ID ECM38_YEAST Reviewed; 660 AA. AC Q05902; D6VYU3; DT 01-MAR-2005, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 08-NOV-2023, entry version 175. DE RecName: Full=Glutathione hydrolase proenzyme; DE EC=3.4.19.13 {ECO:0000269|PubMed:6102906, ECO:0000269|PubMed:6143552}; DE AltName: Full=CIK1 suppressor protein 2; DE AltName: Full=Extracellular mutant protein 38; DE AltName: Full=Gamma-glutamyltransferase; DE EC=2.3.2.2 {ECO:0000269|PubMed:6102906, ECO:0000269|PubMed:6143552}; DE AltName: Full=Gamma-glutamyltranspeptidase; DE Short=Gamma-GT; DE Contains: DE RecName: Full=Glutathione hydrolase heavy chain; DE Contains: DE RecName: Full=Glutathione hydrolase light chain; DE Flags: Precursor; GN Name=ECM38; Synonyms=CIS2; OrderedLocusNames=YLR299W; 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=9169871; RA Johnston M., Hillier L.W., Riles L., Albermann K., Andre B., Ansorge W., RA Benes V., Brueckner M., Delius H., Dubois E., Duesterhoeft A., RA Entian K.-D., Floeth M., Goffeau A., Hebling U., Heumann K., RA Heuss-Neitzel D., Hilbert H., Hilger F., Kleine K., Koetter P., Louis E.J., RA Messenguy F., Mewes H.-W., Miosga T., Moestl D., Mueller-Auer S., RA Nentwich U., Obermaier B., Piravandi E., Pohl T.M., Portetelle D., RA Purnelle B., Rechmann S., Rieger M., Rinke M., Rose M., Scharfe M., RA Scherens B., Scholler P., Schwager C., Schwarz S., Underwood A.P., RA Urrestarazu L.A., Vandenbol M., Verhasselt P., Vierendeels F., Voet M., RA Volckaert G., Voss H., Wambutt R., Wedler E., Wedler H., Zimmermann F.K., RA Zollner A., Hani J., Hoheisel J.D.; RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XII."; RL Nature 387:87-90(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 CATALYTIC ACTIVITY, AND INDUCTION. RX PubMed=6102906; DOI=10.1111/j.1432-1033.1980.tb04407.x; RA Penninckx M., Jaspers C., Wiame J.M.; RT "Glutathione metabolism in relation to the amino-acid permeation systems of RT the yeast Saccharomyces cerevisiae. Occurrence of gamma- RT glutamyltranspeptidase: its regulation and the effects of permeation RT mutations on the enzyme cellular level."; RL Eur. J. Biochem. 104:119-123(1980). RN [4] RP CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND INDUCTION. RX PubMed=6143552; DOI=10.1042/bj2180147; RA Payne G.M., Payne J.W.; RT "Gamma-glutamyltransferase is not involved in the bulk uptake of amino RT acids, peptides or gamma-glutamyl-amino acids in yeast (Saccharomyces RT cerevisiae)."; RL Biochem. J. 218:147-155(1984). RN [5] RP SUBCELLULAR LOCATION. RX PubMed=6143574; DOI=10.1016/0300-9084(84)90193-7; RA Jaspers C.J., Penninckx M.J.; RT "Glutathione metabolism in yeast Saccharomyces cerevisiae. Evidence that RT gamma-glutamyltranspeptidase is a vacuolar enzyme."; RL Biochimie 66:71-74(1984). RN [6] RP ACTIVITY REGULATION. RX PubMed=1674526; DOI=10.1099/00221287-137-3-637; RA Elskens M.T., Jaspers C.J., Penninckx M.J.; RT "Glutathione as an endogenous sulphur source in the yeast Saccharomyces RT cerevisiae."; RL J. Gen. Microbiol. 137:637-644(1991). RN [7] RP IDENTIFICATION. RX PubMed=9335584; DOI=10.1093/genetics/147.2.435; RA Lussier M., White A.-M., Sheraton J., di Paolo T., Treadwell J., RA Southard S.B., Horenstein C.I., Chen-Weiner J., Ram A.F.J., Kapteyn J.C., RA Roemer T.W., Vo D.H., Bondoc D.C., Hall J., Zhong W.-W., Sdicu A.-M., RA Davies J., Klis F.M., Robbins P.W., Bussey H.; RT "Large scale identification of genes involved in cell surface biosynthesis RT and architecture in Saccharomyces cerevisiae."; RL Genetics 147:435-450(1997). RN [8] RP INDUCTION. RX PubMed=9202464; DOI=10.1099/00221287-143-6-1885; RA Mehdi K., Penninckx M.J.; RT "An important role for glutathione and gamma-glutamyltranspeptidase in the RT supply of growth requirements during nitrogen starvation of the yeast RT Saccharomyces cerevisiae."; RL Microbiology 143:1885-1889(1997). RN [9] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=11672438; DOI=10.1042/0264-6021:3590631; RA Mehdi K., Thierie J., Penninckx M.J.; RT "Gamma-glutamyl transpeptidase in the yeast Saccharomyces cerevisiae and RT its role in the vacuolar transport and metabolism of glutathione."; RL Biochem. J. 359:631-637(2001). RN [10] RP INDUCTION. RX PubMed=12529169; DOI=10.1042/bj20021893; RA Springael J.-Y., Penninckx M.J.; RT "Nitrogen-source regulation of yeast gamma-glutamyl transpeptidase RT synthesis involves the regulatory network including the GATA zinc-finger RT factors Gln3, Nil1/Gat1 and Gzf3."; RL Biochem. J. 371:589-595(2003). RN [11] 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 [12] RP VARIANTS ARG-171 AND ASP-494. RC STRAIN=ATCC 76625 / YPH499; RX PubMed=12868055; DOI=10.1002/yea.1012; RA Kumar C., Sharma R., Bachhawat A.K.; RT "Investigations into the polymorphisms at the ECM38 locus of two widely RT used Saccharomyces cerevisiae S288C strains, YPH499 and BY4742."; RL Yeast 20:857-863(2003). CC -!- FUNCTION: Catalyzes the transfer of the gamma-glutamyl moiety of CC glutathione (GSH) and other gamma-glutamyl compounds to amino acids and CC peptides. Major GSH-degrading enzyme, catalyzing the hydrolytic release CC of L-glutamate from GSH. Plays a role in the turnover of the vacuolar CC GSH, serving as an alternative nitrogen source during nitrogen CC starvation. {ECO:0000269|PubMed:11672438}. CC -!- CATALYTIC ACTIVITY: CC Reaction=an alpha-amino acid + an N-terminal (5-L-glutamyl)-[peptide] = CC 5-L-glutamyl amino acid + N-terminal L-alpha-aminoacyl-[peptide]; CC Xref=Rhea:RHEA:23904, Rhea:RHEA-COMP:9780, Rhea:RHEA-COMP:9795, CC ChEBI:CHEBI:77644, ChEBI:CHEBI:78597, ChEBI:CHEBI:78599, CC ChEBI:CHEBI:78608; EC=2.3.2.2; Evidence={ECO:0000269|PubMed:6102906, CC ECO:0000269|PubMed:6143552}; CC -!- CATALYTIC ACTIVITY: CC Reaction=glutathione + H2O = L-cysteinylglycine + L-glutamate; CC Xref=Rhea:RHEA:28807, ChEBI:CHEBI:15377, ChEBI:CHEBI:29985, CC ChEBI:CHEBI:57925, ChEBI:CHEBI:61694; EC=3.4.19.13; CC Evidence={ECO:0000269|PubMed:6102906, ECO:0000269|PubMed:6143552}; CC -!- CATALYTIC ACTIVITY: CC Reaction=an S-substituted glutathione + H2O = an S-substituted L- CC cysteinylglycine + L-glutamate; Xref=Rhea:RHEA:59468, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:29985, ChEBI:CHEBI:90779, CC ChEBI:CHEBI:143103; EC=3.4.19.13; CC Evidence={ECO:0000269|PubMed:6102906, ECO:0000269|PubMed:6143552}; CC -!- ACTIVITY REGULATION: Activity is decreased by glutathione and ammonium CC ion. {ECO:0000269|PubMed:1674526}. CC -!- PATHWAY: Sulfur metabolism; glutathione metabolism. CC -!- SUBUNIT: Heterodimer composed of a light and a heavy chain. The active CC site is located in the light chain. {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Vacuole membrane {ECO:0000269|PubMed:11672438, CC ECO:0000269|PubMed:6143552, ECO:0000269|PubMed:6143574}; Single-pass CC type II membrane protein {ECO:0000269|PubMed:11672438, CC ECO:0000269|PubMed:6143552, ECO:0000269|PubMed:6143574}. CC -!- INDUCTION: Induced upon nitrogen starvation. Repressed by ammonium CC ions. 6-diazo-5-oxo-L-norleucine and L-azaserine are irreversible CC inhibitors whereas serine-borate is a reversible inhibitor. CC {ECO:0000269|PubMed:12529169, ECO:0000269|PubMed:6102906, CC ECO:0000269|PubMed:6143552, ECO:0000269|PubMed:9202464}. CC -!- PTM: Cleaved by autocatalysis into a large and a small subunit. CC -!- MISCELLANEOUS: Present with 672 molecules/cell in log phase SD medium. CC {ECO:0000269|PubMed:14562106}. CC -!- SIMILARITY: Belongs to the gamma-glutamyltransferase family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U17243; AAB67344.1; -; Genomic_DNA. DR EMBL; BK006945; DAA09609.1; -; Genomic_DNA. DR PIR; S50383; S50383. DR RefSeq; NP_013402.1; NM_001182187.1. DR AlphaFoldDB; Q05902; -. DR SMR; Q05902; -. DR BioGRID; 31563; 59. DR DIP; DIP-4682N; -. DR MINT; Q05902; -. DR STRING; 4932.YLR299W; -. DR MEROPS; T03.012; -. DR GlyCosmos; Q05902; 6 sites, No reported glycans. DR MaxQB; Q05902; -. DR PaxDb; 4932-YLR299W; -. DR PeptideAtlas; Q05902; -. DR EnsemblFungi; YLR299W_mRNA; YLR299W; YLR299W. DR GeneID; 851006; -. DR KEGG; sce:YLR299W; -. DR AGR; SGD:S000004290; -. DR SGD; S000004290; ECM38. DR VEuPathDB; FungiDB:YLR299W; -. DR eggNOG; KOG2410; Eukaryota. DR GeneTree; ENSGT00940000156917; -. DR HOGENOM; CLU_014813_4_0_1; -. DR InParanoid; Q05902; -. DR OMA; VCGMGPP; -. DR OrthoDB; 2910309at2759; -. DR BioCyc; MetaCyc:YLR299W-MONOMER; -. DR BioCyc; YEAST:YLR299W-MONOMER; -. DR BRENDA; 3.4.19.13; 984. DR Reactome; R-SCE-174403; Glutathione synthesis and recycling. DR Reactome; R-SCE-2142691; Synthesis of Leukotrienes (LT) and Eoxins (EX). DR Reactome; R-SCE-5423646; Aflatoxin activation and detoxification. DR Reactome; R-SCE-9753281; Paracetamol ADME. DR UniPathway; UPA00204; -. DR BioGRID-ORCS; 851006; 0 hits in 10 CRISPR screens. DR PRO; PR:Q05902; -. DR Proteomes; UP000002311; Chromosome XII. DR RNAct; Q05902; Protein. DR GO; GO:0000324; C:fungal-type vacuole; IDA:SGD. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0005774; C:vacuolar membrane; IEA:UniProtKB-SubCell. DR GO; GO:0036374; F:glutathione hydrolase activity; IMP:SGD. DR GO; GO:0103068; F:leukotriene C4 gamma-glutamyl transferase activity; IEA:UniProtKB-EC. DR GO; GO:0006751; P:glutathione catabolic process; IMP:SGD. DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW. DR GO; GO:0006805; P:xenobiotic metabolic process; IMP:SGD. DR Gene3D; 1.10.246.130; -; 1. DR Gene3D; 3.60.20.40; -; 1. DR InterPro; IPR043138; GGT_lsub_C. DR InterPro; IPR000101; GGT_peptidase. DR InterPro; IPR043137; GGT_ssub. DR InterPro; IPR029055; Ntn_hydrolases_N. DR NCBIfam; TIGR00066; g_glut_trans; 1. DR PANTHER; PTHR11686; GAMMA GLUTAMYL TRANSPEPTIDASE; 1. DR PANTHER; PTHR11686:SF9; GAMMA-GLUTAMYL TRANSPEPTIDASE, ISOFORM A; 1. DR Pfam; PF01019; G_glu_transpept; 1. DR PRINTS; PR01210; GGTRANSPTASE. DR SUPFAM; SSF56235; N-terminal nucleophile aminohydrolases (Ntn hydrolases); 1. DR PROSITE; PS00462; G_GLU_TRANSPEPTIDASE; 1. PE 1: Evidence at protein level; KW Acyltransferase; Glycoprotein; Hydrolase; Membrane; Protease; KW Reference proteome; Signal-anchor; Transferase; Transmembrane; KW Transmembrane helix; Vacuole. FT CHAIN 1..469 FT /note="Glutathione hydrolase heavy chain" FT /evidence="ECO:0000250" FT /id="PRO_0000011078" FT CHAIN 470..660 FT /note="Glutathione hydrolase light chain" FT /evidence="ECO:0000250" FT /id="PRO_0000011079" FT TOPO_DOM 1..13 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 14..34 FT /note="Helical; Signal-anchor for type II membrane protein" FT /evidence="ECO:0000255" FT TOPO_DOM 35..660 FT /note="Lumenal" FT /evidence="ECO:0000255" FT REGION 73..92 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 73..88 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 470 FT /note="Nucleophile" FT /evidence="ECO:0000250" FT BINDING 177 FT /ligand="L-glutamate" FT /ligand_id="ChEBI:CHEBI:29985" FT /evidence="ECO:0000250" FT BINDING 488 FT /ligand="L-glutamate" FT /ligand_id="ChEBI:CHEBI:29985" FT /evidence="ECO:0000250" FT BINDING 490 FT /ligand="L-glutamate" FT /ligand_id="ChEBI:CHEBI:29985" FT /evidence="ECO:0000250" FT BINDING 509 FT /ligand="L-glutamate" FT /ligand_id="ChEBI:CHEBI:29985" FT /evidence="ECO:0000250" FT BINDING 512 FT /ligand="L-glutamate" FT /ligand_id="ChEBI:CHEBI:29985" FT /evidence="ECO:0000250" FT BINDING 540..541 FT /ligand="L-glutamate" FT /ligand_id="ChEBI:CHEBI:29985" FT /evidence="ECO:0000250" FT BINDING 562..563 FT /ligand="L-glutamate" FT /ligand_id="ChEBI:CHEBI:29985" FT /evidence="ECO:0000250" FT CARBOHYD 119 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 191 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 270 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 298 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 454 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 517 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VARIANT 171 FT /note="H -> R (in strain: YPH499)" FT /evidence="ECO:0000269|PubMed:12868055" FT VARIANT 494 FT /note="G -> D (in strain: YPH499; lack of gamma-glutamyl FT transferase activity)" FT /evidence="ECO:0000269|PubMed:12868055" SQ SEQUENCE 660 AA; 73180 MW; 9896E9EBFF822F55 CRC64; MLLCNRKVPK TLNTCFILHI FTLLTLGVLV SGMPSKMVSF ASQETLQRIN NLLRGSANRD VDIIAEYLKK DDDDDGGDKD HHNIDIDPLP RRPSLTPDRQ LLKVGLHGAI SSDLEVCSNL TINEVLLKFP GSNAADAAVT QALCKGMVNF FNSGIGGGGY VVFSGKDDED HLSIDFREKA PMDSHKFMFE NCSLCSKIGG LAVGVPGELM GLYRLFKERG SGQVDWRDLI EPVAKLGSVG WQIGEALGAT LELYEDVFLT LKEDWSFVLN STHDGVLKEG DWIKRPALSN MLMELAKNGS VAPFYDPDHW IAKSMIDTVA KYNGIMNLQD VSSYDVHVTK PLSMKIRKGA NFIPDNDMTV LTSSGSSSGA ALLAALRIMD NFQNQEGGDY EKETTYHLLE SMKWMASARS RLGDFEGEAL PKHIEEVLDP EWALKAVKSI KRNSQDGNFK TLENWTLYDP AYDINNPHGT AHFSIVDSHG NAVSLTTTIN LLFGSLVHDP KTGVIFNNEM DDFAQFNKSN SFELAPSIYN FPEPGKRPLS STAPTIVLSE LGIPDLVVGA SGGSRITTSV LQTIVRTYWY NMPILETIAY PRIHHQLLPD RIELESFPMI GKAVLSTLKE MGYTMKEVFP KSVVNAIRNV RGEWHAVSDY WRKRGISSVY //