ID:PK3CG_HUMAN DESCRIPTION: RecName: Full=Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform; Short=PI3-kinase subunit gamma; Short=PI3K-gamma; Short=PI3Kgamma; Short=PtdIns-3-kinase subunit gamma; EC=2.7.1.153; AltName: Full=Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit gamma; Short=PtdIns-3-kinase subunit p110-gamma; Short=p110gamma; AltName: Full=Phosphoinositide-3-kinase catalytic gamma polypeptide; AltName: Full=Serine/threonine protein kinase PIK3CG; EC=2.7.11.1; AltName: Full=p120-PI3K; 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. 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. 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. Inhibited by AS-604850 and AS-605240. 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. 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 HRAS1; the interaction is required for membrane recruitment and beta-gamma G protein dimer-dependent activation of the PI3K gamma complex PIK3CG:PIK3R6 (By similarity). INTERACTION: Q13370:PDE3B; NbExp=3; IntAct=EBI-1030384, EBI-6172856; O02696:PIK3R5 (xeno); NbExp=6; IntAct=EBI-1030384, EBI-6172343; SUBCELLULAR LOCATION: Cytoplasm. Cell membrane. TISSUE SPECIFICITY: Pancreas, skeletal muscle, liver and heart. MISCELLANEOUS: Candidate 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). 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.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P48736
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
BioCarta from NCI Cancer Genome Anatomy Project h_bcellsurvivalPathway - B Cell Survival Pathway h_gcrPathway - Corticosteroids and cardioprotection h_insulinPathway - Insulin Signaling Pathway h_nfatPathway - NFAT and Hypertrophy of the heart (Transcription in the broken heart) h_pdgfPathway - PDGF Signaling Pathway h_aktPathway - AKT Signaling Pathway h_edg1Pathway - Phospholipids as signalling intermediaries h_erk5Pathway - Role of Erk5 in Neuronal Survival h_ghPathway - Growth Hormone Signaling Pathway h_il7Pathway - IL-7 Signal Transduction h_longevityPathway - The IGF-1 Receptor and Longevity h_pparaPathway - Mechanism of Gene Regulation by Peroxisome Proliferators via PPARa(alpha) h_rac1Pathway - Rac 1 cell motility signaling pathway h_tffPathway - Trefoil Factors Initiate Mucosal Healing h_ecmPathway - Erk and PI-3 Kinase Are Necessary for Collagen Binding in Corneal Epithelia h_metPathway - Signaling of Hepatocyte Growth Factor Receptor h_tcrPathway - T Cell Receptor Signaling Pathway h_ctcfPathway - CTCF: First Multivalent Nuclear Factor h_fcer1Pathway - Fc Epsilon Receptor I Signaling in Mast Cells h_ngfPathway - Nerve growth factor pathway (NGF) h_plcPathway - Phospholipase C Signaling Pathway h_achPathway - Role of nicotinic acetylcholine receptors in the regulation of apoptosis h_gleevecpathway - Inhibition of Cellular Proliferation by Gleevec h_hdacPathway - Control of skeletal myogenesis by HDAC & calcium/calmodulin-dependent kinase (CaMK) h_her2Pathway - Role of ERBB2 in Signal Transduction and Oncology h_Par1Pathway - Thrombin signaling and protease-activated receptors h_TPOPathway - TPO Signaling Pathway h_igf1Pathway - IGF-1 Signaling Pathway h_il2rbPathway - IL-2 Receptor Beta Chain in T cell Activation h_arfPathway - Tumor Suppressor Arf Inhibits Ribosomal Biogenesis h_badPathway - Regulation of BAD phosphorylation h_hcmvPathway - Human Cytomegalovirus and Map Kinase Pathways h_rasPathway - Ras Signaling Pathway h_vegfPathway - VEGF, Hypoxia, and Angiogenesis
Reactome (by CSHL, EBI, and GO)
Protein P48736 (Reactome details) participates in the following event(s):
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
