Disease:


  • OMIM ID: 612339 . 612339
  • OMIM diseaseName:
  • OMIM diseaseClinical_Synopsis:
  • OMIM diseaseText: DESCRIPTION Gamma-glutamyltransferase-1 (GGT1; 612346) is a membrane-bound extracellular enzyme that cleaves gamma-glutamyl peptide bonds in glutathione and other peptides and transfers the gamma-glutamyl moiety to acceptors. Autocatalytic cleavage of the GGT1 precursor polypeptide produces a heavy chain and a light chain that associate with each other to form the functional enzyme. Light chain-only GGTs, such as GGTLC2, contain a region corresponding to the GGT1 light chain, but they lack the membrane-anchoring heavy chain region (Heisterkamp et al., 2008). CLONING Courtay et al. (1994) obtained partial genomic sequences of several GGT genes and pseudogenes, including GGTLC2, which they designated clone 1. Compared with other GGTs, GGTLC2 has a mutation at the splice donor of an 81-bp intron, resulting in an unspliced intron. RT-PCR detected GGTLC2 expression in sigmoid colon and placenta, with weaker expression in lung and thyroid, but not in other tissues examined. By 5-prime and 3-prime RACE of placenta cDNA, Leh et al. (1996) cloned GGTLC2, which they designated GGT type III. The deduced 260-amino acid protein lacks the large GGT subunit, but it retains the small GGT subunit. Compared with other GGTs, GGTLC2 has a 27-amino acid insertion due to the unspliced 81-bp intron. RT-PCR detected GGTLC2 in lymphocytes from nearly half of patients with acute lymphoblastic leukemia, but not in lymphocytes from healthy subjects nor in any hematopoietic cell line examined. Heisterkamp et al. (2008) noted that the glutamate-binding site of GGT1 includes 8 residues in its light chain and 1 residue (arg107) in its heavy chain. They determined that GGTLC2 contains residues corresponding to the 8 glutamate-binding residues in the GGT1 light chain, but it lacks a residue equivalent to arg107 in the GGT1 heavy chain. EST database analysis suggested that GGTLC2 expression is restricted to testis and germ cell tumors. MAPPING By genomic sequence analysis, Heisterkamp et al. (2008) mapped the GGTLC2 gene to chromosome 22q11.2.
  • OMIM diseaseSee_Also:
  • OMIM diseaseAllelic_Variants:
  • OMIM diseaseCreation_Date: Patricia A. Hartz: 10/3/2008
  • OMIM diseaseEdit_History_Data: mgross: 10/07/2008 mgross: 10/6/2008
  • OMIM diseaseContributors:
  • OMIM diseaseReference: 1. Courtay, C.; Heisterkamp, N.; Siest, G.; Groffen, J.: Expression of multiple gamma-glutamyltransferase genes in man. Biochem. J. 297: 503-508, 1994. 2. Heisterkamp, N.; Groffen, J.; Warburton, D.; Sneddon, T. P.: The human gamma-glutamyltransferase gene family. Hum. Genet. 123: 321-332, 2008. 3. Leh, H.; Courtay, C.; Gerardin, P.; Wellman, M.; Siest, G.; Visvikis, A.: Cloning and expression of a novel type (III) of human gamma-glutamyltransferase truncated mRNA. FEBS Lett. 394: 258-262, 1996.