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Literature summary extracted from

  • Erneux, C.; Ghosh, S.; Koenig, S.
    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.
    View publication on PubMed

Activating Compound

EC Number Activating Compound Comment Organism Structure
2.7.1.127 Calmodulin the enzyme is activated by Ca2+/calmodulin. The isozyme contains a CaM binding domain Homo sapiens
2.7.1.127 Calmodulin the enzyme is activated by Ca2+/calmodulin. The isozyme contains a CaM binding domain Rattus norvegicus
2.7.1.127 Calmodulin the enzyme is activated by Ca2+/calmodulin. The isozyme contains a CaM binding domain Mus musculus
2.7.1.127 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
2.7.1.127 Calmodulin the enzyme is highly activated by Ca2+/calmodulin, two or threefold in rat brain. The isozyme contains a CaM binding domain Rattus norvegicus
2.7.1.127 Calmodulin the enzyme is highly activated by Ca2+/calmodulin. The isozyme contains a CaM binding domain Mus musculus
2.7.1.127 Carbachol activates the enzyme up to 7fold in rat brain cortical slices Rattus norvegicus
2.7.1.127 additional information phosphorylation activates the activity of isozyme Itpka Rattus norvegicus
2.7.1.127 additional information the enzyme is stimulated by purinergic agonists in human astrocytoma cells Homo sapiens

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.7.1.127 gene Itpka Homo sapiens
2.7.1.127 gene Itpka Rattus norvegicus
2.7.1.127 gene Itpka Mus musculus
2.7.1.127 gene Itpkb Rattus norvegicus
2.7.1.127 gene Itpkb Homo sapiens
2.7.1.127 gene Itpkb Mus musculus
2.7.1.127 gene Itpkc Rattus norvegicus
2.7.1.127 gene Itpkc Mus musculus
2.7.1.127 gene Itpkc Homo sapiens

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
2.7.1.127 cytoskeleton cytoskeletal localization for isozyme Itpka Homo sapiens 5856
-
2.7.1.127 cytoskeleton cytoskeletal localization for isozyme Itpka Rattus norvegicus 5856
-
2.7.1.127 cytoskeleton cytoskeletal localization for isozyme Itpka Mus musculus 5856
-
2.7.1.127 cytoskeleton cytoskeletal localization for isozyme Itpkb or at the leading edge for Itpkb Rattus norvegicus 5856
-
2.7.1.127 cytoskeleton cytoskeletal localization for isozyme Itpkb or at the leading edge for Itpkb Homo sapiens 5856
-
2.7.1.127 cytoskeleton cytoskeletal localization for isozyme Itpkb or at the leading edge for Itpkb Mus musculus 5856
-
2.7.1.127 endoplasmic reticulum
-
 Rattus norvegicus 5783
-

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
2.7.1.127 Ca2+ the enzyme is activated by Ca2+/calmodulin Homo sapiens
2.7.1.127 Ca2+ the enzyme is activated by Ca2+/calmodulin Rattus norvegicus
2.7.1.127 Ca2+ the enzyme is activated by Ca2+/calmodulin Mus musculus
2.7.1.127 Ca2+ the enzyme is highly activated by Ca2+/calmodulin Rattus norvegicus
2.7.1.127 Ca2+ the enzyme is highly activated by Ca2+/calmodulin Homo sapiens
2.7.1.127 Ca2+ the enzyme is highly activated by Ca2+/calmodulin Mus musculus
2.7.1.127 Mg2+ required Rattus norvegicus
2.7.1.127 Mg2+ required Homo sapiens
2.7.1.127 Mg2+ required Mus musculus

Molecular Weight [Da]

EC Number Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
2.7.1.127 50000
-
-
 Homo sapiens
2.7.1.127 50000
-
-
 Rattus norvegicus
2.7.1.127 50000
-
-
 Mus musculus

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.7.1.127 ATP + 1D-myo-inositol 1,4,5-trisphosphate Rattus norvegicus
-
 ADP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate
-
 ?
2.7.1.127 ATP + 1D-myo-inositol 1,4,5-trisphosphate Homo sapiens
-
 ADP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate
-
 ?
2.7.1.127 ATP + 1D-myo-inositol 1,4,5-trisphosphate Mus musculus
-
 ADP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.7.1.127 Homo sapiens P23677 gene Itpka
-
2.7.1.127 Homo sapiens P27987 gene Itpkb
-
2.7.1.127 Homo sapiens Q96DU7 gene Itpkc
-
2.7.1.127 Mus musculus B2RXC2 gene Itpkb
-
2.7.1.127 Mus musculus Q7TS72 gene Itpkc
-
2.7.1.127 Mus musculus Q8R071 gene Itpka
-
2.7.1.127 Rattus norvegicus P17105 gene Itpka
-
2.7.1.127 Rattus norvegicus P42335 gene Itpkb
-
2.7.1.127 Rattus norvegicus Q80ZG2 gene Itpkc
-

Posttranslational Modification

EC Number Posttranslational Modification Comment Organism
2.7.1.127 phosphoprotein phosphorylation activates the activity of isozyme Itpka Rattus norvegicus
2.7.1.127 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
2.7.1.127 proteolytic modification Itpkb is very sensitive to proteolysis Rattus norvegicus
2.7.1.127 proteolytic modification Itpkb is very sensitive to proteolysis Homo sapiens
2.7.1.127 proteolytic modification Itpkb is very sensitive to proteolysis Mus musculus

Purification (Commentary)

EC Number Purification (Comment) Organism
2.7.1.127 elution of recombinant Itpka isozyme with 0.5% SDS and 0.1 mM EGTA from calmodulin affinity column Rattus norvegicus

Source Tissue

EC Number Source Tissue Comment Organism Textmining
2.7.1.127 astrocytoma cell
-
 Homo sapiens
-
2.7.1.127 blood platelet
-
 Rattus norvegicus
-
2.7.1.127 blood platelet
-
 Homo sapiens
-
2.7.1.127 brain
-
 Rattus norvegicus
-
2.7.1.127 brain
-
 Mus musculus
-
2.7.1.127 brain
-
 Homo sapiens
-
2.7.1.127 brain Itpka is particularly active in neurons of the hippocampus and cerebellum Homo sapiens
-
2.7.1.127 brain Itpka is particularly active in neurons of the hippocampus and cerebellum Rattus norvegicus
-
2.7.1.127 brain Itpka is particularly active in neurons of the hippocampus and cerebellum Mus musculus
-
2.7.1.127 brain Itpkb protein level is increased in the cerebral cortex of most patients with Alzheimer's disease compared with control subjects Homo sapiens
-
2.7.1.127 carcinoma cell
-
 Rattus norvegicus
-
2.7.1.127 carcinoma cell
-
 Homo sapiens
-
2.7.1.127 carcinoma cell
-
 Mus musculus
-
2.7.1.127 embryonic stem cell Itpkb protein level is increased upon differentiation of human embryonic stem cells Homo sapiens
-
2.7.1.127 hippocampus dendritic spines Rattus norvegicus
-
2.7.1.127 intestine
-
 Rattus norvegicus
-
2.7.1.127 intestine
-
 Homo sapiens
-
2.7.1.127 intestine
-
 Mus musculus
-
2.7.1.127 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
-
2.7.1.127 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
-
2.7.1.127 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
-
2.7.1.127 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
-
2.7.1.127 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
-
2.7.1.127 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
-
2.7.1.127 neuron localized to the post-dendritic spines of neurons. Itpka is particularly active in neurons of the hippocampus and cerebellum Homo sapiens
-
2.7.1.127 neuron localized to the post-dendritic spines of neurons. Itpka is particularly active in neurons of the hippocampus and cerebellum Rattus norvegicus
-
2.7.1.127 neuron localized to the post-dendritic spines of neurons. Itpka is particularly active in neurons of the hippocampus and cerebellum Mus musculus
-
2.7.1.127 PC-12 cell
-
 Rattus norvegicus
-
2.7.1.127 testis
-
 Rattus norvegicus
-
2.7.1.127 testis
-
 Homo sapiens
-
2.7.1.127 testis
-
 Mus musculus
-
2.7.1.127 testis high expression level Rattus norvegicus
-
2.7.1.127 thymus
-
 Rattus norvegicus
-
2.7.1.127 thymus
-
 Homo sapiens
-
2.7.1.127 thymus
-
 Mus musculus
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.7.1.127 ATP + 1D-myo-inositol 1,4,5-trisphosphate
-
 Rattus norvegicus ADP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate
-
 ?
2.7.1.127 ATP + 1D-myo-inositol 1,4,5-trisphosphate
-
 Homo sapiens ADP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate
-
 ?
2.7.1.127 ATP + 1D-myo-inositol 1,4,5-trisphosphate
-
 Mus musculus ADP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate
-
 ?

Subunits

EC Number Subunits Comment Organism
2.7.1.127 ? x * 50000, isozyme Itpka from rat brain, SDS-PAGE Rattus norvegicus
2.7.1.127 ? x * 50000, isozyme Itpka, SDS-PAGE Homo sapiens
2.7.1.127 ? x * 50000, isozyme Itpka, SDS-PAGE Mus musculus
2.7.1.127 More isozyme Itpka contains an F-actin binding site at the N-terminal part Homo sapiens
2.7.1.127 More isozyme Itpka contains an F-actin binding site at the N-terminal part Rattus norvegicus
2.7.1.127 More isozyme Itpka contains an F-actin binding site at the N-terminal part Mus musculus
2.7.1.127 More isozyme Itpkb contains an F-actin binding site at the N-terminal part Rattus norvegicus
2.7.1.127 More isozyme Itpkb contains an F-actin binding site at the N-terminal part Homo sapiens
2.7.1.127 More isozyme Itpkb contains an F-actin binding site at the N-terminal part Mus musculus

Synonyms

EC Number Synonyms Comment Organism
2.7.1.127 inositol(1,4,5)P3 3-kinase
-
 Rattus norvegicus
2.7.1.127 inositol(1,4,5)P3 3-kinase
-
 Homo sapiens
2.7.1.127 inositol(1,4,5)P3 3-kinase
-
 Mus musculus
2.7.1.127 inositol(1,4,5)trisphosphate 3-kinase
-
 Mus musculus
2.7.1.127 inositol(1,4,5)trisphosphate 3-kinases
-
 Rattus norvegicus
2.7.1.127 inositol(1,4,5)trisphosphate 3-kinases
-
 Homo sapiens
2.7.1.127 ITPKA
-
 Homo sapiens
2.7.1.127 ITPKA
-
 Rattus norvegicus
2.7.1.127 ITPKA
-
 Mus musculus
2.7.1.127 Itpkb
-
 Rattus norvegicus
2.7.1.127 Itpkb
-
 Homo sapiens
2.7.1.127 Itpkb
-
 Mus musculus
2.7.1.127 Itpkc
-
 Rattus norvegicus
2.7.1.127 Itpkc
-
 Mus musculus
2.7.1.127 Itpkc
-
 Homo sapiens

Cofactor

EC Number Cofactor Comment Organism Structure
2.7.1.127 ATP
-
 Rattus norvegicus
2.7.1.127 ATP
-
 Homo sapiens
2.7.1.127 ATP
-
 Mus musculus

General Information

EC Number General Information Comment Organism
2.7.1.127 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
2.7.1.127 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
2.7.1.127 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
2.7.1.127 malfunction isozyme Itpka-deficient mice exhibit increased LTP in the CA1 region of the hippocampus Mus musculus
2.7.1.127 malfunction mice deficient for Itpkb have a severe defect in thymocytes differentiation and thus lack peripheral T cells Mus musculus
2.7.1.127 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
2.7.1.127 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
2.7.1.127 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
2.7.1.127 additional information isozyme Itpkb contains an F-actin binding site at the N-terminal part Rattus norvegicus
2.7.1.127 additional information isozyme Itpkb contains an F-actin binding site at the N-terminal part Homo sapiens
2.7.1.127 additional information isozyme Itpkb contains an F-actin binding site at the N-terminal part Mus musculus
2.7.1.127 additional information ITPKC functional polymorphism associates with Kawasaki disease susceptibility Homo sapiens
2.7.1.127 physiological function in natural killer (NK) cells, isozyme Itpkb promotes NK-cell terminal maturation but limits NK-cell effector functions Homo sapiens
2.7.1.127 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
2.7.1.127 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
2.7.1.127 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
2.7.1.127 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
2.7.1.127 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
2.7.1.127 physiological function Itpka and Itpkb isoforms inhibit neurite outgrowth in PC12 cells, while isozyme Itpkc does not Rattus norvegicus