GGT1_HUMAN
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 03-AUG-2022, entry version 227.
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 (13R)-S-glutathionyl-(14S)-hydroxy-
CC (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 ---------------------------------------------------------------------------
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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; 19.
DR IntAct; P19440; 11.
DR MINT; P19440; -.
DR STRING; 9606.ENSP00000383232; -.
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 GlyGen; P19440; 7 sites, 26 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; P19440; -.
DR PeptideAtlas; P19440; -.
DR PRIDE; P19440; -.
DR ProteomicsDB; 53662; -. [P19440-1]
DR ProteomicsDB; 53663; -. [P19440-2]
DR ProteomicsDB; 53664; -. [P19440-3]
DR Antibodypedia; 24014; 469 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 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 PhylomeDB; P19440; -.
DR TreeFam; TF313608; -.
DR BioCyc; MetaCyc:MON66-34394; -.
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 1008 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 117 other tissues.
DR ExpressionAtlas; P19440; baseline and differential.
DR Genevisible; P19440; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0036374; F:glutathione hydrolase activity; IDA:UniProtKB.
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:0002951; F:leukotriene-C(4) hydrolase; IDA:BHF-UCL.
DR GO; GO:0000048; F:peptidyltransferase activity; IDA:BHF-UCL.
DR GO; GO:0006520; P:cellular 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 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 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
