ECM38_YEAST
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 03-AUG-2022, entry version 170.
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}.
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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; 58.
DR DIP; DIP-4682N; -.
DR MINT; Q05902; -.
DR STRING; 4932.YLR299W; -.
DR MEROPS; T03.012; -.
DR MaxQB; Q05902; -.
DR PaxDb; Q05902; -.
DR PRIDE; Q05902; -.
DR EnsemblFungi; YLR299W_mRNA; YLR299W; YLR299W.
DR GeneID; 851006; -.
DR KEGG; sce:YLR299W; -.
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 BioCyc; MetaCyc:YLR299W-MON; -.
DR BioCyc; YEAST:YLR299W-MON; -.
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 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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:0102953; F:hypoglycin A gamma-glutamyl transpeptidase activity; IEA:UniProtKB-EC.
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 PANTHER; PTHR11686; PTHR11686; 1.
DR SUPFAM; SSF56235; SSF56235; 1.
DR TIGRFAMs; TIGR00066; g_glut_trans; 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
