ISU2_YEAST
ID ISU2_YEAST Reviewed; 156 AA.
AC Q12056; D6W2T0;
DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Iron sulfur cluster assembly protein 2, mitochondrial;
DE AltName: Full=Iron sulfur cluster scaffold protein 2;
DE Flags: Precursor;
GN Name=ISU2; Synonyms=NUA2; OrderedLocusNames=YOR226C;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 96604 / S288c / FY1679;
RX PubMed=8840505;
RX DOI=10.1002/(sici)1097-0061(199607)12:9<877::aid-yea969>3.0.co;2-s;
RA Galisson F., Dujon B.;
RT "Sequence and analysis of a 33 kb fragment from the right arm of chromosome
RT XV of the yeast Saccharomyces cerevisiae.";
RL Yeast 12:877-885(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169874;
RA Dujon B., Albermann K., Aldea M., Alexandraki D., Ansorge W., Arino J.,
RA Benes V., Bohn C., Bolotin-Fukuhara M., Bordonne R., Boyer J., Camasses A.,
RA Casamayor A., Casas C., Cheret G., Cziepluch C., Daignan-Fornier B.,
RA Dang V.-D., de Haan M., Delius H., Durand P., Fairhead C., Feldmann H.,
RA Gaillon L., Galisson F., Gamo F.-J., Gancedo C., Goffeau A., Goulding S.E.,
RA Grivell L.A., Habbig B., Hand N.J., Hani J., Hattenhorst U., Hebling U.,
RA Hernando Y., Herrero E., Heumann K., Hiesel R., Hilger F., Hofmann B.,
RA Hollenberg C.P., Hughes B., Jauniaux J.-C., Kalogeropoulos A.,
RA Katsoulou C., Kordes E., Lafuente M.J., Landt O., Louis E.J., Maarse A.C.,
RA Madania A., Mannhaupt G., Marck C., Martin R.P., Mewes H.-W., Michaux G.,
RA Paces V., Parle-McDermott A.G., Pearson B.M., Perrin A., Pettersson B.,
RA Poch O., Pohl T.M., Poirey R., Portetelle D., Pujol A., Purnelle B.,
RA Ramezani Rad M., Rechmann S., Schwager C., Schweizer M., Sor F., Sterky F.,
RA Tarassov I.A., Teodoru C., Tettelin H., Thierry A., Tobiasch E.,
RA Tzermia M., Uhlen M., Unseld M., Valens M., Vandenbol M., Vetter I.,
RA Vlcek C., Voet M., Volckaert G., Voss H., Wambutt R., Wedler H.,
RA Wiemann S., Winsor B., Wolfe K.H., Zollner A., Zumstein E., Kleine K.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XV.";
RL Nature 387:98-102(1997).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [4]
RP FUNCTION, PATHWAY, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
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 gene
RT family for iron-sulfur cluster assembly.";
RL J. Mol. Biol. 294:897-907(1999).
RN [5]
RP SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=10468587; DOI=10.1073/pnas.96.18.10206;
RA Schilke B., Voisine C., Beinert H., Craig E.;
RT "Evidence for a conserved system for iron metabolism in the mitochondria of
RT Saccharomyces cerevisiae.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:10206-10211(1999).
RN [6]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [7]
RP FUNCTION, AND PATHWAY.
RX PubMed=15143178; DOI=10.1128/mcb.24.11.4848-4857.2004;
RA Gerber J., Neumann K., Prohl C., Muehlenhoff U., Lill R.;
RT "The yeast scaffold proteins Isu1p and Isu2p are required inside
RT mitochondria for maturation of cytosolic Fe/S proteins.";
RL Mol. Cell. Biol. 24:4848-4857(2004).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=23615440; DOI=10.1091/mbc.e12-09-0644;
RA Uzarska M.A., Dutkiewicz R., Freibert S.A., Lill R., Muehlenhoff U.;
RT "The mitochondrial Hsp70 chaperone Ssq1 facilitates Fe/S cluster transfer
RT from Isu1 to Grx5 by complex formation.";
RL Mol. Biol. Cell 24:1830-1841(2013).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=31040179; DOI=10.1074/jbc.ra119.008600;
RA Pandey A.K., Pain J., Dancis A., Pain D.;
RT "Mitochondria export iron-sulfur and sulfur intermediates to the cytoplasm
RT for iron-sulfur cluster assembly and tRNA thiolation in yeast.";
RL J. Biol. Chem. 294:9489-9502(2019).
CC -!- FUNCTION: Scaffold protein for the de novo synthesis of iron-sulfur
CC (Fe-S) clusters within mitochondria, which is required for maturation
CC of both mitochondrial and cytoplasmic [2Fe-2S] and [4Fe-4S] proteins.
CC First, a [2Fe-2S] cluster is transiently assembled on the scaffold
CC proteins ISU1 and ISU2. In a second step, the cluster is released from
CC ISU1/ISU2, transferred to glutaredoxin GRX5, followed by the formation
CC of mitochondrial [2Fe-2S] proteins, the synthesis of [4Fe-4S] clusters
CC and their target-specific insertion into the recipient apoproteins.
CC Cluster assembly on ISU1/ISU2 depends on the function of the cysteine
CC desulfurase complex NFS1-ISD11, which serves as the sulfur donor for
CC cluster synthesis, the iron-binding protein frataxin (YFH1) as the
CC putative iron donor, and the electron transfer chain comprised of
CC ferredoxin reductase ARH1 and ferredoxin YAH1, which receive their
CC electrons from NADH. Fe-S cluster release from ISU1/ISU2 is achieved by
CC interaction with the Hsp70 chaperone SSQ1, assisted by the DnaJ-like
CC co-chaperone JAC1 and the nucleotide exchange factor MGE1
CC (PubMed:23615440). ISU1 is the major isoform in yeast, while ISU2 is
CC not detectable in cells grown to stationary phase (By similarity). ISU2
CC is the minor isoform in yeast and is not detectable in cells grown to
CC stationary phase (PubMed:10588895). Also involved in production of a
CC sulfur precursor required for thiolation of cytoplasmic tRNAs
CC (PubMed:31040179). {ECO:0000250|UniProtKB:Q03020,
CC ECO:0000269|PubMed:10588895, ECO:0000269|PubMed:23615440,
CC ECO:0000269|PubMed:31040179}.
CC -!- COFACTOR:
CC Name=[2Fe-2S] cluster; Xref=ChEBI:CHEBI:190135;
CC Evidence={ECO:0000250|UniProtKB:Q9UTC6};
CC Note=Binds 1 [2Fe-2S] cluster per subunit.
CC {ECO:0000250|UniProtKB:Q9UTC6};
CC -!- PATHWAY: Cofactor biosynthesis; iron-sulfur cluster biosynthesis.
CC {ECO:0000269|PubMed:10588895, ECO:0000269|PubMed:15143178}.
CC -!- SUBUNIT: Component of the core Fe-S cluster (ISC) assembly machinery.
CC Interacts with frataxin (By similarity). Interacts with the
CC mitochondrial co-chaperones JAC1 and SSQ1 (By similarity). Interacts
CC with NFS1 (By similarity). Interacts with ferredoxin YAH1; interacts
CC with the reduced form (By similarity). {ECO:0000250|UniProtKB:Q9UTC6}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000269|PubMed:10468587, ECO:0000269|PubMed:10588895}.
CC -!- DISRUPTION PHENOTYPE: Cells deleted for both ISU1 and ISU2 have
CC decreased activity of several respiratory enzymes that contain Fe-S
CC clusters. As a result, cells grow poorly on carbon sources requiring
CC respiration and also accumulate abnormally high levels of iron in their
CC mitochondria. Knockdown of ISU1 in ISU2 knockout cells decreases
CC cytosolic tRNA thiolation, and increases association between SSQ1 and
CC GRX5 (PubMed:31040179, PubMed:23615440). {ECO:0000269|PubMed:10468587,
CC ECO:0000269|PubMed:10588895, ECO:0000269|PubMed:23615440,
CC ECO:0000269|PubMed:31040179}.
CC -!- MISCELLANEOUS: Present with 3420 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the NifU family. {ECO:0000305}.
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DR EMBL; Z75133; CAA99445.1; -; Genomic_DNA.
DR EMBL; X92441; CAA63189.1; -; Genomic_DNA.
DR EMBL; BK006948; DAA10996.1; -; Genomic_DNA.
DR PIR; S60953; S60953.
DR RefSeq; NP_014869.3; NM_001183645.3.
DR AlphaFoldDB; Q12056; -.
DR SMR; Q12056; -.
DR BioGRID; 34619; 46.
DR DIP; DIP-4123N; -.
DR IntAct; Q12056; 2.
DR MINT; Q12056; -.
DR STRING; 4932.YOR226C; -.
DR MaxQB; Q12056; -.
DR PaxDb; Q12056; -.
DR PRIDE; Q12056; -.
DR EnsemblFungi; YOR226C_mRNA; YOR226C; YOR226C.
DR GeneID; 854401; -.
DR KEGG; sce:YOR226C; -.
DR SGD; S000005752; ISU2.
DR VEuPathDB; FungiDB:YOR226C; -.
DR eggNOG; KOG3361; Eukaryota.
DR GeneTree; ENSGT00390000015813; -.
DR HOGENOM; CLU_079283_5_0_1; -.
DR InParanoid; Q12056; -.
DR OMA; HKKVIDH; -.
DR BioCyc; YEAST:G3O-33724-MON; -.
DR UniPathway; UPA00266; -.
DR PRO; PR:Q12056; -.
DR Proteomes; UP000002311; Chromosome XV.
DR RNAct; Q12056; protein.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:SGD.
DR GO; GO:0051537; F:2 iron, 2 sulfur cluster binding; IBA:GO_Central.
DR GO; GO:0008198; F:ferrous iron binding; IBA:GO_Central.
DR GO; GO:0006879; P:cellular iron ion homeostasis; IMP:SGD.
DR GO; GO:0016226; P:iron-sulfur cluster assembly; IMP:SGD.
DR GO; GO:0002098; P:tRNA wobble uridine modification; IGI:SGD.
DR CDD; cd06664; IscU_like; 1.
DR InterPro; IPR011339; ISC_FeS_clus_asmbl_IscU.
DR InterPro; IPR002871; NIF_FeS_clus_asmbl_NifU_N.
DR PANTHER; PTHR10093; PTHR10093; 1.
DR Pfam; PF01592; NifU_N; 1.
DR TIGRFAMs; TIGR01999; iscU; 1.
PE 1: Evidence at protein level;
KW 2Fe-2S; Iron; Iron-sulfur; Metal-binding; Mitochondrion;
KW Reference proteome; Transit peptide.
FT TRANSIT 1..26
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 27..156
FT /note="Iron sulfur cluster assembly protein 2,
FT mitochondrial"
FT /id="PRO_0000019701"
SQ SEQUENCE 156 AA; 16930 MW; 9018B4401E93E3EE CRC64;
MFARLANPAH FKPLTGSHIT RAAKRLYHPK VIDHYTNPRN VGSMDKSLAN VGTGIVGAPA
CGDVIKLQIQ VNDKSGIIEN VKFKTFGCGS AIASSSYMTE LVRGMSLDEA VKIKNTEIAK
ELSLPPVKLH CSMLAEDAIK AAIKDYKTKR NPSVLH
