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Literature summary extracted from

  • Franklin, C.C.; Backos, D.S.; Mohar, I.; White, C.C.; Forman, H.J.; Kavanagh, T.J.
    Structure, function, and post-translational regulation of the catalytic and modifier subunits of glutamate cysteine ligase (2008), Mol. Aspects Med., 30, 86-98.
    View publication on PubMedView publication on EuropePMC

Activating Compound

EC Number Activating Compound Comment Organism Structure
6.3.2.2 additional information subunit GCLM increases the Vmax and Kcat of subunit GCLC, and decreases the Km for glutamate and ATP Mus musculus
6.3.2.2 additional information subunit GCLM increases the Vmax and Kcat of subunit GCLC, and decreases the Km for glutamate and ATP Homo sapiens
6.3.2.2 additional information subunit GCLM increases the Vmax and Kcat of subunit GCLC, and decreases the Km for glutamate and ATP Rattus norvegicus

Protein Variants

EC Number Protein Variants Comment Organism
6.3.2.2 additional information construction of Gclc and Gclm transgenic mice designed to conditionally overexpress GCL in the liver, conditional Gcl transgene expression in these mice promotes resistance to acetaminophen-induced liver injury Mus musculus
6.3.2.2 additional information GCLC and GCLM polymorphisms increase disease susceptibility in humans, overview Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
6.3.2.2 buthionine sulfoximine GCL mediates the phosphorylation of buthionine sulfoximine, which is required for its tight and irreversible binding to the active site of GCL Homo sapiens
6.3.2.2 buthionine sulfoximine GCL mediates the phosphorylation of buthionine sulfoximine, which is required for its tight and irreversible binding to the active site of GCL Mus musculus
6.3.2.2 buthionine sulfoximine GCL mediates the phosphorylation of buthionine sulfoximine, which is required for its tight and irreversible binding to the active site of GCL Rattus norvegicus
6.3.2.2 glutathione feedback inhibition, subunit GCLM increases the Ki for GSH-mediated feedback inhibition of GCL, competitive to glutamate Homo sapiens
6.3.2.2 glutathione feedback inhibition, subunit GCLM increases the Ki for GSH-mediated feedback inhibition of GCL, competitive to glutamate Mus musculus
6.3.2.2 glutathione feedback inhibition, subunit GCLM increases the Ki for GSH-mediated feedback inhibition of GCL, competitive to glutamate Rattus norvegicus
6.3.2.2 additional information oxidative stress dramatically affects GCL holoenzyme formation and activity Homo sapiens
6.3.2.2 additional information oxidative stress dramatically affects GCL holoenzyme formation and activity Mus musculus
6.3.2.2 additional information oxidative stress dramatically affects GCL holoenzyme formation and activity Rattus norvegicus

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
6.3.2.2 cytosol
-
Mus musculus 5829
-
6.3.2.2 cytosol
-
Homo sapiens 5829
-
6.3.2.2 cytosol
-
Rattus norvegicus 5829
-
6.3.2.2 membrane
-
Mus musculus 16020
-
6.3.2.2 membrane
-
Homo sapiens 16020
-
6.3.2.2 membrane
-
Rattus norvegicus 16020
-
6.3.2.2 mitochondrion
-
Mus musculus 5739
-
6.3.2.2 mitochondrion
-
Homo sapiens 5739
-
6.3.2.2 mitochondrion
-
Rattus norvegicus 5739
-
6.3.2.2 additional information while GCLC and GCLM are generally considered to be cytosolic proteins there is evidence that they may exhibit altered subcellular localization in certain circumstances Mus musculus
-
-
6.3.2.2 additional information while GCLC and GCLM are generally considered to be cytosolic proteins there is evidence that they may exhibit altered subcellular localization in certain circumstances Homo sapiens
-
-
6.3.2.2 additional information while GCLC and GCLM are generally considered to be cytosolic proteins there is evidence that they may exhibit altered subcellular localization in certain circumstances Rattus norvegicus
-
-

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
6.3.2.2 Mg2+
-
Arabidopsis thaliana
6.3.2.2 Mg2+ required Drosophila melanogaster
6.3.2.2 Mg2+ required Mus musculus
6.3.2.2 Mg2+ required Homo sapiens
6.3.2.2 Mg2+ required Rattus norvegicus

Molecular Weight [Da]

EC Number Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
6.3.2.2 31000
-
1 * 73000, about, GCLC, + 1 * 31000, about, GCLM Mus musculus
6.3.2.2 31000
-
1 * 73000, about, GCLC, + 1 * 31000, about, GCLM Homo sapiens
6.3.2.2 31000
-
1 * 73000, about, GCLC, + 1 * 31000, about, GCLM Rattus norvegicus
6.3.2.2 73000
-
1 * 73000, about, GCLC, + 1 * 31000, about, GCLM Mus musculus
6.3.2.2 73000
-
1 * 73000, about, GCLC, + 1 * 31000, about, GCLM Homo sapiens
6.3.2.2 73000
-
1 * 73000, about, GCLC, + 1 * 31000, about, GCLM Rattus norvegicus

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
6.3.2.2 ATP + L-glutamate + L-cysteine Drosophila melanogaster
-
ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
?
6.3.2.2 ATP + L-glutamate + L-cysteine Arabidopsis thaliana
-
ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
?
6.3.2.2 ATP + L-glutamate + L-cysteine Mus musculus first rate-limiting step in GSH biosynthesis, GCL is a major determinant of cellular GSH levels, pathway overview ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
?
6.3.2.2 ATP + L-glutamate + L-cysteine Homo sapiens first rate-limiting step in GSH biosynthesis, GCL is a major determinant of cellular GSH levels, pathway overview ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
?
6.3.2.2 ATP + L-glutamate + L-cysteine Rattus norvegicus first rate-limiting step in GSH biosynthesis, GCL is a major determinant of cellular GSH levels, pathway overview ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
?
6.3.2.2 additional information Mus musculus post-translational regulation of GCL, overview ?
-
?
6.3.2.2 additional information Rattus norvegicus post-translational regulation of GCL, overview ?
-
?
6.3.2.2 additional information Homo sapiens post-translational regulation of GCL, overview. GCLC and GCLM polymorphisms increase disease susceptibility in humans, overview ?
-
?

Organism

EC Number Organism UniProt Comment Textmining
6.3.2.2 Arabidopsis thaliana
-
-
-
6.3.2.2 Drosophila melanogaster
-
-
-
6.3.2.2 Homo sapiens
-
genes gclC and gclM encoding the two subunits of the enzyme
-
6.3.2.2 Mus musculus
-
genes gclC and gclM encoding the two subunits of the enzyme
-
6.3.2.2 Rattus norvegicus
-
genes gclC and gclM encoding the two subunits of the enzyme
-

Posttranslational Modification

EC Number Posttranslational Modification Comment Organism
6.3.2.2 lipoprotein myristoylation is responsible for regulation of GCL subunit subcellular localization to membranes and mitochondria, overview Mus musculus
6.3.2.2 lipoprotein myristoylation is responsible for regulation of GCL subunit subcellular localization to membranes and mitochondria, overview Homo sapiens
6.3.2.2 lipoprotein myristoylation is responsible for regulation of GCL subunit subcellular localization to membranes and mitochondria, overview Rattus norvegicus
6.3.2.2 additional information post-translational modifications of GCLC, e.g. phosphorylation, myristoylation, caspase-mediated cleavage, have modest effects on GCL activity Mus musculus
6.3.2.2 additional information post-translational modifications of GCLC, e.g. phosphorylation, myristoylation, caspase-mediated cleavage, have modest effects on GCL activity Homo sapiens
6.3.2.2 additional information post-translational modifications of GCLC, e.g. phosphorylation, myristoylation, caspase-mediated cleavage, have modest effects on GCL activity Rattus norvegicus
6.3.2.2 phosphoprotein phosphorylation plays an important role in regulating GCL activity in vivo, phosphorylation of GCLC occurs on serine and threonine residues in vitro and the phosphorylation sites are likely identical for all three kinases protein kinase C, PKC, cAMP-dependent protein kinase, PKA, or Ca2+-calmodulin-dependent protein kinase II, CMKII Mus musculus
6.3.2.2 phosphoprotein phosphorylation plays an important role in regulating GCL activity in vivo, phosphorylation of GCLC occurs on serine and threonine residues in vitro and the phosphorylation sites are likely identical for all three kinases protein kinase C, PKC, cAMP-dependent protein kinase, PKA, or Ca2+-calmodulin-dependent protein kinase II, CMKII Homo sapiens
6.3.2.2 phosphoprotein phosphorylation plays an important role in regulating GCL activity in vivo, phosphorylation of GCLC occurs on serine and threonine residues in vitro and the phosphorylation sites are likely identical for all three kinases protein kinase C, PKC, cAMP-dependent protein kinase, PKA, or Ca2+-calmodulin-dependent protein kinase II, CMKII Rattus norvegicus
6.3.2.2 proteolytic modification caspase-mediated cleavage of GCLC, overview Mus musculus
6.3.2.2 proteolytic modification caspase-mediated cleavage of GCLC, overview Homo sapiens
6.3.2.2 proteolytic modification caspase-mediated cleavage of GCLC, overview Rattus norvegicus

Source Tissue

EC Number Source Tissue Comment Organism Textmining
6.3.2.2 hepatocyte
-
Mus musculus
-
6.3.2.2 hepatocyte
-
Rattus norvegicus
-
6.3.2.2 kidney
-
Rattus norvegicus
-
6.3.2.2 liver
-
Mus musculus
-
6.3.2.2 liver
-
Rattus norvegicus
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
6.3.2.2 ATP + L-glutamate + L-cysteine
-
Drosophila melanogaster ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
?
6.3.2.2 ATP + L-glutamate + L-cysteine
-
Arabidopsis thaliana ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
?
6.3.2.2 ATP + L-glutamate + L-cysteine first rate-limiting step in GSH biosynthesis, GCL is a major determinant of cellular GSH levels, pathway overview Mus musculus ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
?
6.3.2.2 ATP + L-glutamate + L-cysteine first rate-limiting step in GSH biosynthesis, GCL is a major determinant of cellular GSH levels, pathway overview Homo sapiens ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
?
6.3.2.2 ATP + L-glutamate + L-cysteine first rate-limiting step in GSH biosynthesis, GCL is a major determinant of cellular GSH levels, pathway overview Rattus norvegicus ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
?
6.3.2.2 ATP + L-glutamate + L-cysteine GCL-mediated phosphorylation of L-glutamate creating the activated enzyme-bound gamma-glutamylphosphate intermediate Mus musculus ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
?
6.3.2.2 ATP + L-glutamate + L-cysteine GCL-mediated phosphorylation of L-glutamate creating the activated enzyme-bound gamma-glutamylphosphate intermediate Homo sapiens ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
?
6.3.2.2 ATP + L-glutamate + L-cysteine GCL-mediated phosphorylation of L-glutamate creating the activated enzyme-bound gamma-glutamylphosphate intermediate Rattus norvegicus ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
?
6.3.2.2 additional information post-translational regulation of GCL, overview Mus musculus ?
-
?
6.3.2.2 additional information post-translational regulation of GCL, overview Rattus norvegicus ?
-
?
6.3.2.2 additional information post-translational regulation of GCL, overview. GCLC and GCLM polymorphisms increase disease susceptibility in humans, overview Homo sapiens ?
-
?
6.3.2.2 additional information purified rat kidney GCL holoenzyme is capable of undergoing autophosphorylation, the phosphorylation is specific for the GCLC subunit, no phosphorylation of the GCLM subunit Rattus norvegicus ?
-
?

Subunits

EC Number Subunits Comment Organism
6.3.2.2 dimer 1 * 73000, about, GCLC, + 1 * 31000, about, GCLM Mus musculus
6.3.2.2 dimer 1 * 73000, about, GCLC, + 1 * 31000, about, GCLM Homo sapiens
6.3.2.2 dimer 1 * 73000, about, GCLC, + 1 * 31000, about, GCLM Rattus norvegicus
6.3.2.2 dimer GCL reveals two redox-sensitive intramolecular disulfide bonds, CC1 and CC2, located at the homodimer interface that regulate plant GCL activity Arabidopsis thaliana
6.3.2.2 More GCL is a heterodimeric protein composed of catalytic GCLC and modifier GCLM subunits that are expressed from different genes, the catalytic subunit GCLC contains the active site responsible for the ATP-dependent bond formation between the amino group of cysteine and the gamma-carboxyl group of glutamate, the modifier subunit GCLM through direct interaction with GCLC acts to increase the catalytic efficiency of GCLC. GCL subunit protein structures, overview. GCLM is quite sensitive to aggregation in vitro in the absence of GCLC Mus musculus
6.3.2.2 More GCL is a heterodimeric protein composed of catalytic GCLC and modifier GCLM subunits that are expressed from different genes, the catalytic subunit GCLC contains the active site responsible for the ATP-dependent bond formation between the amino group of cysteine and the gamma-carboxyl group of glutamate, the modifier subunit GCLM through direct interaction with GCLC acts to increase the catalytic efficiency of GCLC. GCL subunit protein structures, overview. GCLM is quite sensitive to aggregation in vitro in the absence of GCLC Homo sapiens
6.3.2.2 More GCL is a heterodimeric protein composed of catalytic GCLC and modifier GCLM subunits that are expressed from different genes, the catalytic subunit GCLC contains the active site responsible for the ATP-dependent bond formation between the amino group of cysteine and the gamma-carboxyl group of glutamate, the modifier subunit GCLM through direct interaction with GCLC acts to increase the catalytic efficiency of GCLC. GCL subunit protein structures, overview. GCLM is quite sensitive to aggregation in vitro in the absence of GCLC Rattus norvegicus
6.3.2.2 trimer
-
Drosophila melanogaster

Synonyms

EC Number Synonyms Comment Organism
6.3.2.2 gamma-glutamylcysteine ligase
-
Arabidopsis thaliana
6.3.2.2 GCL
-
Drosophila melanogaster
6.3.2.2 GCL
-
Mus musculus
6.3.2.2 GCL
-
Homo sapiens
6.3.2.2 GCL
-
Rattus norvegicus
6.3.2.2 GCL
-
Arabidopsis thaliana
6.3.2.2 glutamate cysteine ligase
-
Drosophila melanogaster
6.3.2.2 glutamate cysteine ligase
-
Mus musculus
6.3.2.2 glutamate cysteine ligase
-
Homo sapiens
6.3.2.2 glutamate cysteine ligase
-
Rattus norvegicus

Cofactor

EC Number Cofactor Comment Organism Structure
6.3.2.2 ATP
-
Arabidopsis thaliana
6.3.2.2 ATP required Drosophila melanogaster
6.3.2.2 ATP required Mus musculus
6.3.2.2 ATP required Homo sapiens
6.3.2.2 ATP required Rattus norvegicus