Tclin PIK3CG Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform

Protein Summary

Description

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. Phosphoinositide 3-kinases (PI3Ks) phosphorylate inositol lipids and are involved in the immune response. The protein encoded by this gene is a class I catalytic subunit of PI3K. Like other class I catalytic subunits (p110-alpha p110-beta, and p110-delta), the encoded protein binds a p85 regulatory subunit to form PI3K. This gene is located in a commonly deleted segment of chromosome 7 previously identified in myeloid leukemias. Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jun 2015]

Uniprot Accession IDs

• P48736
• A4D0Q6
• Q8IV23
• Q9BZC8
• PI3-kinase subunit gamma

Gene Name

• PIK3CG

Ensembl ID

• ENST00000359195
• ENSP00000352121
• ENSG00000105851
• ENST00000440650
• ENSP00000392258
• ENST00000496166
• ENSP00000419260

Symbol

• PI3K
• PIK3
• PI3CG
• PI3Kgamma
• p110gamma
• p120-PI3K

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
protein domain	1
molecular function	0.99
hub protein	0.95
pathway	0.81

Protein Classes

PANTHER Classes

Protein / Transferase / Kinase / Phosphatidylinositol 4,5-bisphosphate 3-kinase Catalytic Subunit Gamma Isoform

DTO Classes

Protein / Kinase / Non-protein Kinase / Lipid Kinase / Pi3/pi4 Kinase Family / Phosphatidylinositol 4,5-bisphosphate 3-kinase Catalytic Subunit Gamma Isoform

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 681.19   (req: < 5)

Gene RIFs: 326   (req: <= 3)

Antibodies: 890   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 681.19   (req: >= 5)

Gene RIFs: 326   (req: > 3)

Antibodies: 890   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 48

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 641

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 4