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MGP001195

UniProt Annotations

Entry Information
Gene Namegamma-glutamyltransferase 1
Protein EntryGGT1_HUMAN
UniProt IDP19440
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative promoter usage, Alternative splicing; Named isoforms=3; Name=1; IsoId=P19440-1; Sequence=Displayed; Note=Produced by alternative promoter usage.; Name=2; IsoId=P19440-2; Sequence=VSP_001746, VSP_001747; Note=Produced by alternative splicing of isoform 1.; Name=3; IsoId=P19440-3; Sequence=VSP_008132; Note=Produced by alternative promoter usage.;
Catalytic ActivityA (5-L-glutamyl)-peptide + an amino acid = a peptide + a 5-L-glutamyl amino acid.
Catalytic ActivityGlutathione + H(2)O = L-cysteinylglycine + L- glutamate.
Catalytic ActivityLeukotriene C(4) + H(2)O = leukotriene D(4) + L-glutamate.
DiseaseGlutathionuria (GLUTH) [MIM:231950]: Autosomal recessive disease. Note=The disease is caused by mutations affecting the gene represented in this entry.
Enzyme RegulationActivated by autocatalytic cleavage. {ECO:0000269|PubMed:23682772}.
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. {ECO:0000269|PubMed:20622017, ECO:0000269|PubMed:24047895, ECO:0000269|PubMed:7673200, ECO:0000269|PubMed:7759490, ECO:0000269|PubMed:8095045, ECO:0000269|PubMed:8827453}.
MiscellaneousChloride ions bound in the active site cavity may contribute to stabilize the protein fold.
MiscellaneousCys-454 was thought to bind the gamma-glutamyl moiety, but mutagenesis of this residue had no effect on activity.
PathwaySulfur metabolism; glutathione metabolism.
PtmCleaved by autocatalysis into a large and a small subunit and the autocatalytic cleavage is essential to the functional activation of the enzyme.
PtmN-glycosylated on both chains. Contains hexoses, hexosamines and sialic acid residues. Glycosylation profiles tested in kidney and liver tissues reveal the presence of tissue-specific and site- specific glycan composition, despite the overlap in composition among the N-glycans. A total of 36 glycan compositions, with 40 unique structures are observed. Up to 15 different glycans are observed at a single site, with site-specific variation in glycan composition. The difference in glycosylation profiles in the 2 tissues do not affect the enzyme activity. {ECO:0000269|PubMed:15084671, ECO:0000269|PubMed:17924658, ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:19349973, ECO:0000269|PubMed:19463, ECO:0000269|PubMed:20622017, ECO:0000269|PubMed:23682772, ECO:0000269|PubMed:24047895, ECO:0000269|PubMed:2900635}.
Sequence CautionSequence=AAA35899.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};
SimilarityBelongs to the gamma-glutamyltransferase family. {ECO:0000305}.
Subcellular LocationCell membrane {ECO:0000269|PubMed:23682772, ECO:0000269|PubMed:8095045}; Single-pass type II membrane protein {ECO:0000269|PubMed:23682772, ECO:0000269|PubMed:8095045}.
SubunitHeterodimer composed of the light and heavy chains. The active site is located in the light chain. {ECO:0000269|PubMed:24047895, ECO:0000269|PubMed:8095045}.
Tissue SpecificityDetected in fetal and adult kidney and liver, adult pancreas, stomach, intestine, placenta and lung. Isoform 3 is lung-specific. There are several other tissue-specific forms that arise from alternative promoter usage but that produce the same protein.
Web ResourceName=Wikipedia; Note=Gamma-glutamyl transpeptidase entry; URL="http://en.wikipedia.org/wiki/Gamma_glutamyl_transpeptidase";
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