ID GGT1_HUMAN Reviewed; 569 AA. AC P19440; Q08247; Q14404; Q8TBS1; Q9UMK1; DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot. DT 07-MAR-2006, sequence version 2. DT 27-MAR-2024, entry version 235. DE RecName: Full=Glutathione hydrolase 1 proenzyme; DE EC=3.4.19.13 {ECO:0000269|PubMed:17924658, ECO:0000269|PubMed:21447318, ECO:0000269|PubMed:27791009}; DE AltName: Full=Gamma-glutamyltransferase 1; DE AltName: Full=Gamma-glutamyltranspeptidase 1; DE Short=GGT 1; DE EC=2.3.2.2 {ECO:0000269|PubMed:17924658, ECO:0000269|PubMed:21447318, ECO:0000269|PubMed:23682772, ECO:0000269|PubMed:7673200, ECO:0000269|PubMed:7759490, ECO:0000269|PubMed:8095045, ECO:0000269|PubMed:8827453}; DE AltName: Full=Leukotriene-C4 hydrolase; DE EC=3.4.19.14 {ECO:0000269|PubMed:21447318}; DE AltName: CD_antigen=CD224; DE Contains: DE RecName: Full=Glutathione hydrolase 1 heavy chain; DE Contains: DE RecName: Full=Glutathione hydrolase 1 light chain; DE Flags: Precursor; GN Name=GGT1; Synonyms=GGT; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ALA-272. RC TISSUE=Placenta; RX PubMed=2904146; DOI=10.1073/pnas.85.23.8840; RA Rajpert-De Meyts E., Heisterkamp N., Groffen J.; RT "Cloning and nucleotide sequence of human gamma-glutamyl transpeptidase."; RL Proc. Natl. Acad. Sci. U.S.A. 85:8840-8844(1988). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 30-58 AND RP 381-408, AND VARIANT ALA-272. RC TISSUE=Kidney, and Liver; RX PubMed=2907498; DOI=10.1016/0378-1119(88)90307-1; RA Sakamuro D., Yamazoe M., Matsuda Y., Kangawa K., Taniguchi N., Matsuo H., RA Yoshikawa H., Ogasawara N.; RT "The primary structure of human gamma-glutamyl transpeptidase."; RL Gene 73:1-9(1988). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ALA-272. RX PubMed=2563599; DOI=10.1016/0041-008x(89)90052-5; RA Pitot H.C., Goodspeed D.C., Dunn T.J., Hendrich S., Maronpot R.R., RA Moran S.; RT "Regulation of the expression of some genes for enzymes of glutathione RT metabolism in hepatotoxicity and hepatocarcinogenesis."; RL Toxicol. Appl. Pharmacol. 97:23-34(1989). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ALA-272. RC TISSUE=Hepatoblastoma; RX PubMed=2568315; DOI=10.1016/0378-1119(89)90002-4; RA Goodspeed D.C., Dunn T.J., Miller C.D., Pitot H.C.; RT "Human gamma-glutamyl transpeptidase cDNA: comparison of hepatoma and RT kidney mRNA in the human and rat."; RL Gene 76:1-9(1989). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANT ALA-272. RC TISSUE=Liver; RX PubMed=1968061; DOI=10.1016/s0021-9258(19)39761-3; RA Pawlak A., Cohen E.H., Octave J.-N., Schweickhardt R., Wu S.-J., Bulle F., RA Chikhi N., Baik J.-H., Siegrist S., Guellaen G.; RT "An alternatively processed mRNA specific for gamma-glutamyl transpeptidase RT in human tissues."; RL J. Biol. Chem. 265:3256-3262(1990). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ALA-272. RC TISSUE=Pancreas; RX PubMed=1378736; DOI=10.1016/0006-2952(92)90140-e; RA Courtay C., Oster T., Michelet F., Visvikis A., Diederich M., Wellman M., RA Siest G.; RT "Gamma-glutamyltransferase: nucleotide sequence of the human pancreatic RT cDNA. Evidence for a ubiquitous gamma-glutamyltransferase polypeptide in RT human tissues."; RL Biochem. Pharmacol. 43:2527-2533(1992). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), LACK OF FUNCTION OF ISOFORM 3, AND RP TISSUE SPECIFICITY (ISOFORM 3). RC TISSUE=Lung; RX PubMed=7689219; DOI=10.1073/pnas.90.16.7461; RA Wetmore L.A., Gerard C., Drazen J.M.; RT "Human lung expresses unique gamma-glutamyl transpeptidase transcripts."; RL Proc. Natl. Acad. Sci. U.S.A. 90:7461-7465(1993). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84; RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., RA Beare D.M., Dunham I.; RT "A genome annotation-driven approach to cloning the human ORFeome."; RL Genome Biol. 5:R84.1-R84.11(2004). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=10591208; DOI=10.1038/990031; RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C., RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., RA Wright H.; RT "The DNA sequence of human chromosome 22."; RL Nature 402:489-495(1999). RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). RC TISSUE=Lung; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [11] RP PROTEIN SEQUENCE OF 30-48 AND 381-403. RC TISSUE=Kidney; RX PubMed=2896486; DOI=10.1016/0003-9861(88)90390-6; RA Tate S.S., Khadse V., Wellner D.; RT "Renal gamma-glutamyl transpeptidases: structural and immunological RT studies."; RL Arch. Biochem. Biophys. 262:397-408(1988). RN [12] RP ALTERNATIVE SPLICING, AND ALTERNATIVE PROMOTER USAGE. RX PubMed=10392451; DOI=10.1016/s0305-0491(99)00013-9; RA Chikhi N., Holic N., Guellaen G., Laperche Y.; RT "Gamma-glutamyl transpeptidase gene organization and expression: a RT comparative analysis in rat, mouse, pig and human species."; RL Comp. Biochem. Physiol. 122B:367-380(1999). RN [13] RP GLYCOSYLATION, AND SIALIC ACID CONTENT. RC TISSUE=Kidney; RX PubMed=19463; DOI=10.1016/s0021-9258(17)40026-3; RA Tate S.S., Ross M.E.; RT "Human kidney gamma-glutamyl transpeptidase. Catalytic properties, subunit RT structure, and localization of the gamma-glutamyl binding site on the light RT subunit."; RL J. Biol. Chem. 252:6042-6045(1977). RN [14] RP GLYCOSYLATION. RX PubMed=2900635; DOI=10.1016/0006-291x(88)90263-x; RA Tate S.S., Galbraith R.A.; RT "In vitro translation and processing of human hepatoma cell (Hep G2) gamma- RT glutamyl transpeptidase."; RL Biochem. Biophys. Res. Commun. 154:1167-1173(1988). RN [15] RP FUNCTION, CATALYTIC ACTIVITY, AUTOCATALYTIC CLEAVAGE, SUBUNIT, SUBCELLULAR RP LOCATION, AND MUTAGENESIS OF LYS-100; GLU-102; ARG-107; GLU-108; ARG-112; RP ARG-139; ARG-147 AND ARG-150. RX PubMed=8095045; DOI=10.1016/s0021-9258(18)53567-5; RA Ikeda Y., Fujii J., Taniguchi N.; RT "Significance of Arg-107 and Glu-108 in the catalytic mechanism of human RT gamma-glutamyl transpeptidase. Identification by site-directed RT mutagenesis."; RL J. Biol. Chem. 268:3980-3985(1993). RN [16] RP FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF ASP-422; ASP-423 AND CYS-454, RP AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=7759490; DOI=10.1074/jbc.270.21.12471; RA Ikeda Y., Fujii J., Taniguchi N., Meister A.; RT "Human gamma-glutamyl transpeptidase mutants involving conserved aspartate RT residues and the unique cysteine residue of the light subunit."; RL J. Biol. Chem. 270:12471-12475(1995). RN [17] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF SER-385; SER-413; SER-425; RP SER-451 AND SER-452. RX PubMed=7673200; DOI=10.1074/jbc.270.38.22223; RA Ikeda Y., Fujii J., Anderson M.E., Taniguchi N., Meister A.; RT "Involvement of Ser-451 and Ser-452 in the catalysis of human gamma- RT glutamyl transpeptidase."; RL J. Biol. Chem. 270:22223-22228(1995). RN [18] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF HIS-383 AND HIS-505. RX PubMed=8827453; DOI=10.1093/oxfordjournals.jbchem.a021363; RA Ikeda Y., Fujii J., Taniguchi N.; RT "Effects of substitutions of the conserved histidine residues in human RT gamma-glutamyl transpeptidase."; RL J. Biochem. 119:1166-1170(1996). RN [19] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-511. RC TISSUE=Bile; RX PubMed=15084671; DOI=10.1074/mcp.m400015-mcp200; RA Kristiansen T.Z., Bunkenborg J., Gronborg M., Molina H., Thuluvath P.J., RA Argani P., Goggins M.G., Maitra A., Pandey A.; RT "A proteomic analysis of human bile."; RL Mol. Cell. Proteomics 3:715-728(2004). RN [20] RP CATALYTIC ACTIVITY, ACTIVE SITE, GLYCOSYLATION AT ASN-120; ASN-266; ASN-344 RP AND ASN-511, IDENTIFICATION BY MASS SPECTROMETRY, AND FUNCTION. RX PubMed=17924658; DOI=10.1021/bi700956c; RA Castonguay R., Halim D., Morin M., Furtos A., Lherbet C., Bonneil E., RA Thibault P., Keillor J.W.; RT "Kinetic characterization and identification of the acylation and RT glycosylation sites of recombinant human gamma-glutamyltranspeptidase."; RL Biochemistry 46:12253-12262(2007). RN [21] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-120; ASN-230 AND ASN-511. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of multiple RT enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [22] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-120. RC TISSUE=Leukemic T-cell; RX PubMed=19349973; DOI=10.1038/nbt.1532; RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., RA Schiess R., Aebersold R., Watts J.D.; RT "Mass-spectrometric identification and relative quantification of N-linked RT cell surface glycoproteins."; RL Nat. Biotechnol. 27:378-386(2009). RN [23] RP GLYCOSYLATION AT ASN-95; ASN-120; ASN-230; ASN-266; ASN-297; ASN-344 AND RP ASN-511. RX PubMed=20622017; DOI=10.1074/jbc.m110.145938; RA West M.B., Segu Z.M., Feasley C.L., Kang P., Klouckova I., Li C., RA Novotny M.V., West C.M., Mechref Y., Hanigan M.H.; RT "Analysis of site-specific glycosylation of renal and hepatic gamma- RT glutamyl transpeptidase from normal human tissue."; RL J. Biol. Chem. 285:29511-29524(2010). RN [24] RP CATALYTIC ACTIVITY, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE RP SPECIFICITY, ACTIVITY REGULATION, AND PATHWAY. RX PubMed=21447318; DOI=10.1016/j.ab.2011.03.026; RA Wickham S., West M.B., Cook P.F., Hanigan M.H.; RT "Gamma-glutamyl compounds: substrate specificity of gamma-glutamyl RT transpeptidase enzymes."; RL Anal. Biochem. 414:208-214(2011). RN [25] RP FUNCTION, CATALYTIC ACTIVITY, AUTOCATALYTIC CLEAVAGE, ACTIVITY REGULATION, RP SUBCELLULAR LOCATION, GLYCOSYLATION, AND MUTAGENESIS OF CYS-192 AND RP GLU-193. RX PubMed=23682772; DOI=10.1089/ars.2012.4997; RA West M.B., Wickham S., Parks E.E., Sherry D.M., Hanigan M.H.; RT "Human GGT2 does not autocleave into a functional enzyme: a cautionary tale RT for interpretation of microarray data on redox signaling."; RL Antioxid. Redox Signal. 19:1877-1888(2013). RN [26] RP X-RAY CRYSTALLOGRAPHY (1.67 ANGSTROMS) IN COMPLEX WITH GLUTAMATE AND RP CHLORIDE IONS, FUNCTION, CATALYTIC ACTIVITY, AUTOCATALYTIC CLEAVAGE, RP SUBUNIT, MUTAGENESIS OF GLN-545, DISULFIDE BONDS, AND GLYCOSYLATION AT RP ASN-95; ASN-120; ASN-230; ASN-266; ASN-344 AND ASN-511. RX PubMed=24047895; DOI=10.1074/jbc.m113.498139; RA West M.B., Chen Y., Wickham S., Heroux A., Cahill K., Hanigan M.H., RA Mooers B.H.; RT "Novel insights into eukaryotic gamma-glutamyl transpeptidase 1 from the RT crystal structure of the glutamate-bound human enzyme."; RL J. Biol. Chem. 288:31902-31913(2013). RN [27] {ECO:0007744|PDB:4Z9O, ECO:0007744|PDB:4ZBK, ECO:0007744|PDB:4ZC6, ECO:0007744|PDB:4ZCG} RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH SERINE-BORATE AND RP GLUTAMATE, AND GLYCOSYLATION AT ASN-95; ASN-120; ASN-230; ASN-266; ASN-344 RP AND ASN-511. RX PubMed=26013825; DOI=10.1074/jbc.m115.659680; RA Terzyan S.S., Burgett A.W., Heroux A., Smith C.A., Mooers B.H., RA Hanigan M.H.; RT "Human gamma-Glutamyl Transpeptidase 1: Structures of the free enzyme, RT inhibitor-bound tetrahedral transition states, and glutamate-bound enzyme RT reveal novel movement within the active site during catalysis."; RL J. Biol. Chem. 290:17576-17586(2015). RN [28] RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=27791009; DOI=10.1073/pnas.1607003113; RA Dalli J., Vlasakov I., Riley I.R., Rodriguez A.R., Spur B.W., Petasis N.A., RA Chiang N., Serhan C.N.; RT "Maresin conjugates in tissue regeneration biosynthesis enzymes in human RT macrophages."; RL Proc. Natl. Acad. Sci. U.S.A. 113:12232-12237(2016). RN [29] RP INVOLVEMENT IN GLUTH. RX PubMed=29483667; DOI=10.1038/s41431-018-0122-6; RA Darin N., Leckstroem K., Sikora P., Lindgren J., Almen G., Asin-Cayuela J.; RT "Gamma-glutamyl transpeptidase deficiency caused by a large homozygous RT intragenic deletion in GGT1."; RL Eur. J. Hum. Genet. 26:808-817(2018). CC -!- FUNCTION: Cleaves the gamma-glutamyl bond of extracellular glutathione CC (gamma-Glu-Cys-Gly), glutathione conjugates (such as maresin conjugate CC (13R)-S-glutathionyl-(14S)-hydroxy-(4Z,7Z,9E,11E,16Z,19Z)- CC docosahexaenoate, MCTR1) and other gamma-glutamyl compounds (such as CC leukotriene C4, LTC4) (PubMed:17924658, PubMed:21447318, CC PubMed:27791009). The metabolism of glutathione by GGT1 releases free CC glutamate and the dipeptide cysteinyl-glycine, which is hydrolyzed to CC cysteine and glycine by dipeptidases (PubMed:27791009). In the presence CC of high concentrations of dipeptides and some amino acids, can also CC catalyze a transpeptidation reaction, transferring the gamma-glutamyl CC moiety to an acceptor amino acid to form a new gamma-glutamyl compound CC (PubMed:17924658, PubMed:7673200, PubMed:7759490, PubMed:8095045, CC PubMed:8827453, PubMed:21447318). Contributes to cysteine homeostasis, CC glutathione homeostasis and in the conversion of the leukotriene LTC4 CC to LTD4. {ECO:0000269|PubMed:17924658, ECO:0000269|PubMed:20622017, CC ECO:0000269|PubMed:21447318, ECO:0000269|PubMed:24047895, CC ECO:0000269|PubMed:27791009, ECO:0000269|PubMed:7673200, CC ECO:0000269|PubMed:7759490, ECO:0000269|PubMed:8095045, CC ECO:0000269|PubMed:8827453}. CC -!- FUNCTION: [Isoform 3]: Seems to be inactive. CC {ECO:0000269|PubMed:7689219}. 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:17924658, CC ECO:0000269|PubMed:21447318, ECO:0000269|PubMed:23682772, CC ECO:0000269|PubMed:7673200, ECO:0000269|PubMed:7759490, CC ECO:0000269|PubMed:8095045, ECO:0000269|PubMed:8827453}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23905; CC Evidence={ECO:0000305|PubMed:8095045}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:23906; CC Evidence={ECO:0000250|UniProtKB:P07314}; 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:17924658, ECO:0000269|PubMed:21447318}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:28808; CC Evidence={ECO:0000305|PubMed:21447318}; 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:17924658, ECO:0000269|PubMed:21447318, CC ECO:0000269|PubMed:27791009}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59469; CC Evidence={ECO:0000305|PubMed:21447318, ECO:0000305|PubMed:27791009}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + leukotriene C4 = L-glutamate + leukotriene D4; CC Xref=Rhea:RHEA:31563, ChEBI:CHEBI:15377, ChEBI:CHEBI:29985, CC ChEBI:CHEBI:57973, ChEBI:CHEBI:63166; EC=3.4.19.14; CC Evidence={ECO:0000269|PubMed:21447318}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31564; CC Evidence={ECO:0000305|PubMed:21447318}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(13R)-S-glutathionyl-(14S)-hydroxy-(4Z,7Z,9E,11E,16Z,19Z)- CC docosahexaenoate + H2O = (13R)-S-cysteinylglycyl-(14S)-hydroxy- CC (4Z,7Z,9E,11E,16Z,19Z)-docosahexaenoate + L-glutamate; CC Xref=Rhea:RHEA:53512, ChEBI:CHEBI:15377, ChEBI:CHEBI:29985, CC ChEBI:CHEBI:137407, ChEBI:CHEBI:137408; CC Evidence={ECO:0000269|PubMed:27791009}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53513; CC Evidence={ECO:0000305|PubMed:27791009}; CC -!- ACTIVITY REGULATION: Activated by autocatalytic cleavage CC (PubMed:23682772). Inhibited by serine-borate (PubMed:21447318). CC {ECO:0000269|PubMed:21447318, ECO:0000269|PubMed:23682772}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=11 mM for glycylglycine {ECO:0000269|PubMed:7759490}; CC KM=10.6 uM for glutathione {ECO:0000269|PubMed:21447318}; CC KM=8.8 uM for oxidized-glutathione {ECO:0000269|PubMed:21447318}; CC KM=1.3 mM for D-gamma-glutamyl-p-nitroanalide CC {ECO:0000269|PubMed:7759490}; CC KM=9.9 uM for S-methylglutathion {ECO:0000269|PubMed:21447318}; CC KM=33.4 uM for gamma-glutamyl leucine {ECO:0000269|PubMed:21447318}; CC KM=10.8 uM for leukotriene C4 {ECO:0000269|PubMed:21447318}; CC KM=4.6 uM for CC (13R)-S-glutathionyl-(14S)-hydroxy-(4Z,7Z,9E,11E,16Z,19Z)-docosahexaenoate CC {ECO:0000269|PubMed:27791009}; CC -!- PATHWAY: Lipid metabolism; leukotriene D4 biosynthesis. CC {ECO:0000269|PubMed:21447318}. CC -!- PATHWAY: Sulfur metabolism; glutathione metabolism. CC {ECO:0000269|PubMed:21447318}. CC -!- SUBUNIT: Heterodimer composed of the light and heavy chains. The active CC site is located in the light chain. {ECO:0000269|PubMed:24047895, CC ECO:0000269|PubMed:8095045}. CC -!- INTERACTION: CC P19440-3; Q92993: KAT5; NbExp=3; IntAct=EBI-21558069, EBI-399080; CC P19440-3; Q8TAP4-4: LMO3; NbExp=3; IntAct=EBI-21558069, EBI-11742507; CC P19440-3; P17252: PRKCA; NbExp=3; IntAct=EBI-21558069, EBI-1383528; CC P19440-3; Q15047-2: SETDB1; NbExp=3; IntAct=EBI-21558069, EBI-9090795; CC P19440-3; P61981: YWHAG; NbExp=3; IntAct=EBI-21558069, EBI-359832; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23682772, CC ECO:0000269|PubMed:8095045}; Single-pass type II membrane protein CC {ECO:0000250|UniProtKB:P07314}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P19440-1; Sequence=Displayed; CC Name=2; CC IsoId=P19440-2; Sequence=VSP_001746, VSP_001747; CC Name=3; CC IsoId=P19440-3; Sequence=VSP_008132; CC -!- TISSUE SPECIFICITY: Detected in fetal and adult kidney and liver, adult CC pancreas, stomach, intestine, placenta and lung. There are several CC other tissue-specific forms that arise from alternative promoter usage CC but that produce the same protein. CC -!- TISSUE SPECIFICITY: [Isoform 3]: Lung-specific. CC {ECO:0000269|PubMed:7689219}. CC -!- PTM: N-glycosylated on both chains. Contains hexoses, hexosamines and CC sialic acid residues. Glycosylation profiles tested in kidney and liver CC tissues reveal the presence of tissue-specific and site-specific glycan CC composition, despite the overlap in composition among the N-glycans. A CC total of 36 glycan compositions, with 40 unique structures are CC observed. Up to 15 different glycans are observed at a single site, CC with site-specific variation in glycan composition. The difference in CC glycosylation profiles in the 2 tissues do not affect the enzyme CC activity. {ECO:0000269|PubMed:15084671, ECO:0000269|PubMed:17924658, CC ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:19349973, CC ECO:0000269|PubMed:19463, ECO:0000269|PubMed:20622017, CC ECO:0000269|PubMed:23682772, ECO:0000269|PubMed:24047895, CC ECO:0000269|PubMed:2900635}. CC -!- PTM: Cleaved by autocatalysis into a large and a small subunit and the CC autocatalytic cleavage is essential to the functional activation of the CC enzyme. {ECO:0000269|PubMed:23682772}. CC -!- DISEASE: Glutathionuria (GLUTH) [MIM:231950]: A very rare, autosomal CC recessive metabolic disorder characterized by the presence of CC glutathione in the urine, due to generalized gamma-glutamyl CC transpeptidase deficiency. Most patients manifest mild to moderate CC intellectual disability, and behavioral disturbance. Seizures, tremor, CC marfanoid features and strabismus are observed in some patients. CC {ECO:0000269|PubMed:29483667}. Note=The disease is caused by variants CC affecting the gene represented in this entry. A large homozygous CC deletion that removes several exons of all isoforms of GGT1 has been CC found in one family affected by glutathionuria. CC {ECO:0000269|PubMed:29483667}. CC -!- MISCELLANEOUS: Cys-454 was thought to bind the gamma-glutamyl moiety, CC but mutagenesis of this residue had no effect on activity. CC {ECO:0000269|PubMed:7759490}. CC -!- MISCELLANEOUS: Chloride ions bound in the active site cavity may CC contribute to stabilize the protein fold. CC {ECO:0000305|PubMed:24047895}. CC -!- MISCELLANEOUS: [Isoform 1]: Produced by alternative promoter usage. CC -!- MISCELLANEOUS: [Isoform 2]: Produced by alternative splicing of isoform CC 1. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 3]: Produced by alternative promoter usage. CC {ECO:0000305}. CC -!- SIMILARITY: Belongs to the gamma-glutamyltransferase family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA35899.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Gamma-glutamyl transpeptidase entry; CC URL="https://en.wikipedia.org/wiki/Gamma_glutamyl_transpeptidase"; 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; J04131; AAA52547.1; -; mRNA. DR EMBL; M24087; AAA35899.1; ALT_INIT; mRNA. DR EMBL; M24903; AAA52546.1; -; mRNA. DR EMBL; J05235; AAA35889.1; -; mRNA. DR EMBL; X60069; CAA42674.1; -; mRNA. DR EMBL; L20490; AAA02884.1; -; mRNA. DR EMBL; L20493; AAA02886.1; -; mRNA. DR EMBL; CR456494; CAG30380.1; -; mRNA. DR EMBL; AP000356; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC025927; AAH25927.1; -; mRNA. DR EMBL; BC069473; AAH69473.1; -; mRNA. DR EMBL; BC069504; AAH69504.1; -; mRNA. DR EMBL; BC128238; AAI28239.1; -; mRNA. DR EMBL; BC128239; AAI28240.1; -; mRNA. DR CCDS; CCDS42992.1; -. [P19440-1] DR PIR; A31253; EKHUEX. DR PIR; A48987; A48987. DR PIR; A60439; A60439. DR PIR; JS0067; JS0067. DR PIR; PS0312; PS0312. DR RefSeq; NP_001275762.1; NM_001288833.1. [P19440-1] DR RefSeq; NP_038265.2; NM_013421.2. [P19440-1] DR RefSeq; NP_038347.2; NM_013430.2. [P19440-1] DR PDB; 4GDX; X-ray; 1.67 A; A=2-374, B=375-569. DR PDB; 4GG2; X-ray; 2.21 A; A=28-380, B=381-569. DR PDB; 4Z9O; X-ray; 2.30 A; A=28-380, B=381-569. DR PDB; 4ZBK; X-ray; 2.18 A; A=28-380, B=381-569. DR PDB; 4ZC6; X-ray; 2.10 A; A=28-380, B=381-569. DR PDB; 4ZCG; X-ray; 2.22 A; A=28-380, B=381-569. DR PDB; 5V4Q; X-ray; 2.20 A; A=28-380, B=381-569. DR PDBsum; 4GDX; -. DR PDBsum; 4GG2; -. DR PDBsum; 4Z9O; -. DR PDBsum; 4ZBK; -. DR PDBsum; 4ZC6; -. DR PDBsum; 4ZCG; -. DR PDBsum; 5V4Q; -. DR AlphaFoldDB; P19440; -. DR SMR; P19440; -. DR BioGRID; 108946; 23. DR IntAct; P19440; 11. DR MINT; P19440; -. DR STRING; 9606.ENSP00000248923; -. DR BindingDB; P19440; -. DR ChEMBL; CHEMBL5696; -. DR DrugBank; DB00143; Glutathione. DR DrugCentral; P19440; -. DR SwissLipids; SLP:000001454; -. DR MEROPS; T03.006; -. DR GlyConnect; 1261; 27 N-Linked glycans (4 sites). DR GlyCosmos; P19440; 7 sites, 29 glycans. DR GlyGen; P19440; 7 sites, 29 N-linked glycans (4 sites). DR iPTMnet; P19440; -. DR PhosphoSitePlus; P19440; -. DR BioMuta; GGT1; -. DR DMDM; 93140064; -. DR CPTAC; CPTAC-2217; -. DR EPD; P19440; -. DR jPOST; P19440; -. DR MassIVE; P19440; -. DR MaxQB; P19440; -. DR PaxDb; 9606-ENSP00000383232; -. DR PeptideAtlas; P19440; -. DR ProteomicsDB; 53662; -. [P19440-1] DR ProteomicsDB; 53663; -. [P19440-2] DR ProteomicsDB; 53664; -. [P19440-3] DR Pumba; P19440; -. DR Antibodypedia; 24014; 502 antibodies from 37 providers. DR DNASU; 2678; -. DR Ensembl; ENST00000400380.5; ENSP00000383231.1; ENSG00000100031.19. [P19440-1] DR Ensembl; ENST00000400382.6; ENSP00000383232.1; ENSG00000100031.19. [P19440-1] DR Ensembl; ENST00000401885.5; ENSP00000384381.1; ENSG00000100031.19. [P19440-3] DR Ensembl; ENST00000403838.5; ENSP00000384820.1; ENSG00000100031.19. [P19440-3] DR Ensembl; ENST00000404532.5; ENSP00000385445.1; ENSG00000100031.19. [P19440-3] DR Ensembl; ENST00000425895.5; ENSP00000387499.1; ENSG00000100031.19. [P19440-2] DR GeneID; 2678; -. DR KEGG; hsa:2678; -. DR MANE-Select; ENST00000400382.6; ENSP00000383232.1; NM_001288833.2; NP_001275762.1. DR UCSC; uc003aan.2; human. [P19440-1] DR AGR; HGNC:4250; -. DR CTD; 2678; -. DR DisGeNET; 2678; -. DR GeneCards; GGT1; -. DR GeneReviews; GGT1; -. DR HGNC; HGNC:4250; GGT1. DR HPA; ENSG00000100031; Tissue enhanced (kidney, liver). DR MalaCards; GGT1; -. DR MIM; 231950; phenotype. DR MIM; 612346; gene. DR neXtProt; NX_P19440; -. DR OpenTargets; ENSG00000100031; -. DR Orphanet; 33573; Gamma-glutamyl transpeptidase deficiency. DR PharmGKB; PA28662; -. DR VEuPathDB; HostDB:ENSG00000100031; -. DR eggNOG; KOG2410; Eukaryota. DR GeneTree; ENSGT00940000154601; -. DR HOGENOM; CLU_014813_1_3_1; -. DR InParanoid; P19440; -. DR OMA; KATKNMF; -. DR OrthoDB; 2910309at2759; -. DR PhylomeDB; P19440; -. DR TreeFam; TF313608; -. DR BioCyc; MetaCyc:MONOMER66-34394; -. DR PathwayCommons; P19440; -. DR Reactome; R-HSA-174403; Glutathione synthesis and recycling. DR Reactome; R-HSA-2142691; Synthesis of Leukotrienes (LT) and Eoxins (EX). DR Reactome; R-HSA-5423646; Aflatoxin activation and detoxification. DR Reactome; R-HSA-5579022; Defective GGT1 causes GLUTH. DR Reactome; R-HSA-9035968; Defective GGT1 in aflatoxin detoxification causes GLUTH. DR Reactome; R-HSA-9664535; LTC4-CYSLTR mediated IL4 production. DR Reactome; R-HSA-9753281; Paracetamol ADME. DR SABIO-RK; P19440; -. DR SignaLink; P19440; -. DR UniPathway; UPA00204; -. DR UniPathway; UPA00880; -. DR BioGRID-ORCS; 2678; 104 hits in 1073 CRISPR screens. DR ChiTaRS; GGT1; human. DR GeneWiki; GGT1; -. DR GenomeRNAi; 2678; -. DR Pharos; P19440; Tbio. DR PRO; PR:P19440; -. DR Proteomes; UP000005640; Chromosome 22. DR RNAct; P19440; Protein. DR Bgee; ENSG00000100031; Expressed in right lobe of liver and 119 other cell types or tissues. DR ExpressionAtlas; P19440; baseline and differential. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0036374; F:glutathione hydrolase activity; IDA:UniProtKB. DR GO; GO:0103068; F:leukotriene C4 gamma-glutamyl transferase activity; IEA:UniProtKB-EC. DR GO; GO:0002951; F:leukotriene-C(4) hydrolase; IDA:BHF-UCL. DR GO; GO:0000048; F:peptidyltransferase activity; IDA:BHF-UCL. DR GO; GO:0006520; P:amino acid metabolic process; IDA:UniProtKB. DR GO; GO:0019344; P:cysteine biosynthetic process; ISS:UniProtKB. DR GO; GO:0006631; P:fatty acid metabolic process; IDA:BHF-UCL. DR GO; GO:0006536; P:glutamate metabolic process; IDA:UniProtKB. DR GO; GO:0006750; P:glutathione biosynthetic process; ISS:UniProtKB. DR GO; GO:0006751; P:glutathione catabolic process; IDA:UniProtKB. DR GO; GO:1901750; P:leukotriene D4 biosynthetic process; IDA:BHF-UCL. DR GO; GO:0006691; P:leukotriene metabolic process; IDA:UniProtKB. DR GO; GO:0031179; P:peptide modification; IBA:GO_Central. DR GO; GO:0006508; P:proteolysis; IMP:UniProtKB. DR GO; GO:0002682; P:regulation of immune system process; ISS:UniProtKB. DR GO; GO:0050727; P:regulation of inflammatory response; ISS:UniProtKB. DR GO; GO:0007283; P:spermatogenesis; ISS:UniProtKB. DR GO; GO:0031638; P:zymogen activation; IDA:UniProtKB. 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:SF56; GLUTATHIONE HYDROLASE 1 PROENZYME-RELATED; 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. DR Genevisible; P19440; HS. PE 1: Evidence at protein level; KW 3D-structure; Acyltransferase; Alternative promoter usage; KW Alternative splicing; Cell membrane; Direct protein sequencing; KW Disease variant; Disulfide bond; Glutathione biosynthesis; Glycoprotein; KW Hydrolase; Intellectual disability; Lipid metabolism; Membrane; Protease; KW Reference proteome; Sialic acid; Signal-anchor; Transferase; Transmembrane; KW Transmembrane helix; Zymogen. FT CHAIN 1..380 FT /note="Glutathione hydrolase 1 heavy chain" FT /id="PRO_0000011058" FT CHAIN 381..569 FT /note="Glutathione hydrolase 1 light chain" FT /evidence="ECO:0000269|PubMed:2907498" FT /id="PRO_0000011059" FT TOPO_DOM 1..4 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:P07314" FT TRANSMEM 5..26 FT /note="Helical; Signal-anchor for type II membrane protein" FT /evidence="ECO:0000250|UniProtKB:P07314" FT TOPO_DOM 27..569 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:P07314" FT ACT_SITE 381 FT /note="Nucleophile" FT /evidence="ECO:0000269|PubMed:17924658, FT ECO:0000269|PubMed:26013825" FT BINDING 107 FT /ligand="L-glutamate" FT /ligand_id="ChEBI:CHEBI:29985" FT /evidence="ECO:0000269|PubMed:24047895" FT BINDING 399..401 FT /ligand="L-glutamate" FT /ligand_id="ChEBI:CHEBI:29985" FT /evidence="ECO:0000269|PubMed:24047895, FT ECO:0000269|PubMed:26013825" FT BINDING 423 FT /ligand="L-glutamate" FT /ligand_id="ChEBI:CHEBI:29985" FT /evidence="ECO:0000269|PubMed:26013825" FT BINDING 451..452 FT /ligand="L-glutamate" FT /ligand_id="ChEBI:CHEBI:29985" FT /evidence="ECO:0000269|PubMed:24047895, FT ECO:0000269|PubMed:26013825" FT BINDING 474 FT /ligand="L-glutamate" FT /ligand_id="ChEBI:CHEBI:29985" FT /evidence="ECO:0000269|PubMed:26013825" FT CARBOHYD 95 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:20622017, FT ECO:0000269|PubMed:24047895, ECO:0000269|PubMed:26013825" FT CARBOHYD 120 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:17924658, FT ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:19349973, FT ECO:0000269|PubMed:20622017, ECO:0000269|PubMed:24047895, FT ECO:0000269|PubMed:26013825" FT CARBOHYD 230 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:20622017, ECO:0000269|PubMed:24047895, FT ECO:0000269|PubMed:26013825" FT CARBOHYD 266 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:17924658, FT ECO:0000269|PubMed:20622017, ECO:0000269|PubMed:24047895, FT ECO:0000269|PubMed:26013825" FT CARBOHYD 297 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:20622017" FT CARBOHYD 344 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:17924658, FT ECO:0000269|PubMed:20622017, ECO:0000269|PubMed:24047895, FT ECO:0000269|PubMed:26013825" FT CARBOHYD 511 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:15084671, FT ECO:0000269|PubMed:17924658, ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:20622017, ECO:0000269|PubMed:24047895, FT ECO:0000269|PubMed:26013825" FT DISULFID 50..74 FT /evidence="ECO:0000269|PubMed:24047895" FT DISULFID 192..196 FT /evidence="ECO:0000269|PubMed:24047895" FT VAR_SEQ 1..344 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:7689219" FT /id="VSP_008132" FT VAR_SEQ 341..366 FT /note="VVRNMTSEFFAAQLRAQISDDTTHPI -> ASSGVSAGGPQHDLRVLRCPAP FT GPDL (in isoform 2)" FT /evidence="ECO:0000303|PubMed:1968061" FT /id="VSP_001746" FT VAR_SEQ 367..569 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:1968061" FT /id="VSP_001747" FT VARIANT 51 FT /note="S -> L (in dbSNP:rs2330837)" FT /id="VAR_025545" FT VARIANT 52 FT /note="K -> E (in dbSNP:rs2330838)" FT /id="VAR_018373" FT VARIANT 177 FT /note="A -> V (in dbSNP:rs3895576)" FT /id="VAR_018374" FT VARIANT 272 FT /note="V -> A (in dbSNP:rs4049829)" FT /evidence="ECO:0000269|PubMed:1378736, FT ECO:0000269|PubMed:1968061, ECO:0000269|PubMed:2563599, FT ECO:0000269|PubMed:2568315, ECO:0000269|PubMed:2904146, FT ECO:0000269|PubMed:2907498" FT /id="VAR_018372" FT VARIANT 419 FT /note="N -> D (in dbSNP:rs17004876)" FT /id="VAR_025546" FT VARIANT 435 FT /note="V -> A (in dbSNP:rs1062459)" FT /id="VAR_049181" FT MUTAGEN 100 FT /note="K->N: No effect on gamma-glutamyltranspeptidase FT activity." FT /evidence="ECO:0000269|PubMed:8095045" FT MUTAGEN 102 FT /note="E->Q: No effect on gamma-glutamyltranspeptidase FT activity." FT /evidence="ECO:0000269|PubMed:8095045" FT MUTAGEN 107 FT /note="R->K: Reduces enzyme gamma-glutamyltranspeptidase FT activity by 99%." FT /evidence="ECO:0000269|PubMed:8095045" FT MUTAGEN 107 FT /note="R->Q,H: Abolishes gamma-glutamyltranspeptidase FT activity." FT /evidence="ECO:0000269|PubMed:8095045" FT MUTAGEN 108 FT /note="E->Q: Reduces gamma-glutamyltranspeptidase activity FT by 98%." FT /evidence="ECO:0000269|PubMed:8095045" FT MUTAGEN 112 FT /note="R->Q: No effect on gamma-glutamyltranspeptidase FT activity." FT /evidence="ECO:0000269|PubMed:8095045" FT MUTAGEN 139 FT /note="R->Q: No effect on gamma-glutamyltranspeptidase FT activity." FT /evidence="ECO:0000269|PubMed:8095045" FT MUTAGEN 147 FT /note="R->Q: No effect on gamma-glutamyltranspeptidase FT activity." FT /evidence="ECO:0000269|PubMed:8095045" FT MUTAGEN 150 FT /note="R->Q: No effect on gamma-glutamyltranspeptidase FT activity." FT /evidence="ECO:0000269|PubMed:8095045" FT MUTAGEN 192 FT /note="C->W: Loss of autocatalytic cleavage, cell membrane FT localization and decrease in gamma-glutamyltranspeptidase FT activity; when associated with Y-193." FT /evidence="ECO:0000269|PubMed:23682772" FT MUTAGEN 193 FT /note="E->Y: Loss of autocatalytic cleavage, cell membrane FT localization and decrease in gamma-glutamyltranspeptidase FT activity; when associated with W-192." FT /evidence="ECO:0000269|PubMed:23682772" FT MUTAGEN 383 FT /note="H->A: Reduces gamma-glutamyltranspeptidase activity FT by 66%." FT /evidence="ECO:0000269|PubMed:8827453" FT MUTAGEN 385 FT /note="S->A: No effect on gamma-glutamyltranspeptidase FT activity." FT /evidence="ECO:0000269|PubMed:7673200" FT MUTAGEN 413 FT /note="S->A: No effect on gamma-glutamyltranspeptidase FT activity." FT /evidence="ECO:0000269|PubMed:7673200" FT MUTAGEN 422 FT /note="D->A: Reduces enzyme gamma-glutamyltranspeptidase FT activity by 90%." FT /evidence="ECO:0000269|PubMed:7759490" FT MUTAGEN 423 FT /note="D->A: Abolishes gamma-glutamyltranspeptidase FT activity. Increases KM for D-gamma-glutamyl-p-nitroanalide FT by over 1000-fold." FT /evidence="ECO:0000269|PubMed:7759490" FT MUTAGEN 425 FT /note="S->A: No effect on gamma-glutamyltranspeptidase FT activity." FT /evidence="ECO:0000269|PubMed:7673200" FT MUTAGEN 451 FT /note="S->A: Reduces gamma-glutamyltranspeptidase activity FT by 99%. Abolishes activity; when associated with A-452." FT /evidence="ECO:0000269|PubMed:7673200" FT MUTAGEN 452 FT /note="S->A: Reduces gamma-glutamyltranspeptidase activity FT by 99%. Abolishes activity; when associated with A-451." FT /evidence="ECO:0000269|PubMed:7673200" FT MUTAGEN 454 FT /note="C->A: No effect on gamma-glutamyltranspeptidase FT activity." FT /evidence="ECO:0000269|PubMed:7759490" FT MUTAGEN 505 FT /note="H->A: Reduces gamma-glutamyltranspeptidase activity FT by 90%." FT /evidence="ECO:0000269|PubMed:8827453" FT MUTAGEN 545 FT /note="Q->K: Reduces enzyme activity by 97%." FT /evidence="ECO:0000269|PubMed:24047895" FT CONFLICT 30..31 FT /note="SK -> KS (in Ref. 11; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 47 FT /note="A -> K (in Ref. 11; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 139 FT /note="R -> E (in Ref. 5; AAA35889)" FT /evidence="ECO:0000305" FT CONFLICT 356 FT /note="A -> S (in Ref. 10; AAI28240)" FT /evidence="ECO:0000305" FT CONFLICT 361 FT /note="D -> H (in Ref. 10; AAI28240)" FT /evidence="ECO:0000305" FT CONFLICT 372 FT /note="E -> D (in Ref. 7; AAA02886)" FT /evidence="ECO:0000305" FT STRAND 36..40 FT /evidence="ECO:0007829|PDB:4GDX" FT STRAND 42..44 FT /evidence="ECO:0007829|PDB:4GDX" FT HELIX 48..59 FT /evidence="ECO:0007829|PDB:4GDX" FT HELIX 64..78 FT /evidence="ECO:0007829|PDB:4GDX" FT TURN 79..82 FT /evidence="ECO:0007829|PDB:4GDX" FT STRAND 87..95 FT /evidence="ECO:0007829|PDB:4GDX" FT TURN 96..99 FT /evidence="ECO:0007829|PDB:4GDX" FT STRAND 100..106 FT /evidence="ECO:0007829|PDB:4GDX" FT HELIX 122..126 FT /evidence="ECO:0007829|PDB:4GDX" FT HELIX 129..131 FT /evidence="ECO:0007829|PDB:4GDX" FT HELIX 137..148 FT /evidence="ECO:0007829|PDB:4GDX" FT HELIX 153..166 FT /evidence="ECO:0007829|PDB:4GDX" FT HELIX 172..180 FT /evidence="ECO:0007829|PDB:4GDX" FT HELIX 182..187 FT /evidence="ECO:0007829|PDB:4GDX" FT HELIX 189..195 FT /evidence="ECO:0007829|PDB:4GDX" FT STRAND 206..208 FT /evidence="ECO:0007829|PDB:4GDX" FT HELIX 211..223 FT /evidence="ECO:0007829|PDB:4GDX" FT HELIX 226..229 FT /evidence="ECO:0007829|PDB:4GDX" FT HELIX 234..243 FT /evidence="ECO:0007829|PDB:4GDX" FT HELIX 250..255 FT /evidence="ECO:0007829|PDB:4GDX" FT STRAND 259..263 FT /evidence="ECO:0007829|PDB:4GDX" FT STRAND 265..269 FT /evidence="ECO:0007829|PDB:4GDX" FT STRAND 272..276 FT /evidence="ECO:0007829|PDB:4GDX" FT HELIX 283..294 FT /evidence="ECO:0007829|PDB:4GDX" FT HELIX 300..303 FT /evidence="ECO:0007829|PDB:4GDX" FT HELIX 306..327 FT /evidence="ECO:0007829|PDB:4GDX" FT TURN 333..335 FT /evidence="ECO:0007829|PDB:4GDX" FT HELIX 339..345 FT /evidence="ECO:0007829|PDB:4GDX" FT HELIX 348..355 FT /evidence="ECO:0007829|PDB:4GDX" FT HELIX 366..369 FT /evidence="ECO:0007829|PDB:4GDX" FT STRAND 382..387 FT /evidence="ECO:0007829|PDB:4GDX" FT STRAND 393..399 FT /evidence="ECO:0007829|PDB:4GDX" FT TURN 403..406 FT /evidence="ECO:0007829|PDB:4GDX" FT STRAND 407..409 FT /evidence="ECO:0007829|PDB:4ZC6" FT TURN 411..413 FT /evidence="ECO:0007829|PDB:4GDX" FT HELIX 420..423 FT /evidence="ECO:0007829|PDB:4GDX" FT STRAND 427..429 FT /evidence="ECO:0007829|PDB:5V4Q" FT STRAND 432..434 FT /evidence="ECO:0007829|PDB:4Z9O" FT HELIX 439..441 FT /evidence="ECO:0007829|PDB:4GDX" FT STRAND 456..460 FT /evidence="ECO:0007829|PDB:4GDX" FT STRAND 465..476 FT /evidence="ECO:0007829|PDB:4GDX" FT HELIX 477..489 FT /evidence="ECO:0007829|PDB:4GDX" FT HELIX 495..500 FT /evidence="ECO:0007829|PDB:4GDX" FT STRAND 508..511 FT /evidence="ECO:0007829|PDB:4GDX" FT STRAND 513..515 FT /evidence="ECO:0007829|PDB:4GDX" FT HELIX 521..529 FT /evidence="ECO:0007829|PDB:4GDX" FT STRAND 534..536 FT /evidence="ECO:0007829|PDB:4GDX" FT STRAND 543..550 FT /evidence="ECO:0007829|PDB:4GDX" FT STRAND 553..557 FT /evidence="ECO:0007829|PDB:4GDX" FT TURN 560..562 FT /evidence="ECO:0007829|PDB:4GDX" SQ SEQUENCE 569 AA; 61410 MW; 71AE12485239A69F CRC64; MKKKLVVLGL LAVVLVLVIV GLCLWLPSAS KEPDNHVYTR AAVAADAKQC SKIGRDALRD GGSAVDAAIA ALLCVGLMNA HSMGIGGGLF LTIYNSTTRK AEVINAREVA PRLAFATMFN SSEQSQKGGL SVAVPGEIRG YELAHQRHGR LPWARLFQPS IQLARQGFPV GKGLAAALEN KRTVIEQQPV LCEVFCRDRK VLREGERLTL PQLADTYETL AIEGAQAFYN GSLTAQIVKD IQAAGGIVTA EDLNNYRAEL IEHPLNISLG DVVLYMPSAP LSGPVLALIL NILKGYNFSR ESVESPEQKG LTYHRIVEAF RFAYAKRTLL GDPKFVDVTE VVRNMTSEFF AAQLRAQISD DTTHPISYYK PEFYTPDDGG TAHLSVVAED GSAVSATSTI NLYFGSKVRS PVSGILFNNE MDDFSSPSIT NEFGVPPSPA NFIQPGKQPL SSMCPTIMVG QDGQVRMVVG AAGGTQITTA TALAIIYNLW FGYDVKRAVE EPRLHNQLLP NVTTVERNID QAVTAALETR HHHTQIASTF IAVVQAIVRT AGGWAAASDS RKGGEPAGY //