gamma-glutamyltransferase-1 (GGT1, gamma-glutamyltranspeptidase-1, CD224 antigen)

Function

• initiates extracellular glutathione (GSH) breakdown
• provides cells with a local cysteine supply
• contributes to maintain intracelular GSH level
• part of cell antioxidant defense mechanism
• catalyzes transfer of glutamyl moiety of glutathione to amino acids & dipeptide acceptors
• alternatively, glutathione can be hydrolyzed to give cys-gly & gamma glutamate (reversible)
• isoform 3 seems to be inactive
• sulfur metabolism; glutathione metabolism

(5-L-glutamyl)-peptide + an amino acid
              <-->
peptide + 5-L-glutamyl amino acid

Structure

• heterodimer composed of the light & heavy chains
• the active site is located in the light chain
• belongs to the gamma-glutamyltransferase family
• contains hexoses, hexosamines & sialic acid residues
• not known if the sialic acid residues are present on N-linked glycans or on O-linked glycans
• N-glycosylated on both chains

Compartment

membrane

Alternative splicing

• named isoforms=3
• alternative promoter usage

Expression

• detected in fetal & adult kidney & liver, adult pancreas, stomach, intestine, placenta & lung
• isoform 3 is lung-specific
• several other tissue-specific forms that arise from alternative promoter usage but that produce the same protein

Pathology

• defects in GGT1 are a cause of glutathionuria

Notes

• Cys-454 was thought to bind the gamma-glutamyl moiety, but mutagenesis of this residue had no effect on activity

More general terms

• gamma-glutamyltransferase (GGT) or gamma-glutamyltranspeptidase
• glycoprotein
• CD antigen

Database

• UniProt: http://www.uniprot.org/uniprot/P19440.html
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:2678
• OMIM: https://mirror.omim.org/entry/231950