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)

Taxonomic identifier

559292 [NCBI]

Taxonomic lineage

Eukaryota › Fungi › Dikarya › Ascomycota › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces

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. Ref.10
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. 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 Ref.9. 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 matrix Inferred from direct assay Ref.7. Source: SGD
Molecular function	ferrous iron binding Inferred from direct assay. Source: SGD ferroxidase activity Inferred from direct assay. Source: SGD iron chaperone activity Inferred from direct assay. Source: SGD protein binding Inferred from physical interaction Ref.11. Source: IntAct
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

63 – 67

5

Helix

76 – 89

14

Beta strand

92 – 94

3

Beta strand

96 – 99

4

Beta strand

101 – 103

3

Beta strand

106 – 113

8

Turn

114 – 116

3

Beta strand

117 – 123

7

Beta strand

126 – 134

9

Turn

135 – 137

3

Beta strand

138 – 147

10

Beta strand

149 – 151

3

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: 9169867] [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: 17322287] [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: 9180083] [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: 9988680] [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: 10545606] [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: 10428860] [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: 10588895] [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: 12947415] [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: 14562106] [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: 15961414] [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: 16371422] [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: 18319250] [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: 19884169] [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: 17027502] [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: 18393441] [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	[»]

ProteinModelPortal

Q07540.

SMR

Q07540. Positions 52-174.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-7485N.

IntAct

Q07540. 11 interactions.

MINT

MINT-4300743.

STRING

Q07540.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblFungi

YDL120W; YDL120W; YDL120W.

GeneID

851437.

KEGG

sce:YDL120W.

NMPDR

fig|4932.3.peg.900.

Organism-specific databases

CYGD

YDL120w.

SGD

S000002278. YFH1.

Phylogenomic databases

eggNOG

fuNOG11011.

GeneTree

EFGT00050000006737.

HOGENOM

HBG396998.

OrthoDB

EOG4WHCWJ.

Gene expression databases

ArrayExpress

Q07540.

Genevestigator

Q07540.

GermOnline

YDL120W. Saccharomyces cerevisiae.

Family and domain databases

InterPro

IPR017789. Frataxin.
IPR002908. Frataxin-like.
IPR020895. Frataxin_CS.
[Graphical view]

Gene3D

G3DSA:3.30.920.10. Frataxin_like. 1 hit.

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

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:	December 14, 2011
This is version 112 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program