LMP000808 UniProt Annotations
Gene Name phosphatidylinositol 3-kinase catalytic delta polypeptide Protein Entry Q8CI98_MOUSE UniProt ID Q8CI98 Species Mouse
Comment type Description Alternative Products Event=Alternative splicing; Named isoforms=2; Name=1; Synonyms=p110-delta; IsoId=O35904-1; Sequence=Displayed; Name=2; IsoId=O35904-2; Sequence=VSP_044411, VSP_044412; Note=No experimental confirmation available.; Catalytic Activity ATP + 1-phosphatidyl-1D-myo-inositol 4,5- bisphosphate = ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5- trisphosphate. Disruption Phenotype Null mutants are viable and fertile but display defective adaptive and innate immune responses due to signaling defects in multiple cell types including B-, T- and mast and natural killer cells. {ECO:0000269|PubMed:12130661, ECO:0000269|PubMed:12235209, ECO:0000269|PubMed:15496927, ECO:0000269|PubMed:18259608, ECO:0000269|PubMed:18809712}. Enzyme Regulation Activated by growth factors and cytokine receptors through a tyrosine-kinase-dependent mechanism. Activated by RAS. IC87114 inhibits lipid kinase activity and is selective in cells at doses up to 5-10 uM. Among other effects, IC87114 reduces allergic responses, prevents the recruitment of antigen-specific T cells into target tissue, and affects natural killer cell chemotaxis. {ECO:0000269|PubMed:15496927, ECO:0000269|PubMed:18259608, ECO:0000269|PubMed:19297623}. Function Phosphoinositide-3-kinase (PI3K) that phosphorylates PftdIns(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. 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. Have 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. Have 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. {ECO:0000269|PubMed:12130661, ECO:0000269|PubMed:12235209, ECO:0000269|PubMed:15496927, ECO:0000269|PubMed:16116162, ECO:0000269|PubMed:18259608, ECO:0000269|PubMed:18809712, ECO:0000269|PubMed:19297623}. Interaction P26450:Pik3r1; NbExp=2; IntAct=EBI-6470774, EBI-641764; Pathway Phospholipid metabolism; phosphatidylinositol phosphate biosynthesis. Ptm Autophosphorylation on Ser-1038 results in the almost complete inactivation of the lipid kinase activity. {ECO:0000250}. Similarity Belongs to the PI3/PI4-kinase family. {ECO:0000255|PROSITE-ProRule:PRU00877, ECO:0000255|PROSITE- ProRule:PRU00879, ECO:0000255|PROSITE-ProRule:PRU00880}. Similarity Contains 1 C2 PI3K-type domain. {ECO:0000255|PROSITE- ProRule:PRU00880}. Similarity Contains 1 PI3K-ABD domain. {ECO:0000255|PROSITE- ProRule:PRU00877}. Similarity Contains 1 PI3K/PI4K domain. {ECO:0000255|PROSITE- ProRule:PRU00269}. Similarity Contains 1 PI3K-RBD domain. {ECO:0000255|PROSITE- ProRule:PRU00879}. Similarity Contains 1 PIK helical domain. {ECO:0000255|PROSITE- ProRule:PRU00878}. Subcellular Location Cytoplasm {ECO:0000250}. Subunit Heterodimer of a catalytic subunit PIK3CD and a p85 regulatory subunit (PIK3R1, PIK3R2 or PIK3R3). Interacts with ERAS and HRAS. {ECO:0000269|PubMed:12774123}. Tissue Specificity Isoform 1 is expressed in spleen and lung (at protein level). Isoform 1 is expressed predominantly in leukocytes. {ECO:0000269|PubMed:22020336}.
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