PIK3CD encodes p110Ξ΄, a class IA phosphoinositide 3-kinase catalytic subunit enriched in leukocytes. Complexes with p85-family regulatory subunits generate PIP3 at activated membranes and couple antigen, costimulatory and other receptor inputs to AKT, BTK and additional phosphoinositide-sensitive effectors. This signaling supports lymphocyte activation, differentiation and migration, alongside myeloid and mast-cell functions. p110Ξ΄ also acts in endothelial and tumor-cell contexts. Its biochemical substrate range includes phosphatidylinositol and PI4P, and Ser1039 autophosphorylation can inhibit lipid kinase activity. A shorter splice product has distinct Ras-regulatory properties.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | MODIFY | Summary: p110Ξ΄ has a cytosolic pool available for recruitment to receptor-associated membranes. Reason: The soluble pool is part of the normal signaling mechanism, not peripheral simply because activated enzyme encounters membrane substrates. Curated cytoplasmic localization in PMID:22020336 and the class IA recruitment studies support this assignment; refine the general cytoplasm term to the existing cytosol term. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000005673 SUPPORTS TRANSFER cytoplasm: The soluble pool is part of the normal signaling mechanism, not peripheral simply because activated enzyme encounters membrane substrates. Curated cytoplasmic localization in PMID:22020336 and the class IA recruitment studies support this assignment; refine the general cytoplasm term to the existing cytosol term. Proposed replacements: cytosol Supporting Evidence: file:human/PIK3CD/PIK3CD-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22020336}. |
| GO:0016477 cell migration | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Supported cell-migration role in specific leukocyte and glioma contexts, but non-core relative to lipid kinase signaling. Reason: PIK3CD knockdown decreases glioma-cell migration and PI3Kdelta also affects leukocyte migration; these are downstream context-specific outputs rather than the core function. Supporting Evidence: PMID:22079609 Interestingly, knockdown of p110Ξ΄ decreased the cell migration and invasion ability of all GBM cell lines tested. PMID:20940048 PI3KΞ΄ participates in the development, activation and migration of T cells and NK cells. |
| GO:0005942 phosphatidylinositol 3-kinase complex | IBA GO_REF:0000033 | MODIFY | Summary: p110Ξ΄ is the catalytic subunit of a class IA PI3K complex. Reason: Refine the general PI3K-complex claim to the p85-family heterodimer demonstrated for p110Ξ΄, preserving the PAINT assessment of conserved complex participation. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000799655 SUPPORTS TRANSFER phosphatidylinositol 3-kinase complex: Refine the general PI3K-complex claim to the p85-family heterodimer demonstrated for p110Ξ΄, preserving the PAINT assessment of conserved complex participation. Proposed replacements: phosphatidylinositol 3-kinase complex, class IA Supporting Evidence: file:human/PIK3CD/PIK3CD-uniprot.txt Heterodimer of a catalytic subunit PIK3CD and a p85 regulatory subunit (PIK3R1, PIK3R2 or PIK3R3). PMID:9235916 Recombinant p110delta phosphorylates phosphatidylinositol and coimmunoprecipitates with p85. |
| GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction | IBA GO_REF:0000033 | ACCEPT | Summary: Supported PI3K/AKT signaling annotation downstream of PIK3CD-generated PIP3. Reason: PIP3 produced by p110delta recruits AKT-linked signaling modules. This pathway term captures the central signaling output of PI3Kdelta even when the initiating receptor or cell type differs. Supporting Evidence: file:human/PIK3CD/PIK3CD-deep-research-falcon.md **PIK3CD** encodes the catalytic subunit **p110Ξ΄** of **class IA phosphoinositide 3-kinase (PI3KΞ΄)**, a lipid kinase that produces **PI(3,4,5)P3 (PIP3)** at membranes downstream of receptor signaling in immune cells, particularly in lymphocytes. file:human/PIK3CD/PIK3CD-deep-research-falcon.md In immune cells, class IA PI3K (including p110Ξ΄) propagates signaling downstream of **BCR, TCR, CD28, ICOS, CD19, BAFF-R, CD40** (and related receptor/adaptor systems), framing the major immune-cell BP terms relevant for PIK3CD. PMID:20940048 PI3KΞ΄ is a lipid kinase of the PI3K class IA family involved in early signaling events of leukocytes responding to a wide variety of stimuli. file:human/PIK3CD/PIK3CD-uniprot.txt Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396). |
| GO:0036092 phosphatidylinositol-3-phosphate biosynthetic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: p110Ξ΄ has biochemical capacity to produce PI3P from phosphatidylinositol. Reason: PMID:9113989 and PMID:9235916 establish the broad lipid-substrate range of p110Ξ΄. GO:0016303 is the specific PI-to-PI3P reaction, not a generic parent of the PIP2-to-PIP3 reaction. Preserve this chemistry and the compatible PAINT inference while distinguishing it from the dominant receptor-signaling substrate. Supporting Evidence: PMID:9235916 Recombinant p110delta phosphorylates phosphatidylinositol and coimmunoprecipitates with p85. PMID:9113989 p110delta displays a broad phosphoinositide lipid substrate specificity and interacts with SH2/SH3 domain-containing p85 adaptor proteins and with GTP-bound Ras. |
| GO:0048015 phosphatidylinositol-mediated signaling | IBA GO_REF:0000033 | MODIFY | Summary: The phosphatidylinositol-mediated signaling term is correct but too broad for PIK3CD. Reason: PIK3CD is specifically a class IA PIP3-producing PI3K that feeds PI3K/AKT receptor signaling, so the more specific PI3K/AKT signal-transduction term is preferred. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000005673 SUPPORTS TRANSFER phosphatidylinositol-mediated signaling: PIK3CD is specifically a class IA PIP3-producing PI3K that feeds PI3K/AKT receptor signaling, so the more specific PI3K/AKT signal-transduction term is preferred. Proposed replacements: phosphatidylinositol 3-kinase/protein kinase B signal transduction Supporting Evidence: file:human/PIK3CD/PIK3CD-deep-research-falcon.md **PIK3CD** encodes the catalytic subunit **p110Ξ΄** of **class IA phosphoinositide 3-kinase (PI3KΞ΄)**, a lipid kinase that produces **PI(3,4,5)P3 (PIP3)** at membranes downstream of receptor signaling in immune cells, particularly in lymphocytes. file:human/PIK3CD/PIK3CD-deep-research-falcon.md In immune cells, class IA PI3K (including p110Ξ΄) propagates signaling downstream of **BCR, TCR, CD28, ICOS, CD19, BAFF-R, CD40** (and related receptor/adaptor systems), framing the major immune-cell BP terms relevant for PIK3CD. file:human/PIK3CD/PIK3CD-uniprot.txt Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396). |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Supported core activated-site localization. PI3Kdelta is recruited to plasma-membrane receptor/adaptor complexes where its phosphoinositide substrates reside. Reason: Membrane recruitment is central to class IA PI3Kdelta activity because PIP2 substrate is membrane localized and receptor phosphotyrosine signals recruit the p85-p110delta complex to the plasma membrane. Supporting Evidence: file:human/PIK3CD/PIK3CD-deep-research-falcon.md Upon receptor phosphotyrosine signaling, SH2-containing p85 recruits the p85-p110Ξ΄ complex to the plasma membrane where phosphoinositide substrates reside. Reactome:R-HSA-1676048 At the plasma membrane, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunits form complexes with regulatory subunits. file:human/PIK3CD/PIK3CD-uniprot.txt Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396). |
| GO:0016303 1-phosphatidylinositol-3-kinase activity | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: p110Ξ΄ has biochemical capacity to produce PI3P from phosphatidylinositol. Reason: PMID:9113989 and PMID:9235916 establish the broad lipid-substrate range of p110Ξ΄. GO:0016303 is the specific PI-to-PI3P reaction, not a generic parent of the PIP2-to-PIP3 reaction. Preserve this chemistry and the compatible PAINT inference while distinguishing it from the dominant receptor-signaling substrate. Supporting Evidence: PMID:9235916 Recombinant p110delta phosphorylates phosphatidylinositol and coimmunoprecipitates with p85. PMID:9113989 p110delta displays a broad phosphoinositide lipid substrate specificity and interacts with SH2/SH3 domain-containing p85 adaptor proteins and with GTP-bound Ras. |
| GO:0035005 1-phosphatidylinositol-4-phosphate 3-kinase activity | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: p110Ξ΄ has biochemical capacity to produce PI(3,4)P2 from PI4P. Reason: PMID:9113989 and PMID:9235916 establish the broad lipid-substrate range of p110Ξ΄. GO:0016303 is the specific PI-to-PI3P reaction, not a generic parent of the PIP2-to-PIP3 reaction. Preserve this chemistry and the compatible PAINT inference while distinguishing it from the dominant receptor-signaling substrate. Supporting Evidence: PMID:9235916 Recombinant p110delta phosphorylates phosphatidylinositol and coimmunoprecipitates with p85. PMID:9113989 p110delta displays a broad phosphoinositide lipid substrate specificity and interacts with SH2/SH3 domain-containing p85 adaptor proteins and with GTP-bound Ras. |
| GO:0000166 nucleotide binding | IEA GO_REF:0000043 | MODIFY | Summary: The supported nucleotide ligand is ATP. Reason: Refine nucleotide binding to ATP binding, which is directly required by the measured phosphotransfer reaction. Proposed replacements: ATP binding Supporting Evidence: file:human/PIK3CD/PIK3CD-uniprot.txt Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396). |
| GO:0002250 adaptive immune response | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: Supported adaptive-immune output, but this is a systems-level consequence of PI3Kdelta immune receptor signaling rather than the core molecular function. Reason: Human disease genetics and leukocyte studies support a role in adaptive immunity, but the core function should remain PIP3-producing class IA PI3K signaling. Supporting Evidence: PMID:27616589 Here, we review the roles of PI3KΞ΄ in adaptive immunity, describe the clinical manifestations and mechanisms of disease in APDS and highlight new insights into PI3KΞ΄ gleaned from these patients, as well as implications of these findings for clinical therapy. PMID:20940048 As a result of the broad effects of PI3KΞ΄ in leukocyte functions, the disruption of PI3KΞ΄ expression or activity leads to decreased inflammatory and immune responses in vivo. |
| GO:0002376 immune system process | IEA GO_REF:0000043 | MODIFY | Summary: p110Ξ΄ participates in both adaptive and innate immune responses. Reason: The broad immune-system process is correct but can be refined to the two supported response categories already present. p110Ξ΄ catalyzes a signaling step in these responses; it is not merely a consumed substrate. Proposed replacements: adaptive immune response innate immune response Supporting Evidence: file:human/PIK3CD/PIK3CD-uniprot.txt Mediates immune responses. |
| GO:0002443 leukocyte mediated immunity | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Supported leukocyte/immune response involvement, but non-core and broad relative to receptor-proximal PI3Kdelta signaling. Reason: PIK3CD is leukocyte-enriched and affects immune responses, yet this broad immune-process term should not define the core function. Supporting Evidence: PMID:20940048 PI3KΞ΄ is a lipid kinase of the PI3K class IA family involved in early signaling events of leukocytes responding to a wide variety of stimuli. PMID:27616589 Here, we review the roles of PI3KΞ΄ in adaptive immunity, describe the clinical manifestations and mechanisms of disease in APDS and highlight new insights into PI3KΞ΄ gleaned from these patients, as well as implications of these findings for clinical therapy. |
| GO:0005524 ATP binding | IEA GO_REF:0000043 | ACCEPT | Summary: ATP is the phosphate donor bound by the p110Ξ΄ catalytic domain. Reason: ATP binding is an integral biochemical property of the kinase, not non-core merely because many kinases share it. PMID:15135396 characterizes ATP-dependent human p110Ξ΄ catalysis. Supporting Evidence: file:human/PIK3CD/PIK3CD-uniprot.txt Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396). |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | MODIFY | Summary: p110Ξ΄ has a cytosolic pool available for recruitment to receptor-associated membranes. Reason: The soluble pool is part of the normal signaling mechanism, not peripheral simply because activated enzyme encounters membrane substrates. Curated cytoplasmic localization in PMID:22020336 and the class IA recruitment studies support this assignment; refine the general cytoplasm term to the existing cytosol term. Proposed replacements: cytosol Supporting Evidence: file:human/PIK3CD/PIK3CD-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22020336}. |
| GO:0005829 cytosol | IEA GO_REF:0000117 | ACCEPT | Summary: p110Ξ΄ has a cytosolic pool available for recruitment to receptor-associated membranes. Reason: The soluble pool is part of the normal signaling mechanism, not peripheral simply because activated enzyme encounters membrane substrates. Curated cytoplasmic localization in PMID:22020336 and the class IA recruitment studies support this assignment; refine the general cytoplasm term to the existing cytosol term. Supporting Evidence: file:human/PIK3CD/PIK3CD-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22020336}. |
| GO:0005943 phosphatidylinositol 3-kinase complex, class IA | IEA GO_REF:0000117 | ACCEPT | Summary: p110Ξ΄ forms class IA heterodimers with p85-family regulatory subunits. Reason: The complex subtype is supported by recombinant p85 association and curated subunit identity, independently of the electronic rule that supplied this row. Supporting Evidence: file:human/PIK3CD/PIK3CD-uniprot.txt Heterodimer of a catalytic subunit PIK3CD and a p85 regulatory subunit (PIK3R1, PIK3R2 or PIK3R3). PMID:9235916 Recombinant p110delta phosphorylates phosphatidylinositol and coimmunoprecipitates with p85. |
| GO:0006629 lipid metabolic process | IEA GO_REF:0000043 | MODIFY | Summary: The lipid metabolic process term is directionally correct but too broad for PIK3CD. Reason: PIK3CD is specifically a phosphoinositide lipid kinase that produces 3-phosphoinositides/PIP3 in signaling contexts; phosphatidylinositol phosphate biosynthesis is the more informative same-aspect process replacement, while the specific PI(4,5)P2 3-kinase molecular function is handled separately. Proposed replacements: phosphatidylinositol phosphate biosynthetic process Supporting Evidence: file:human/PIK3CD/PIK3CD-deep-research-falcon.md Class I/IA PI3Ks, including p110Ξ΄, phosphorylate PI(4,5)P2 to PI(3,4,5)P3; this is the core enzymatic activity of PIK3CD. PMID:9113989 p110delta displays a broad phosphoinositide lipid substrate specificity and interacts with SH2/SH3 domain-containing p85 adaptor proteins and with GTP-bound Ras. file:human/PIK3CD/PIK3CD-uniprot.txt Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396). |
| GO:0006935 chemotaxis | IEA GO_REF:0000043 | MODIFY | Summary: The generic chemotaxis annotation should be narrowed to the specific leukocyte chemotaxis processes supported for PIK3CD. Reason: The evidence supports T-cell, B-cell, neutrophil, and mast-cell chemotaxis contexts rather than chemotaxis as a broad parent term. Proposed replacements: T cell chemotaxis B cell chemotaxis neutrophil chemotaxis mast cell chemotaxis Supporting Evidence: PMID:20940048 PI3KΞ΄ participates in the development, activation and migration of T cells and NK cells. PMID:20940048 The role of PI3KΞ΄ in myeloid cell activities, such as inflammation driven cell infiltration, neutrophil oxidative burst, immune complex mediated macrophage activation, as well as mast cell maturation and degranulation, has been well illustrated in various studies. |
| GO:0006954 inflammatory response | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: Supported inflammatory-response involvement, but it is a downstream physiological output of PI3Kdelta activity. Reason: PI3Kdelta disruption alters inflammatory responses in vivo and PI3K lipid messengers control leukocyte signaling, but inflammation is a non-core phenotype/process relative to lipid kinase signaling. Supporting Evidence: PMID:17290298 Phosphoinositide 3-kinases (PI3Ks) generate lipid-based second messengers that control an array of intracellular signalling pathways that are known to have important roles in leukocytes. PMID:20940048 As a result of the broad effects of PI3KΞ΄ in leukocyte functions, the disruption of PI3KΞ΄ expression or activity leads to decreased inflammatory and immune responses in vivo. |
| GO:0007166 cell surface receptor signaling pathway | IEA GO_REF:0000117 | MODIFY | Summary: The broad cell-surface receptor signaling annotation should be narrowed to the immune receptor signaling pathways where PIK3CD has strong support. Reason: PIK3CD acts downstream of immune receptors such as BCR, TCR, and CD28. Those terms are more informative and better supported than the generic cell-surface receptor signaling parent. Proposed replacements: B cell receptor signaling pathway T cell receptor signaling pathway T cell costimulation Supporting Evidence: file:human/PIK3CD/PIK3CD-deep-research-falcon.md In immune cells, class IA PI3K (including p110Ξ΄) propagates signaling downstream of **BCR, TCR, CD28, ICOS, CD19, BAFF-R, CD40** (and related receptor/adaptor systems), framing the major immune-cell BP terms relevant for PIK3CD. file:human/PIK3CD/PIK3CD-uniprot.txt Required for B-cell receptor (BCR) signaling. file:human/PIK3CD/PIK3CD-uniprot.txt Required for T-cell receptor (TCR) signaling. file:human/PIK3CD/PIK3CD-uniprot.txt Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396). |
| GO:0010595 positive regulation of endothelial cell migration | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Supported endothelial/angiogenesis context, but non-core and tissue/pathology-specific relative to PI3Kdelta immune receptor signaling. Reason: Cultured endothelial-cell work supports VEGF-induced Akt activation, proliferation, migration, tube formation, and retinal angiogenesis. This is a real contextual role, not the primary leukocyte-enriched core function. Supporting Evidence: PMID:31915155 Using genetic and pharmacological approaches, we show that p110Ξ΄ activity in cultured ECs controls Akt activation, cell proliferation, migration, and tube formation induced by vascular endothelial growth factor, basic fibroblast growth factor, and epidermal growth factor. file:human/PIK3CD/PIK3CD-deep-research-falcon.md Many downstream readouts (e.g., pAKT, pS6) are not isoform-specific, and class I PI3Ks share overlapping functions; p110Ξ΄ is leukocyte-enriched but not exclusively expressed, so immune-context evidence is strongest for PIK3CD-specific BP claims. file:human/PIK3CD/PIK3CD-uniprot.txt Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396). |
| GO:0010628 positive regulation of gene expression | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: p110Ξ΄ positively regulates expression of migration-associated proteins in glioma cells. Reason: PMID:22079609 measures decreased FAK and CDC42 protein abundance following selective p110Ξ΄ depletion. This supports regulation of gene-product expression without implying direct DNA binding or a universal transcriptional mechanism. Mouse stromal mRNA evidence in PMID:24009720 provides a separate native context. Supporting Evidence: PMID:22079609 Mechanistically, p110Ξ΄ knockdown reduced the protein levels of focal adhesion kinase and cell division cycle 42, key regulators of cellular migration. |
| GO:0016301 kinase activity | IEA GO_REF:0000120 | MODIFY | Summary: p110Ξ΄ transfers phosphate to defined phosphoinositide substrates and to its own Ser1039. Reason: Refine the broad kinase activity without discarding genuine protein kinase chemistry. The three lipid activities and the demonstrated serine autophosphorylation are independently supported; lack of p85 phosphorylation does not mean absence of protein kinase activity. Proposed replacements: 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity 1-phosphatidylinositol-3-kinase activity 1-phosphatidylinositol-4-phosphate 3-kinase activity protein serine kinase activity Supporting Evidence: PMID:9235916 Recombinant p110delta phosphorylates phosphatidylinositol and coimmunoprecipitates with p85. PMID:9113989 p110delta displays a broad phosphoinositide lipid substrate specificity and interacts with SH2/SH3 domain-containing p85 adaptor proteins and with GTP-bound Ras. PMID:10064595 The single site of autophosphorylation was mapped to Ser1039 at the C-terminus of p110delta. |
| GO:0016303 1-phosphatidylinositol-3-kinase activity | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: p110Ξ΄ has biochemical capacity to produce PI3P from phosphatidylinositol. Reason: PMID:9113989 and PMID:9235916 establish the broad lipid-substrate range of p110Ξ΄. GO:0016303 is the specific PI-to-PI3P reaction, not a generic parent of the PIP2-to-PIP3 reaction. Preserve this chemistry and the compatible PAINT inference while distinguishing it from the dominant receptor-signaling substrate. Supporting Evidence: PMID:9235916 Recombinant p110delta phosphorylates phosphatidylinositol and coimmunoprecipitates with p85. PMID:9113989 p110delta displays a broad phosphoinositide lipid substrate specificity and interacts with SH2/SH3 domain-containing p85 adaptor proteins and with GTP-bound Ras. |
| GO:0016740 transferase activity | IEA GO_REF:0000043 | MODIFY | Summary: p110Ξ΄ transfers phosphate to defined phosphoinositide substrates and to its own Ser1039. Reason: Refine the broad transferase activity without discarding genuine protein kinase chemistry. The three lipid activities and the demonstrated serine autophosphorylation are independently supported; lack of p85 phosphorylation does not mean absence of protein kinase activity. Proposed replacements: 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity 1-phosphatidylinositol-3-kinase activity 1-phosphatidylinositol-4-phosphate 3-kinase activity protein serine kinase activity Supporting Evidence: PMID:9235916 Recombinant p110delta phosphorylates phosphatidylinositol and coimmunoprecipitates with p85. PMID:9113989 p110delta displays a broad phosphoinositide lipid substrate specificity and interacts with SH2/SH3 domain-containing p85 adaptor proteins and with GTP-bound Ras. PMID:10064595 The single site of autophosphorylation was mapped to Ser1039 at the C-terminus of p110delta. |
| GO:0022603 regulation of anatomical structure morphogenesis | IEA GO_REF:0000117 | MODIFY | Summary: p110Ξ΄ supports endothelial growth and angiogenic tissue organization. Reason: Full PMID:31915155 combines human retinal microvascular endothelial perturbation with a mouse oxygen-induced retinopathy model. Refine this broad developmental/morphogenetic term to the supported positive angiogenesis role; downstream signaling participation is real and does not require the kinase to be a structural vessel component. Proposed replacements: positive regulation of angiogenesis Supporting Evidence: PMID:31915155 Using genetic and pharmacological approaches, we show that p110Ξ΄ activity in cultured ECs controls Akt activation, cell proliferation, migration, and tube formation induced by vascular endothelial growth factor, basic fibroblast growth factor, and epidermal growth factor. |
| GO:0030154 cell differentiation | IEA GO_REF:0000043 | MODIFY | Summary: The generic cell differentiation annotation should be narrowed to the specific leukocyte differentiation processes supported for PIK3CD. Reason: The evidence supports B-cell, T-cell, NK-cell, and mast-cell differentiation contexts rather than undifferentiated cell differentiation as a generic parent. Proposed replacements: B cell differentiation T cell differentiation natural killer cell differentiation mast cell differentiation Supporting Evidence: PMID:20200404 Thus, we provide novel evidence that p110gamma and p110delta have overlapping and cell-extrinsic roles in the development, peripheral maintenance, and function of B cells. PMID:17371229 In addition, p110delta regulates the differentiation of peripheral Th (helper T-cells) towards the Th1 and Th2 lineages. PMID:20940048 PI3KΞ΄ participates in the development, activation and migration of T cells and NK cells. |
| GO:0030155 regulation of cell adhesion | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: p110Ξ΄ regulates adhesion in defined leukocyte signaling contexts. Reason: The curated synthesis records SCF-mediated adhesion alongside proliferation and migration. Retain regulation of adhesion at this level rather than declaring it over-annotation simply because adhesion is a downstream output. Supporting Evidence: file:human/PIK3CD/PIK3CD-uniprot.txt Involved in stem cell factor (SCF)-mediated proliferation, adhesion and migration. |
| GO:0033031 positive regulation of neutrophil apoptotic process | IEA GO_REF:0000117 | UNDECIDED | Summary: The precise p110Ξ΄ contribution to FcΞ±RI-induced neutrophil death remains unresolved. Reason: The accessible PMID:25339672 text establishes class IA PI3K-dependent death and distinguishes apoptosis in unprimed cells from additional caspase-independent death after priming. It does not expose the isoform-selective experiment needed to assign positive regulation of neutrophil apoptosis specifically to p110Ξ΄. This limits verification, not the plausibility of the curated claim. |
| GO:0042113 B cell activation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Supported B-cell activation/function annotation, but downstream of the more core BCR signaling role. Reason: PIK3CD is important for B-cell development and function. B-cell activation is real, but BCR signaling and PI3K/AKT signaling are the more precise core process annotations. Supporting Evidence: PMID:20200404 Thus, we provide novel evidence that p110gamma and p110delta have overlapping and cell-extrinsic roles in the development, peripheral maintenance, and function of B cells. file:human/PIK3CD/PIK3CD-uniprot.txt Required for B-cell receptor (BCR) signaling. |
| GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction | IEA GO_REF:0000120 | ACCEPT | Summary: Supported PI3K/AKT signaling annotation downstream of PIK3CD-generated PIP3. Reason: PIP3 produced by p110delta recruits AKT-linked signaling modules. This pathway term captures the central signaling output of PI3Kdelta even when the initiating receptor or cell type differs. Supporting Evidence: file:human/PIK3CD/PIK3CD-deep-research-falcon.md **PIK3CD** encodes the catalytic subunit **p110Ξ΄** of **class IA phosphoinositide 3-kinase (PI3KΞ΄)**, a lipid kinase that produces **PI(3,4,5)P3 (PIP3)** at membranes downstream of receptor signaling in immune cells, particularly in lymphocytes. file:human/PIK3CD/PIK3CD-deep-research-falcon.md In immune cells, class IA PI3K (including p110Ξ΄) propagates signaling downstream of **BCR, TCR, CD28, ICOS, CD19, BAFF-R, CD40** (and related receptor/adaptor systems), framing the major immune-cell BP terms relevant for PIK3CD. PMID:20940048 PI3KΞ΄ is a lipid kinase of the PI3K class IA family involved in early signaling events of leukocytes responding to a wide variety of stimuli. file:human/PIK3CD/PIK3CD-uniprot.txt Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396). |
| GO:0045087 innate immune response | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Supported innate-immune involvement, but this is a broad non-core immune-system output. Reason: PI3Kdelta contributes to myeloid and innate leukocyte activities, but the precise core function is receptor-linked PIP3 production rather than innate immunity as a whole. Supporting Evidence: PMID:20940048 The role of PI3KΞ΄ in myeloid cell activities, such as inflammation driven cell infiltration, neutrophil oxidative burst, immune complex mediated macrophage activation, as well as mast cell maturation and degranulation, has been well illustrated in various studies. PMID:17290298 Phosphoinositide 3-kinases (PI3Ks) generate lipid-based second messengers that control an array of intracellular signalling pathways that are known to have important roles in leukocytes. |
| GO:0046854 phosphatidylinositol phosphate biosynthetic process | IEA GO_REF:0000002 | ACCEPT | Summary: p110Ξ΄ synthesizes D3-phosphorylated phosphoinositides. Reason: This product-class process describes the actual kinase reaction. PI3P, PI(3,4)P2 and PIP3 capabilities should not be conflated with one another, nor should the PI3P reaction be called exclusive to class III PI3K. Supporting Evidence: PMID:9235916 Recombinant p110delta phosphorylates phosphatidylinositol and coimmunoprecipitates with p85. PMID:9113989 p110delta displays a broad phosphoinositide lipid substrate specificity and interacts with SH2/SH3 domain-containing p85 adaptor proteins and with GTP-bound Ras. file:human/PIK3CD/PIK3CD-uniprot.txt Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396). |
| GO:0046934 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: p110Ξ΄ catalyzes ATP-dependent PI(4,5)P2 phosphorylation to PIP3. Reason: PMID:15135396 directly characterizes the human p85/p110Ξ΄ enzyme with PIP2 substrate. This is the principal phosphoinositide second-messenger reaction of p110Ξ΄ in receptor signaling. Supporting Evidence: file:human/PIK3CD/PIK3CD-uniprot.txt Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396). |
| GO:0051094 positive regulation of developmental process | IEA GO_REF:0000117 | MODIFY | Summary: p110Ξ΄ supports endothelial growth and angiogenic tissue organization. Reason: Full PMID:31915155 combines human retinal microvascular endothelial perturbation with a mouse oxygen-induced retinopathy model. Refine this broad developmental/morphogenetic term to the supported positive angiogenesis role; downstream signaling participation is real and does not require the kinase to be a structural vessel component. Proposed replacements: positive regulation of angiogenesis Supporting Evidence: PMID:31915155 Using genetic and pharmacological approaches, we show that p110Ξ΄ activity in cultured ECs controls Akt activation, cell proliferation, migration, and tube formation induced by vascular endothelial growth factor, basic fibroblast growth factor, and epidermal growth factor. |
| GO:0051240 positive regulation of multicellular organismal process | IEA GO_REF:0000117 | MODIFY | Summary: p110Ξ΄ supports endothelial growth and angiogenic tissue organization. Reason: Full PMID:31915155 combines human retinal microvascular endothelial perturbation with a mouse oxygen-induced retinopathy model. Refine this broad developmental/morphogenetic term to the supported positive angiogenesis role; downstream signaling participation is real and does not require the kinase to be a structural vessel component. Proposed replacements: positive regulation of angiogenesis Supporting Evidence: PMID:31915155 Using genetic and pharmacological approaches, we show that p110Ξ΄ activity in cultured ECs controls Akt activation, cell proliferation, migration, and tube formation induced by vascular endothelial growth factor, basic fibroblast growth factor, and epidermal growth factor. |
| GO:2000026 regulation of multicellular organismal development | IEA GO_REF:0000117 | MODIFY | Summary: p110Ξ΄ supports endothelial growth and angiogenic tissue organization. Reason: Full PMID:31915155 combines human retinal microvascular endothelial perturbation with a mouse oxygen-induced retinopathy model. Refine this broad developmental/morphogenetic term to the supported positive angiogenesis role; downstream signaling participation is real and does not require the kinase to be a structural vessel component. Proposed replacements: positive regulation of angiogenesis Supporting Evidence: PMID:31915155 Using genetic and pharmacological approaches, we show that p110Ξ΄ activity in cultured ECs controls Akt activation, cell proliferation, migration, and tube formation induced by vascular endothelial growth factor, basic fibroblast growth factor, and epidermal growth factor. |
| GO:0005515 protein binding | IPI PMID:21827948 Dynamics of the phosphoinositide 3-kinase p110Ξ΄ interaction ... | REMOVE | Summary: The measured partner association remains useful provenance. Reason: Remove bare protein binding under the current policy; the PMID:21827948 interaction with UniProtKB:P27986 is not being declared false. Complex assembly and catalytic functions are retained separately. |
| GO:0005515 protein binding | IPI PMID:22020336 p37Ξ΄ is a new isoform of PI3K p110Ξ΄ that increases cell prol... | REMOVE | Summary: The measured partner association remains useful provenance. Reason: Remove bare protein binding under the current policy; the PMID:22020336 interaction with UniProtKB:P01112 is not being declared false. Complex assembly and catalytic functions are retained separately. |
| GO:0005515 protein binding | IPI PMID:24165795 Dominant-activating germline mutations in the gene encoding ... | REMOVE | Summary: The measured partner association remains useful provenance. Reason: Remove bare protein binding under the current policy; the PMID:24165795 interaction with UniProtKB:P27986 is not being declared false. Complex assembly and catalytic functions are retained separately. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: The measured partner association remains useful provenance. Reason: Remove bare protein binding under the current policy; the PMID:28514442 interaction with UniProtKB:Q92569 is not being declared false. Complex assembly and catalytic functions are retained separately. |
| GO:0005515 protein binding | IPI PMID:31031754 Case Study: Mechanism for Increased Follicular Helper T Cell... | REMOVE | Summary: The measured partner association remains useful provenance. Reason: Remove bare protein binding under the current policy; the PMID:31031754 interaction with UniProtKB:P27986 is not being declared false. Complex assembly and catalytic functions are retained separately. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: The measured partner association remains useful provenance. Reason: Remove bare protein binding under the current policy; the PMID:32296183 interaction with UniProtKB:P27986-2 is not being declared false. Complex assembly and catalytic functions are retained separately. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: The measured partner association remains useful provenance. Reason: Remove bare protein binding under the current policy; the PMID:33961781 interaction with UniProtKB:Q92569 is not being declared false. Complex assembly and catalytic functions are retained separately. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | REMOVE | Summary: The measured partner association remains useful provenance. Reason: Remove bare protein binding under the current policy; the PMID:35271311 interaction with UniProtKB:P27986 is not being declared false. Complex assembly and catalytic functions are retained separately. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: The measured partner association remains useful provenance. Reason: Remove bare protein binding under the current policy; the PMID:40205054 interaction with UniProtKB:Q92569 is not being declared false. Complex assembly and catalytic functions are retained separately. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: p110Ξ΄ has a cytosolic pool available for recruitment to receptor-associated membranes. Reason: The soluble pool is part of the normal signaling mechanism, not peripheral simply because activated enzyme encounters membrane substrates. Curated cytoplasmic localization in PMID:22020336 and the class IA recruitment studies support this assignment; refine the general cytoplasm term to the existing cytosol term. Supporting Evidence: file:human/PIK3CD/PIK3CD-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22020336}. |
| GO:0005515 protein binding | IPI PMID:32606397 PI3K activation is enhanced by FOXM1D binding to p110 and p8... | REMOVE | Summary: The measured partner association remains useful provenance. Reason: Remove bare protein binding under the current policy; the PMID:32606397 interaction with UniProtKB:Q08050-4 is not being declared false. Complex assembly and catalytic functions are retained separately. |
| GO:0031295 T cell costimulation | TAS Reactome:R-HSA-389356 | ACCEPT | Summary: Supported CD28/T-cell costimulation context for PI3Kdelta signaling. Reason: CD28 is a direct immune receptor context in which PI3K participates in costimulatory signaling and PIP3 generation. This is part of the core immune-receptor signaling frame for PIK3CD. Supporting Evidence: file:human/PIK3CD/PIK3CD-deep-research-falcon.md In immune cells, class IA PI3K (including p110Ξ΄) propagates signaling downstream of **BCR, TCR, CD28, ICOS, CD19, BAFF-R, CD40** (and related receptor/adaptor systems), framing the major immune-cell BP terms relevant for PIK3CD. Reactome:R-HSA-389356 The cytoplasmic tail of CD28, upon ligand binding, undergoes phosphorylation by Src family kinases like LCK and FYN, triggering downstream signaling pathways involving PI3K, VAV-1, Tec family kinases, AKT, and other adaptor proteins (Sharpe & Freeman 2002; Chen & Flies 2013). Reactome:R-HSA-389158 Upon binding to CD28, the PI3K enzyme catalyzes the phosphorylation of phosphatidylinositol 4,5-bisphosphate (PIP2) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). file:human/PIK3CD/PIK3CD-uniprot.txt Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396). |
| GO:0046934 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity | TAS Reactome:R-HSA-389158 | ACCEPT | Summary: p110Ξ΄ catalyzes ATP-dependent PI(4,5)P2 phosphorylation to PIP3. Reason: PMID:15135396 directly characterizes the human p85/p110Ξ΄ enzyme with PIP2 substrate. This is the principal phosphoinositide second-messenger reaction of p110Ξ΄ in receptor signaling. Supporting Evidence: file:human/PIK3CD/PIK3CD-uniprot.txt Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396). |
| GO:0006955 immune response | NAS PMID:27616589 PI3KΞ΄ and primary immunodeficiencies. | KEEP AS NON CORE | Summary: Supported leukocyte/immune response involvement, but non-core and broad relative to receptor-proximal PI3Kdelta signaling. Reason: PIK3CD is leukocyte-enriched and affects immune responses, yet this broad immune-process term should not define the core function. Supporting Evidence: PMID:20940048 PI3KΞ΄ is a lipid kinase of the PI3K class IA family involved in early signaling events of leukocytes responding to a wide variety of stimuli. PMID:27616589 Here, we review the roles of PI3KΞ΄ in adaptive immunity, describe the clinical manifestations and mechanisms of disease in APDS and highlight new insights into PI3KΞ΄ gleaned from these patients, as well as implications of these findings for clinical therapy. |
| GO:0030183 B cell differentiation | NAS PMID:20200404 The catalytic PI3K isoforms p110gamma and p110delta contribu... | KEEP AS NON CORE | Summary: Supported B-cell differentiation/development role, but non-core relative to PI3Kdelta catalytic signaling. Reason: B-cell developmental phenotypes are well supported, but they are downstream organism/cell lineage consequences of PIP3-producing PI3Kdelta signaling. Supporting Evidence: PMID:20200404 Thus, we provide novel evidence that p110gamma and p110delta have overlapping and cell-extrinsic roles in the development, peripheral maintenance, and function of B cells. file:human/PIK3CD/PIK3CD-uniprot.txt Required for B-cell receptor (BCR) signaling. |
| GO:0030217 T cell differentiation | NAS PMID:17371229 The PI3K p110delta controls T-cell development, differentiat... | KEEP AS NON CORE | Summary: Supported T-cell differentiation role, but non-core relative to receptor-proximal PI3Kdelta signaling. Reason: T-cell differentiation is a supported immune-cell outcome of p110delta activity, not the core molecular function itself. Supporting Evidence: PMID:17371229 In addition, p110delta regulates the differentiation of peripheral Th (helper T-cells) towards the Th1 and Th2 lineages. PMID:20940048 PI3KΞ΄ participates in the development, activation and migration of T cells and NK cells. |
| GO:0038084 vascular endothelial growth factor signaling pathway | IGI PMID:31915155 PI3KΞ΄ as a Novel Therapeutic Target in Pathological Angiogen... | KEEP AS NON CORE | Summary: Supported endothelial/angiogenesis context, but non-core and tissue/pathology-specific relative to PI3Kdelta immune receptor signaling. Reason: Cultured endothelial-cell work supports VEGF-induced Akt activation, proliferation, migration, tube formation, and retinal angiogenesis. This is a real contextual role, not the primary leukocyte-enriched core function. Supporting Evidence: PMID:31915155 Using genetic and pharmacological approaches, we show that p110Ξ΄ activity in cultured ECs controls Akt activation, cell proliferation, migration, and tube formation induced by vascular endothelial growth factor, basic fibroblast growth factor, and epidermal growth factor. file:human/PIK3CD/PIK3CD-deep-research-falcon.md Many downstream readouts (e.g., pAKT, pS6) are not isoform-specific, and class I PI3Ks share overlapping functions; p110Ξ΄ is leukocyte-enriched but not exclusively expressed, so immune-context evidence is strongest for PIK3CD-specific BP claims. file:human/PIK3CD/PIK3CD-uniprot.txt Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396). |
| GO:0010595 positive regulation of endothelial cell migration | IGI PMID:31915155 PI3KΞ΄ as a Novel Therapeutic Target in Pathological Angiogen... | KEEP AS NON CORE | Summary: Supported endothelial/angiogenesis context, but non-core and tissue/pathology-specific relative to PI3Kdelta immune receptor signaling. Reason: Cultured endothelial-cell work supports VEGF-induced Akt activation, proliferation, migration, tube formation, and retinal angiogenesis. This is a real contextual role, not the primary leukocyte-enriched core function. Supporting Evidence: PMID:31915155 Using genetic and pharmacological approaches, we show that p110Ξ΄ activity in cultured ECs controls Akt activation, cell proliferation, migration, and tube formation induced by vascular endothelial growth factor, basic fibroblast growth factor, and epidermal growth factor. file:human/PIK3CD/PIK3CD-deep-research-falcon.md Many downstream readouts (e.g., pAKT, pS6) are not isoform-specific, and class I PI3Ks share overlapping functions; p110Ξ΄ is leukocyte-enriched but not exclusively expressed, so immune-context evidence is strongest for PIK3CD-specific BP claims. file:human/PIK3CD/PIK3CD-uniprot.txt Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396). |
| GO:0001938 positive regulation of endothelial cell proliferation | IGI PMID:31915155 PI3KΞ΄ as a Novel Therapeutic Target in Pathological Angiogen... | KEEP AS NON CORE | Summary: Supported endothelial/angiogenesis context, but non-core and tissue/pathology-specific relative to PI3Kdelta immune receptor signaling. Reason: Cultured endothelial-cell work supports VEGF-induced Akt activation, proliferation, migration, tube formation, and retinal angiogenesis. This is a real contextual role, not the primary leukocyte-enriched core function. Supporting Evidence: PMID:31915155 Using genetic and pharmacological approaches, we show that p110Ξ΄ activity in cultured ECs controls Akt activation, cell proliferation, migration, and tube formation induced by vascular endothelial growth factor, basic fibroblast growth factor, and epidermal growth factor. file:human/PIK3CD/PIK3CD-deep-research-falcon.md Many downstream readouts (e.g., pAKT, pS6) are not isoform-specific, and class I PI3Ks share overlapping functions; p110Ξ΄ is leukocyte-enriched but not exclusively expressed, so immune-context evidence is strongest for PIK3CD-specific BP claims. file:human/PIK3CD/PIK3CD-uniprot.txt Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396). |
| GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction | IGI PMID:31915155 PI3KΞ΄ as a Novel Therapeutic Target in Pathological Angiogen... | ACCEPT | Summary: Supported PI3K/AKT signaling annotation downstream of PIK3CD-generated PIP3. Reason: PIP3 produced by p110delta recruits AKT-linked signaling modules. This pathway term captures the central signaling output of PI3Kdelta even when the initiating receptor or cell type differs. Supporting Evidence: file:human/PIK3CD/PIK3CD-deep-research-falcon.md **PIK3CD** encodes the catalytic subunit **p110Ξ΄** of **class IA phosphoinositide 3-kinase (PI3KΞ΄)**, a lipid kinase that produces **PI(3,4,5)P3 (PIP3)** at membranes downstream of receptor signaling in immune cells, particularly in lymphocytes. file:human/PIK3CD/PIK3CD-deep-research-falcon.md In immune cells, class IA PI3K (including p110Ξ΄) propagates signaling downstream of **BCR, TCR, CD28, ICOS, CD19, BAFF-R, CD40** (and related receptor/adaptor systems), framing the major immune-cell BP terms relevant for PIK3CD. PMID:20940048 PI3KΞ΄ is a lipid kinase of the PI3K class IA family involved in early signaling events of leukocytes responding to a wide variety of stimuli. file:human/PIK3CD/PIK3CD-uniprot.txt Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396). |
| GO:0045766 positive regulation of angiogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Supported endothelial/angiogenesis context, but non-core and tissue/pathology-specific relative to PI3Kdelta immune receptor signaling. Reason: Cultured endothelial-cell work supports VEGF-induced Akt activation, proliferation, migration, tube formation, and retinal angiogenesis. This is a real contextual role, not the primary leukocyte-enriched core function. Supporting Evidence: PMID:31915155 Using genetic and pharmacological approaches, we show that p110Ξ΄ activity in cultured ECs controls Akt activation, cell proliferation, migration, and tube formation induced by vascular endothelial growth factor, basic fibroblast growth factor, and epidermal growth factor. file:human/PIK3CD/PIK3CD-deep-research-falcon.md Many downstream readouts (e.g., pAKT, pS6) are not isoform-specific, and class I PI3Ks share overlapping functions; p110Ξ΄ is leukocyte-enriched but not exclusively expressed, so immune-context evidence is strongest for PIK3CD-specific BP claims. file:human/PIK3CD/PIK3CD-uniprot.txt Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396). |
| GO:1905278 positive regulation of epithelial tube formation | IGI PMID:31915155 PI3KΞ΄ as a Novel Therapeutic Target in Pathological Angiogen... | KEEP AS NON CORE | Summary: Supported endothelial/angiogenesis context, but non-core and tissue/pathology-specific relative to PI3Kdelta immune receptor signaling. Reason: Cultured endothelial-cell work supports VEGF-induced Akt activation, proliferation, migration, tube formation, and retinal angiogenesis. This is a real contextual role, not the primary leukocyte-enriched core function. Supporting Evidence: PMID:31915155 Using genetic and pharmacological approaches, we show that p110Ξ΄ activity in cultured ECs controls Akt activation, cell proliferation, migration, and tube formation induced by vascular endothelial growth factor, basic fibroblast growth factor, and epidermal growth factor. file:human/PIK3CD/PIK3CD-deep-research-falcon.md Many downstream readouts (e.g., pAKT, pS6) are not isoform-specific, and class I PI3Ks share overlapping functions; p110Ξ΄ is leukocyte-enriched but not exclusively expressed, so immune-context evidence is strongest for PIK3CD-specific BP claims. file:human/PIK3CD/PIK3CD-uniprot.txt Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396). |
| GO:0033031 positive regulation of neutrophil apoptotic process | IMP PMID:25339672 Human IgA Fc receptor FcΞ±RI (CD89) triggers different forms ... | UNDECIDED | Summary: The precise p110Ξ΄ contribution to FcΞ±RI-induced neutrophil death remains unresolved. Reason: The accessible PMID:25339672 text establishes class IA PI3K-dependent death and distinguishes apoptosis in unprimed cells from additional caspase-independent death after priming. It does not expose the isoform-selective experiment needed to assign positive regulation of neutrophil apoptosis specifically to p110Ξ΄. This limits verification, not the plausibility of the curated claim. |
| GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction | IMP PMID:25339672 Human IgA Fc receptor FcΞ±RI (CD89) triggers different forms ... | ACCEPT | Summary: Supported PI3K/AKT signaling annotation downstream of PIK3CD-generated PIP3. Reason: PIP3 produced by p110delta recruits AKT-linked signaling modules. This pathway term captures the central signaling output of PI3Kdelta even when the initiating receptor or cell type differs. Supporting Evidence: file:human/PIK3CD/PIK3CD-deep-research-falcon.md **PIK3CD** encodes the catalytic subunit **p110Ξ΄** of **class IA phosphoinositide 3-kinase (PI3KΞ΄)**, a lipid kinase that produces **PI(3,4,5)P3 (PIP3)** at membranes downstream of receptor signaling in immune cells, particularly in lymphocytes. file:human/PIK3CD/PIK3CD-deep-research-falcon.md In immune cells, class IA PI3K (including p110Ξ΄) propagates signaling downstream of **BCR, TCR, CD28, ICOS, CD19, BAFF-R, CD40** (and related receptor/adaptor systems), framing the major immune-cell BP terms relevant for PIK3CD. PMID:20940048 PI3KΞ΄ is a lipid kinase of the PI3K class IA family involved in early signaling events of leukocytes responding to a wide variety of stimuli. file:human/PIK3CD/PIK3CD-uniprot.txt Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396). |
| GO:0001779 natural killer cell differentiation | TAS PMID:20940048 Phosphoinositide 3-kinase delta (PI3KΞ΄) in leukocyte signali... | KEEP AS NON CORE | Summary: Supported NK-cell differentiation role, but non-core relative to PI3Kdelta catalytic signaling. Reason: PI3Kdelta participates in NK-cell development and migration, but this is a leukocyte-specific cellular outcome rather than the core lipid kinase function. Supporting Evidence: PMID:20940048 PI3KΞ΄ participates in the development, activation and migration of T cells and NK cells. PMID:20940048 PI3KΞ΄ is a lipid kinase of the PI3K class IA family involved in early signaling events of leukocytes responding to a wide variety of stimuli. |
| GO:0001819 positive regulation of cytokine production | TAS PMID:20940048 Phosphoinositide 3-kinase delta (PI3KΞ΄) in leukocyte signali... | KEEP AS NON CORE | Summary: Supported cytokine-production role, but non-core and downstream of immune receptor signaling. Reason: Cytokine-production changes are leukocyte outputs of PI3Kdelta signaling, not the primary biochemical function. Supporting Evidence: PMID:20940048 As a result of the broad effects of PI3KΞ΄ in leukocyte functions, the disruption of PI3KΞ΄ expression or activity leads to decreased inflammatory and immune responses in vivo. file:human/PIK3CD/PIK3CD-uniprot.txt Required for T-cell receptor (TCR) signaling. |
| GO:0002250 adaptive immune response | TAS PMID:17290298 PI3K delta and PI3K gamma: partners in crime in inflammation... | KEEP AS NON CORE | Summary: Supported adaptive-immune output, but this is a systems-level consequence of PI3Kdelta immune receptor signaling rather than the core molecular function. Reason: Human disease genetics and leukocyte studies support a role in adaptive immunity, but the core function should remain PIP3-producing class IA PI3K signaling. Supporting Evidence: PMID:27616589 Here, we review the roles of PI3KΞ΄ in adaptive immunity, describe the clinical manifestations and mechanisms of disease in APDS and highlight new insights into PI3KΞ΄ gleaned from these patients, as well as implications of these findings for clinical therapy. PMID:20940048 As a result of the broad effects of PI3KΞ΄ in leukocyte functions, the disruption of PI3KΞ΄ expression or activity leads to decreased inflammatory and immune responses in vivo. |
| GO:0002551 mast cell chemotaxis | TAS PMID:20940048 Phosphoinositide 3-kinase delta (PI3KΞ΄) in leukocyte signali... | KEEP AS NON CORE | Summary: Supported leukocyte migration/chemotaxis/extravasation role, but non-core relative to receptor-proximal PI3Kdelta signaling. Reason: PI3Kdelta affects migration of multiple leukocyte types, but these are cell-type-specific outputs of the core PIP3-generating immune signaling function. Supporting Evidence: PMID:20940048 PI3KΞ΄ participates in the development, activation and migration of T cells and NK cells. PMID:20940048 The role of PI3KΞ΄ in myeloid cell activities, such as inflammation driven cell infiltration, neutrophil oxidative burst, immune complex mediated macrophage activation, as well as mast cell maturation and degranulation, has been well illustrated in various studies. |
| GO:0002679 respiratory burst involved in defense response | TAS PMID:20940048 Phosphoinositide 3-kinase delta (PI3KΞ΄) in leukocyte signali... | KEEP AS NON CORE | Summary: Supported neutrophil respiratory-burst role, but non-core relative to the catalytic PI3Kdelta signaling function. Reason: PI3Kdelta contributes to neutrophil respiratory burst as a myeloid effector output, but this is not the core molecular function. Supporting Evidence: PMID:20940048 The role of PI3KΞ΄ in myeloid cell activities, such as inflammation driven cell infiltration, neutrophil oxidative burst, immune complex mediated macrophage activation, as well as mast cell maturation and degranulation, has been well illustrated in various studies. |
| GO:0006954 inflammatory response | TAS PMID:17290298 PI3K delta and PI3K gamma: partners in crime in inflammation... | KEEP AS NON CORE | Summary: Supported inflammatory-response involvement, but it is a downstream physiological output of PI3Kdelta activity. Reason: PI3Kdelta disruption alters inflammatory responses in vivo and PI3K lipid messengers control leukocyte signaling, but inflammation is a non-core phenotype/process relative to lipid kinase signaling. Supporting Evidence: PMID:17290298 Phosphoinositide 3-kinases (PI3Ks) generate lipid-based second messengers that control an array of intracellular signalling pathways that are known to have important roles in leukocytes. PMID:20940048 As a result of the broad effects of PI3KΞ΄ in leukocyte functions, the disruption of PI3KΞ΄ expression or activity leads to decreased inflammatory and immune responses in vivo. |
| GO:0006954 inflammatory response | TAS PMID:20940048 Phosphoinositide 3-kinase delta (PI3KΞ΄) in leukocyte signali... | KEEP AS NON CORE | Summary: Supported inflammatory-response involvement, but it is a downstream physiological output of PI3Kdelta activity. Reason: PI3Kdelta disruption alters inflammatory responses in vivo and PI3K lipid messengers control leukocyte signaling, but inflammation is a non-core phenotype/process relative to lipid kinase signaling. Supporting Evidence: PMID:17290298 Phosphoinositide 3-kinases (PI3Ks) generate lipid-based second messengers that control an array of intracellular signalling pathways that are known to have important roles in leukocytes. PMID:20940048 As a result of the broad effects of PI3KΞ΄ in leukocyte functions, the disruption of PI3KΞ΄ expression or activity leads to decreased inflammatory and immune responses in vivo. |
| GO:0010818 T cell chemotaxis | TAS PMID:20940048 Phosphoinositide 3-kinase delta (PI3KΞ΄) in leukocyte signali... | KEEP AS NON CORE | Summary: Supported leukocyte migration/chemotaxis/extravasation role, but non-core relative to receptor-proximal PI3Kdelta signaling. Reason: PI3Kdelta affects migration of multiple leukocyte types, but these are cell-type-specific outputs of the core PIP3-generating immune signaling function. Supporting Evidence: PMID:20940048 PI3KΞ΄ participates in the development, activation and migration of T cells and NK cells. PMID:20940048 The role of PI3KΞ΄ in myeloid cell activities, such as inflammation driven cell infiltration, neutrophil oxidative burst, immune complex mediated macrophage activation, as well as mast cell maturation and degranulation, has been well illustrated in various studies. |
| GO:0016303 1-phosphatidylinositol-3-kinase activity | TAS PMID:17290298 PI3K delta and PI3K gamma: partners in crime in inflammation... | KEEP AS NON CORE | Summary: p110Ξ΄ has biochemical capacity to produce PI3P from phosphatidylinositol. Reason: PMID:9113989 and PMID:9235916 establish the broad lipid-substrate range of p110Ξ΄. GO:0016303 is the specific PI-to-PI3P reaction, not a generic parent of the PIP2-to-PIP3 reaction. Preserve this chemistry and the compatible PAINT inference while distinguishing it from the dominant receptor-signaling substrate. Supporting Evidence: PMID:9235916 Recombinant p110delta phosphorylates phosphatidylinositol and coimmunoprecipitates with p85. PMID:9113989 p110delta displays a broad phosphoinositide lipid substrate specificity and interacts with SH2/SH3 domain-containing p85 adaptor proteins and with GTP-bound Ras. |
| GO:0030101 natural killer cell activation | TAS PMID:20940048 Phosphoinositide 3-kinase delta (PI3KΞ΄) in leukocyte signali... | KEEP AS NON CORE | Summary: Supported NK-cell activation context, but non-core relative to receptor-proximal PI3Kdelta signaling. Reason: NK-cell activation is a supported immune output; the central curatable function remains PI3Kdelta PIP3 production in leukocyte signaling. Supporting Evidence: PMID:20940048 PI3KΞ΄ participates in the development, activation and migration of T cells and NK cells. PMID:20940048 PI3KΞ΄ is a lipid kinase of the PI3K class IA family involved in early signaling events of leukocytes responding to a wide variety of stimuli. |
| GO:0030217 T cell differentiation | TAS PMID:20940048 Phosphoinositide 3-kinase delta (PI3KΞ΄) in leukocyte signali... | KEEP AS NON CORE | Summary: Supported T-cell differentiation role, but non-core relative to receptor-proximal PI3Kdelta signaling. Reason: T-cell differentiation is a supported immune-cell outcome of p110delta activity, not the core molecular function itself. Supporting Evidence: PMID:17371229 In addition, p110delta regulates the differentiation of peripheral Th (helper T-cells) towards the Th1 and Th2 lineages. PMID:20940048 PI3KΞ΄ participates in the development, activation and migration of T cells and NK cells. |
| GO:0030593 neutrophil chemotaxis | TAS PMID:20940048 Phosphoinositide 3-kinase delta (PI3KΞ΄) in leukocyte signali... | KEEP AS NON CORE | Summary: Supported leukocyte migration/chemotaxis/extravasation role, but non-core relative to receptor-proximal PI3Kdelta signaling. Reason: PI3Kdelta affects migration of multiple leukocyte types, but these are cell-type-specific outputs of the core PIP3-generating immune signaling function. Supporting Evidence: PMID:20940048 PI3KΞ΄ participates in the development, activation and migration of T cells and NK cells. PMID:20940048 The role of PI3KΞ΄ in myeloid cell activities, such as inflammation driven cell infiltration, neutrophil oxidative burst, immune complex mediated macrophage activation, as well as mast cell maturation and degranulation, has been well illustrated in various studies. |
| GO:0035747 natural killer cell chemotaxis | TAS PMID:20940048 Phosphoinositide 3-kinase delta (PI3KΞ΄) in leukocyte signali... | KEEP AS NON CORE | Summary: Supported leukocyte migration/chemotaxis/extravasation role, but non-core relative to receptor-proximal PI3Kdelta signaling. Reason: PI3Kdelta affects migration of multiple leukocyte types, but these are cell-type-specific outputs of the core PIP3-generating immune signaling function. Supporting Evidence: PMID:20940048 PI3KΞ΄ participates in the development, activation and migration of T cells and NK cells. PMID:20940048 The role of PI3KΞ΄ in myeloid cell activities, such as inflammation driven cell infiltration, neutrophil oxidative burst, immune complex mediated macrophage activation, as well as mast cell maturation and degranulation, has been well illustrated in various studies. |
| GO:0035754 B cell chemotaxis | TAS PMID:20940048 Phosphoinositide 3-kinase delta (PI3KΞ΄) in leukocyte signali... | KEEP AS NON CORE | Summary: Supported leukocyte migration/chemotaxis/extravasation role, but non-core relative to receptor-proximal PI3Kdelta signaling. Reason: PI3Kdelta affects migration of multiple leukocyte types, but these are cell-type-specific outputs of the core PIP3-generating immune signaling function. Supporting Evidence: PMID:20940048 PI3KΞ΄ participates in the development, activation and migration of T cells and NK cells. PMID:20940048 The role of PI3KΞ΄ in myeloid cell activities, such as inflammation driven cell infiltration, neutrophil oxidative burst, immune complex mediated macrophage activation, as well as mast cell maturation and degranulation, has been well illustrated in various studies. |
| GO:0042110 T cell activation | TAS PMID:20940048 Phosphoinositide 3-kinase delta (PI3KΞ΄) in leukocyte signali... | KEEP AS NON CORE | Summary: Supported T-cell activation/function annotation, but downstream of the more core TCR/CD28 signaling role. Reason: PIK3CD contributes to T-cell development, activation, and migration. The T-cell activation process is supported but is a cellular outcome of the core TCR/CD28 PI3K signaling function. Supporting Evidence: PMID:20940048 PI3KΞ΄ participates in the development, activation and migration of T cells and NK cells. file:human/PIK3CD/PIK3CD-uniprot.txt Required for T-cell receptor (TCR) signaling. |
| GO:0042113 B cell activation | TAS PMID:20940048 Phosphoinositide 3-kinase delta (PI3KΞ΄) in leukocyte signali... | KEEP AS NON CORE | Summary: Supported B-cell activation/function annotation, but downstream of the more core BCR signaling role. Reason: PIK3CD is important for B-cell development and function. B-cell activation is real, but BCR signaling and PI3K/AKT signaling are the more precise core process annotations. Supporting Evidence: PMID:20200404 Thus, we provide novel evidence that p110gamma and p110delta have overlapping and cell-extrinsic roles in the development, peripheral maintenance, and function of B cells. file:human/PIK3CD/PIK3CD-uniprot.txt Required for B-cell receptor (BCR) signaling. |
| GO:0043303 mast cell degranulation | TAS PMID:20940048 Phosphoinositide 3-kinase delta (PI3KΞ΄) in leukocyte signali... | KEEP AS NON CORE | Summary: Supported mast-cell degranulation role, but non-core relative to the catalytic PI3Kdelta function. Reason: PI3Kdelta contributes to mast-cell degranulation, but this is a cell-type-specific effector output rather than the core molecular function. Supporting Evidence: PMID:20940048 The role of PI3KΞ΄ in myeloid cell activities, such as inflammation driven cell infiltration, neutrophil oxidative burst, immune complex mediated macrophage activation, as well as mast cell maturation and degranulation, has been well illustrated in various studies. |
| GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction | TAS PMID:17290298 PI3K delta and PI3K gamma: partners in crime in inflammation... | ACCEPT | Summary: Supported PI3K/AKT signaling annotation downstream of PIK3CD-generated PIP3. Reason: PIP3 produced by p110delta recruits AKT-linked signaling modules. This pathway term captures the central signaling output of PI3Kdelta even when the initiating receptor or cell type differs. Supporting Evidence: file:human/PIK3CD/PIK3CD-deep-research-falcon.md **PIK3CD** encodes the catalytic subunit **p110Ξ΄** of **class IA phosphoinositide 3-kinase (PI3KΞ΄)**, a lipid kinase that produces **PI(3,4,5)P3 (PIP3)** at membranes downstream of receptor signaling in immune cells, particularly in lymphocytes. file:human/PIK3CD/PIK3CD-deep-research-falcon.md In immune cells, class IA PI3K (including p110Ξ΄) propagates signaling downstream of **BCR, TCR, CD28, ICOS, CD19, BAFF-R, CD40** (and related receptor/adaptor systems), framing the major immune-cell BP terms relevant for PIK3CD. PMID:20940048 PI3KΞ΄ is a lipid kinase of the PI3K class IA family involved in early signaling events of leukocytes responding to a wide variety of stimuli. file:human/PIK3CD/PIK3CD-uniprot.txt Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396). |
| GO:0045087 innate immune response | TAS PMID:17290298 PI3K delta and PI3K gamma: partners in crime in inflammation... | KEEP AS NON CORE | Summary: Supported innate-immune involvement, but this is a broad non-core immune-system output. Reason: PI3Kdelta contributes to myeloid and innate leukocyte activities, but the precise core function is receptor-linked PIP3 production rather than innate immunity as a whole. Supporting Evidence: PMID:20940048 The role of PI3KΞ΄ in myeloid cell activities, such as inflammation driven cell infiltration, neutrophil oxidative burst, immune complex mediated macrophage activation, as well as mast cell maturation and degranulation, has been well illustrated in various studies. PMID:17290298 Phosphoinositide 3-kinases (PI3Ks) generate lipid-based second messengers that control an array of intracellular signalling pathways that are known to have important roles in leukocytes. |
| GO:0045087 innate immune response | TAS PMID:20940048 Phosphoinositide 3-kinase delta (PI3KΞ΄) in leukocyte signali... | KEEP AS NON CORE | Summary: Supported innate-immune involvement, but this is a broad non-core immune-system output. Reason: PI3Kdelta contributes to myeloid and innate leukocyte activities, but the precise core function is receptor-linked PIP3 production rather than innate immunity as a whole. Supporting Evidence: PMID:20940048 The role of PI3KΞ΄ in myeloid cell activities, such as inflammation driven cell infiltration, neutrophil oxidative burst, immune complex mediated macrophage activation, as well as mast cell maturation and degranulation, has been well illustrated in various studies. PMID:17290298 Phosphoinositide 3-kinases (PI3Ks) generate lipid-based second messengers that control an array of intracellular signalling pathways that are known to have important roles in leukocytes. |
| GO:0050852 T cell receptor signaling pathway | TAS PMID:20940048 Phosphoinositide 3-kinase delta (PI3KΞ΄) in leukocyte signali... | ACCEPT | Summary: Supported TCR signaling role for PI3Kdelta. Reason: UniProt and the literature synthesis identify p110delta as required for TCR signaling, making this one of the core immune receptor signaling processes for PIK3CD. Supporting Evidence: file:human/PIK3CD/PIK3CD-uniprot.txt Required for T-cell receptor (TCR) signaling. file:human/PIK3CD/PIK3CD-deep-research-falcon.md In immune cells, class IA PI3K (including p110Ξ΄) propagates signaling downstream of **BCR, TCR, CD28, ICOS, CD19, BAFF-R, CD40** (and related receptor/adaptor systems), framing the major immune-cell BP terms relevant for PIK3CD. PMID:20940048 PI3KΞ΄ participates in the development, activation and migration of T cells and NK cells. file:human/PIK3CD/PIK3CD-uniprot.txt Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396). |
| GO:0050853 B cell receptor signaling pathway | TAS PMID:20940048 Phosphoinositide 3-kinase delta (PI3KΞ΄) in leukocyte signali... | ACCEPT | Summary: Supported BCR signaling role for PI3Kdelta. Reason: p110delta is required for BCR signaling and B-cell functional outputs; this is one of the strongest process annotations for PIK3CD. Supporting Evidence: file:human/PIK3CD/PIK3CD-uniprot.txt Required for B-cell receptor (BCR) signaling. file:human/PIK3CD/PIK3CD-deep-research-falcon.md In immune cells, class IA PI3K (including p110Ξ΄) propagates signaling downstream of **BCR, TCR, CD28, ICOS, CD19, BAFF-R, CD40** (and related receptor/adaptor systems), framing the major immune-cell BP terms relevant for PIK3CD. PMID:20200404 Thus, we provide novel evidence that p110gamma and p110delta have overlapping and cell-extrinsic roles in the development, peripheral maintenance, and function of B cells. file:human/PIK3CD/PIK3CD-uniprot.txt Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396). |
| GO:0060374 mast cell differentiation | TAS PMID:20940048 Phosphoinositide 3-kinase delta (PI3KΞ΄) in leukocyte signali... | KEEP AS NON CORE | Summary: Supported mast-cell differentiation role, but non-core relative to the catalytic PI3Kdelta function. Reason: Mast-cell maturation/differentiation is a supported leukocyte-cell output of PI3Kdelta signaling, not the core molecular activity. Supporting Evidence: PMID:20940048 The role of PI3KΞ΄ in myeloid cell activities, such as inflammation driven cell infiltration, neutrophil oxidative burst, immune complex mediated macrophage activation, as well as mast cell maturation and degranulation, has been well illustrated in various studies. |
| GO:0072672 neutrophil extravasation | TAS PMID:20940048 Phosphoinositide 3-kinase delta (PI3KΞ΄) in leukocyte signali... | KEEP AS NON CORE | Summary: Supported leukocyte migration/chemotaxis/extravasation role, but non-core relative to receptor-proximal PI3Kdelta signaling. Reason: PI3Kdelta affects migration of multiple leukocyte types, but these are cell-type-specific outputs of the core PIP3-generating immune signaling function. Supporting Evidence: PMID:20940048 PI3KΞ΄ participates in the development, activation and migration of T cells and NK cells. PMID:20940048 The role of PI3KΞ΄ in myeloid cell activities, such as inflammation driven cell infiltration, neutrophil oxidative burst, immune complex mediated macrophage activation, as well as mast cell maturation and degranulation, has been well illustrated in various studies. |
| GO:0010628 positive regulation of gene expression | IMP PMID:22079609 The catalytic phosphoinositol 3-kinase isoform p110Ξ΄ is requ... | KEEP AS NON CORE | Summary: p110Ξ΄ positively regulates expression of migration-associated proteins in glioma cells. Reason: PMID:22079609 measures decreased FAK and CDC42 protein abundance following selective p110Ξ΄ depletion. This supports regulation of gene-product expression without implying direct DNA binding or a universal transcriptional mechanism. Mouse stromal mRNA evidence in PMID:24009720 provides a separate native context. Supporting Evidence: PMID:22079609 Mechanistically, p110Ξ΄ knockdown reduced the protein levels of focal adhesion kinase and cell division cycle 42, key regulators of cellular migration. |
| GO:0030335 positive regulation of cell migration | IMP PMID:22079609 The catalytic phosphoinositol 3-kinase isoform p110Ξ΄ is requ... | KEEP AS NON CORE | Summary: Supported cell-migration role in specific leukocyte and glioma contexts, but non-core relative to lipid kinase signaling. Reason: PIK3CD knockdown decreases glioma-cell migration and PI3Kdelta also affects leukocyte migration; these are downstream context-specific outputs rather than the core function. Supporting Evidence: PMID:22079609 Interestingly, knockdown of p110Ξ΄ decreased the cell migration and invasion ability of all GBM cell lines tested. PMID:20940048 PI3KΞ΄ participates in the development, activation and migration of T cells and NK cells. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1676048 | ACCEPT | Summary: p110Ξ΄ has a cytosolic pool available for recruitment to receptor-associated membranes. Reason: The soluble pool is part of the normal signaling mechanism, not peripheral simply because activated enzyme encounters membrane substrates. Curated cytoplasmic localization in PMID:22020336 and the class IA recruitment studies support this assignment; refine the general cytoplasm term to the existing cytosol term. Supporting Evidence: file:human/PIK3CD/PIK3CD-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22020336}. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1676109 | ACCEPT | Summary: p110Ξ΄ has a cytosolic pool available for recruitment to receptor-associated membranes. Reason: The soluble pool is part of the normal signaling mechanism, not peripheral simply because activated enzyme encounters membrane substrates. Curated cytoplasmic localization in PMID:22020336 and the class IA recruitment studies support this assignment; refine the general cytoplasm term to the existing cytosol term. Supporting Evidence: file:human/PIK3CD/PIK3CD-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22020336}. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9012657 | ACCEPT | Summary: p110Ξ΄ has a cytosolic pool available for recruitment to receptor-associated membranes. Reason: The soluble pool is part of the normal signaling mechanism, not peripheral simply because activated enzyme encounters membrane substrates. Curated cytoplasmic localization in PMID:22020336 and the class IA recruitment studies support this assignment; refine the general cytoplasm term to the existing cytosol term. Supporting Evidence: file:human/PIK3CD/PIK3CD-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22020336}. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9021627 | ACCEPT | Summary: p110Ξ΄ has a cytosolic pool available for recruitment to receptor-associated membranes. Reason: The soluble pool is part of the normal signaling mechanism, not peripheral simply because activated enzyme encounters membrane substrates. Curated cytoplasmic localization in PMID:22020336 and the class IA recruitment studies support this assignment; refine the general cytoplasm term to the existing cytosol term. Supporting Evidence: file:human/PIK3CD/PIK3CD-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22020336}. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9027275 | ACCEPT | Summary: p110Ξ΄ has a cytosolic pool available for recruitment to receptor-associated membranes. Reason: The soluble pool is part of the normal signaling mechanism, not peripheral simply because activated enzyme encounters membrane substrates. Curated cytoplasmic localization in PMID:22020336 and the class IA recruitment studies support this assignment; refine the general cytoplasm term to the existing cytosol term. Supporting Evidence: file:human/PIK3CD/PIK3CD-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22020336}. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9606887 | ACCEPT | Summary: p110Ξ΄ has a cytosolic pool available for recruitment to receptor-associated membranes. Reason: The soluble pool is part of the normal signaling mechanism, not peripheral simply because activated enzyme encounters membrane substrates. Curated cytoplasmic localization in PMID:22020336 and the class IA recruitment studies support this assignment; refine the general cytoplasm term to the existing cytosol term. Supporting Evidence: file:human/PIK3CD/PIK3CD-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22020336}. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2045911 | ACCEPT | Summary: Supported core activated-site localization. PI3Kdelta is recruited to plasma-membrane receptor/adaptor complexes where its phosphoinositide substrates reside. Reason: Membrane recruitment is central to class IA PI3Kdelta activity because PIP2 substrate is membrane localized and receptor phosphotyrosine signals recruit the p85-p110delta complex to the plasma membrane. Supporting Evidence: file:human/PIK3CD/PIK3CD-deep-research-falcon.md Upon receptor phosphotyrosine signaling, SH2-containing p85 recruits the p85-p110Ξ΄ complex to the plasma membrane where phosphoinositide substrates reside. Reactome:R-HSA-1676048 At the plasma membrane, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunits form complexes with regulatory subunits. file:human/PIK3CD/PIK3CD-uniprot.txt Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2076220 | ACCEPT | Summary: Supported core activated-site localization. PI3Kdelta is recruited to plasma-membrane receptor/adaptor complexes where its phosphoinositide substrates reside. Reason: Membrane recruitment is central to class IA PI3Kdelta activity because PIP2 substrate is membrane localized and receptor phosphotyrosine signals recruit the p85-p110delta complex to the plasma membrane. Supporting Evidence: file:human/PIK3CD/PIK3CD-deep-research-falcon.md Upon receptor phosphotyrosine signaling, SH2-containing p85 recruits the p85-p110Ξ΄ complex to the plasma membrane where phosphoinositide substrates reside. Reactome:R-HSA-1676048 At the plasma membrane, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunits form complexes with regulatory subunits. file:human/PIK3CD/PIK3CD-uniprot.txt Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2316434 | ACCEPT | Summary: Supported core activated-site localization. PI3Kdelta is recruited to plasma-membrane receptor/adaptor complexes where its phosphoinositide substrates reside. Reason: Membrane recruitment is central to class IA PI3Kdelta activity because PIP2 substrate is membrane localized and receptor phosphotyrosine signals recruit the p85-p110delta complex to the plasma membrane. Supporting Evidence: file:human/PIK3CD/PIK3CD-deep-research-falcon.md Upon receptor phosphotyrosine signaling, SH2-containing p85 recruits the p85-p110Ξ΄ complex to the plasma membrane where phosphoinositide substrates reside. Reactome:R-HSA-1676048 At the plasma membrane, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunits form complexes with regulatory subunits. file:human/PIK3CD/PIK3CD-uniprot.txt Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2400009 | ACCEPT | Summary: Supported core activated-site localization. PI3Kdelta is recruited to plasma-membrane receptor/adaptor complexes where its phosphoinositide substrates reside. Reason: Membrane recruitment is central to class IA PI3Kdelta activity because PIP2 substrate is membrane localized and receptor phosphotyrosine signals recruit the p85-p110delta complex to the plasma membrane. Supporting Evidence: file:human/PIK3CD/PIK3CD-deep-research-falcon.md Upon receptor phosphotyrosine signaling, SH2-containing p85 recruits the p85-p110Ξ΄ complex to the plasma membrane where phosphoinositide substrates reside. Reactome:R-HSA-1676048 At the plasma membrane, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunits form complexes with regulatory subunits. file:human/PIK3CD/PIK3CD-uniprot.txt Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-388830 | ACCEPT | Summary: Supported core activated-site localization. PI3Kdelta is recruited to plasma-membrane receptor/adaptor complexes where its phosphoinositide substrates reside. Reason: Membrane recruitment is central to class IA PI3Kdelta activity because PIP2 substrate is membrane localized and receptor phosphotyrosine signals recruit the p85-p110delta complex to the plasma membrane. Supporting Evidence: file:human/PIK3CD/PIK3CD-deep-research-falcon.md Upon receptor phosphotyrosine signaling, SH2-containing p85 recruits the p85-p110Ξ΄ complex to the plasma membrane where phosphoinositide substrates reside. Reactome:R-HSA-1676048 At the plasma membrane, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunits form complexes with regulatory subunits. file:human/PIK3CD/PIK3CD-uniprot.txt Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-388832 | ACCEPT | Summary: Supported core activated-site localization. PI3Kdelta is recruited to plasma-membrane receptor/adaptor complexes where its phosphoinositide substrates reside. Reason: Membrane recruitment is central to class IA PI3Kdelta activity because PIP2 substrate is membrane localized and receptor phosphotyrosine signals recruit the p85-p110delta complex to the plasma membrane. Supporting Evidence: file:human/PIK3CD/PIK3CD-deep-research-falcon.md Upon receptor phosphotyrosine signaling, SH2-containing p85 recruits the p85-p110Ξ΄ complex to the plasma membrane where phosphoinositide substrates reside. Reactome:R-HSA-1676048 At the plasma membrane, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunits form complexes with regulatory subunits. file:human/PIK3CD/PIK3CD-uniprot.txt Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-389158 | ACCEPT | Summary: Supported core activated-site localization. PI3Kdelta is recruited to plasma-membrane receptor/adaptor complexes where its phosphoinositide substrates reside. Reason: Membrane recruitment is central to class IA PI3Kdelta activity because PIP2 substrate is membrane localized and receptor phosphotyrosine signals recruit the p85-p110delta complex to the plasma membrane. Supporting Evidence: file:human/PIK3CD/PIK3CD-deep-research-falcon.md Upon receptor phosphotyrosine signaling, SH2-containing p85 recruits the p85-p110Ξ΄ complex to the plasma membrane where phosphoinositide substrates reside. Reactome:R-HSA-1676048 At the plasma membrane, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunits form complexes with regulatory subunits. file:human/PIK3CD/PIK3CD-uniprot.txt Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-508247 | ACCEPT | Summary: Supported core activated-site localization. PI3Kdelta is recruited to plasma-membrane receptor/adaptor complexes where its phosphoinositide substrates reside. Reason: Membrane recruitment is central to class IA PI3Kdelta activity because PIP2 substrate is membrane localized and receptor phosphotyrosine signals recruit the p85-p110delta complex to the plasma membrane. Supporting Evidence: file:human/PIK3CD/PIK3CD-deep-research-falcon.md Upon receptor phosphotyrosine signaling, SH2-containing p85 recruits the p85-p110Ξ΄ complex to the plasma membrane where phosphoinositide substrates reside. Reactome:R-HSA-1676048 At the plasma membrane, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunits form complexes with regulatory subunits. file:human/PIK3CD/PIK3CD-uniprot.txt Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-879917 | ACCEPT | Summary: Supported core activated-site localization. PI3Kdelta is recruited to plasma-membrane receptor/adaptor complexes where its phosphoinositide substrates reside. Reason: Membrane recruitment is central to class IA PI3Kdelta activity because PIP2 substrate is membrane localized and receptor phosphotyrosine signals recruit the p85-p110delta complex to the plasma membrane. Supporting Evidence: file:human/PIK3CD/PIK3CD-deep-research-falcon.md Upon receptor phosphotyrosine signaling, SH2-containing p85 recruits the p85-p110Ξ΄ complex to the plasma membrane where phosphoinositide substrates reside. Reactome:R-HSA-1676048 At the plasma membrane, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunits form complexes with regulatory subunits. file:human/PIK3CD/PIK3CD-uniprot.txt Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8854905 | ACCEPT | Summary: Supported core activated-site localization. PI3Kdelta is recruited to plasma-membrane receptor/adaptor complexes where its phosphoinositide substrates reside. Reason: Membrane recruitment is central to class IA PI3Kdelta activity because PIP2 substrate is membrane localized and receptor phosphotyrosine signals recruit the p85-p110delta complex to the plasma membrane. Supporting Evidence: file:human/PIK3CD/PIK3CD-deep-research-falcon.md Upon receptor phosphotyrosine signaling, SH2-containing p85 recruits the p85-p110Ξ΄ complex to the plasma membrane where phosphoinositide substrates reside. Reactome:R-HSA-1676048 At the plasma membrane, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunits form complexes with regulatory subunits. file:human/PIK3CD/PIK3CD-uniprot.txt Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-912627 | ACCEPT | Summary: Supported core activated-site localization. PI3Kdelta is recruited to plasma-membrane receptor/adaptor complexes where its phosphoinositide substrates reside. Reason: Membrane recruitment is central to class IA PI3Kdelta activity because PIP2 substrate is membrane localized and receptor phosphotyrosine signals recruit the p85-p110delta complex to the plasma membrane. Supporting Evidence: file:human/PIK3CD/PIK3CD-deep-research-falcon.md Upon receptor phosphotyrosine signaling, SH2-containing p85 recruits the p85-p110Ξ΄ complex to the plasma membrane where phosphoinositide substrates reside. Reactome:R-HSA-1676048 At the plasma membrane, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunits form complexes with regulatory subunits. file:human/PIK3CD/PIK3CD-uniprot.txt Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-914182 | ACCEPT | Summary: Supported core activated-site localization. PI3Kdelta is recruited to plasma-membrane receptor/adaptor complexes where its phosphoinositide substrates reside. Reason: Membrane recruitment is central to class IA PI3Kdelta activity because PIP2 substrate is membrane localized and receptor phosphotyrosine signals recruit the p85-p110delta complex to the plasma membrane. Supporting Evidence: file:human/PIK3CD/PIK3CD-deep-research-falcon.md Upon receptor phosphotyrosine signaling, SH2-containing p85 recruits the p85-p110Ξ΄ complex to the plasma membrane where phosphoinositide substrates reside. Reactome:R-HSA-1676048 At the plasma membrane, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunits form complexes with regulatory subunits. file:human/PIK3CD/PIK3CD-uniprot.txt Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9606887 | ACCEPT | Summary: Supported core activated-site localization. PI3Kdelta is recruited to plasma-membrane receptor/adaptor complexes where its phosphoinositide substrates reside. Reason: Membrane recruitment is central to class IA PI3Kdelta activity because PIP2 substrate is membrane localized and receptor phosphotyrosine signals recruit the p85-p110delta complex to the plasma membrane. Supporting Evidence: file:human/PIK3CD/PIK3CD-deep-research-falcon.md Upon receptor phosphotyrosine signaling, SH2-containing p85 recruits the p85-p110Ξ΄ complex to the plasma membrane where phosphoinositide substrates reside. Reactome:R-HSA-1676048 At the plasma membrane, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunits form complexes with regulatory subunits. file:human/PIK3CD/PIK3CD-uniprot.txt Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396). |
| GO:0005942 phosphatidylinositol 3-kinase complex | NAS PMID:9113989 P110delta, a novel phosphoinositide 3-kinase in leukocytes. | MODIFY | Summary: p110Ξ΄ is the catalytic subunit of a class IA PI3K complex. Reason: Refine the general PI3K-complex claim to the p85-family heterodimer demonstrated for p110Ξ΄, preserving the PAINT assessment of conserved complex participation. Proposed replacements: phosphatidylinositol 3-kinase complex, class IA Supporting Evidence: file:human/PIK3CD/PIK3CD-uniprot.txt Heterodimer of a catalytic subunit PIK3CD and a p85 regulatory subunit (PIK3R1, PIK3R2 or PIK3R3). PMID:9235916 Recombinant p110delta phosphorylates phosphatidylinositol and coimmunoprecipitates with p85. |
| GO:0005942 phosphatidylinositol 3-kinase complex | NAS PMID:9235916 p110delta, a novel phosphatidylinositol 3-kinase catalytic s... | MODIFY | Summary: p110Ξ΄ is the catalytic subunit of a class IA PI3K complex. Reason: Refine the general PI3K-complex claim to the p85-family heterodimer demonstrated for p110Ξ΄, preserving the PAINT assessment of conserved complex participation. Proposed replacements: phosphatidylinositol 3-kinase complex, class IA Supporting Evidence: file:human/PIK3CD/PIK3CD-uniprot.txt Heterodimer of a catalytic subunit PIK3CD and a p85 regulatory subunit (PIK3R1, PIK3R2 or PIK3R3). PMID:9235916 Recombinant p110delta phosphorylates phosphatidylinositol and coimmunoprecipitates with p85. |
| GO:0006468 protein phosphorylation | NAS PMID:9113989 P110delta, a novel phosphoinositide 3-kinase in leukocytes. | MODIFY | Summary: p110Ξ΄ performs regulatory protein autophosphorylation. Reason: PMID:9113989 explicitly reports intrinsic autophosphorylation and PMID:10064595 maps Ser1039 and measures inhibition of lipid kinase activity. Refine the broad protein-phosphorylation process to autophosphorylation; replacing it with lipid phosphorylation would lose a real, independently measured reaction. Proposed replacements: protein autophosphorylation Supporting Evidence: PMID:10064595 The single site of autophosphorylation was mapped to Ser1039 at the C-terminus of p110delta. PMID:9113989 Unlike p110alpha, p110delta does not phosphorylate p85 but instead harbors an intrinsic autophosphorylation capacity. |
| GO:0007165 signal transduction | NAS PMID:9113989 P110delta, a novel phosphoinositide 3-kinase in leukocytes. | MODIFY | Summary: The generic signal-transduction annotation should be narrowed to PI3K/AKT and immune receptor signaling. Reason: PIK3CD participates in signaling by generating PIP3 downstream of receptor activation. The generic signal transduction parent obscures the specific PI3K/AKT, BCR, and TCR pathways supported by the evidence. Proposed replacements: phosphatidylinositol 3-kinase/protein kinase B signal transduction B cell receptor signaling pathway T cell receptor signaling pathway Supporting Evidence: PMID:9113989 p110delta displays a broad phosphoinositide lipid substrate specificity and interacts with SH2/SH3 domain-containing p85 adaptor proteins and with GTP-bound Ras. file:human/PIK3CD/PIK3CD-deep-research-falcon.md In immune cells, class IA PI3K (including p110Ξ΄) propagates signaling downstream of **BCR, TCR, CD28, ICOS, CD19, BAFF-R, CD40** (and related receptor/adaptor systems), framing the major immune-cell BP terms relevant for PIK3CD. file:human/PIK3CD/PIK3CD-uniprot.txt Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396). |
| GO:0016303 1-phosphatidylinositol-3-kinase activity | NAS PMID:9235916 p110delta, a novel phosphatidylinositol 3-kinase catalytic s... | KEEP AS NON CORE | Summary: p110Ξ΄ has biochemical capacity to produce PI3P from phosphatidylinositol. Reason: PMID:9113989 and PMID:9235916 establish the broad lipid-substrate range of p110Ξ΄. GO:0016303 is the specific PI-to-PI3P reaction, not a generic parent of the PIP2-to-PIP3 reaction. Preserve this chemistry and the compatible PAINT inference while distinguishing it from the dominant receptor-signaling substrate. Supporting Evidence: PMID:9235916 Recombinant p110delta phosphorylates phosphatidylinositol and coimmunoprecipitates with p85. PMID:9113989 p110delta displays a broad phosphoinositide lipid substrate specificity and interacts with SH2/SH3 domain-containing p85 adaptor proteins and with GTP-bound Ras. |
| GO:0005515 protein binding | IPI PMID:22020336 p37Ξ΄ is a new isoform of PI3K p110Ξ΄ that increases cell prol... | REMOVE | Summary: The measured partner association remains useful provenance. Reason: Remove bare protein binding under the current policy; the PMID:22020336 interaction with UniProtKB:P27986 is not being declared false. Complex assembly and catalytic functions are retained separately. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: The measured partner association remains useful provenance. Reason: Remove bare protein binding under the current policy; the PMID:32296183 interaction with UniProtKB:Q92569 is not being declared false. Complex assembly and catalytic functions are retained separately. |
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Download this section (compressed HTML)Q: How much do PI-to-PI3P and PI4P-to-PI(3,4)P2 reactions contribute to native p110Ξ΄ signaling relative to its dominant PIP3 production?
Q: Which kinase accounts for receptor-associated p110Ξ΄ Ser1039 phosphorylation in cells, and how does it tune pathway duration?
Q: What is the isoform-selective and death-mode-specific contribution of p110Ξ΄ in FcΞ±RI-stimulated human neutrophils?
Experiment: Use isoform-selective genetic rescue in human primary B and T cells to separate PIK3CD-specific BCR, TCR, and CD28 signaling outputs from overlapping PIK3CA/PIK3CB/PIK3CG class I PI3K activity.
Type: primary-cell genetic rescue and phosphoprotein/PIP3 readout
Experiment: Measure PI(4,5)P2-to-PIP3 and PI4P-to-PI(3,4)P2 product formation for p110delta-p85 complexes under matched in vitro and membrane-recruitment conditions to clarify whether PI4P kinase annotations should remain non-core.
Type: lipid kinase substrate-specificity assay
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