PIK3CG

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0001819 positive regulation of cytokine production	TAS PMID:19075988 Isoform selective phosphoinositide 3-kinase gamma and delta ...	KEEP AS NON CORE	Summary: Cytokine production is a context-dependent output of p110γ signaling. Reason: The original therapeutic review discusses immune regulation. Retain positive regulation in the lymphocyte contexts summarized in curated evidence; human p110γ deficiency can instead increase myeloid IL-12/IL-23 production (PMID:31554793), so the sign is not universal. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Regulates T-lymphocyte proliferation, activation, and cytokine production.
GO:0002250 adaptive immune response	TAS PMID:17290298 PI3K delta and PI3K gamma: partners in crime in inflammation...	KEEP AS NON CORE	Summary: p110γ contributes to adaptive immune responses. Reason: Adaptive immune participation includes lymphocyte development and activation. This does not imply that p110γ is the default class IA catalytic subunit of the BCR signalosome. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Together with PIK3CD participates in T-lymphocyte development.
GO:0002407 dendritic cell chemotaxis	TAS PMID:18278175 Targeting phosphoinositide 3-kinase gamma to fight inflammat...	KEEP AS NON CORE	Summary: p110γ supports dendritic-cell movement. Reason: Retain the cell-type-specific chemotaxis claim summarized by PMID:18278175 and curated synthesis, without labeling that review as a direct human migration assay. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Controls motility of dendritic cells.
GO:0002679 respiratory burst involved in defense response	TAS PMID:19075988 Isoform selective phosphoinositide 3-kinase gamma and delta ...	KEEP AS NON CORE	Summary: p110γ contributes to the neutrophil respiratory burst. Reason: The signaling kinase participates in activation of the oxidase response; it is not itself the enzyme producing superoxide. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Together with PIK3CD participates in neutrophil respiratory burst.
GO:0003376 sphingosine-1-phosphate receptor signaling pathway	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: p110γ contributes to S1P-induced endothelial migration and Rac1 activation. Reason: PMID:18558630 assays human umbilical-vein and mouse lung endothelial cells. Retain the measured receptor/migration/Rac context; distinguish it from the p110β-selective AKT requirement in the same study. Supporting Evidence: PMID:18558630 Both PI3Kbeta and gamma isoforms are required for full migration induced by S1P, with Rac1 being a major mediator downstream of both isoforms.
GO:0003376 sphingosine-1-phosphate receptor signaling pathway	IMP PMID:18558630 Overlapping and distinct roles for PI3Kbeta and gamma isofor...	KEEP AS NON CORE	Summary: p110γ contributes to S1P-induced endothelial migration and Rac1 activation. Reason: PMID:18558630 assays human umbilical-vein and mouse lung endothelial cells. Retain the measured receptor/migration/Rac context; distinguish it from the p110β-selective AKT requirement in the same study. Supporting Evidence: PMID:18558630 Both PI3Kbeta and gamma isoforms are required for full migration induced by S1P, with Rac1 being a major mediator downstream of both isoforms.
GO:0004672 protein kinase activity	TAS PMID:19376709 Twice upon a time: PI3K's secret double life exposed.	MODIFY	Summary: p110γ has experimentally demonstrated protein serine kinase activity in addition to lipid kinase activities. Reason: Ser1101 autophosphorylation (PMID:12502714) and tropomyosin phosphorylation in the receptor-endocytosis study (PMID:16094730) establish genuine protein kinase chemistry. Preserve this activity when refining a broad kinase term; lipid kinase activity alone is not an adequate replacement. Proposed replacements: protein serine kinase activity Supporting Evidence: PMID:12502714 Autophosphorylation sites of both PI3K isoforms were mapped to C-terminal serine residues of the catalytic p110 subunit (i.e. serine 1070 of p110 beta and serine 1101 of p110 gamma).
GO:0004674 protein serine/threonine kinase activity	IEA GO_REF:0000003	MODIFY	Summary: p110γ has experimentally demonstrated protein serine kinase activity in addition to lipid kinase activities. Reason: Ser1101 autophosphorylation (PMID:12502714) and tropomyosin phosphorylation in the receptor-endocytosis study (PMID:16094730) establish genuine protein kinase chemistry. Preserve this activity when refining a broad kinase term; lipid kinase activity alone is not an adequate replacement. Proposed replacements: protein serine kinase activity Supporting Evidence: PMID:12502714 Autophosphorylation sites of both PI3K isoforms were mapped to C-terminal serine residues of the catalytic p110 subunit (i.e. serine 1070 of p110 beta and serine 1101 of p110 gamma).
GO:0005515 protein binding	IPI PMID:12507995 Roles of G beta gamma in membrane recruitment and activation...	REMOVE	Summary: The interaction reported by PMID:12507995 is preserved as provenance. Reason: Bare protein binding is uninformative under the current binding policy; this removes the generic annotation, not the interaction with UniProtKB:O02696. A partner-specific activity is not inferred from co-association alone.
GO:0005515 protein binding	IPI PMID:21393242 A phosphodiesterase 3B-based signaling complex integrates ex...	REMOVE	Summary: The interaction reported by PMID:21393242 is preserved as provenance. Reason: Bare protein binding is uninformative under the current binding policy; this removes the generic annotation, not the interaction with UniProtKB:Q13370. A partner-specific activity is not inferred from co-association alone.
GO:0005515 protein binding	IPI PMID:23824069 PKCβ phosphorylates PI3Kγ to activate it and release it from...	REMOVE	Summary: The interaction reported by PMID:23824069 is preserved as provenance. Reason: Bare protein binding is uninformative under the current binding policy; this removes the generic annotation, not the interaction with UniProtKB:P68404-2. A partner-specific activity is not inferred from co-association alone.
GO:0005515 protein binding	IPI PMID:23824069 PKCβ phosphorylates PI3Kγ to activate it and release it from...	REMOVE	Summary: The interaction reported by PMID:23824069 is preserved as provenance. Reason: Bare protein binding is uninformative under the current binding policy; this removes the generic annotation, not the interaction with UniProtKB:Q3U6Q4. A partner-specific activity is not inferred from co-association alone.
GO:0005515 protein binding	IPI PMID:25556234 New host factors important for respiratory syncytial virus (...	REMOVE	Summary: The interaction reported by PMID:25556234 is preserved as provenance. Reason: Bare protein binding is uninformative under the current binding policy; this removes the generic annotation, not the interaction with UniProtKB:P0DOE7. A partner-specific activity is not inferred from co-association alone.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	REMOVE	Summary: The interaction reported by PMID:32814053 is preserved as provenance. Reason: Bare protein binding is uninformative under the current binding policy; this removes the generic annotation, not the interaction with UniProtKB:P05067. A partner-specific activity is not inferred from co-association alone.
GO:0005515 protein binding	IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei...	REMOVE	Summary: The interaction reported by PMID:35512704 is preserved as provenance. Reason: Bare protein binding is uninformative under the current binding policy; this removes the generic annotation, not the interaction with UniProtKB:P15056. A partner-specific activity is not inferred from co-association alone.
GO:0005737 cytoplasm	EXP PMID:12163475 Phosphoinositide 3-kinase regulates beta2-adrenergic recepto...	MODIFY	Summary: p110γ is recruited from a soluble cytosolic pool to the plasma membrane. Reason: Refine the general compartment to the supported soluble and membrane-associated pools as applicable. PMID:12507995 and PMID:12163475 distinguish recruitment from permanent membrane integration; the original PMID:12163475 assertion is compatible with that distribution. Proposed replacements: cytosol plasma membrane Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Activation by GPCRs is assisted by the regulatory subunits (PIK3R5 or PIK3R6) leading to the translocation from the cytosol to the plasma membrane and to kinase activation.
GO:0005737 cytoplasm	IBA GO_REF:0000033	MODIFY	Summary: p110γ is recruited from a soluble cytosolic pool to the plasma membrane. Reason: Refine the general compartment to the supported soluble and membrane-associated pools as applicable. PMID:12507995 and PMID:12163475 distinguish recruitment from permanent membrane integration; the original GO_REF:0000033 assertion is compatible with that distribution. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000005673 SUPPORTS TRANSFER cytoplasm: Refine the general compartment to the supported soluble and membrane-associated pools as applicable. PMID:12507995 and PMID:12163475 distinguish recruitment from permanent membrane integration; the original GO_REF:0000033 assertion is compatible with that distribution. Proposed replacements: cytosol plasma membrane Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Activation by GPCRs is assisted by the regulatory subunits (PIK3R5 or PIK3R6) leading to the translocation from the cytosol to the plasma membrane and to kinase activation.
GO:0005737 cytoplasm	IDA PMID:12507995 Roles of G beta gamma in membrane recruitment and activation...	MODIFY	Summary: p110γ is recruited from a soluble cytosolic pool to the plasma membrane. Reason: Refine the general compartment to the supported soluble and membrane-associated pools as applicable. PMID:12507995 and PMID:12163475 distinguish recruitment from permanent membrane integration; the original PMID:12507995 assertion is compatible with that distribution. Proposed replacements: cytosol plasma membrane Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Activation by GPCRs is assisted by the regulatory subunits (PIK3R5 or PIK3R6) leading to the translocation from the cytosol to the plasma membrane and to kinase activation.
GO:0005737 cytoplasm	IEA GO_REF:0000044	MODIFY	Summary: p110γ is recruited from a soluble cytosolic pool to the plasma membrane. Reason: Refine the general compartment to the supported soluble and membrane-associated pools as applicable. PMID:12507995 and PMID:12163475 distinguish recruitment from permanent membrane integration; the original GO_REF:0000044 assertion is compatible with that distribution. Proposed replacements: cytosol plasma membrane Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Activation by GPCRs is assisted by the regulatory subunits (PIK3R5 or PIK3R6) leading to the translocation from the cytosol to the plasma membrane and to kinase activation.
GO:0005829 cytosol	IDA GO_REF:0000052	ACCEPT	Summary: p110γ occupies the cytosol pool during regulated membrane recruitment. Reason: Retain this compartment as part of the catalytic cycle: regulatory-subunit-assisted recruitment brings cytosolic p110γ to membrane phosphoinositide substrates. GO_REF:0000052 is consistent with this independently documented distribution. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Activation by GPCRs is assisted by the regulatory subunits (PIK3R5 or PIK3R6) leading to the translocation from the cytosol to the plasma membrane and to kinase activation.
GO:0005829 cytosol	TAS Reactome:R-HSA-1676048	ACCEPT	Summary: p110γ occupies the cytosol pool during regulated membrane recruitment. Reason: Retain this compartment as part of the catalytic cycle: regulatory-subunit-assisted recruitment brings cytosolic p110γ to membrane phosphoinositide substrates. Reactome:R-HSA-1676048 is consistent with this independently documented distribution. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Activation by GPCRs is assisted by the regulatory subunits (PIK3R5 or PIK3R6) leading to the translocation from the cytosol to the plasma membrane and to kinase activation.
GO:0005829 cytosol	TAS Reactome:R-HSA-1676109	ACCEPT	Summary: p110γ occupies the cytosol pool during regulated membrane recruitment. Reason: Retain this compartment as part of the catalytic cycle: regulatory-subunit-assisted recruitment brings cytosolic p110γ to membrane phosphoinositide substrates. Reactome:R-HSA-1676109 is consistent with this independently documented distribution. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Activation by GPCRs is assisted by the regulatory subunits (PIK3R5 or PIK3R6) leading to the translocation from the cytosol to the plasma membrane and to kinase activation.
GO:0005829 cytosol	TAS Reactome:R-HSA-2316434	ACCEPT	Summary: p110γ occupies the cytosol pool during regulated membrane recruitment. Reason: Retain this compartment as part of the catalytic cycle: regulatory-subunit-assisted recruitment brings cytosolic p110γ to membrane phosphoinositide substrates. Reactome:R-HSA-2316434 is consistent with this independently documented distribution. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Activation by GPCRs is assisted by the regulatory subunits (PIK3R5 or PIK3R6) leading to the translocation from the cytosol to the plasma membrane and to kinase activation.
GO:0005829 cytosol	TAS Reactome:R-HSA-2400009	ACCEPT	Summary: p110γ occupies the cytosol pool during regulated membrane recruitment. Reason: Retain this compartment as part of the catalytic cycle: regulatory-subunit-assisted recruitment brings cytosolic p110γ to membrane phosphoinositide substrates. Reactome:R-HSA-2400009 is consistent with this independently documented distribution. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Activation by GPCRs is assisted by the regulatory subunits (PIK3R5 or PIK3R6) leading to the translocation from the cytosol to the plasma membrane and to kinase activation.
GO:0005829 cytosol	TAS Reactome:R-HSA-388830	ACCEPT	Summary: p110γ occupies the cytosol pool during regulated membrane recruitment. Reason: Retain this compartment as part of the catalytic cycle: regulatory-subunit-assisted recruitment brings cytosolic p110γ to membrane phosphoinositide substrates. Reactome:R-HSA-388830 is consistent with this independently documented distribution. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Activation by GPCRs is assisted by the regulatory subunits (PIK3R5 or PIK3R6) leading to the translocation from the cytosol to the plasma membrane and to kinase activation.
GO:0005829 cytosol	TAS Reactome:R-HSA-388832	ACCEPT	Summary: p110γ occupies the cytosol pool during regulated membrane recruitment. Reason: Retain this compartment as part of the catalytic cycle: regulatory-subunit-assisted recruitment brings cytosolic p110γ to membrane phosphoinositide substrates. Reactome:R-HSA-388832 is consistent with this independently documented distribution. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Activation by GPCRs is assisted by the regulatory subunits (PIK3R5 or PIK3R6) leading to the translocation from the cytosol to the plasma membrane and to kinase activation.
GO:0005829 cytosol	TAS Reactome:R-HSA-389158	ACCEPT	Summary: p110γ occupies the cytosol pool during regulated membrane recruitment. Reason: Retain this compartment as part of the catalytic cycle: regulatory-subunit-assisted recruitment brings cytosolic p110γ to membrane phosphoinositide substrates. Reactome:R-HSA-389158 is consistent with this independently documented distribution. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Activation by GPCRs is assisted by the regulatory subunits (PIK3R5 or PIK3R6) leading to the translocation from the cytosol to the plasma membrane and to kinase activation.
GO:0005829 cytosol	TAS Reactome:R-HSA-392295	ACCEPT	Summary: p110γ occupies the cytosol pool during regulated membrane recruitment. Reason: Retain this compartment as part of the catalytic cycle: regulatory-subunit-assisted recruitment brings cytosolic p110γ to membrane phosphoinositide substrates. Reactome:R-HSA-392295 is consistent with this independently documented distribution. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Activation by GPCRs is assisted by the regulatory subunits (PIK3R5 or PIK3R6) leading to the translocation from the cytosol to the plasma membrane and to kinase activation.
GO:0005829 cytosol	TAS Reactome:R-HSA-392300	ACCEPT	Summary: p110γ occupies the cytosol pool during regulated membrane recruitment. Reason: Retain this compartment as part of the catalytic cycle: regulatory-subunit-assisted recruitment brings cytosolic p110γ to membrane phosphoinositide substrates. Reactome:R-HSA-392300 is consistent with this independently documented distribution. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Activation by GPCRs is assisted by the regulatory subunits (PIK3R5 or PIK3R6) leading to the translocation from the cytosol to the plasma membrane and to kinase activation.
GO:0005829 cytosol	TAS Reactome:R-HSA-437118	ACCEPT	Summary: p110γ occupies the cytosol pool during regulated membrane recruitment. Reason: Retain this compartment as part of the catalytic cycle: regulatory-subunit-assisted recruitment brings cytosolic p110γ to membrane phosphoinositide substrates. Reactome:R-HSA-437118 is consistent with this independently documented distribution. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Activation by GPCRs is assisted by the regulatory subunits (PIK3R5 or PIK3R6) leading to the translocation from the cytosol to the plasma membrane and to kinase activation.
GO:0005829 cytosol	TAS Reactome:R-HSA-437162	ACCEPT	Summary: p110γ occupies the cytosol pool during regulated membrane recruitment. Reason: Retain this compartment as part of the catalytic cycle: regulatory-subunit-assisted recruitment brings cytosolic p110γ to membrane phosphoinositide substrates. Reactome:R-HSA-437162 is consistent with this independently documented distribution. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Activation by GPCRs is assisted by the regulatory subunits (PIK3R5 or PIK3R6) leading to the translocation from the cytosol to the plasma membrane and to kinase activation.
GO:0005829 cytosol	TAS Reactome:R-HSA-9012657	ACCEPT	Summary: p110γ occupies the cytosol pool during regulated membrane recruitment. Reason: Retain this compartment as part of the catalytic cycle: regulatory-subunit-assisted recruitment brings cytosolic p110γ to membrane phosphoinositide substrates. Reactome:R-HSA-9012657 is consistent with this independently documented distribution. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Activation by GPCRs is assisted by the regulatory subunits (PIK3R5 or PIK3R6) leading to the translocation from the cytosol to the plasma membrane and to kinase activation.
GO:0005829 cytosol	TAS Reactome:R-HSA-9021627	ACCEPT	Summary: p110γ occupies the cytosol pool during regulated membrane recruitment. Reason: Retain this compartment as part of the catalytic cycle: regulatory-subunit-assisted recruitment brings cytosolic p110γ to membrane phosphoinositide substrates. Reactome:R-HSA-9021627 is consistent with this independently documented distribution. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Activation by GPCRs is assisted by the regulatory subunits (PIK3R5 or PIK3R6) leading to the translocation from the cytosol to the plasma membrane and to kinase activation.
GO:0005829 cytosol	TAS Reactome:R-HSA-9027275	ACCEPT	Summary: p110γ occupies the cytosol pool during regulated membrane recruitment. Reason: Retain this compartment as part of the catalytic cycle: regulatory-subunit-assisted recruitment brings cytosolic p110γ to membrane phosphoinositide substrates. Reactome:R-HSA-9027275 is consistent with this independently documented distribution. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Activation by GPCRs is assisted by the regulatory subunits (PIK3R5 or PIK3R6) leading to the translocation from the cytosol to the plasma membrane and to kinase activation.
GO:0005886 plasma membrane	EXP PMID:12163475 Phosphoinositide 3-kinase regulates beta2-adrenergic recepto...	ACCEPT	Summary: p110γ occupies the plasma membrane pool during regulated membrane recruitment. Reason: Retain this compartment as part of the catalytic cycle: regulatory-subunit-assisted recruitment brings cytosolic p110γ to membrane phosphoinositide substrates. PMID:12163475 is consistent with this independently documented distribution. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Activation by GPCRs is assisted by the regulatory subunits (PIK3R5 or PIK3R6) leading to the translocation from the cytosol to the plasma membrane and to kinase activation.
GO:0005886 plasma membrane	IBA GO_REF:0000033	ACCEPT	Summary: p110γ occupies the plasma membrane pool during regulated membrane recruitment. Reason: Retain this compartment as part of the catalytic cycle: regulatory-subunit-assisted recruitment brings cytosolic p110γ to membrane phosphoinositide substrates. GO_REF:0000033 is consistent with this independently documented distribution. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Activation by GPCRs is assisted by the regulatory subunits (PIK3R5 or PIK3R6) leading to the translocation from the cytosol to the plasma membrane and to kinase activation.
GO:0005886 plasma membrane	IDA GO_REF:0000052	ACCEPT	Summary: p110γ occupies the plasma membrane pool during regulated membrane recruitment. Reason: Retain this compartment as part of the catalytic cycle: regulatory-subunit-assisted recruitment brings cytosolic p110γ to membrane phosphoinositide substrates. GO_REF:0000052 is consistent with this independently documented distribution. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Activation by GPCRs is assisted by the regulatory subunits (PIK3R5 or PIK3R6) leading to the translocation from the cytosol to the plasma membrane and to kinase activation.
GO:0005886 plasma membrane	IEA GO_REF:0000044	ACCEPT	Summary: p110γ occupies the plasma membrane pool during regulated membrane recruitment. Reason: Retain this compartment as part of the catalytic cycle: regulatory-subunit-assisted recruitment brings cytosolic p110γ to membrane phosphoinositide substrates. GO_REF:0000044 is consistent with this independently documented distribution. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Activation by GPCRs is assisted by the regulatory subunits (PIK3R5 or PIK3R6) leading to the translocation from the cytosol to the plasma membrane and to kinase activation.
GO:0005943 phosphatidylinositol 3-kinase complex, class IA	EXP PMID:10358071 Characterizing the interactions between the two subunits of ...	MODIFY	Summary: p110γ forms class IB complexes with p101 or p84/p87. Reason: Class IA denotes p85-family regulatory complexes; p110γ instead binds PIK3R5/PIK3R6. PMID:10358071 characterizes the p101 complex, and PMID:7624799 reports no p85 interaction. For the PAINT PTN000799659 assertion, this is a subfamily/complex-type correction, not rejection based on donor count. Proposed replacements: phosphatidylinositol 3-kinase complex, class IB Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Heterodimer of a catalytic subunit PIK3CG and a PIK3R5 or PIK3R6 regulatory subunit. PMID:7624799 The p110 gamma enzyme was activated in vitro by both the alpha and beta gamma subunits of heterotrimeric guanosine triphosphate (GTP)-binding proteins (G proteins) and did not interact with p85.
GO:0005943 phosphatidylinositol 3-kinase complex, class IA	IBA GO_REF:0000033	MODIFY	Summary: p110γ forms class IB complexes with p101 or p84/p87. Reason: Class IA denotes p85-family regulatory complexes; p110γ instead binds PIK3R5/PIK3R6. PMID:10358071 characterizes the p101 complex, and PMID:7624799 reports no p85 interaction. For the PAINT PTN000799659 assertion, this is a subfamily/complex-type correction, not rejection based on donor count. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN000799659 SUPPORTS SOURCE BUT NOT TARGET PTN000799659 class IA complex placement is incompatible with directly characterized p110γ-p101/p84 class IB complexes and lack of p85 association; this is a complex-subfamily boundary correction, not a donor-count objection. Proposed replacements: phosphatidylinositol 3-kinase complex, class IB Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Heterodimer of a catalytic subunit PIK3CG and a PIK3R5 or PIK3R6 regulatory subunit. PMID:7624799 The p110 gamma enzyme was activated in vitro by both the alpha and beta gamma subunits of heterotrimeric guanosine triphosphate (GTP)-binding proteins (G proteins) and did not interact with p85.
GO:0005944 phosphatidylinositol 3-kinase complex, class IB	IBA GO_REF:0000033	ACCEPT	Summary: p110γ forms class IB complexes with p101 or p84/p87. Reason: Class IA denotes p85-family regulatory complexes; p110γ instead binds PIK3R5/PIK3R6. PMID:10358071 characterizes the p101 complex, and PMID:7624799 reports no p85 interaction. For the PAINT PTN000799659 assertion, this is a subfamily/complex-type correction, not rejection based on donor count. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Heterodimer of a catalytic subunit PIK3CG and a PIK3R5 or PIK3R6 regulatory subunit. PMID:7624799 The p110 gamma enzyme was activated in vitro by both the alpha and beta gamma subunits of heterotrimeric guanosine triphosphate (GTP)-binding proteins (G proteins) and did not interact with p85.
GO:0005944 phosphatidylinositol 3-kinase complex, class IB	IDA PMID:12507995 Roles of G beta gamma in membrane recruitment and activation...	ACCEPT	Summary: p110γ forms class IB complexes with p101 or p84/p87. Reason: Class IA denotes p85-family regulatory complexes; p110γ instead binds PIK3R5/PIK3R6. PMID:10358071 characterizes the p101 complex, and PMID:7624799 reports no p85 interaction. For the PAINT PTN000799659 assertion, this is a subfamily/complex-type correction, not rejection based on donor count. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Heterodimer of a catalytic subunit PIK3CG and a PIK3R5 or PIK3R6 regulatory subunit. PMID:7624799 The p110 gamma enzyme was activated in vitro by both the alpha and beta gamma subunits of heterotrimeric guanosine triphosphate (GTP)-binding proteins (G proteins) and did not interact with p85.
GO:0006954 inflammatory response	TAS PMID:17290298 PI3K delta and PI3K gamma: partners in crime in inflammation...	KEEP AS NON CORE	Summary: p110γ participates in immune and inflammatory signaling. Reason: Retain the immune-system contribution supported by curated synthesis and human loss-of-function PMID:31554793. These terms do not assign a universal pro-inflammatory sign: cellular context determines whether p110γ promotes effector activation or restrains cytokine excess. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Involved in immune, inflammatory and allergic responses.
GO:0006955 immune response	NAS PMID:31480354 Function, Regulation and Biological Roles of PI3Kγ Variants.	KEEP AS NON CORE	Summary: p110γ participates in immune and inflammatory signaling. Reason: Retain the immune-system contribution supported by curated synthesis and human loss-of-function PMID:31554793. These terms do not assign a universal pro-inflammatory sign: cellular context determines whether p110γ promotes effector activation or restrains cytokine excess. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Involved in immune, inflammatory and allergic responses.
GO:0007186 G protein-coupled receptor signaling pathway	EXP PMID:10358071 Characterizing the interactions between the two subunits of ...	ACCEPT	Summary: Class IB PI3K couples G-protein inputs to lipid second-messenger synthesis. Reason: Direct human p110γ biochemistry supports G-protein activation. This conserved core route is not exclusive: PMID:23824069 also establishes PKCβ-dependent regulation after FcεRI/Ca2+ stimulation. Supporting Evidence: PMID:7624799 The p110 gamma enzyme was activated in vitro by both the alpha and beta gamma subunits of heterotrimeric guanosine triphosphate (GTP)-binding proteins (G proteins) and did not interact with p85.
GO:0007186 G protein-coupled receptor signaling pathway	IDA PMID:12507995 Roles of G beta gamma in membrane recruitment and activation...	ACCEPT	Summary: Class IB PI3K couples G-protein inputs to lipid second-messenger synthesis. Reason: Direct human p110γ biochemistry supports G-protein activation. This conserved core route is not exclusive: PMID:23824069 also establishes PKCβ-dependent regulation after FcεRI/Ca2+ stimulation. Supporting Evidence: PMID:7624799 The p110 gamma enzyme was activated in vitro by both the alpha and beta gamma subunits of heterotrimeric guanosine triphosphate (GTP)-binding proteins (G proteins) and did not interact with p85.
GO:0007186 G protein-coupled receptor signaling pathway	TAS PMID:7624799 Cloning and characterization of a G protein-activated human ...	ACCEPT	Summary: Class IB PI3K couples G-protein inputs to lipid second-messenger synthesis. Reason: Direct human p110γ biochemistry supports G-protein activation. This conserved core route is not exclusive: PMID:23824069 also establishes PKCβ-dependent regulation after FcεRI/Ca2+ stimulation. Supporting Evidence: PMID:7624799 The p110 gamma enzyme was activated in vitro by both the alpha and beta gamma subunits of heterotrimeric guanosine triphosphate (GTP)-binding proteins (G proteins) and did not interact with p85.
GO:0007200 phospholipase C-activating G protein-coupled receptor signaling pathway	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: p110γ participates in a PLC-activating formyl-peptide receptor pathway. Reason: The mouse Q9JHG7 transfer concerns a multistep neutrophil pathway. Participation does not mean that p110γ directly catalyzes PLC activation or precedes PLC in every signaling sequence. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt In neutrophils, participates in a phospholipase C-activating N-formyl peptide-activated GPCR (G protein-coupled receptor) signaling pathway downstream of RASGRP4-mediated Ras-activation, to promote neutrophil functional responses (By similarity).
GO:0010595 positive regulation of endothelial cell migration	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: p110γ contributes to S1P-induced endothelial migration and Rac1 activation. Reason: PMID:18558630 assays human umbilical-vein and mouse lung endothelial cells. Retain the measured receptor/migration/Rac context; distinguish it from the p110β-selective AKT requirement in the same study. Supporting Evidence: PMID:18558630 Both PI3Kbeta and gamma isoforms are required for full migration induced by S1P, with Rac1 being a major mediator downstream of both isoforms.
GO:0010595 positive regulation of endothelial cell migration	IMP PMID:18558630 Overlapping and distinct roles for PI3Kbeta and gamma isofor...	KEEP AS NON CORE	Summary: p110γ contributes to S1P-induced endothelial migration and Rac1 activation. Reason: PMID:18558630 assays human umbilical-vein and mouse lung endothelial cells. Retain the measured receptor/migration/Rac context; distinguish it from the p110β-selective AKT requirement in the same study. Supporting Evidence: PMID:18558630 Both PI3Kbeta and gamma isoforms are required for full migration induced by S1P, with Rac1 being a major mediator downstream of both isoforms.
GO:0010818 T cell chemotaxis	TAS PMID:18278175 Targeting phosphoinositide 3-kinase gamma to fight inflammat...	KEEP AS NON CORE	Summary: p110γ participates in T-cell chemotaxis. Reason: Retain the lymphocyte-migration context summarized in PMID:18278175; this is a physiological output of lipid signaling, not a separate catalytic activity. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Participates in T-lymphocyte migration.
GO:0016020 membrane	HDA PMID:19946888 Defining the membrane proteome of NK cells.	MODIFY	Summary: p110γ is recruited from a soluble cytosolic pool to the plasma membrane. Reason: Refine the general compartment to the supported soluble and membrane-associated pools as applicable. PMID:12507995 and PMID:12163475 distinguish recruitment from permanent membrane integration; the original PMID:19946888 assertion is compatible with that distribution. Proposed replacements: plasma membrane Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Activation by GPCRs is assisted by the regulatory subunits (PIK3R5 or PIK3R6) leading to the translocation from the cytosol to the plasma membrane and to kinase activation.
GO:0016020 membrane	IDA PMID:12507995 Roles of G beta gamma in membrane recruitment and activation...	MODIFY	Summary: p110γ is recruited from a soluble cytosolic pool to the plasma membrane. Reason: Refine the general compartment to the supported soluble and membrane-associated pools as applicable. PMID:12507995 and PMID:12163475 distinguish recruitment from permanent membrane integration; the original PMID:12507995 assertion is compatible with that distribution. Proposed replacements: plasma membrane Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Activation by GPCRs is assisted by the regulatory subunits (PIK3R5 or PIK3R6) leading to the translocation from the cytosol to the plasma membrane and to kinase activation.
GO:0016301 kinase activity	IEA GO_REF:0000002	MODIFY	Summary: p110γ has experimentally demonstrated protein serine kinase activity in addition to lipid kinase activities. Reason: Ser1101 autophosphorylation (PMID:12502714) and tropomyosin phosphorylation in the receptor-endocytosis study (PMID:16094730) establish genuine protein kinase chemistry. Preserve this activity when refining a broad kinase term; lipid kinase activity alone is not an adequate replacement. 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:12502714 Autophosphorylation sites of both PI3K isoforms were mapped to C-terminal serine residues of the catalytic p110 subunit (i.e. serine 1070 of p110 beta and serine 1101 of p110 gamma).
GO:0016303 1-phosphatidylinositol-3-kinase activity	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: p110γ can generate PI3P from phosphatidylinositol. Reason: The human p110γ comparator in PMID:16123124 directly produces all three D3-phosphorylated lipid products. This is a real substrate-specific activity, distinct from the major PIP3 signaling reaction; a class I identity does not make PI3P production false. The PAINT inference is supported by the measured target chemistry. Supporting Evidence: PMID:16123124 Whereas yeast and mammalian IPMKs form only a single product, PI3K also forms PI(3,4)P 2 and PI (3)P in addition to PI(3,4,5)P 3 when incubated with lipid extracts, consistent with previous reports ( 9 ).
GO:0016303 1-phosphatidylinositol-3-kinase activity	IDA PMID:11277933 Human phosphatidylinositol 4-kinase isoform PI4K92. Expressi...	KEEP AS NON CORE	Summary: p110γ can generate PI3P from phosphatidylinositol. Reason: The human p110γ comparator in PMID:16123124 directly produces all three D3-phosphorylated lipid products. This is a real substrate-specific activity, distinct from the major PIP3 signaling reaction; a class I identity does not make PI3P production false. The PAINT inference is supported by the measured target chemistry. Supporting Evidence: PMID:16123124 Whereas yeast and mammalian IPMKs form only a single product, PI3K also forms PI(3,4)P 2 and PI (3)P in addition to PI(3,4,5)P 3 when incubated with lipid extracts, consistent with previous reports ( 9 ).
GO:0016303 1-phosphatidylinositol-3-kinase activity	IDA PMID:16123124 Inositol polyphosphate multikinase is a nuclear PI3-kinase w...	KEEP AS NON CORE	Summary: p110γ can generate PI3P from phosphatidylinositol. Reason: The human p110γ comparator in PMID:16123124 directly produces all three D3-phosphorylated lipid products. This is a real substrate-specific activity, distinct from the major PIP3 signaling reaction; a class I identity does not make PI3P production false. The PAINT inference is supported by the measured target chemistry. Supporting Evidence: PMID:16123124 Whereas yeast and mammalian IPMKs form only a single product, PI3K also forms PI(3,4)P 2 and PI (3)P in addition to PI(3,4,5)P 3 when incubated with lipid extracts, consistent with previous reports ( 9 ).
GO:0016303 1-phosphatidylinositol-3-kinase activity	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: p110γ can generate PI3P from phosphatidylinositol. Reason: The human p110γ comparator in PMID:16123124 directly produces all three D3-phosphorylated lipid products. This is a real substrate-specific activity, distinct from the major PIP3 signaling reaction; a class I identity does not make PI3P production false. The PAINT inference is supported by the measured target chemistry. Supporting Evidence: PMID:16123124 Whereas yeast and mammalian IPMKs form only a single product, PI3K also forms PI(3,4)P 2 and PI (3)P in addition to PI(3,4,5)P 3 when incubated with lipid extracts, consistent with previous reports ( 9 ).
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: p110γ can generate PI3P from phosphatidylinositol. Reason: The human p110γ comparator in PMID:16123124 directly produces all three D3-phosphorylated lipid products. This is a real substrate-specific activity, distinct from the major PIP3 signaling reaction; a class I identity does not make PI3P production false. The PAINT inference is supported by the measured target chemistry. Supporting Evidence: PMID:16123124 Whereas yeast and mammalian IPMKs form only a single product, PI3K also forms PI(3,4)P 2 and PI (3)P in addition to PI(3,4,5)P 3 when incubated with lipid extracts, consistent with previous reports ( 9 ).
GO:0016303 1-phosphatidylinositol-3-kinase activity	TAS PMID:7624799 Cloning and characterization of a G protein-activated human ...	KEEP AS NON CORE	Summary: p110γ can generate PI3P from phosphatidylinositol. Reason: The human p110γ comparator in PMID:16123124 directly produces all three D3-phosphorylated lipid products. This is a real substrate-specific activity, distinct from the major PIP3 signaling reaction; a class I identity does not make PI3P production false. The PAINT inference is supported by the measured target chemistry. Supporting Evidence: PMID:16123124 Whereas yeast and mammalian IPMKs form only a single product, PI3K also forms PI(3,4)P 2 and PI (3)P in addition to PI(3,4,5)P 3 when incubated with lipid extracts, consistent with previous reports ( 9 ).
GO:0016477 cell migration	IBA GO_REF:0000033	MODIFY	Summary: p110γ supports directional leukocyte and endothelial migration. Reason: Refine the PAINT inherited migration capacity to established cell-type-specific roles rather than rejecting it because its extant evidence spans taxa. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000005674 SUPPORTS TRANSFER cell migration: Refine the PAINT inherited migration capacity to established cell-type-specific roles rather than rejecting it because its extant evidence spans taxa. Proposed replacements: neutrophil chemotaxis T cell chemotaxis dendritic cell chemotaxis natural killer cell chemotaxis positive regulation of endothelial cell migration Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Modulates leukocyte chemotaxis to inflammatory sites and in response to chemoattractant agents.
GO:0030593 neutrophil chemotaxis	TAS PMID:17290298 PI3K delta and PI3K gamma: partners in crime in inflammation...	KEEP AS NON CORE	Summary: p110γ supports neutrophil chemotaxis. Reason: Neutrophil directional migration is a well-established p110γ signaling output; contributions of other class I isoforms do not negate this participation. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Together with PIK3CD is involved in neutrophil chemotaxis and extravasation.
GO:0033628 regulation of cell adhesion mediated by integrin	TAS PMID:18278175 Targeting phosphoinositide 3-kinase gamma to fight inflammat...	KEEP AS NON CORE	Summary: p110γ regulates integrin-dependent adhesion. Reason: Retain integrin regulation as a signaling/scaffold output. The evidence distinguishes this contribution from direct ligand binding by integrin and from lipid-kinase-dependent chemotaxis. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Regulates alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) adhesive function in platelets downstream of P2Y12 through a lipid kinase activity-independent mechanism.
GO:0035005 1-phosphatidylinositol-4-phosphate 3-kinase activity	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: p110γ can generate PI(3,4)P2 from PI4P. Reason: The human p110γ comparator in PMID:16123124 directly produces all three D3-phosphorylated lipid products. This is a real substrate-specific activity, distinct from the major PIP3 signaling reaction; a class I identity does not make PI3P production false. The PAINT inference is supported by the measured target chemistry. Supporting Evidence: PMID:16123124 Whereas yeast and mammalian IPMKs form only a single product, PI3K also forms PI(3,4)P 2 and PI (3)P in addition to PI(3,4,5)P 3 when incubated with lipid extracts, consistent with previous reports ( 9 ).
GO:0035005 1-phosphatidylinositol-4-phosphate 3-kinase activity	IDA PMID:16123124 Inositol polyphosphate multikinase is a nuclear PI3-kinase w...	KEEP AS NON CORE	Summary: p110γ can generate PI(3,4)P2 from PI4P. Reason: The human p110γ comparator in PMID:16123124 directly produces all three D3-phosphorylated lipid products. This is a real substrate-specific activity, distinct from the major PIP3 signaling reaction; a class I identity does not make PI3P production false. The PAINT inference is supported by the measured target chemistry. Supporting Evidence: PMID:16123124 Whereas yeast and mammalian IPMKs form only a single product, PI3K also forms PI(3,4)P 2 and PI (3)P in addition to PI(3,4,5)P 3 when incubated with lipid extracts, consistent with previous reports ( 9 ).
GO:0035005 1-phosphatidylinositol-4-phosphate 3-kinase activity	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: p110γ can generate PI(3,4)P2 from PI4P. Reason: The human p110γ comparator in PMID:16123124 directly produces all three D3-phosphorylated lipid products. This is a real substrate-specific activity, distinct from the major PIP3 signaling reaction; a class I identity does not make PI3P production false. The PAINT inference is supported by the measured target chemistry. Supporting Evidence: PMID:16123124 Whereas yeast and mammalian IPMKs form only a single product, PI3K also forms PI(3,4)P 2 and PI (3)P in addition to PI(3,4,5)P 3 when incubated with lipid extracts, consistent with previous reports ( 9 ).
GO:0035022 positive regulation of Rac protein signal transduction	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: p110γ contributes to S1P-induced endothelial migration and Rac1 activation. Reason: PMID:18558630 assays human umbilical-vein and mouse lung endothelial cells. Retain the measured receptor/migration/Rac context; distinguish it from the p110β-selective AKT requirement in the same study. Supporting Evidence: PMID:18558630 Both PI3Kbeta and gamma isoforms are required for full migration induced by S1P, with Rac1 being a major mediator downstream of both isoforms.
GO:0035022 positive regulation of Rac protein signal transduction	IMP PMID:18558630 Overlapping and distinct roles for PI3Kbeta and gamma isofor...	KEEP AS NON CORE	Summary: p110γ contributes to S1P-induced endothelial migration and Rac1 activation. Reason: PMID:18558630 assays human umbilical-vein and mouse lung endothelial cells. Retain the measured receptor/migration/Rac context; distinguish it from the p110β-selective AKT requirement in the same study. Supporting Evidence: PMID:18558630 Both PI3Kbeta and gamma isoforms are required for full migration induced by S1P, with Rac1 being a major mediator downstream of both isoforms.
GO:0035747 natural killer cell chemotaxis	TAS PMID:18278175 Targeting phosphoinositide 3-kinase gamma to fight inflammat...	KEEP AS NON CORE	Summary: p110γ contributes to natural-killer-cell migration. Reason: Retain the comparative immune-cell role summarized by PMID:18278175; do not assert exclusive p110γ dependence or a direct human assay from this review. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Together with PIK3CD is involved in natural killer (NK) cell development and migration towards the sites of inflammation.
GO:0036092 phosphatidylinositol-3-phosphate biosynthetic process	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: p110γ can generate PI3P from phosphatidylinositol. Reason: The human p110γ comparator in PMID:16123124 directly produces all three D3-phosphorylated lipid products. This is a real substrate-specific activity, distinct from the major PIP3 signaling reaction; a class I identity does not make PI3P production false. The PAINT inference is supported by the measured target chemistry. Supporting Evidence: PMID:16123124 Whereas yeast and mammalian IPMKs form only a single product, PI3K also forms PI(3,4)P 2 and PI (3)P in addition to PI(3,4,5)P 3 when incubated with lipid extracts, consistent with previous reports ( 9 ).
GO:0042098 T cell proliferation	TAS PMID:19075988 Isoform selective phosphoinositide 3-kinase gamma and delta ...	KEEP AS NON CORE	Summary: p110γ modulates T-cell proliferation. Reason: Retain this lymphocyte output, with genetic and inhibitor evidence synthesized in the cited review; the effect is context-dependent rather than a universal growth requirement. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Regulates T-lymphocyte proliferation, activation, and cytokine production.
GO:0042110 T cell activation	TAS PMID:17290298 PI3K delta and PI3K gamma: partners in crime in inflammation...	KEEP AS NON CORE	Summary: p110γ contributes to T-cell activation. Reason: T-cell activation is a supported physiological context. This annotation does not identify p110γ as the sole lipid kinase in TCR signaling. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Regulates T-lymphocyte proliferation, activation, and cytokine production.
GO:0042593 glucose homeostasis	IDA PMID:8396927 Insulin-stimulated GLUT4 translocation is relevant to the ph...	UNDECIDED	Summary: The p110γ-specific basis of the glucose-homeostasis annotation remains unresolved. Reason: PMID:8396927 examines wortmannin-sensitive insulin/GLUT4 signaling, but its accessible text does not isolate p110γ from other PI3K isoforms. The broad inhibitor phenotype is insufficient to assign this isoform a native glucose-homeostasis role; it is also not evidence that the role is absent.
GO:0042802 identical protein binding	IPI PMID:20562859 Network organization of the human autophagy system.	UNDECIDED	Summary: The exact p110γ self-association assay needs confirmation. Reason: The original PMID:20562859 interaction record asserts self-binding, and UniProt records two experiments. The examined PKCβ/p84 study focuses on heteromeric regulatory complexes; I have not resolved the self-association construct or supplemental interaction record. Heterodimer formation does not contradict additional self-association.
GO:0042802 identical protein binding	IPI PMID:23824069 PKCβ phosphorylates PI3Kγ to activate it and release it from...	UNDECIDED	Summary: The exact p110γ self-association assay needs confirmation. Reason: The original PMID:23824069 interaction record asserts self-binding, and UniProt records two experiments. The examined PKCβ/p84 study focuses on heteromeric regulatory complexes; I have not resolved the self-association construct or supplemental interaction record. Heterodimer formation does not contradict additional self-association.
GO:0043303 mast cell degranulation	TAS PMID:17290298 PI3K delta and PI3K gamma: partners in crime in inflammation...	KEEP AS NON CORE	Summary: p110γ contributes to mast-cell activation and degranulation. Reason: Retain the mast-cell context summarized in the original review. PMID:23824069 supplies direct receptor/Ca2+-dependent p110γ regulation in mast cells; do not require this route to be a GPCR-only input. Supporting Evidence: PMID:23824069 PKCβ phosphorylates Ser582 in the helical domain of the PI3Kγ catalytic subunit p110γ in response to clustering of the high-affinity IgE receptor (FcεRI) and/or store-operated Ca²⁺- influx in mast cells.
GO:0043406 positive regulation of MAP kinase activity	IDA PMID:12507995 Roles of G beta gamma in membrane recruitment and activation...	KEEP AS NON CORE	Summary: p110γ can promote MAP-kinase activation downstream of G-protein signaling. Reason: Retain the functional signaling output curated from PMID:12507995. It is a downstream kinase cascade, not evidence that p110γ directly phosphorylates MAP kinases. Supporting Evidence: PMID:7624799 The p110 gamma enzyme was activated in vitro by both the alpha and beta gamma subunits of heterotrimeric guanosine triphosphate (GTP)-binding proteins (G proteins) and did not interact with p85.
GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction	IBA GO_REF:0000033	ACCEPT	Summary: p110γ-generated PIP3 supports downstream AKT signaling. Reason: PIP3 synthesis is an actual catalytic step of this pathway. PMID:12507995 establishes this signaling capacity; the S1P endothelial study PMID:18558630 finds that its migration output is AKT-dependent for p110β rather than p110γ, which limits that assay but does not negate p110γ–AKT signaling in other contexts. The Epac/angiogenesis context is independently supported by PMID:21393242. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology.
GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction	IDA PMID:12507995 Roles of G beta gamma in membrane recruitment and activation...	ACCEPT	Summary: p110γ-generated PIP3 supports downstream AKT signaling. Reason: PIP3 synthesis is an actual catalytic step of this pathway. PMID:12507995 establishes this signaling capacity; the S1P endothelial study PMID:18558630 finds that its migration output is AKT-dependent for p110β rather than p110γ, which limits that assay but does not negate p110γ–AKT signaling in other contexts. The Epac/angiogenesis context is independently supported by PMID:21393242. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology.
GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction	IEA GO_REF:0000120	ACCEPT	Summary: p110γ-generated PIP3 supports downstream AKT signaling. Reason: PIP3 synthesis is an actual catalytic step of this pathway. PMID:12507995 establishes this signaling capacity; the S1P endothelial study PMID:18558630 finds that its migration output is AKT-dependent for p110β rather than p110γ, which limits that assay but does not negate p110γ–AKT signaling in other contexts. The Epac/angiogenesis context is independently supported by PMID:21393242. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology.
GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction	IMP PMID:18558630 Overlapping and distinct roles for PI3Kbeta and gamma isofor...	ACCEPT	Summary: p110γ-generated PIP3 supports downstream AKT signaling. Reason: PIP3 synthesis is an actual catalytic step of this pathway. PMID:12507995 establishes this signaling capacity; the S1P endothelial study PMID:18558630 finds that its migration output is AKT-dependent for p110β rather than p110γ, which limits that assay but does not negate p110γ–AKT signaling in other contexts. The Epac/angiogenesis context is independently supported by PMID:21393242. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology.
GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction	IMP PMID:21840392 Epac1 and PDZ-GEF cooperate in Rap1 mediated endothelial jun...	ACCEPT	Summary: p110γ-generated PIP3 supports downstream AKT signaling. Reason: PIP3 synthesis is an actual catalytic step of this pathway. PMID:12507995 establishes this signaling capacity; the S1P endothelial study PMID:18558630 finds that its migration output is AKT-dependent for p110β rather than p110γ, which limits that assay but does not negate p110γ–AKT signaling in other contexts. The Epac/angiogenesis context is independently supported by PMID:21393242. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology.
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: p110γ-generated PIP3 supports downstream AKT signaling. Reason: PIP3 synthesis is an actual catalytic step of this pathway. PMID:12507995 establishes this signaling capacity; the S1P endothelial study PMID:18558630 finds that its migration output is AKT-dependent for p110β rather than p110γ, which limits that assay but does not negate p110γ–AKT signaling in other contexts. The Epac/angiogenesis context is independently supported by PMID:21393242. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology.
GO:0045087 innate immune response	TAS PMID:17290298 PI3K delta and PI3K gamma: partners in crime in inflammation...	KEEP AS NON CORE	Summary: p110γ participates in immune and inflammatory signaling. Reason: Retain the immune-system contribution supported by curated synthesis and human loss-of-function PMID:31554793. These terms do not assign a universal pro-inflammatory sign: cellular context determines whether p110γ promotes effector activation or restrains cytokine excess. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Involved in immune, inflammatory and allergic responses.
GO:0045765 regulation of angiogenesis	IMP PMID:21840392 Epac1 and PDZ-GEF cooperate in Rap1 mediated endothelial jun...	KEEP AS NON CORE	Summary: p110γ participates in endothelial angiogenic signaling complexes. Reason: The accessible PMID:21840392 abstract foregrounds Epac1/PDZGEF and does not resolve the p110γ assay. Independent full PMID:21393242 establishes a PDE3B–EPAC–p84/p110γ complex in human arterial endothelial cells and angiogenic behavior, so the biological claim is retained without treating the original citation as fully verified. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Through simultaneous binding of PDE3B to RAPGEF3 and PIK3R6 is assembled in a signaling complex in which the PI3K gamma complex is activated by RAPGEF3 and which is involved in angiogenesis.
GO:0046854 phosphatidylinositol phosphate biosynthetic process	IDA PMID:12502714 Identification and characterization of the autophosphorylati...	ACCEPT	Summary: p110γ synthesizes D3-phosphorylated phosphoinositides. Reason: The biosynthetic process describes actual phosphate transfer to lipid substrates. The three experimentally measured products are retained without reducing this broad product class to PI3P alone. Supporting Evidence: PMID:16123124 Whereas yeast and mammalian IPMKs form only a single product, PI3K also forms PI(3,4)P 2 and PI (3)P in addition to PI(3,4,5)P 3 when incubated with lipid extracts, consistent with previous reports ( 9 ).
GO:0046854 phosphatidylinositol phosphate biosynthetic process	IEA GO_REF:0000002	ACCEPT	Summary: p110γ synthesizes D3-phosphorylated phosphoinositides. Reason: The biosynthetic process describes actual phosphate transfer to lipid substrates. The three experimentally measured products are retained without reducing this broad product class to PI3P alone. Supporting Evidence: PMID:16123124 Whereas yeast and mammalian IPMKs form only a single product, PI3K also forms PI(3,4)P 2 and PI (3)P in addition to PI(3,4,5)P 3 when incubated with lipid extracts, consistent with previous reports ( 9 ).
GO:0046875 ephrin receptor binding	IPI PMID:11416136 The EphA8 receptor regulates integrin activity through p110g...	KEEP AS NON CORE	Summary: p110γ binds the EphA8 receptor in an adhesion-regulating complex. Reason: PMID:11416136 establishes EphA8 association and PI3K-dependent integrin regulation in the tested receptor-expression system. Retain the interaction without extrapolating it to every ephrin receptor. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Interacts with EPHA8; regulates integrin-mediated cell adhesion to substrate.
GO:0046934 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity	EXP PMID:31554793 Human PI3Kγ deficiency and its microbiota-dependent mouse mo...	ACCEPT	Summary: p110γ phosphorylates PI(4,5)P2 to PIP3. Reason: This is the defining membrane second-messenger reaction. Human p110γ is directly assayed in PMID:15135396 and PMID:16123124; patient loss-of-function in PMID:31554793 independently links impaired catalysis to immune disease. Supporting Evidence: PMID:16123124 Whereas yeast and mammalian IPMKs form only a single product, PI3K also forms PI(3,4)P 2 and PI (3)P in addition to PI(3,4,5)P 3 when incubated with lipid extracts, consistent with previous reports ( 9 ).
GO:0046934 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity	IBA GO_REF:0000033	ACCEPT	Summary: p110γ phosphorylates PI(4,5)P2 to PIP3. Reason: This is the defining membrane second-messenger reaction. Human p110γ is directly assayed in PMID:15135396 and PMID:16123124; patient loss-of-function in PMID:31554793 independently links impaired catalysis to immune disease. Supporting Evidence: PMID:16123124 Whereas yeast and mammalian IPMKs form only a single product, PI3K also forms PI(3,4)P 2 and PI (3)P in addition to PI(3,4,5)P 3 when incubated with lipid extracts, consistent with previous reports ( 9 ).
GO:0046934 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity	IDA PMID:12502714 Identification and characterization of the autophosphorylati...	ACCEPT	Summary: p110γ phosphorylates PI(4,5)P2 to PIP3. Reason: This is the defining membrane second-messenger reaction. Human p110γ is directly assayed in PMID:15135396 and PMID:16123124; patient loss-of-function in PMID:31554793 independently links impaired catalysis to immune disease. Supporting Evidence: PMID:16123124 Whereas yeast and mammalian IPMKs form only a single product, PI3K also forms PI(3,4)P 2 and PI (3)P in addition to PI(3,4,5)P 3 when incubated with lipid extracts, consistent with previous reports ( 9 ).
GO:0046934 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity	IDA PMID:15135396 Cloning, expression, purification, and characterization of t...	ACCEPT	Summary: p110γ phosphorylates PI(4,5)P2 to PIP3. Reason: This is the defining membrane second-messenger reaction. Human p110γ is directly assayed in PMID:15135396 and PMID:16123124; patient loss-of-function in PMID:31554793 independently links impaired catalysis to immune disease. Supporting Evidence: PMID:16123124 Whereas yeast and mammalian IPMKs form only a single product, PI3K also forms PI(3,4)P 2 and PI (3)P in addition to PI(3,4,5)P 3 when incubated with lipid extracts, consistent with previous reports ( 9 ).
GO:0046934 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity	IDA PMID:16123124 Inositol polyphosphate multikinase is a nuclear PI3-kinase w...	ACCEPT	Summary: p110γ phosphorylates PI(4,5)P2 to PIP3. Reason: This is the defining membrane second-messenger reaction. Human p110γ is directly assayed in PMID:15135396 and PMID:16123124; patient loss-of-function in PMID:31554793 independently links impaired catalysis to immune disease. Supporting Evidence: PMID:16123124 Whereas yeast and mammalian IPMKs form only a single product, PI3K also forms PI(3,4)P 2 and PI (3)P in addition to PI(3,4,5)P 3 when incubated with lipid extracts, consistent with previous reports ( 9 ).
GO:0046934 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity	IEA GO_REF:0000120	ACCEPT	Summary: p110γ phosphorylates PI(4,5)P2 to PIP3. Reason: This is the defining membrane second-messenger reaction. Human p110γ is directly assayed in PMID:15135396 and PMID:16123124; patient loss-of-function in PMID:31554793 independently links impaired catalysis to immune disease. Supporting Evidence: PMID:16123124 Whereas yeast and mammalian IPMKs form only a single product, PI3K also forms PI(3,4)P 2 and PI (3)P in addition to PI(3,4,5)P 3 when incubated with lipid extracts, consistent with previous reports ( 9 ).
GO:0048015 phosphatidylinositol-mediated signaling	IBA GO_REF:0000033	ACCEPT	Summary: p110γ-generated PIP3 supports downstream AKT signaling. Reason: PIP3 synthesis is an actual catalytic step of this pathway. PMID:12507995 establishes this signaling capacity; the S1P endothelial study PMID:18558630 finds that its migration output is AKT-dependent for p110β rather than p110γ, which limits that assay but does not negate p110γ–AKT signaling in other contexts. The Epac/angiogenesis context is independently supported by PMID:21393242. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology.
GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IDA PMID:12507995 Roles of G beta gamma in membrane recruitment and activation...	ACCEPT	Summary: p110γ-generated PIP3 supports downstream AKT signaling. Reason: PIP3 synthesis is an actual catalytic step of this pathway. PMID:12507995 establishes this signaling capacity; the S1P endothelial study PMID:18558630 finds that its migration output is AKT-dependent for p110β rather than p110γ, which limits that assay but does not negate p110γ–AKT signaling in other contexts. The Epac/angiogenesis context is independently supported by PMID:21393242. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology.
GO:0055118 negative regulation of cardiac muscle contraction	TAS PMID:19147653 Cardiac regulation by phosphoinositide 3-kinases and PTEN.	KEEP AS NON CORE	Summary: p110γ can restrain cardiac contractility. Reason: Retain the cardiac signaling/scaffold function reviewed in PMID:19147653 and established comparatively in PMID:15294162; do not attribute every effect to the lipid kinase reaction. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Negative regulator of cardiac contractility. Modulates cardiac contractility by anchoring protein kinase A (PKA) and PDE3B activation, reducing cAMP levels.
GO:0070527 platelet aggregation	TAS PMID:21035500 Regulation and roles of PI3Kβ, a major actor in platelet sig...	KEEP AS NON CORE	Summary: p110γ participates in platelet aggregation. Reason: PMID:21035500 emphasizes p110β but is a review of isoform cooperation. Independent curated evidence retains p110γ participation, including P2Y12/integrin regulation, without claiming it is the dominant platelet PI3K. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Together with PIK3CB promotes platelet aggregation and thrombosis.
GO:0072672 neutrophil extravasation	TAS PMID:18278175 Targeting phosphoinositide 3-kinase gamma to fight inflammat...	KEEP AS NON CORE	Summary: p110γ participates in neutrophil extravasation. Reason: The kinase contributes signaling for vascular exit and migration; this is retained as a contextual immune function. Supporting Evidence: file:human/PIK3CG/PIK3CG-uniprot.txt Together with PIK3CD is involved in neutrophil chemotaxis and extravasation.
GO:0106310 protein serine kinase activity	EXP PMID:16094730 Protein kinase activity of phosphoinositide 3-kinase regulat...	ACCEPT	Summary: p110γ has experimentally demonstrated protein serine kinase activity in addition to lipid kinase activities. Reason: Ser1101 autophosphorylation (PMID:12502714) and tropomyosin phosphorylation in the receptor-endocytosis study (PMID:16094730) establish genuine protein kinase chemistry. Preserve this activity when refining a broad kinase term; lipid kinase activity alone is not an adequate replacement. Supporting Evidence: PMID:12502714 Autophosphorylation sites of both PI3K isoforms were mapped to C-terminal serine residues of the catalytic p110 subunit (i.e. serine 1070 of p110 beta and serine 1101 of p110 gamma).
GO:0106310 protein serine kinase activity	IDA PMID:12502714 Identification and characterization of the autophosphorylati...	ACCEPT	Summary: p110γ has experimentally demonstrated protein serine kinase activity in addition to lipid kinase activities. Reason: Ser1101 autophosphorylation (PMID:12502714) and tropomyosin phosphorylation in the receptor-endocytosis study (PMID:16094730) establish genuine protein kinase chemistry. Preserve this activity when refining a broad kinase term; lipid kinase activity alone is not an adequate replacement. Supporting Evidence: PMID:12502714 Autophosphorylation sites of both PI3K isoforms were mapped to C-terminal serine residues of the catalytic p110 subunit (i.e. serine 1070 of p110 beta and serine 1101 of p110 gamma).
GO:0106310 protein serine kinase activity	IEA GO_REF:0000116	ACCEPT	Summary: p110γ has experimentally demonstrated protein serine kinase activity in addition to lipid kinase activities. Reason: Ser1101 autophosphorylation (PMID:12502714) and tropomyosin phosphorylation in the receptor-endocytosis study (PMID:16094730) establish genuine protein kinase chemistry. Preserve this activity when refining a broad kinase term; lipid kinase activity alone is not an adequate replacement. Supporting Evidence: PMID:12502714 Autophosphorylation sites of both PI3K isoforms were mapped to C-terminal serine residues of the catalytic p110 subunit (i.e. serine 1070 of p110 beta and serine 1101 of p110 gamma).

Gene Description

Existing Annotations Review

Core Functions

ATP-dependent PIP3 synthesis by class IB p110γ complexes couples G-protein and context-dependent Ras/PKC inputs to membrane signaling. Regulatory-subunit identity determines recruitment and sensitivity; the route is not universal across immune receptors.

Protein serine phosphorylation includes C-terminal p110γ autophosphorylation and tropomyosin phosphorylation implicated in beta-adrenergic receptor internalization; this chemistry is distinct from its lipid kinase reaction.

References

Suggested Questions for Experts

📚 Additional Documentation

Notes

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