., Kleine K., Mewes H.-W., Zollner A., Zaccaria P. Nature 387:75-78(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 204508 / S288c.
[2]	Saccharomyces Genome Database Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases Cited for: GENOME REANNOTATION. Strain: ATCC 204508 / S288c.
[3]	"Approaching a complete repository of sequence-verified protein-encoding clones for Saccharomyces cerevisiae." Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F., Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J., Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J. , Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D., LaBaer J. Genome Res. 17:536-543(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 204508 / S288c.
[4]	"Regulation of mitochondrial iron accumulation by Yfh1p, a putative homolog of frataxin." Babcock M., de Silva D., Oaks R., Davis-Kaplan S., Jiralerspong S., Montermini L., Pandolfo M., Kaplan J. Science 276:1709-1712(1997) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[5]	"The yeast frataxin homologue mediates mitochondrial iron efflux. Evidence for a mitochondrial iron cycle." Radisky D.C., Babcock M.C., Kaplan J. J. Biol. Chem. 274:4497-4499(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[6]	"Maturation of frataxin within mammalian and yeast mitochondria: one-step processing by matrix processing peptidase." Gordon D.M., Shi Q., Dancis A., Pain D. Hum. Mol. Genet. 8:2255-2262(1999) [PubMed] [Europe PMC] [Abstract] Cited for: PROCESSING.
[7]	"Yeast and human frataxin are processed to mature form in two sequential steps by the mitochondrial processing peptidase." Branda S.S., Cavadini P., Adamec J., Kalousek F., Taroni F., Isaya G. J. Biol. Chem. 274:22763-22769(1999) [PubMed] [Europe PMC] [Abstract] Cited for: PROCESSING.
[8]	"Saccharomyces cerevisiae ISU1 and ISU2: members of a well-conserved gene family for iron-sulfur cluster assembly." Garland S.A., Hoff K., Vickery L.E., Culotta V.C. J. Mol. Biol. 294:897-907(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ISU1.
[9]	"An interaction between frataxin and Isu1/Nfs1 that is crucial for Fe/S cluster synthesis on Isu1." Gerber J., Muhlenhoff U., Lill R. EMBO Rep. 4:906-911(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ISU1.
[10]	"Global analysis of protein expression in yeast." Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., O'Shea E.K., Weissman J.S. Nature 425:737-741(2003) [PubMed] [Europe PMC] [Abstract] Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
[11]	"Frataxin interacts functionally with mitochondrial electron transport chain proteins." Gonzalez-Cabo P., Vazquez-Manrique R.P., Garcia-Gimeno M.A., Sanz P., Palau F. Hum. Mol. Genet. 14:2091-2098(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH YHB1; SDH1; SDH2; AIM45 AND CIR1.
[12]	"Mitochondrial iron detoxification is a primary function of frataxin that limits oxidative damage and preserves cell longevity." Gakh O., Park S., Liu G., Macomber L., Imlay J.A., Ferreira G.C., Isaya G. Hum. Mol. Genet. 15:467-479(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF ASP-79; ASP-82; GLU-93; ASP-97 AND GLU-103.
[13]	"Binding of yeast frataxin to the scaffold for Fe-S cluster biogenesis, Isu." Wang T., Craig E.A. J. Biol. Chem. 283:12674-12679(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ISU1, MUTAGENESIS OF 122-ASN--GLU-124.
[14]	"Frataxin interacts with Isu1 through a conserved tryptophan in its beta-sheet." Leidgens S., De Smet S., Foury F. Hum. Mol. Genet. 19:276-286(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN IRON-SULFUR CLUSTER BIOSYNTHESIS, INTERACTION WITH ISU1, MUTAGENESIS OF GLN-129; ILE-130; TRP-131 AND ARG-141.
[15]	"The structures of frataxin oligomers reveal the mechanism for the delivery and detoxification of iron." Karlberg T., Schagerlof U., Gakh O., Park S., Ryde U., Lindahl M., Leath K., Garman E., Isaya G., Al-Karadaghi S. Structure 14:1535-1546(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.01 ANGSTROMS) OF 52-174 ALONE AND IN COMPLEX WITH IRON, ELECTRON MICROSCOPY OF MUTANT ALA-73, FUNCTION, SUBUNIT.
[16]	"Structural basis of the iron storage function of frataxin from single-particle reconstruction of the iron-loaded oligomer." Schagerlof U., Elmlund H., Gakh O., Nordlund G., Hebert H., Lindahl M., Isaya G., Al-Karadaghi S. Biochemistry 47:4948-4954(2008) [PubMed] [Europe PMC] [Abstract] Cited for: ELECTRON MICROSCOPY OF MUTANT ALA-73 (13 ANGSTROMS), SUBUNIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Z74168 Genomic DNA. Translation: CAA98688.1.
AY558160 Genomic DNA. Translation: AAS56486.1.
BK006938 Genomic DNA. Translation: DAA11740.1.

PIR

S67663.

RefSeq

NP_010163.1. NM_001180179.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2FQL	X-ray	3.01	A	52-174	[»]
2GA5	NMR	-	A	53-174	[»]
3OEQ	X-ray	2.96	A	52-174	[»]
3OER	X-ray	3.20	A	52-174	[»]
4EC2	X-ray	3.00	A	52-174	[»]

ProteinModelPortal

Q07540.

SMR

Q07540. Positions 52-172.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-7485N.

IntAct

Q07540. 11 interactions.

MINT

MINT-4300743.

STRING

4932.YDL120W.

Proteomic databases

PaxDb

Q07540.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblFungi

YDL120W; YDL120W; YDL120W.

GeneID

851437.

KEGG

sce:YDL120W.

Organism-specific databases

CYGD

YDL120w.

SGD

S000002278. YFH1.

Phylogenomic databases

eggNOG

COG1965.

GeneTree

ENSGT00390000005811.

HOGENOM

HOG000190729.

OrthoDB

EOG4WHCWJ.

Enzyme and pathway databases

Reactome

REACT_118590. Mitochondrial Protein Import (yeast).
REACT_85873. Metabolism of proteins.

Gene expression databases

Genevestigator

Q07540.

GermOnline

YDL120W. Saccharomyces cerevisiae.

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]

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

EvolutionaryTrace

Q07540.

NextBio

968672.

Entry information

Entry name

FRDA_YEAST

Accession

Primary (citable) accession number: Q07540
Secondary accession number(s): D6VRN0

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 125 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program