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Literature summary for 2.7.1.127 extracted from
- D-myo-inositol 1,4,5-trisphosphate 3-kinase A is activated by receptor activation through a calcium:calmodulin-dependent protein kinase II phosphorylation mechanism (1997), EMBO J., 16, 1943-1952.
Activating Compound
| Activating Compound | Comment | Organism | Structure |
|---|---|---|---|
| CaM kinase II | phosphorylates and activates | Rattus norvegicus | |
| CaM kinase II | phosphorylation of Thr-311 results in 8-10fold enzyme activation in the presence of 0.01 mM free Ca2+ and 0.002 mM calmodulin and in a 25fold increase in sensitivity to the Ca2+/calmodulin complex | Homo sapiens | |
| Carbachol | - |
Homo sapiens |  |
| Carbachol | 3-5fold activation, maximal at 0.01-0.05 mM, isoenzyme A, increases the phosphorylation of enzyme | Rattus norvegicus | |
| UTP | - |
Rattus norvegicus | |
| UTP | activation, recombinant isoenzyme A overexpressed in CHO cells | Homo sapiens | |
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| isoenzyme A is cloned and overexpressed in CHO cells | Homo sapiens |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| KN-62 | calmodulin-dependent protein kinase II inhibitor; prevents the carbachol- or UTP-mediated activation | Homo sapiens | |
| KN-62 | calmodulin-dependent protein kinase II inhibitor; prevents the carbachol- or UTP-mediated activation | Rattus norvegicus | |
| KN-93 | calmodulin-dependent protein kinase II inhibitor; prevents the carbachol- or UTP-mediated activation | Homo sapiens | |
| KN-93 | calmodulin-dependent protein kinase II inhibitor; prevents the carbachol- or UTP-mediated activation | Rattus norvegicus | |
KM Value [mM]
| KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 0.004 | - |
1D-myo-inositol 1,4,5-trisphosphate | pH 7.4 | Homo sapiens | |
| 0.004 | - |
1D-myo-inositol 1,4,5-trisphosphate | pH 7.5 | Rattus norvegicus | |
| 0.004 | - |
1D-myo-inositol 1,4,5-trisphosphate | 37°C, isoform A | Homo sapiens | |
| 0.004 | - |
1D-myo-inositol 1,4,5-trisphosphate | 37°C, isoform A | Rattus norvegicus | |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Ca2+ | phosphorylation of Thr-311 of isoenzyme A by CaM kinase II results in a 25fold increase in sensitivity to the Ca2+/calmodulin complex | Homo sapiens | |
| Ca2+ | activation by Ca2+/calmodulin | Homo sapiens | |
| Ca2+ | activation by Ca2+/calmodulin | Rattus norvegicus | |
Molecular Weight [Da]
| Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
|---|---|---|---|
| 53000 | - |
x * 53000, isoenzyme A, SDS-PAGE | Homo sapiens |
| 53000 | - |
x * 53000, isoenzyme A, SDS-PAGE | Rattus norvegicus |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + 1D-myo-inositol 1,4,5-trisphosphate | Homo sapiens | regulation mechanism of isoenzyme A in brain involving CaM kinase II-mediated phosphorylation, role of Ins(1,4,5)P3 3-kinase in brain | ADP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate | - |
? | |
| ATP + 1D-myo-inositol 1,4,5-trisphosphate | Rattus norvegicus | regulation mechanism of isoenzyme A in brain involving CaM kinase II-mediated phosphorylation, role of Ins(1,4,5)P3 3-kinase in brain | ADP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate | - |
? | |
| ATP + 1D-myo-inositol 1,4,5-trisphosphate | Rattus norvegicus | inositol phosphate metabolism | ADP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | - |
recombinant isoenzyme A overexpressed in CHO cells | - |
| Rattus norvegicus | - |
adult | - |
| Rattus norvegicus | - |
male sprague-dawley rats | - |
| Rattus norvegicus | - |
isoenzyme A | - |
Posttranslational Modification
| Posttranslational Modification | Comment | Organism |
|---|---|---|
| phosphoprotein | - |
Rattus norvegicus |
| phosphoprotein | phosphorylation of Thr-311 by CaM kinase II results in 8-10fold enzyme activation in the presence of 0.01 mM free Ca2+ and 0.002 mM calmodulin and in a 25fold increase in sensitivity to the Ca2+/calmodulin complex | Homo sapiens |
Purification (Commentary)
| Purification (Comment) | Organism |
|---|---|
| recombinant isoenzyme A overexpressed in CHO cells | Homo sapiens |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| brain | cortex | Rattus norvegicus | - |
| brain | isoenzyme A is the major isoform present in neuronal cells | Homo sapiens | - |
| brain | isoenzyme A is the major isoform present in neuronal cells | Rattus norvegicus | - |
Specific Activity [micromol/min/mg]
| Specific Activity Minimum [µmol/min/mg] | Specific Activity Maximum [µmol/min/mg] | Comment | Organism |
|---|---|---|---|
| 0.0048 | - |
37°C, isoenzyme A, rat cortical slices | Homo sapiens |
| 1.7 | - |
pH 7.4, 37°C, purified recombinant isoenzyme A overexpressed in CHO cells | Rattus norvegicus |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + 1D-myo-inositol 1,4,5-trisphosphate | regulation mechanism of isoenzyme A involving CaM kinase II-mediated phosphorylation | Homo sapiens | ADP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate | - |
? | |
| ATP + 1D-myo-inositol 1,4,5-trisphosphate | regulation mechanism of isoenzyme A involving CaM kinase II-mediated phosphorylation | Rattus norvegicus | ADP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate | - |
? | |
| ATP + 1D-myo-inositol 1,4,5-trisphosphate | regulation mechanism of isoenzyme A in brain involving CaM kinase II-mediated phosphorylation, role of Ins(1,4,5)P3 3-kinase in brain | Homo sapiens | ADP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate | - |
? | |
| ATP + 1D-myo-inositol 1,4,5-trisphosphate | regulation mechanism of isoenzyme A in brain involving CaM kinase II-mediated phosphorylation, role of Ins(1,4,5)P3 3-kinase in brain | Rattus norvegicus | ADP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate | - |
? | |
| ATP + 1D-myo-inositol 1,4,5-trisphosphate | inositol phosphate metabolism | Rattus norvegicus | ADP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| ? | x * 53000, isoenzyme A, SDS-PAGE | Homo sapiens |
| ? | x * 53000, isoenzyme A, SDS-PAGE | Rattus norvegicus |
Temperature Optimum [°C]
| Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
|---|---|---|---|
| 37 | - |
assay at | Homo sapiens |
| 37 | - |
assay at | Rattus norvegicus |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 7.4 | - |
assay at | Homo sapiens |
| 7.5 | - |
assay at | Rattus norvegicus |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| ATP | - |
Homo sapiens | |
| ATP | - |
Rattus norvegicus | |
| Calmodulin | activation by Ca2+/calmodulin | Homo sapiens | |
| Calmodulin | activation by Ca2+/calmodulin | Rattus norvegicus | |
| Calmodulin | phosphorylation of Thr-311 of isoenzyme A by CaM kinase II results in a 25fold increase in sensitivity to the Ca2+/calmodulin complex, maximally 2-2.5fold stimulation by the Ca2+/calmodulin complex | Homo sapiens | |
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