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Information on EC 4.3.2.7 - glutathione-specific gamma-glutamylcyclotransferase
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4.3.2.7 glutathione-specific gamma-glutamylcyclotransferaseIUBMB Comments
The enzyme, found in bacteria, fungi and animals, is specific for glutathione (cf. EC 4.3.2.9, gamma-glutamylcyclotransferase). The enzyme acts as a cyclotransferase, cleaving the amide bond via transamidation using the alpha-amine of the L-glutamyl residue, releasing it as the cyclic 5-oxo-L-proline.
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The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Synonyms
chac1, chac2, glutathione-specific gamma-glutamylcyclotransferase, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
CHAC
-
-
-
-
CHAC1
CHAC2
gamma-GCG
-
-
-
-
RipAY
RSp1022
CHAC1
-
-
-
-
CHAC2
-
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
glutathione = L-cysteinylglycine + 5-oxo-L-proline
-
-
-
-
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SYSTEMATIC NAME
IUBMB Comments
glutathione gamma-glutamyl cyclotransferase (5-oxo-L-proline producing)
The enzyme, found in bacteria, fungi and animals, is specific for glutathione (cf. EC 4.3.2.9, gamma-glutamylcyclotransferase). The enzyme acts as a cyclotransferase, cleaving the amide bond via transamidation using the alpha-amine of the L-glutamyl residue, releasing it as the cyclic 5-oxo-L-proline.
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
gamma-glutamyl-L-alanine
5-oxo-L-proline + L-alanine
-
poor substrate
-
-
?
additional information
?
-
no activity against either gamma-glutamyl amino acids or oxidized glutathione
-
-
?
additional information
?
-
-
no activity against either gamma-glutamyl amino acids or oxidized glutathione
-
-
?
additional information
?
-
no activity against either gamma-glutamyl amino acids or oxidized glutathione
-
-
?
additional information
?
-
-
no activity against either gamma-glutamyl amino acids or oxidized glutathione
-
-
?
additional information
?
-
no substrate: gamma-glutamyl amino acids such as gamma-Glu-Ala, gamma-Glu-Cys, gamma-Glu-Met, gamma-Glu-His and gamma-Glu-Lys
-
-
?
additional information
?
-
-
no substrate: gamma-glutamyl amino acids such as gamma-Glu-Cys, gamma-Glu-Met, gamma-Glu-His and gamma-Glu-Lys
-
-
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Atherosclerosis
Human CHAC1 Protein Degrades Glutathione, and mRNA Induction Is Regulated by the Transcription Factors ATF4 and ATF3 and a Bipartite ATF/CRE Regulatory Element.
Breast Neoplasms
CHAC1 degradation of glutathione enhances cystine-starvation-induced necroptosis and ferroptosis in human triple negative breast cancer cells via the GCN2-eIF2?-ATF4 pathway.
Breast Neoplasms
Development of a novel prognostic score for breast cancer patients using mRNA expression of CHAC1.
Breast Neoplasms
Structural and Functional Analyses of Human ChaC2 in Glutathione Metabolism.
Carcinogenesis
Nisin, an apoptogenic bacteriocin and food preservative, attenuates HNSCC tumorigenesis via CHAC1.
Carcinoma
Ferroptosis-related gene CHAC1 is a valid indicator for the poor prognosis of kidney renal clear cell carcinoma.
Cardiovascular Diseases
Source of Dietary Fat in Pig Diet Affects Adipose Expression of Genes Related to Cancer, Cardiovascular, and Neurodegenerative Diseases.
Colorectal Neoplasms
CHAC2, downregulated in gastric and colorectal cancers, acted as a tumor suppressor inducing apoptosis and autophagy through unfolded protein response.
Cystic Fibrosis
CHAC1 Is Differentially Expressed in Normal and Cystic Fibrosis Bronchial Epithelial Cells and Regulates the Inflammatory Response Induced by Pseudomonas aeruginosa.
Glioma
The CHAC1-inhibited Notch3 pathway is involved in temozolomide-induced glioma cytotoxicity.
Infections
CHAC1 Is Differentially Expressed in Normal and Cystic Fibrosis Bronchial Epithelial Cells and Regulates the Inflammatory Response Induced by Pseudomonas aeruginosa.
Infections
CHAC1 overexpression in human gastric parietal cells with Helicobacter pylori infection in the secretory canaliculi.
Infections
Helicobacter pylori induces somatic mutations in TP53 via overexpression of CHAC1 in infected gastric epithelial cells.
Neoplasm Metastasis
Higher expression of cation transport regulator-like protein 1 (CHAC1) predicts of poor outcomes in uveal melanoma (UM) patients.
Neoplasms
CHAC2, downregulated in gastric and colorectal cancers, acted as a tumor suppressor inducing apoptosis and autophagy through unfolded protein response.
Neoplasms
Development of a novel prognostic score for breast cancer patients using mRNA expression of CHAC1.
Neoplasms
Elevated mRNA expression of CHAC1 splicing variants is associated with poor outcome for breast and ovarian cancer patients.
Neoplasms
Ferroptosis-related gene CHAC1 is a valid indicator for the poor prognosis of kidney renal clear cell carcinoma.
Neoplasms
Helicobacter pylori induces somatic mutations in TP53 via overexpression of CHAC1 in infected gastric epithelial cells.
Neoplasms
Higher expression of cation transport regulator-like protein 1 (CHAC1) predicts of poor outcomes in uveal melanoma (UM) patients.
Neoplasms
Nisin, an apoptogenic bacteriocin and food preservative, attenuates HNSCC tumorigenesis via CHAC1.
Neoplasms
Source of Dietary Fat in Pig Diet Affects Adipose Expression of Genes Related to Cancer, Cardiovascular, and Neurodegenerative Diseases.
Neoplasms
The CHAC1-inhibited Notch3 pathway is involved in temozolomide-induced glioma cytotoxicity.
Neoplasms
Xylitol acts as an anticancer monosaccharide to induce selective cancer death via regulation of the glutathione level.
Ovarian Neoplasms
Elevated mRNA expression of CHAC1 splicing variants is associated with poor outcome for breast and ovarian cancer patients.
Periodontitis
Detection of Serum miRNAs Affecting Liver Apoptosis in a Periodontitis Rat Model.
Prostatic Neoplasms
ChaC glutathione specific ?-glutamylcyclotransferase 1 inhibits cell viability and increases the sensitivity of prostate cancer cells to docetaxel by inducing endoplasmic reticulum stress and ferroptosis.
Squamous Cell Carcinoma of Head and Neck
Nisin, an apoptogenic bacteriocin and food preservative, attenuates HNSCC tumorigenesis via CHAC1.
Squamous Cell Carcinoma of Head and Neck
RNA-Seq analysis of peripheral blood mononuclear cells reveals unique transcriptional signatures associated with radiotherapy response of nasopharyngeal carcinoma and prognosis of head and neck cancer.
Starvation
CHAC1 degradation of glutathione enhances cystine-starvation-induced necroptosis and ferroptosis in human triple negative breast cancer cells via the GCN2-eIF2?-ATF4 pathway.
Stomach Neoplasms
Helicobacter pylori induces somatic mutations in TP53 via overexpression of CHAC1 in infected gastric epithelial cells.
Stomach Neoplasms
Metformin inhibits gastric cancer cell proliferation by regulation of a novel Loc100506691-CHAC1 axis.
Teratoma
CHAC2 is essential for self-renewal and glutathione maintenance in human embryonic stem cells.
Triple Negative Breast Neoplasms
CHAC1 degradation of glutathione enhances cystine-starvation-induced necroptosis and ferroptosis in human triple negative breast cancer cells via the GCN2-eIF2?-ATF4 pathway.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
physiological function
-
expression of RipAY causes growth inhibition of yeast Saccharomyces cerevisiae, and a decrease of 70% of the intracellular glutathione level. Addition of exogenous glutathione does not restore RipAY-dependent growth inhibition. Inoculation of Ralstonia solanacearum into eggplant leaves causes a decrease in intracellular glutathione. In vitro, RipAY protein purified from a bacterial expression system does not exhibit any GGCT activity, whereas robust GGCT activity is seen upon its interaction with eukaryotic thioredoxins
physiological function
-
gamma-glutamyl cyclotransferase acts specifically to degrade glutathione but not other gamma-glutamyl peptides. The overexpression leads to glutathione depletion and enhanced apoptosis in yeast
physiological function
gamma-glutamyl cyclotransferase acts specifically to degrade glutathione but not other gamma-glutamyl peptides. The overexpression leads to glutathione depletion and enhanced apoptosis in yeast
physiological function
isoform ChaC2 degrades glutathione at lower efficiency than its ChaC1 homologue
physiological function
isoform ChaC2 degrades glutathione at lower efficiency than its ChaC1 homologue
physiological function
-
expression of RipAY causes growth inhibition of yeast Saccharomyces cerevisiae, and a decrease of 70% of the intracellular glutathione level. Addition of exogenous glutathione does not restore RipAY-dependent growth inhibition. Inoculation of Ralstonia solanacearum into eggplant leaves causes a decrease in intracellular glutathione. In vitro, RipAY protein purified from a bacterial expression system does not exhibit any GGCT activity, whereas robust GGCT activity is seen upon its interaction with eukaryotic thioredoxins
-
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
monomer
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
to 1.43 A resolution. The catalytic site is defined by a fortuitous benzoic acid molecule bound to the crystal structure
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
E115Q
-
mutation of putative catalytic glutamate residue, loss of activity
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
medicine
higher levels of ChaC1 transcripts are present in all the tumorigenic cell lines examined
analysis
-
development of a 5-oxoprolinase-coupled, sensitive, 5-oxoproline detection-based gamma-GCT assay. Development of an alternative assay that exploits the Cys-Gly generation from glutathione. Cys-Gly is converted into free cysteine and glycine with the help of Dug1p (a peptidase from Saccharomyces cerevisiae), followed by estimation of cysteine
analysis
development of a a 5-oxoprolinase-coupled, sensitive, 5-oxoproline detection-based gamma-GCT assay. Development of an alternative assay that exploits the Cys-Gly generation from glutathione. Cys-Gly is converted into free cysteine and glycine with the help of Dug1p (a peptidase from Saccharomyces cerevisiae), followed by estimation of cysteine
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Kumar, A.; Tikoo, S.; Maity, S.; Sengupta, S.; Sengupta, S.; Kaur, A.; Bachhawat, A.K.
Mammalian proapoptotic factor ChaC1 and its homologues function as gamma-glutamyl cyclotransferases acting specifically on glutathione
EMBO Rep.
13
1095-1101
2012
Saccharomyces cerevisiae, Mus musculus (Q8R3J5)
brenda
Fujiwara, S.; Kawazoe, T.; Ohnishi, K.; Kitagawa, T.; Popa, C.; Valls, M.; Genin, S.; Nakamura, K.; Kuramitsu, Y.; Tanaka, N.; Tabuchi, M.
RipAY, a plant pathogen effector protein, exhibits robust gamma-glutamyl cyclotransferase activity when stimulated by eukaryotic thioredoxins
J. Biol. Chem.
291
6813-6830
2016
Ralstonia solanacearum, Ralstonia solanacearum OE1-1
brenda
Kaur, A.; Gautam, R.; Srivastava, R.; Chandel, A.; Kumar, A.; Karthikeyan, S.; Bachhawat, A.K.
ChaC2, an enzyme for slow turnover of cytosolic glutathione
J. Biol. Chem.
292
638-651
2017
Saccharomyces cerevisiae (P32656), Saccharomyces cerevisiae, Homo sapiens (Q8WUX2), Homo sapiens, Mus musculus (Q9CQG1), Mus musculus
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Release 2023.1 (January 2023)
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