Names & Taxonomy
- Uniprot ID:
- P48736
- Entry Name:
- PK3CG_HUMAN
- Status:
- reviewed
- Protein Names:
- Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (PI3-kinase subunit gamma) (PI3K-gamma) (PI3Kgamma) (PtdIns-3-kinase subunit gamma) (EC 2.7.1.153) (Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit gamma) (PtdIns-3-kinase subunit p110-gamma) (p110gamma) (Phosphoinositide-3-kinase catalytic gamma polypeptide) (Serine/threonine protein kinase PIK3CG) (EC 2.7.11.1) (p120-PI3K)
- Gene Names:
- PIK3CG
- Gene Names Primary:
- PIK3CG
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 1102
- Sequence:
- MELENYKQPVVLREDNCRRRRRMKPRSAAASLSSMELIPIEFVLPTSQRKCKSPETALLHVAGHGNVEQMKAQVWLRALETSVAADFYHRLGPHHFLLLYQKKGQWYEIYDKYQVVQTLDCLRYWKATHRSPGQIHLVQRHPPSEESQAFQRQLTALIGYDVTDVSNVHDDELEFTRRGLVTPRMAEVASRDPKLYAMHPWVTSKPLPEYLWKKIANNCIFIVIHRSTTSQTIKVSPDDTPGAILQSFFTKMAKKKSLMDIPESQSEQDFVLRVCGRDEYLVGETPIKNFQWVRHCLKNGEEIHVVLDTPPDPALDEVRKEEWPLVDDCTGVTGYHEQLTIHGKDHESVFTVSLWDCDRKFRVKIRGIDIPVLPRNTDLTVFVEANIQHGQQVLCQRRTSPKPFTEEVLWNVWLEFSIKIKDLPKGALLNLQIYCGKAPALSSKASAESPSSESKGKVQLLYYVNLLLIDHRFLLRRGEYVLHMWQISGKGEDQGSFNADKLTSATNPDKENSMSISILLDNYCHPIALPKHQPTPDPEGDRVRAEMPNQLRKQLEAIIATDPLNPLTAEDKELLWHFRYESLKHPKAYPKLFSSVKWGQQEIVAKTYQLLARREVWDQSALDVGLTMQLLDCNFSDENVRAIAVQKLESLEDDDVLHYLLQLVQAVKFEPYHDSALARFLLKRGLRNKRIGHFLFWFLRSEIAQSRHYQQRFAVILEAYLRGCGTAMLHDFTQQVQVIEMLQKVTLDIKSLSAEKYDVSSQVISQLKQKLENLQNSQLPESFRVPYDPGLKAGALAIEKCKVMASKKKPLWLEFKCADPTALSNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTIAKIQQSTVGNTGAFKDEVLNHWLKEKSPTEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMITETGNLFHIDFGHILGNYKSFLGINKERVPFVLTPDFLFVMGTSGKKTSPHFQKFQDICVKAYLALRHHTNLLIILFSMMLMTGMPQLTSKEDIEYIRDALTVGKNEEDAKKYFLDQIEVCRDKGWTVQFNWFLHLVLGIKQGEKHSA
- Proteomes:
- UP000005640
Subcellular location
- Subcellular Location:
- Cytoplasm
Function
- 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.
- Pathway:
- Phospholipid metabolism; phosphatidylinositol phosphate biosynthesis.
- Catalytic Activity:
- ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate = ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate.; ATP + a protein = ADP + a phosphoprotein.
- Enzyme Regulation:
- 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.
- Gene Ontology Go:
- cytoplasm
cytosol
mast cell granule
membrane
phosphatidylinositol 3-kinase complex, class IB
plasma membrane
1-phosphatidylinositol-3-kinase activity
1-phosphatidylinositol-4-phosphate 3-kinase activity
ATP binding
ephrin receptor binding
phosphatidylinositol 3-kinase activity
phosphatidylinositol-4,5-bisphosphate 3-kinase activity
protein kinase activity
protein serine/threonine kinase activity
adaptive immune response
angiogenesis
blood coagulation
cellular response to cAMP
cytokine production
dendritic cell chemotaxis
endocytosis
G-protein coupled receptor signaling pathway
hepatocyte apoptotic process
inflammatory response
innate immune response
mast cell degranulation
natural killer cell chemotaxis
negative regulation of cardiac muscle contraction
negative regulation of fibroblast apoptotic process
negative regulation of triglyceride catabolic process
neutrophil chemotaxis
neutrophil extravasation
phosphatidylinositol 3-kinase signaling
phosphatidylinositol biosynthetic process
phospholipid metabolic process
platelet activation
platelet aggregation
positive regulation of acute inflammatory response
positive regulation of cytosolic calcium ion concentration
positive regulation of MAP kinase activity
positive regulation of protein kinase B signaling
regulation of calcium ion transmembrane transport
regulation of cell adhesion mediated by integrin
respiratory burst involved in defense response
secretory granule localization
small molecule metabolic process
T cell activation
T cell chemotaxis
T cell proliferation - Gene Ontology Biological Process:
- adaptive immune response
angiogenesis
blood coagulation
cellular response to cAMP
cytokine production
dendritic cell chemotaxis
endocytosis
G-protein coupled receptor signaling pathway
hepatocyte apoptotic process
inflammatory response
innate immune response
mast cell degranulation
natural killer cell chemotaxis
negative regulation of cardiac muscle contraction
negative regulation of fibroblast apoptotic process
negative regulation of triglyceride catabolic process
neutrophil chemotaxis
neutrophil extravasation
phosphatidylinositol 3-kinase signaling
phosphatidylinositol biosynthetic process
phospholipid metabolic process
platelet activation
platelet aggregation
positive regulation of acute inflammatory response
positive regulation of cytosolic calcium ion concentration
positive regulation of MAP kinase activity
positive regulation of protein kinase B signaling
regulation of calcium ion transmembrane transport
regulation of cell adhesion mediated by integrin
respiratory burst involved in defense response
secretory granule localization
small molecule metabolic process
T cell activation
T cell chemotaxis
T cell proliferation - Gene Ontology Molecular Function:
- 1-phosphatidylinositol-3-kinase activity
1-phosphatidylinositol-4-phosphate 3-kinase activity
ATP binding
ephrin receptor binding
phosphatidylinositol 3-kinase activity
phosphatidylinositol-4,5-bisphosphate 3-kinase activity
protein kinase activity
protein serine/threonine kinase activity - Gene Ontology Cellular Component:
- cytoplasm
cytosol
mast cell granule
membrane
phosphatidylinositol 3-kinase complex, class IB
plasma membrane - Keywords:
- 3D-structure
ATP-binding
Angiogenesis
Cell membrane
Chemotaxis
Complete proteome
Cytoplasm
Endocytosis
Immunity
Inflammatory response
Kinase
Membrane
Nucleotide-binding
Phosphoprotein
Reference proteome
Serine/threonine-protein kinase
Transferase - Interacts With:
- Q13370; O02696