CHAC_YEAST
ID CHAC_YEAST Reviewed; 232 AA.
AC P32656; D3DM71;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1993, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Glutathione-specific gamma-glutamylcyclotransferase {ECO:0000305|PubMed:23070364};
DE Short=Gamma-GCG {ECO:0000303|PubMed:23070364};
DE EC=4.3.2.7 {ECO:0000269|PubMed:23070364};
GN Name=GCG1 {ECO:0000303|PubMed:23070364};
GN OrderedLocusNames=YER163C {ECO:0000312|SGD:S000000965}; ORFNames=SYGP-ORF3;
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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169868;
RA Dietrich F.S., Mulligan J.T., Hennessy K.M., Yelton M.A., Allen E.,
RA Araujo R., Aviles E., Berno A., Brennan T., Carpenter J., Chen E.,
RA Cherry J.M., Chung E., Duncan M., Guzman E., Hartzell G., Hunicke-Smith S.,
RA Hyman R.W., Kayser A., Komp C., Lashkari D., Lew H., Lin D., Mosedale D.,
RA Nakahara K., Namath A., Norgren R., Oefner P., Oh C., Petel F.X.,
RA Roberts D., Sehl P., Schramm S., Shogren T., Smith V., Taylor P., Wei Y.,
RA Botstein D., Davis R.W.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome V.";
RL Nature 387:78-81(1997).
RN [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=17322287; DOI=10.1101/gr.6037607;
RA Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F.,
RA Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J.,
RA Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J.,
RA Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D.,
RA LaBaer J.;
RT "Approaching a complete repository of sequence-verified protein-encoding
RT clones for Saccharomyces cerevisiae.";
RL Genome Res. 17:536-543(2007).
RN [4]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=14562095; DOI=10.1038/nature02026;
RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA Weissman J.S., O'Shea E.K.;
RT "Global analysis of protein localization in budding yeast.";
RL Nature 425:686-691(2003).
RN [5]
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 [6]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP MUTAGENESIS OF GLU-115.
RX PubMed=23070364; DOI=10.1038/embor.2012.156;
RA Kumar A., Tikoo S., Maity S., Sengupta S., Sengupta S., Kaur A.,
RA Bachhawat A.K.;
RT "Mammalian proapoptotic factor ChaC1 and its homologues function as gamma-
RT glutamyl cyclotransferases acting specifically on glutathione.";
RL EMBO Rep. 13:1095-1101(2012).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.34 ANGSTROMS) IN COMPLEX WITH BENZOATE.
RX PubMed=27913623; DOI=10.1074/jbc.m116.727479;
RA Kaur A., Gautam R., Srivastava R., Chandel A., Kumar A., Karthikeyan S.,
RA Bachhawat A.K.;
RT "ChaC2, an enzyme for slow turnover of cytosolic glutathione.";
RL J. Biol. Chem. 292:638-651(2017).
CC -!- FUNCTION: Catalyzes the cleavage of glutathione into 5-oxo-L-proline
CC and a Cys-Gly dipeptide. Acts specifically on glutathione, but not on
CC other gamma-glutamyl peptides. Allows utilization of gluthathione
CC through subsequent cleavage of the Cys-Gly dipeptide by Cys-Gly
CC metallodipeptidase DUG1. {ECO:0000269|PubMed:23070364}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glutathione = 5-oxo-L-proline + L-cysteinylglycine;
CC Xref=Rhea:RHEA:47724, ChEBI:CHEBI:57925, ChEBI:CHEBI:58402,
CC ChEBI:CHEBI:61694; EC=4.3.2.7;
CC Evidence={ECO:0000269|PubMed:23070364};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.52 mM for glutathione {ECO:0000269|PubMed:23070364};
CC Vmax=110 umol/h/mg enzyme {ECO:0000269|PubMed:23070364};
CC Note=kcat is 50.8 min(-1) for glutathione.
CC {ECO:0000269|PubMed:23070364};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095}. Nucleus
CC {ECO:0000269|PubMed:14562095}.
CC -!- MISCELLANEOUS: Present with 1300 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the gamma-glutamylcyclotransferase family. ChaC
CC subfamily. {ECO:0000305}.
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DR EMBL; U18917; AAB64690.1; -; Genomic_DNA.
DR EMBL; AY692652; AAT92671.1; -; Genomic_DNA.
DR EMBL; BK006939; DAA07825.1; -; Genomic_DNA.
DR PIR; S30817; S30817.
DR RefSeq; NP_011090.3; NM_001179053.3.
DR PDB; 5HWI; X-ray; 1.75 A; A=1-232.
DR PDB; 5HWK; X-ray; 1.34 A; A/B=1-232.
DR PDBsum; 5HWI; -.
DR PDBsum; 5HWK; -.
DR AlphaFoldDB; P32656; -.
DR SMR; P32656; -.
DR BioGRID; 36916; 96.
DR DIP; DIP-4233N; -.
DR IntAct; P32656; 1.
DR STRING; 4932.YER163C; -.
DR iPTMnet; P32656; -.
DR MaxQB; P32656; -.
DR PaxDb; P32656; -.
DR PRIDE; P32656; -.
DR EnsemblFungi; YER163C_mRNA; YER163C; YER163C.
DR GeneID; 856910; -.
DR KEGG; sce:YER163C; -.
DR SGD; S000000965; GCG1.
DR VEuPathDB; FungiDB:YER163C; -.
DR eggNOG; KOG3182; Eukaryota.
DR GeneTree; ENSGT00390000003855; -.
DR HOGENOM; CLU_070703_0_0_1; -.
DR InParanoid; P32656; -.
DR OMA; LLWYTDF; -.
DR BioCyc; MetaCyc:G3O-30324-MON; -.
DR BioCyc; YEAST:G3O-30324-MON; -.
DR BRENDA; 4.3.2.7; 984.
DR Reactome; R-SCE-174403; Glutathione synthesis and recycling.
DR SABIO-RK; P32656; -.
DR PRO; PR:P32656; -.
DR Proteomes; UP000002311; Chromosome V.
DR RNAct; P32656; protein.
DR GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR GO; GO:0005634; C:nucleus; HDA:SGD.
DR GO; GO:0003839; F:gamma-glutamylcyclotransferase activity; IDA:SGD.
DR GO; GO:0061928; F:glutathione specific gamma-glutamylcyclotransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0006751; P:glutathione catabolic process; IDA:SGD.
DR CDD; cd06661; GGCT_like; 1.
DR InterPro; IPR006840; ChaC.
DR InterPro; IPR013024; GGCT-like.
DR PANTHER; PTHR12192; PTHR12192; 1.
DR Pfam; PF04752; ChaC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Lyase; Nucleus; Reference proteome.
FT CHAIN 1..232
FT /note="Glutathione-specific gamma-glutamylcyclotransferase"
FT /id="PRO_0000202657"
FT ACT_SITE 115
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:O75223"
FT BINDING 10..15
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O75223"
FT MUTAGEN 115
FT /note="E->Q: Loss of catalytic activity against
FT glutathione."
FT /evidence="ECO:0000269|PubMed:23070364"
FT STRAND 8..14
FT /evidence="ECO:0007829|PDB:5HWK"
FT HELIX 15..18
FT /evidence="ECO:0007829|PDB:5HWK"
FT STRAND 25..48
FT /evidence="ECO:0007829|PDB:5HWK"
FT STRAND 50..52
FT /evidence="ECO:0007829|PDB:5HWK"
FT STRAND 54..61
FT /evidence="ECO:0007829|PDB:5HWK"
FT HELIX 62..65
FT /evidence="ECO:0007829|PDB:5HWK"
FT HELIX 69..78
FT /evidence="ECO:0007829|PDB:5HWK"
FT HELIX 87..89
FT /evidence="ECO:0007829|PDB:5HWK"
FT STRAND 91..99
FT /evidence="ECO:0007829|PDB:5HWK"
FT HELIX 101..113
FT /evidence="ECO:0007829|PDB:5HWK"
FT TURN 115..118
FT /evidence="ECO:0007829|PDB:5HWI"
FT STRAND 119..126
FT /evidence="ECO:0007829|PDB:5HWK"
FT HELIX 132..134
FT /evidence="ECO:0007829|PDB:5HWK"
FT HELIX 135..144
FT /evidence="ECO:0007829|PDB:5HWK"
FT TURN 149..151
FT /evidence="ECO:0007829|PDB:5HWI"
FT STRAND 154..163
FT /evidence="ECO:0007829|PDB:5HWK"
FT HELIX 176..185
FT /evidence="ECO:0007829|PDB:5HWK"
FT HELIX 193..205
FT /evidence="ECO:0007829|PDB:5HWK"
FT HELIX 219..232
FT /evidence="ECO:0007829|PDB:5HWK"
SQ SEQUENCE 232 AA; 26294 MW; 6B0B5306F348A59D CRC64;
MTNDNSGIWV LGYGSLIYKP PSHYTHRIPA IIHGFARRFW QSSTDHRGTP ANPGRVATLI
PYEDIIRQTA FLKNVNLYSE SAPIQDPDDL VTIGVVYYIP PEHAQEVREY LNVREQNGYT
LHEVEVHLET NREHEAELGE ALEQLPRHNK SGKRVLLTSV YIGTIDNEAF VGPETVDETA
KVIAVSHGPS GSNYEYLAKL EQALAQMPIM KERGRITDHY LTALLETVNK YR
