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Protein

Iron sulfur cluster assembly protein 1, mitochondrial

Gene

ISU1

Organism
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Scaffold protein for the de novo synthesis of iron-sulfur (Fe-S) clusters within mitochondria, which is required for maturation of both mitochondrial and cytoplasmic [2Fe-2S] and [4Fe-4S] proteins. First, a [2Fe-2S] cluster is transiently assembled on the scaffold proteins ISU1 and ISU2. In a second step, the cluster is released from ISU1/ISU2, transferred to glutaredoxin GRX5, followed by the formation of mitochondrial [2Fe-2S] proteins, the synthesis of [4Fe-4S] clusters and their target-specific insertion into the recipient apoproteins. Cluster assembly on ISU1/ISU2 depends on the function of the cysteine desulfurase complex NFS1-ISD11, which serves as the sulfur donor for cluster synthesis, the iron-binding protein frataxin (YFH1) as the putative iron donor, and the electron transfer chain comprised of ferredoxin reductase ARH1 and ferredoxin YAH1, which receive their electrons from NADH. Fe-S cluster release from ISU1/ISU2 is achieved by interaction with the Hsp70 chaperone SSQ1, assisted by the DnaJ-like co-chaperone JAC1 and the nucleotide exchange factor MGE1. ISU1 is the major isoform in yeast, while ISU2 is not detectable in cells grown to stationary phase (PubMed:10588895, PubMed:12970193, PubMed:14741370, PubMed:15123690, PubMed:16341089, PubMed:16431909, PubMed:23615440, PubMed:25358379).8 Publications

Cofactori

[2Fe-2S] cluster1 PublicationNote: Binds 1 [2Fe-2S] cluster per subunit.By similarity

Pathwayi: iron-sulfur cluster biosynthesis

This protein is involved in the pathway iron-sulfur cluster biosynthesis, which is part of Cofactor biosynthesis.4 Publications
View all proteins of this organism that are known to be involved in the pathway iron-sulfur cluster biosynthesis and in Cofactor biosynthesis.

GO - Molecular functioni

  • 2 iron, 2 sulfur cluster binding Source: UniProtKB-KW
  • ferrous iron binding Source: SGD

GO - Biological processi

  • cellular iron ion homeostasis Source: SGD
  • iron-sulfur cluster assembly Source: SGD
  • tRNA wobble uridine modification Source: SGD
Complete GO annotation...

Keywords - Ligandi

2Fe-2S, Iron, Iron-sulfur, Metal-binding

Enzyme and pathway databases

BioCyciMetaCyc:G3O-34034-MONOMER.
YEAST:G3O-34034-MONOMER.
ReactomeiR-SCE-1362409. Mitochondrial iron-sulfur cluster biogenesis.
UniPathwayiUPA00266.

Names & Taxonomyi

Protein namesi
Recommended name:
Iron sulfur cluster assembly protein 1, mitochondrial
Alternative name(s):
Iron sulfur cluster scaffold protein 1
Gene namesi
Name:ISU1
Synonyms:NUA1
Ordered Locus Names:YPL135W
OrganismiSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Taxonomic identifieri559292 [NCBI]
Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces
Proteomesi
  • UP000002311 Componenti: Chromosome XVI

Organism-specific databases

EuPathDBiFungiDB:YPL135W.
SGDiS000006056. ISU1.

Subcellular locationi

GO - Cellular componenti

  • mitochondrial matrix Source: SGD
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Disruption phenotypei

Cells deleted for both ISU1 and ISU2 have decreased activity of several respiratory enzymes that contain Fe-S clusters. As a result, cells grow poorly on carbon sources requiring respiration and also accumulate abnormally high levels of iron in their mitochondria.2 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi63 – 631L → S in ISU1(LVF/SSS); no growth and abolishes interaction with both JAC1 and NFS1; when associated with S-72 and S-94. 1 Publication
Mutagenesisi69 – 691C → A: Fails to complement an isu1 deletion mutation. 1 Publication
Mutagenesisi72 – 721V → S in ISU1(LVF/SSS); no growth and abolishes interaction with both JAC1 and NFS1; when associated with S-63 and S-94. 1 Publication
Mutagenesisi94 – 941F → S in ISU1(LVF/SSS); no growth and abolishes interaction with both JAC1 and NFS1; when associated with S-63 and S-72. 1 Publication
Mutagenesisi96 – 961C → A: Fails to complement an isu1 deletion mutation. 1 Publication
Mutagenesisi132 – 1321L → A: No growth. 1 Publication
Mutagenesisi133 – 1331P → A: Wild-type growth. 1 Publication
Mutagenesisi134 – 1363PVK → AAA: No growth; no interaction with frataxin and SSQ1. 2 Publications
Mutagenesisi134 – 1341P → A: Slow growth; no interaction with SSQ1. 1 Publication
Mutagenesisi135 – 1351V → A: Wild-type growth; no interaction with SSQ1. 1 Publication
Mutagenesisi136 – 1361K → A: No growth; no interaction with SSQ1. 1 Publication
Mutagenesisi139 – 1391C → A: Fails to complement an isu1 deletion mutation. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transit peptidei1 – 2727MitochondrionSequence analysisAdd
BLAST
Chaini28 – 165138Iron sulfur cluster assembly protein 1, mitochondrialPRO_0000019700Add
BLAST

Proteomic databases

MaxQBiQ03020.

Interactioni

Subunit structurei

Component of the core Fe-S cluster (ISC) assembly machinery. Interacts with frataxin (PubMed:14741370, PubMed:12947415, PubMed:20815377, PubMed:25228696). Interacts with the mitochondrial co-chaperones JAC1 and SSQ1 (PubMed:12756240, PubMed:15123690, PubMed:22306468, PubMed:23946486). Interacts with NFS1 (PubMed:23946486, PubMed:25228696). Interacts with ferredoxin YAH1; interacts with the reduced form (PubMed:25358379).9 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
JAC1P531933EBI-29901,EBI-23714
NFS1P253742EBI-29901,EBI-11991
SSQ1Q059314EBI-29901,EBI-35227
YFH1Q075404EBI-29901,EBI-2206814

Protein-protein interaction databases

BioGridi36046. 53 interactions.
DIPiDIP-6556N.
IntActiQ03020. 10 interactions.
MINTiMINT-677697.

Structurei

3D structure databases

ProteinModelPortaliQ03020.
SMRiQ03020. Positions 35-158.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the NifU family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

GeneTreeiENSGT00390000015813.
HOGENOMiHOG000069228.
InParanoidiQ03020.
OMAiECGDVMR.
OrthoDBiEOG7N9079.

Family and domain databases

InterProiIPR011339. ISC_FeS_clus_asmbl_IscU.
IPR002871. NIF_FeS_clus_asmbl_NifU_N.
[Graphical view]
PfamiPF01592. NifU_N. 1 hit.
[Graphical view]
TIGRFAMsiTIGR01999. iscU. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q03020-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLPVITRFAR PALMAIRPVN AMGVLRASSI TKRLYHPKVI EHYTHPRNVG
60 70 80 90 100
SLDKKLPNVG TGLVGAPACG DVMRLQIKVN DSTGVIEDVK FKTFGCGSAI
110 120 130 140 150
ASSSYMTELV QGMTLDDAAK IKNTEIAKEL SLPPVKLHCS MLAEDAIKAA
160
IKDYKSKRNT PTMLS
Length:165
Mass (Da):17,895
Last modified:November 1, 1996 - v1
Checksum:iE240845A27D2E9EE
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U43703 Genomic DNA. Translation: AAB68224.1.
BK006949 Genomic DNA. Translation: DAA11298.1.
PIRiS69049.
RefSeqiNP_015190.1. NM_001183949.1.

Genome annotation databases

EnsemblFungiiYPL135W; YPL135W; YPL135W.
GeneIDi855968.
KEGGisce:YPL135W.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U43703 Genomic DNA. Translation: AAB68224.1.
BK006949 Genomic DNA. Translation: DAA11298.1.
PIRiS69049.
RefSeqiNP_015190.1. NM_001183949.1.

3D structure databases

ProteinModelPortaliQ03020.
SMRiQ03020. Positions 35-158.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi36046. 53 interactions.
DIPiDIP-6556N.
IntActiQ03020. 10 interactions.
MINTiMINT-677697.

Proteomic databases

MaxQBiQ03020.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblFungiiYPL135W; YPL135W; YPL135W.
GeneIDi855968.
KEGGisce:YPL135W.

Organism-specific databases

EuPathDBiFungiDB:YPL135W.
SGDiS000006056. ISU1.

Phylogenomic databases

GeneTreeiENSGT00390000015813.
HOGENOMiHOG000069228.
InParanoidiQ03020.
OMAiECGDVMR.
OrthoDBiEOG7N9079.

Enzyme and pathway databases

UniPathwayiUPA00266.
BioCyciMetaCyc:G3O-34034-MONOMER.
YEAST:G3O-34034-MONOMER.
ReactomeiR-SCE-1362409. Mitochondrial iron-sulfur cluster biogenesis.

Miscellaneous databases

NextBioi980777.
PROiQ03020.

Family and domain databases

InterProiIPR011339. ISC_FeS_clus_asmbl_IscU.
IPR002871. NIF_FeS_clus_asmbl_NifU_N.
[Graphical view]
PfamiPF01592. NifU_N. 1 hit.
[Graphical view]
TIGRFAMsiTIGR01999. iscU. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The nucleotide sequence of Saccharomyces cerevisiae chromosome XVI."
    Bussey H., Storms R.K., Ahmed A., Albermann K., Allen E., Ansorge W., Araujo R., Aparicio A., Barrell B.G., Badcock K., Benes V., Botstein D., Bowman S., Brueckner M., Carpenter J., Cherry J.M., Chung E., Churcher C.M.
    , Coster F., Davis K., Davis R.W., Dietrich F.S., Delius H., DiPaolo T., Dubois E., Duesterhoeft A., Duncan M., Floeth M., Fortin N., Friesen J.D., Fritz C., Goffeau A., Hall J., Hebling U., Heumann K., Hilbert H., Hillier L.W., Hunicke-Smith S., Hyman R.W., Johnston M., Kalman S., Kleine K., Komp C., Kurdi O., Lashkari D., Lew H., Lin A., Lin D., Louis E.J., Marathe R., Messenguy F., Mewes H.-W., Mirtipati S., Moestl D., Mueller-Auer S., Namath A., Nentwich U., Oefner P., Pearson D., Petel F.X., Pohl T.M., Purnelle B., Rajandream M.A., Rechmann S., Rieger M., Riles L., Roberts D., Schaefer M., Scharfe M., Scherens B., Schramm S., Schroeder M., Sdicu A.-M., Tettelin H., Urrestarazu L.A., Ushinsky S., Vierendeels F., Vissers S., Voss H., Walsh S.V., Wambutt R., Wang Y., Wedler E., Wedler H., Winnett E., Zhong W.-W., Zollner A., Vo D.H., Hani J.
    Nature 387:103-105(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: ATCC 204508 / S288c.
  2. Cited for: GENOME REANNOTATION.
    Strain: ATCC 204508 / S288c.
  3. "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: FUNCTION, PATHWAY, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, MUTAGENESIS OF CYS-69; CYS-96 AND CYS-139.
  4. "Evidence for a conserved system for iron metabolism in the mitochondria of Saccharomyces cerevisiae."
    Schilke B., Voisine C., Beinert H., Craig E.
    Proc. Natl. Acad. Sci. U.S.A. 96:10206-10211(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE.
  5. "Components involved in assembly and dislocation of iron-sulfur clusters on the scaffold protein Isu1p."
    Muehlenhoff U., Gerber J., Richhardt N., Lill R.
    EMBO J. 22:4815-4825(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, COFACTOR.
  6. "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 FRATAXIN.
  7. "Ssq1, a mitochondrial Hsp70 involved in iron-sulfur (Fe/S) center biogenesis. Similarities to and differences from its bacterial counterpart."
    Dutkiewicz R., Schilke B., Knieszner H., Walter W., Craig E.A., Marszalek J.
    J. Biol. Chem. 278:29719-29727(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH JAC1 AND SSQ1.
  8. Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
  9. "Mitochondrial functional interactions between frataxin and Isu1p, the iron-sulfur cluster scaffold protein, in Saccharomyces cerevisiae."
    Ramazzotti A., Vanmansart V., Foury F.
    FEBS Lett. 557:215-220(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH FRATAXIN.
  10. "Sequence-specific interaction between mitochondrial Fe-S scaffold protein Isu and Hsp70 Ssq1 is essential for their in vivo function."
    Dutkiewicz R., Schilke B., Cheng S., Knieszner H., Craig E.A., Marszalek J.
    J. Biol. Chem. 279:29167-29174(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH JAC1 AND SSQ1, MUTAGENESIS OF LEU-132; PRO-133; PRO-134; VAL-135 AND LYS-136.
  11. "The yeast scaffold proteins Isu1p and Isu2p are required inside mitochondria for maturation of cytosolic Fe/S proteins."
    Gerber J., Neumann K., Prohl C., Muehlenhoff U., Lill R.
    Mol. Cell. Biol. 24:4848-4857(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.
  12. "Essential role of Isd11 in mitochondrial iron-sulfur cluster synthesis on Isu scaffold proteins."
    Wiedemann N., Urzica E., Guiard B., Mueller H., Lohaus C., Meyer H.E., Ryan M.T., Meisinger C., Muehlenhoff U., Lill R., Pfanner N.
    EMBO J. 25:184-195(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  13. "The Hsp70 chaperone Ssq1p is dispensable for iron-sulfur cluster formation on the scaffold protein Isu1p."
    Dutkiewicz R., Marszalek J., Schilke B., Craig E.A., Lill R., Muehlenhoff U.
    J. Biol. Chem. 281:7801-7808(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  14. "Molecular details of the yeast frataxin-Isu1 interaction during mitochondrial Fe-S cluster assembly."
    Cook J.D., Kondapalli K.C., Rawat S., Childs W.C., Murugesan Y., Dancis A., Stemmler T.L.
    Biochemistry 49:8756-8765(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH FRATAXIN.
  15. "Interaction of J-protein co-chaperone Jac1 with Fe-S scaffold Isu is indispensable in vivo and conserved in evolution."
    Ciesielski S.J., Schilke B.A., Osipiuk J., Bigelow L., Mulligan R., Majewska J., Joachimiak A., Marszalek J., Craig E.A., Dutkiewicz R.
    J. Mol. Biol. 417:1-12(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH JAC1.
  16. "Binding of the chaperone Jac1 protein and cysteine desulfurase Nfs1 to the iron-sulfur cluster scaffold Isu protein is mutually exclusive."
    Majewska J., Ciesielski S.J., Schilke B., Kominek J., Blenska A., Delewski W., Song J.Y., Marszalek J., Craig E.A., Dutkiewicz R.
    J. Biol. Chem. 288:29134-29142(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH JAC1 AND NFS1, MUTAGENESIS OF LEU-63; VAL-72 AND PHE-94.
  17. "The mitochondrial Hsp70 chaperone Ssq1 facilitates Fe/S cluster transfer from Isu1 to Grx5 by complex formation."
    Uzarska M.A., Dutkiewicz R., Freibert S.A., Lill R., Muehlenhoff U.
    Mol. Biol. Cell 24:1830-1841(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  18. "Overlapping binding sites of the frataxin homologue assembly factor and the heat shock protein 70 transfer factor on the Isu iron-sulfur cluster scaffold protein."
    Manicki M., Majewska J., Ciesielski S., Schilke B., Blenska A., Kominek J., Marszalek J., Craig E.A., Dutkiewicz R.
    J. Biol. Chem. 289:30268-30278(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH FRATAXIN AND NFS1, MUTAGENESIS OF 134-PRO--LYS-136.
  19. "Functional reconstitution of mitochondrial Fe/S cluster synthesis on Isu1 reveals the involvement of ferredoxin."
    Webert H., Freibert S.A., Gallo A., Heidenreich T., Linne U., Amlacher S., Hurt E., Muehlenhoff U., Banci L., Lill R.
    Nat. Commun. 5:5013-5013(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  20. "Molecular modeling of the binding modes of the iron-sulfur protein to the Jac1 co-chaperone from Saccharomyces cerevisiae by all-atom and coarse-grained approaches."
    Mozolewska M.A., Krupa P., Scheraga H.A., Liwo A.
    Proteins 83:1414-1426(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: 3D-STRUCTURE MODELING OF INTERACTION WITH JAC1.

Entry informationi

Entry nameiISU1_YEAST
AccessioniPrimary (citable) accession number: Q03020
Secondary accession number(s): D6W3N2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 26, 2005
Last sequence update: November 1, 1996
Last modified: May 11, 2016
This is version 120 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Miscellaneousi

Miscellaneous

Present with 10800 molecules/cell in log phase SD medium.1 Publication

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families
  3. Yeast
    Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD
  4. Yeast chromosome XVI
    Yeast (Saccharomyces cerevisiae) chromosome XVI: entries and gene names

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.