NameGamma-glutamyltranspeptidase 1
Synonyms
  • 2.3.2.2
  • Gamma-glutamyltransferase 1
  • GGT
  • GGT 1
  • Glutathione hydrolase 1
  • Leukotriene-C4 hydrolase
Gene NameGGT1
OrganismHuman
Amino acid sequence
>lcl|BSEQ0001772|Gamma-glutamyltranspeptidase 1
MKKKLVVLGLLAVVLVLVIVGLCLWLPSASKEPDNHVYTRAAVAADAKQCSKIGRDALRD
GGSAVDAAIAALLCVGLMNAHSMGIGGGLFLTIYNSTTRKAEVINAREVAPRLAFATMFN
SSEQSQKGGLSVAVPGEIRGYELAHQRHGRLPWARLFQPSIQLARQGFPVGKGLAAALEN
KRTVIEQQPVLCEVFCRDRKVLREGERLTLPQLADTYETLAIEGAQAFYNGSLTAQIVKD
IQAAGGIVTAEDLNNYRAELIEHPLNISLGDVVLYMPSAPLSGPVLALILNILKGYNFSR
ESVESPEQKGLTYHRIVEAFRFAYAKRTLLGDPKFVDVTEVVRNMTSEFFAAQLRAQISD
DTTHPISYYKPEFYTPDDGGTAHLSVVAEDGSAVSATSTINLYFGSKVRSPVSGILFNNE
MDDFSSPSITNEFGVPPSPANFIQPGKQPLSSMCPTIMVGQDGQVRMVVGAAGGTQITTA
TALAIIYNLWFGYDVKRAVEEPRLHNQLLPNVTTVERNIDQAVTAALETRHHHTQIASTF
IAVVQAIVRTAGGWAAASDSRKGGEPAGY
Number of residues569
Molecular Weight61409.67
Theoretical pI7.14
GO Classification
Functions
  • gamma-glutamyltransferase activity
  • glutathione hydrolase activity
Processes
  • regulation of immune system process
  • leukotriene biosynthetic process
  • regulation of inflammatory response
  • xenobiotic metabolic process
  • arachidonic acid metabolic process
  • leukotriene metabolic process
  • cysteine biosynthetic process
  • glutathione metabolic process
  • spermatogenesis
  • glutamate metabolic process
  • glutathione biosynthetic process
  • glutathione derivative biosynthetic process
  • zymogen activation
  • cellular amino acid metabolic process
  • small molecule metabolic process
  • glutathione catabolic process
Components
  • extracellular exosome
  • anchored component of external side of plasma membrane
  • plasma membrane
  • extracellular space
  • integral component of membrane
General FunctionGlutathione hydrolase activity
Specific FunctionCleaves the gamma-glutamyl bond of extracellular glutathione (gamma-Glu-Cys-Gly), glutathione conjugates, and other gamma-glutamyl compounds. The metabolism of glutathione releases free glutamate and the dipeptide, cysteinyl-glycine, which is hydrolyzed to cysteine and glycine by dipeptidases. In the presence of high concentrations of dipeptides and some amino acids, can also catalyze a transpeptidation reaction, transferring the gamma-glutamyl moiety to an acceptor amino acid to form a new gamma-glutamyl compound. Initiates extracellular glutathione (GSH) breakdown, provides cells with a local cysteine supply and contributes to maintain intracellular GSH level. It is part of the cell antioxidant defense mechanism. Isoform 3 seems to be inactive.
Pfam Domain Function
Transmembrane Regions5-26
GenBank Protein ID183138
UniProtKB IDP19440
UniProtKB Entry NameGGT1_HUMAN
Cellular LocationCell membrane
Gene sequence
>lcl|BSEQ0010627|Gamma-glutamyltranspeptidase 1 (GGT1)
ATGAAGAAGAAGTTAGTGGTGCTGGGCCTGCTGGCCGTGGTCCTGGTGCTGGTCATTGTC
GGCCTCTGTCTCTGGCTGCCCTCAGCCTCCAAGGAACCTGACAACCATGTGTACACCAGG
GCTGCCGTGGCCGCGGATGCCAAGCAGTGCTCGAAGATTGGGAGGGATGCACTGCGGGAC
GGTGGCTCTGCGGTGGATGCAGCCATTGCAGCCCTGTTGTGTGTGGGGCTCATGAATGCC
CACAGCATGGGCATCGGGGGTGGCCTCTTCCTCACCATCTACAACAGCACCACACGAAAA
GCTGAGGTCATCAACGCCCGCGAGGTGGCCCCCAGGCTGGCCTTTGCCACCATGTTCAAC
AGCTCGGAGCAGTCCCAGAAGGGGGGGCTGTCGGTGGCGGTGCCTGGGGAGATCCGAGGC
TATGAGCTGGCACACCAGCGGCATGGGCGGCTGCCCTGGGCTCGCCTCTTCCAGCCCAGC
ATCCAGCTGGCCCGCCAGGGCTTCCCCGTGGGCAAGGGCTTGGCGGCAGCCCTGGAAAAC
AAGCGGACCGTCATCGAGCAGCAGCCTGTCTTGTGTGAGGTGTTCTGCCGGGATAGAAAG
GTGCTTCGGGAGGGGGAGAGACTGACCCTGCCGCAGCTGGCTGACACCTACGAGACGCTG
GCCATCGAGGGTGCCCAGGCCTTCTACAACGGCAGCCTCACGGCCCAGATTGTGAAGGAC
ATCCAGGCGGCCGGGGGCATTGTGACAGCTGAGGACCTGAACAACTACCGTGCTGAGCTG
ATCGAGCACCCGCTGAACATCAGCCTGGGAGACGTGGTGCTGTACATGCCCAGTGCGCCG
CTCAGCGGGCCCGTGCTGGCCCTCATCCTCAACATCCTCAAAGGGTACAACTTCTCCCGG
GAGAGCGTGGAGAGCCCCGAGCAGAAGGGCCTGACGTACCACCGCATCGTAGAGGCTTTC
CGGTTTGCCTACGCCAAGAGGACCCTGCTTGGGGACCCCAAGTTTGTGGATGTGACTGAG
GTGGTCCGCAACATGACCTCCGAGTTCTTCGCTGCCCAGCTCCGGGCCCAGATCTCTGAC
GACACCACTCACCCGATCTCCTACTACAAGCCCGAGTTCTACACGCCGGATGACGGGGGC
ACTGCTCACCTGTCTGTCGTCGCAGAGGACGGCAGTGCTGTGTCCGCCACCAGCACCATC
AACCTCTACTTTGGCTCCAAGGTCCGCTCCCCGGTCAGCGGGATCCTGTTCAATAATGAA
ATGGACGACTTCAGCTCTCCCAGCATCACCAACGAGTTTGGGGTACCCCCCTCACCTGCC
AATTTCATCCAGCCAGGGAAGCAGCCGCTCTCGTCCATGTGCCCGACGATCATGGTGGGC
CAGGACGGCCAGGTCCGGATGGTGGTGGGAGCTGCTGGGGGCACACAGATCACCACGGCC
ACTGCACTGGCCATCATCTACAACCTCTGGTTCGGCTATGACGTGAAGCGGGCCGTGGAG
GAGCCCCGGCTGCACAACCAGCTTCTGCCCAACGTCACGACAGTGGAGAGAAACATTGAC
CAGGCAGTGACTGCAGCCCTGGAGACCCGGCACCATCACACCCAGATCGCGTCCACCTTC
ATCGCTGTGGTGCAAGCCATCGTCCGCACGGCTGGTGGCTGGGCAGCTGCCTCGGACTCC
AGGAAAGGCGGGGAGCCTGCCGGCTACTGA
GenBank Gene IDJ04131
GeneCard IDNot Available
GenAtlas IDGGT1
HGNC IDHGNC:4250
Chromosome Location22
Locus22q11.23
References
  1. Rajpert-De Meyts E, Heisterkamp N, Groffen J: Cloning and nucleotide sequence of human gamma-glutamyl transpeptidase. Proc Natl Acad Sci U S A. 1988 Dec;85(23):8840-4. 2904146
  2. Sakamuro D, Yamazoe M, Matsuda Y, Kangawa K, Taniguchi N, Matsuo H, Yoshikawa H, Ogasawara N: The primary structure of human gamma-glutamyl transpeptidase. Gene. 1988 Dec 15;73(1):1-9. 2907498
  3. Pitot HC, Goodspeed D, Dunn T, Hendrich S, Maronpot RR, Moran S: Regulation of the expression of some genes for enzymes of glutathione metabolism in hepatotoxicity and hepatocarcinogenesis. Toxicol Appl Pharmacol. 1989 Jan;97(1):23-34. 2563599
  4. Goodspeed DC, Dunn TJ, Miller CD, Pitot HC: Human gamma-glutamyl transpeptidase cDNA: comparison of hepatoma and kidney mRNA in the human and rat. Gene. 1989 Mar 15;76(1):1-9. 2568315
  5. Pawlak A, Cohen EH, Octave JN, Schweickhardt R, Wu SJ, Bulle F, Chikhi N, Baik JH, Siegrist S, Guellaen G: An alternatively processed mRNA specific for gamma-glutamyl transpeptidase in human tissues. J Biol Chem. 1990 Feb 25;265(6):3256-62. 1968061
  6. Courtay C, Oster T, Michelet F, Visvikis A, Diederich M, Wellman M, Siest G: Gamma-glutamyltransferase: nucleotide sequence of the human pancreatic cDNA. Evidence for a ubiquitous gamma-glutamyltransferase polypeptide in human tissues. Biochem Pharmacol. 1992 Jun 23;43(12):2527-33. 1378736
  7. Wetmore LA, Gerard C, Drazen JM: Human lung expresses unique gamma-glutamyl transpeptidase transcripts. Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7461-5. 7689219
  8. Collins JE, Wright CL, Edwards CA, Davis MP, Grinham JA, Cole CG, Goward ME, Aguado B, Mallya M, Mokrab Y, Huckle EJ, Beare DM, Dunham I: A genome annotation-driven approach to cloning the human ORFeome. Genome Biol. 2004;5(10):R84. Epub 2004 Sep 30. 15461802
  9. Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP, et al.: The DNA sequence of human chromosome 22. Nature. 1999 Dec 2;402(6761):489-95. 10591208
  10. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  11. Tate SS, Khadse V, Wellner D: Renal gamma-glutamyl transpeptidases: structural and immunological studies. Arch Biochem Biophys. 1988 May 1;262(2):397-408. 2896486
  12. Chikhi N, Holic N, Guellaen G, Laperche Y: Gamma-glutamyl transpeptidase gene organization and expression: a comparative analysis in rat, mouse, pig and human species. Comp Biochem Physiol B Biochem Mol Biol. 1999 Apr;122(4):367-80. 10392451
  13. Tate SS, Ross ME: Human kidney gamma-glutamyl transpeptidase. Catalytic properties, subunit structure, and localization of the gamma-glutamyl binding site on the light subunit. J Biol Chem. 1977 Sep 10;252(17):6042-5. 19463
  14. Tate SS, Galbraith RA: In vitro translation and processing of human hepatoma cell (Hep G2) gamma-glutamyl transpeptidase. Biochem Biophys Res Commun. 1988 Aug 15;154(3):1167-73. 2900635
  15. Ikeda Y, Fujii J, Taniguchi N: Significance of Arg-107 and Glu-108 in the catalytic mechanism of human gamma-glutamyl transpeptidase. Identification by site-directed mutagenesis. J Biol Chem. 1993 Feb 25;268(6):3980-5. 8095045
  16. Ikeda Y, Fujii J, Taniguchi N, Meister A: Human gamma-glutamyl transpeptidase mutants involving conserved aspartate residues and the unique cysteine residue of the light subunit. J Biol Chem. 1995 May 26;270(21):12471-5. 7759490
  17. Ikeda Y, Fujii J, Anderson ME, Taniguchi N, Meister A: Involvement of Ser-451 and Ser-452 in the catalysis of human gamma-glutamyl transpeptidase. J Biol Chem. 1995 Sep 22;270(38):22223-8. 7673200
  18. Ikeda Y, Fujii J, Taniguchi N: Effects of substitutions of the conserved histidine residues in human gamma-glutamyl transpeptidase. J Biochem. 1996 Jun;119(6):1166-70. 8827453
  19. Kristiansen TZ, Bunkenborg J, Gronborg M, Molina H, Thuluvath PJ, Argani P, Goggins MG, Maitra A, Pandey A: A proteomic analysis of human bile. Mol Cell Proteomics. 2004 Jul;3(7):715-28. Epub 2004 Apr 14. 15084671
  20. Castonguay R, Halim D, Morin M, Furtos A, Lherbet C, Bonneil E, Thibault P, Keillor JW: Kinetic characterization and identification of the acylation and glycosylation sites of recombinant human gamma-glutamyltranspeptidase. Biochemistry. 2007 Oct 30;46(43):12253-62. Epub 2007 Oct 9. 17924658
  21. Chen R, Jiang X, Sun D, Han G, Wang F, Ye M, Wang L, Zou H: Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry. J Proteome Res. 2009 Feb;8(2):651-61. doi: 10.1021/pr8008012. 19159218
  22. Wollscheid B, Bausch-Fluck D, Henderson C, O'Brien R, Bibel M, Schiess R, Aebersold R, Watts JD: Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins. Nat Biotechnol. 2009 Apr;27(4):378-86. doi: 10.1038/nbt.1532. Epub 2009 Apr 6. 19349973
  23. West MB, Segu ZM, Feasley CL, Kang P, Klouckova I, Li C, Novotny MV, West CM, Mechref Y, Hanigan MH: Analysis of site-specific glycosylation of renal and hepatic gamma-glutamyl transpeptidase from normal human tissue. J Biol Chem. 2010 Sep 17;285(38):29511-24. doi: 10.1074/jbc.M110.145938. Epub 2010 Jul 9. 20622017
  24. West MB, Wickham S, Parks EE, Sherry DM, Hanigan MH: Human GGT2 does not autocleave into a functional enzyme: A cautionary tale for interpretation of microarray data on redox signaling. Antioxid Redox Signal. 2013 Dec 1;19(16):1877-88. doi: 10.1089/ars.2012.4997. Epub 2013 Jun 28. 23682772
  25. West MB, Chen Y, Wickham S, Heroux A, Cahill K, Hanigan MH, Mooers BH: Novel insights into eukaryotic gamma-glutamyltranspeptidase 1 from the crystal structure of the glutamate-bound human enzyme. J Biol Chem. 2013 Nov 1;288(44):31902-13. doi: 10.1074/jbc.M113.498139. Epub 2013 Sep 18. 24047895