NFS1_YEAST
ID NFS1_YEAST Reviewed; 497 AA.
AC P25374; D6VQZ7;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2004, sequence version 2.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Cysteine desulfurase, mitochondrial {ECO:0000303|PubMed:15220327};
DE EC=2.8.1.7 {ECO:0000269|PubMed:15220327};
DE AltName: Full=tRNA-splicing protein SPL1 {ECO:0000303|PubMed:8444805};
DE Flags: Precursor;
GN Name=NFS1 {ECO:0000312|SGD:S000000522};
GN Synonyms=SPL1 {ECO:0000303|PubMed:8444805};
GN OrderedLocusNames=YCL017C {ECO:0000312|SGD:S000000522};
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], AND FUNCTION.
RX PubMed=8444805; DOI=10.1128/jb.175.5.1433-1442.1993;
RA Leong-Morgenthaler P.M., Kolman C., Oliver S.G., Hottinger H., Soell D.;
RT "SPL1-1, a Saccharomyces cerevisiae mutation affecting tRNA splicing.";
RL J. Bacteriol. 175:1433-1442(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=1574125; DOI=10.1038/357038a0;
RA Oliver S.G., van der Aart Q.J.M., Agostoni-Carbone M.L., Aigle M.,
RA Alberghina L., Alexandraki D., Antoine G., Anwar R., Ballesta J.P.G.,
RA Benit P., Berben G., Bergantino E., Biteau N., Bolle P.-A.,
RA Bolotin-Fukuhara M., Brown A., Brown A.J.P., Buhler J.-M., Carcano C.,
RA Carignani G., Cederberg H., Chanet R., Contreras R., Crouzet M.,
RA Daignan-Fornier B., Defoor E., Delgado M.D., Demolder J., Doira C.,
RA Dubois E., Dujon B., Duesterhoeft A., Erdmann D., Esteban M., Fabre F.,
RA Fairhead C., Faye G., Feldmann H., Fiers W., Francingues-Gaillard M.-C.,
RA Franco L., Frontali L., Fukuhara H., Fuller L.J., Galland P., Gent M.E.,
RA Gigot D., Gilliquet V., Glansdorff N., Goffeau A., Grenson M., Grisanti P.,
RA Grivell L.A., de Haan M., Haasemann M., Hatat D., Hoenicka J.,
RA Hegemann J.H., Herbert C.J., Hilger F., Hohmann S., Hollenberg C.P.,
RA Huse K., Iborra F., Indge K.J., Isono K., Jacq C., Jacquet M., James C.M.,
RA Jauniaux J.-C., Jia Y., Jimenez A., Kelly A., Kleinhans U., Kreisl P.,
RA Lanfranchi G., Lewis C., van der Linden C.G., Lucchini G.,
RA Lutzenkirchen K., Maat M.J., Mallet L., Mannhaupt G., Martegani E.,
RA Mathieu A., Maurer C.T.C., McConnell D., McKee R.A., Messenguy F.,
RA Mewes H.-W., Molemans F., Montague M.A., Muzi Falconi M., Navas L.,
RA Newlon C.S., Noone D., Pallier C., Panzeri L., Pearson B.M., Perea J.,
RA Philippsen P., Pierard A., Planta R.J., Plevani P., Poetsch B., Pohl F.M.,
RA Purnelle B., Ramezani Rad M., Rasmussen S.W., Raynal A., Remacha M.A.,
RA Richterich P., Roberts A.B., Rodriguez F., Sanz E.,
RA Schaaff-Gerstenschlaeger I., Scherens B., Schweitzer B., Shu Y., Skala J.,
RA Slonimski P.P., Sor F., Soustelle C., Spiegelberg R., Stateva L.I.,
RA Steensma H.Y., Steiner S., Thierry A., Thireos G., Tzermia M.,
RA Urrestarazu L.A., Valle G., Vetter I., van Vliet-Reedijk J.C., Voet M.,
RA Volckaert G., Vreken P., Wang H., Warmington J.R., von Wettstein D.,
RA Wicksteed B.L., Wilson C., Wurst H., Xu G., Yoshikawa A., Zimmermann F.K.,
RA Sgouros J.G.;
RT "The complete DNA sequence of yeast chromosome III.";
RL Nature 357:38-46(1992).
RN [3]
RP SEQUENCE REVISION TO 150.
RA Valles G., Volckaerts G.;
RL Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 459-497.
RX PubMed=6396161; DOI=10.1016/0378-1119(84)90218-x;
RA Froman B.E., Tait R.C., Rodriguez R.L.;
RT "Nucleotide sequence of the 3' terminal region of the LEU2 gene from
RT Saccharomyces cerevisiae.";
RL Gene 31:257-261(1984).
RN [6]
RP SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=10406803; DOI=10.1093/emboj/18.14.3981;
RA Kispal G., Csere P., Prohl C., Lill R.;
RT "The mitochondrial proteins Atm1p and Nfs1p are essential for biogenesis of
RT cytosolic Fe/S proteins.";
RL EMBO J. 18:3981-3989(1999).
RN [7]
RP SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, FUNCTION, AND MUTAGENESIS OF
RP ILE-191.
RX PubMed=10551871; DOI=10.1074/jbc.274.46.33025;
RA Li J., Kogan M., Knight S.A., Pain D., Dancis A.;
RT "Yeast mitochondrial protein, Nfs1p, coordinately regulates iron-sulfur
RT cluster proteins, cellular iron uptake, and iron distribution.";
RL J. Biol. Chem. 274:33025-33034(1999).
RN [8]
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 [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=14722066; DOI=10.1074/jbc.m312448200;
RA Nakai Y., Umeda N., Suzuki T., Nakai M., Hayashi H., Watanabe K.,
RA Kagamiyama H.;
RT "Yeast Nfs1p is involved in thio-modification of both mitochondrial and
RT cytoplasmic tRNAs.";
RL J. Biol. Chem. 279:12363-12368(2004).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, DISRUPTION
RP PHENOTYPE, AND DOMAIN.
RX PubMed=15220327; DOI=10.1074/jbc.m406516200;
RA Muhlenhoff U., Balk J., Richhardt N., Kaiser J.T., Sipos K., Kispal G.,
RA Lill R.;
RT "Functional characterization of the eukaryotic cysteine desulfurase Nfs1p
RT from Saccharomyces cerevisiae.";
RL J. Biol. Chem. 279:36906-36915(2004).
RN [11]
RP 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 [12]
RP FUNCTION, AND MUTAGENESIS OF ILE-191.
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: Catalyzes the removal of elemental sulfur from cysteine to
CC produce alanine (PubMed:15220327). It supplies the inorganic sulfur for
CC iron-sulfur (Fe-S) clusters (PubMed:10406803, PubMed:10551871,
CC PubMed:15220327, PubMed:31040179). Plays a role in both tRNA-processing
CC and mitochondrial metabolism (PubMed:15220327). Involved in the 2-thio-
CC modification of both 5-carboxymethylaminomethyl-2-thiouridine in
CC mitochondrial tRNAs and 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2U)
CC in cytoplasmic tRNAs (PubMed:14722066, PubMed:15220327,
CC PubMed:8444805). {ECO:0000269|PubMed:10406803,
CC ECO:0000269|PubMed:10551871, ECO:0000269|PubMed:14722066,
CC ECO:0000269|PubMed:15220327, ECO:0000269|PubMed:31040179,
CC ECO:0000269|PubMed:8444805}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[sulfur carrier]-H + L-cysteine = [sulfur carrier]-SH + L-
CC alanine; Xref=Rhea:RHEA:43892, Rhea:RHEA-COMP:14737, Rhea:RHEA-
CC COMP:14739, ChEBI:CHEBI:29917, ChEBI:CHEBI:35235, ChEBI:CHEBI:57972,
CC ChEBI:CHEBI:64428; EC=2.8.1.7;
CC Evidence={ECO:0000269|PubMed:15220327};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000250|UniProtKB:P0A6B9};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 8.5. {ECO:0000269|PubMed:15220327};
CC -!- INTERACTION:
CC P25374; Q6Q560: ISD11; NbExp=10; IntAct=EBI-11991, EBI-784315;
CC P25374; Q03020: ISU1; NbExp=3; IntAct=EBI-11991, EBI-29901;
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:10406803,
CC ECO:0000269|PubMed:10551871}.
CC -!- DOMAIN: the N-terminal beta-strand formed by residues 99-104 is
CC essential for the function. {ECO:0000269|PubMed:15220327}.
CC -!- DISRUPTION PHENOTYPE: Impairs cysteine desulfurase activity of
CC mitochondria. Leads to strong accumulation of free iron, not bound to
CC heme or Fe/S clusters, in mitochondria, as well as to decreased amounts
CC of the mitochondrial Fe/S proteins including aconitase and succinate
CC dehydrogenase. Leads also to accumulation of 5-
CC methoxycarbonylmethyluridine (mcm5U) and a concomitant decrease in 5-
CC methoxycarbonylmethyl-2-thiouridine (mcm5s2U) in cytoplasmic tRNAs.
CC Increases association between GRX5 and SSQ1 (PubMed:23615440).
CC {ECO:0000269|PubMed:10406803, ECO:0000269|PubMed:10551871,
CC ECO:0000269|PubMed:14722066, ECO:0000269|PubMed:15220327,
CC ECO:0000269|PubMed:23615440}.
CC -!- MISCELLANEOUS: Present with 504 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the class-V pyridoxal-phosphate-dependent
CC aminotransferase family. NifS/IscS subfamily. {ECO:0000305}.
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DR EMBL; M98808; AAA34814.1; -; Genomic_DNA.
DR EMBL; X59720; CAA42344.2; -; Genomic_DNA.
DR EMBL; M12909; AAA66918.1; -; Genomic_DNA.
DR EMBL; BK006937; DAA07466.1; -; Genomic_DNA.
DR PIR; S19343; S19343.
DR RefSeq; NP_009912.2; NM_001178664.1.
DR AlphaFoldDB; P25374; -.
DR SMR; P25374; -.
DR BioGRID; 30967; 422.
DR ComplexPortal; CPX-392; Mitochondrial NIAUFX iron-sulfur cluster assembly complex.
DR DIP; DIP-2948N; -.
DR IntAct; P25374; 14.
DR MINT; P25374; -.
DR STRING; 4932.YCL017C; -.
DR MaxQB; P25374; -.
DR PaxDb; P25374; -.
DR PRIDE; P25374; -.
DR EnsemblFungi; YCL017C_mRNA; YCL017C; YCL017C.
DR GeneID; 850343; -.
DR KEGG; sce:YCL017C; -.
DR SGD; S000000522; NFS1.
DR VEuPathDB; FungiDB:YCL017C; -.
DR eggNOG; KOG1549; Eukaryota.
DR GeneTree; ENSGT00940000155740; -.
DR HOGENOM; CLU_003433_0_2_1; -.
DR InParanoid; P25374; -.
DR OMA; KGLYWAR; -.
DR BioCyc; MetaCyc:G3O-29283-MON; -.
DR BioCyc; YEAST:G3O-29283-MON; -.
DR Reactome; R-SCE-1362409; Mitochondrial iron-sulfur cluster biogenesis.
DR Reactome; R-SCE-947581; Molybdenum cofactor biosynthesis.
DR PRO; PR:P25374; -.
DR Proteomes; UP000002311; Chromosome III.
DR RNAct; P25374; protein.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:1990229; C:iron-sulfur cluster assembly complex; IC:ComplexPortal.
DR GO; GO:1990221; C:L-cysteine desulfurase complex; IPI:SGD.
DR GO; GO:0005739; C:mitochondrion; IDA:SGD.
DR GO; GO:0005634; C:nucleus; IDA:SGD.
DR GO; GO:0031071; F:cysteine desulfurase activity; IDA:SGD.
DR GO; GO:0051536; F:iron-sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
DR GO; GO:0044571; P:[2Fe-2S] cluster assembly; IEA:InterPro.
DR GO; GO:0006879; P:cellular iron ion homeostasis; IMP:SGD.
DR GO; GO:0016226; P:iron-sulfur cluster assembly; IDA:SGD.
DR GO; GO:0070903; P:mitochondrial tRNA thio-modification; IMP:SGD.
DR GO; GO:0034227; P:tRNA thio-modification; IMP:SGD.
DR GO; GO:0002098; P:tRNA wobble uridine modification; IMP:SGD.
DR Gene3D; 3.40.640.10; -; 1.
DR Gene3D; 3.90.1150.10; -; 1.
DR HAMAP; MF_00331; Cys_desulf_IscS; 1.
DR InterPro; IPR000192; Aminotrans_V_dom.
DR InterPro; IPR020578; Aminotrans_V_PyrdxlP_BS.
DR InterPro; IPR010240; Cys_deSase_IscS.
DR InterPro; IPR015424; PyrdxlP-dep_Trfase.
DR InterPro; IPR015421; PyrdxlP-dep_Trfase_major.
DR InterPro; IPR015422; PyrdxlP-dep_Trfase_small.
DR PANTHER; PTHR11601:SF34; PTHR11601:SF34; 1.
DR Pfam; PF00266; Aminotran_5; 1.
DR SUPFAM; SSF53383; SSF53383; 1.
DR TIGRFAMs; TIGR02006; IscS; 1.
DR PROSITE; PS00595; AA_TRANSFER_CLASS_5; 1.
PE 1: Evidence at protein level;
KW Iron; Iron-sulfur; Metal-binding; Mitochondrion; Pyridoxal phosphate;
KW Reference proteome; Transferase; Transit peptide; tRNA processing.
FT TRANSIT 1..33
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 34..497
FT /note="Cysteine desulfurase, mitochondrial"
FT /id="PRO_0000001304"
FT ACT_SITE 421
FT /note="Cysteine persulfide intermediate"
FT /evidence="ECO:0000250|UniProtKB:P0A6B7"
FT BINDING 168..169
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P0A6B9"
FT BINDING 248
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:O29689"
FT BINDING 276
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P0A6B9"
FT BINDING 296..298
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P0A6B9"
FT BINDING 336
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P0A6B9"
FT BINDING 421
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /note="via persulfide group"
FT /evidence="ECO:0000250|UniProtKB:O29689"
FT MOD_RES 299
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000250|UniProtKB:P0A6B9"
FT MUTAGEN 191
FT /note="I->S: Disrupts iron-sulfur (Fe-S) cluster assembly
FT and decreases cytosolic tRNA thiolation. Exhibits
FT constitutive up-regulation of the genes of the cellular
FT iron uptake system."
FT /evidence="ECO:0000269|PubMed:10551871,
FT ECO:0000269|PubMed:31040179"
FT CONFLICT 150
FT /note="H -> Y (in Ref. 1; AAA34814)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 497 AA; 54467 MW; D709E326B3921BCC CRC64;
MLKSTATRSI TRLSQVYNVP AATYRACLVS RRFYSPPAAG VKLDDNFSLE THTDIQAAAK
AQASARASAS GTTPDAVVAS GSTAMSHAYQ ENTGFGTRPI YLDMQATTPT DPRVLDTMLK
FYTGLYGNPH SNTHSYGWET NTAVENARAH VAKMINADPK EIIFTSGATE SNNMVLKGVP
RFYKKTKKHI ITTRTEHKCV LEAARAMMKE GFEVTFLNVD DQGLIDLKEL EDAIRPDTCL
VSVMAVNNEI GVIQPIKEIG AICRKNKIYF HTDAAQAYGK IHIDVNEMNI DLLSISSHKI
YGPKGIGAIY VRRRPRVRLE PLLSGGGQER GLRSGTLAPP LVAGFGEAAR LMKKEFDNDQ
AHIKRLSDKL VKGLLSAEHT TLNGSPDHRY PGCVNVSFAY VEGESLLMAL RDIALSSGSA
CTSASLEPSY VLHALGKDDA LAHSSIRFGI GRFSTEEEVD YVVKAVSDRV KFLRELSPLW
EMVQEGIDLN SIKWSGH
