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 | MODIFY | Summary: The annotation is directionally correct but too broad for PLCG2; the specific biology is PIP2 phospholipase activity and phosphoinositide-mediated receptor signaling. Reason: Modify to the specific PLCG2 catalytic/signaling terms because generic lipid metabolism, phospholipid catabolism, hydrolase activity, or signal transduction hides the defining PIP2 phospholipase mechanism. Proposed replacements: phosphatidylinositol-mediated signaling |
| GO:0010634 positive regulation of epithelial cell migration | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: This epithelial migration annotation is weakly connected to PLC-gamma family signaling but is not characteristic of hematopoietic PLCG2 biology. Reason: Mark as over-annotated because PLCG2 is primarily a hematopoietic/microglial receptor-signaling PLC; the review evidence supports immune receptor signaling rather than a core epithelial migration function. |
| 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: The annotation is directionally correct but too broad for PLCG2; the specific biology is PIP2 phospholipase activity and phosphoinositide-mediated receptor signaling. Reason: Modify to the specific PLCG2 catalytic/signaling terms because generic lipid metabolism, phospholipid catabolism, hydrolase activity, or signal transduction hides the defining PIP2 phospholipase mechanism. Proposed replacements: phosphatidylinositol-mediated signaling |
| GO:0007165 signal transduction | IEA GO_REF:0000002 | MODIFY | Summary: The annotation is directionally correct but too broad for PLCG2; the specific biology is PIP2 phospholipase activity and phosphoinositide-mediated receptor signaling. Reason: Modify to the specific PLCG2 catalytic/signaling terms because generic lipid metabolism, phospholipid catabolism, hydrolase activity, or signal transduction hides the defining PIP2 phospholipase mechanism. Proposed replacements: phosphatidylinositol-mediated signaling |
| GO:0008081 phosphoric diester hydrolase activity | IEA GO_REF:0000002 | MODIFY | Summary: The annotation is directionally correct but too broad for PLCG2; the specific biology is PIP2 phospholipase activity and phosphoinositide-mediated receptor signaling. Reason: Modify to the specific PLCG2 catalytic/signaling terms because generic lipid metabolism, phospholipid catabolism, hydrolase activity, or signal transduction hides the defining PIP2 phospholipase mechanism. Proposed replacements: phosphatidylinositol-4,5-bisphosphate phospholipase C activity |
| GO:0009395 phospholipid catabolic process | IEA GO_REF:0000002 | MODIFY | Summary: The annotation is directionally correct but too broad for PLCG2; the specific biology is PIP2 phospholipase activity and phosphoinositide-mediated receptor signaling. Reason: Modify to the specific PLCG2 catalytic/signaling terms because generic lipid metabolism, phospholipid catabolism, hydrolase activity, or signal transduction hides the defining PIP2 phospholipase mechanism. Proposed replacements: phosphatidylinositol-mediated signaling |
| 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: The annotation is directionally correct but too broad for PLCG2; the specific biology is PIP2 phospholipase activity and phosphoinositide-mediated receptor signaling. Reason: Modify to the specific PLCG2 catalytic/signaling terms because generic lipid metabolism, phospholipid catabolism, hydrolase activity, or signal transduction hides the defining PIP2 phospholipase mechanism. Proposed replacements: phosphatidylinositol-mediated signaling |
| 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 evidence reflects PLCG2 SH2-domain or phosphorylation-dependent recruitment to phosphorylated receptors/adaptors rather than generic protein binding. Reason: Modify generic protein binding to phosphotyrosine/phosphorylation-dependent binding because PLCG2 recruitment depends on SH2-domain recognition of phosphorylated receptor or adaptor motifs in immune and growth-factor signaling contexts. Proposed replacements: phosphotyrosine residue binding phosphorylation-dependent protein binding |
| GO:0005515 protein binding | IPI PMID:16273093 A quantitative protein interaction network for the ErbB rece... | MODIFY | Summary: The interaction evidence reflects PLCG2 SH2-domain or phosphorylation-dependent recruitment to phosphorylated receptors/adaptors rather than generic protein binding. Reason: Modify generic protein binding to phosphotyrosine/phosphorylation-dependent binding because PLCG2 recruitment depends on SH2-domain recognition of phosphorylated receptor or adaptor motifs in immune and growth-factor signaling contexts. Proposed replacements: phosphotyrosine residue binding phosphorylation-dependent protein binding |
| GO:0005515 protein binding | IPI PMID:24642916 Fine specificity and molecular competition in SLAM family re... | MODIFY | Summary: The interaction evidence reflects PLCG2 SH2-domain or phosphorylation-dependent recruitment to phosphorylated receptors/adaptors rather than generic protein binding. Reason: Modify generic protein binding to phosphotyrosine/phosphorylation-dependent binding because PLCG2 recruitment depends on SH2-domain recognition of phosphorylated receptor or adaptor motifs in immune and growth-factor signaling contexts. Proposed replacements: phosphotyrosine residue binding phosphorylation-dependent protein binding |
| GO:0005515 protein binding | IPI PMID:24658140 The mammalian-membrane two-hybrid assay (MaMTH) for probing ... | MARK AS OVER ANNOTATED | Summary: This generic or high-throughput interaction/localization annotation does not define PLCG2 core molecular function. Reason: Mark as over-annotated because generic protein binding or broad screen-derived evidence is less informative than the specific PLCG2 phospholipase activity, phosphotyrosine-dependent recruitment, and immune-receptor signaling terms. |
| GO:0005515 protein binding | IPI PMID:24728074 Enhanced prediction of Src homology 2 (SH2) domain binding p... | MODIFY | Summary: The interaction evidence reflects PLCG2 SH2-domain or phosphorylation-dependent recruitment to phosphorylated receptors/adaptors rather than generic protein binding. Reason: Modify generic protein binding to phosphotyrosine/phosphorylation-dependent binding because PLCG2 recruitment depends on SH2-domain recognition of phosphorylated receptor or adaptor motifs in immune and growth-factor signaling contexts. Proposed replacements: phosphotyrosine residue binding phosphorylation-dependent protein binding |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | MARK AS OVER ANNOTATED | Summary: This generic or high-throughput interaction/localization annotation does not define PLCG2 core molecular function. Reason: Mark as over-annotated because generic protein binding or broad screen-derived evidence is less informative than the specific PLCG2 phospholipase activity, phosphotyrosine-dependent recruitment, and immune-receptor signaling terms. |
| GO:0005515 protein binding | IPI PMID:25814554 Phospho-tyrosine dependent protein-protein interaction netwo... | MODIFY | Summary: The interaction evidence reflects PLCG2 SH2-domain or phosphorylation-dependent recruitment to phosphorylated receptors/adaptors rather than generic protein binding. Reason: Modify generic protein binding to phosphotyrosine/phosphorylation-dependent binding because PLCG2 recruitment depends on SH2-domain recognition of phosphorylated receptor or adaptor motifs in immune and growth-factor signaling contexts. Proposed replacements: phosphotyrosine residue binding phosphorylation-dependent protein binding |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | MARK AS OVER ANNOTATED | Summary: This generic or high-throughput interaction/localization annotation does not define PLCG2 core molecular function. Reason: Mark as over-annotated because generic protein binding or broad screen-derived evidence is less informative than the specific PLCG2 phospholipase activity, phosphotyrosine-dependent recruitment, and immune-receptor signaling terms. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: This generic or high-throughput interaction/localization annotation does not define PLCG2 core molecular function. Reason: Mark as over-annotated because generic protein binding or broad screen-derived evidence is less informative than the specific PLCG2 phospholipase activity, phosphotyrosine-dependent recruitment, and immune-receptor signaling terms. |
| GO:0005515 protein binding | IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei... | MARK AS OVER ANNOTATED | Summary: This generic or high-throughput interaction/localization annotation does not define PLCG2 core molecular function. Reason: Mark as over-annotated because generic protein binding or broad screen-derived evidence is less informative than the specific PLCG2 phospholipase activity, phosphotyrosine-dependent recruitment, and immune-receptor signaling terms. |
| 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: The annotation is directionally correct but too broad for PLCG2; the specific biology is PIP2 phospholipase activity and phosphoinositide-mediated receptor signaling. Reason: Modify to the specific PLCG2 catalytic/signaling terms because generic lipid metabolism, phospholipid catabolism, hydrolase activity, or signal transduction hides the defining PIP2 phospholipase mechanism. Proposed replacements: phosphatidylinositol-4,5-bisphosphate phospholipase C activity |
| GO:0004629 C-type glycerophospholipase activity | TAS Reactome:R-HSA-114689 | MODIFY | Summary: The annotation is directionally correct but too broad for PLCG2; the specific biology is PIP2 phospholipase activity and phosphoinositide-mediated receptor signaling. Reason: Modify to the specific PLCG2 catalytic/signaling terms because generic lipid metabolism, phospholipid catabolism, hydrolase activity, or signal transduction hides the defining PIP2 phospholipase mechanism. Proposed replacements: phosphatidylinositol-4,5-bisphosphate phospholipase C activity |
| GO:0035556 intracellular signal transduction | ISS GO_REF:0000024 | MODIFY | Summary: The annotation is directionally correct but too broad for PLCG2; the specific biology is PIP2 phospholipase activity and phosphoinositide-mediated receptor signaling. Reason: Modify to the specific PLCG2 catalytic/signaling terms because generic lipid metabolism, phospholipid catabolism, hydrolase activity, or signal transduction hides the defining PIP2 phospholipase mechanism. Proposed replacements: phosphatidylinositol-mediated signaling |
| 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). |
| 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). |
| GO:0097110 scaffold protein binding | IPI PMID:23555801 BANK1 and BLK act through phospholipase C gamma 2 in B-cell ... | ACCEPT | Summary: PLCG2 binds kinase/scaffold/adaptor proteins that recruit and activate it in immune-receptor signaling complexes. Reason: Retain because Btk/Syk/BLNK and BANK1 evidence supports PLCG2 recruitment and activation through kinase and scaffold/adaptor complexes in BCR and related immune signaling (PMID:11606584, PMID:23555801). |
| 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: The annotation is directionally correct but too broad for PLCG2; the specific biology is PIP2 phospholipase activity and phosphoinositide-mediated receptor signaling. Reason: Modify to the specific PLCG2 catalytic/signaling terms because generic lipid metabolism, phospholipid catabolism, hydrolase activity, or signal transduction hides the defining PIP2 phospholipase mechanism. Proposed replacements: phosphatidylinositol-mediated signaling |
| 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... | UNDECIDED | Summary: The cached abstract supports PLCG2 signaling in microglia but does not show the specific protein tyrosine kinase binding assertion. Reason: Use UNDECIDED because the annotation is experimental IPI but the cached publication is abstract-only and does not expose the full evidence for direct protein tyrosine kinase binding; per review policy, do not overrule curator evidence from incomplete full text (PMID:32514138). |
| 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). |
| 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). |
| 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). |
| GO:0035556 intracellular signal transduction | IDA PMID:14656219 Glycoproteins VI and Ib-IX-V stimulate tyrosine phosphorylat... | MODIFY | Summary: The annotation is directionally correct but too broad for PLCG2; the specific biology is PIP2 phospholipase activity and phosphoinositide-mediated receptor signaling. Reason: Modify to the specific PLCG2 catalytic/signaling terms because generic lipid metabolism, phospholipid catabolism, hydrolase activity, or signal transduction hides the defining PIP2 phospholipase mechanism. Proposed replacements: phosphatidylinositol-mediated signaling |
| 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). |
| 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). |
| 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 binds kinase/scaffold/adaptor proteins that recruit and activate it in immune-receptor signaling complexes. Reason: Retain because Btk/Syk/BLNK and BANK1 evidence supports PLCG2 recruitment and activation through kinase and scaffold/adaptor complexes in BCR and related immune signaling (PMID:11606584, PMID:23555801). |
| GO:0035556 intracellular signal transduction | IDA PMID:11606584 Tyrosine residues in phospholipase Cgamma 2 essential for th... | MODIFY | Summary: The annotation is directionally correct but too broad for PLCG2; the specific biology is PIP2 phospholipase activity and phosphoinositide-mediated receptor signaling. Reason: Modify to the specific PLCG2 catalytic/signaling terms because generic lipid metabolism, phospholipid catabolism, hydrolase activity, or signal transduction hides the defining PIP2 phospholipase mechanism. Proposed replacements: phosphatidylinositol-mediated signaling |
| 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: PLCG2 binds kinase/scaffold/adaptor proteins that recruit and activate it in immune-receptor signaling complexes. Reason: Retain because Btk/Syk/BLNK and BANK1 evidence supports PLCG2 recruitment and activation through kinase and scaffold/adaptor complexes in BCR and related immune signaling (PMID:11606584, PMID:23555801). |
| 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 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: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... | MARK AS OVER ANNOTATED | Summary: This generic or high-throughput interaction/localization annotation does not define PLCG2 core molecular function. Reason: Mark as over-annotated because exosome detection in a B-cell exosome proteomics dataset is not a defining PLCG2 localization or function (PMID:20458337). |
| 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... | REMOVE | Summary: The cited Wilms tumor expression study does not establish PLCG2 as a Wnt signaling pathway component. Reason: Remove because the abstract describes tumor/kidney expression profiling and reports lack of PLCG2 expression in WT/fetal kidney rather than functional involvement of PLCG2 in Wnt signaling (PMID:18784435). |
| 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: PLCG2 hydrolyzes PIP2 rather than synthesizing phosphatidylinositol lipids. Reason: Modify because phosphatidylinositol biosynthetic process has the wrong direction for PLCG2; the supported biology is phosphatidylinositol-mediated signaling through PIP2 hydrolysis to IP3 and DAG (PMID:11043765, PMID:11331309, PMID:12181444). Proposed replacements: phosphatidylinositol-mediated signaling |
| GO:0006661 phosphatidylinositol biosynthetic process | IDA PMID:12181444 Activation of phospholipase Cgamma2 by tyrosine phosphorylat... | MODIFY | Summary: PLCG2 hydrolyzes PIP2 rather than synthesizing phosphatidylinositol lipids. Reason: Modify because phosphatidylinositol biosynthetic process has the wrong direction for PLCG2; the supported biology is phosphatidylinositol-mediated signaling through PIP2 hydrolysis to IP3 and DAG (PMID:11043765, PMID:11331309, PMID:12181444). Proposed replacements: phosphatidylinositol-mediated signaling |
| 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). |
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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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