. "SEQUENCE 1102 AA; 126400 MW; 7675848792D76734 CRC64;"^^ . "FUNCTION: Phosphoinositide-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. Contribute to cardiac hypertrophy under pathological stress. CATALYTIC ACTIVITY: ATP + 1-phosphatidyl-1D-myo-inositol 4,5- bisphosphate = ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5- trisphosphate. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. ENZYME REGULATION: Activated 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. Wortmannin sensitive in nM range. Inhibited by AS252424. PATHWAY: Phospholipid metabolism; phosphatidylinositol phosphate biosynthesis. SUBUNIT: Heterodimer of a catalytic subunit PIK3CG and a PIK3R5 or PIK3R6 regulatory subunit. Interacts with ADRBK1 through the PIK helical domain (By similarity). Interaction with ADRBK1 is required for targeting to agonist-occupied receptor. Interacts with PDE3B. Interacts with TPM2 (By similarity). Interacts with EPHA8; regulates integrin-mediated cell adhesion to substrate. SUBCELLULAR LOCATION: Cytoplasm (By similarity). Cell membrane (By similarity). PTM: Phosphorylated at Thr-1024 by PKA. Phosphorylation inhibits lipid kinase activity. DISRUPTION PHENOTYPE: Viable and fertile. Display abnormalities when the immune system is stressed. Reduced leukocyte migration in response to chemotactic agents and towards the site of inflammation. Reduced neutrophil oxidative burst in response to chemotactic agents. Reduced thymocyte survival and defective T lymphocyte activation. Protected from leukocyte infiltration of synovia in a model of rheumatoid arthritis. Dendritic cell showed reduced response to chemokines and migration to draining lymph nodes under inflammatory conditions. Platelets have defects in thrombus formation. Increased cardiac contractility. Display myocardial damage after transverse aortic constriction. SIMILARITY: Belongs to the PI3/PI4-kinase family. SIMILARITY: Contains 1 C2 PI3K-type domain. SIMILARITY: Contains 1 PI3K-ABD domain. SIMILARITY: Contains 1 PI3K-RBD domain. SIMILARITY: Contains 1 PI3K/PI4K domain. SIMILARITY: Contains 1 PIK helical domain. GENE SYNONYMS:Pik3cg Pi3kg1. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License."^^ . . . . . . . . "PK3CG_MOUSE"^^ . "2.7.11.1"^^ . "2.7.1.153"^^ . "Phosphoinositide-3-kinase catalytic gamma polypeptide"^^ . "PtdIns-3-kinase subunit gamma"^^ . "PI3K-gamma"^^ . "p120-PI3K"^^ . "PI3-kinase subunit gamma"^^ . "PI3Kgamma"^^ . "PtdIns-3-kinase subunit p110-gamma"^^ . "p110gamma"^^ . "Pik3cg"^^ . "Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit gamma"^^ . "Serine/threonine protein kinase PIK3CG"^^ . . . . "MELENYEQPVVLREDNLRRRRRMKPRSAAGSLSSMELIPIEFVLPTSQRISKTPETALLHVAGHGNVEQMKAQVWLRALETSVAAEFYHRLGPDQFLLLYQKKGQWYEIYDRYQVVQTLDCLHYWKLMHKSPGQIHVVQRHVPSEETLAFQKQLTSLIGYDVTDISNVHDDELEFTRRRLVTPRMAEVAGRDAKLYAMHPWVTSKPLPDYLSKKIANNCIFIVIHRGTTSQTIKVSADDTPGTILQSFFTKMAKKKSLMNISESQSEQDFVLRVCGRDEYLVGETPLKNFQWVRQCLKNGDEIHLVLDTPPDPALDEVRKEEWPLVDDCTGVTGYHEQLTIHGKDHESVFTVSLWDCDRKFRVKIRGIDIPVLPRNTDLTVFVEANIQHGQQVLCQRRTSPKPFAEEVLWNVWLEFGIKIKDLPKGALLNLQIYCCKTPSLSSKASAETPGSESKGKAQLLYYVNLLLIDHRFLLRHGDYVLHMWQISGKAEEQGSFNADKLTSATNPDKENSMSISILLDNYCHPIALPKHRPTPDPEGDRVRAEMPNQLRKQLEAIIATDPLNPLTAEDKELLWHFRYESLKHPKAYPKLFSSVKWGQQEIVAKTYQLLARREIWDQSALDVGLTMQLLDCNFSDENVRAIAVQKLESLEDDDVLHYLLQLVQAVKFEPYHDSALARFLLKRGLRNKRIGHFLFWFLRSEIAQSRHYQQRFAVILEAYLRGCGTAMLQDFTQQVHVIEMLQKVTIDIKSLSAEKYDVSSQVISQLKQKLESLQNSNLPESFRVPYDPGLKAGTLVIEKCKVMASKKKPLWLEFKCADPTVLSNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTIAQIQQSTVGNTGAFKDEVLNHWLKEKCPIEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMISETGNLFHIDFGHILGNYKSFLGINKERVPFVLTPDFLFVMGSSGKKTSPHFQKFQDVCVRAYLALRHHTNLLIILFSMMLMTGMPQLTSKEDIEYIRDALTVGKSEEDAKKYFLDQIEVCRDKGWTVQFNWFLHLVLGIKQGEKHSA"^^ . "Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform"^^ .