GSH1_YEAST
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 03-AUG-2022, entry version 166.
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=ATP + L-cysteine + L-glutamate = ADP + gamma-L-glutamyl-L-
CC cysteine + H(+) + phosphate; 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 PDBsum; 3IG5; -.
DR PDBsum; 3IG8; -.
DR PDBsum; 3LVV; -.
DR PDBsum; 3LVW; -.
DR AlphaFoldDB; P32477; -.
DR SMR; P32477; -.
DR BioGRID; 33656; 468.
DR IntAct; P32477; 10.
DR STRING; 4932.YJL101C; -.
DR iPTMnet; P32477; -.
DR MaxQB; P32477; -.
DR PaxDb; P32477; -.
DR PRIDE; P32477; -.
DR EnsemblFungi; YJL101C_mRNA; YJL101C; YJL101C.
DR GeneID; 853344; -.
DR KEGG; sce:YJL101C; -.
DR SGD; S000003637; GSH1.
DR VEuPathDB; FungiDB:YJL101C; -.
DR eggNOG; KOG3754; Eukaryota.
DR GeneTree; ENSGT00390000011908; -.
DR HOGENOM; CLU_010467_0_0_1; -.
DR InParanoid; P32477; -.
DR OMA; YISQDPR; -.
DR BioCyc; YEAST:YJL101C-MON; -.
DR BRENDA; 6.3.2.2; 984.
DR UniPathway; UPA00142; UER00209.
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:0005524; F:ATP binding; IEA:UniProtKB-KW.
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 InterPro; IPR004308; GCS.
DR InterPro; IPR014746; Gln_synth/guanido_kin_cat_dom.
DR PANTHER; PTHR11164; PTHR11164; 1.
DR Pfam; PF03074; GCS; 1.
DR SUPFAM; SSF55931; SSF55931; 1.
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 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 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 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 561..564
FT /evidence="ECO:0007829|PDB:3IG5"
FT HELIX 566..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
