- OMIM ID: 612339
- OMIM diseaseName:
- OMIM diseaseClinical_Synopsis:
- OMIM diseaseText:
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).
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
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.
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
- OMIM diseaseContributors:
- OMIM diseaseReference: 1. Courtay, C.; Heisterkamp, N.; Siest, G.; Groffen, J.: Expression
of multiple gamma-glutamyltransferase genes in man. Biochem. J. 297:
2. Heisterkamp, N.; Groffen, J.; Warburton, D.; Sneddon, T. P.: The
human gamma-glutamyltransferase gene family. Hum. Genet. 123: 321-332,
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.