Biomarker: GGT

Histology type: endometrial carcinoma

Country: Poland

Region: Cracow

Followed up time :

Subgroup 1 name : endometrial adenocarcionoma

Subgroup 1 number: 98

Subgroup 2 name: Healthy controls

Subgroup 2 number: 60

Conclusion: We concluded that impaired GGT expression has the potential to become a valuable tool for stratifying EEC patients' prognosis and treatment planning.

Sample type : tissue

Sample method: immunohistochemistry

Expression pattern : expression

Expression elevation: Every tumour was scored according to the intensity of staining and number of stained cells (0, expression in < 25%; 1, 26 – 50%; 2, 51 – 75%; and 3, > 76% of cells). Positive staining was observed in the cell membrane, particularly in the apical part of glandular cells (staining scored as 1 - weak, 2 - moderate or 3 - strong). In cases where staining was classified as 3 (strong), the apical part of the cytoplasm also exhibited a positive reaction for GGT. The final immunoreactivity score was determined by multiplying the intensity scores by the extent of the positivity scores of stained cells, providing a score range of 0 – 9.

Statictics: Mean (SD)

Subgroup 1 age: 59.31 (± 9.76)

Subgroup 2 age: 59.80 (± 11.56)

UniProt ID: P19440

UniProt Link: https://www.uniprot.org/uniprotkb/P19440/entry

Biological function from UniProt: #Glutathione biosynthesis #Lipid metabolism

Molecular function from UniProt:

Tissue specificity from UniProt: Detected in fetal and adult kidney and liver, adult pancreas, stomach, intestine, placenta and lung. There are several other tissue-specific forms that arise from alternative promoter usage but that produce the same protein.Isoform 3 Lung-specific

Subcellular UniProt: #Cell membrane #Membrane

Alternative name from UniProt:

Caution: Cleaves the gamma-glutamyl bond of extracellular glutathione (gamma-Glu-Cys-Gly), glutathione conjugates (such as maresin conjugate (13R)-S-glutathionyl-(14S)-hydroxy-(4Z,7Z,9E,11E,16Z,19Z)-docosahexaenoate, MCTR1) and other gamma-glutamyl compounds (such as leukotriene C4, LTC4) (PubMed:17924658, PubMed:21447318, PubMed:27791009). The metabolism of glutathione by GGT1 releases free glutamate and the dipeptide cysteinyl-glycine, which is hydrolyzed to cysteine and glycine by dipeptidases (PubMed:27791009). 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 (PubMed:17924658, PubMed:7673200, PubMed:7759490, PubMed:8095045, PubMed:8827453, PubMed:21447318). Contributes to cysteine homeostasis, glutathione homeostasis and in the conversion of the leukotriene LTC4 to LTD4 .Isoform 3 Seems to be inactive.

Cleaved: Cleaved into 2 chains Glutathione hydrolase 1 heavy chain Glutathione hydrolase 1 light chain

Miscellaneous: Cys-454 was thought to bind the gamma-glutamyl moiety, but mutagenesis of this residue had no effect on activity. Chloride ions bound in the active site cavity may contribute to stabilize the protein fold

Catalytic activity: an alpha-amino acid + an N-terminal (5-L-glutamyl)-[peptide] = 5-L-glutamyl amino acid + N-terminal L-alpha-aminoacyl-[peptide] This reaction proceeds in the forward and the backwardBy Similarity directions.glutathione + H2O = L-cysteinylglycine + L-glutamate This reaction proceeds in the forward direction.an S-substituted glutathione + H2O = an S-substituted L-cysteinylglycine + L-glutamate This reaction proceeds in the forward direction .H2O + leukotriene C4 = L-glutamate + leukotriene D41 Publication This reaction proceeds in the forward direction.(13R)-S-glutathionyl-(14S)-hydroxy-(4Z,7Z,9E,11E,16Z,19Z)-docosahexaenoate + H2O = (13R)-S-cysteinylglycyl-(14S)-hydroxy-(4Z,7Z,9E,11E,16Z,19Z)-docosahexaenoate + L-glutamate This reaction proceeds in the forward direction.

Activity regulation: Activated by autocatalytic cleavage (PubMed:23682772). Inhibited by serine-borate (PubMed:21447318).

Recommended name: Glutathione hydrolase 1 proenzyme

Gene name from HGNC: GGT1 (CD224, D22S672, D22S732, GGT)

CD antigen name: CD224

HPA class: CD markers Disease related genes Enzymes Metabolic proteins Plasma proteins Potential drug targets

AlphaFold DB: P19440

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/P19440

HPA link: https://www.proteinatlas.org/ENSG00000100031-GGT1

Tissue specificity RNA from HPA: Tissue enhanced (kidney, liver)

Tissue expression from HPA: Selective cytoplasmic expression in renal tubules of kidney, epididymis, liver and pancreas.

Single cell type specificity Cell type enhanced (Proximal enterocytes, Ductal cells, Alveolar cells type 1, Proximal tubular cells, Distal enterocytes, Cholangiocytes, Hepatocytes)

Immune cell specificity: Low immune cell specificity

Subcellular summary HPA Located in Vesicles (Single cell variability)

Cancer prognostic summary HPA Prognostic marker in renal cancer (favorable) and ovarian cancer (favorable)

Pathology link: https://www.proteinatlas.org/ENSG00000100031-GGT1/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000100031-GGT1/pathology/endometrial+cancer

Phenotype ID: 231950

Disease: Glutathionuria (GLUTH)

Note1: The disease is caused by variants affecting the gene represented in this entry. A large homozygous deletion that removes several exons of all isoforms of GGT1 has been found in one family affected by glutathionuria

OMIM: 612346

OMIM link1: https://www.omim.org/entry/231950

OMIM link2: https://www.omim.org/entry/612346

HGNC ID: HGNC:4250

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:4250