Activating Compound | Comment | Organism | Structure |
---|---|---|---|
Epidermal growth factor | kidney-type glutaminase activity in cells is stimulated by EGF | Homo sapiens |
Cloned (Comment) | Organism |
---|---|
expression of HA-tagged or FLAG-tagged wild-type and mutant kidney-type glutaminase in 293T cells | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
L321A/F322A/L323 | site-directed mutagenesis | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl) ethyl sulfide | i.e. BPTES, binds to an allosteric pocket at the dimer interface of kidney-type glutaminase, triggering a dramatic conformational change of the key loop (Glu312-Pro329) near the catalytic site and rendering it inactive, allosteric inhibition. Binding of BPTES stabilizes the inactive tetramers of the catalytic domain of kidney-type glutaminase. The binding mode of BPTES on the hydrophobic pocket determines its specificity to the kidney-type glutaminase isoform KGA | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
L-glutamine + H2O | Homo sapiens | - |
L-glutamate + NH3 | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
kidney-type glutaminase isoform KGA | - |
Posttranslational Modification | Comment | Organism |
---|---|---|
phosphoprotein | phosphorylation-dependent regulation of kidney-type glutaminase | Homo sapiens |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
kidney | kidney-type glutaminase isoform KGA | Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
L-glutamine + H2O | - |
Homo sapiens | L-glutamate + NH3 | - |
? |
Subunits | Comment | Organism |
---|---|---|
dimer | active kidney-type glutaminase | Homo sapiens |
tetramer | inactive kidney-type glutaminase | Homo sapiens |
Synonyms | Comment | Organism |
---|---|---|
KGA | - |
Homo sapiens |
kidney-type glutaminase | - |
Homo sapiens |
General Information | Comment | Organism |
---|---|---|
malfunction | treating cells that coexpressed Mek2-K101A and kidney-type glutaminase with suboptimal level of BPTES leads to synergistic inhibition on cell proliferation | Homo sapiens |
additional information | Ile221-Leu533 is the catalytic domain of kidney-type glutaminase | Homo sapiens |
physiological function | kidney-type glutaminase activity in cells is stimulated by EGF, and kidney-type glutaminase associates with all three kinase components of the Raf-1/Mek2/Erk signaling module, interaction mode, the bound ligand makes several hydrogen-bonding contacts to Gln285, Ser286, Asn335, Glu381, Asn388, Tyr414, Tyr466, and Val484, overview. The kidney-type glutaminase active and inhibitory sites show a dynamic nature, cross-talk and regulation of kidney-type glutaminase activities by EGF-mediated Raf-Mek-Erk signaling. The enhanced activity is abrogated by kinase-dead, dominant negative mutants of Raf-1 (Raf-1-K375M) andMek2 (Mek2-K101A), protein phosphatase PP2A, and Mek-inhibitor U0126, indicative of phosphorylation-dependent regulation. kidney-type glutaminase can interact equally well with the wild-type or mutant forms of Raf-1 and Mek2. The activity of kidney-type glutaminase is directly regulated by Raf-Mek-Erk downstream of EGF receptor | Homo sapiens |