InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PIK3CG

Summary

InnateDB Protein

IDBP-35340.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

PIK3CG

Protein Name

phosphoinositide-3-kinase, catalytic, gamma polypeptide

Synonyms

p110gamma; p120-PI3K; PI3CG; PI3K; PI3Kgamma; PIK3;

Species

Homo sapiens

Ensembl Protein

ENSP00000352121

InnateDB Gene

IDBG-35338 (PIK3CG)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:12163475, ECO:0000269PubMed:15294162, ECO:0000269PubMed:16094730, ECO:0000269PubMed:21393242, ECO:0000269PubMed:7624799}.

Subcellular Localization

Cytoplasm {ECO:0000269PubMed:12163475}. Cell membrane {ECO:0000269PubMed:12163475}.

Disease Associations

Tissue Specificity

Pancreas, skeletal muscle, liver and heart. {ECO:0000269PubMed:7624799}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 44 experimentally validated interaction(s) in this database.
They are also associated with 12 interaction(s) predicted by orthology.

Experimentally validated
Total	44 [view]
Protein-Protein	43 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	12 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0005488	binding
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016303	1-phosphatidylinositol-3-kinase activity
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0016773	phosphotransferase activity, alcohol group as acceptor
GO:0035004	phosphatidylinositol 3-kinase activity
GO:0035005	1-phosphatidylinositol-4-phosphate 3-kinase activity
GO:0046875	ephrin receptor binding
GO:0046934	phosphatidylinositol-4,5-bisphosphate 3-kinase activity

Biological Process

GO:0001525	angiogenesis
GO:0001816	cytokine production
GO:0002250	adaptive immune response
GO:0002407	dendritic cell chemotaxis
GO:0002675	positive regulation of acute inflammatory response
GO:0002679	respiratory burst involved in defense response
GO:0006468	protein phosphorylation
GO:0006644	phospholipid metabolic process
GO:0006661	phosphatidylinositol biosynthetic process
GO:0006897	endocytosis
GO:0006954	inflammatory response
GO:0007186	G-protein coupled receptor signaling pathway
GO:0007204	positive regulation of cytosolic calcium ion concentration
GO:0007596	blood coagulation
GO:0010818	T cell chemotaxis
GO:0010897	negative regulation of triglyceride catabolic process
GO:0014065	phosphatidylinositol 3-kinase signaling
GO:0030168	platelet activation
GO:0030593	neutrophil chemotaxis
GO:0032252	secretory granule localization
GO:0033628	regulation of cell adhesion mediated by integrin
GO:0035747	natural killer cell chemotaxis
GO:0036092	phosphatidylinositol-3-phosphate biosynthetic process
GO:0042098	T cell proliferation
GO:0042110	T cell activation
GO:0043303	mast cell degranulation
GO:0043406	positive regulation of MAP kinase activity
GO:0044281	small molecule metabolic process
GO:0045087	innate immune response
GO:0046854	phosphatidylinositol phosphorylation
GO:0048015	phosphatidylinositol-mediated signaling
GO:0051897	positive regulation of protein kinase B signaling
GO:0055118	negative regulation of cardiac muscle contraction
GO:0070527	platelet aggregation
GO:0072672	neutrophil extravasation
GO:0097284	hepatocyte apoptotic process
GO:2000270	negative regulation of fibroblast apoptotic process

Cellular Component

GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0005942	phosphatidylinositol 3-kinase complex
GO:0005944	1-phosphatidylinositol-4-phosphate 3-kinase, class IB complex
GO:0016020	membrane
GO:0042629	mast cell granule

Protein Structure and Domains

PDB ID

InterPro

IPR000008 C2 domain
IPR000341 Phosphatidylinositol 3-kinase Ras-binding (PI3K RBD) domain
IPR000403 Phosphatidylinositol 3-/4-kinase, catalytic domain
IPR001263 Phosphoinositide 3-kinase, accessory (PIK) domain
IPR002420 Phosphatidylinositol 3-kinase, C2 domain
IPR011009 Protein kinase-like domain
IPR016024 Armadillo-type fold
IPR029071 Ubiquitin-related domain

PFAM

PF00168
PF00794
PF00454
PF00613
PF00792

PRINTS

PR00360

PIRSF

SMART

SM00239
SM00144
SM00146
SM00145
SM00142

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt