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 PLCγ2 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 PLCγ2 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 PLCγ2 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 PLCγ2 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 PLCγ2 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 PLCγ2 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 PLCγ2 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 PLCγ2 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 PLCγ2 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 PLCγ2 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 PLCγ2 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).
|
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
Automated deep research was attempted with just deep-research-falcon human PLCG2 --fallback perplexity-lite, but the run timed out before producing a deep-research file. This review therefore uses the cached GOA publications, the UniProt record, Reactome-derived entries, and the PANTHER family fetch.
PLCG2 encodes phospholipase C-gamma 2, a hematopoietic and microglial phosphoinositide-specific phospholipase C. The central biochemical activity is receptor-regulated hydrolysis of phosphatidylinositol 4,5-bisphosphate to IP3 and DAG: activated PLC-gamma2 "converts phosphatidylinositol 4,5-bisphosphate into the second messenger inositol 1,4,5-trisphosphate (IP3)" PMID:11043765. The general PLC-gamma reaction also generates "two second messengers: inositol 1,4,5-trisphosphate (I 1,4,5-P3) and diacylglycerol" PMID:11331309.
Activation is controlled by tyrosine phosphorylation and SH2-domain recruitment. In B-cell signaling, Tyr753 and Tyr759 are important for PLCG2 function, with Btk directly phosphorylating PLCG2 while Syk phosphorylates BLNK to create docking sites [PMID:11606584 "two tyrosine residues, Tyr(753) and Tyr(759), were important for the PLCgamma2 signaling function"; PMID:11606584 "function of Syk is to phosphorylate BLNK, providing binding sites for PLCgamma2"]. Independent biochemical work in recombinant PLCG2 and platelets supports Tyr753/Tyr759 as activating phosphorylation sites [PMID:12181444 "phosphorylation of PLCgamma2 led to activation of the recombinant enzyme"; PMID:12181444 "collagen, a PLCgamma2-dependent agonist, induces phosphorylation of PLCgamma2 at Y753 and Y759"].
Protein recruitment annotations should be interpreted specifically, not as generic "protein binding." PLCG2 binds phosphorylated receptor/adaptor motifs via SH2-domain biology and can be regulated by scaffold/adaptor complexes such as BLNK and BANK1. BANK1 work showed that "PLCg2 interacts with BANK1 and that the interaction is promoted by B-cell receptor" stimulation PMID:23555801, with dependence on BANK1 tyrosine/proline residues PMID:23555801. A structural study also supports direct Rac2-dependent activation of PLCG2 PMID:19394299.
PLCG2 has important evolved immune-cell roles. It is central in BCR signaling and calcium mobilization, with BCR pathway reviews emphasizing Syk, Btk, BLNK, PLCG2, IP3, and calcium release [PMID:11043765 "the intracellular protein tyrosine kinases Syk and Btk in PLC-gamma2 activation"; PMID:11043765 "Binding of IP3 to the IP3 receptors is essential for triggering a calcium release from the ER"]. It also functions in platelets and myeloid/microglial cells. In human iPSC-derived microglia-like cells, TREM2 signals through PLCG2 to mediate survival, phagocytosis, neuronal debris processing, and lipid metabolism; PLCG2 also mediates TLR-linked inflammatory responses [PMID:32514138 "TREM2 signals through PLCgamma2 to mediate cell survival, phagocytosis, processing of neuronal debris, and lipid metabolism"; PMID:32514138 "PLCG2 also signals downstream of Toll-like receptors to mediate inflammatory responses"].
For curation, the specific molecular-function term phosphatidylinositol-4,5-bisphosphate phospholipase C activity should be retained as core. Broad terms such as phosphoric diester hydrolase activity, C-type glycerophospholipase activity, lipid metabolic process, and signal transduction are true in spirit but less informative than the specific PIP2 phospholipase and receptor-proximal signaling terms. phosphatidylinositol biosynthetic process is the wrong direction for PLCG2 and should be replaced by phosphatidylinositol-mediated signaling or PIP2 phospholipase activity. Generic protein binding annotations should be modified to phosphotyrosine residue binding/phosphorylation-dependent protein binding when the evidence is SH2-phosphopeptide recruitment, or marked over-annotated when they come from high-throughput interaction screens without a clear PLCG2-specific mechanism.
Second-pass audit confirmed the existing action calls and reference-review
coverage. No YAML changes were needed in this pass.
The single UNDECIDED annotation is GO:1990782 protein tyrosine kinase binding
from PMID:32514138. The cached abstract supports PLCG2 signaling in microglia
but does not expose the full IPI evidence for direct protein tyrosine kinase
binding, so this remains UNDECIDED under the project rule not to overrule
experimental annotations from abstract-only evidence.
The REMOVE annotation for GO:0016055 Wnt signaling pathway remains appropriate:
the cited PMID:18784435 abstract describes Wilms tumor/fetal kidney expression
profiling and lack of PLCG2 expression, not functional PLCG2 involvement in Wnt
signaling.
The core function remains receptor-activated PIP2 phospholipase C activity that
generates IP3 and DAG, plus phosphotyrosine/adaptor-dependent recruitment in
immune receptor signaling complexes. Alzheimer relevance should be captured
through microglial receptor-proximal PLCG2 signaling, calcium/lipid
second-messenger output, phagocytosis, survival, and inflammatory response
biology rather than disease-progression annotations.
id: P16885
gene_symbol: PLCG2
product_type: PROTEIN
status: COMPLETE
taxon:
id: NCBITaxon:9606
label: Homo sapiens
description: '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.'
existing_annotations:
- term:
id: GO:0004435
label: phosphatidylinositol-4,5-bisphosphate phospholipase C activity
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: enables
review:
summary: PLCG2 is a phosphoinositide-specific phospholipase C that
hydrolyzes PIP2 to IP3 and DAG after receptor-induced activation.
action: ACCEPT
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).
- term:
id: GO:0046488
label: phosphatidylinositol metabolic process
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
summary: The annotation is directionally correct but too broad for PLCG2;
the specific biology is PIP2 phospholipase activity and
phosphoinositide-mediated receptor signaling.
action: MODIFY
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_replacement_terms:
- id: GO:0048015
label: phosphatidylinositol-mediated signaling
- term:
id: GO:0010634
label: positive regulation of epithelial cell migration
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
summary: This epithelial migration annotation is weakly connected to
PLC-gamma family signaling but is not characteristic of hematopoietic
PLCG2 biology.
action: MARK_AS_OVER_ANNOTATED
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.
- term:
id: GO:0048015
label: phosphatidylinositol-mediated signaling
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
summary: This captures PLCG2-mediated phosphoinositide signaling downstream
of immune and growth-factor receptor activation.
action: ACCEPT
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).
- term:
id: GO:0032587
label: ruffle membrane
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: is_active_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0051209
label: release of sequestered calcium ion into cytosol
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
summary: PLCG2 produces IP3 downstream of receptor activation, driving
calcium release and calcium-mediated signaling.
action: ACCEPT
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).
- term:
id: GO:0004435
label: phosphatidylinositol-4,5-bisphosphate phospholipase C activity
evidence_type: IEA
original_reference_id: GO_REF:0000120
qualifier: enables
review:
summary: PLCG2 is a phosphoinositide-specific phospholipase C that
hydrolyzes PIP2 to IP3 and DAG after receptor-induced activation.
action: ACCEPT
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).
- term:
id: GO:0006629
label: lipid metabolic process
evidence_type: IEA
original_reference_id: GO_REF:0000002
qualifier: involved_in
review:
summary: The annotation is directionally correct but too broad for PLCG2;
the specific biology is PIP2 phospholipase activity and
phosphoinositide-mediated receptor signaling.
action: MODIFY
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_replacement_terms:
- id: GO:0048015
label: phosphatidylinositol-mediated signaling
- term:
id: GO:0007165
label: signal transduction
evidence_type: IEA
original_reference_id: GO_REF:0000002
qualifier: involved_in
review:
summary: The annotation is directionally correct but too broad for PLCG2;
the specific biology is PIP2 phospholipase activity and
phosphoinositide-mediated receptor signaling.
action: MODIFY
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_replacement_terms:
- id: GO:0048015
label: phosphatidylinositol-mediated signaling
- term:
id: GO:0008081
label: phosphoric diester hydrolase activity
evidence_type: IEA
original_reference_id: GO_REF:0000002
qualifier: enables
review:
summary: The annotation is directionally correct but too broad for PLCG2;
the specific biology is PIP2 phospholipase activity and
phosphoinositide-mediated receptor signaling.
action: MODIFY
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_replacement_terms:
- id: GO:0004435
label: phosphatidylinositol-4,5-bisphosphate phospholipase C activity
- term:
id: GO:0009395
label: phospholipid catabolic process
evidence_type: IEA
original_reference_id: GO_REF:0000002
qualifier: involved_in
review:
summary: The annotation is directionally correct but too broad for PLCG2;
the specific biology is PIP2 phospholipase activity and
phosphoinositide-mediated receptor signaling.
action: MODIFY
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_replacement_terms:
- id: GO:0048015
label: phosphatidylinositol-mediated signaling
- term:
id: GO:0010628
label: positive regulation of gene expression
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: involved_in
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0019722
label: calcium-mediated signaling
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: involved_in
review:
summary: PLCG2 produces IP3 downstream of receptor activation, driving
calcium release and calcium-mediated signaling.
action: ACCEPT
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).
- term:
id: GO:0032587
label: ruffle membrane
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0035556
label: intracellular signal transduction
evidence_type: IEA
original_reference_id: GO_REF:0000120
qualifier: involved_in
review:
summary: The annotation is directionally correct but too broad for PLCG2;
the specific biology is PIP2 phospholipase activity and
phosphoinositide-mediated receptor signaling.
action: MODIFY
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_replacement_terms:
- id: GO:0048015
label: phosphatidylinositol-mediated signaling
- term:
id: GO:0038095
label: Fc-epsilon receptor signaling pathway
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: involved_in
review:
summary: PLCG2 is a receptor-proximal transducer in immune-receptor
pathways, especially BCR, Fc receptor, C-type lectin, and related
hematopoietic signaling.
action: ACCEPT
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).
- term:
id: GO:0045121
label: membrane raft
evidence_type: IEA
original_reference_id: GO_REF:0000120
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0050851
label: antigen receptor-mediated signaling pathway
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: involved_in
review:
summary: PLCG2 is a receptor-proximal transducer in immune-receptor
pathways, especially BCR, Fc receptor, C-type lectin, and related
hematopoietic signaling.
action: ACCEPT
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).
- term:
id: GO:1902533
label: positive regulation of intracellular signal transduction
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: involved_in
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:15644415
qualifier: enables
review:
summary: The interaction evidence reflects PLCG2 SH2-domain or
phosphorylation-dependent recruitment to phosphorylated receptors/adaptors
rather than generic protein binding.
action: MODIFY
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_replacement_terms:
- id: GO:0001784
label: phosphotyrosine residue binding
- id: GO:0140031
label: phosphorylation-dependent protein binding
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:16273093
qualifier: enables
review:
summary: The interaction evidence reflects PLCG2 SH2-domain or
phosphorylation-dependent recruitment to phosphorylated receptors/adaptors
rather than generic protein binding.
action: MODIFY
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_replacement_terms:
- id: GO:0001784
label: phosphotyrosine residue binding
- id: GO:0140031
label: phosphorylation-dependent protein binding
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:24642916
qualifier: enables
review:
summary: The interaction evidence reflects PLCG2 SH2-domain or
phosphorylation-dependent recruitment to phosphorylated receptors/adaptors
rather than generic protein binding.
action: MODIFY
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_replacement_terms:
- id: GO:0001784
label: phosphotyrosine residue binding
- id: GO:0140031
label: phosphorylation-dependent protein binding
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:24658140
qualifier: enables
review:
summary: This generic or high-throughput interaction/localization annotation
does not define PLCG2 core molecular function.
action: MARK_AS_OVER_ANNOTATED
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.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:24728074
qualifier: enables
review:
summary: The interaction evidence reflects PLCG2 SH2-domain or
phosphorylation-dependent recruitment to phosphorylated receptors/adaptors
rather than generic protein binding.
action: MODIFY
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_replacement_terms:
- id: GO:0001784
label: phosphotyrosine residue binding
- id: GO:0140031
label: phosphorylation-dependent protein binding
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:25241761
qualifier: enables
review:
summary: This generic or high-throughput interaction/localization annotation
does not define PLCG2 core molecular function.
action: MARK_AS_OVER_ANNOTATED
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.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:25814554
qualifier: enables
review:
summary: The interaction evidence reflects PLCG2 SH2-domain or
phosphorylation-dependent recruitment to phosphorylated receptors/adaptors
rather than generic protein binding.
action: MODIFY
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_replacement_terms:
- id: GO:0001784
label: phosphotyrosine residue binding
- id: GO:0140031
label: phosphorylation-dependent protein binding
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:31980649
qualifier: enables
review:
summary: This generic or high-throughput interaction/localization annotation
does not define PLCG2 core molecular function.
action: MARK_AS_OVER_ANNOTATED
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.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:33961781
qualifier: enables
review:
summary: This generic or high-throughput interaction/localization annotation
does not define PLCG2 core molecular function.
action: MARK_AS_OVER_ANNOTATED
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.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:35512704
qualifier: enables
review:
summary: This generic or high-throughput interaction/localization annotation
does not define PLCG2 core molecular function.
action: MARK_AS_OVER_ANNOTATED
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.
- term:
id: GO:0001775
label: cell activation
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0001878
label: response to yeast
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0002092
label: positive regulation of receptor internalization
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0002223
label: stimulatory C-type lectin receptor signaling pathway
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: PLCG2 is a receptor-proximal transducer in immune-receptor
pathways, especially BCR, Fc receptor, C-type lectin, and related
hematopoietic signaling.
action: ACCEPT
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).
- term:
id: GO:0002224
label: toll-like receptor signaling pathway
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0002281
label: macrophage activation involved in immune response
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0002732
label: positive regulation of dendritic cell cytokine production
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0005829
label: cytosol
evidence_type: IEA
original_reference_id: GO_REF:0000120
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0030183
label: B cell differentiation
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0032481
label: positive regulation of type I interferon production
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0032733
label: positive regulation of interleukin-10 production
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0032735
label: positive regulation of interleukin-12 production
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0032743
label: positive regulation of interleukin-2 production
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0032747
label: positive regulation of interleukin-23 production
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0032755
label: positive regulation of interleukin-6 production
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0032760
label: positive regulation of tumor necrosis factor production
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0043122
label: regulation of canonical NF-kappaB signal transduction
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0043410
label: positive regulation of MAPK cascade
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0050853
label: B cell receptor signaling pathway
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: PLCG2 is a receptor-proximal transducer in immune-receptor
pathways, especially BCR, Fc receptor, C-type lectin, and related
hematopoietic signaling.
action: ACCEPT
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).
- term:
id: GO:0051209
label: release of sequestered calcium ion into cytosol
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: PLCG2 produces IP3 downstream of receptor activation, driving
calcium release and calcium-mediated signaling.
action: ACCEPT
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).
- term:
id: GO:0061760
label: antifungal innate immune response
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0140031
label: phosphorylation-dependent protein binding
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: enables
review:
summary: PLCG2 contains SH2 domains and is recruited through
phosphorylation-dependent binding to receptor/adaptor motifs.
action: ACCEPT
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).
- term:
id: GO:1990858
label: cellular response to lectin
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0002223
label: stimulatory C-type lectin receptor signaling pathway
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5621481
qualifier: involved_in
review:
summary: PLCG2 is a receptor-proximal transducer in immune-receptor
pathways, especially BCR, Fc receptor, C-type lectin, and related
hematopoietic signaling.
action: ACCEPT
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).
- term:
id: GO:0030168
label: platelet activation
evidence_type: TAS
original_reference_id: Reactome:R-HSA-76002
qualifier: involved_in
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0038095
label: Fc-epsilon receptor signaling pathway
evidence_type: TAS
original_reference_id: Reactome:R-HSA-2454202
qualifier: involved_in
review:
summary: PLCG2 is a receptor-proximal transducer in immune-receptor
pathways, especially BCR, Fc receptor, C-type lectin, and related
hematopoietic signaling.
action: ACCEPT
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).
- term:
id: GO:0004435
label: phosphatidylinositol-4,5-bisphosphate phospholipase C activity
evidence_type: TAS
original_reference_id: Reactome:R-HSA-2730847
qualifier: enables
review:
summary: PLCG2 is a phosphoinositide-specific phospholipase C that
hydrolyzes PIP2 to IP3 and DAG after receptor-induced activation.
action: ACCEPT
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).
- term:
id: GO:0004435
label: phosphatidylinositol-4,5-bisphosphate phospholipase C activity
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5607735
qualifier: enables
review:
summary: PLCG2 is a phosphoinositide-specific phospholipase C that
hydrolyzes PIP2 to IP3 and DAG after receptor-induced activation.
action: ACCEPT
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).
- term:
id: GO:0004629
label: C-type glycerophospholipase activity
evidence_type: TAS
original_reference_id: Reactome:R-HSA-1112666
qualifier: enables
review:
summary: The annotation is directionally correct but too broad for PLCG2;
the specific biology is PIP2 phospholipase activity and
phosphoinositide-mediated receptor signaling.
action: MODIFY
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_replacement_terms:
- id: GO:0004435
label: phosphatidylinositol-4,5-bisphosphate phospholipase C activity
- term:
id: GO:0004629
label: C-type glycerophospholipase activity
evidence_type: TAS
original_reference_id: Reactome:R-HSA-114689
qualifier: enables
review:
summary: The annotation is directionally correct but too broad for PLCG2;
the specific biology is PIP2 phospholipase activity and
phosphoinositide-mediated receptor signaling.
action: MODIFY
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_replacement_terms:
- id: GO:0004435
label: phosphatidylinositol-4,5-bisphosphate phospholipase C activity
- term:
id: GO:0035556
label: intracellular signal transduction
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: The annotation is directionally correct but too broad for PLCG2;
the specific biology is PIP2 phospholipase activity and
phosphoinositide-mediated receptor signaling.
action: MODIFY
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_replacement_terms:
- id: GO:0048015
label: phosphatidylinositol-mediated signaling
- term:
id: GO:0004435
label: phosphatidylinositol-4,5-bisphosphate phospholipase C activity
evidence_type: EXP
original_reference_id: PMID:23000145
qualifier: enables
review:
summary: PLCG2 is a phosphoinositide-specific phospholipase C that
hydrolyzes PIP2 to IP3 and DAG after receptor-induced activation.
action: ACCEPT
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).
- term:
id: GO:0045121
label: membrane raft
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0010628
label: positive regulation of gene expression
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: acts_upstream_of
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0043123
label: positive regulation of canonical NF-kappaB signal transduction
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:1902533
label: positive regulation of intracellular signal transduction
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0042113
label: B cell activation
evidence_type: IDA
original_reference_id: PMID:30107486
qualifier: involved_in
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0032755
label: positive regulation of interleukin-6 production
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0048471
label: perinuclear region of cytoplasm
evidence_type: IDA
original_reference_id: PMID:23555801
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0050853
label: B cell receptor signaling pathway
evidence_type: TAS
original_reference_id: PMID:23555801
qualifier: involved_in
review:
summary: PLCG2 is a receptor-proximal transducer in immune-receptor
pathways, especially BCR, Fc receptor, C-type lectin, and related
hematopoietic signaling.
action: ACCEPT
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).
- term:
id: GO:0097110
label: scaffold protein binding
evidence_type: IPI
original_reference_id: PMID:23555801
qualifier: enables
review:
summary: PLCG2 binds kinase/scaffold/adaptor proteins that recruit and
activate it in immune-receptor signaling complexes.
action: ACCEPT
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).
- term:
id: GO:0004435
label: phosphatidylinositol-4,5-bisphosphate phospholipase C activity
evidence_type: IMP
original_reference_id: PMID:32514138
qualifier: enables
review:
summary: PLCG2 is a phosphoinositide-specific phospholipase C that
hydrolyzes PIP2 to IP3 and DAG after receptor-induced activation.
action: ACCEPT
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).
- term:
id: GO:0010628
label: positive regulation of gene expression
evidence_type: IMP
original_reference_id: PMID:32514138
qualifier: acts_upstream_of_or_within
review:
summary: Human microglia-like cell experiments support PLCG2 downstream of
TREM2 for phagocytosis, lipid handling, survival, transcriptional
responses, and inflammatory signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0019216
label: regulation of lipid metabolic process
evidence_type: IMP
original_reference_id: PMID:32514138
qualifier: acts_upstream_of
review:
summary: Human microglia-like cell experiments support PLCG2 downstream of
TREM2 for phagocytosis, lipid handling, survival, transcriptional
responses, and inflammatory signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0031663
label: lipopolysaccharide-mediated signaling pathway
evidence_type: IMP
original_reference_id: PMID:32514138
qualifier: involved_in
review:
summary: Human microglia-like cell experiments support PLCG2 downstream of
TREM2 for phagocytosis, lipid handling, survival, transcriptional
responses, and inflammatory signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0035556
label: intracellular signal transduction
evidence_type: IMP
original_reference_id: PMID:32514138
qualifier: involved_in
review:
summary: The annotation is directionally correct but too broad for PLCG2;
the specific biology is PIP2 phospholipase activity and
phosphoinositide-mediated receptor signaling.
action: MODIFY
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_replacement_terms:
- id: GO:0048015
label: phosphatidylinositol-mediated signaling
- term:
id: GO:0048678
label: response to axon injury
evidence_type: IMP
original_reference_id: PMID:32514138
qualifier: involved_in
review:
summary: Human microglia-like cell experiments support PLCG2 downstream of
TREM2 for phagocytosis, lipid handling, survival, transcriptional
responses, and inflammatory signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0060100
label: positive regulation of phagocytosis, engulfment
evidence_type: IMP
original_reference_id: PMID:32514138
qualifier: acts_upstream_of_or_within
review:
summary: Human microglia-like cell experiments support PLCG2 downstream of
TREM2 for phagocytosis, lipid handling, survival, transcriptional
responses, and inflammatory signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0071396
label: cellular response to lipid
evidence_type: IMP
original_reference_id: PMID:32514138
qualifier: involved_in
review:
summary: Human microglia-like cell experiments support PLCG2 downstream of
TREM2 for phagocytosis, lipid handling, survival, transcriptional
responses, and inflammatory signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0150078
label: positive regulation of neuroinflammatory response
evidence_type: IMP
original_reference_id: PMID:32514138
qualifier: involved_in
review:
summary: Human microglia-like cell experiments support PLCG2 downstream of
TREM2 for phagocytosis, lipid handling, survival, transcriptional
responses, and inflammatory signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:1900227
label: positive regulation of NLRP3 inflammasome complex assembly
evidence_type: IMP
original_reference_id: PMID:32514138
qualifier: acts_upstream_of_or_within
review:
summary: Human microglia-like cell experiments support PLCG2 downstream of
TREM2 for phagocytosis, lipid handling, survival, transcriptional
responses, and inflammatory signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:1990782
label: protein tyrosine kinase binding
evidence_type: IPI
original_reference_id: PMID:32514138
qualifier: enables
review:
summary: The cached abstract supports PLCG2 signaling in microglia but does
not show the specific protein tyrosine kinase binding assertion.
action: UNDECIDED
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).
- term:
id: GO:0001775
label: cell activation
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0001878
label: response to yeast
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0002223
label: stimulatory C-type lectin receptor signaling pathway
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: PLCG2 is a receptor-proximal transducer in immune-receptor
pathways, especially BCR, Fc receptor, C-type lectin, and related
hematopoietic signaling.
action: ACCEPT
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).
- term:
id: GO:0002224
label: toll-like receptor signaling pathway
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0002281
label: macrophage activation involved in immune response
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0002732
label: positive regulation of dendritic cell cytokine production
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0032733
label: positive regulation of interleukin-10 production
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0032735
label: positive regulation of interleukin-12 production
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0032743
label: positive regulation of interleukin-2 production
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0032747
label: positive regulation of interleukin-23 production
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0032760
label: positive regulation of tumor necrosis factor production
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0043122
label: regulation of canonical NF-kappaB signal transduction
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0043410
label: positive regulation of MAPK cascade
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0050850
label: positive regulation of calcium-mediated signaling
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: acts_upstream_of_or_within
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0060907
label: positive regulation of macrophage cytokine production
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: acts_upstream_of
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0061760
label: antifungal innate immune response
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0070884
label: regulation of calcineurin-NFAT signaling cascade
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: acts_upstream_of_or_within
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:1903428
label: positive regulation of reactive oxygen species biosynthetic process
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: acts_upstream_of
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:1990858
label: cellular response to lectin
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0005737
label: cytoplasm
evidence_type: IDA
original_reference_id: PMID:11331309
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0005886
label: plasma membrane
evidence_type: IDA
original_reference_id: PMID:11331309
qualifier: is_active_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0032587
label: ruffle membrane
evidence_type: IDA
original_reference_id: PMID:11331309
qualifier: is_active_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0035556
label: intracellular signal transduction
evidence_type: IDA
original_reference_id: PMID:14656219
qualifier: involved_in
review:
summary: The annotation is directionally correct but too broad for PLCG2;
the specific biology is PIP2 phospholipase activity and
phosphoinositide-mediated receptor signaling.
action: MODIFY
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_replacement_terms:
- id: GO:0048015
label: phosphatidylinositol-mediated signaling
- term:
id: GO:0050853
label: B cell receptor signaling pathway
evidence_type: IDA
original_reference_id: PMID:15509800
qualifier: involved_in
review:
summary: PLCG2 is a receptor-proximal transducer in immune-receptor
pathways, especially BCR, Fc receptor, C-type lectin, and related
hematopoietic signaling.
action: ACCEPT
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).
- term:
id: GO:0097708
label: intracellular vesicle
evidence_type: IDA
original_reference_id: PMID:11331309
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0005886
label: plasma membrane
evidence_type: IDA
original_reference_id: PMID:11606584
qualifier: is_active_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0019901
label: protein kinase binding
evidence_type: IPI
original_reference_id: PMID:11606584
qualifier: enables
review:
summary: PLCG2 binds kinase/scaffold/adaptor proteins that recruit and
activate it in immune-receptor signaling complexes.
action: ACCEPT
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).
- term:
id: GO:0035556
label: intracellular signal transduction
evidence_type: IDA
original_reference_id: PMID:11606584
qualifier: involved_in
review:
summary: The annotation is directionally correct but too broad for PLCG2;
the specific biology is PIP2 phospholipase activity and
phosphoinositide-mediated receptor signaling.
action: MODIFY
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_replacement_terms:
- id: GO:0048015
label: phosphatidylinositol-mediated signaling
- term:
id: GO:0050853
label: B cell receptor signaling pathway
evidence_type: IMP
original_reference_id: PMID:11606584
qualifier: involved_in
review:
summary: PLCG2 is a receptor-proximal transducer in immune-receptor
pathways, especially BCR, Fc receptor, C-type lectin, and related
hematopoietic signaling.
action: ACCEPT
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).
- term:
id: GO:0097110
label: scaffold protein binding
evidence_type: IPI
original_reference_id: PMID:11606584
qualifier: enables
review:
summary: PLCG2 binds kinase/scaffold/adaptor proteins that recruit and
activate it in immune-receptor signaling complexes.
action: ACCEPT
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).
- term:
id: GO:1902808
label: positive regulation of cell cycle G1/S phase transition
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0019722
label: calcium-mediated signaling
evidence_type: IMP
original_reference_id: PMID:11606584
qualifier: involved_in
review:
summary: PLCG2 produces IP3 downstream of receptor activation, driving
calcium release and calcium-mediated signaling.
action: ACCEPT
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).
- term:
id: GO:0071277
label: cellular response to calcium ion
evidence_type: IMP
original_reference_id: PMID:11606584
qualifier: involved_in
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0001784
label: phosphotyrosine residue binding
evidence_type: IPI
original_reference_id: PMID:20624904
qualifier: enables
review:
summary: PLCG2 contains SH2 domains and is recruited through
phosphorylation-dependent binding to receptor/adaptor motifs.
action: ACCEPT
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).
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5607755
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5621347
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5621363
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5607735
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5607755
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5621347
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0070062
label: extracellular exosome
evidence_type: HDA
original_reference_id: PMID:20458337
qualifier: located_in
review:
summary: This generic or high-throughput interaction/localization annotation
does not define PLCG2 core molecular function.
action: MARK_AS_OVER_ANNOTATED
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).
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-2029268
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-2029270
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-2396594
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-2396606
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-2424476
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-2424481
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-2424484
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-2424486
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-2424487
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-2730833
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-2730840
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-2730841
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-2730851
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-2730856
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-2730858
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-2730889
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-2730892
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9606151
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9606894
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9664270
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9664278
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9691421
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-1112666
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-202407
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-2029268
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-2029272
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-2424485
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-2424487
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-2730847
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9664271
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9664278
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-114689
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-1855221
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-429497
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0016055
label: Wnt signaling pathway
evidence_type: TAS
original_reference_id: PMID:18784435
qualifier: involved_in
review:
summary: The cited Wilms tumor expression study does not establish PLCG2 as
a Wnt signaling pathway component.
action: REMOVE
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).
- term:
id: GO:0004435
label: phosphatidylinositol-4,5-bisphosphate phospholipase C activity
evidence_type: IDA
original_reference_id: PMID:11606584
qualifier: enables
review:
summary: PLCG2 is a phosphoinositide-specific phospholipase C that
hydrolyzes PIP2 to IP3 and DAG after receptor-induced activation.
action: ACCEPT
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).
- term:
id: GO:0004435
label: phosphatidylinositol-4,5-bisphosphate phospholipase C activity
evidence_type: IDA
original_reference_id: PMID:12181444
qualifier: enables
review:
summary: PLCG2 is a phosphoinositide-specific phospholipase C that
hydrolyzes PIP2 to IP3 and DAG after receptor-induced activation.
action: ACCEPT
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).
- term:
id: GO:0005886
label: plasma membrane
evidence_type: IDA
original_reference_id: PMID:11606584
qualifier: located_in
review:
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.
action: ACCEPT
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).
- term:
id: GO:0006661
label: phosphatidylinositol biosynthetic process
evidence_type: IDA
original_reference_id: PMID:11606584
qualifier: involved_in
review:
summary: PLCG2 hydrolyzes PIP2 rather than synthesizing phosphatidylinositol
lipids.
action: MODIFY
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_replacement_terms:
- id: GO:0048015
label: phosphatidylinositol-mediated signaling
- term:
id: GO:0006661
label: phosphatidylinositol biosynthetic process
evidence_type: IDA
original_reference_id: PMID:12181444
qualifier: involved_in
review:
summary: PLCG2 hydrolyzes PIP2 rather than synthesizing phosphatidylinositol
lipids.
action: MODIFY
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_replacement_terms:
- id: GO:0048015
label: phosphatidylinositol-mediated signaling
- term:
id: GO:0019722
label: calcium-mediated signaling
evidence_type: NAS
original_reference_id: PMID:11043765
qualifier: involved_in
review:
summary: PLCG2 produces IP3 downstream of receptor activation, driving
calcium release and calcium-mediated signaling.
action: ACCEPT
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).
- term:
id: GO:0030183
label: B cell differentiation
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: This immune-cell process is a plausible downstream or
cell-type-specific outcome of PLCG2 receptor signaling.
action: KEEP_AS_NON_CORE
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).
- term:
id: GO:0050852
label: T cell receptor signaling pathway
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: This annotation is plausible for PLCG2 but was not central to the
reviewed catalytic/receptor-proximal mechanism.
action: KEEP_AS_NON_CORE
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.
- term:
id: GO:0050853
label: B cell receptor signaling pathway
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: PLCG2 is a receptor-proximal transducer in immune-receptor
pathways, especially BCR, Fc receptor, C-type lectin, and related
hematopoietic signaling.
action: ACCEPT
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).
- term:
id: GO:0051209
label: release of sequestered calcium ion into cytosol
evidence_type: IDA
original_reference_id: PMID:11606584
qualifier: involved_in
review:
summary: PLCG2 produces IP3 downstream of receptor activation, driving
calcium release and calcium-mediated signaling.
action: ACCEPT
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).
references:
- id: GO_REF:0000002
title: Gene Ontology annotation through association of InterPro records with
GO terms
findings: []
- id: GO_REF:0000024
title: Manual transfer of experimentally-verified manual GO annotation data to
orthologs by curator judgment of sequence similarity
findings: []
- id: GO_REF:0000033
title: Annotation inferences using phylogenetic trees
findings: []
- id: GO_REF:0000107
title: Automatic transfer of experimentally verified manual GO annotation data
to orthologs using Ensembl Compara
findings: []
- id: GO_REF:0000117
title: Electronic Gene Ontology annotations created by ARBA machine learning
models
findings: []
- id: GO_REF:0000120
title: Combined Automated Annotation using Multiple IEA Methods
findings: []
- id: PMID:11043765
title: Regulation of the phospholipase C-gamma2 pathway in B cells.
findings: []
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: Cached abstract directly supports BCR PLCG2-calcium pathway,
Syk/Btk/BLNK recruitment, and PIP2-to-IP3 signaling.
- id: PMID:11331309
title: Real time fluorescence imaging of PLC gamma translocation and its
interaction with the epidermal growth factor receptor.
findings: []
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: Cached full text supports PLC-gamma membrane/ruffle
translocation, receptor binding, substrate access, and vesicle
internalization; used for PLCG2 localization by isoform-conserved
mechanism.
- id: PMID:11606584
title: Tyrosine residues in phospholipase Cgamma 2 essential for the enzyme
function in B-cell signaling.
findings: []
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: Cached abstract directly supports Tyr753/Tyr759 function,
BTK/SYK/BLNK mechanism, calcium responses, and kinase/scaffold binding
decisions.
- id: PMID:12181444
title: Activation of phospholipase Cgamma2 by tyrosine phosphorylation.
findings: []
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: Cached abstract directly supports recombinant PLCG2 catalytic
activation by tyrosine phosphorylation and platelet Tyr753/Tyr759
phosphorylation.
- id: PMID:14656219
title: Glycoproteins VI and Ib-IX-V stimulate tyrosine phosphorylation of
tyrosine kinase Syk and phospholipase Cgamma2 at distinct sites.
findings: []
- id: PMID:15509800
title: Mechanism of B-cell receptor-induced phosphorylation and activation of
phospholipase C-gamma2.
findings: []
- id: PMID:15644415
title: A systematic scan of interactions with tyrosine motifs in the
erythropoietin receptor using a mammalian 2-hybrid approach.
findings: []
- id: PMID:16273093
title: A quantitative protein interaction network for the ErbB receptors using
protein microarrays.
findings: []
- id: PMID:18784435
title: Molecular profiling of isolated histological components of wilms tumor
implicates a common role for the Wnt signaling pathway in kidney and tumor
development.
findings: []
reference_review:
relevance: LOW
correctness: MISCITED
review_notes: Cached abstract is an expression-profiling Wilms tumor paper
and does not establish PLCG2 as a Wnt signaling component; used to remove
the Wnt annotation.
- id: PMID:20458337
title: MHC class II-associated proteins in B-cell exosomes and potential
functional implications for exosome biogenesis.
findings: []
reference_review:
relevance: LOW
correctness: VERIFIED
review_notes: Cached abstract supports B-cell exosome proteomics detection
only; relevant to over-annotation decision for extracellular exosome.
- id: PMID:20624904
title: Tarp regulates early Chlamydia-induced host cell survival through
interactions with the human adaptor protein SHC1.
findings: []
- id: PMID:23000145
title: A hypermorphic missense mutation in PLCG2, encoding phospholipase Cγ2,
causes a dominantly inherited autoinflammatory disease with
immunodeficiency.
findings: []
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: Cached abstract supports PLCG2 phospholipase activity and
immune-pathway dysregulation from a hypermorphic PLCG2 variant.
- id: PMID:23555801
title: BANK1 and BLK act through phospholipase C gamma 2 in B-cell signaling.
findings: []
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: Cached full text supports BANK1-PLCG2 interaction promoted by
BCR stimulation and dependent on tyrosine/proline residues.
- id: PMID:24642916
title: Fine specificity and molecular competition in SLAM family receptor
signalling.
findings: []
- id: PMID:24658140
title: The mammalian-membrane two-hybrid assay (MaMTH) for probing
membrane-protein interactions in human cells.
findings: []
- id: PMID:24728074
title: Enhanced prediction of Src homology 2 (SH2) domain binding potentials
using a fluorescence polarization-derived c-Met, c-Kit, ErbB, and androgen
receptor interactome.
findings: []
- id: PMID:25241761
title: Using an in situ proximity ligation assay to systematically profile
endogenous protein-protein interactions in a pathway network.
findings: []
- id: PMID:25814554
title: Phospho-tyrosine dependent protein-protein interaction network.
findings: []
- id: PMID:30107486
title: CD21 and FCRL5 form a receptor complex with robust B-cell activating
capacity.
findings: []
- id: PMID:31980649
title: Extensive rewiring of the EGFR network in colorectal cancer cells
expressing transforming levels of KRAS(G13D).
findings: []
- id: PMID:32514138
title: Alzheimer's-associated PLCγ2 is a signaling node required for both
TREM2 function and the inflammatory response in human microglia.
findings: []
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: Cached abstract supports PLCG2 downstream of TREM2 and TLR
signaling in human microglia-like cells, including phagocytosis, lipid
metabolism, transcriptional and inflammatory phenotypes.
- id: PMID:33961781
title: Dual proteome-scale networks reveal cell-specific remodeling of the
human interactome.
findings: []
- id: PMID:35512704
title: Systematic discovery of mutation-directed neo-protein-protein
interactions in cancer.
findings: []
- id: Reactome:R-HSA-1112666
title: BLNK (SLP-65) Signalosome hydrolyzes phosphatidyinositol bisphosphate
forming diacylglycerol and inositol-1,4,5-trisphosphate
findings: []
- id: Reactome:R-HSA-114689
title: PLC gamma 2-mediated PIP2 hydrolysis
findings: []
- id: Reactome:R-HSA-1855221
title: PI(4,5)P2 is hydrolysed to I(1,4,5)P3 and DAG by tethered PLC[1] at the
plasma membrane
findings: []
- id: Reactome:R-HSA-202407
title: PLC-gamma1 hydrolyses PIP2
findings: []
- id: Reactome:R-HSA-2029268
title: Phosphorylation and activation of PLCG
findings: []
- id: Reactome:R-HSA-2029270
title: Recruitment of PLCgamma to membrane
findings: []
- id: Reactome:R-HSA-2029272
title: Release of PLCG from FCGR
findings: []
- id: Reactome:R-HSA-2396594
title: Phosphorylation of SLP-76 by p-SYK
findings: []
- id: Reactome:R-HSA-2396606
title: Recruitment of PLC-gamma to SLP-76 and p-5Y-LAT
findings: []
- id: Reactome:R-HSA-2424476
title: Activation of RAC1 by VAV2/3
findings: []
- id: Reactome:R-HSA-2424481
title: Recruitment of VAV and BTK to p-SLP-76
findings: []
- id: Reactome:R-HSA-2424484
title: Phosphorylation of BTK by p-SYK
findings: []
- id: Reactome:R-HSA-2424485
title: Release of p-PLCG1
findings: []
- id: Reactome:R-HSA-2424486
title: Phosphorylation and activation of VAV2/VAV3 by SYK
findings: []
- id: Reactome:R-HSA-2424487
title: Phosphorylation of PLC-gamma by p-BTK/p-SYK
findings: []
- id: Reactome:R-HSA-2454202
title: Fc epsilon receptor (FCERI) signaling
findings: []
- id: Reactome:R-HSA-2730833
title: Phosphorylation of TEC kinases by p-SYK
findings: []
- id: Reactome:R-HSA-2730840
title: Activation of RAC1 by VAV
findings: []
- id: Reactome:R-HSA-2730841
title: Phosphorylation and activation of VAV
findings: []
- id: Reactome:R-HSA-2730847
title: Hydrolysis of PIP2 by PLCG
findings: []
- id: Reactome:R-HSA-2730851
title: Phosphorylation of SLP-76 by p-SYK
findings: []
- id: Reactome:R-HSA-2730856
title: Autophosphorylation of PAK
findings: []
- id: Reactome:R-HSA-2730858
title: Autophosphorylation of BTK/ITK
findings: []
- id: Reactome:R-HSA-2730889
title: Recruitment of PAK to the membrane by binding active RAC1
findings: []
- id: Reactome:R-HSA-2730892
title: Recruitment of VAV to p-SLP-76
findings: []
- id: Reactome:R-HSA-429497
title: SLP-76 stimulates PLC gamma 2
findings: []
- id: Reactome:R-HSA-5607735
title: p-Y753,Y759-PLCG2 hydrolyses PIP2
findings: []
- id: Reactome:R-HSA-5607755
title: p-Y753,Y759-PLCG2 translocates from cytosol to plasma membrane
findings: []
- id: Reactome:R-HSA-5621347
title: PLCG2 translocates from cytosol to plasma membrane
findings: []
- id: Reactome:R-HSA-5621363
title: SYK phosphorylates PLCG2 in p-6Y-SYK:p-Y65,Y76-FCER1G:PLCG2
findings: []
- id: Reactome:R-HSA-5621481
title: C-type lectin receptors (CLRs)
findings: []
- id: Reactome:R-HSA-76002
title: Platelet activation, signaling and aggregation
findings: []
- id: Reactome:R-HSA-9606151
title: Phosphorylated BLNK (SLP65, in
Antigen:p-BCR:p-SYK:p-BLNK:CIN85:GRB2:SOS1) binds BTK, PLCG2, VAV1, NCK1
findings: []
- id: Reactome:R-HSA-9606894
title: p-DAPP1 (p-BAM32) binds PLCG2
findings: []
- id: Reactome:R-HSA-9664270
title: Recruitment of PLCgamma to membrane due to FCGR3A effect
findings: []
- id: Reactome:R-HSA-9664271
title: Release of PLCG from FCGR3A
findings: []
- id: Reactome:R-HSA-9664278
title: Phosphorylation and activation of PLCG due to FCGR3A effect
findings: []
- id: Reactome:R-HSA-9691421
title: BTK binds BTK inhibitors
findings: []
- id: PMID:19394299
title: Structural insights into formation of an active signaling complex
between Rac and phospholipase C gamma 2.
findings: []
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: Cached PubMed abstract; supports direct Rac2/spPH-domain
interaction and PLCG2 activation mechanism.
- id: PMID:22236196
title: Cold urticaria, immunodeficiency, and autoimmunity related to PLCG2
deletions.
findings: []
reference_review:
relevance: MEDIUM
correctness: VERIFIED
review_notes: Cached full text; supports human immune-dysregulation
relevance of PLCG2 variants, but is not central to GO term decisions.
core_functions:
- description: Receptor-activated phosphatidylinositol 4,5-bisphosphate
phospholipase C activity that generates IP3 and DAG, coupling immune and
growth-factor receptor inputs to calcium and lipid second-messenger
signaling.
supported_by:
- reference_id: PMID:11043765
supporting_text: The activated PLC-gamma2 converts phosphatidylinositol
4,5-bisphosphate into the second messenger inositol 1,4,5-trisphosphate
(IP3)
- reference_id: PMID:12181444
supporting_text: phosphorylation of PLCgamma2 led to activation of the
recombinant enzyme
- reference_id: PMID:23000145
supporting_text: PLCG2 encodes phospholipase Cgamma2 (PLCgamma2), an enzyme
with a critical regulatory role in various immune and inflammatory
pathways.
molecular_function:
id: GO:0004435
label: phosphatidylinositol-4,5-bisphosphate phospholipase C activity
directly_involved_in:
- id: GO:0048015
label: phosphatidylinositol-mediated signaling
- id: GO:0051209
label: release of sequestered calcium ion into cytosol
- id: GO:0019722
label: calcium-mediated signaling
locations:
- id: GO:0005829
label: cytosol
- id: GO:0005886
label: plasma membrane
- id: GO:0045121
label: membrane raft
- id: GO:0032587
label: ruffle membrane
- description: Phosphorylation-dependent recruitment and activation in
immune-receptor signaling complexes through SH2/phosphotyrosine, kinase,
scaffold, and small GTPase-linked interactions.
supported_by:
- reference_id: PMID:11606584
supporting_text: function of Syk is to phosphorylate BLNK, providing binding
sites for PLCgamma2
- reference_id: PMID:23555801
supporting_text: PLCg2 interacts with BANK1 and that the interaction is
promoted by B-cell receptor
- reference_id: PMID:19394299
supporting_text: the crystal structure of the complex of Rac2 bound to the
split pleckstrin homology (spPH) domain of phospholipase C-gamma(2)
molecular_function:
id: GO:0001784
label: phosphotyrosine residue binding
directly_involved_in:
- id: GO:0050853
label: B cell receptor signaling pathway
- id: GO:0050851
label: antigen receptor-mediated signaling pathway
- id: GO:0002223
label: stimulatory C-type lectin receptor signaling pathway
locations:
- id: GO:0005829
label: cytosol
- id: GO:0005886
label: plasma membrane
- id: GO:0045121
label: membrane raft
suggested_questions:
- question: Which PLCG2 receptor contexts should be considered core across
hematopoietic and microglial biology rather than retained as
cell-type-specific downstream processes?
- question: 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?
- question: Should Reactome PLCG1/PLCG entity-set events that annotate PLCG2 be
split or qualified to avoid isoform ambiguity?
suggested_experiments:
- hypothesis: Endogenous PLCG2 has receptor-context-specific activation kinetics
in microglia and macrophages.
description: 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.
experiment_type: primary-cell signaling time course
- hypothesis: SH2-domain recruitment and Rac-dependent activation make separable
contributions to PLCG2 signaling output.
description: Use PLCG2 SH2-domain and Rac-binding mutants to separate
phosphotyrosine-adaptor recruitment from Rac-dependent activation in
immune-cell signaling assays.
experiment_type: mutational structure-function assay
- hypothesis: Alzheimer-associated PLCG2 variants alter receptor-proximal
phospholipase activity and downstream microglial phenotypes.
description: 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.
experiment_type: iPSC-derived microglia variant assay