The human gamma-glutamyltransferase gene family |
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Authors: | Nora Heisterkamp John Groffen David Warburton Tam P Sneddon |
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Institution: | (1) Division of Hematology/Oncology, The Saban Research Institute of Childrens Hospital, Los Angeles, CA 90027, USA;(2) Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA;(3) Developmental Biology Program and Department of Surgery, The Saban Research Institute of Childrens Hospital, Los Angeles, CA 90027, USA;(4) HUGO Gene Nomenclature Committee (HGNC), Department of Biology, University College London, London, NW1 2HE, UK |
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Abstract: | Assays for gamma-glutamyl transferase (GGT1, EC 2.3.2.2) activity in blood are widely used in a clinical setting to measure
tissue damage. The well-characterized GGT1 is an extracellular enzyme that is anchored to the plasma membrane of cells. There,
it hydrolyzes and transfers γ-glutamyl moieties from glutathione and other γ-glutamyl compounds to acceptors. As such, it
has a critical function in the metabolism of glutathione and in the conversion of the leukotriene LTC4 to LTD4. GGT deficiency
in man is rare and for the few patients reported to date, mutations in GGT1 have not been described. These patients do secrete glutathione in urine and fail to metabolize LTC4. Earlier pre-genome investigations
had indicated that besides GGT1, the human genome contains additional related genes or sequences. These sequences were given multiple different names, leading
to inconsistencies and confusion. Here we systematically evaluated all human sequences related to GGT1 using genomic and cDNA database searches and identified thirteen genes belonging to the extended GGT family, of which at least six appear to be active. In collaboration with the HUGO Gene Nomenclature Committee (HGNC) we have
designated possible active genes with nucleotide or amino acid sequence similarity to GGT1, as GGT5 (formerly GGL, GGTLA1/GGT-rel), GGT6 (formerly rat ggt6 homologue) and GGT7 (formerly GGTL3, GGT4). Two loci have the potential to encode only the light chain portion of GGT and have now been designated GGTLC1 (formerly GGTL6, GGTLA4) and GGTLC2. Of the five full-length genes, three lack of significant nucleotide sequence homology but have significant (GGT5, GGT7) or very limited (GGT6) amino acid similarity to GGT1 and belong to separate families. GGT6 and GGT7 have not yet been described, raising the possibility that leukotriene synthesis, glutathione metabolism or γ-glutamyl transfer
is regulated by their, as of yet uncharacterized, enzymatic activities. In view of the widespread clinical use of assays that
measure γ-glutamyl transfer activity, this would appear to be of significant interest.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. |
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