MGP Database

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MGP002293

UniProt Annotations

Entry Information
Gene Namephosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma
Protein EntryPK3CG_HUMAN
UniProt IDP48736
SpeciesHuman
Comments
Comment typeDescription
Catalytic ActivityATP + 1-phosphatidyl-1D-myo-inositol 4,5- bisphosphate = ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5- trisphosphate.
Catalytic ActivityATP + a protein = ADP + a phosphoprotein.
Enzyme RegulationActivated by both the alpha and the beta-gamma G proteins following stimulation of G protein-coupled receptors (GPCRs). Activation by GPCRs is assisted by the regulatory subunits (PIK3R5 or PIK3R6) leading to the translocation from the cytosol to the plasma membrane and to kinase activation. Inhibited by AS-604850 and AS-605240. {ECO:0000269|PubMed:16127437, ECO:0000269|PubMed:7624799}.
FunctionPhosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Links G-protein coupled receptor activation to PIP3 production. Involved in immune, inflammatory and allergic responses. Modulates leukocyte chemotaxis to inflammatory sites and in response to chemoattractant agents. May control leukocyte polarization and migration by regulating the spatial accumulation of PIP3 and by regulating the organization of F-actin formation and integrin- based adhesion at the leading edge. Controls motility of dendritic cells. Together with PIK3CD is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in T-lymphocyte migration. Regulates T-lymphocyte proliferation and cytokine production. Together with PIK3CD participates in T-lymphocyte development. Required for B- lymphocyte development and signaling. Together with PIK3CD participates in neutrophil respiratory burst. Together with PIK3CD is involved in neutrophil chemotaxis and extravasation. Together with PIK3CB promotes platelet aggregation and thrombosis. Regulates alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) adhesive function in platelets downstream of P2Y12 through a lipid kinase activity-independent mechanism. May have also a lipid kinase activity-dependent function in platelet aggregation. Involved in endothelial progenitor cell migration. Negative regulator of cardiac contractility. Modulates cardiac contractility by anchoring protein kinase A (PKA) and PDE3B activation, reducing cAMP levels. Regulates cardiac contractility also by promoting beta-adrenergic receptor internalization by binding to ADRBK1 and by non-muscle tropomyosin phosphorylation. Also has serine/threonine protein kinase activity: both lipid and protein kinase activities are required for beta-adrenergic receptor endocytosis. May also have a scaffolding role in modulating cardiac contractility. Contributes to cardiac hypertrophy under pathological stress. Through simultaneous binding of PDE3B to RAPGEF3 and PIK3R6 is assembled in a signaling complex in which the PI3K gamma complex is activated by RAPGEF3 and which is involved in angiogenesis. {ECO:0000269|PubMed:12163475, ECO:0000269|PubMed:15294162, ECO:0000269|PubMed:16094730, ECO:0000269|PubMed:21393242, ECO:0000269|PubMed:7624799}.
InteractionQ13370:PDE3B; NbExp=3; IntAct=EBI-1030384, EBI-6172856; O02696:PIK3R5 (xeno); NbExp=6; IntAct=EBI-1030384, EBI-6172343;
MiscellaneousCandidate target in therapy for inflammatory diseases. Selective inhibitors and protein ablation are anti- inflammatory in multiple disease models such as asthma, rheumatoid arthritis, allergy, systemic lupus erythematosus, airway inflammation, lung injury and pancreatitis (PubMed:18278175). {ECO:0000305|PubMed:18278175}.
PathwayPhospholipid metabolism; phosphatidylinositol phosphate biosynthesis.
SimilarityBelongs to the PI3/PI4-kinase family. {ECO:0000255|PROSITE-ProRule:PRU00877, ECO:0000255|PROSITE- ProRule:PRU00879, ECO:0000255|PROSITE-ProRule:PRU00880}.
SimilarityContains 1 C2 PI3K-type domain. {ECO:0000255|PROSITE- ProRule:PRU00880}.
SimilarityContains 1 PI3K-ABD domain. {ECO:0000255|PROSITE- ProRule:PRU00877}.
SimilarityContains 1 PI3K/PI4K domain. {ECO:0000255|PROSITE- ProRule:PRU00269}.
SimilarityContains 1 PI3K-RBD domain. {ECO:0000255|PROSITE- ProRule:PRU00879}.
SimilarityContains 1 PIK helical domain. {ECO:0000255|PROSITE- ProRule:PRU00878}.
Subcellular LocationCytoplasm {ECO:0000269|PubMed:12163475}. Cell membrane {ECO:0000269|PubMed:12163475}.
SubunitHeterodimer of a catalytic subunit PIK3CG and a PIK3R5 or PIK3R6 regulatory subunit. Interacts with ADRBK1 through the PIK helical domain. Interaction with ADRBK1 is required for targeting to agonist-occupied receptor. Interacts with PDE3B (By similarity). Interacts with TPM2. Interacts with EPHA8; regulates integrin-mediated cell adhesion to substrate. Interacts with HRAS; the interaction is required for membrane recruitment and beta- gamma G protein dimer-dependent activation of the PI3K gamma complex PIK3CG:PIK3R6 (By similarity). {ECO:0000250}.
Tissue SpecificityPancreas, skeletal muscle, liver and heart. {ECO:0000269|PubMed:7624799}.
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