Cloning and nucleotide sequence of human gamma-glutamyl transpeptidase

We have identified the gene for human gamma-glutamyl transpeptidase [GGT; glutamine:D-glutamyl-peptide 5-glutamyltransferase (also called gamma-glutamyltransferase), EC 2.3.2.2] in a BCR gene-related region located in band q11----qter of chromosome 22. Two cDNAs complementary to the GGT mRNA have been isolated from a human placental library constructed in phage lambda gt11. The largest cDNA has a size of 2535 base pairs (bp) and an open reading frame of 1707 nucleotides encoding 569 amino acids. By using a probe corresponding to this cDNA, a mRNA of approximately 2.4 kilobases was detected by RNA blot-hybridization analysis in mouse kidney RNA. The GGT precursor encoded by the coding sequence would have an estimated Mr of 61,400. We compared our nucleotide and deduced amino acid sequences with the published results of rat kidney cDNAs. The human and rat amino acid sequences are similar; however, a considerable discrepancy in nucleotide sequence was found within a 180-bp fragment of the heavy chain, resulting in a completely different amino acid sequence for this region. In addition, the 5' untranslated sequence of the human cDNA (669 bp) is substantially larger than that determined in the rat cDNA (227 bp). Our results may be valuable for further studies on the protein structure of human GGT as well as studies on the regulation of the enzyme.