lmmol · Proteins

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

UniProt P48736 Organism Homo sapiens Gene PIK3CG EC 2.7.1.137, 2.7.1.153, 2.7.1.154, 2.7.11.1

Also known as: PIK3CG

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, activation, 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. In neutrophils, participates in a phospholipase C-activating N-formyl peptide-activated GPCR (G protein-coupled receptor) signaling pathway downstream of RASGRP4-mediated Ras-activation, to promote neutrophil functional responses (By similarity).

Classification

Family (Pfam)
PF00454 PI3_PI4_kinase, PF00792 PI3K_C2, PF00794 PI3K_rbd, PF00613 PI3Ka, PF19710 PIK3CG_ABD
InterPro
ARM-type_fold, C2_domain_sf, Kinase-like_dom_sf, PI3/4_kinase, PI3/4_kinase_cat_dom, PI3/4_kinase_cat_sf, PI3/4_kinase_CS, PI3K-type_C2_dom, PI3K_ABD, PI3K_accessory_dom, PI3K_accessory_sf, PI3K_Ras-bd_dom, PIK3CG_ABD, Ubiquitin-like_domsf
Functional cluster
Zinc-Finger & Ubiquitination Proteins

Experimental structures · PDB · 107

A predicted model is available from AlphaFold.

Gene Ontology · 47

Disease associations

Drugs targeting this protein · 27

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Literature · 22 cited papers

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