Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

PIK3CG (P48736) - Overview - Molecular Target Synopsis

Protein


PIK3CG, Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
Enzyme Classification 2.7.1.153
UniProt P48736

Also Known as PK3CG_HUMAN, PIK3CG

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 GRK2 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. Heterodimer of a catalytic subunit PIK3CG and a PIK3R5 or PIK3R6 regulatory subunit. Interacts with GRK2 through the PIK helical domain. Interaction with GRK2 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.

6FH5
PI3KG IN COMPLEX WITH COMPOUND 7
RCSB/PDB
Inspect Structure
See all 3D Structures for PIK3CG

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: PIK3CG is active in the following subcellular-locations: cell membrane, cytoplasm.
GO terms: PIK3CG is active in the following subcellular-locations: cytoplasm, cytosol, mast cell granule, membrane, phosphatidylinositol 3-kinase complex, phosphatidylinositol 3-kinase complex, plasma membrane.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project PIK3CG has gain in 9 cell-lines, loss in 1 cell-lines and no signal in 995 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: MOLT_4, CAKI_1, SK_OV_3

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: MOLP-8, A3/KAW, A4/Fuk

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: CD14-positive monocyte, K562, CD20-positive B cell

(see details)

RNA Interference


PIK3CG was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: OV90, HCC38. (see details)

3D Structures


For PIK3CG there are:
93 structures (93 chains) solved
91 are solved in complex with at least one small molecule ligand
1 are solved with an approved drug

PIK3CG is solved in complex with the approved drug(s):

6E2/COPANLISIB (5G2N_A).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


PIK3CG has been screened with 2659 compounds (3034 bioactivities), 1154 compounds have bioactivities that show binding affinity of <= 500nM (1328 bioactivities). (see details)