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Information on EC 4.3.2.9 - gamma-glutamylcyclotransferase and Organism(s) Homo sapiens and UniProt Accession Q9BVM4
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4.3.2.9 gamma-glutamylcyclotransferaseIUBMB Comments
The enzyme, found in animals and plants, acts on derivatives of L-glutamate, L-2-aminobutanoate, L-alanine and glycine. 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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Word Map
- 4.3.2.9
-
2.3.2.2
-
smoking
- gamma-gt
- triglyceride
- gsh
-
alt
-
drinker
-
confound
- glycylglycine
-
carbohydrate-deficient
- bilirubin
-
c-reactive
-
middle-aged
-
hepatobiliary
-
all-cause
-
coffee
-
waist
- 5-oxoproline
-
transpeptidation
-
abstinence
-
corpuscular
-
gamma-glutamyl-transferase
-
glutamyltransferase
- acivicin
-
abstain
- medicine
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
gamma-glutamyl cyclotransferase, c7orf24, ripay, gamma-glutamylcyclotransferase, ggct2;1, ggact, protein c7orf24, a2ld1, ggct2;2, ggct2;3, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
C7orf24
cyclotransferase, gamma-glutamyl
-
-
-
-
gamma-glutamyl cyclotransferase
gamma-glutamyl-amino acid cyclotransferase
-
-
-
-
gamma-L-glutamylcyclotransferase
-
-
-
-
GGCT
L-glutamic cyclase
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
alpha-(gamma-L-glutamyl)-L-amino acid = alpha-L-amino acid + 5-oxo-L-proline
mechanism
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
aminoacyl group transfer
aminoacyl group transfer
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
alpha-(gamma-L-glutamyl)-L-amino-acid gamma-glutamyl cyclotransferase (5-oxo-L-proline producing)
The enzyme, found in animals and plants, acts on derivatives of L-glutamate, L-2-aminobutanoate, L-alanine and glycine. 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.
CAS REGISTRY NUMBER
COMMENTARY
9045-44-7
-
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
5-L-glutamyl-1-naphthylamide
5-oxoproline + naphthylamine
-
best substrate
-
?
5-L-glutamyl-5-L-glutamyl-4-nitroanilide
5-oxoproline + 5-L-glutamyl-4-nitroanilide
-
-
-
-
?
5-L-glutamyl-L-5-L-glutamyl-L-4-nitroanilide
5-L-oxoproline + 5-L-glutamyl-L-p-nitroanilide
5-L-glutamyl-L-alanine
5-oxoproline + L-alanine
-
low activity compared to glutathione
-
-
?
D-gamma-glutamyl-O-[[(4-methyl-2-oxo-2H-1-benzopyran-7-yl)oxy]carbonyl]-L-serine
5-oxoproline + O-[[(4-methyl-2-oxo-2H-1-benzopyran-7-yl)oxy]carbonyl]-L-serine
-
-
-
-
?
gamma-L-Glu-epsilon-N-benzyloxycarbonyl-L-Lys
epsilon-N-benzyloxycarbonyl-L-Lys + 5-oxo-L-proline
-
-
-
?
gamma-L-glutamyl-L-amino acid
5-oxoproline + L-amino acid
-
enzyme of L-glutamyl-cycle
-
?
L-gamma-glutamyl-O-[(4-methylumbelliferyl)carbonyl]-L-serine
(2S)-2-amino-3-([[(4-methyl-2-oxo-2H-1-benzopyran-7-yl)oxy]carbonyl]oxy)propanoic acid + 5-oxo-L-proline
fluorogenic probe
-
-
?
N5-((S)-1-carboxy-3-(ethyl(((3-oxo-3H-phenoxazin-7-yl)oxy)carbonyl)amino)propyl)-L-glutamine
(2S)-2-amino-4-(ethyl[[(3-oxo-3H-phenoxazin-7-yl)oxy]carbonyl]amino)butanoic acid + 5-oxo-L-proline
fluorogenic probe
-
-
?
5-L-glutamyl-L-5-L-glutamyl-L-4-nitroanilide
5-L-oxoproline + 5-L-glutamyl-L-p-nitroanilide
-
best substrate
-
?
5-L-glutamyl-L-5-L-glutamyl-L-4-nitroanilide
5-L-oxoproline + 5-L-glutamyl-L-p-nitroanilide
-
best substrate
-
?
5-L-glutamyl-L-alpha-aminobutyrate
5-L-oxoproline + L-alpha-aminobutyrate
-
-
-
?
5-L-glutamyl-L-alpha-aminobutyrate
5-L-oxoproline + L-alpha-aminobutyrate
-
-
-
?
5-L-glutamyl-L-alpha-aminobutyrate
5-L-oxoproline + L-alpha-aminobutyrate
-
-
-
?
5-L-glutamyl-L-amino acid
5-oxoproline + L-amino acid
-
-
i.e. 2-pyrrolidone-5-carboxylic acid
?
5-L-glutamyl-L-amino acid
5-oxoproline + L-amino acid
-
stereospecific
-
?
5-L-glutamyl-L-amino acid
5-oxoproline + L-amino acid
-
no activity with LD-, DD- and DL-isomers of 5-L-glutamyl-5-L-glutamyl-4-nitroanilide
i.e. 2-pyrrolidone-5-carboxylic acid
?
5-L-glutamyl-L-amino acid
5-oxoproline + L-amino acid
-
no activity with L-glutamine
-
?
5-L-glutamyl-L-amino acid
5-oxoproline + L-amino acid
-
no activity with L-glutamine
-
?
5-L-glutamyl-L-amino acid
5-oxoproline + L-amino acid
-
no activity with: glutathione, i.e. gamma-L-glutamyl-L-cysteinylglycine
i.e. 2-pyrrolidone-5-carboxylic acid
?
5-L-glutamyl-L-amino acid
5-oxoproline + L-amino acid
-
no activity with L-glutamyl-beta-alanine, L-glutamyl-3-aminoisobutyrate
-
?
5-L-glutamyl-L-amino acid
5-oxoproline + L-amino acid
-
highly specific for 5-L-glutamyl peptides
-
?
5-L-glutamyl-L-amino acid
5-oxoproline + L-amino acid
-
preferred substrates: 5-L-glutamyl-5-L-glutamyl-amino acids
-
?
5-L-glutamyl-L-amino acid
5-oxoproline + L-amino acid
-
no activity with: 5-glutamyl-4-nitroanilide
i.e. 2-pyrrolidone-5-carboxylic acid
?
5-L-glutamyl-L-phenylalanine
5-oxoproline + L-phenylalanine
-
poor substrate
-
?
5-L-glutamyl-L-phenylalanine
5-oxoproline + L-phenylalanine
-
poor substrate
-
?
5-L-glutamyl-S-methyl-L-cysteine
5-oxoproline + S-methyl-L-cysteine
-
-
-
?
5-L-glutamyl-S-methyl-L-cysteine
5-oxoproline + S-methyl-L-cysteine
-
-
-
?
additional information
?
-
-
N-terminal pyroglutamate formation is a posttranslational event in the processing of bioactive neuropeptides such as thyrotropin-releasing hormone and neurotensin during their maturation in the secretory pathway. The enzyme also catalyzes N-terminal glutamate cyclization
-
-
?
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
gamma-L-glutamyl-L-amino acid
5-oxoproline + L-amino acid
-
enzyme of L-glutamyl-cycle
-
?
additional information
?
-
-
N-terminal pyroglutamate formation is a posttranslational event in the processing of bioactive neuropeptides such as thyrotropin-releasing hormone and neurotensin during their maturation in the secretory pathway. The enzyme also catalyzes N-terminal glutamate cyclization
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
N2-(4-carboxybutanoyl)-N6-(7-nitro-2,1,3-benzoxadiazol-4-yl)-L-lysine
53% inhibition
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.38
L-gamma-glutamyl-O-[(4-methylumbelliferyl)carbonyl]-L-serine
pH 6.5, temperature not specified in the publication
0.56
N5-((S)-1-carboxy-3-(ethyl(((3-oxo-3H-phenoxazin-7-yl)oxy)carbonyl)amino)propyl)-L-glutamine
pH 8.0, temperature not specified in the publication
0.28
gamma-L-Glu-epsilon-N-benzyloxycarbonyl-L-Lys
pH 6.5, temperature not specified in the publication
0.32
gamma-L-Glu-epsilon-N-benzyloxycarbonyl-L-Lys
pH 8.0, temperature not specified in the publication
additional information
additional information
-
Km-values for Gln-containing peptides
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.8 - 8.2
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
additional information
-
not detected in bone marrow, eye, Fallopian tube, heart, ovary, pancreas, pituitary gland, skin, spinal cord, thymus, placenta, and prostate gland
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
enzyme knockdown inhibits glioma cell T98G and U251 proliferation and colony formation
physiological function
-
enzyme overexpression promotes the expression of Notch receptors and activates Akt signaling in glioma cells
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
the structures of GGACT, GGACT in complex with 5-oxoproline, and the E82Q mutant are solved to a resolution of 1.20, 1.20 and 0.98 A, respectively
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
G23A
kcat/KM for gamma-glutamyl-L-alanine is 8.4fold lower than wild-type value
Y105F
kcat/KM for gamma-glutamyl-L-alanine is 650fold lower than wild-type value
Y125F
kcat/KM for gamma-glutamyl-L-alanine is 3.7fold lower than wild-type value
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
by Ni-agarose chromatography, subsequent removal of all additional N-terminal residues by cleavage with the catalytic domain of mouse ubiquitin specific protease 2
by affinity chromatography on glutathione-Sepharose 4B beads and subsequently by elution through digestion with PreScission protease
pH 4.2, ammonium sulfate, heat, Sephadex G-75, carboxymethyl cellulose, DEAE-cellulose
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
into the vector pGEM-T for sequencing and subsequently into pHUE for expression of the protein in Escherichia coli BL21DE3 cells
into the vector pGEX6P1 for expression in Escherichia coli BL21 cells, into the plasmids pCIneo-FLAG, pCIneo-T7 and pEGFP-C1, into the vector pGEM-T
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
the enzyme expression is upregulated in cancer cells (58% in cervical, 38% in lung, 72% in colon, and 46% in breast cancer)
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
-
in patients with gastrointestinal fistula, levels of alkaline phosphatase and gamma-glutamylcyclotransferase increase significantly on the third day after beginning of enteral feeding and decrease gradually afterwards. The longer the total parenteral nutrition lasted, the more severe the enteral refeeding syndrome becomes. Early enteral nutrition is useful in preventing it
medicine
-
enzyme overexpression defines a subgroup of breast tumors with poor clinical outcome. The enzyme is a cancer biomarker and a serological marker
medicine
-
gamma-glutamylcyclotransferase is a target molecule for cancer diagnosis and treatment
medicine
GGCT silencing significantly suppresses proliferation of colorectal cancer cells and arrests cell cycle at the G0/G1 phase by regulating the expression of p21, p27, and cyclin E. GGCT silencing triggers the apoptosis of colorectal cancer cells by activating caspase-3 and cleaved poly-ADPribose polymerase pathways and downregulating the phosphorylation proline-rich Akt substrate of 40 kDa (PRAS40) expression levels. GGCT silencing combined with 5-fluorouracil treatment further induces the apoptotic rate of colorectal cancer cells
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Orlowski, M.; Richman, P.G.; Meister, A.
Isolation and properties of gamma-L-glutamylcyclotransferase from human brain
Biochemistry
8
1048-1055
1969
Ovis aries, Homo sapiens
Board, P.G.; Moore, K.A.; Smith, J.E.
Purification and properties of gamma-glutamylcyclotransferase from human erythrocytes
Biochem. J.
173
427-431
1978
Homo sapiens
York, M.J.; Kuchel, P.W.; Chapman, B.E.
A proton nuclear magnetic resonance study of gamma-glutamyl-amino acid cyclotransferase in human erythrocytes
J. Biol. Chem.
259
15085-15088
1984
Homo sapiens
Orlowski, M.; Meister, A.
Enzymology of pyrrolidone carboxylic acid
The Enzymes, 3rd Ed. (Boyer, P. D. , ed. )
4
123-151
1971
Cavia porcellus, Homo sapiens, Mus musculus, Ovis aries, Rattus norvegicus
-
Szweczuk, A.; Connell, G.E.
Specificity of gamma-glutamyl cyclotransferase
Can. J. Biochem.
53
706-712
1975
Homo sapiens, Rattus norvegicus, Sus scrofa
York, M.J.; Crossley, M.J.; Hyslop, S.J.; Fisher, M.L.; Kuchel, P.W.
gamma-Glutamylcyclotransferase: inhibition by D-beta-aminoglutaryl-L-alanine and analysis of the solvent kinetic isotope effect
Eur. J. Biochem.
184
97-101
1989
Homo sapiens
Korotkina, R.N.; Matskevich, G.N.; Devlikanova, A.S.; Vishnevskii, A.A.; Kunitsyn, A.G.; Karelin, A.A.
Activity of glutathione-metabolizing and antioxidant enzymes in malignant and benign tumors of human lungs
Bull. Exp. Biol. Med.
133
606-608
2002
Homo sapiens
Schilling, S.; Hoffmann, T.; Manhart, S.; Hoffmann, M.; Demuth, H.U.
Glutaminyl cyclases unfold glutamyl cyclase activity under mild acid conditions
FEBS Lett.
563
191-196
2004
Carica papaya, Homo sapiens
Ren, J.; Mao, Y.; Wang, G.; Wang, X.; Fan, C.; Wang, Z.; Li, J.
Enteral refeeding syndrome after long-term total parenteral nutrition
Chin. Med. J.
119
1856-1860
2006
Homo sapiens
Oakley, A.J.; Yamada, T.; Liu, D.; Coggan, M.; Clark, A.G.; Board, P.G.
The identification and structural characterization of C7orf24 as gamma-glutamyl cyclotransferase. An essential enzyme in the gamma-glutamyl cycle
J. Biol. Chem.
283
22031-22042
2008
Homo sapiens (O75223)
Oakley, A.J.; Coggan, M.; Board, P.G.
Identification and characterization of {gamma}-glutamylamine cyclotransferase: An enzyme responsible for {gamma}-glutamyl-{epsilon}-lysine catabolism
J. Biol. Chem.
285
9642-9648
2010
Homo sapiens (Q9BVM4)
Azumi, K.; Ikeda, Y.; Takeuchi, T.; Nomura, T.; Sabau, S.; Hamada, J.; Okada, F.; Hosokawa, M.; Yokosawa, H.
Localization and characterization of gamma-glutamyl cyclotransferase in cancer cells
Mol. Med. Rep.
2
385-391
2009
Rattus norvegicus, Homo sapiens (O75223), Homo sapiens
Gromov, P.; Gromova, I.; Friis, E.; Timmermans-Wielenga, V.; Rank, F.; Simon, R.; Sauter, G.; Moreira, J.M.
Proteomic profiling of mammary carcinomas identifies C7orf24, a gamma-glutamyl cyclotransferase, as a potential cancer biomarker
J. Proteome Res.
9
3941-3953
2010
Homo sapiens
Shen, S.H.; Yu, N.; Liu, X.Y.; Tan, G.W.; Wang, Z.X.
Gamma-glutamylcyclotransferase promotes the growth of human glioma cells by activating Notch-Akt signaling
Biochem. Biophys. Res. Commun.
471
616-620
2016
Homo sapiens
Kageyama, S.; Hanada, E.; Ii, H.; Tomita, K.; Yoshiki, T.; Kawauchi, A.
gamma-Glutamylcyclotransferase: A novel target molecule for cancer diagnosis and treatment
BioMed Res. Int.
2015
345219
2015
Homo sapiens
Yoshiya, T.; Tsuda, S.; Mochizuki, M.; Hidaka, K.; Tsuda, Y.; Kiso, Y.; Kageyama, S.; Ii, H.; Yoshiki, T.; Nishiuchi, Y.
A fluorogenic probe for gamma-glutamyl cyclotransferase: application of an enzyme-triggered O-to-N acyl migration-type reaction
ChemBioChem
14
2110-2113
2013
Homo sapiens
Dong, J.; Zhou, Y.; Liao, Z.; Huang, Q.; Feng, S.; Li, Y.
Role of gamma-glutamyl cyclotransferase as a therapeutic target for colorectal cancer based on the lentivirus-mediated system
Anticancer Drugs
27
1011-1020
2016
Homo sapiens (O75223)
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