PIK3CD

Phosphoinositide 3-kinases (PI3Ks) phosphorylate inositol lipids and are involved in the immune response. The protein encoded by this gene is a class I PI3K found primarily in leukocytes. Like other class I PI3Ks (p110-alpha p110-beta, and p110-gamma), the encoded protein binds p85 adapter proteins and GTP-bound RAS. However, unlike the other class I PI3Ks, this protein phosphorylates itself, not p85 protein.[provided by RefSeq, Jul 2010]

Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Delta

Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides (PubMed:9235916).
Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396).
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. Mediates immune responses. Plays a role in B-cell development, proliferation, migration, and function. Required for B-cell receptor (BCR) signaling. Mediates B-cell proliferation response to anti-IgM, anti-CD40 and IL4 stimulation. Promotes cytokine production in response to TLR4 and TLR9. Required for antibody class switch mediated by TLR9. Involved in the antigen presentation function of B-cells. Involved in B-cell chemotaxis in response to CXCL13 and sphingosine 1-phosphate (S1P). Required for proliferation, signaling and cytokine production of naive, effector and memory T-cells. Required for T-cell receptor (TCR) signaling. Mediates TCR signaling events at the immune synapse. Activation by TCR leads to antigen-dependent memory T-cell migration and retention to antigenic tissues. Together with PIK3CG participates in T-cell development. Contributes to T-helper cell expansion and differentiation. Required for T-cell migration mediated by homing receptors SELL/CD62L, CCR7 and S1PR1 and antigen dependent recruitment of T-cells. Together with PIK3CG is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in NK cell receptor activation. Plays a role in NK cell maturation and cytokine production. Together with PIK3CG is involved in neutrophil chemotaxis and extravasation. Together with PIK3CG participates in neutrophil respiratory burst. Plays important roles in mast-cell development and mast cell mediated allergic response. Involved in stem cell factor (SCF)-mediated proliferation, adhesion and migration. Required for allergen-IgE-induced degranulation and cytokine release. The lipid kinase activity is required for its biological function. Isoform 2 may be involved in stabilizing total RAS levels, resulting in increased ERK phosphorylation and increased PI3K activity.

Adaptive immune responseManual Assertion Based On ExperimentTAS:UniProtKB
B cell activationManual Assertion Based On ExperimentTAS:UniProtKB
B cell chemotaxisManual Assertion Based On ExperimentTAS:UniProtKB
B cell differentiation1 PublicationIC:ComplexPortal
B cell receptor signaling pathwayManual Assertion Based On ExperimentTAS:UniProtKB
Cell migrationManual Assertion Based On ExperimentIBA:GO_Central
Immune response1 PublicationIC:ComplexPortal
Inflammatory responseManual Assertion Based On ExperimentTAS:UniProtKB
Innate immune responseManual Assertion Based On ExperimentTAS:UniProtKB
Mast cell chemotaxisManual Assertion Based On ExperimentTAS:UniProtKB
Mast cell degranulationManual Assertion Based On ExperimentTAS:UniProtKB
Mast cell differentiationManual Assertion Based On ExperimentTAS:UniProtKB
Natural killer cell activationManual Assertion Based On ExperimentTAS:UniProtKB
Natural killer cell chemotaxisManual Assertion Based On ExperimentTAS:UniProtKB
Natural killer cell differentiationManual Assertion Based On ExperimentTAS:UniProtKB
Neutrophil chemotaxisManual Assertion Based On ExperimentTAS:UniProtKB
Neutrophil extravasationManual Assertion Based On ExperimentTAS:UniProtKB
Phosphatidylinositol 3-kinase signalingManual Assertion Based On ExperimentIMP:CAFA
Phosphatidylinositol phosphate biosynthetic processManual Assertion Based On ExperimentIBA:GO_Central
Phosphatidylinositol-3-phosphate biosynthetic processManual Assertion Based On ExperimentIBA:GO_Central
Phosphatidylinositol-mediated signalingManual Assertion Based On ExperimentIBA:GO_Central
PhosphorylationManual Assertion Based On ExperimentIDA:MGI
Positive regulation of angiogenesisISS:BHF-UCL
Positive regulation of cell migrationManual Assertion Based On ExperimentIMP:CACAO
Positive regulation of cell migration by vascular endothelial growth factor signaling pathwayManual Assertion Based On ExperimentIGI:BHF-UCL
Positive regulation of cytokine productionManual Assertion Based On ExperimentTAS:UniProtKB
Positive regulation of endothelial cell migrationManual Assertion Based On ExperimentIGI:BHF-UCL
Positive regulation of endothelial cell proliferationManual Assertion Based On ExperimentIGI:BHF-UCL
Positive regulation of epithelial tube formationManual Assertion Based On ExperimentIGI:BHF-UCL
Positive regulation of gene expressionManual Assertion Based On ExperimentIMP:CACAO
Positive regulation of neutrophil apoptotic processManual Assertion Based On ExperimentIMP:CAFA
Positive regulation of protein kinase B signalingManual Assertion Based On ExperimentIGI:BHF-UCL
Protein phosphorylation1 PublicationNAS:UniProtKB
Respiratory burst involved in defense responseManual Assertion Based On ExperimentTAS:UniProtKB
Signal transduction1 PublicationNAS:UniProtKB
T cell activationManual Assertion Based On ExperimentTAS:UniProtKB
T cell chemotaxisManual Assertion Based On ExperimentTAS:UniProtKB
T cell differentiationManual Assertion Based On ExperimentTAS:UniProtKB
T cell receptor signaling pathwayManual Assertion Based On ExperimentTAS:UniProtKB

Cytoplasm

Immunodeficiency 14A, autosomal dominant (IMD14A):
A disorder characterized by recurrent respiratory infections, progressive airway damage, lymphopenia, increased circulating transitional B cells, increased immunoglobulin M, reduced immunoglobulin G2 levels in serum, and impaired vaccine responses.
Immunodeficiency 14B, autosomal recessive (IMD14B):
An autosomal recessive, primary immunodeficiency characterized by recurrent sinopulmonary infections apparent in early childhood. Some patients may develop inflammatory bowel disease or osteomyelitis. Immunological features include hypogammaglobulinemia, decreased levels of B cells, and evidence of impaired immune-mediated cytotoxicity and defective T-cell function.
Roifman-Chitayat syndrome (ROCHIS):
An autosomal recessive digenic disorder characterized by global developmental delay, variable neurologic features such as seizures and ataxia, optic atrophy, dysmorphic facial features, distal skeletal anomalies, and recurrent invasive infections due to combined immunodeficiency.

Autophosphorylation on Ser-1039 results in the almost complete inactivation of the lipid kinase activity.