PLCG2 encodes phospholipase C-gamma 2, a multidomain phosphoinositide-specific phospholipase C enriched in hematopoietic cells and microglia. After recruitment to activated receptor signaling complexes through SH2/phosphotyrosine and adaptor interactions, PLCG2 hydrolyzes phosphatidylinositol 4,5-bisphosphate at plasma-membrane and membrane-raft signaling sites to generate inositol 1,4,5-trisphosphate and diacylglycerol, coupling B-cell, Fc receptor, C-type lectin, platelet, TREM2, Toll-like receptor, and related immune pathways to calcium mobilization, lipid signaling, transcriptional responses, phagocytosis, inflammatory signaling, and other hematopoietic or myeloid cell outcomes.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004435 phosphatidylinositol-4,5-bisphosphate phospholipase C activity | IBA GO_REF:0000033 | ACCEPT | Summary: PLCG2 is a phosphoinositide-specific phospholipase C that hydrolyzes PIP2 to IP3 and DAG after receptor-induced activation. Reason: Retain as core because PLCG2/PLC-gamma2 directly catalyzes phosphatidylinositol-4,5-bisphosphate hydrolysis, with experimental support for recombinant and cellular activity and activation by Tyr753/Tyr759 phosphorylation (PMID:11043765, PMID:11606584, PMID:12181444, PMID:23000145). |
| GO:0046488 phosphatidylinositol metabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: PLCG2 directly metabolizes a phosphorylated phosphatidylinositol substrate. Reason: PIP2 hydrolysis is actual participation in phosphatidylinositol metabolism. The existing term correctly captures substrate-class metabolism; it should not be replaced solely by a signaling term that omits the chemical transformation. Supporting Evidence: PMID:11043765 The activated PLC-gamma2 converts phosphatidylinositol 4,5-bisphosphate into the second messenger inositol 1,4,5-trisphosphate (IP3), which in turn binds to IP3 receptors located on the endoplasmic reticulum (ER). |
| GO:0010634 positive regulation of epithelial cell migration | IBA GO_REF:0000033 | UNDECIDED | Summary: The inherited epithelial-migration function needs target-specific resolution. Reason: PAINT node PTN000741536 represents a considered ancestral-function placement, with PLCΞ³1 evidence among its descendants. Hematopoietic enrichment of PLCΞ³2 does not demonstrate loss of epithelial migration signaling. The recovered target literature does not resolve the epithelial assay or the appropriate branch boundary, so the former expression-based over-annotation argument is withdrawn. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN000741536 UNRESOLVED positive regulation of epithelial cell migration: PAINT node PTN000741536 represents a considered ancestral-function placement, with PLCΞ³1 evidence among its descendants. Hematopoietic enrichment of PLCΞ³2 does not demonstrate loss of epithelial migration signaling. The recovered target literature does not resolve the epithelial assay or the appropriate branch boundary, so the former expression-based over-annotation argument is withdrawn. |
| GO:0048015 phosphatidylinositol-mediated signaling | IBA GO_REF:0000033 | ACCEPT | Summary: This captures PLCG2-mediated phosphoinositide signaling downstream of immune and growth-factor receptor activation. Reason: Retain because the core PLCG2 reaction converts PIP2 into IP3 and DAG, linking receptor tyrosine/SYK/BTK signaling to calcium and DAG-dependent intracellular signaling (PMID:11043765, PMID:11331309, PMID:11606584). |
| GO:0032587 ruffle membrane | IBA GO_REF:0000033 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0051209 release of sequestered calcium ion into cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: PLCG2 produces IP3 downstream of receptor activation, driving calcium release and calcium-mediated signaling. Reason: Retain as core signaling output because BCR and platelet studies show PLCG2-dependent calcium responses and phosphorylation-dependent activation of PLCG2 upstream of IP3-mediated calcium release (PMID:11043765, PMID:11606584, PMID:12181444). |
| GO:0004435 phosphatidylinositol-4,5-bisphosphate phospholipase C activity | IEA GO_REF:0000120 | ACCEPT | Summary: PLCG2 is a phosphoinositide-specific phospholipase C that hydrolyzes PIP2 to IP3 and DAG after receptor-induced activation. Reason: Retain as core because PLCG2/PLC-gamma2 directly catalyzes phosphatidylinositol-4,5-bisphosphate hydrolysis, with experimental support for recombinant and cellular activity and activation by Tyr753/Tyr759 phosphorylation (PMID:11043765, PMID:11606584, PMID:12181444, PMID:23000145). |
| GO:0006629 lipid metabolic process | IEA GO_REF:0000002 | MODIFY | Summary: PLCG2 catalyzes glycerophospholipid breakdown. Reason: PIP2 is a glycerophospholipid, and its hydrolysis to DAG and IP3 supports the more specific catabolic process. Refine the broad lipid/phospholipid category without substituting a signaling outcome for the catabolic chemistry. Proposed replacements: glycerophospholipid catabolic process Supporting Evidence: PMID:11043765 The activated PLC-gamma2 converts phosphatidylinositol 4,5-bisphosphate into the second messenger inositol 1,4,5-trisphosphate (IP3), which in turn binds to IP3 receptors located on the endoplasmic reticulum (ER). |
| GO:0007165 signal transduction | IEA GO_REF:0000002 | MODIFY | Summary: PLCG2 converts receptor input into phosphoinositide and calcium signals. Reason: Refine general signal transduction to phosphatidylinositol-mediated signaling and calcium-mediated signaling. GO_REF:0000002 is interpreted in its own context: immune/BCR studies include human PLCΞ³2 expressed in chicken DT40 cells, whereas platelet and microglial studies test distinct receptor systems. Calcium release is mediated by IP3 receptors downstream of PLCG2 catalysis, not by PLCG2 acting as an ion channel. Proposed replacements: phosphatidylinositol-mediated signaling calcium-mediated signaling Supporting Evidence: PMID:11043765 The activated PLC-gamma2 converts phosphatidylinositol 4,5-bisphosphate into the second messenger inositol 1,4,5-trisphosphate (IP3), which in turn binds to IP3 receptors located on the endoplasmic reticulum (ER). |
| GO:0008081 phosphoric diester hydrolase activity | IEA GO_REF:0000002 | MODIFY | Summary: PLCG2 hydrolyzes the phosphodiester bond of PI(4,5)P2. Reason: Refine phosphoric diester hydrolase activity to the measured PIP2 phospholipase C activity. The reaction releases IP3 and DAG; it is more specific than generic phosphodiester hydrolysis or C-type glycerophospholipase activity. Proposed replacements: phosphatidylinositol-4,5-bisphosphate phospholipase C activity Supporting Evidence: PMID:11043765 The activated PLC-gamma2 converts phosphatidylinositol 4,5-bisphosphate into the second messenger inositol 1,4,5-trisphosphate (IP3), which in turn binds to IP3 receptors located on the endoplasmic reticulum (ER). PMID:12181444 In vitro phosphorylation experiments with recombinant PLCgamma2 and recombinant Lck, Fyn, and Lyn tyrosine kinases showed that phosphorylation of PLCgamma2 led to activation of the recombinant enzyme. |
| GO:0009395 phospholipid catabolic process | IEA GO_REF:0000002 | MODIFY | Summary: PLCG2 catalyzes glycerophospholipid breakdown. Reason: PIP2 is a glycerophospholipid, and its hydrolysis to DAG and IP3 supports the more specific catabolic process. Refine the broad lipid/phospholipid category without substituting a signaling outcome for the catabolic chemistry. Proposed replacements: glycerophospholipid catabolic process Supporting Evidence: PMID:11043765 The activated PLC-gamma2 converts phosphatidylinositol 4,5-bisphosphate into the second messenger inositol 1,4,5-trisphosphate (IP3), which in turn binds to IP3 receptors located on the endoplasmic reticulum (ER). |
| GO:0010628 positive regulation of gene expression | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0019722 calcium-mediated signaling | IEA GO_REF:0000117 | ACCEPT | Summary: PLCG2 produces IP3 downstream of receptor activation, driving calcium release and calcium-mediated signaling. Reason: Retain as core signaling output because BCR and platelet studies show PLCG2-dependent calcium responses and phosphorylation-dependent activation of PLCG2 upstream of IP3-mediated calcium release (PMID:11043765, PMID:11606584, PMID:12181444). |
| GO:0032587 ruffle membrane | IEA GO_REF:0000117 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0035556 intracellular signal transduction | IEA GO_REF:0000120 | MODIFY | Summary: PLCG2 converts receptor input into phosphoinositide and calcium signals. Reason: Refine general signal transduction to phosphatidylinositol-mediated signaling and calcium-mediated signaling. GO_REF:0000120 is interpreted in its own context: immune/BCR studies include human PLCΞ³2 expressed in chicken DT40 cells, whereas platelet and microglial studies test distinct receptor systems. Calcium release is mediated by IP3 receptors downstream of PLCG2 catalysis, not by PLCG2 acting as an ion channel. Proposed replacements: phosphatidylinositol-mediated signaling calcium-mediated signaling Supporting Evidence: PMID:11043765 The activated PLC-gamma2 converts phosphatidylinositol 4,5-bisphosphate into the second messenger inositol 1,4,5-trisphosphate (IP3), which in turn binds to IP3 receptors located on the endoplasmic reticulum (ER). |
| GO:0038095 Fc-epsilon receptor signaling pathway | IEA GO_REF:0000117 | ACCEPT | Summary: PLCG2 is a receptor-proximal transducer in immune-receptor pathways, especially BCR, Fc receptor, C-type lectin, and related hematopoietic signaling. Reason: Retain as core or near-core immune signaling biology because PLCG2 is recruited and activated by receptor-coupled tyrosine kinase/adaptor modules such as Syk, Btk, BLNK, BANK1, FCER/FCGR, and C-type lectin pathways (PMID:11043765, PMID:11606584, PMID:23555801; Reactome PLCG2 events). |
| GO:0045121 membrane raft | IEA GO_REF:0000120 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0050851 antigen receptor-mediated signaling pathway | IEA GO_REF:0000117 | ACCEPT | Summary: PLCG2 is a receptor-proximal transducer in immune-receptor pathways, especially BCR, Fc receptor, C-type lectin, and related hematopoietic signaling. Reason: Retain as core or near-core immune signaling biology because PLCG2 is recruited and activated by receptor-coupled tyrosine kinase/adaptor modules such as Syk, Btk, BLNK, BANK1, FCER/FCGR, and C-type lectin pathways (PMID:11043765, PMID:11606584, PMID:23555801; Reactome PLCG2 events). |
| GO:1902533 positive regulation of intracellular signal transduction | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0005515 protein binding | IPI PMID:15644415 A systematic scan of interactions with tyrosine motifs in th... | MODIFY | Summary: The interaction is more informatively represented by phosphotyrosine recognition. Reason: The cited PMID:15644415 uses phosphorylated receptor/adaptor motifs or SH2-domain binding. Independent direct human PLCΞ³2 SH2-domain SPR in PMID:24642916 establishes phosphotyrosine recognition. Domain/peptide assays show biochemical recognition potential and do not by themselves establish an obligatory full-length native complex with every screened partner. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:24642916 Recombinant PLCΞ³2 SH2 domains also bound immobilized EAT-2 Y127 and LAT Y132 peptides with comparable affinity |
| GO:0005515 protein binding | IPI PMID:16273093 A quantitative protein interaction network for the ErbB rece... | MODIFY | Summary: The interaction is more informatively represented by phosphotyrosine recognition. Reason: The cited PMID:16273093 uses phosphorylated receptor/adaptor motifs or SH2-domain binding. Independent direct human PLCΞ³2 SH2-domain SPR in PMID:24642916 establishes phosphotyrosine recognition. Domain/peptide assays show biochemical recognition potential and do not by themselves establish an obligatory full-length native complex with every screened partner. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:24642916 Recombinant PLCΞ³2 SH2 domains also bound immobilized EAT-2 Y127 and LAT Y132 peptides with comparable affinity |
| GO:0005515 protein binding | IPI PMID:24642916 Fine specificity and molecular competition in SLAM family re... | MODIFY | Summary: The interaction is more informatively represented by phosphotyrosine recognition. Reason: The cited PMID:24642916 uses phosphorylated receptor/adaptor motifs or SH2-domain binding. Independent direct human PLCΞ³2 SH2-domain SPR in PMID:24642916 establishes phosphotyrosine recognition. Domain/peptide assays show biochemical recognition potential and do not by themselves establish an obligatory full-length native complex with every screened partner. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:24642916 Recombinant PLCΞ³2 SH2 domains also bound immobilized EAT-2 Y127 and LAT Y132 peptides with comparable affinity |
| GO:0005515 protein binding | IPI PMID:24658140 The mammalian-membrane two-hybrid assay (MaMTH) for probing ... | REMOVE | Summary: The reported association is preserved without a generic binding annotation. Reason: Bare protein binding is uninformative under current policy. The interaction with UniProtKB:P00533 in PMID:24658140 is not being rejected; a specific recruitment mechanism is not inferred solely from the association. |
| GO:0005515 protein binding | IPI PMID:24728074 Enhanced prediction of Src homology 2 (SH2) domain binding p... | MODIFY | Summary: The interaction is more informatively represented by phosphotyrosine recognition. Reason: The cited PMID:24728074 uses phosphorylated receptor/adaptor motifs or SH2-domain binding. Independent direct human PLCΞ³2 SH2-domain SPR in PMID:24642916 establishes phosphotyrosine recognition. Domain/peptide assays show biochemical recognition potential and do not by themselves establish an obligatory full-length native complex with every screened partner. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:24642916 Recombinant PLCΞ³2 SH2 domains also bound immobilized EAT-2 Y127 and LAT Y132 peptides with comparable affinity |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | REMOVE | Summary: The reported association is preserved without a generic binding annotation. Reason: Bare protein binding is uninformative under current policy. The interaction with UniProtKB:P00533 in PMID:25241761 is not being rejected; a specific recruitment mechanism is not inferred solely from the association. |
| GO:0005515 protein binding | IPI PMID:25814554 Phospho-tyrosine dependent protein-protein interaction netwo... | REMOVE | Summary: The reported association is preserved without a generic binding annotation. Reason: Bare protein binding is uninformative under current policy. The interaction with UniProtKB:O43242 in PMID:25814554 is not being rejected; a specific recruitment mechanism is not inferred solely from the association. |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | REMOVE | Summary: The reported association is preserved without a generic binding annotation. Reason: Bare protein binding is uninformative under current policy. The interaction with UniProtKB:P00533 in PMID:31980649 is not being rejected; a specific recruitment mechanism is not inferred solely from the association. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: The reported association is preserved without a generic binding annotation. Reason: Bare protein binding is uninformative under current policy. The interaction with UniProtKB:P78381 in PMID:33961781 is not being rejected; a specific recruitment mechanism is not inferred solely from the association. |
| GO:0005515 protein binding | IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei... | REMOVE | Summary: The reported association is preserved without a generic binding annotation. Reason: Bare protein binding is uninformative under current policy. The interaction with UniProtKB:P00533 in PMID:35512704 is not being rejected; a specific recruitment mechanism is not inferred solely from the association. |
| GO:0001775 cell activation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0001878 response to yeast | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0002092 positive regulation of receptor internalization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0002223 stimulatory C-type lectin receptor signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: PLCG2 is a receptor-proximal transducer in immune-receptor pathways, especially BCR, Fc receptor, C-type lectin, and related hematopoietic signaling. Reason: Retain as core or near-core immune signaling biology because PLCG2 is recruited and activated by receptor-coupled tyrosine kinase/adaptor modules such as Syk, Btk, BLNK, BANK1, FCER/FCGR, and C-type lectin pathways (PMID:11043765, PMID:11606584, PMID:23555801; Reactome PLCG2 events). |
| GO:0002224 toll-like receptor signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0002281 macrophage activation involved in immune response | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0002732 positive regulation of dendritic cell cytokine production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0005829 cytosol | IEA GO_REF:0000120 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0030183 B cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0032481 positive regulation of type I interferon production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0032733 positive regulation of interleukin-10 production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0032735 positive regulation of interleukin-12 production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0032743 positive regulation of interleukin-2 production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0032747 positive regulation of interleukin-23 production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0032755 positive regulation of interleukin-6 production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0032760 positive regulation of tumor necrosis factor production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0043122 regulation of canonical NF-kappaB signal transduction | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0043410 positive regulation of MAPK cascade | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0050853 B cell receptor signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: PLCG2 is a receptor-proximal transducer in immune-receptor pathways, especially BCR, Fc receptor, C-type lectin, and related hematopoietic signaling. Reason: Retain as core or near-core immune signaling biology because PLCG2 is recruited and activated by receptor-coupled tyrosine kinase/adaptor modules such as Syk, Btk, BLNK, BANK1, FCER/FCGR, and C-type lectin pathways (PMID:11043765, PMID:11606584, PMID:23555801; Reactome PLCG2 events). |
| GO:0051209 release of sequestered calcium ion into cytosol | IEA GO_REF:0000107 | ACCEPT | Summary: PLCG2 produces IP3 downstream of receptor activation, driving calcium release and calcium-mediated signaling. Reason: Retain as core signaling output because BCR and platelet studies show PLCG2-dependent calcium responses and phosphorylation-dependent activation of PLCG2 upstream of IP3-mediated calcium release (PMID:11043765, PMID:11606584, PMID:12181444). |
| GO:0061760 antifungal innate immune response | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0140031 phosphorylation-dependent protein binding | IEA GO_REF:0000107 | ACCEPT | Summary: PLCG2 contains SH2 domains and is recruited through phosphorylation-dependent binding to receptor/adaptor motifs. Reason: Retain because PLCG2 recruitment to receptor signaling complexes depends on SH2/phosphotyrosine interactions, including BLNK/BANK1/EAT-2 and receptor-coupled contexts (PMID:11043765, PMID:11606584, PMID:23555801, PMID:24642916). |
| GO:1990858 cellular response to lectin | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0002223 stimulatory C-type lectin receptor signaling pathway | TAS Reactome:R-HSA-5621481 | ACCEPT | Summary: PLCG2 is a receptor-proximal transducer in immune-receptor pathways, especially BCR, Fc receptor, C-type lectin, and related hematopoietic signaling. Reason: Retain as core or near-core immune signaling biology because PLCG2 is recruited and activated by receptor-coupled tyrosine kinase/adaptor modules such as Syk, Btk, BLNK, BANK1, FCER/FCGR, and C-type lectin pathways (PMID:11043765, PMID:11606584, PMID:23555801; Reactome PLCG2 events). |
| GO:0030168 platelet activation | TAS Reactome:R-HSA-76002 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0038095 Fc-epsilon receptor signaling pathway | TAS Reactome:R-HSA-2454202 | ACCEPT | Summary: PLCG2 is a receptor-proximal transducer in immune-receptor pathways, especially BCR, Fc receptor, C-type lectin, and related hematopoietic signaling. Reason: Retain as core or near-core immune signaling biology because PLCG2 is recruited and activated by receptor-coupled tyrosine kinase/adaptor modules such as Syk, Btk, BLNK, BANK1, FCER/FCGR, and C-type lectin pathways (PMID:11043765, PMID:11606584, PMID:23555801; Reactome PLCG2 events). |
| GO:0004435 phosphatidylinositol-4,5-bisphosphate phospholipase C activity | TAS Reactome:R-HSA-2730847 | ACCEPT | Summary: PLCG2 is a phosphoinositide-specific phospholipase C that hydrolyzes PIP2 to IP3 and DAG after receptor-induced activation. Reason: Retain as core because PLCG2/PLC-gamma2 directly catalyzes phosphatidylinositol-4,5-bisphosphate hydrolysis, with experimental support for recombinant and cellular activity and activation by Tyr753/Tyr759 phosphorylation (PMID:11043765, PMID:11606584, PMID:12181444, PMID:23000145). |
| GO:0004435 phosphatidylinositol-4,5-bisphosphate phospholipase C activity | TAS Reactome:R-HSA-5607735 | ACCEPT | Summary: PLCG2 is a phosphoinositide-specific phospholipase C that hydrolyzes PIP2 to IP3 and DAG after receptor-induced activation. Reason: Retain as core because PLCG2/PLC-gamma2 directly catalyzes phosphatidylinositol-4,5-bisphosphate hydrolysis, with experimental support for recombinant and cellular activity and activation by Tyr753/Tyr759 phosphorylation (PMID:11043765, PMID:11606584, PMID:12181444, PMID:23000145). |
| GO:0004629 C-type glycerophospholipase activity | TAS Reactome:R-HSA-1112666 | MODIFY | Summary: PLCG2 hydrolyzes the phosphodiester bond of PI(4,5)P2. Reason: Refine C-type glycerophospholipase activity to the measured PIP2 phospholipase C activity. The reaction releases IP3 and DAG; it is more specific than generic phosphodiester hydrolysis or C-type glycerophospholipase activity. Proposed replacements: phosphatidylinositol-4,5-bisphosphate phospholipase C activity Supporting Evidence: PMID:11043765 The activated PLC-gamma2 converts phosphatidylinositol 4,5-bisphosphate into the second messenger inositol 1,4,5-trisphosphate (IP3), which in turn binds to IP3 receptors located on the endoplasmic reticulum (ER). PMID:12181444 In vitro phosphorylation experiments with recombinant PLCgamma2 and recombinant Lck, Fyn, and Lyn tyrosine kinases showed that phosphorylation of PLCgamma2 led to activation of the recombinant enzyme. |
| GO:0004629 C-type glycerophospholipase activity | TAS Reactome:R-HSA-114689 | MODIFY | Summary: PLCG2 hydrolyzes the phosphodiester bond of PI(4,5)P2. Reason: Refine C-type glycerophospholipase activity to the measured PIP2 phospholipase C activity. The reaction releases IP3 and DAG; it is more specific than generic phosphodiester hydrolysis or C-type glycerophospholipase activity. Proposed replacements: phosphatidylinositol-4,5-bisphosphate phospholipase C activity Supporting Evidence: PMID:11043765 The activated PLC-gamma2 converts phosphatidylinositol 4,5-bisphosphate into the second messenger inositol 1,4,5-trisphosphate (IP3), which in turn binds to IP3 receptors located on the endoplasmic reticulum (ER). PMID:12181444 In vitro phosphorylation experiments with recombinant PLCgamma2 and recombinant Lck, Fyn, and Lyn tyrosine kinases showed that phosphorylation of PLCgamma2 led to activation of the recombinant enzyme. |
| GO:0035556 intracellular signal transduction | ISS GO_REF:0000024 | MODIFY | Summary: PLCG2 converts receptor input into phosphoinositide and calcium signals. Reason: Refine general signal transduction to phosphatidylinositol-mediated signaling and calcium-mediated signaling. GO_REF:0000024 is interpreted in its own context: immune/BCR studies include human PLCΞ³2 expressed in chicken DT40 cells, whereas platelet and microglial studies test distinct receptor systems. Calcium release is mediated by IP3 receptors downstream of PLCG2 catalysis, not by PLCG2 acting as an ion channel. Proposed replacements: phosphatidylinositol-mediated signaling calcium-mediated signaling Supporting Evidence: PMID:11043765 The activated PLC-gamma2 converts phosphatidylinositol 4,5-bisphosphate into the second messenger inositol 1,4,5-trisphosphate (IP3), which in turn binds to IP3 receptors located on the endoplasmic reticulum (ER). |
| GO:0004435 phosphatidylinositol-4,5-bisphosphate phospholipase C activity | EXP PMID:23000145 A hypermorphic missense mutation in PLCG2, encoding phosphol... | ACCEPT | Summary: PLCG2 is a phosphoinositide-specific phospholipase C that hydrolyzes PIP2 to IP3 and DAG after receptor-induced activation. Reason: Retain as core because PLCG2/PLC-gamma2 directly catalyzes phosphatidylinositol-4,5-bisphosphate hydrolysis, with experimental support for recombinant and cellular activity and activation by Tyr753/Tyr759 phosphorylation (PMID:11043765, PMID:11606584, PMID:12181444, PMID:23000145). |
| GO:0045121 membrane raft | ISS GO_REF:0000024 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0010628 positive regulation of gene expression | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:1902533 positive regulation of intracellular signal transduction | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0042113 B cell activation | IDA PMID:30107486 CD21 and FCRL5 form a receptor complex with robust B-cell ac... | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0032755 positive regulation of interleukin-6 production | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0048471 perinuclear region of cytoplasm | IDA PMID:23555801 BANK1 and BLK act through phospholipase C gamma 2 in B-cell ... | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). Supporting Evidence: PMID:23555801 In non-stimulated cells, the few BANK1-PLCG2 interactions are close to the nuclei, they lose the perinuclear localization at one minute of stimulation and at 20 minutes return to a position close to the nuclei. |
| GO:0050853 B cell receptor signaling pathway | TAS PMID:23555801 BANK1 and BLK act through phospholipase C gamma 2 in B-cell ... | ACCEPT | Summary: PLCG2 is a receptor-proximal transducer in immune-receptor pathways, especially BCR, Fc receptor, C-type lectin, and related hematopoietic signaling. Reason: Retain as core or near-core immune signaling biology because PLCG2 is recruited and activated by receptor-coupled tyrosine kinase/adaptor modules such as Syk, Btk, BLNK, BANK1, FCER/FCGR, and C-type lectin pathways (PMID:11043765, PMID:11606584, PMID:23555801; Reactome PLCG2 events). Supporting Evidence: PMID:23555801 We found that the molecular switch PLCg2 interacts with BANK1 and that the interaction is promoted by B-cell receptor (BCR) stimulation. |
| GO:0097110 scaffold protein binding | IPI PMID:23555801 BANK1 and BLK act through phospholipase C gamma 2 in B-cell ... | ACCEPT | Summary: Phosphorylated BLNK provides docking sites for PLCG2. Reason: PMID:11606584 combines human PLCΞ³2 rescue in chicken DT40 cells and purified complex analysis. The BLNK partner identifier in this row is avian Q9YGC1; the experiment supports scaffold recognition by human PLCG2 but is not a native human BLNK-pair assay. Supporting Evidence: PMID:11606584 Using purified proteins to analyze the formation of complexes, we suggest that function of Syk is to phosphorylate BLNK, providing binding sites for PLCgamma2. |
| GO:0004435 phosphatidylinositol-4,5-bisphosphate phospholipase C activity | IMP PMID:32514138 Alzheimer's-associated PLCΞ³2 is a signaling node required fo... | ACCEPT | Summary: PLCG2 is a phosphoinositide-specific phospholipase C that hydrolyzes PIP2 to IP3 and DAG after receptor-induced activation. Reason: Retain as core because PLCG2/PLC-gamma2 directly catalyzes phosphatidylinositol-4,5-bisphosphate hydrolysis, with experimental support for recombinant and cellular activity and activation by Tyr753/Tyr759 phosphorylation (PMID:11043765, PMID:11606584, PMID:12181444, PMID:23000145). |
| GO:0010628 positive regulation of gene expression | IMP PMID:32514138 Alzheimer's-associated PLCΞ³2 is a signaling node required fo... | KEEP AS NON CORE | Summary: Human microglia-like cell experiments support PLCG2 downstream of TREM2 for phagocytosis, lipid handling, survival, transcriptional responses, and inflammatory signaling. Reason: Keep as non-core because these Alzheimer-relevant microglial phenotypes are important cellular consequences of PLCG2 signaling, but they are downstream of its core phospholipase and immune-receptor transducer functions (PMID:32514138). |
| GO:0019216 regulation of lipid metabolic process | IMP PMID:32514138 Alzheimer's-associated PLCΞ³2 is a signaling node required fo... | KEEP AS NON CORE | Summary: Human microglia-like cell experiments support PLCG2 downstream of TREM2 for phagocytosis, lipid handling, survival, transcriptional responses, and inflammatory signaling. Reason: Keep as non-core because these Alzheimer-relevant microglial phenotypes are important cellular consequences of PLCG2 signaling, but they are downstream of its core phospholipase and immune-receptor transducer functions (PMID:32514138). |
| GO:0031663 lipopolysaccharide-mediated signaling pathway | IMP PMID:32514138 Alzheimer's-associated PLCΞ³2 is a signaling node required fo... | KEEP AS NON CORE | Summary: Human microglia-like cell experiments support PLCG2 downstream of TREM2 for phagocytosis, lipid handling, survival, transcriptional responses, and inflammatory signaling. Reason: Keep as non-core because these Alzheimer-relevant microglial phenotypes are important cellular consequences of PLCG2 signaling, but they are downstream of its core phospholipase and immune-receptor transducer functions (PMID:32514138). |
| GO:0035556 intracellular signal transduction | IMP PMID:32514138 Alzheimer's-associated PLCΞ³2 is a signaling node required fo... | MODIFY | Summary: PLCG2 converts receptor input into phosphoinositide and calcium signals. Reason: Refine general signal transduction to phosphatidylinositol-mediated signaling and calcium-mediated signaling. PMID:32514138 is interpreted in its own context: immune/BCR studies include human PLCΞ³2 expressed in chicken DT40 cells, whereas platelet and microglial studies test distinct receptor systems. Calcium release is mediated by IP3 receptors downstream of PLCG2 catalysis, not by PLCG2 acting as an ion channel. Proposed replacements: phosphatidylinositol-mediated signaling calcium-mediated signaling Supporting Evidence: PMID:11043765 The activated PLC-gamma2 converts phosphatidylinositol 4,5-bisphosphate into the second messenger inositol 1,4,5-trisphosphate (IP3), which in turn binds to IP3 receptors located on the endoplasmic reticulum (ER). |
| GO:0048678 response to axon injury | IMP PMID:32514138 Alzheimer's-associated PLCΞ³2 is a signaling node required fo... | KEEP AS NON CORE | Summary: Human microglia-like cell experiments support PLCG2 downstream of TREM2 for phagocytosis, lipid handling, survival, transcriptional responses, and inflammatory signaling. Reason: Keep as non-core because these Alzheimer-relevant microglial phenotypes are important cellular consequences of PLCG2 signaling, but they are downstream of its core phospholipase and immune-receptor transducer functions (PMID:32514138). |
| GO:0060100 positive regulation of phagocytosis, engulfment | IMP PMID:32514138 Alzheimer's-associated PLCΞ³2 is a signaling node required fo... | KEEP AS NON CORE | Summary: Human microglia-like cell experiments support PLCG2 downstream of TREM2 for phagocytosis, lipid handling, survival, transcriptional responses, and inflammatory signaling. Reason: Keep as non-core because these Alzheimer-relevant microglial phenotypes are important cellular consequences of PLCG2 signaling, but they are downstream of its core phospholipase and immune-receptor transducer functions (PMID:32514138). |
| GO:0071396 cellular response to lipid | IMP PMID:32514138 Alzheimer's-associated PLCΞ³2 is a signaling node required fo... | KEEP AS NON CORE | Summary: Human microglia-like cell experiments support PLCG2 downstream of TREM2 for phagocytosis, lipid handling, survival, transcriptional responses, and inflammatory signaling. Reason: Keep as non-core because these Alzheimer-relevant microglial phenotypes are important cellular consequences of PLCG2 signaling, but they are downstream of its core phospholipase and immune-receptor transducer functions (PMID:32514138). |
| GO:0150078 positive regulation of neuroinflammatory response | IMP PMID:32514138 Alzheimer's-associated PLCΞ³2 is a signaling node required fo... | KEEP AS NON CORE | Summary: Human microglia-like cell experiments support PLCG2 downstream of TREM2 for phagocytosis, lipid handling, survival, transcriptional responses, and inflammatory signaling. Reason: Keep as non-core because these Alzheimer-relevant microglial phenotypes are important cellular consequences of PLCG2 signaling, but they are downstream of its core phospholipase and immune-receptor transducer functions (PMID:32514138). |
| GO:1900227 positive regulation of NLRP3 inflammasome complex assembly | IMP PMID:32514138 Alzheimer's-associated PLCΞ³2 is a signaling node required fo... | KEEP AS NON CORE | Summary: Human microglia-like cell experiments support PLCG2 downstream of TREM2 for phagocytosis, lipid handling, survival, transcriptional responses, and inflammatory signaling. Reason: Keep as non-core because these Alzheimer-relevant microglial phenotypes are important cellular consequences of PLCG2 signaling, but they are downstream of its core phospholipase and immune-receptor transducer functions (PMID:32514138). |
| GO:1990782 protein tyrosine kinase binding | IPI PMID:32514138 Alzheimer's-associated PLCΞ³2 is a signaling node required fo... | ACCEPT | Summary: PLCG2 binds protein tyrosine kinases in activation complexes. Reason: The exact SYK interaction in the accessible PMID:32514138 record is incompletely exposed, but the gene-level tyrosine-kinase binding claim is independently supported by BTK/Src-family biochemical work in PMID:11606584 and PMID:12181444. Retain the functional partner class without representing the unverified SYK-specific assay as directly inspected. Independent PMID:27609517 directly recovers human platelet SYK with PLCΞ³2 tandem SH2 domains, although much more weakly than with PLCΞ³1. This supports the binding class without resolving the specific microglial interaction assay in PMID:32514138. Supporting Evidence: PMID:11606584 Of the two kinases that previously have been proposed to phosphorylate PLCgamma2, Btk, and Syk, purified Btk had much greater ability to phosphorylate recombinant PLCgamma2 in vitro, whereas Syk efficiently phosphorylated adapter protein BLNK. PMID:12181444 In vitro phosphorylation experiments with recombinant PLCgamma2 and recombinant Lck, Fyn, and Lyn tyrosine kinases showed that phosphorylation of PLCgamma2 led to activation of the recombinant enzyme. PMID:27609517 Notably, binding of human platelet Syk, but not that of SLP-76, to the SH2(NC) of PLCΞ³2, the major functional form of PLCΞ³ in platelets ( 43 , 44 ), was much weaker than its binding to the SH2(NC) of PLCΞ³1 ( Fig. 4 A ). |
| GO:0001775 cell activation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0001878 response to yeast | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0002223 stimulatory C-type lectin receptor signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: PLCG2 is a receptor-proximal transducer in immune-receptor pathways, especially BCR, Fc receptor, C-type lectin, and related hematopoietic signaling. Reason: Retain as core or near-core immune signaling biology because PLCG2 is recruited and activated by receptor-coupled tyrosine kinase/adaptor modules such as Syk, Btk, BLNK, BANK1, FCER/FCGR, and C-type lectin pathways (PMID:11043765, PMID:11606584, PMID:23555801; Reactome PLCG2 events). |
| GO:0002224 toll-like receptor signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0002281 macrophage activation involved in immune response | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0002732 positive regulation of dendritic cell cytokine production | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0032733 positive regulation of interleukin-10 production | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0032735 positive regulation of interleukin-12 production | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0032743 positive regulation of interleukin-2 production | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0032747 positive regulation of interleukin-23 production | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0032760 positive regulation of tumor necrosis factor production | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0043122 regulation of canonical NF-kappaB signal transduction | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0043410 positive regulation of MAPK cascade | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0050850 positive regulation of calcium-mediated signaling | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0060907 positive regulation of macrophage cytokine production | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0061760 antifungal innate immune response | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0070884 regulation of calcineurin-NFAT signaling cascade | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:1903428 positive regulation of reactive oxygen species biosynthetic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:1990858 cellular response to lectin | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0005737 cytoplasm | IDA PMID:11331309 Real time fluorescence imaging of PLC gamma translocation an... | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). The full methods identify human PLCΞ³2 constructs; the EGF localization experiments use fluorescently tagged proteins in a heterologous expression setting, rather than a constitutive location in every native human cell. Supporting Evidence: PMID:11331309 As shown in Fig. 2, in the absence of EGF, PLCΞ³1 and PLCΞ³2 were distributed throughout the cytoplasm and excluded from the nucleus and plasma membrane. |
| GO:0005886 plasma membrane | IDA PMID:11331309 Real time fluorescence imaging of PLC gamma translocation an... | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). The full methods identify human PLCΞ³2 constructs; the EGF localization experiments use fluorescently tagged proteins in a heterologous expression setting, rather than a constitutive location in every native human cell. Supporting Evidence: PMID:11331309 After addition of EGF, the translocation to the plasma membrane was largely completed within 2β3 min for both PLCΞ³1 and PLCΞ³2 and was accompanied by a reduction of fluorescence in the cytoplasm (Fig. 2). |
| GO:0032587 ruffle membrane | IDA PMID:11331309 Real time fluorescence imaging of PLC gamma translocation an... | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). The full methods identify human PLCΞ³2 constructs; the EGF localization experiments use fluorescently tagged proteins in a heterologous expression setting, rather than a constitutive location in every native human cell. Supporting Evidence: PMID:11331309 Colocalization with the receptor was observed in the plasma membrane and in membrane ruffles where PI 4,5-P(2) substrate could also be visualized. |
| GO:0035556 intracellular signal transduction | IDA PMID:14656219 Glycoproteins VI and Ib-IX-V stimulate tyrosine phosphorylat... | MODIFY | Summary: PLCG2 converts receptor input into phosphoinositide and calcium signals. Reason: Refine general signal transduction to phosphatidylinositol-mediated signaling and calcium-mediated signaling. PMID:14656219 is interpreted in its own context: immune/BCR studies include human PLCΞ³2 expressed in chicken DT40 cells, whereas platelet and microglial studies test distinct receptor systems. Calcium release is mediated by IP3 receptors downstream of PLCG2 catalysis, not by PLCG2 acting as an ion channel. Proposed replacements: phosphatidylinositol-mediated signaling calcium-mediated signaling Supporting Evidence: PMID:11043765 The activated PLC-gamma2 converts phosphatidylinositol 4,5-bisphosphate into the second messenger inositol 1,4,5-trisphosphate (IP3), which in turn binds to IP3 receptors located on the endoplasmic reticulum (ER). |
| GO:0050853 B cell receptor signaling pathway | IDA PMID:15509800 Mechanism of B-cell receptor-induced phosphorylation and act... | ACCEPT | Summary: PLCG2 is a receptor-proximal transducer in immune-receptor pathways, especially BCR, Fc receptor, C-type lectin, and related hematopoietic signaling. Reason: Retain as core or near-core immune signaling biology because PLCG2 is recruited and activated by receptor-coupled tyrosine kinase/adaptor modules such as Syk, Btk, BLNK, BANK1, FCER/FCGR, and C-type lectin pathways (PMID:11043765, PMID:11606584, PMID:23555801; Reactome PLCG2 events). Supporting Evidence: PMID:15509800 Examination of the effects of various pharmacological inhibitors and of RNA interference in Ramos cells suggested that Btk is largely, but not completely, responsible for phosphorylation of Y753 and Y759, whereas phosphorylation of Y1217 is independent of Btk. |
| GO:0097708 intracellular vesicle | IDA PMID:11331309 Real time fluorescence imaging of PLC gamma translocation an... | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). The full methods identify human PLCΞ³2 constructs; the EGF localization experiments use fluorescently tagged proteins in a heterologous expression setting, rather than a constitutive location in every native human cell. Supporting Evidence: PMID:11331309 At the same time, PLCΞ³2 was entirely associated with the intracellular vesicles (Fig. 8 B, left, top and bottom). |
| GO:0005886 plasma membrane | IDA PMID:11606584 Tyrosine residues in phospholipase Cgamma 2 essential for th... | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0019901 protein kinase binding | IPI PMID:11606584 Tyrosine residues in phospholipase Cgamma 2 essential for th... | ACCEPT | Summary: PLCG2 interacts with protein kinases that regulate its catalytic activity. Reason: The original PMID:11606584 supports kinaseβPLCG2 association/enzymatic engagement. PMID:11606584 distinguishes efficient BTK phosphorylation of recombinant human PLCΞ³2 from SYK phosphorylation of BLNK; PMID:12181444 directly tests LCK, FYN and LYN. This does not mean every kinase is equally effective or required in every native cell. Supporting Evidence: PMID:11606584 Of the two kinases that previously have been proposed to phosphorylate PLCgamma2, Btk, and Syk, purified Btk had much greater ability to phosphorylate recombinant PLCgamma2 in vitro, whereas Syk efficiently phosphorylated adapter protein BLNK. PMID:12181444 In vitro phosphorylation experiments with recombinant PLCgamma2 and recombinant Lck, Fyn, and Lyn tyrosine kinases showed that phosphorylation of PLCgamma2 led to activation of the recombinant enzyme. |
| GO:0035556 intracellular signal transduction | IDA PMID:11606584 Tyrosine residues in phospholipase Cgamma 2 essential for th... | MODIFY | Summary: PLCG2 converts receptor input into phosphoinositide and calcium signals. Reason: Refine general signal transduction to phosphatidylinositol-mediated signaling and calcium-mediated signaling. PMID:11606584 is interpreted in its own context: immune/BCR studies include human PLCΞ³2 expressed in chicken DT40 cells, whereas platelet and microglial studies test distinct receptor systems. Calcium release is mediated by IP3 receptors downstream of PLCG2 catalysis, not by PLCG2 acting as an ion channel. Proposed replacements: phosphatidylinositol-mediated signaling calcium-mediated signaling Supporting Evidence: PMID:11043765 The activated PLC-gamma2 converts phosphatidylinositol 4,5-bisphosphate into the second messenger inositol 1,4,5-trisphosphate (IP3), which in turn binds to IP3 receptors located on the endoplasmic reticulum (ER). |
| GO:0050853 B cell receptor signaling pathway | IMP PMID:11606584 Tyrosine residues in phospholipase Cgamma 2 essential for th... | ACCEPT | Summary: PLCG2 is a receptor-proximal transducer in immune-receptor pathways, especially BCR, Fc receptor, C-type lectin, and related hematopoietic signaling. Reason: Retain as core or near-core immune signaling biology because PLCG2 is recruited and activated by receptor-coupled tyrosine kinase/adaptor modules such as Syk, Btk, BLNK, BANK1, FCER/FCGR, and C-type lectin pathways (PMID:11043765, PMID:11606584, PMID:23555801; Reactome PLCG2 events). |
| GO:0097110 scaffold protein binding | IPI PMID:11606584 Tyrosine residues in phospholipase Cgamma 2 essential for th... | ACCEPT | Summary: Phosphorylated BLNK provides docking sites for PLCG2. Reason: PMID:11606584 combines human PLCΞ³2 rescue in chicken DT40 cells and purified complex analysis. The BLNK partner identifier in this row is avian Q9YGC1; the experiment supports scaffold recognition by human PLCG2 but is not a native human BLNK-pair assay. Supporting Evidence: PMID:11606584 Using purified proteins to analyze the formation of complexes, we suggest that function of Syk is to phosphorylate BLNK, providing binding sites for PLCgamma2. |
| GO:1902808 positive regulation of cell cycle G1/S phase transition | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0019722 calcium-mediated signaling | IMP PMID:11606584 Tyrosine residues in phospholipase Cgamma 2 essential for th... | ACCEPT | Summary: PLCG2 produces IP3 downstream of receptor activation, driving calcium release and calcium-mediated signaling. Reason: Retain as core signaling output because BCR and platelet studies show PLCG2-dependent calcium responses and phosphorylation-dependent activation of PLCG2 upstream of IP3-mediated calcium release (PMID:11043765, PMID:11606584, PMID:12181444). |
| GO:0071277 cellular response to calcium ion | IMP PMID:11606584 Tyrosine residues in phospholipase Cgamma 2 essential for th... | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0001784 phosphotyrosine residue binding | IPI PMID:20624904 Tarp regulates early Chlamydia-induced host cell survival th... | ACCEPT | Summary: PLCG2 SH2 domains recognize phosphotyrosine-containing motifs. Reason: Direct recombinant human SH2-domain SPR against EAT-2 and LAT phosphopeptides (PMID:24642916) supports this recruitment activity independently of a family-domain label. Supporting Evidence: PMID:24642916 Recombinant PLCΞ³2 SH2 domains also bound immobilized EAT-2 Y127 and LAT Y132 peptides with comparable affinity |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5607755 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5621347 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5621363 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5607735 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5607755 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5621347 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | KEEP AS NON CORE | Summary: Detected in an extracellular-vesicle proteome. The protein is plausible EV content, but this is not where it functions. Reason: Cytoplasmic/membrane-raft phospholipase. Cytosolic protein with lipid or membrane-protein binding ability; MISEV2018 (PMID:30637094) category 2a lists such proteins (ESCRT components, ALIX, annexins, HSPA8 and others) as expected EV contents. True, but not its core location. (Manual re-review for OMICS_EVIDENCE, 2026-10-10; previous action: MARK_AS_OVER_ANNOTATED.) |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2029268 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2029270 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2396594 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2396606 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2424476 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2424481 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2424484 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2424486 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2424487 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730833 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730840 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730841 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730851 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730856 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730858 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730889 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730892 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9606151 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9606894 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9664270 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9664278 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9691421 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-1112666 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202407 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2029268 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2029272 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2424485 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2424487 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2730847 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9664271 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9664278 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-114689 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-1855221 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-429497 | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0016055 Wnt signaling pathway | TAS PMID:18784435 Molecular profiling of isolated histological components of w... | UNDECIDED | Summary: The functional Wnt-pathway assignment is not resolved by the accessible tumor-expression study. Reason: PMID:18784435 reports PLCG2 expression patterns in Wilms tumor and fetal kidney and interprets them alongside Wnt-pathway genes. Expression absence in sampled tissues is not a direct test excluding PLCG2 from Wnt signaling. Full experimental context remains inaccessible after normal refresh; the prior abstract-based REMOVE was therefore not justified. |
| GO:0004435 phosphatidylinositol-4,5-bisphosphate phospholipase C activity | IDA PMID:11606584 Tyrosine residues in phospholipase Cgamma 2 essential for th... | ACCEPT | Summary: PLCG2 is a phosphoinositide-specific phospholipase C that hydrolyzes PIP2 to IP3 and DAG after receptor-induced activation. Reason: Retain as core because PLCG2/PLC-gamma2 directly catalyzes phosphatidylinositol-4,5-bisphosphate hydrolysis, with experimental support for recombinant and cellular activity and activation by Tyr753/Tyr759 phosphorylation (PMID:11043765, PMID:11606584, PMID:12181444, PMID:23000145). |
| GO:0004435 phosphatidylinositol-4,5-bisphosphate phospholipase C activity | IDA PMID:12181444 Activation of phospholipase Cgamma2 by tyrosine phosphorylat... | ACCEPT | Summary: PLCG2 is a phosphoinositide-specific phospholipase C that hydrolyzes PIP2 to IP3 and DAG after receptor-induced activation. Reason: Retain as core because PLCG2/PLC-gamma2 directly catalyzes phosphatidylinositol-4,5-bisphosphate hydrolysis, with experimental support for recombinant and cellular activity and activation by Tyr753/Tyr759 phosphorylation (PMID:11043765, PMID:11606584, PMID:12181444, PMID:23000145). |
| GO:0005886 plasma membrane | IDA PMID:11606584 Tyrosine residues in phospholipase Cgamma 2 essential for th... | ACCEPT | Summary: PLCG2 functions from cytosolic pools that transiently translocate to plasma-membrane, membrane-raft, and ruffle signaling sites and can later appear in internal vesicles. Reason: Retain because PLC-gamma localization to plasma membrane and membrane ruffles is tied to receptor binding, access to PI(4,5)P2 substrate, activation, and later internalization; PLCG2 also has Reactome and UniProt support for cytosol/plasma-membrane signaling locations (PMID:11331309). |
| GO:0006661 phosphatidylinositol biosynthetic process | IDA PMID:11606584 Tyrosine residues in phospholipase Cgamma 2 essential for th... | MODIFY | Summary: The direct PLCG2 product is IP3, generated by cleavage of PIP2. Reason: This is a reaction-role correction: PLCG2 does not synthesize phosphatidylinositol in the cited activation assays. Its supported product-forming process is inositol trisphosphate biosynthesis, coupled to glycerophospholipid cleavage. The replacement is not claimed to be a descendant of phosphatidylinositol biosynthesis. Proposed replacements: inositol trisphosphate biosynthetic process Supporting Evidence: PMID:11043765 The activated PLC-gamma2 converts phosphatidylinositol 4,5-bisphosphate into the second messenger inositol 1,4,5-trisphosphate (IP3), which in turn binds to IP3 receptors located on the endoplasmic reticulum (ER). PMID:12181444 In vitro phosphorylation experiments with recombinant PLCgamma2 and recombinant Lck, Fyn, and Lyn tyrosine kinases showed that phosphorylation of PLCgamma2 led to activation of the recombinant enzyme. |
| GO:0006661 phosphatidylinositol biosynthetic process | IDA PMID:12181444 Activation of phospholipase Cgamma2 by tyrosine phosphorylat... | MODIFY | Summary: The direct PLCG2 product is IP3, generated by cleavage of PIP2. Reason: This is a reaction-role correction: PLCG2 does not synthesize phosphatidylinositol in the cited activation assays. Its supported product-forming process is inositol trisphosphate biosynthesis, coupled to glycerophospholipid cleavage. The replacement is not claimed to be a descendant of phosphatidylinositol biosynthesis. Proposed replacements: inositol trisphosphate biosynthetic process Supporting Evidence: PMID:11043765 The activated PLC-gamma2 converts phosphatidylinositol 4,5-bisphosphate into the second messenger inositol 1,4,5-trisphosphate (IP3), which in turn binds to IP3 receptors located on the endoplasmic reticulum (ER). PMID:12181444 In vitro phosphorylation experiments with recombinant PLCgamma2 and recombinant Lck, Fyn, and Lyn tyrosine kinases showed that phosphorylation of PLCgamma2 led to activation of the recombinant enzyme. |
| GO:0019722 calcium-mediated signaling | NAS PMID:11043765 Regulation of the phospholipase C-gamma2 pathway in B cells. | ACCEPT | Summary: PLCG2 produces IP3 downstream of receptor activation, driving calcium release and calcium-mediated signaling. Reason: Retain as core signaling output because BCR and platelet studies show PLCG2-dependent calcium responses and phosphorylation-dependent activation of PLCG2 upstream of IP3-mediated calcium release (PMID:11043765, PMID:11606584, PMID:12181444). |
| GO:0030183 B cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: This immune-cell process is a plausible downstream or cell-type-specific outcome of PLCG2 receptor signaling. Reason: Keep as non-core because PLCG2 can regulate B-cell, platelet, NK-cell, myeloid, and microglial responses, but the annotation reflects an effector phenotype downstream of the core PIP2 phospholipase/receptor-proximal signaling mechanism (PMID:11043765, PMID:23555801, PMID:32514138). |
| GO:0050852 T cell receptor signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: This annotation is plausible for PLCG2 but was not central to the reviewed catalytic/receptor-proximal mechanism. Reason: Keep as non-core pending deeper evidence review; it is compatible with PLCG2 signaling biology but does not define the core PIP2 phospholipase function. |
| GO:0050853 B cell receptor signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: PLCG2 is a receptor-proximal transducer in immune-receptor pathways, especially BCR, Fc receptor, C-type lectin, and related hematopoietic signaling. Reason: Retain as core or near-core immune signaling biology because PLCG2 is recruited and activated by receptor-coupled tyrosine kinase/adaptor modules such as Syk, Btk, BLNK, BANK1, FCER/FCGR, and C-type lectin pathways (PMID:11043765, PMID:11606584, PMID:23555801; Reactome PLCG2 events). |
| GO:0051209 release of sequestered calcium ion into cytosol | IDA PMID:11606584 Tyrosine residues in phospholipase Cgamma 2 essential for th... | ACCEPT | Summary: PLCG2 produces IP3 downstream of receptor activation, driving calcium release and calcium-mediated signaling. Reason: Retain as core signaling output because BCR and platelet studies show PLCG2-dependent calcium responses and phosphorylation-dependent activation of PLCG2 upstream of IP3-mediated calcium release (PMID:11043765, PMID:11606584, PMID:12181444). |
| GO:0005515 protein binding | IPI PMID:16273093 A quantitative protein interaction network for the ErbB rece... | MODIFY | Summary: The interaction is more informatively represented by phosphotyrosine recognition. Reason: The cited PMID:16273093 uses phosphorylated receptor/adaptor motifs or SH2-domain binding. Independent direct human PLCΞ³2 SH2-domain SPR in PMID:24642916 establishes phosphotyrosine recognition. Domain/peptide assays show biochemical recognition potential and do not by themselves establish an obligatory full-length native complex with every screened partner. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:24642916 Recombinant PLCΞ³2 SH2 domains also bound immobilized EAT-2 Y127 and LAT Y132 peptides with comparable affinity |
| GO:0005515 protein binding | IPI PMID:24728074 Enhanced prediction of Src homology 2 (SH2) domain binding p... | MODIFY | Summary: The interaction is more informatively represented by phosphotyrosine recognition. Reason: The cited PMID:24728074 uses phosphorylated receptor/adaptor motifs or SH2-domain binding. Independent direct human PLCΞ³2 SH2-domain SPR in PMID:24642916 establishes phosphotyrosine recognition. Domain/peptide assays show biochemical recognition potential and do not by themselves establish an obligatory full-length native complex with every screened partner. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:24642916 Recombinant PLCΞ³2 SH2 domains also bound immobilized EAT-2 Y127 and LAT Y132 peptides with comparable affinity |
| GO:0005515 protein binding | IPI PMID:24728074 Enhanced prediction of Src homology 2 (SH2) domain binding p... | MODIFY | Summary: The interaction is more informatively represented by phosphotyrosine recognition. Reason: The cited PMID:24728074 uses phosphorylated receptor/adaptor motifs or SH2-domain binding. Independent direct human PLCΞ³2 SH2-domain SPR in PMID:24642916 establishes phosphotyrosine recognition. Domain/peptide assays show biochemical recognition potential and do not by themselves establish an obligatory full-length native complex with every screened partner. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:24642916 Recombinant PLCΞ³2 SH2 domains also bound immobilized EAT-2 Y127 and LAT Y132 peptides with comparable affinity |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | REMOVE | Summary: The reported association is preserved without a generic binding annotation. Reason: Bare protein binding is uninformative under current policy. The interaction with UniProtKB:P04626 in PMID:25241761 is not being rejected; a specific recruitment mechanism is not inferred solely from the association. |
| GO:0005515 protein binding | IPI PMID:25814554 Phospho-tyrosine dependent protein-protein interaction netwo... | REMOVE | Summary: The reported association is preserved without a generic binding annotation. Reason: Bare protein binding is uninformative under current policy. The interaction with UniProtKB:O95073-2 in PMID:25814554 is not being rejected; a specific recruitment mechanism is not inferred solely from the association. |
| GO:0005515 protein binding | IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei... | REMOVE | Summary: The reported association is preserved without a generic binding annotation. Reason: Bare protein binding is uninformative under current policy. The interaction with UniProtKB:P15056 in PMID:35512704 is not being rejected; a specific recruitment mechanism is not inferred solely from the association. |
| GO:0019901 protein kinase binding | IPI PMID:11606584 Tyrosine residues in phospholipase Cgamma 2 essential for th... | ACCEPT | Summary: PLCG2 interacts with protein kinases that regulate its catalytic activity. Reason: The original PMID:11606584 supports kinaseβPLCG2 association/enzymatic engagement. PMID:11606584 distinguishes efficient BTK phosphorylation of recombinant human PLCΞ³2 from SYK phosphorylation of BLNK; PMID:12181444 directly tests LCK, FYN and LYN. This does not mean every kinase is equally effective or required in every native cell. Supporting Evidence: PMID:11606584 Of the two kinases that previously have been proposed to phosphorylate PLCgamma2, Btk, and Syk, purified Btk had much greater ability to phosphorylate recombinant PLCgamma2 in vitro, whereas Syk efficiently phosphorylated adapter protein BLNK. PMID:12181444 In vitro phosphorylation experiments with recombinant PLCgamma2 and recombinant Lck, Fyn, and Lyn tyrosine kinases showed that phosphorylation of PLCgamma2 led to activation of the recombinant enzyme. |
| GO:0019901 protein kinase binding | IPI PMID:11606584 Tyrosine residues in phospholipase Cgamma 2 essential for th... | ACCEPT | Summary: PLCG2 interacts with protein kinases that regulate its catalytic activity. Reason: The original PMID:11606584 supports kinaseβPLCG2 association/enzymatic engagement. PMID:11606584 distinguishes efficient BTK phosphorylation of recombinant human PLCΞ³2 from SYK phosphorylation of BLNK; PMID:12181444 directly tests LCK, FYN and LYN. This does not mean every kinase is equally effective or required in every native cell. Supporting Evidence: PMID:11606584 Of the two kinases that previously have been proposed to phosphorylate PLCgamma2, Btk, and Syk, purified Btk had much greater ability to phosphorylate recombinant PLCgamma2 in vitro, whereas Syk efficiently phosphorylated adapter protein BLNK. PMID:12181444 In vitro phosphorylation experiments with recombinant PLCgamma2 and recombinant Lck, Fyn, and Lyn tyrosine kinases showed that phosphorylation of PLCgamma2 led to activation of the recombinant enzyme. |
| GO:0019901 protein kinase binding | IPI PMID:11606584 Tyrosine residues in phospholipase Cgamma 2 essential for th... | ACCEPT | Summary: PLCG2 interacts with protein kinases that regulate its catalytic activity. Reason: The original PMID:11606584 supports kinaseβPLCG2 association/enzymatic engagement. PMID:11606584 distinguishes efficient BTK phosphorylation of recombinant human PLCΞ³2 from SYK phosphorylation of BLNK; PMID:12181444 directly tests LCK, FYN and LYN. This does not mean every kinase is equally effective or required in every native cell. Supporting Evidence: PMID:11606584 Of the two kinases that previously have been proposed to phosphorylate PLCgamma2, Btk, and Syk, purified Btk had much greater ability to phosphorylate recombinant PLCgamma2 in vitro, whereas Syk efficiently phosphorylated adapter protein BLNK. PMID:12181444 In vitro phosphorylation experiments with recombinant PLCgamma2 and recombinant Lck, Fyn, and Lyn tyrosine kinases showed that phosphorylation of PLCgamma2 led to activation of the recombinant enzyme. |
| GO:0035556 intracellular signal transduction | ISS GO_REF:0000024 | MODIFY | Summary: PLCG2 converts receptor input into phosphoinositide and calcium signals. Reason: Refine general signal transduction to phosphatidylinositol-mediated signaling and calcium-mediated signaling. GO_REF:0000024 is interpreted in its own context: immune/BCR studies include human PLCΞ³2 expressed in chicken DT40 cells, whereas platelet and microglial studies test distinct receptor systems. Calcium release is mediated by IP3 receptors downstream of PLCG2 catalysis, not by PLCG2 acting as an ion channel. Proposed replacements: phosphatidylinositol-mediated signaling calcium-mediated signaling Supporting Evidence: PMID:11043765 The activated PLC-gamma2 converts phosphatidylinositol 4,5-bisphosphate into the second messenger inositol 1,4,5-trisphosphate (IP3), which in turn binds to IP3 receptors located on the endoplasmic reticulum (ER). |
| GO:0097110 scaffold protein binding | IPI PMID:11606584 Tyrosine residues in phospholipase Cgamma 2 essential for th... | ACCEPT | Summary: Phosphorylated BLNK provides docking sites for PLCG2. Reason: PMID:11606584 combines human PLCΞ³2 rescue in chicken DT40 cells and purified complex analysis. The BLNK partner identifier in this row is avian Q9YGC1; the experiment supports scaffold recognition by human PLCG2 but is not a native human BLNK-pair assay. Supporting Evidence: PMID:11606584 Using purified proteins to analyze the formation of complexes, we suggest that function of Syk is to phosphorylate BLNK, providing binding sites for PLCgamma2. |
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Download this section (compressed HTML)Q: Which PLCG2 receptor contexts should be considered core across hematopoietic and microglial biology rather than retained as cell-type-specific downstream processes?
Q: Can full-text evidence for the PMID:32514138 protein tyrosine kinase binding annotation be reviewed to decide whether GO:1990782 should be accepted or replaced by a more specific recruitment term?
Q: Should Reactome PLCG1/PLCG entity-set events that annotate PLCG2 be split or qualified to avoid isoform ambiguity?
Experiment: Measure endogenous PLCG2 recruitment, phosphorylation, PIP2 hydrolysis, and calcium output after TREM2, Fc receptor, C-type lectin, and TLR stimulation in primary human microglia or macrophages.
Hypothesis: Endogenous PLCG2 has receptor-context-specific activation kinetics in microglia and macrophages.
Type: primary-cell signaling time course
Experiment: Use PLCG2 SH2-domain and Rac-binding mutants to separate phosphotyrosine-adaptor recruitment from Rac-dependent activation in immune-cell signaling assays.
Hypothesis: SH2-domain recruitment and Rac-dependent activation make separable contributions to PLCG2 signaling output.
Type: mutational structure-function assay
Experiment: Test whether Alzheimer-associated PLCG2 variants alter core PIP2 phospholipase activity, membrane recruitment kinetics, and downstream phagocytosis/lipid-response phenotypes in matched human microglia-like cells.
Hypothesis: Alzheimer-associated PLCG2 variants alter receptor-proximal phospholipase activity and downstream microglial phenotypes.
Type: iPSC-derived microglia variant assay
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