Activating Compound | Comment | Organism | Structure |
---|---|---|---|
additional information | subunit GCLM increases the Vmax and Kcat of subunit GCLC, and decreases the Km for glutamate and ATP | Mus musculus | |
additional information | subunit GCLM increases the Vmax and Kcat of subunit GCLC, and decreases the Km for glutamate and ATP | Homo sapiens | |
additional information | subunit GCLM increases the Vmax and Kcat of subunit GCLC, and decreases the Km for glutamate and ATP | Rattus norvegicus |
Protein Variants | Comment | Organism |
---|---|---|
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 |
additional information | GCLC and GCLM polymorphisms increase disease susceptibility in humans, overview | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
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 | |
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 | |
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 | |
glutathione | feedback inhibition, subunit GCLM increases the Ki for GSH-mediated feedback inhibition of GCL, competitive to glutamate | Homo sapiens | |
glutathione | feedback inhibition, subunit GCLM increases the Ki for GSH-mediated feedback inhibition of GCL, competitive to glutamate | Mus musculus | |
glutathione | feedback inhibition, subunit GCLM increases the Ki for GSH-mediated feedback inhibition of GCL, competitive to glutamate | Rattus norvegicus | |
additional information | oxidative stress dramatically affects GCL holoenzyme formation and activity | Homo sapiens | |
additional information | oxidative stress dramatically affects GCL holoenzyme formation and activity | Mus musculus | |
additional information | oxidative stress dramatically affects GCL holoenzyme formation and activity | Rattus norvegicus |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
cytosol | - |
Mus musculus | 5829 | - |
cytosol | - |
Homo sapiens | 5829 | - |
cytosol | - |
Rattus norvegicus | 5829 | - |
membrane | - |
Mus musculus | 16020 | - |
membrane | - |
Homo sapiens | 16020 | - |
membrane | - |
Rattus norvegicus | 16020 | - |
mitochondrion | - |
Mus musculus | 5739 | - |
mitochondrion | - |
Homo sapiens | 5739 | - |
mitochondrion | - |
Rattus norvegicus | 5739 | - |
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 | - |
- |
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 | - |
- |
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 | Comment | Organism | Structure |
---|---|---|---|
Mg2+ | - |
Arabidopsis thaliana | |
Mg2+ | required | Drosophila melanogaster | |
Mg2+ | required | Mus musculus | |
Mg2+ | required | Homo sapiens | |
Mg2+ | required | Rattus norvegicus |
Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
---|---|---|---|
31000 | - |
1 * 73000, about, GCLC, + 1 * 31000, about, GCLM | Mus musculus |
31000 | - |
1 * 73000, about, GCLC, + 1 * 31000, about, GCLM | Homo sapiens |
31000 | - |
1 * 73000, about, GCLC, + 1 * 31000, about, GCLM | Rattus norvegicus |
73000 | - |
1 * 73000, about, GCLC, + 1 * 31000, about, GCLM | Mus musculus |
73000 | - |
1 * 73000, about, GCLC, + 1 * 31000, about, GCLM | Homo sapiens |
73000 | - |
1 * 73000, about, GCLC, + 1 * 31000, about, GCLM | Rattus norvegicus |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + L-glutamate + L-cysteine | Drosophila melanogaster | - |
ADP + phosphate + gamma-L-glutamyl-L-cysteine | - |
? | |
ATP + L-glutamate + L-cysteine | Arabidopsis thaliana | - |
ADP + phosphate + gamma-L-glutamyl-L-cysteine | - |
? | |
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 | - |
? | |
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 | - |
? | |
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 | - |
? | |
additional information | Mus musculus | post-translational regulation of GCL, overview | ? | - |
? | |
additional information | Rattus norvegicus | post-translational regulation of GCL, overview | ? | - |
? | |
additional information | Homo sapiens | post-translational regulation of GCL, overview. GCLC and GCLM polymorphisms increase disease susceptibility in humans, overview | ? | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Arabidopsis thaliana | - |
- |
- |
Drosophila melanogaster | - |
- |
- |
Homo sapiens | - |
genes gclC and gclM encoding the two subunits of the enzyme | - |
Mus musculus | - |
genes gclC and gclM encoding the two subunits of the enzyme | - |
Rattus norvegicus | - |
genes gclC and gclM encoding the two subunits of the enzyme | - |
Posttranslational Modification | Comment | Organism |
---|---|---|
lipoprotein | myristoylation is responsible for regulation of GCL subunit subcellular localization to membranes and mitochondria, overview | Mus musculus |
lipoprotein | myristoylation is responsible for regulation of GCL subunit subcellular localization to membranes and mitochondria, overview | Homo sapiens |
lipoprotein | myristoylation is responsible for regulation of GCL subunit subcellular localization to membranes and mitochondria, overview | Rattus norvegicus |
additional information | post-translational modifications of GCLC, e.g. phosphorylation, myristoylation, caspase-mediated cleavage, have modest effects on GCL activity | Mus musculus |
additional information | post-translational modifications of GCLC, e.g. phosphorylation, myristoylation, caspase-mediated cleavage, have modest effects on GCL activity | Homo sapiens |
additional information | post-translational modifications of GCLC, e.g. phosphorylation, myristoylation, caspase-mediated cleavage, have modest effects on GCL activity | Rattus norvegicus |
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 |
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 |
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 |
proteolytic modification | caspase-mediated cleavage of GCLC, overview | Mus musculus |
proteolytic modification | caspase-mediated cleavage of GCLC, overview | Homo sapiens |
proteolytic modification | caspase-mediated cleavage of GCLC, overview | Rattus norvegicus |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
hepatocyte | - |
Mus musculus | - |
hepatocyte | - |
Rattus norvegicus | - |
kidney | - |
Rattus norvegicus | - |
liver | - |
Mus musculus | - |
liver | - |
Rattus norvegicus | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + L-glutamate + L-cysteine | - |
Drosophila melanogaster | ADP + phosphate + gamma-L-glutamyl-L-cysteine | - |
? | |
ATP + L-glutamate + L-cysteine | - |
Arabidopsis thaliana | ADP + phosphate + gamma-L-glutamyl-L-cysteine | - |
? | |
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 | - |
? | |
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 | - |
? | |
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 | - |
? | |
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 | - |
? | |
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 | - |
? | |
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 | - |
? | |
additional information | post-translational regulation of GCL, overview | Mus musculus | ? | - |
? | |
additional information | post-translational regulation of GCL, overview | Rattus norvegicus | ? | - |
? | |
additional information | post-translational regulation of GCL, overview. GCLC and GCLM polymorphisms increase disease susceptibility in humans, overview | Homo sapiens | ? | - |
? | |
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 | Comment | Organism |
---|---|---|
dimer | 1 * 73000, about, GCLC, + 1 * 31000, about, GCLM | Mus musculus |
dimer | 1 * 73000, about, GCLC, + 1 * 31000, about, GCLM | Homo sapiens |
dimer | 1 * 73000, about, GCLC, + 1 * 31000, about, GCLM | Rattus norvegicus |
dimer | GCL reveals two redox-sensitive intramolecular disulfide bonds, CC1 and CC2, located at the homodimer interface that regulate plant GCL activity | Arabidopsis thaliana |
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 |
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 |
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 |
trimer | - |
Drosophila melanogaster |
Synonyms | Comment | Organism |
---|---|---|
gamma-glutamylcysteine ligase | - |
Arabidopsis thaliana |
GCL | - |
Drosophila melanogaster |
GCL | - |
Mus musculus |
GCL | - |
Homo sapiens |
GCL | - |
Rattus norvegicus |
GCL | - |
Arabidopsis thaliana |
glutamate cysteine ligase | - |
Drosophila melanogaster |
glutamate cysteine ligase | - |
Mus musculus |
glutamate cysteine ligase | - |
Homo sapiens |
glutamate cysteine ligase | - |
Rattus norvegicus |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
ATP | - |
Arabidopsis thaliana | |
ATP | required | Drosophila melanogaster | |
ATP | required | Mus musculus | |
ATP | required | Homo sapiens | |
ATP | required | Rattus norvegicus |