ID   GSH1_YEAST              Reviewed;         678 AA.
AC   P32477; D6VW83;
DT   01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1993, sequence version 1.
DT   02-SEP-2026, entry version 182.
DE   RecName: Full=Glutamate--cysteine ligase;
DE            EC=6.3.2.2 {ECO:0000269|PubMed:1687097};
DE   AltName: Full=Gamma-ECS;
DE            Short=GCS;
DE   AltName: Full=Gamma-glutamylcysteine synthetase;
GN   Name=GSH1; OrderedLocusNames=YJL101C; ORFNames=J0832;
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], FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=1687097; DOI=10.1002/yea.320070907;
RA   Ohtake Y., Yabuuchi S.;
RT   "Molecular cloning of the gamma-glutamylcysteine synthetase gene of
RT   Saccharomyces cerevisiae.";
RL   Yeast 7:953-961(1991).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=8100487; DOI=10.1007/bf00312627;
RA   Lisowsky T.;
RT   "A high copy number of yeast gamma-glutamylcysteine synthetase suppresses a
RT   nuclear mutation affecting mitochondrial translation.";
RL   Curr. Genet. 23:408-413(1993).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=ATCC 96604 / S288c / FY1679;
RX   PubMed=7483851; DOI=10.1002/yea.320110909;
RA   Rasmussen S.W.;
RT   "A 37.5 kb region of yeast chromosome X includes the SME1, MEF2, GSH1 and
RT   CSD3 genes, a TCP-1-related gene, an open reading frame similar to the
RT   DAL80 gene, and a tRNA(Arg).";
RL   Yeast 11:873-883(1995).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=8641269; DOI=10.1002/j.1460-2075.1996.tb00557.x;
RA   Galibert F., Alexandraki D., Baur A., Boles E., Chalwatzis N., Chuat J.-C.,
RA   Coster F., Cziepluch C., de Haan M., Domdey H., Durand P., Entian K.-D.,
RA   Gatius M., Goffeau A., Grivell L.A., Hennemann A., Herbert C.J.,
RA   Heumann K., Hilger F., Hollenberg C.P., Huang M.-E., Jacq C.,
RA   Jauniaux J.-C., Katsoulou C., Kirchrath L., Kleine K., Kordes E.,
RA   Koetter P., Liebl S., Louis E.J., Manus V., Mewes H.-W., Miosga T.,
RA   Obermaier B., Perea J., Pohl T.M., Portetelle D., Pujol A., Purnelle B.,
RA   Ramezani Rad M., Rasmussen S.W., Rose M., Rossau R.,
RA   Schaaff-Gerstenschlaeger I., Smits P.H.M., Scarcez T., Soriano N.,
RA   To Van D., Tzermia M., Van Broekhoven A., Vandenbol M., Wedler H.,
RA   von Wettstein D., Wambutt R., Zagulski M., Zollner A., Karpfinger-Hartl L.;
RT   "Complete nucleotide sequence of Saccharomyces cerevisiae chromosome X.";
RL   EMBO J. 15:2031-2049(1996).
RN   [5]
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   [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).
CC   -!- FUNCTION: Catalyzes the ATP-dependent condensation of cysteine and
CC       glutamate to form the dipeptide gamma-glutamylcysteine (gamma-GC), the
CC       first and rate-limiting step in the production of glutathione (GSH).
CC       {ECO:0000305|PubMed:1687097}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-cysteine + L-glutamate + ATP = gamma-L-glutamyl-L-cysteine +
CC         ADP + phosphate + H(+); Xref=Rhea:RHEA:13285, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:29985, ChEBI:CHEBI:30616, ChEBI:CHEBI:35235,
CC         ChEBI:CHEBI:43474, ChEBI:CHEBI:58173, ChEBI:CHEBI:456216; EC=6.3.2.2;
CC         Evidence={ECO:0000269|PubMed:1687097};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13286;
CC         Evidence={ECO:0000269|PubMed:1687097};
CC   -!- ACTIVITY REGULATION: Feedback inhibition by glutathione.
CC   -!- PATHWAY: Sulfur metabolism; glutathione biosynthesis; glutathione from
CC       L-cysteine and L-glutamate: step 1/2. {ECO:0000305|PubMed:1687097}.
CC   -!- MISCELLANEOUS: Present with 5130 molecules/cell in log phase SD medium.
CC       {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: Belongs to the glutamate--cysteine ligase type 3 family.
CC       {ECO:0000305}.
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DR   EMBL; D90220; BAA14251.1; -; Genomic_DNA.
DR   EMBL; Z17312; CAA78960.1; -; Genomic_DNA.
DR   EMBL; X85021; CAA59393.1; -; Genomic_DNA.
DR   EMBL; Z49376; CAA89396.1; -; Genomic_DNA.
DR   EMBL; BK006943; DAA08699.1; -; Genomic_DNA.
DR   PIR; S28648; S28648.
DR   RefSeq; NP_012434.1; NM_001181534.1.
DR   PDB; 3IG5; X-ray; 2.10 A; A=1-678.
DR   PDB; 3IG8; X-ray; 2.69 A; A=1-678.
DR   PDB; 3LVV; X-ray; 2.20 A; A=1-678.
DR   PDB; 3LVW; X-ray; 2.50 A; A=1-678.
DR   AlphaFoldDB; P32477; -.
DR   MDposit; P32477; -.
DR   MDRepo; P32477; -.
DR   SMR; P32477; -.
DR   BioGRID; 33656; 474.
DR   FunCoup; P32477; 499.
DR   IntAct; P32477; 10.
DR   STRING; 4932.YJL101C; -.
DR   iPTMnet; P32477; -.
DR   PaxDb; 4932-YJL101C; -.
DR   PeptideAtlas; P32477; -.
DR   EnsemblFungi; YJL101C_mRNA; YJL101C; YJL101C.
DR   GeneID; 853344; -.
DR   KEGG; sce:YJL101C; -.
DR   AGR; SGD:S000003637; -.
DR   SGD; S000003637; GSH1.
DR   VEuPathDB; FungiDB:YJL101C; -.
DR   eggNOG; KOG3754; Eukaryota.
DR   HOGENOM; CLU_010467_0_0_1; -.
DR   InParanoid; P32477; -.
DR   OMA; IAHMFIR; -.
DR   OrthoDB; 7939818at2759; -.
DR   BioCyc; YEAST:YJL101C-MONOMER; -.
DR   BRENDA; 6.3.2.2; 984.
DR   UniPathway; UPA00142; UER00209.
DR   BioGRID-ORCS; 853344; 10 hits in 10 CRISPR screens.
DR   EvolutionaryTrace; P32477; -.
DR   PRO; PR:P32477; -.
DR   Proteomes; UP000002311; Chromosome X.
DR   RNAct; P32477; protein.
DR   GO; GO:0005737; C:cytoplasm; IDA:SGD.
DR   GO; GO:0004357; F:glutamate-cysteine ligase activity; IDA:SGD.
DR   GO; GO:0006750; P:glutathione biosynthetic process; IDA:SGD.
DR   GO; GO:0046686; P:response to cadmium ion; IDA:SGD.
DR   GO; GO:0042542; P:response to hydrogen peroxide; IMP:SGD.
DR   FunFam; 1.10.150.710:FF:000001; Glutamate--cysteine ligase; 1.
DR   FunFam; 1.10.8.960:FF:000004; Glutamate--cysteine ligase; 1.
DR   FunFam; 3.30.590.50:FF:000006; Glutamate--cysteine ligase; 1.
DR   FunFam; 3.30.590.50:FF:000004; Glutamate-cysteine ligase Gcs1; 1.
DR   Gene3D; 1.10.8.960; -; 1.
DR   Gene3D; 3.30.590.50; -; 2.
DR   Gene3D; 1.10.150.710; Glutamate cysteine ligase subdomain; 1.
DR   InterPro; IPR004308; GCS.
DR   InterPro; IPR014746; Gln_synth/guanido_kin_cat_dom.
DR   PANTHER; PTHR11164; GLUTAMATE CYSTEINE LIGASE; 1.
DR   PANTHER; PTHR11164:SF0; GLUTAMATE--CYSTEINE LIGASE CATALYTIC SUBUNIT; 1.
DR   Pfam; PF03074; GCS; 1.
DR   SUPFAM; SSF55931; Glutamine synthetase/guanido kinase; 1.
DR   PDBsum; 3IG5; -.
DR   PDBsum; 3IG8; -.
DR   PDBsum; 3LVV; -.
DR   PDBsum; 3LVW; -.
PE   1: Evidence at protein level;
KW   3D-structure; ATP-binding; Glutathione biosynthesis; Ligase;
KW   Nucleotide-binding; Reference proteome.
FT   CHAIN           1..678
FT                   /note="Glutamate--cysteine ligase"
FT                   /id="PRO_0000192572"
FT   CONFLICT        299
FT                   /note="A -> R (in Ref. 2; CAA78960)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        492
FT                   /note="L -> V (in Ref. 2; CAA78960)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        526..527
FT                   /note="IL -> MV (in Ref. 2; CAA78960)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        542
FT                   /note="D -> V (in Ref. 2; CAA78960)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        550
FT                   /note="I -> M (in Ref. 2; CAA78960)"
FT                   /evidence="ECO:0000305"
FT   HELIX           3..6
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   HELIX           12..15
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   HELIX           16..18
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   HELIX           19..37
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   STRAND          46..59
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   TURN            60..63
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   STRAND          64..67
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   HELIX           74..77
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   TURN            78..82
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   HELIX           83..88
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   STRAND          91..94
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   STRAND          101..108
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   STRAND          110..112
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   HELIX           117..142
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   STRAND          149..154
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   TURN            160..163
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   STRAND          168..171
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   TURN            179..181
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   HELIX           188..190
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   HELIX           196..208
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   STRAND          214..218
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   HELIX           240..242
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   HELIX           244..247
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   STRAND          252..255
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   HELIX           259..262
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   STRAND          266..275
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   HELIX           276..286
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   HELIX           289..296
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   STRAND          306..310
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   HELIX           314..320
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   TURN            326..330
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   TURN            336..338
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   HELIX           340..342
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   HELIX           348..353
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   HELIX           354..356
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   STRAND          361..364
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   HELIX           377..379
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   HELIX           388..395
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   HELIX           401..403
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   HELIX           404..413
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   HELIX           423..425
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   TURN            430..432
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   HELIX           435..441
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   STRAND          447..451
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   STRAND          467..471
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   HELIX           480..499
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   TURN            500..503
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   HELIX           510..519
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   HELIX           525..528
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   STRAND          530..535
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   STRAND          537..539
FT                   /evidence="ECO:0007829|PDB:3LVV"
FT   STRAND          545..549
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   HELIX           550..555
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   TURN            557..559
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   HELIX           562..566
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   HELIX           567..572
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   HELIX           580..585
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   TURN            587..589
FT                   /evidence="ECO:0007829|PDB:3LVV"
FT   HELIX           590..603
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   HELIX           610..619
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   STRAND          626..629
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   HELIX           632..646
FT                   /evidence="ECO:0007829|PDB:3IG5"
FT   HELIX           650..652
FT                   /evidence="ECO:0007829|PDB:3LVV"
FT   HELIX           654..669
FT                   /evidence="ECO:0007829|PDB:3IG5"
SQ   SEQUENCE   678 AA;  78254 MW;  65A345988A0C5AAC CRC64;
     MGLLALGTPL QWFESRTYNE HIRDEGIEQL LYIFQAAGKR DNDPLFWGDE LEYMVVDFDD
     KERNSMLDVC HDKILTELNM EDSSLCEAND VSFHPEYGRY MLEATPASPY LNYVGSYVEV
     NMQKRRAIAE YKLSEYARQD SKNNLHVGSR SVPLTLTVFP RMGCPDFINI KDPWNHKNAA
     SRSLFLPDEV INRHVRFPNL TASIRTRRGE KVCMNVPMYK DIATPETDDS IYDRDWFLPE
     DKEAKLASKP GFIYMDSMGF GMGCSCLQVT FQAPNINKAR YLYDALVNFA PIMLAFSAAA
     PAFKGWLADQ DVRWNVISGA VDDRTPKERG VAPLLPKYNK NGFGGIAKDV QDKVLEIPKS
     RYSSVDLFLG GSKFFNRTYN DTNVPINEKV LGRLLENDKA PLDYDLAKHF AHLYIRDPVS
     TFEELLNQDN KTSSNHFENI QSTNWQTLRF KPPTQQATPD KKDSPGWRVE FRPFEVQLLD
     FENAAYSVLI YLIVDSILTF SDNINAYIHM SKVWENMKIA HHRDAILFEK FHWKKSFRND
     TDVETEDYSI SEIFHNPENG IFPQFVTPIL CQKGFVTKDW KELKHSSKHE RLYYYLKLIS
     DRASGELPTT AKFFRNFVLQ HPDYKHDSKI SKSINYDLLS TCDRLTHLDD SKGELTSFLG
     AEIAEYVKKN KPSIESKC
//