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Literature summary for 2.7.1.127 extracted from
- Inositol(1,4,5)P3 3-kinase isoenzymes: catalytic properties and importance of targeting to F-actin to understand function (2016), Adv. Biol. Regul., 60, 135-143.
Activating Compound
| Activating Compound | Comment | Organism | Structure |
|---|---|---|---|
| Calmodulin | the enzyme is activated by Ca2+/calmodulin. The isozyme contains a CaM binding domain | Homo sapiens |  |
| Calmodulin | the enzyme is activated by Ca2+/calmodulin. The isozyme contains a CaM binding domain | Rattus norvegicus | |
| Calmodulin | the enzyme is activated by Ca2+/calmodulin. The isozyme contains a CaM binding domain | Mus musculus | |
| Calmodulin | the enzyme is highly activated by Ca2+/calmodulin, ten to twentyfold increase in activity in human platelets. The isozyme contains a CaM binding domain | Homo sapiens | |
| Calmodulin | the enzyme is highly activated by Ca2+/calmodulin, two or threefold in rat brain. The isozyme contains a CaM binding domain | Rattus norvegicus | |
| Calmodulin | the enzyme is highly activated by Ca2+/calmodulin. The isozyme contains a CaM binding domain | Mus musculus | |
| Carbachol | activates the enzyme up to 7fold in rat brain cortical slices | Rattus norvegicus | |
| additional information | phosphorylation activates the activity of isozyme Itpka | Rattus norvegicus | |
| additional information | the enzyme is stimulated by purinergic agonists in human astrocytoma cells | Homo sapiens |
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| gene Itpka | Homo sapiens |
| gene Itpka | Rattus norvegicus |
| gene Itpka | Mus musculus |
| gene Itpkb | Rattus norvegicus |
| gene Itpkb | Homo sapiens |
| gene Itpkb | Mus musculus |
| gene Itpkc | Rattus norvegicus |
| gene Itpkc | Mus musculus |
| gene Itpkc | Homo sapiens |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| cytoskeleton | cytoskeletal localization for isozyme Itpka | Homo sapiens | 5856 | - |
| cytoskeleton | cytoskeletal localization for isozyme Itpka | Rattus norvegicus | 5856 | - |
| cytoskeleton | cytoskeletal localization for isozyme Itpka | Mus musculus | 5856 | - |
| cytoskeleton | cytoskeletal localization for isozyme Itpkb or at the leading edge for Itpkb | Rattus norvegicus | 5856 | - |
| cytoskeleton | cytoskeletal localization for isozyme Itpkb or at the leading edge for Itpkb | Homo sapiens | 5856 | - |
| cytoskeleton | cytoskeletal localization for isozyme Itpkb or at the leading edge for Itpkb | Mus musculus | 5856 | - |
| endoplasmic reticulum | - |
Rattus norvegicus | 5783 | - |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Ca2+ | the enzyme is activated by Ca2+/calmodulin | Homo sapiens | |
| Ca2+ | the enzyme is activated by Ca2+/calmodulin | Rattus norvegicus | |
| Ca2+ | the enzyme is activated by Ca2+/calmodulin | Mus musculus | |
| Ca2+ | the enzyme is highly activated by Ca2+/calmodulin | Rattus norvegicus | |
| Ca2+ | the enzyme is highly activated by Ca2+/calmodulin | Homo sapiens | |
| Ca2+ | the enzyme is highly activated by Ca2+/calmodulin | Mus musculus | |
| Mg2+ | required | Rattus norvegicus | |
| Mg2+ | required | Homo sapiens | |
| Mg2+ | required | Mus musculus | |
Molecular Weight [Da]
| Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
|---|---|---|---|
| 50000 | - |
- |
Homo sapiens |
| 50000 | - |
- |
Rattus norvegicus |
| 50000 | - |
- |
Mus musculus |
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 | Rattus norvegicus | - |
ADP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate | - |
? | |
| ATP + 1D-myo-inositol 1,4,5-trisphosphate | Homo sapiens | - |
ADP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate | - |
? | |
| ATP + 1D-myo-inositol 1,4,5-trisphosphate | Mus musculus | - |
ADP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | P23677 | gene Itpka | - |
| Homo sapiens | P27987 | gene Itpkb | - |
| Homo sapiens | Q96DU7 | gene Itpkc | - |
| Mus musculus | B2RXC2 | gene Itpkb | - |
| Mus musculus | Q7TS72 | gene Itpkc | - |
| Mus musculus | Q8R071 | gene Itpka | - |
| Rattus norvegicus | P17105 | gene Itpka | - |
| Rattus norvegicus | P42335 | gene Itpkb | - |
| Rattus norvegicus | Q80ZG2 | gene Itpkc | - |
Posttranslational Modification
| Posttranslational Modification | Comment | Organism |
|---|---|---|
| phosphoprotein | phosphorylation activates the activity of isozyme Itpka | Rattus norvegicus |
| proteolytic modification | Itpka undergoes proteolysis in intact cells, leading to the accumulation of a stable C-terminal domain of 83 kDa to the endoplasmic reticulum, incubation of Itpka at 37°C for 30 min totally destroys Ins(1,4,5)P3 3-kinase activity unless the enzyme is mixed with 0.1% SDS | Rattus norvegicus |
| proteolytic modification | Itpkb is very sensitive to proteolysis | Rattus norvegicus |
| proteolytic modification | Itpkb is very sensitive to proteolysis | Homo sapiens |
| proteolytic modification | Itpkb is very sensitive to proteolysis | Mus musculus |
Purification (Commentary)
| Purification (Comment) | Organism |
|---|---|
| elution of recombinant Itpka isozyme with 0.5% SDS and 0.1 mM EGTA from calmodulin affinity column | Rattus norvegicus |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| astrocytoma cell | - |
Homo sapiens | - |
| blood platelet | - |
Rattus norvegicus | - |
| blood platelet | - |
Homo sapiens | - |
| brain | - |
Rattus norvegicus | - |
| brain | - |
Mus musculus | - |
| brain | - |
Homo sapiens | - |
| brain | Itpka is particularly active in neurons of the hippocampus and cerebellum | Homo sapiens | - |
| brain | Itpka is particularly active in neurons of the hippocampus and cerebellum | Rattus norvegicus | - |
| brain | Itpka is particularly active in neurons of the hippocampus and cerebellum | Mus musculus | - |
| brain | Itpkb protein level is increased in the cerebral cortex of most patients with Alzheimer's disease compared with control subjects | Homo sapiens | - |
| carcinoma cell | - |
Rattus norvegicus | - |
| carcinoma cell | - |
Homo sapiens | - |
| carcinoma cell | - |
Mus musculus | - |
| embryonic stem cell | Itpkb protein level is increased upon differentiation of human embryonic stem cells | Homo sapiens | - |
| hippocampus | dendritic spines | Rattus norvegicus | - |
| intestine | - |
Rattus norvegicus | - |
| intestine | - |
Homo sapiens | - |
| intestine | - |
Mus musculus | - |
| additional information | enzyme activity determined in cell homogenates with Ins(1,4,5)P3 and ATP as substrate is generally very low compared to Ins(1,4,5)P3 5-phosphatase, EC 3.1.3.56, except in a few tissues such as brain, testis, thymus or intestine | Homo sapiens | - |
| additional information | enzyme activity determined in cell homogenates with Ins(1,4,5)P3 and ATP as substrate is generally very low compared to Ins(1,4,5)P3 5-phosphatase, EC 3.1.3.56, except in a few tissues such as brain, testis, thymus or intestine | Rattus norvegicus | - |
| additional information | enzyme activity determined in cell homogenates with Ins(1,4,5)P3 and ATP as substrate is generally very low compared to Ins(1,4,5)P3 5-phosphatase, EC 3.1.3.56, except in a few tissues such as brain, testis, thymus or intestine | Mus musculus | - |
| additional information | enzyme activity determined in cell homogenates with Ins(1,4,5)P3 and ATP as substrate is generally very low compared to Ins(1,4,5)P3 5-phosphatase, EC 3.1.3.56, except in a few tissues such as brain, testis, thymus or intestine. Itpkb and Itpkc are widespread expressed in many different tissues and cell lines | Rattus norvegicus | - |
| additional information | enzyme activity determined in cell homogenates with Ins(1,4,5)P3 and ATP as substrate is generally very low compared to Ins(1,4,5)P3 5-phosphatase, EC 3.1.3.56, except in a few tissues such as brain, testis, thymus or intestine. Itpkb and Itpkc are widespread expressed in many different tissues and cell lines | Homo sapiens | - |
| additional information | enzyme activity determined in cell homogenates with Ins(1,4,5)P3 and ATP as substrate is generally very low compared to Ins(1,4,5)P3 5-phosphatase, EC 3.1.3.56, except in a few tissues such as brain, testis, thymus or intestine. Itpkb and Itpkc are widespread expressed in many different tissues and cell lines | Mus musculus | - |
| neuron | localized to the post-dendritic spines of neurons. Itpka is particularly active in neurons of the hippocampus and cerebellum | Homo sapiens | - |
| neuron | localized to the post-dendritic spines of neurons. Itpka is particularly active in neurons of the hippocampus and cerebellum | Rattus norvegicus | - |
| neuron | localized to the post-dendritic spines of neurons. Itpka is particularly active in neurons of the hippocampus and cerebellum | Mus musculus | - |
| PC-12 cell | - |
Rattus norvegicus | - |
| testis | - |
Rattus norvegicus | - |
| testis | - |
Homo sapiens | - |
| testis | - |
Mus musculus | - |
| testis | high expression level | Rattus norvegicus | - |
| thymus | - |
Rattus norvegicus | - |
| thymus | - |
Homo sapiens | - |
| thymus | - |
Mus musculus | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + 1D-myo-inositol 1,4,5-trisphosphate | - |
Rattus norvegicus | ADP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate | - |
? | |
| ATP + 1D-myo-inositol 1,4,5-trisphosphate | - |
Homo sapiens | ADP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate | - |
? | |
| ATP + 1D-myo-inositol 1,4,5-trisphosphate | - |
Mus musculus | ADP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| ? | x * 50000, isozyme Itpka from rat brain, SDS-PAGE | Rattus norvegicus |
| ? | x * 50000, isozyme Itpka, SDS-PAGE | Homo sapiens |
| ? | x * 50000, isozyme Itpka, SDS-PAGE | Mus musculus |
| More | isozyme Itpka contains an F-actin binding site at the N-terminal part | Homo sapiens |
| More | isozyme Itpka contains an F-actin binding site at the N-terminal part | Rattus norvegicus |
| More | isozyme Itpka contains an F-actin binding site at the N-terminal part | Mus musculus |
| More | isozyme Itpkb contains an F-actin binding site at the N-terminal part | Rattus norvegicus |
| More | isozyme Itpkb contains an F-actin binding site at the N-terminal part | Homo sapiens |
| More | isozyme Itpkb contains an F-actin binding site at the N-terminal part | Mus musculus |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| inositol(1,4,5)P3 3-kinase | - |
Rattus norvegicus |
| inositol(1,4,5)P3 3-kinase | - |
Homo sapiens |
| inositol(1,4,5)P3 3-kinase | - |
Mus musculus |
| inositol(1,4,5)trisphosphate 3-kinase | - |
Mus musculus |
| inositol(1,4,5)trisphosphate 3-kinases | - |
Rattus norvegicus |
| inositol(1,4,5)trisphosphate 3-kinases | - |
Homo sapiens |
| ITPKA | - |
Homo sapiens |
| ITPKA | - |
Rattus norvegicus |
| ITPKA | - |
Mus musculus |
| Itpkb | - |
Rattus norvegicus |
| Itpkb | - |
Homo sapiens |
| Itpkb | - |
Mus musculus |
| Itpkc | - |
Rattus norvegicus |
| Itpkc | - |
Mus musculus |
| Itpkc | - |
Homo sapiens |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| ATP | - |
Rattus norvegicus | |
| ATP | - |
Homo sapiens | |
| ATP | - |
Mus musculus | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| evolution | inositol(1,4,5)trisphosphate 3-kinases (Itpks) occur in three isoenzyme forms, Itpka/b and c, in human, rat and mouse. They share a catalytic domain relatively well conserved at the C-terminal end and a quite isoenzyme specific regulatory domain at the N-terminal end of the protein | Rattus norvegicus |
| evolution | inositol(1,4,5)trisphosphate 3-kinases (Itpks) occur in three isoenzyme forms, Itpka/b and c, in human, rat and mouse. They share a catalytic domain relatively well conserved at the C-terminal end and a quite isoenzyme specific regulatory domain at the N-terminal end of the protein | Homo sapiens |
| evolution | inositol(1,4,5)trisphosphate 3-kinases (Itpks) occur in three isoenzyme forms, Itpka/b and c, in human, rat and mouse. They share a catalytic domain relatively well conserved at the C-terminal end and a quite isoenzyme specific regulatory domain at the N-terminal end of the protein | Mus musculus |
| malfunction | isozyme Itpka-deficient mice exhibit increased LTP in the CA1 region of the hippocampus | Mus musculus |
| malfunction | mice deficient for Itpkb have a severe defect in thymocytes differentiation and thus lack peripheral T cells | Mus musculus |
| metabolism | 1D-myo-inositol 1,3,4,5-tetrakisphosphate, Ins(1,3,4,5)P4 can interact with a relatively specific Ins(1,3,4,5)P4 binding protein Rasa3, alternatively, Ins(1,3,4,5)P4 can also compete with phosphoinositides to the binding of PH domain containing proteins such as Akt, protein kinase B. In neutrophils and hematopoietic progenitors, elevated levels of Ins(1,3,4,5)P4 inhibit the recruitment of Akt at the plasma membrane, and its activation, acting as a competitor of PtdIns(3,4,5)P3 binding to its PH domain | Rattus norvegicus |
| metabolism | 1D-myo-inositol 1,3,4,5-tetrakisphosphate, Ins(1,3,4,5)P4 can interact with a relatively specific Ins(1,3,4,5)P4 binding protein Rasa3, alternatively, Ins(1,3,4,5)P4 can also compete with phosphoinositides to the binding of PH domain containing proteins such as Akt, protein kinase B. In neutrophils and hematopoietic progenitors, elevated levels of Ins(1,3,4,5)P4 inhibit the recruitment of Akt at the plasma membrane, and its activation, acting as a competitor of PtdIns(3,4,5)P3 binding to its PH domain | Homo sapiens |
| metabolism | 1D-myo-inositol 1,3,4,5-tetrakisphosphate, Ins(1,3,4,5)P4 can interact with a relatively specific Ins(1,3,4,5)P4 binding protein Rasa3, alternatively, Ins(1,3,4,5)P4 can also compete with phosphoinositides to the binding of PH domain containing proteins such as Akt, protein kinase B. In neutrophils and hematopoietic progenitors, elevated levels of Ins(1,3,4,5)P4 inhibit the recruitment of Akt at the plasma membrane, and its activation, acting as a competitor of PtdIns(3,4,5)P3 binding to its PH domain | Mus musculus |
| additional information | isozyme Itpkb contains an F-actin binding site at the N-terminal part | Rattus norvegicus |
| additional information | isozyme Itpkb contains an F-actin binding site at the N-terminal part | Homo sapiens |
| additional information | isozyme Itpkb contains an F-actin binding site at the N-terminal part | Mus musculus |
| additional information | ITPKC functional polymorphism associates with Kawasaki disease susceptibility | Homo sapiens |
| physiological function | in natural killer (NK) cells, isozyme Itpkb promotes NK-cell terminal maturation but limits NK-cell effector functions | Homo sapiens |
| physiological function | in natural killer (NK) cells, isozyme Itpkb promotes NK-cell terminal maturation but limits NK-cell effector functions. Itpka and Itpkb isoforms inhibit neurite outgrowth in PC12 cells, while isozyme Itpkc does not | Rattus norvegicus |
| physiological function | in natural killer (NK) cells, isozyme Itpkb promotes NK-cell terminal maturation but limits NK-cell effector functions. Itpkb controls hematopoietic stem cell homeostasis and prevents lethal hematopoietic failure in mice | Mus musculus |
| physiological function | isozyme Itpka contains an F-actin binding site at the N-terminal part that confers to Itpka the properties of an F-actin bundling protein with two major consequences: it can reorganize the cytoskeletal network, particularly in dendritic spines, and it can provide an opportunity for Ins(1,3,4,5)P4 to act very locally as second messenger. Isozyme Itpka is an F-actin bundling protein regulating dendritic spines structural plasticity and a scaffold protein for synaptic rac signaling, Itpka overexpression induces cytoskeletal reorganization, high expression of Itpka in cancer cells increases invasion and migration in vitro | Homo sapiens |
| physiological function | isozyme Itpka contains an F-actin binding site at the N-terminal part that confers to Itpka the properties of an F-actin bundling protein with two major consequences: it can reorganize the cytoskeletal network, particularly in dendritic spines, and it can provide an opportunity for Ins(1,3,4,5)P4 to act very locally as second messenger. Isozyme Itpka is an F-actin bundling protein regulating dendritic spines structural plasticity and a scaffold protein for synaptic rac signaling, Itpka overexpression induces cytoskeletal reorganization, high expression of Itpka in cancer cells increases invasion and migration in vitro | Mus musculus |
| physiological function | isozyme Itpka contains an F-actin binding site at the N-terminal part that confers to Itpka the properties of an F-actin bundling protein with two major consequences: it can reorganize the cytoskeletal network, particularly in dendritic spines, and it can provide an opportunity for Ins(1,3,4,5)P4 to act very locally as second messenger. Isozyme Itpka is an F-actin bundling protein regulating dendritic spines structural plasticity and a scaffold protein for synaptic rac signaling, Itpka overexpression induces cytoskeletal reorganization, high expression of Itpka in cancer cells increases invasion and migration in vitro. Itpka and Itpkb isoforms inhibit neurite outgrowth in PC12 cells, while isozyme Itpkc does not | Rattus norvegicus |
| physiological function | Itpka and Itpkb isoforms inhibit neurite outgrowth in PC12 cells, while isozyme Itpkc does not | Rattus norvegicus |
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