TREM2 is a type I plasma-membrane immunoglobulin-superfamily receptor expressed mainly by microglia and other myeloid-lineage cells. Together with the TYROBP/DAP12 adaptor, TREM2 converts ligand binding at the cell surface into intracellular signaling through kinases and PLCG2-linked pathways that support cell survival, calcium/ERK signaling, phagocytosis, chemotaxis, microglial activation, and lipid handling. TREM2 recognizes lipid-rich and damage-associated ligands, including aminophospholipids exposed on apoptotic cells, lipoprotein particles and apolipoproteins, and amyloid-beta-lipoprotein complexes. Disease-model annotations involving amyloid plaques, synapse pruning, neuroinflammation, osteoclast biology, and dendritic cell maturation are important contexts but are secondary to the core receptor-ligand signaling and phagocytic myeloid-cell functions.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
|
GO:0005886
plasma membrane
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface receptor role.
Reason: Cell-surface/plasma-membrane localization is essential for ligand binding and DAP12/TYROBP-mediated signal transduction.
Supporting Evidence:
PMID:11602640
TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is associated with DAP12.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:27995897
Nasu-Hakola mutations impact protein stability and decrease folded TREM2 surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
|
|
GO:0004888
transmembrane signaling receptor activity
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: TREM2 transmembrane signaling receptor activity is a core plasma-membrane receptor function coupled to TYROBP/DAP12 signaling.
Reason: TREM2 is a myeloid/microglial cell-surface receptor whose ligand engagement drives intracellular signaling through DAP12/TYROBP-linked kinase pathways.
Supporting Evidence:
PMID:11602640
TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is associated with DAP12.
PMID:11602640
TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC maturation, and DC survival through activation of protein tyrosine kinases and extracellular signal-regulated kinase.
PMID:32514138
TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis, processing of neuronal debris, and lipid metabolism.
|
|
GO:0007165
signal transduction
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: signal transduction is a core downstream consequence of TREM2 receptor signaling.
Reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support calcium/ERK/PI3K-related activation and intracellular signaling.
Supporting Evidence:
PMID:11602640
TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC maturation, and DC survival through activation of protein tyrosine kinases and extracellular signal-regulated kinase.
PMID:32514138
TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis, processing of neuronal debris, and lipid metabolism.
|
|
GO:0045088
regulation of innate immune response
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: regulation of innate immune response is a core downstream consequence of TREM2 receptor signaling.
Reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support calcium/ERK/PI3K-related activation and intracellular signaling.
Supporting Evidence:
PMID:11602640
TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC maturation, and DC survival through activation of protein tyrosine kinases and extracellular signal-regulated kinase.
PMID:32514138
TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis, processing of neuronal debris, and lipid metabolism.
|
|
GO:0050850
positive regulation of calcium-mediated signaling
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: positive regulation of calcium-mediated signaling is a core downstream consequence of TREM2 receptor signaling.
Reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support calcium/ERK/PI3K-related activation and intracellular signaling.
Supporting Evidence:
PMID:11602640
TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC maturation, and DC survival through activation of protein tyrosine kinases and extracellular signal-regulated kinase.
PMID:32514138
TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis, processing of neuronal debris, and lipid metabolism.
|
|
GO:0060100
positive regulation of phagocytosis, engulfment
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: positive regulation of phagocytosis, engulfment is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment, activation, and migration responses.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:0070374
positive regulation of ERK1 and ERK2 cascade
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: positive regulation of ERK1 and ERK2 cascade is a core downstream consequence of TREM2 receptor signaling.
Reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support calcium/ERK/PI3K-related activation and intracellular signaling.
Supporting Evidence:
PMID:11602640
TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC maturation, and DC survival through activation of protein tyrosine kinases and extracellular signal-regulated kinase.
PMID:32514138
TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis, processing of neuronal debris, and lipid metabolism.
|
|
GO:0120035
regulation of plasma membrane bounded cell projection organization
|
IBA
GO_REF:0000033 |
KEEP AS NON CORE |
Summary: regulation of plasma membrane bounded cell projection organization is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:1903980
positive regulation of microglial cell activation
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: positive regulation of microglial cell activation is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment, activation, and migration responses.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:0004888
transmembrane signaling receptor activity
|
IEA
GO_REF:0000117 |
ACCEPT |
Summary: TREM2 transmembrane signaling receptor activity is a core plasma-membrane receptor function coupled to TYROBP/DAP12 signaling.
Reason: TREM2 is a myeloid/microglial cell-surface receptor whose ligand engagement drives intracellular signaling through DAP12/TYROBP-linked kinase pathways.
Supporting Evidence:
PMID:11602640
TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is associated with DAP12.
PMID:11602640
TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC maturation, and DC survival through activation of protein tyrosine kinases and extracellular signal-regulated kinase.
PMID:32514138
TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis, processing of neuronal debris, and lipid metabolism.
|
|
GO:0005576
extracellular region
|
IEA
GO_REF:0000044 |
KEEP AS NON CORE |
Summary: The extracellular-region annotation likely reflects secreted or shed TREM2 isoforms/fragments rather than the core membrane receptor.
Reason: Retain as non-core because soluble TREM2 biology is relevant, but the primary TREM2 function is cell-surface receptor signaling.
|
|
GO:0005886
plasma membrane
|
IEA
GO_REF:0000120 |
ACCEPT |
Summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface receptor role.
Reason: Cell-surface/plasma-membrane localization is essential for ligand binding and DAP12/TYROBP-mediated signal transduction.
Supporting Evidence:
PMID:11602640
TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is associated with DAP12.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:27995897
Nasu-Hakola mutations impact protein stability and decrease folded TREM2 surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
|
|
GO:0006909
phagocytosis
|
IEA
GO_REF:0000117 |
ACCEPT |
Summary: phagocytosis is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment, activation, and migration responses.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:0008289
lipid binding
|
IEA
GO_REF:0000117 |
ACCEPT |
Summary: TREM2 lipid binding is part of its ligand-sensing receptor biology.
Reason: TREM2 ligand recognition includes lipid-rich particles and supports microglial lipid handling.
Supporting Evidence:
PMID:27477018
we identified a set of lipoprotein particles (including LDL) and apolipoproteins (including CLU/APOJ and APOE) as ligands
PMID:31902528
TREM2 senses lipids and mediates myelin phagocytosis
|
|
GO:0035176
social behavior
|
IEA
GO_REF:0000117 |
KEEP AS NON CORE |
Summary: social behavior is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:0048468
cell development
|
IEA
GO_REF:0000117 |
KEEP AS NON CORE |
Summary: cell development is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:0050850
positive regulation of calcium-mediated signaling
|
IEA
GO_REF:0000117 |
ACCEPT |
Summary: positive regulation of calcium-mediated signaling is a core downstream consequence of TREM2 receptor signaling.
Reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support calcium/ERK/PI3K-related activation and intracellular signaling.
Supporting Evidence:
PMID:11602640
TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC maturation, and DC survival through activation of protein tyrosine kinases and extracellular signal-regulated kinase.
PMID:32514138
TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis, processing of neuronal debris, and lipid metabolism.
|
|
GO:0071396
cellular response to lipid
|
IEA
GO_REF:0000117 |
ACCEPT |
Summary: cellular response to lipid is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 ligand sensing and phagocytic challenge regulate microglial lipid/cholesterol handling.
Supporting Evidence:
PMID:31902528
TREM2 senses lipids and mediates myelin phagocytosis
PMID:31902528
Our studies identify TREM2 as a key transcriptional regulator of cholesterol transport and metabolism under conditions of chronic myelin phagocytic activity
PMID:27477018
Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL, CLU, and APOE in heterologous cells
|
|
GO:0097367
carbohydrate derivative binding
|
IEA
GO_REF:0000117 |
KEEP AS NON CORE |
Summary: carbohydrate derivative binding is retained as non-core TREM2-associated biology pending deeper reference-specific adjudication.
Reason: The annotation is not part of the primary receptor-ligand signaling and phagocytic microglial function set, but the local evidence was not sufficient to remove it.
|
|
GO:1900226
negative regulation of NLRP3 inflammasome complex assembly
|
IEA
GO_REF:0000117 |
KEEP AS NON CORE |
Summary: negative regulation of NLRP3 inflammasome complex assembly is retained as non-core TREM2-associated biology pending deeper reference-specific adjudication.
Reason: The annotation is not part of the primary receptor-ligand signaling and phagocytic microglial function set, but the local evidence was not sufficient to remove it.
|
|
GO:0005515
protein binding
|
IPI
PMID:11602640 A DAP12-mediated pathway regulates expression of CC chemokin... |
MARK AS OVER ANNOTATED |
Summary: Generic protein binding annotation for TREM2.
Reason: The interaction may be real, but this term is too generic. Specific ligand-binding, receptor-activity, TYROBP/DAP12 signaling, or phagocytosis annotations are more informative.
|
|
GO:0005515
protein binding
|
IPI
PMID:28490631 A split-luciferase complementation, real-time reporting assa... |
MARK AS OVER ANNOTATED |
Summary: Generic protein binding annotation for TREM2.
Reason: The interaction may be real, but this term is too generic. Specific ligand-binding, receptor-activity, TYROBP/DAP12 signaling, or phagocytosis annotations are more informative.
|
|
GO:0005515
protein binding
|
IPI
PMID:29611543 Intracellular trafficking of TREM2 is regulated by presenili... |
MARK AS OVER ANNOTATED |
Summary: Generic protein binding annotation for TREM2.
Reason: The interaction may be real, but this term is too generic. Specific ligand-binding, receptor-activity, TYROBP/DAP12 signaling, or phagocytosis annotations are more informative.
|
|
GO:0005515
protein binding
|
IPI
PMID:30341064 High-affinity interactions and signal transduction between A... |
MARK AS OVER ANNOTATED |
Summary: Generic protein binding annotation for TREM2.
Reason: The interaction may be real, but this term is too generic. Specific ligand-binding, receptor-activity, TYROBP/DAP12 signaling, or phagocytosis annotations are more informative.
|
|
GO:0001530
lipopolysaccharide binding
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: lipopolysaccharide binding is electronically inferred pathogen-associated ligand or defense biology.
Reason: Retain as non-core because TREM-family receptors participate in myeloid immune sensing, but the cached human TREM2 evidence reviewed here emphasizes lipids, apoptotic cells, and microglial phagocytic ligands.
|
|
GO:0001774
microglial cell activation
|
IEA
GO_REF:0000107 |
ACCEPT |
Summary: microglial cell activation is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment, activation, and migration responses.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:0002282
microglial cell activation involved in immune response
|
IEA
GO_REF:0000107 |
ACCEPT |
Summary: microglial cell activation involved in immune response is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment, activation, and migration responses.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:0002291
T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell
|
IEA
GO_REF:0000120 |
KEEP AS NON CORE |
Summary: T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:0002862
negative regulation of inflammatory response to antigenic stimulus
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: negative regulation of inflammatory response to antigenic stimulus is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:0002931
response to ischemia
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: response to ischemia is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:0010507
negative regulation of autophagy
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: negative regulation of autophagy is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:0010628
positive regulation of gene expression
|
IEA
GO_REF:0000120 |
KEEP AS NON CORE |
Summary: positive regulation of gene expression is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:0010875
positive regulation of cholesterol efflux
|
IEA
GO_REF:0000107 |
ACCEPT |
Summary: positive regulation of cholesterol efflux is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 ligand sensing and phagocytic challenge regulate microglial lipid/cholesterol handling.
Supporting Evidence:
PMID:31902528
TREM2 senses lipids and mediates myelin phagocytosis
PMID:31902528
Our studies identify TREM2 as a key transcriptional regulator of cholesterol transport and metabolism under conditions of chronic myelin phagocytic activity
PMID:27477018
Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL, CLU, and APOE in heterologous cells
|
|
GO:0010887
negative regulation of cholesterol storage
|
IEA
GO_REF:0000107 |
ACCEPT |
Summary: negative regulation of cholesterol storage is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 ligand sensing and phagocytic challenge regulate microglial lipid/cholesterol handling.
Supporting Evidence:
PMID:31902528
TREM2 senses lipids and mediates myelin phagocytosis
PMID:31902528
Our studies identify TREM2 as a key transcriptional regulator of cholesterol transport and metabolism under conditions of chronic myelin phagocytic activity
PMID:27477018
Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL, CLU, and APOE in heterologous cells
|
|
GO:0010891
negative regulation of triglyceride storage
|
IEA
GO_REF:0000107 |
ACCEPT |
Summary: negative regulation of triglyceride storage is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 ligand sensing and phagocytic challenge regulate microglial lipid/cholesterol handling.
Supporting Evidence:
PMID:31902528
TREM2 senses lipids and mediates myelin phagocytosis
PMID:31902528
Our studies identify TREM2 as a key transcriptional regulator of cholesterol transport and metabolism under conditions of chronic myelin phagocytic activity
PMID:27477018
Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL, CLU, and APOE in heterologous cells
|
|
GO:0010983
positive regulation of high-density lipoprotein particle clearance
|
IEA
GO_REF:0000107 |
ACCEPT |
Summary: positive regulation of high-density lipoprotein particle clearance is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 ligand sensing and phagocytic challenge regulate microglial lipid/cholesterol handling.
Supporting Evidence:
PMID:31902528
TREM2 senses lipids and mediates myelin phagocytosis
PMID:31902528
Our studies identify TREM2 as a key transcriptional regulator of cholesterol transport and metabolism under conditions of chronic myelin phagocytic activity
PMID:27477018
Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL, CLU, and APOE in heterologous cells
|
|
GO:0017154
semaphorin receptor activity
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: semaphorin receptor activity is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:0030215
semaphorin receptor binding
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: semaphorin receptor binding is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:0032006
regulation of TOR signaling
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: regulation of TOR signaling is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:0032008
positive regulation of TOR signaling
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: positive regulation of TOR signaling is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:0032497
detection of lipopolysaccharide
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: detection of lipopolysaccharide is electronically inferred pathogen-associated ligand or defense biology.
Reason: Retain as non-core because TREM-family receptors participate in myeloid immune sensing, but the cached human TREM2 evidence reviewed here emphasizes lipids, apoptotic cells, and microglial phagocytic ligands.
|
|
GO:0032499
detection of peptidoglycan
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: detection of peptidoglycan is electronically inferred pathogen-associated ligand or defense biology.
Reason: Retain as non-core because TREM-family receptors participate in myeloid immune sensing, but the cached human TREM2 evidence reviewed here emphasizes lipids, apoptotic cells, and microglial phagocytic ligands.
|
|
GO:0032675
regulation of interleukin-6 production
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: regulation of interleukin-6 production is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:0032691
negative regulation of interleukin-1 beta production
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: negative regulation of interleukin-1 beta production is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:0032720
negative regulation of tumor necrosis factor production
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: negative regulation of tumor necrosis factor production is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:0032733
positive regulation of interleukin-10 production
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: positive regulation of interleukin-10 production is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:0034136
negative regulation of toll-like receptor 2 signaling pathway
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: negative regulation of toll-like receptor 2 signaling pathway is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:0034144
negative regulation of toll-like receptor 4 signaling pathway
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: negative regulation of toll-like receptor 4 signaling pathway is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:0034151
regulation of toll-like receptor 6 signaling pathway
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: regulation of toll-like receptor 6 signaling pathway is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:0034241
positive regulation of macrophage fusion
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: positive regulation of macrophage fusion is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:0034351
negative regulation of glial cell apoptotic process
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: negative regulation of glial cell apoptotic process is retained as non-core TREM2-associated biology pending deeper reference-specific adjudication.
Reason: The annotation is not part of the primary receptor-ligand signaling and phagocytic microglial function set, but the local evidence was not sufficient to remove it.
|
|
GO:0038023
signaling receptor activity
|
IEA
GO_REF:0000107 |
ACCEPT |
Summary: TREM2 signaling receptor activity is a core plasma-membrane receptor function coupled to TYROBP/DAP12 signaling.
Reason: TREM2 is a myeloid/microglial cell-surface receptor whose ligand engagement drives intracellular signaling through DAP12/TYROBP-linked kinase pathways.
Supporting Evidence:
PMID:11602640
TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is associated with DAP12.
PMID:11602640
TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC maturation, and DC survival through activation of protein tyrosine kinases and extracellular signal-regulated kinase.
PMID:32514138
TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis, processing of neuronal debris, and lipid metabolism.
|
|
GO:0042742
defense response to bacterium
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: defense response to bacterium is electronically inferred pathogen-associated ligand or defense biology.
Reason: Retain as non-core because TREM-family receptors participate in myeloid immune sensing, but the cached human TREM2 evidence reviewed here emphasizes lipids, apoptotic cells, and microglial phagocytic ligands.
|
|
GO:0042834
peptidoglycan binding
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: peptidoglycan binding is electronically inferred pathogen-associated ligand or defense biology.
Reason: Retain as non-core because TREM-family receptors participate in myeloid immune sensing, but the cached human TREM2 evidence reviewed here emphasizes lipids, apoptotic cells, and microglial phagocytic ligands.
|
|
GO:0043066
negative regulation of apoptotic process
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: negative regulation of apoptotic process is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:0043124
negative regulation of canonical NF-kappaB signal transduction
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: negative regulation of canonical NF-kappaB signal transduction is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:0043268
positive regulation of potassium ion transport
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: positive regulation of potassium ion transport is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:0043277
apoptotic cell clearance
|
IEA
GO_REF:0000107 |
ACCEPT |
Summary: apoptotic cell clearance is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment, activation, and migration responses.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:0045088
regulation of innate immune response
|
IEA
GO_REF:0000107 |
ACCEPT |
Summary: regulation of innate immune response is a core downstream consequence of TREM2 receptor signaling.
Reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support calcium/ERK/PI3K-related activation and intracellular signaling.
Supporting Evidence:
PMID:11602640
TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC maturation, and DC survival through activation of protein tyrosine kinases and extracellular signal-regulated kinase.
PMID:32514138
TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis, processing of neuronal debris, and lipid metabolism.
|
|
GO:0045672
positive regulation of osteoclast differentiation
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: positive regulation of osteoclast differentiation is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
Supporting Evidence:
PMID:12925681
loss of function mutations in DAP12 and TREM2 result in an inefficient and delayed differentiation of osteoclasts
|
|
GO:0045728
respiratory burst after phagocytosis
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: respiratory burst after phagocytosis is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:0045960
positive regulation of complement activation, classical pathway
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: positive regulation of complement activation, classical pathway is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:0048143
astrocyte activation
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: astrocyte activation is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:0048678
response to axon injury
|
IEA
GO_REF:0000120 |
KEEP AS NON CORE |
Summary: response to axon injury is Alzheimer-relevant TREM2 biology, but it is a context-specific substrate/phenotype rather than the broad core receptor function.
Reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial function; do not treat them as disease-progression hypotheses in the core function.
Supporting Evidence:
PMID:27477018
β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up by microglia in a TREM2-dependent fashion.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:0050766
positive regulation of phagocytosis
|
IEA
GO_REF:0000107 |
ACCEPT |
Summary: positive regulation of phagocytosis is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment, activation, and migration responses.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:0050866
negative regulation of cell activation
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: negative regulation of cell activation is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:0050921
positive regulation of chemotaxis
|
IEA
GO_REF:0000107 |
ACCEPT |
Summary: positive regulation of chemotaxis is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment, activation, and migration responses.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:0051897
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
|
IEA
GO_REF:0000107 |
ACCEPT |
Summary: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction is a core downstream consequence of TREM2 receptor signaling.
Reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support calcium/ERK/PI3K-related activation and intracellular signaling.
Supporting Evidence:
PMID:11602640
TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC maturation, and DC survival through activation of protein tyrosine kinases and extracellular signal-regulated kinase.
PMID:32514138
TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis, processing of neuronal debris, and lipid metabolism.
|
|
GO:0051898
negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
|
IEA
GO_REF:0000120 |
ACCEPT |
Summary: negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction is a core downstream consequence of TREM2 receptor signaling.
Reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support calcium/ERK/PI3K-related activation and intracellular signaling.
Supporting Evidence:
PMID:11602640
TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC maturation, and DC survival through activation of protein tyrosine kinases and extracellular signal-regulated kinase.
PMID:32514138
TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis, processing of neuronal debris, and lipid metabolism.
|
|
GO:0055088
lipid homeostasis
|
IEA
GO_REF:0000107 |
ACCEPT |
Summary: lipid homeostasis is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 ligand sensing and phagocytic challenge regulate microglial lipid/cholesterol handling.
Supporting Evidence:
PMID:31902528
TREM2 senses lipids and mediates myelin phagocytosis
PMID:31902528
Our studies identify TREM2 as a key transcriptional regulator of cholesterol transport and metabolism under conditions of chronic myelin phagocytic activity
PMID:27477018
Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL, CLU, and APOE in heterologous cells
|
|
GO:0060075
regulation of resting membrane potential
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: regulation of resting membrane potential is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:0060100
positive regulation of phagocytosis, engulfment
|
IEA
GO_REF:0000120 |
ACCEPT |
Summary: positive regulation of phagocytosis, engulfment is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment, activation, and migration responses.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:0061518
microglial cell proliferation
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: microglial cell proliferation is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:0061889
negative regulation of astrocyte activation
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: negative regulation of astrocyte activation is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:0070345
negative regulation of fat cell proliferation
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: negative regulation of fat cell proliferation is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:0070374
positive regulation of ERK1 and ERK2 cascade
|
IEA
GO_REF:0000120 |
ACCEPT |
Summary: positive regulation of ERK1 and ERK2 cascade is a core downstream consequence of TREM2 receptor signaling.
Reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support calcium/ERK/PI3K-related activation and intracellular signaling.
Supporting Evidence:
PMID:11602640
TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC maturation, and DC survival through activation of protein tyrosine kinases and extracellular signal-regulated kinase.
PMID:32514138
TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis, processing of neuronal debris, and lipid metabolism.
|
|
GO:0070392
detection of lipoteichoic acid
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: detection of lipoteichoic acid is electronically inferred pathogen-associated ligand or defense biology.
Reason: Retain as non-core because TREM-family receptors participate in myeloid immune sensing, but the cached human TREM2 evidence reviewed here emphasizes lipids, apoptotic cells, and microglial phagocytic ligands.
|
|
GO:0070891
lipoteichoic acid binding
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: lipoteichoic acid binding is electronically inferred pathogen-associated ligand or defense biology.
Reason: Retain as non-core because TREM-family receptors participate in myeloid immune sensing, but the cached human TREM2 evidence reviewed here emphasizes lipids, apoptotic cells, and microglial phagocytic ligands.
|
|
GO:0071223
cellular response to lipoteichoic acid
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: cellular response to lipoteichoic acid is electronically inferred pathogen-associated ligand or defense biology.
Reason: Retain as non-core because TREM-family receptors participate in myeloid immune sensing, but the cached human TREM2 evidence reviewed here emphasizes lipids, apoptotic cells, and microglial phagocytic ligands.
|
|
GO:0071224
cellular response to peptidoglycan
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: cellular response to peptidoglycan is electronically inferred pathogen-associated ligand or defense biology.
Reason: Retain as non-core because TREM-family receptors participate in myeloid immune sensing, but the cached human TREM2 evidence reviewed here emphasizes lipids, apoptotic cells, and microglial phagocytic ligands.
|
|
GO:0071333
cellular response to glucose stimulus
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: cellular response to glucose stimulus is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:0071456
cellular response to hypoxia
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: cellular response to hypoxia is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:0071526
semaphorin-plexin signaling pathway
|
IEA
GO_REF:0000120 |
KEEP AS NON CORE |
Summary: semaphorin-plexin signaling pathway is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:0071640
regulation of macrophage inflammatory protein 1 alpha production
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: regulation of macrophage inflammatory protein 1 alpha production is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:0097062
dendritic spine maintenance
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: dendritic spine maintenance is Alzheimer-relevant TREM2 biology, but it is a context-specific substrate/phenotype rather than the broad core receptor function.
Reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial function; do not treat them as disease-progression hypotheses in the core function.
Supporting Evidence:
PMID:27477018
β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up by microglia in a TREM2-dependent fashion.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:0097242
amyloid-beta clearance
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: amyloid-beta clearance is Alzheimer-relevant TREM2 biology, but it is a context-specific substrate/phenotype rather than the broad core receptor function.
Reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial function; do not treat them as disease-progression hypotheses in the core function.
Supporting Evidence:
PMID:27477018
β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up by microglia in a TREM2-dependent fashion.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:0098657
import into cell
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: import into cell is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:0110089
regulation of hippocampal neuron apoptotic process
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: regulation of hippocampal neuron apoptotic process is Alzheimer-relevant TREM2 biology, but it is a context-specific substrate/phenotype rather than the broad core receptor function.
Reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial function; do not treat them as disease-progression hypotheses in the core function.
Supporting Evidence:
PMID:27477018
β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up by microglia in a TREM2-dependent fashion.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:0120035
regulation of plasma membrane bounded cell projection organization
|
IEA
GO_REF:0000120 |
KEEP AS NON CORE |
Summary: regulation of plasma membrane bounded cell projection organization is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:0150062
complement-mediated synapse pruning
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: complement-mediated synapse pruning is Alzheimer-relevant TREM2 biology, but it is a context-specific substrate/phenotype rather than the broad core receptor function.
Reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial function; do not treat them as disease-progression hypotheses in the core function.
Supporting Evidence:
PMID:27477018
β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up by microglia in a TREM2-dependent fashion.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:0150076
neuroinflammatory response
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: neuroinflammatory response is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:0150078
positive regulation of neuroinflammatory response
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: positive regulation of neuroinflammatory response is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:0150079
negative regulation of neuroinflammatory response
|
IEA
GO_REF:0000120 |
KEEP AS NON CORE |
Summary: negative regulation of neuroinflammatory response is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:0150094
amyloid-beta clearance by cellular catabolic process
|
IEA
GO_REF:0000120 |
KEEP AS NON CORE |
Summary: amyloid-beta clearance by cellular catabolic process is Alzheimer-relevant TREM2 biology, but it is a context-specific substrate/phenotype rather than the broad core receptor function.
Reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial function; do not treat them as disease-progression hypotheses in the core function.
Supporting Evidence:
PMID:27477018
β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up by microglia in a TREM2-dependent fashion.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:1900015
regulation of cytokine production involved in inflammatory response
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: regulation of cytokine production involved in inflammatory response is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:1900016
negative regulation of cytokine production involved in inflammatory response
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: negative regulation of cytokine production involved in inflammatory response is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:1900223
positive regulation of amyloid-beta clearance
|
IEA
GO_REF:0000120 |
KEEP AS NON CORE |
Summary: positive regulation of amyloid-beta clearance is Alzheimer-relevant TREM2 biology, but it is a context-specific substrate/phenotype rather than the broad core receptor function.
Reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial function; do not treat them as disease-progression hypotheses in the core function.
Supporting Evidence:
PMID:27477018
β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up by microglia in a TREM2-dependent fashion.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:1901224
positive regulation of non-canonical NF-kappaB signal transduction
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: positive regulation of non-canonical NF-kappaB signal transduction is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:1901800
positive regulation of proteasomal protein catabolic process
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: positive regulation of proteasomal protein catabolic process is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:1902533
positive regulation of intracellular signal transduction
|
IEA
GO_REF:0000107 |
ACCEPT |
Summary: positive regulation of intracellular signal transduction is a core downstream consequence of TREM2 receptor signaling.
Reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support calcium/ERK/PI3K-related activation and intracellular signaling.
Supporting Evidence:
PMID:11602640
TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC maturation, and DC survival through activation of protein tyrosine kinases and extracellular signal-regulated kinase.
PMID:32514138
TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis, processing of neuronal debris, and lipid metabolism.
|
|
GO:1903376
regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway is Alzheimer-relevant TREM2 biology, but it is a context-specific substrate/phenotype rather than the broad core receptor function.
Reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial function; do not treat them as disease-progression hypotheses in the core function.
Supporting Evidence:
PMID:27477018
β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up by microglia in a TREM2-dependent fashion.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:1903753
negative regulation of p38MAPK cascade
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: negative regulation of p38MAPK cascade is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:1903980
positive regulation of microglial cell activation
|
IEA
GO_REF:0000120 |
ACCEPT |
Summary: positive regulation of microglial cell activation is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment, activation, and migration responses.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:1904093
negative regulation of autophagic cell death
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: negative regulation of autophagic cell death is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:1904141
positive regulation of microglial cell migration
|
IEA
GO_REF:0000120 |
ACCEPT |
Summary: positive regulation of microglial cell migration is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment, activation, and migration responses.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:1904646
cellular response to amyloid-beta
|
IEA
GO_REF:0000120 |
KEEP AS NON CORE |
Summary: cellular response to amyloid-beta is Alzheimer-relevant TREM2 biology, but it is a context-specific substrate/phenotype rather than the broad core receptor function.
Reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial function; do not treat them as disease-progression hypotheses in the core function.
Supporting Evidence:
PMID:27477018
β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up by microglia in a TREM2-dependent fashion.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:1904951
positive regulation of establishment of protein localization
|
IEA
GO_REF:0000120 |
KEEP AS NON CORE |
Summary: positive regulation of establishment of protein localization is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:1905291
positive regulation of CAMKK-AMPK signaling cascade
|
IEA
GO_REF:0000107 |
ACCEPT |
Summary: positive regulation of CAMKK-AMPK signaling cascade is a core downstream consequence of TREM2 receptor signaling.
Reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support calcium/ERK/PI3K-related activation and intracellular signaling.
Supporting Evidence:
PMID:11602640
TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC maturation, and DC survival through activation of protein tyrosine kinases and extracellular signal-regulated kinase.
PMID:32514138
TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis, processing of neuronal debris, and lipid metabolism.
|
|
GO:1905581
positive regulation of low-density lipoprotein particle clearance
|
IEA
GO_REF:0000107 |
ACCEPT |
Summary: positive regulation of low-density lipoprotein particle clearance is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 ligand sensing and phagocytic challenge regulate microglial lipid/cholesterol handling.
Supporting Evidence:
PMID:31902528
TREM2 senses lipids and mediates myelin phagocytosis
PMID:31902528
Our studies identify TREM2 as a key transcriptional regulator of cholesterol transport and metabolism under conditions of chronic myelin phagocytic activity
PMID:27477018
Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL, CLU, and APOE in heterologous cells
|
|
GO:1905805
excitatory synapse pruning
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: excitatory synapse pruning is Alzheimer-relevant TREM2 biology, but it is a context-specific substrate/phenotype rather than the broad core receptor function.
Reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial function; do not treat them as disease-progression hypotheses in the core function.
Supporting Evidence:
PMID:27477018
β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up by microglia in a TREM2-dependent fashion.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:1905907
negative regulation of amyloid fibril formation
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: negative regulation of amyloid fibril formation is Alzheimer-relevant TREM2 biology, but it is a context-specific substrate/phenotype rather than the broad core receptor function.
Reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial function; do not treat them as disease-progression hypotheses in the core function.
Supporting Evidence:
PMID:27477018
β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up by microglia in a TREM2-dependent fashion.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:1990782
protein tyrosine kinase binding
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: protein tyrosine kinase binding is a specific interaction context for TREM2 but not the main molecular-function term.
Reason: Retain as non-core because the interaction may be real, while more informative core terms describe receptor activity and lipid/lipoprotein/aminophospholipid ligand binding.
|
|
GO:2001171
positive regulation of ATP biosynthetic process
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: positive regulation of ATP biosynthetic process is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:1902533
positive regulation of intracellular signal transduction
|
IDA
PMID:32514138 Alzheimer's-associated PLCγ2 is a signaling node required fo... |
ACCEPT |
Summary: positive regulation of intracellular signal transduction is a core downstream consequence of TREM2 receptor signaling.
Reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support calcium/ERK/PI3K-related activation and intracellular signaling.
Supporting Evidence:
PMID:11602640
TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC maturation, and DC survival through activation of protein tyrosine kinases and extracellular signal-regulated kinase.
PMID:32514138
TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis, processing of neuronal debris, and lipid metabolism.
|
|
GO:0005886
plasma membrane
|
EXP
PMID:25615530 Disease-Associated Mutations of TREM2 Alter the Processing o... |
ACCEPT |
Summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface receptor role.
Reason: Cell-surface/plasma-membrane localization is essential for ligand binding and DAP12/TYROBP-mediated signal transduction.
Supporting Evidence:
PMID:11602640
TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is associated with DAP12.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:27995897
Nasu-Hakola mutations impact protein stability and decrease folded TREM2 surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
|
|
GO:0005886
plasma membrane
|
EXP
PMID:28768830 Neurodegeneration-associated mutant TREM2 proteins abortivel... |
ACCEPT |
Summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface receptor role.
Reason: Cell-surface/plasma-membrane localization is essential for ligand binding and DAP12/TYROBP-mediated signal transduction.
Supporting Evidence:
PMID:11602640
TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is associated with DAP12.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:27995897
Nasu-Hakola mutations impact protein stability and decrease folded TREM2 surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
|
|
GO:0005886
plasma membrane
|
EXP
PMID:28923481 ADAM17 is the main sheddase for the generation of human trig... |
ACCEPT |
Summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface receptor role.
Reason: Cell-surface/plasma-membrane localization is essential for ligand binding and DAP12/TYROBP-mediated signal transduction.
Supporting Evidence:
PMID:11602640
TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is associated with DAP12.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:27995897
Nasu-Hakola mutations impact protein stability and decrease folded TREM2 surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
|
|
GO:0010468
regulation of gene expression
|
ISS
PMID:29518356 TREM2 Is a Receptor for β-Amyloid that Mediates Microglial F... |
KEEP AS NON CORE |
Summary: regulation of gene expression is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:0032675
regulation of interleukin-6 production
|
ISS
PMID:29518356 TREM2 Is a Receptor for β-Amyloid that Mediates Microglial F... |
KEEP AS NON CORE |
Summary: regulation of interleukin-6 production is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:0043268
positive regulation of potassium ion transport
|
ISS
PMID:29518356 TREM2 Is a Receptor for β-Amyloid that Mediates Microglial F... |
KEEP AS NON CORE |
Summary: positive regulation of potassium ion transport is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:0071640
regulation of macrophage inflammatory protein 1 alpha production
|
ISS
PMID:29518356 TREM2 Is a Receptor for β-Amyloid that Mediates Microglial F... |
KEEP AS NON CORE |
Summary: regulation of macrophage inflammatory protein 1 alpha production is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:1902533
positive regulation of intracellular signal transduction
|
ISS
PMID:29518356 TREM2 Is a Receptor for β-Amyloid that Mediates Microglial F... |
ACCEPT |
Summary: positive regulation of intracellular signal transduction is a core downstream consequence of TREM2 receptor signaling.
Reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support calcium/ERK/PI3K-related activation and intracellular signaling.
Supporting Evidence:
PMID:11602640
TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC maturation, and DC survival through activation of protein tyrosine kinases and extracellular signal-regulated kinase.
PMID:32514138
TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis, processing of neuronal debris, and lipid metabolism.
|
|
GO:1902533
positive regulation of intracellular signal transduction
|
IDA
PMID:31902528 TREM2 Regulates Microglial Cholesterol Metabolism upon Chron... |
ACCEPT |
Summary: positive regulation of intracellular signal transduction is a core downstream consequence of TREM2 receptor signaling.
Reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support calcium/ERK/PI3K-related activation and intracellular signaling.
Supporting Evidence:
PMID:11602640
TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC maturation, and DC survival through activation of protein tyrosine kinases and extracellular signal-regulated kinase.
PMID:32514138
TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis, processing of neuronal debris, and lipid metabolism.
|
|
GO:0002116
semaphorin receptor complex
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: semaphorin receptor complex is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:0002291
T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell
|
IDA
PMID:16715077 Plexin-A1 and its interaction with DAP12 in immune responses... |
KEEP AS NON CORE |
Summary: T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:0005886
plasma membrane
|
IDA
PMID:16715077 Plexin-A1 and its interaction with DAP12 in immune responses... |
ACCEPT |
Summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface receptor role.
Reason: Cell-surface/plasma-membrane localization is essential for ligand binding and DAP12/TYROBP-mediated signal transduction.
Supporting Evidence:
PMID:11602640
TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is associated with DAP12.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:27995897
Nasu-Hakola mutations impact protein stability and decrease folded TREM2 surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
|
|
GO:0017154
semaphorin receptor activity
|
IDA
PMID:16715077 Plexin-A1 and its interaction with DAP12 in immune responses... |
KEEP AS NON CORE |
Summary: semaphorin receptor activity is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:0071526
semaphorin-plexin signaling pathway
|
IDA
PMID:16715077 Plexin-A1 and its interaction with DAP12 in immune responses... |
KEEP AS NON CORE |
Summary: semaphorin-plexin signaling pathway is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:0004888
transmembrane signaling receptor activity
|
IDA
PMID:29518356 TREM2 Is a Receptor for β-Amyloid that Mediates Microglial F... |
ACCEPT |
Summary: TREM2 transmembrane signaling receptor activity is a core plasma-membrane receptor function coupled to TYROBP/DAP12 signaling.
Reason: TREM2 is a myeloid/microglial cell-surface receptor whose ligand engagement drives intracellular signaling through DAP12/TYROBP-linked kinase pathways.
Supporting Evidence:
PMID:11602640
TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is associated with DAP12.
PMID:11602640
TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC maturation, and DC survival through activation of protein tyrosine kinases and extracellular signal-regulated kinase.
PMID:32514138
TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis, processing of neuronal debris, and lipid metabolism.
|
|
GO:0004888
transmembrane signaling receptor activity
|
IDA
PMID:30333625 LILRB4 signalling in leukaemia cells mediates T cell suppres... |
ACCEPT |
Summary: TREM2 transmembrane signaling receptor activity is a core plasma-membrane receptor function coupled to TYROBP/DAP12 signaling.
Reason: TREM2 is a myeloid/microglial cell-surface receptor whose ligand engagement drives intracellular signaling through DAP12/TYROBP-linked kinase pathways.
Supporting Evidence:
PMID:11602640
TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is associated with DAP12.
PMID:11602640
TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC maturation, and DC survival through activation of protein tyrosine kinases and extracellular signal-regulated kinase.
PMID:32514138
TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis, processing of neuronal debris, and lipid metabolism.
|
|
GO:0005886
plasma membrane
|
IDA
PMID:24078628 Sequential proteolytic processing of the triggering receptor... |
ACCEPT |
Summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface receptor role.
Reason: Cell-surface/plasma-membrane localization is essential for ligand binding and DAP12/TYROBP-mediated signal transduction.
Supporting Evidence:
PMID:11602640
TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is associated with DAP12.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:27995897
Nasu-Hakola mutations impact protein stability and decrease folded TREM2 surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
|
|
GO:0005886
plasma membrane
|
IDA
PMID:27477018 TREM2 Binds to Apolipoproteins, Including APOE and CLU/APOJ,... |
ACCEPT |
Summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface receptor role.
Reason: Cell-surface/plasma-membrane localization is essential for ligand binding and DAP12/TYROBP-mediated signal transduction.
Supporting Evidence:
PMID:11602640
TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is associated with DAP12.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:27995897
Nasu-Hakola mutations impact protein stability and decrease folded TREM2 surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
|
|
GO:0071402
cellular response to lipoprotein particle stimulus
|
IDA
PMID:27477018 TREM2 Binds to Apolipoproteins, Including APOE and CLU/APOJ,... |
ACCEPT |
Summary: cellular response to lipoprotein particle stimulus is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 ligand sensing and phagocytic challenge regulate microglial lipid/cholesterol handling.
Supporting Evidence:
PMID:31902528
TREM2 senses lipids and mediates myelin phagocytosis
PMID:31902528
Our studies identify TREM2 as a key transcriptional regulator of cholesterol transport and metabolism under conditions of chronic myelin phagocytic activity
PMID:27477018
Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL, CLU, and APOE in heterologous cells
|
|
GO:0097242
amyloid-beta clearance
|
IDA
PMID:27477018 TREM2 Binds to Apolipoproteins, Including APOE and CLU/APOJ,... |
KEEP AS NON CORE |
Summary: amyloid-beta clearance is Alzheimer-relevant TREM2 biology, but it is a context-specific substrate/phenotype rather than the broad core receptor function.
Reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial function; do not treat them as disease-progression hypotheses in the core function.
Supporting Evidence:
PMID:27477018
β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up by microglia in a TREM2-dependent fashion.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:0008013
beta-catenin binding
|
IPI
PMID:30683932 TREM2 acts as a tumor suppressor in hepatocellular carcinoma... |
KEEP AS NON CORE |
Summary: beta-catenin binding is a specific interaction context for TREM2 but not the main molecular-function term.
Reason: Retain as non-core because the interaction may be real, while more informative core terms describe receptor activity and lipid/lipoprotein/aminophospholipid ligand binding.
|
|
GO:0051898
negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
|
IMP
PMID:30683932 TREM2 acts as a tumor suppressor in hepatocellular carcinoma... |
ACCEPT |
Summary: negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction is a core downstream consequence of TREM2 receptor signaling.
Reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support calcium/ERK/PI3K-related activation and intracellular signaling.
Supporting Evidence:
PMID:11602640
TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC maturation, and DC survival through activation of protein tyrosine kinases and extracellular signal-regulated kinase.
PMID:32514138
TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis, processing of neuronal debris, and lipid metabolism.
|
|
GO:0050921
positive regulation of chemotaxis
|
ISS
GO_REF:0000024 |
ACCEPT |
Summary: positive regulation of chemotaxis is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment, activation, and migration responses.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:0120035
regulation of plasma membrane bounded cell projection organization
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: regulation of plasma membrane bounded cell projection organization is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:1904141
positive regulation of microglial cell migration
|
ISS
GO_REF:0000024 |
ACCEPT |
Summary: positive regulation of microglial cell migration is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment, activation, and migration responses.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:0010507
negative regulation of autophagy
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: negative regulation of autophagy is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:0032006
regulation of TOR signaling
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: regulation of TOR signaling is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:0032008
positive regulation of TOR signaling
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: positive regulation of TOR signaling is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:1904093
negative regulation of autophagic cell death
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: negative regulation of autophagic cell death is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:1905291
positive regulation of CAMKK-AMPK signaling cascade
|
ISS
GO_REF:0000024 |
ACCEPT |
Summary: positive regulation of CAMKK-AMPK signaling cascade is a core downstream consequence of TREM2 receptor signaling.
Reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support calcium/ERK/PI3K-related activation and intracellular signaling.
Supporting Evidence:
PMID:11602640
TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC maturation, and DC survival through activation of protein tyrosine kinases and extracellular signal-regulated kinase.
PMID:32514138
TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis, processing of neuronal debris, and lipid metabolism.
|
|
GO:2001171
positive regulation of ATP biosynthetic process
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: positive regulation of ATP biosynthetic process is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:1900223
positive regulation of amyloid-beta clearance
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: positive regulation of amyloid-beta clearance is Alzheimer-relevant TREM2 biology, but it is a context-specific substrate/phenotype rather than the broad core receptor function.
Reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial function; do not treat them as disease-progression hypotheses in the core function.
Supporting Evidence:
PMID:27477018
β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up by microglia in a TREM2-dependent fashion.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:0006910
phagocytosis, recognition
|
IMP
PMID:32514138 Alzheimer's-associated PLCγ2 is a signaling node required fo... |
ACCEPT |
Summary: phagocytosis, recognition is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment, activation, and migration responses.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
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: positive regulation of gene expression is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:0019216
regulation of lipid metabolic process
|
IMP
PMID:32514138 Alzheimer's-associated PLCγ2 is a signaling node required fo... |
ACCEPT |
Summary: regulation of lipid metabolic process is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 ligand sensing and phagocytic challenge regulate microglial lipid/cholesterol handling.
Supporting Evidence:
PMID:31902528
TREM2 senses lipids and mediates myelin phagocytosis
PMID:31902528
Our studies identify TREM2 as a key transcriptional regulator of cholesterol transport and metabolism under conditions of chronic myelin phagocytic activity
PMID:27477018
Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL, CLU, and APOE in heterologous cells
|
|
GO:0038023
signaling receptor activity
|
IMP
PMID:32514138 Alzheimer's-associated PLCγ2 is a signaling node required fo... |
ACCEPT |
Summary: TREM2 signaling receptor activity is a core plasma-membrane receptor function coupled to TYROBP/DAP12 signaling.
Reason: TREM2 is a myeloid/microglial cell-surface receptor whose ligand engagement drives intracellular signaling through DAP12/TYROBP-linked kinase pathways.
Supporting Evidence:
PMID:11602640
TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is associated with DAP12.
PMID:11602640
TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC maturation, and DC survival through activation of protein tyrosine kinases and extracellular signal-regulated kinase.
PMID:32514138
TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis, processing of neuronal debris, and lipid metabolism.
|
|
GO:0048678
response to axon injury
|
IMP
PMID:32514138 Alzheimer's-associated PLCγ2 is a signaling node required fo... |
KEEP AS NON CORE |
Summary: response to axon injury is Alzheimer-relevant TREM2 biology, but it is a context-specific substrate/phenotype rather than the broad core receptor function.
Reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial function; do not treat them as disease-progression hypotheses in the core function.
Supporting Evidence:
PMID:27477018
β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up by microglia in a TREM2-dependent fashion.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:0060100
positive regulation of phagocytosis, engulfment
|
IMP
PMID:32514138 Alzheimer's-associated PLCγ2 is a signaling node required fo... |
ACCEPT |
Summary: positive regulation of phagocytosis, engulfment is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment, activation, and migration responses.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:0071396
cellular response to lipid
|
IMP
PMID:32514138 Alzheimer's-associated PLCγ2 is a signaling node required fo... |
ACCEPT |
Summary: cellular response to lipid is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 ligand sensing and phagocytic challenge regulate microglial lipid/cholesterol handling.
Supporting Evidence:
PMID:31902528
TREM2 senses lipids and mediates myelin phagocytosis
PMID:31902528
Our studies identify TREM2 as a key transcriptional regulator of cholesterol transport and metabolism under conditions of chronic myelin phagocytic activity
PMID:27477018
Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL, CLU, and APOE in heterologous cells
|
|
GO:0150079
negative regulation of neuroinflammatory response
|
IMP
PMID:32514138 Alzheimer's-associated PLCγ2 is a signaling node required fo... |
KEEP AS NON CORE |
Summary: negative regulation of neuroinflammatory response is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:1900226
negative regulation of NLRP3 inflammasome complex assembly
|
IMP
PMID:32514138 Alzheimer's-associated PLCγ2 is a signaling node required fo... |
KEEP AS NON CORE |
Summary: negative regulation of NLRP3 inflammasome complex assembly is retained as non-core TREM2-associated biology pending deeper reference-specific adjudication.
Reason: The annotation is not part of the primary receptor-ligand signaling and phagocytic microglial function set, but the local evidence was not sufficient to remove it.
|
|
GO:0038160
CXCL12-activated CXCR4 signaling pathway
|
IMP
PMID:33097708 Gene expression and functional deficits underlie TREM2-knock... |
KEEP AS NON CORE |
Summary: CXCL12-activated CXCR4 signaling pathway is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:0050829
defense response to Gram-negative bacterium
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: defense response to Gram-negative bacterium is electronically inferred pathogen-associated ligand or defense biology.
Reason: Retain as non-core because TREM-family receptors participate in myeloid immune sensing, but the cached human TREM2 evidence reviewed here emphasizes lipids, apoptotic cells, and microglial phagocytic ligands.
|
|
GO:0070269
pyroptotic inflammatory response
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: pyroptotic inflammatory response is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:1900016
negative regulation of cytokine production involved in inflammatory response
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: negative regulation of cytokine production involved in inflammatory response is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:1900226
negative regulation of NLRP3 inflammasome complex assembly
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: negative regulation of NLRP3 inflammasome complex assembly is retained as non-core TREM2-associated biology pending deeper reference-specific adjudication.
Reason: The annotation is not part of the primary receptor-ligand signaling and phagocytic microglial function set, but the local evidence was not sufficient to remove it.
|
|
GO:0150079
negative regulation of neuroinflammatory response
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: negative regulation of neuroinflammatory response is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:1903753
negative regulation of p38MAPK cascade
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: negative regulation of p38MAPK cascade is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:0034144
negative regulation of toll-like receptor 4 signaling pathway
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: negative regulation of toll-like receptor 4 signaling pathway is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:0050866
negative regulation of cell activation
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: negative regulation of cell activation is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:0051897
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
|
ISS
GO_REF:0000024 |
ACCEPT |
Summary: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction is a core downstream consequence of TREM2 receptor signaling.
Reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support calcium/ERK/PI3K-related activation and intracellular signaling.
Supporting Evidence:
PMID:11602640
TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC maturation, and DC survival through activation of protein tyrosine kinases and extracellular signal-regulated kinase.
PMID:32514138
TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis, processing of neuronal debris, and lipid metabolism.
|
|
GO:0061889
negative regulation of astrocyte activation
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: negative regulation of astrocyte activation is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:0110089
regulation of hippocampal neuron apoptotic process
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: regulation of hippocampal neuron apoptotic process is Alzheimer-relevant TREM2 biology, but it is a context-specific substrate/phenotype rather than the broad core receptor function.
Reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial function; do not treat them as disease-progression hypotheses in the core function.
Supporting Evidence:
PMID:27477018
β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up by microglia in a TREM2-dependent fashion.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:1903376
regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway is Alzheimer-relevant TREM2 biology, but it is a context-specific substrate/phenotype rather than the broad core receptor function.
Reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial function; do not treat them as disease-progression hypotheses in the core function.
Supporting Evidence:
PMID:27477018
β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up by microglia in a TREM2-dependent fashion.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:0001786
phosphatidylserine binding
|
IDA
PMID:31101881 Aminophospholipids are signal-transducing TREM2 ligands on a... |
ACCEPT |
Summary: TREM2 phosphatidylserine binding is part of its ligand-sensing receptor biology.
Reason: Aminophospholipid and anionic lipid recognition is a core TREM2 ligand-sensing function for apoptotic-cell and debris responses.
Supporting Evidence:
PMID:31101881
TREM2-dependent signal transduction in response to apoptotic Neuro2a cells is mediated by aminophospholipid ligands, phosphatidylserine and phosphatidylethanolamine
|
|
GO:0002282
microglial cell activation involved in immune response
|
ISS
GO_REF:0000024 |
ACCEPT |
Summary: microglial cell activation involved in immune response is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment, activation, and migration responses.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:0007613
memory
|
IDA
PMID:31462511 Increased soluble TREM2 in cerebrospinal fluid is associated... |
KEEP AS NON CORE |
Summary: memory is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:0008429
phosphatidylethanolamine binding
|
IDA
PMID:31101881 Aminophospholipids are signal-transducing TREM2 ligands on a... |
ACCEPT |
Summary: TREM2 phosphatidylethanolamine binding is part of its ligand-sensing receptor biology.
Reason: Aminophospholipid and anionic lipid recognition is a core TREM2 ligand-sensing function for apoptotic-cell and debris responses.
Supporting Evidence:
PMID:31101881
TREM2-dependent signal transduction in response to apoptotic Neuro2a cells is mediated by aminophospholipid ligands, phosphatidylserine and phosphatidylethanolamine
|
|
GO:0034136
negative regulation of toll-like receptor 2 signaling pathway
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: negative regulation of toll-like receptor 2 signaling pathway is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:0034151
regulation of toll-like receptor 6 signaling pathway
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: regulation of toll-like receptor 6 signaling pathway is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:0097062
dendritic spine maintenance
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: dendritic spine maintenance is Alzheimer-relevant TREM2 biology, but it is a context-specific substrate/phenotype rather than the broad core receptor function.
Reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial function; do not treat them as disease-progression hypotheses in the core function.
Supporting Evidence:
PMID:27477018
β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up by microglia in a TREM2-dependent fashion.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:0150094
amyloid-beta clearance by cellular catabolic process
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: amyloid-beta clearance by cellular catabolic process is Alzheimer-relevant TREM2 biology, but it is a context-specific substrate/phenotype rather than the broad core receptor function.
Reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial function; do not treat them as disease-progression hypotheses in the core function.
Supporting Evidence:
PMID:27477018
β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up by microglia in a TREM2-dependent fashion.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:0150094
amyloid-beta clearance by cellular catabolic process
|
IMP
PMID:33097708 Gene expression and functional deficits underlie TREM2-knock... |
KEEP AS NON CORE |
Summary: amyloid-beta clearance by cellular catabolic process is Alzheimer-relevant TREM2 biology, but it is a context-specific substrate/phenotype rather than the broad core receptor function.
Reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial function; do not treat them as disease-progression hypotheses in the core function.
Supporting Evidence:
PMID:27477018
β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up by microglia in a TREM2-dependent fashion.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:0001774
microglial cell activation
|
ISS
GO_REF:0000024 |
ACCEPT |
Summary: microglial cell activation is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment, activation, and migration responses.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:0002862
negative regulation of inflammatory response to antigenic stimulus
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: negative regulation of inflammatory response to antigenic stimulus is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:0007613
memory
|
IMP
PMID:29518357 Elevated TREM2 Gene Dosage Reprograms Microglia Responsivity... |
KEEP AS NON CORE |
Summary: memory is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:0034351
negative regulation of glial cell apoptotic process
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: negative regulation of glial cell apoptotic process is retained as non-core TREM2-associated biology pending deeper reference-specific adjudication.
Reason: The annotation is not part of the primary receptor-ligand signaling and phagocytic microglial function set, but the local evidence was not sufficient to remove it.
|
|
GO:0043124
negative regulation of canonical NF-kappaB signal transduction
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: negative regulation of canonical NF-kappaB signal transduction is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:0050766
positive regulation of phagocytosis
|
ISS
GO_REF:0000024 |
ACCEPT |
Summary: positive regulation of phagocytosis is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment, activation, and migration responses.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:0050766
positive regulation of phagocytosis
|
IMP
PMID:29518357 Elevated TREM2 Gene Dosage Reprograms Microglia Responsivity... |
ACCEPT |
Summary: positive regulation of phagocytosis is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment, activation, and migration responses.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:0051898
negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
|
ISS
GO_REF:0000024 |
ACCEPT |
Summary: negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction is a core downstream consequence of TREM2 receptor signaling.
Reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support calcium/ERK/PI3K-related activation and intracellular signaling.
Supporting Evidence:
PMID:11602640
TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC maturation, and DC survival through activation of protein tyrosine kinases and extracellular signal-regulated kinase.
PMID:32514138
TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis, processing of neuronal debris, and lipid metabolism.
|
|
GO:1900015
regulation of cytokine production involved in inflammatory response
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: regulation of cytokine production involved in inflammatory response is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:0060100
positive regulation of phagocytosis, engulfment
|
IMP
PMID:33097708 Gene expression and functional deficits underlie TREM2-knock... |
ACCEPT |
Summary: positive regulation of phagocytosis, engulfment is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment, activation, and migration responses.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:1902227
negative regulation of macrophage colony-stimulating factor signaling pathway
|
IMP
PMID:33097708 Gene expression and functional deficits underlie TREM2-knock... |
KEEP AS NON CORE |
Summary: negative regulation of macrophage colony-stimulating factor signaling pathway is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:1904141
positive regulation of microglial cell migration
|
IMP
PMID:33097708 Gene expression and functional deficits underlie TREM2-knock... |
ACCEPT |
Summary: positive regulation of microglial cell migration is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment, activation, and migration responses.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:1905808
positive regulation of synapse pruning
|
IMP
PMID:33097708 Gene expression and functional deficits underlie TREM2-knock... |
KEEP AS NON CORE |
Summary: positive regulation of synapse pruning is Alzheimer-relevant TREM2 biology, but it is a context-specific substrate/phenotype rather than the broad core receptor function.
Reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial function; do not treat them as disease-progression hypotheses in the core function.
Supporting Evidence:
PMID:27477018
β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up by microglia in a TREM2-dependent fashion.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:0035176
social behavior
|
IMP
PMID:29752066 The Microglial Innate Immune Receptor TREM2 Is Required for ... |
KEEP AS NON CORE |
Summary: social behavior is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:0045088
regulation of innate immune response
|
ISS
GO_REF:0000024 |
ACCEPT |
Summary: regulation of innate immune response is a core downstream consequence of TREM2 receptor signaling.
Reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support calcium/ERK/PI3K-related activation and intracellular signaling.
Supporting Evidence:
PMID:11602640
TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC maturation, and DC survival through activation of protein tyrosine kinases and extracellular signal-regulated kinase.
PMID:32514138
TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis, processing of neuronal debris, and lipid metabolism.
|
|
GO:0045728
respiratory burst after phagocytosis
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: respiratory burst after phagocytosis is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:0045960
positive regulation of complement activation, classical pathway
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: positive regulation of complement activation, classical pathway is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:0061518
microglial cell proliferation
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: microglial cell proliferation is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:0150062
complement-mediated synapse pruning
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: complement-mediated synapse pruning is Alzheimer-relevant TREM2 biology, but it is a context-specific substrate/phenotype rather than the broad core receptor function.
Reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial function; do not treat them as disease-progression hypotheses in the core function.
Supporting Evidence:
PMID:27477018
β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up by microglia in a TREM2-dependent fashion.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:0060100
positive regulation of phagocytosis, engulfment
|
ISS
GO_REF:0000024 |
ACCEPT |
Summary: positive regulation of phagocytosis, engulfment is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment, activation, and migration responses.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:1905805
excitatory synapse pruning
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: excitatory synapse pruning is Alzheimer-relevant TREM2 biology, but it is a context-specific substrate/phenotype rather than the broad core receptor function.
Reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial function; do not treat them as disease-progression hypotheses in the core function.
Supporting Evidence:
PMID:27477018
β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up by microglia in a TREM2-dependent fashion.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:0048678
response to axon injury
|
IMP
PMID:31235932 TREM2 function impedes tau seeding in neuritic plaques. |
KEEP AS NON CORE |
Summary: response to axon injury is Alzheimer-relevant TREM2 biology, but it is a context-specific substrate/phenotype rather than the broad core receptor function.
Reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial function; do not treat them as disease-progression hypotheses in the core function.
Supporting Evidence:
PMID:27477018
β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up by microglia in a TREM2-dependent fashion.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:1900223
positive regulation of amyloid-beta clearance
|
IMP
PMID:31235932 TREM2 function impedes tau seeding in neuritic plaques. |
KEEP AS NON CORE |
Summary: positive regulation of amyloid-beta clearance is Alzheimer-relevant TREM2 biology, but it is a context-specific substrate/phenotype rather than the broad core receptor function.
Reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial function; do not treat them as disease-progression hypotheses in the core function.
Supporting Evidence:
PMID:27477018
β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up by microglia in a TREM2-dependent fashion.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:0001786
phosphatidylserine binding
|
IDA
PMID:31902528 TREM2 Regulates Microglial Cholesterol Metabolism upon Chron... |
ACCEPT |
Summary: TREM2 phosphatidylserine binding is part of its ligand-sensing receptor biology.
Reason: Aminophospholipid and anionic lipid recognition is a core TREM2 ligand-sensing function for apoptotic-cell and debris responses.
Supporting Evidence:
PMID:31101881
TREM2-dependent signal transduction in response to apoptotic Neuro2a cells is mediated by aminophospholipid ligands, phosphatidylserine and phosphatidylethanolamine
|
|
GO:0010875
positive regulation of cholesterol efflux
|
ISS
GO_REF:0000024 |
ACCEPT |
Summary: positive regulation of cholesterol efflux is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 ligand sensing and phagocytic challenge regulate microglial lipid/cholesterol handling.
Supporting Evidence:
PMID:31902528
TREM2 senses lipids and mediates myelin phagocytosis
PMID:31902528
Our studies identify TREM2 as a key transcriptional regulator of cholesterol transport and metabolism under conditions of chronic myelin phagocytic activity
PMID:27477018
Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL, CLU, and APOE in heterologous cells
|
|
GO:0010887
negative regulation of cholesterol storage
|
ISS
GO_REF:0000024 |
ACCEPT |
Summary: negative regulation of cholesterol storage is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 ligand sensing and phagocytic challenge regulate microglial lipid/cholesterol handling.
Supporting Evidence:
PMID:31902528
TREM2 senses lipids and mediates myelin phagocytosis
PMID:31902528
Our studies identify TREM2 as a key transcriptional regulator of cholesterol transport and metabolism under conditions of chronic myelin phagocytic activity
PMID:27477018
Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL, CLU, and APOE in heterologous cells
|
|
GO:0010891
negative regulation of triglyceride storage
|
ISS
GO_REF:0000024 |
ACCEPT |
Summary: negative regulation of triglyceride storage is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 ligand sensing and phagocytic challenge regulate microglial lipid/cholesterol handling.
Supporting Evidence:
PMID:31902528
TREM2 senses lipids and mediates myelin phagocytosis
PMID:31902528
Our studies identify TREM2 as a key transcriptional regulator of cholesterol transport and metabolism under conditions of chronic myelin phagocytic activity
PMID:27477018
Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL, CLU, and APOE in heterologous cells
|
|
GO:0048678
response to axon injury
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: response to axon injury is Alzheimer-relevant TREM2 biology, but it is a context-specific substrate/phenotype rather than the broad core receptor function.
Reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial function; do not treat them as disease-progression hypotheses in the core function.
Supporting Evidence:
PMID:27477018
β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up by microglia in a TREM2-dependent fashion.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:0120146
sulfatide binding
|
IDA
PMID:31902528 TREM2 Regulates Microglial Cholesterol Metabolism upon Chron... |
ACCEPT |
Summary: TREM2 sulfatide binding is part of its ligand-sensing receptor biology.
Reason: Aminophospholipid and anionic lipid recognition is a core TREM2 ligand-sensing function for apoptotic-cell and debris responses.
Supporting Evidence:
PMID:31101881
TREM2-dependent signal transduction in response to apoptotic Neuro2a cells is mediated by aminophospholipid ligands, phosphatidylserine and phosphatidylethanolamine
|
|
GO:0140052
cellular response to oxidised low-density lipoprotein particle stimulus
|
IDA
PMID:31902528 TREM2 Regulates Microglial Cholesterol Metabolism upon Chron... |
ACCEPT |
Summary: cellular response to oxidised low-density lipoprotein particle stimulus is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 ligand sensing and phagocytic challenge regulate microglial lipid/cholesterol handling.
Supporting Evidence:
PMID:31902528
TREM2 senses lipids and mediates myelin phagocytosis
PMID:31902528
Our studies identify TREM2 as a key transcriptional regulator of cholesterol transport and metabolism under conditions of chronic myelin phagocytic activity
PMID:27477018
Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL, CLU, and APOE in heterologous cells
|
|
GO:1903980
positive regulation of microglial cell activation
|
ISS
GO_REF:0000024 |
ACCEPT |
Summary: positive regulation of microglial cell activation is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment, activation, and migration responses.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:1904951
positive regulation of establishment of protein localization
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: positive regulation of establishment of protein localization is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:1905907
negative regulation of amyloid fibril formation
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: negative regulation of amyloid fibril formation is Alzheimer-relevant TREM2 biology, but it is a context-specific substrate/phenotype rather than the broad core receptor function.
Reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial function; do not treat them as disease-progression hypotheses in the core function.
Supporting Evidence:
PMID:27477018
β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up by microglia in a TREM2-dependent fashion.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:0019209
kinase activator activity
|
IMP
PMID:31902528 TREM2 Regulates Microglial Cholesterol Metabolism upon Chron... |
ACCEPT |
Summary: kinase activator activity is a core downstream consequence of TREM2 receptor signaling.
Reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support calcium/ERK/PI3K-related activation and intracellular signaling.
Supporting Evidence:
PMID:11602640
TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC maturation, and DC survival through activation of protein tyrosine kinases and extracellular signal-regulated kinase.
PMID:32514138
TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis, processing of neuronal debris, and lipid metabolism.
|
|
GO:0010983
positive regulation of high-density lipoprotein particle clearance
|
ISS
GO_REF:0000024 |
ACCEPT |
Summary: positive regulation of high-density lipoprotein particle clearance is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 ligand sensing and phagocytic challenge regulate microglial lipid/cholesterol handling.
Supporting Evidence:
PMID:31902528
TREM2 senses lipids and mediates myelin phagocytosis
PMID:31902528
Our studies identify TREM2 as a key transcriptional regulator of cholesterol transport and metabolism under conditions of chronic myelin phagocytic activity
PMID:27477018
Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL, CLU, and APOE in heterologous cells
|
|
GO:0055088
lipid homeostasis
|
ISS
GO_REF:0000024 |
ACCEPT |
Summary: lipid homeostasis is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 ligand sensing and phagocytic challenge regulate microglial lipid/cholesterol handling.
Supporting Evidence:
PMID:31902528
TREM2 senses lipids and mediates myelin phagocytosis
PMID:31902528
Our studies identify TREM2 as a key transcriptional regulator of cholesterol transport and metabolism under conditions of chronic myelin phagocytic activity
PMID:27477018
Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL, CLU, and APOE in heterologous cells
|
|
GO:0070345
negative regulation of fat cell proliferation
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: negative regulation of fat cell proliferation is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:1905581
positive regulation of low-density lipoprotein particle clearance
|
ISS
GO_REF:0000024 |
ACCEPT |
Summary: positive regulation of low-density lipoprotein particle clearance is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 ligand sensing and phagocytic challenge regulate microglial lipid/cholesterol handling.
Supporting Evidence:
PMID:31902528
TREM2 senses lipids and mediates myelin phagocytosis
PMID:31902528
Our studies identify TREM2 as a key transcriptional regulator of cholesterol transport and metabolism under conditions of chronic myelin phagocytic activity
PMID:27477018
Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL, CLU, and APOE in heterologous cells
|
|
GO:0044853
plasma membrane raft
|
IDA
PMID:31413141 The MS4A gene cluster is a key modulator of soluble TREM2 an... |
ACCEPT |
Summary: TREM2 localization to plasma membrane raft is consistent with its type I cell-surface receptor role.
Reason: Cell-surface/plasma-membrane localization is essential for ligand binding and DAP12/TYROBP-mediated signal transduction.
Supporting Evidence:
PMID:11602640
TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is associated with DAP12.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:27995897
Nasu-Hakola mutations impact protein stability and decrease folded TREM2 surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
|
|
GO:0001774
microglial cell activation
|
ISS
PMID:29518356 TREM2 Is a Receptor for β-Amyloid that Mediates Microglial F... |
ACCEPT |
Summary: microglial cell activation is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment, activation, and migration responses.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:0048143
astrocyte activation
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: astrocyte activation is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:0005886
plasma membrane
|
IMP
PMID:24990881 TREM2 mutations implicated in neurodegeneration impair cell ... |
ACCEPT |
Summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface receptor role.
Reason: Cell-surface/plasma-membrane localization is essential for ligand binding and DAP12/TYROBP-mediated signal transduction.
Supporting Evidence:
PMID:11602640
TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is associated with DAP12.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:27995897
Nasu-Hakola mutations impact protein stability and decrease folded TREM2 surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
|
|
GO:0005886
plasma membrane
|
IMP
PMID:27589997 Rare TREM2 variants associated with Alzheimer's disease disp... |
ACCEPT |
Summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface receptor role.
Reason: Cell-surface/plasma-membrane localization is essential for ligand binding and DAP12/TYROBP-mediated signal transduction.
Supporting Evidence:
PMID:11602640
TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is associated with DAP12.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:27995897
Nasu-Hakola mutations impact protein stability and decrease folded TREM2 surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
|
|
GO:0005886
plasma membrane
|
IMP
PMID:28855300 An Alzheimer-associated TREM2 variant occurs at the ADAM cle... |
ACCEPT |
Summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface receptor role.
Reason: Cell-surface/plasma-membrane localization is essential for ligand binding and DAP12/TYROBP-mediated signal transduction.
Supporting Evidence:
PMID:11602640
TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is associated with DAP12.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:27995897
Nasu-Hakola mutations impact protein stability and decrease folded TREM2 surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
|
|
GO:0060100
positive regulation of phagocytosis, engulfment
|
IMP
PMID:28855300 An Alzheimer-associated TREM2 variant occurs at the ADAM cle... |
ACCEPT |
Summary: positive regulation of phagocytosis, engulfment is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment, activation, and migration responses.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:1901076
positive regulation of engulfment of apoptotic cell
|
IMP
PMID:24990881 TREM2 mutations implicated in neurodegeneration impair cell ... |
ACCEPT |
Summary: positive regulation of engulfment of apoptotic cell is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment, activation, and migration responses.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:1903980
positive regulation of microglial cell activation
|
IMP
PMID:24990881 TREM2 mutations implicated in neurodegeneration impair cell ... |
ACCEPT |
Summary: positive regulation of microglial cell activation is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment, activation, and migration responses.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:0030316
osteoclast differentiation
|
IMP
PMID:12925681 DAP12/TREM2 deficiency results in impaired osteoclast differ... |
KEEP AS NON CORE |
Summary: osteoclast differentiation is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
Supporting Evidence:
PMID:12925681
loss of function mutations in DAP12 and TREM2 result in an inefficient and delayed differentiation of osteoclasts
|
|
GO:0005886
plasma membrane
|
IMP
PMID:28855301 TREM2 shedding by cleavage at the H157-S158 bond is accelera... |
ACCEPT |
Summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface receptor role.
Reason: Cell-surface/plasma-membrane localization is essential for ligand binding and DAP12/TYROBP-mediated signal transduction.
Supporting Evidence:
PMID:11602640
TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is associated with DAP12.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:27995897
Nasu-Hakola mutations impact protein stability and decrease folded TREM2 surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
|
|
GO:0050714
positive regulation of protein secretion
|
IMP
PMID:27044754 FRMD4A-cytohesin signaling modulates the cellular release of... |
KEEP AS NON CORE |
Summary: positive regulation of protein secretion is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:0043277
apoptotic cell clearance
|
ISS
GO_REF:0000024 |
ACCEPT |
Summary: apoptotic cell clearance is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment, activation, and migration responses.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:0008289
lipid binding
|
TAS
PMID:29518356 TREM2 Is a Receptor for β-Amyloid that Mediates Microglial F... |
ACCEPT |
Summary: TREM2 lipid binding is part of its ligand-sensing receptor biology.
Reason: TREM2 ligand recognition includes lipid-rich particles and supports microglial lipid handling.
Supporting Evidence:
PMID:27477018
we identified a set of lipoprotein particles (including LDL) and apolipoproteins (including CLU/APOJ and APOE) as ligands
PMID:31902528
TREM2 senses lipids and mediates myelin phagocytosis
|
|
GO:0038023
signaling receptor activity
|
ISS
PMID:29518356 TREM2 Is a Receptor for β-Amyloid that Mediates Microglial F... |
ACCEPT |
Summary: TREM2 signaling receptor activity is a core plasma-membrane receptor function coupled to TYROBP/DAP12 signaling.
Reason: TREM2 is a myeloid/microglial cell-surface receptor whose ligand engagement drives intracellular signaling through DAP12/TYROBP-linked kinase pathways.
Supporting Evidence:
PMID:11602640
TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is associated with DAP12.
PMID:11602640
TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC maturation, and DC survival through activation of protein tyrosine kinases and extracellular signal-regulated kinase.
PMID:32514138
TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis, processing of neuronal debris, and lipid metabolism.
|
|
GO:0060075
regulation of resting membrane potential
|
ISS
PMID:29518356 TREM2 Is a Receptor for β-Amyloid that Mediates Microglial F... |
KEEP AS NON CORE |
Summary: regulation of resting membrane potential is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:0120035
regulation of plasma membrane bounded cell projection organization
|
IGI
PMID:29518356 TREM2 Is a Receptor for β-Amyloid that Mediates Microglial F... |
KEEP AS NON CORE |
Summary: regulation of plasma membrane bounded cell projection organization is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:1901800
positive regulation of proteasomal protein catabolic process
|
ISS
PMID:29518356 TREM2 Is a Receptor for β-Amyloid that Mediates Microglial F... |
KEEP AS NON CORE |
Summary: positive regulation of proteasomal protein catabolic process is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:1904141
positive regulation of microglial cell migration
|
ISS
PMID:29518356 TREM2 Is a Receptor for β-Amyloid that Mediates Microglial F... |
ACCEPT |
Summary: positive regulation of microglial cell migration is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
Reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment, activation, and migration responses.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:1904646
cellular response to amyloid-beta
|
ISS
PMID:29518356 TREM2 Is a Receptor for β-Amyloid that Mediates Microglial F... |
KEEP AS NON CORE |
Summary: cellular response to amyloid-beta is Alzheimer-relevant TREM2 biology, but it is a context-specific substrate/phenotype rather than the broad core receptor function.
Reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial function; do not treat them as disease-progression hypotheses in the core function.
Supporting Evidence:
PMID:27477018
β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up by microglia in a TREM2-dependent fashion.
PMID:33097708
TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
|
|
GO:1990782
protein tyrosine kinase binding
|
ISS
PMID:29518356 TREM2 Is a Receptor for β-Amyloid that Mediates Microglial F... |
KEEP AS NON CORE |
Summary: protein tyrosine kinase binding is a specific interaction context for TREM2 but not the main molecular-function term.
Reason: Retain as non-core because the interaction may be real, while more informative core terms describe receptor activity and lipid/lipoprotein/aminophospholipid ligand binding.
|
|
GO:0001540
amyloid-beta binding
|
IPI
PMID:29518356 TREM2 Is a Receptor for β-Amyloid that Mediates Microglial F... |
ACCEPT |
Summary: TREM2 amyloid-beta binding is part of its ligand-sensing receptor biology.
Reason: Amyloid-beta binding is disease-relevant but mechanistically tied to TREM2 ligand uptake through lipoprotein-associated complexes; retain as part of ligand recognition.
Supporting Evidence:
PMID:27477018
β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up by microglia in a TREM2-dependent fashion.
|
|
GO:0044877
protein-containing complex binding
|
IPI
PMID:29518356 TREM2 Is a Receptor for β-Amyloid that Mediates Microglial F... |
MARK AS OVER ANNOTATED |
Summary: Generic protein-containing complex binding annotation for TREM2.
Reason: The interaction may be real, but this term is too generic. Specific ligand-binding, receptor-activity, TYROBP/DAP12 signaling, or phagocytosis annotations are more informative.
|
|
GO:0010628
positive regulation of gene expression
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: positive regulation of gene expression is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:0098657
import into cell
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: import into cell is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:0008035
high-density lipoprotein particle binding
|
IDA
PMID:27477018 TREM2 Binds to Apolipoproteins, Including APOE and CLU/APOJ,... |
ACCEPT |
Summary: TREM2 high-density lipoprotein particle binding is part of its ligand-sensing receptor biology.
Reason: TREM2 recognizes apolipoproteins and lipoprotein particles and promotes their uptake by microglia or receptor-expressing cells.
Supporting Evidence:
PMID:27477018
we identified a set of lipoprotein particles (including LDL) and apolipoproteins (including CLU/APOJ and APOE) as ligands
PMID:27477018
Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL, CLU, and APOE in heterologous cells
|
|
GO:0030169
low-density lipoprotein particle binding
|
IDA
PMID:27477018 TREM2 Binds to Apolipoproteins, Including APOE and CLU/APOJ,... |
ACCEPT |
Summary: TREM2 low-density lipoprotein particle binding is part of its ligand-sensing receptor biology.
Reason: TREM2 recognizes apolipoproteins and lipoprotein particles and promotes their uptake by microglia or receptor-expressing cells.
Supporting Evidence:
PMID:27477018
we identified a set of lipoprotein particles (including LDL) and apolipoproteins (including CLU/APOJ and APOE) as ligands
PMID:27477018
Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL, CLU, and APOE in heterologous cells
|
|
GO:0034185
apolipoprotein binding
|
IPI
PMID:27477018 TREM2 Binds to Apolipoproteins, Including APOE and CLU/APOJ,... |
ACCEPT |
Summary: TREM2 apolipoprotein binding is part of its ligand-sensing receptor biology.
Reason: TREM2 recognizes apolipoproteins and lipoprotein particles and promotes their uptake by microglia or receptor-expressing cells.
Supporting Evidence:
PMID:27477018
we identified a set of lipoprotein particles (including LDL) and apolipoproteins (including CLU/APOJ and APOE) as ligands
PMID:27477018
Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL, CLU, and APOE in heterologous cells
|
|
GO:0034186
apolipoprotein A-I binding
|
IPI
PMID:27477018 TREM2 Binds to Apolipoproteins, Including APOE and CLU/APOJ,... |
ACCEPT |
Summary: TREM2 apolipoprotein A-I binding is part of its ligand-sensing receptor biology.
Reason: TREM2 recognizes apolipoproteins and lipoprotein particles and promotes their uptake by microglia or receptor-expressing cells.
Supporting Evidence:
PMID:27477018
we identified a set of lipoprotein particles (including LDL) and apolipoproteins (including CLU/APOJ and APOE) as ligands
PMID:27477018
Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL, CLU, and APOE in heterologous cells
|
|
GO:0034189
very-low-density lipoprotein particle binding
|
IDA
PMID:27477018 TREM2 Binds to Apolipoproteins, Including APOE and CLU/APOJ,... |
ACCEPT |
Summary: TREM2 very-low-density lipoprotein particle binding is part of its ligand-sensing receptor biology.
Reason: TREM2 recognizes apolipoproteins and lipoprotein particles and promotes their uptake by microglia or receptor-expressing cells.
Supporting Evidence:
PMID:27477018
we identified a set of lipoprotein particles (including LDL) and apolipoproteins (including CLU/APOJ and APOE) as ligands
PMID:27477018
Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL, CLU, and APOE in heterologous cells
|
|
GO:0071813
lipoprotein particle binding
|
IDA
PMID:27477018 TREM2 Binds to Apolipoproteins, Including APOE and CLU/APOJ,... |
ACCEPT |
Summary: TREM2 lipoprotein particle binding is part of its ligand-sensing receptor biology.
Reason: TREM2 recognizes apolipoproteins and lipoprotein particles and promotes their uptake by microglia or receptor-expressing cells.
Supporting Evidence:
PMID:27477018
we identified a set of lipoprotein particles (including LDL) and apolipoproteins (including CLU/APOJ and APOE) as ligands
PMID:27477018
Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL, CLU, and APOE in heterologous cells
|
|
GO:0034241
positive regulation of macrophage fusion
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: positive regulation of macrophage fusion is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:0030316
osteoclast differentiation
|
IMP
PMID:21841309 OSCAR is a collagen receptor that costimulates osteoclastoge... |
KEEP AS NON CORE |
Summary: osteoclast differentiation is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
Supporting Evidence:
PMID:12925681
loss of function mutations in DAP12 and TREM2 result in an inefficient and delayed differentiation of osteoclasts
|
|
GO:0005543
phospholipid binding
|
IDA
PMID:27995897 Neurodegenerative disease mutations in TREM2 reveal a functi... |
ACCEPT |
Summary: TREM2 phospholipid binding is part of its ligand-sensing receptor biology.
Reason: Aminophospholipid and anionic lipid recognition is a core TREM2 ligand-sensing function for apoptotic-cell and debris responses.
Supporting Evidence:
PMID:31101881
TREM2-dependent signal transduction in response to apoptotic Neuro2a cells is mediated by aminophospholipid ligands, phosphatidylserine and phosphatidylethanolamine
|
|
GO:0005886
plasma membrane
|
IDA
PMID:27995897 Neurodegenerative disease mutations in TREM2 reveal a functi... |
ACCEPT |
Summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface receptor role.
Reason: Cell-surface/plasma-membrane localization is essential for ligand binding and DAP12/TYROBP-mediated signal transduction.
Supporting Evidence:
PMID:11602640
TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is associated with DAP12.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:27995897
Nasu-Hakola mutations impact protein stability and decrease folded TREM2 surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
|
|
GO:0070374
positive regulation of ERK1 and ERK2 cascade
|
IMP
PMID:27995897 Neurodegenerative disease mutations in TREM2 reveal a functi... |
ACCEPT |
Summary: positive regulation of ERK1 and ERK2 cascade is a core downstream consequence of TREM2 receptor signaling.
Reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support calcium/ERK/PI3K-related activation and intracellular signaling.
Supporting Evidence:
PMID:11602640
TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC maturation, and DC survival through activation of protein tyrosine kinases and extracellular signal-regulated kinase.
PMID:32514138
TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis, processing of neuronal debris, and lipid metabolism.
|
|
GO:0002588
positive regulation of antigen processing and presentation of peptide antigen via MHC class II
|
IDA
PMID:11602640 A DAP12-mediated pathway regulates expression of CC chemokin... |
KEEP AS NON CORE |
Summary: positive regulation of antigen processing and presentation of peptide antigen via MHC class II is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
|
GO:0016020
membrane
|
IDA
PMID:11602640 A DAP12-mediated pathway regulates expression of CC chemokin... |
ACCEPT |
Summary: TREM2 localization to membrane is consistent with its type I cell-surface receptor role.
Reason: Cell-surface/plasma-membrane localization is essential for ligand binding and DAP12/TYROBP-mediated signal transduction.
Supporting Evidence:
PMID:11602640
TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is associated with DAP12.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:27995897
Nasu-Hakola mutations impact protein stability and decrease folded TREM2 surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
|
|
GO:0050850
positive regulation of calcium-mediated signaling
|
IDA
PMID:11602640 A DAP12-mediated pathway regulates expression of CC chemokin... |
ACCEPT |
Summary: positive regulation of calcium-mediated signaling is a core downstream consequence of TREM2 receptor signaling.
Reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support calcium/ERK/PI3K-related activation and intracellular signaling.
Supporting Evidence:
PMID:11602640
TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC maturation, and DC survival through activation of protein tyrosine kinases and extracellular signal-regulated kinase.
PMID:32514138
TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis, processing of neuronal debris, and lipid metabolism.
|
|
GO:0070374
positive regulation of ERK1 and ERK2 cascade
|
IDA
PMID:11602640 A DAP12-mediated pathway regulates expression of CC chemokin... |
ACCEPT |
Summary: positive regulation of ERK1 and ERK2 cascade is a core downstream consequence of TREM2 receptor signaling.
Reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support calcium/ERK/PI3K-related activation and intracellular signaling.
Supporting Evidence:
PMID:11602640
TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC maturation, and DC survival through activation of protein tyrosine kinases and extracellular signal-regulated kinase.
PMID:32514138
TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis, processing of neuronal debris, and lipid metabolism.
|
|
GO:0097028
dendritic cell differentiation
|
IDA
PMID:11602640 A DAP12-mediated pathway regulates expression of CC chemokin... |
KEEP AS NON CORE |
Summary: dendritic cell differentiation is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:0097110
scaffold protein binding
|
IPI
PMID:11602640 A DAP12-mediated pathway regulates expression of CC chemokin... |
KEEP AS NON CORE |
Summary: scaffold protein binding is a specific interaction context for TREM2 but not the main molecular-function term.
Reason: Retain as non-core because the interaction may be real, while more informative core terms describe receptor activity and lipid/lipoprotein/aminophospholipid ligand binding.
|
|
GO:1903078
positive regulation of protein localization to plasma membrane
|
IDA
PMID:11602640 A DAP12-mediated pathway regulates expression of CC chemokin... |
KEEP AS NON CORE |
Summary: positive regulation of protein localization to plasma membrane is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:1903082
positive regulation of C-C chemokine receptor CCR7 signaling pathway
|
IDA
PMID:11602640 A DAP12-mediated pathway regulates expression of CC chemokin... |
KEEP AS NON CORE |
Summary: positive regulation of C-C chemokine receptor CCR7 signaling pathway is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:2000350
positive regulation of CD40 signaling pathway
|
IDA
PMID:11602640 A DAP12-mediated pathway regulates expression of CC chemokin... |
KEEP AS NON CORE |
Summary: positive regulation of CD40 signaling pathway is retained as context-specific TREM2-associated biology.
Reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the core TREM2 receptor-ligand signaling mechanism.
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-210289 |
ACCEPT |
Summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface receptor role.
Reason: Cell-surface/plasma-membrane localization is essential for ligand binding and DAP12/TYROBP-mediated signal transduction.
Supporting Evidence:
PMID:11602640
TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is associated with DAP12.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:27995897
Nasu-Hakola mutations impact protein stability and decrease folded TREM2 surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-210300 |
ACCEPT |
Summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface receptor role.
Reason: Cell-surface/plasma-membrane localization is essential for ligand binding and DAP12/TYROBP-mediated signal transduction.
Supporting Evidence:
PMID:11602640
TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is associated with DAP12.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:27995897
Nasu-Hakola mutations impact protein stability and decrease folded TREM2 surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-2395412 |
ACCEPT |
Summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface receptor role.
Reason: Cell-surface/plasma-membrane localization is essential for ligand binding and DAP12/TYROBP-mediated signal transduction.
Supporting Evidence:
PMID:11602640
TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is associated with DAP12.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:27995897
Nasu-Hakola mutations impact protein stability and decrease folded TREM2 surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-2395801 |
ACCEPT |
Summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface receptor role.
Reason: Cell-surface/plasma-membrane localization is essential for ligand binding and DAP12/TYROBP-mediated signal transduction.
Supporting Evidence:
PMID:11602640
TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is associated with DAP12.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:27995897
Nasu-Hakola mutations impact protein stability and decrease folded TREM2 surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-2396594 |
ACCEPT |
Summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface receptor role.
Reason: Cell-surface/plasma-membrane localization is essential for ligand binding and DAP12/TYROBP-mediated signal transduction.
Supporting Evidence:
PMID:11602640
TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is associated with DAP12.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:27995897
Nasu-Hakola mutations impact protein stability and decrease folded TREM2 surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-2424480 |
ACCEPT |
Summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface receptor role.
Reason: Cell-surface/plasma-membrane localization is essential for ligand binding and DAP12/TYROBP-mediated signal transduction.
Supporting Evidence:
PMID:11602640
TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is associated with DAP12.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:27995897
Nasu-Hakola mutations impact protein stability and decrease folded TREM2 surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-2424482 |
ACCEPT |
Summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface receptor role.
Reason: Cell-surface/plasma-membrane localization is essential for ligand binding and DAP12/TYROBP-mediated signal transduction.
Supporting Evidence:
PMID:11602640
TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is associated with DAP12.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:27995897
Nasu-Hakola mutations impact protein stability and decrease folded TREM2 surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-2424484 |
ACCEPT |
Summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface receptor role.
Reason: Cell-surface/plasma-membrane localization is essential for ligand binding and DAP12/TYROBP-mediated signal transduction.
Supporting Evidence:
PMID:11602640
TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is associated with DAP12.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:27995897
Nasu-Hakola mutations impact protein stability and decrease folded TREM2 surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-2424486 |
ACCEPT |
Summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface receptor role.
Reason: Cell-surface/plasma-membrane localization is essential for ligand binding and DAP12/TYROBP-mediated signal transduction.
Supporting Evidence:
PMID:11602640
TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is associated with DAP12.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:27995897
Nasu-Hakola mutations impact protein stability and decrease folded TREM2 surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-2424487 |
ACCEPT |
Summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface receptor role.
Reason: Cell-surface/plasma-membrane localization is essential for ligand binding and DAP12/TYROBP-mediated signal transduction.
Supporting Evidence:
PMID:11602640
TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is associated with DAP12.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:27995897
Nasu-Hakola mutations impact protein stability and decrease folded TREM2 surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-416725 |
ACCEPT |
Summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface receptor role.
Reason: Cell-surface/plasma-membrane localization is essential for ligand binding and DAP12/TYROBP-mediated signal transduction.
Supporting Evidence:
PMID:11602640
TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is associated with DAP12.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:27995897
Nasu-Hakola mutations impact protein stability and decrease folded TREM2 surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-5696358 |
ACCEPT |
Summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface receptor role.
Reason: Cell-surface/plasma-membrane localization is essential for ligand binding and DAP12/TYROBP-mediated signal transduction.
Supporting Evidence:
PMID:11602640
TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is associated with DAP12.
PMID:24990881
missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
PMID:27995897
Nasu-Hakola mutations impact protein stability and decrease folded TREM2 surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
|
|
GO:0006959
humoral immune response
|
TAS
PMID:10799849 Cutting edge: inflammatory responses can be triggered by TRE... |
KEEP AS NON CORE |
Summary: humoral immune response is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
Reason: TREM2 modulates myeloid and microglial immune responses, but specific cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
Supporting Evidence:
PMID:24990881
TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis.
|
Q: Which TREM2 ligand classes are normal in-vivo microglial ligands across brain states, and which are disease-model or injury-specific substrates?
Suggested experts: microglial biology experts, GO immune receptor curators
Q: How should TREM2/TYROBP/DAP12 signaling be represented without over-curating every downstream cytokine, kinase, survival, or metabolic phenotype as a core function?
Suggested experts: innate immune signaling curators, microglial signaling experts
Q: Which amyloid-beta, synapse-pruning, and neuroinflammatory annotations reflect evolved TREM2 biology versus Alzheimer model-stage-specific phenotypes?
Suggested experts: Alzheimer microglia experts, GO neuroimmune curators
Experiment: Compare endogenous human TREM2 knock-in and knockout microglia across defined ligands: apoptotic cells, purified aminophospholipids, APOE/CLU lipoprotein particles, myelin debris, synaptosomes, and amyloid-beta-lipoprotein complexes.
Hypothesis: TREM2 core ligand sensing can be decomposed into ligand classes with distinct requirements for TYROBP/DAP12, PLCG2, SYK, and calcium signaling.
Type: ligand-defined microglial uptake and signaling assays
Experiment: Use in-vivo baseline, injury, demyelination, and amyloid/tau model time courses to separate normal TREM2-dependent phagocytic functions from disease-stage-specific microglial states.
Hypothesis: Some TREM2 annotations, especially amyloid clearance and synapse pruning, are context-specific outputs of the same core receptor-phagocytosis program.
Type: time-course in-vivo microglial transcriptomics and functional assays
Experiment: Quantify cell-surface TREM2, soluble TREM2, and TYROBP-associated signaling after endogenous AD-risk variant knock-in under non-disease and challenge conditions.
Hypothesis: Disease-associated variants alter ligand binding, surface trafficking, or signaling amplitude without changing the core receptor function category.
Type: endogenous variant knock-in receptor trafficking and signaling
just fetch-gene-pmids human TREM2 completed successfully; all 31 PMID-backed publication caches were present after refresh.timeout 180 just deep-research-falcon human TREM2 --fallback perplexity-lite, but the process timed out and no provider deep-research artifact was written. These notes therefore rely on the cached UniProt, GOA, and publication files.just validate human TREM2 passes cleanly.TREM2 is a plasma-membrane immunoreceptor expressed prominently in myeloid cells, including microglia. Its core function is ligand sensing through an extracellular immunoglobulin-like domain, with signaling through TYROBP/DAP12 and downstream kinase/Ca2+/ERK pathways. The original receptor characterization supports the surface receptor and DAP12 coupling model: PMID:11602640 The same study supports downstream signaling and survival/maturation responses: PMID:11602640
The best-supported ligand biology is lipid/apolipoprotein and damage-associated membrane sensing. TREM2 binds apolipoprotein and lipoprotein ligands, including APOE and CLU/APOJ: PMID:27477018 This ligand binding is functionally tied to uptake: PMID:27477018 and to microglial handling of amyloid-lipoprotein complexes: PMID:27477018
Independent ligand work supports aminophospholipids on apoptotic cells as signal-transducing TREM2 ligands: PMID:31101881 Myelin/lipid challenge studies further support lipid sensing as a microglial core function: PMID:31902528 and identify a role in cholesterol-related transcriptional adaptation after chronic phagocytosis: PMID:31902528
Human microglia data support the downstream functional consequences of TREM2 loss: PMID:33097708 and broader functional deficits in phagocytosis and migration. Earlier disease-variant work supports a microglial innate immune and phagocytic framing: PMID:24990881 Variant studies also distinguish Nasu-Hakola and Alzheimer-risk mechanisms, with many Alzheimer-associated variants affecting ligand binding rather than complete loss of surface expression: PMID:27995897
protein binding and broad complex-binding annotations as over-annotated because they obscure the better-supported ligand and receptor-adapter biology.Final action distribution: 117 ACCEPT, 151 KEEP_AS_NON_CORE, 5 MARK_AS_OVER_ANNOTATED.
The second-pass audit added manual reference_review metadata for the main TREM2 receptor, DAP12 signaling, lipid/apolipoprotein ligand, amyloid-beta ligand, apoptotic-cell aminophospholipid ligand, myelin/cholesterol-response, and human microglia loss-of-function papers. No annotation action changes were needed: TREM2 remains curated as a myeloid/microglial immunoreceptor for damage-associated lipid, apolipoprotein, apoptotic-cell, and amyloid-associated ligands, with plaque, synaptic, and broad inflammatory phenotypes retained as non-core context where appropriate.
id: Q9NZC2
gene_symbol: TREM2
product_type: PROTEIN
status: COMPLETE
taxon:
id: NCBITaxon:9606
label: Homo sapiens
description: 'TREM2 is a type I plasma-membrane immunoglobulin-superfamily receptor expressed mainly by
microglia and other myeloid-lineage cells. Together with the TYROBP/DAP12 adaptor, TREM2 converts ligand
binding at the cell surface into intracellular signaling through kinases and PLCG2-linked pathways that
support cell survival, calcium/ERK signaling, phagocytosis, chemotaxis, microglial activation, and lipid
handling. TREM2 recognizes lipid-rich and damage-associated ligands, including aminophospholipids exposed
on apoptotic cells, lipoprotein particles and apolipoproteins, and amyloid-beta-lipoprotein complexes.
Disease-model annotations involving amyloid plaques, synapse pruning, neuroinflammation, osteoclast
biology, and dendritic cell maturation are important contexts but are secondary to the core receptor-ligand
signaling and phagocytic myeloid-cell functions.'
alternative_products:
- name: '1'
id: Q9NZC2-1
- name: 2 (TREM-2V)
id: Q9NZC2-2
sequence_note: VSP_010792
- name: '3'
id: Q9NZC2-3
sequence_note: VSP_010793
existing_annotations:
- term:
id: GO:0005886
label: plasma membrane
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: is_active_in
review:
summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface
receptor role.
action: ACCEPT
reason: Cell-surface/plasma-membrane localization is essential for ligand binding and
DAP12/TYROBP-mediated signal transduction.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is
associated with DAP12.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:27995897
supporting_text: Nasu-Hakola mutations impact protein stability and decrease folded TREM2
surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
- term:
id: GO:0004888
label: transmembrane signaling receptor activity
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: enables
review:
summary: TREM2 transmembrane signaling receptor activity is a core plasma-membrane receptor
function coupled to TYROBP/DAP12 signaling.
action: ACCEPT
reason: TREM2 is a myeloid/microglial cell-surface receptor whose ligand engagement drives
intracellular signaling through DAP12/TYROBP-linked kinase pathways.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is
associated with DAP12.
- reference_id: PMID:11602640
supporting_text: TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC
maturation, and DC survival through activation of protein tyrosine kinases and extracellular
signal-regulated kinase.
- reference_id: PMID:32514138
supporting_text: TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis,
processing of neuronal debris, and lipid metabolism.
- term:
id: GO:0007165
label: signal transduction
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
summary: signal transduction is a core downstream consequence of TREM2 receptor signaling.
action: ACCEPT
reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support
calcium/ERK/PI3K-related activation and intracellular signaling.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC
maturation, and DC survival through activation of protein tyrosine kinases and extracellular
signal-regulated kinase.
- reference_id: PMID:32514138
supporting_text: TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis,
processing of neuronal debris, and lipid metabolism.
- term:
id: GO:0045088
label: regulation of innate immune response
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
summary: regulation of innate immune response is a core downstream consequence of TREM2 receptor
signaling.
action: ACCEPT
reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support
calcium/ERK/PI3K-related activation and intracellular signaling.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC
maturation, and DC survival through activation of protein tyrosine kinases and extracellular
signal-regulated kinase.
- reference_id: PMID:32514138
supporting_text: TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis,
processing of neuronal debris, and lipid metabolism.
- term:
id: GO:0050850
label: positive regulation of calcium-mediated signaling
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
summary: positive regulation of calcium-mediated signaling is a core downstream consequence of
TREM2 receptor signaling.
action: ACCEPT
reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support
calcium/ERK/PI3K-related activation and intracellular signaling.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC
maturation, and DC survival through activation of protein tyrosine kinases and extracellular
signal-regulated kinase.
- reference_id: PMID:32514138
supporting_text: TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis,
processing of neuronal debris, and lipid metabolism.
- term:
id: GO:0060100
label: positive regulation of phagocytosis, engulfment
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
summary: positive regulation of phagocytosis, engulfment is part of TREM2-mediated
microglial/myeloid phagocytic or lipid-response biology.
action: ACCEPT
reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment,
activation, and migration responses.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:0070374
label: positive regulation of ERK1 and ERK2 cascade
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
summary: positive regulation of ERK1 and ERK2 cascade is a core downstream consequence of TREM2
receptor signaling.
action: ACCEPT
reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support
calcium/ERK/PI3K-related activation and intracellular signaling.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC
maturation, and DC survival through activation of protein tyrosine kinases and extracellular
signal-regulated kinase.
- reference_id: PMID:32514138
supporting_text: TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis,
processing of neuronal debris, and lipid metabolism.
- term:
id: GO:0120035
label: regulation of plasma membrane bounded cell projection organization
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
summary: regulation of plasma membrane bounded cell projection organization is retained as
context-specific TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:1903980
label: positive regulation of microglial cell activation
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
summary: positive regulation of microglial cell activation is part of TREM2-mediated
microglial/myeloid phagocytic or lipid-response biology.
action: ACCEPT
reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment,
activation, and migration responses.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:0004888
label: transmembrane signaling receptor activity
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: enables
review:
summary: TREM2 transmembrane signaling receptor activity is a core plasma-membrane receptor
function coupled to TYROBP/DAP12 signaling.
action: ACCEPT
reason: TREM2 is a myeloid/microglial cell-surface receptor whose ligand engagement drives
intracellular signaling through DAP12/TYROBP-linked kinase pathways.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is
associated with DAP12.
- reference_id: PMID:11602640
supporting_text: TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC
maturation, and DC survival through activation of protein tyrosine kinases and extracellular
signal-regulated kinase.
- reference_id: PMID:32514138
supporting_text: TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis,
processing of neuronal debris, and lipid metabolism.
- term:
id: GO:0005576
label: extracellular region
evidence_type: IEA
original_reference_id: GO_REF:0000044
qualifier: located_in
review:
summary: The extracellular-region annotation likely reflects secreted or shed TREM2
isoforms/fragments rather than the core membrane receptor.
action: KEEP_AS_NON_CORE
reason: Retain as non-core because soluble TREM2 biology is relevant, but the primary TREM2
function is cell-surface receptor signaling.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: IEA
original_reference_id: GO_REF:0000120
qualifier: located_in
review:
summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface
receptor role.
action: ACCEPT
reason: Cell-surface/plasma-membrane localization is essential for ligand binding and
DAP12/TYROBP-mediated signal transduction.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is
associated with DAP12.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:27995897
supporting_text: Nasu-Hakola mutations impact protein stability and decrease folded TREM2
surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
- term:
id: GO:0006909
label: phagocytosis
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: involved_in
review:
summary: phagocytosis is part of TREM2-mediated microglial/myeloid phagocytic or lipid-response
biology.
action: ACCEPT
reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment,
activation, and migration responses.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:0008289
label: lipid binding
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: enables
review:
summary: TREM2 lipid binding is part of its ligand-sensing receptor biology.
action: ACCEPT
reason: TREM2 ligand recognition includes lipid-rich particles and supports microglial lipid
handling.
supported_by:
- reference_id: PMID:27477018
supporting_text: we identified a set of lipoprotein particles (including LDL) and
apolipoproteins (including CLU/APOJ and APOE) as ligands
- reference_id: PMID:31902528
supporting_text: TREM2 senses lipids and mediates myelin phagocytosis
- term:
id: GO:0035176
label: social behavior
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: involved_in
review:
summary: social behavior is retained as context-specific TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:0048468
label: cell development
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: involved_in
review:
summary: cell development is retained as context-specific TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:0050850
label: positive regulation of calcium-mediated signaling
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: involved_in
review:
summary: positive regulation of calcium-mediated signaling is a core downstream consequence of
TREM2 receptor signaling.
action: ACCEPT
reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support
calcium/ERK/PI3K-related activation and intracellular signaling.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC
maturation, and DC survival through activation of protein tyrosine kinases and extracellular
signal-regulated kinase.
- reference_id: PMID:32514138
supporting_text: TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis,
processing of neuronal debris, and lipid metabolism.
- term:
id: GO:0071396
label: cellular response to lipid
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: involved_in
review:
summary: cellular response to lipid is part of TREM2-mediated microglial/myeloid phagocytic or
lipid-response biology.
action: ACCEPT
reason: TREM2 ligand sensing and phagocytic challenge regulate microglial lipid/cholesterol
handling.
supported_by:
- reference_id: PMID:31902528
supporting_text: TREM2 senses lipids and mediates myelin phagocytosis
- reference_id: PMID:31902528
supporting_text: Our studies identify TREM2 as a key transcriptional regulator of cholesterol
transport and metabolism under conditions of chronic myelin phagocytic activity
- reference_id: PMID:27477018
supporting_text: Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL,
CLU, and APOE in heterologous cells
- term:
id: GO:0097367
label: carbohydrate derivative binding
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: enables
review:
summary: carbohydrate derivative binding is retained as non-core TREM2-associated biology
pending deeper reference-specific adjudication.
action: KEEP_AS_NON_CORE
reason: The annotation is not part of the primary receptor-ligand signaling and phagocytic
microglial function set, but the local evidence was not sufficient to remove it.
- term:
id: GO:1900226
label: negative regulation of NLRP3 inflammasome complex assembly
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: involved_in
review:
summary: negative regulation of NLRP3 inflammasome complex assembly is retained as non-core
TREM2-associated biology pending deeper reference-specific adjudication.
action: KEEP_AS_NON_CORE
reason: The annotation is not part of the primary receptor-ligand signaling and phagocytic
microglial function set, but the local evidence was not sufficient to remove it.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:11602640
qualifier: enables
review:
summary: Generic protein binding annotation for TREM2.
action: MARK_AS_OVER_ANNOTATED
reason: The interaction may be real, but this term is too generic. Specific ligand-binding,
receptor-activity, TYROBP/DAP12 signaling, or phagocytosis annotations are more informative.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:28490631
qualifier: enables
review:
summary: Generic protein binding annotation for TREM2.
action: MARK_AS_OVER_ANNOTATED
reason: The interaction may be real, but this term is too generic. Specific ligand-binding,
receptor-activity, TYROBP/DAP12 signaling, or phagocytosis annotations are more informative.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:29611543
qualifier: enables
review:
summary: Generic protein binding annotation for TREM2.
action: MARK_AS_OVER_ANNOTATED
reason: The interaction may be real, but this term is too generic. Specific ligand-binding,
receptor-activity, TYROBP/DAP12 signaling, or phagocytosis annotations are more informative.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:30341064
qualifier: enables
review:
summary: Generic protein binding annotation for TREM2.
action: MARK_AS_OVER_ANNOTATED
reason: The interaction may be real, but this term is too generic. Specific ligand-binding,
receptor-activity, TYROBP/DAP12 signaling, or phagocytosis annotations are more informative.
- term:
id: GO:0001530
label: lipopolysaccharide binding
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: enables
review:
summary: lipopolysaccharide binding is electronically inferred pathogen-associated ligand or
defense biology.
action: KEEP_AS_NON_CORE
reason: Retain as non-core because TREM-family receptors participate in myeloid immune sensing,
but the cached human TREM2 evidence reviewed here emphasizes lipids, apoptotic cells, and
microglial phagocytic ligands.
- term:
id: GO:0001774
label: microglial cell activation
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: microglial cell activation is part of TREM2-mediated microglial/myeloid phagocytic or
lipid-response biology.
action: ACCEPT
reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment,
activation, and migration responses.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:0002282
label: microglial cell activation involved in immune response
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: microglial cell activation involved in immune response is part of TREM2-mediated
microglial/myeloid phagocytic or lipid-response biology.
action: ACCEPT
reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment,
activation, and migration responses.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:0002291
label: T cell activation via T cell receptor contact with antigen bound to MHC molecule on
antigen presenting cell
evidence_type: IEA
original_reference_id: GO_REF:0000120
qualifier: involved_in
review:
summary: T cell activation via T cell receptor contact with antigen bound to MHC molecule on
antigen presenting cell is a plausible downstream immune/inflammatory consequence of TREM2
signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- term:
id: GO:0002862
label: negative regulation of inflammatory response to antigenic stimulus
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: negative regulation of inflammatory response to antigenic stimulus is a plausible
downstream immune/inflammatory consequence of TREM2 signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- term:
id: GO:0002931
label: response to ischemia
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: response to ischemia is retained as context-specific TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:0010507
label: negative regulation of autophagy
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: negative regulation of autophagy is retained as context-specific TREM2-associated
biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:0010628
label: positive regulation of gene expression
evidence_type: IEA
original_reference_id: GO_REF:0000120
qualifier: involved_in
review:
summary: positive regulation of gene expression is retained as context-specific TREM2-associated
biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:0010875
label: positive regulation of cholesterol efflux
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: positive regulation of cholesterol efflux is part of TREM2-mediated microglial/myeloid
phagocytic or lipid-response biology.
action: ACCEPT
reason: TREM2 ligand sensing and phagocytic challenge regulate microglial lipid/cholesterol
handling.
supported_by:
- reference_id: PMID:31902528
supporting_text: TREM2 senses lipids and mediates myelin phagocytosis
- reference_id: PMID:31902528
supporting_text: Our studies identify TREM2 as a key transcriptional regulator of cholesterol
transport and metabolism under conditions of chronic myelin phagocytic activity
- reference_id: PMID:27477018
supporting_text: Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL,
CLU, and APOE in heterologous cells
- term:
id: GO:0010887
label: negative regulation of cholesterol storage
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: negative regulation of cholesterol storage is part of TREM2-mediated microglial/myeloid
phagocytic or lipid-response biology.
action: ACCEPT
reason: TREM2 ligand sensing and phagocytic challenge regulate microglial lipid/cholesterol
handling.
supported_by:
- reference_id: PMID:31902528
supporting_text: TREM2 senses lipids and mediates myelin phagocytosis
- reference_id: PMID:31902528
supporting_text: Our studies identify TREM2 as a key transcriptional regulator of cholesterol
transport and metabolism under conditions of chronic myelin phagocytic activity
- reference_id: PMID:27477018
supporting_text: Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL,
CLU, and APOE in heterologous cells
- term:
id: GO:0010891
label: negative regulation of triglyceride storage
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: negative regulation of triglyceride storage is part of TREM2-mediated
microglial/myeloid phagocytic or lipid-response biology.
action: ACCEPT
reason: TREM2 ligand sensing and phagocytic challenge regulate microglial lipid/cholesterol
handling.
supported_by:
- reference_id: PMID:31902528
supporting_text: TREM2 senses lipids and mediates myelin phagocytosis
- reference_id: PMID:31902528
supporting_text: Our studies identify TREM2 as a key transcriptional regulator of cholesterol
transport and metabolism under conditions of chronic myelin phagocytic activity
- reference_id: PMID:27477018
supporting_text: Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL,
CLU, and APOE in heterologous cells
- term:
id: GO:0010983
label: positive regulation of high-density lipoprotein particle clearance
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: positive regulation of high-density lipoprotein particle clearance is part of
TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
action: ACCEPT
reason: TREM2 ligand sensing and phagocytic challenge regulate microglial lipid/cholesterol
handling.
supported_by:
- reference_id: PMID:31902528
supporting_text: TREM2 senses lipids and mediates myelin phagocytosis
- reference_id: PMID:31902528
supporting_text: Our studies identify TREM2 as a key transcriptional regulator of cholesterol
transport and metabolism under conditions of chronic myelin phagocytic activity
- reference_id: PMID:27477018
supporting_text: Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL,
CLU, and APOE in heterologous cells
- term:
id: GO:0017154
label: semaphorin receptor activity
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: enables
review:
summary: semaphorin receptor activity is retained as context-specific TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:0030215
label: semaphorin receptor binding
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: enables
review:
summary: semaphorin receptor binding is retained as context-specific TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:0032006
label: regulation of TOR signaling
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: regulation of TOR signaling is retained as context-specific TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:0032008
label: positive regulation of TOR signaling
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: positive regulation of TOR signaling is retained as context-specific TREM2-associated
biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:0032497
label: detection of lipopolysaccharide
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: detection of lipopolysaccharide is electronically inferred pathogen-associated ligand
or defense biology.
action: KEEP_AS_NON_CORE
reason: Retain as non-core because TREM-family receptors participate in myeloid immune sensing,
but the cached human TREM2 evidence reviewed here emphasizes lipids, apoptotic cells, and
microglial phagocytic ligands.
- term:
id: GO:0032499
label: detection of peptidoglycan
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: detection of peptidoglycan is electronically inferred pathogen-associated ligand or
defense biology.
action: KEEP_AS_NON_CORE
reason: Retain as non-core because TREM-family receptors participate in myeloid immune sensing,
but the cached human TREM2 evidence reviewed here emphasizes lipids, apoptotic cells, and
microglial phagocytic ligands.
- term:
id: GO:0032675
label: regulation of interleukin-6 production
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: regulation of interleukin-6 production is a plausible downstream immune/inflammatory
consequence of TREM2 signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- term:
id: GO:0032691
label: negative regulation of interleukin-1 beta production
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: negative regulation of interleukin-1 beta production is a plausible downstream
immune/inflammatory consequence of TREM2 signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- term:
id: GO:0032720
label: negative regulation of tumor necrosis factor production
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: negative regulation of tumor necrosis factor production is a plausible downstream
immune/inflammatory consequence of TREM2 signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- 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: positive regulation of interleukin-10 production is a plausible downstream
immune/inflammatory consequence of TREM2 signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- term:
id: GO:0034136
label: negative regulation of toll-like receptor 2 signaling pathway
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: negative regulation of toll-like receptor 2 signaling pathway is a plausible downstream
immune/inflammatory consequence of TREM2 signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- term:
id: GO:0034144
label: negative regulation of toll-like receptor 4 signaling pathway
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: negative regulation of toll-like receptor 4 signaling pathway is a plausible downstream
immune/inflammatory consequence of TREM2 signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- term:
id: GO:0034151
label: regulation of toll-like receptor 6 signaling pathway
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: regulation of toll-like receptor 6 signaling pathway is a plausible downstream
immune/inflammatory consequence of TREM2 signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- term:
id: GO:0034241
label: positive regulation of macrophage fusion
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: positive regulation of macrophage fusion is retained as context-specific
TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:0034351
label: negative regulation of glial cell apoptotic process
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: negative regulation of glial cell apoptotic process is retained as non-core
TREM2-associated biology pending deeper reference-specific adjudication.
action: KEEP_AS_NON_CORE
reason: The annotation is not part of the primary receptor-ligand signaling and phagocytic
microglial function set, but the local evidence was not sufficient to remove it.
- term:
id: GO:0038023
label: signaling receptor activity
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: enables
review:
summary: TREM2 signaling receptor activity is a core plasma-membrane receptor function coupled
to TYROBP/DAP12 signaling.
action: ACCEPT
reason: TREM2 is a myeloid/microglial cell-surface receptor whose ligand engagement drives
intracellular signaling through DAP12/TYROBP-linked kinase pathways.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is
associated with DAP12.
- reference_id: PMID:11602640
supporting_text: TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC
maturation, and DC survival through activation of protein tyrosine kinases and extracellular
signal-regulated kinase.
- reference_id: PMID:32514138
supporting_text: TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis,
processing of neuronal debris, and lipid metabolism.
- term:
id: GO:0042742
label: defense response to bacterium
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: defense response to bacterium is electronically inferred pathogen-associated ligand or
defense biology.
action: KEEP_AS_NON_CORE
reason: Retain as non-core because TREM-family receptors participate in myeloid immune sensing,
but the cached human TREM2 evidence reviewed here emphasizes lipids, apoptotic cells, and
microglial phagocytic ligands.
- term:
id: GO:0042834
label: peptidoglycan binding
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: enables
review:
summary: peptidoglycan binding is electronically inferred pathogen-associated ligand or defense
biology.
action: KEEP_AS_NON_CORE
reason: Retain as non-core because TREM-family receptors participate in myeloid immune sensing,
but the cached human TREM2 evidence reviewed here emphasizes lipids, apoptotic cells, and
microglial phagocytic ligands.
- term:
id: GO:0043066
label: negative regulation of apoptotic process
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: negative regulation of apoptotic process is retained as context-specific
TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:0043124
label: negative regulation of canonical NF-kappaB signal transduction
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: negative regulation of canonical NF-kappaB signal transduction is a plausible
downstream immune/inflammatory consequence of TREM2 signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- term:
id: GO:0043268
label: positive regulation of potassium ion transport
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: positive regulation of potassium ion transport is retained as context-specific
TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:0043277
label: apoptotic cell clearance
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: apoptotic cell clearance is part of TREM2-mediated microglial/myeloid phagocytic or
lipid-response biology.
action: ACCEPT
reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment,
activation, and migration responses.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:0045088
label: regulation of innate immune response
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: regulation of innate immune response is a core downstream consequence of TREM2 receptor
signaling.
action: ACCEPT
reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support
calcium/ERK/PI3K-related activation and intracellular signaling.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC
maturation, and DC survival through activation of protein tyrosine kinases and extracellular
signal-regulated kinase.
- reference_id: PMID:32514138
supporting_text: TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis,
processing of neuronal debris, and lipid metabolism.
- term:
id: GO:0045672
label: positive regulation of osteoclast differentiation
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: positive regulation of osteoclast differentiation is retained as context-specific
TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
supported_by:
- reference_id: PMID:12925681
supporting_text: loss of function mutations in DAP12 and TREM2 result in an inefficient and
delayed differentiation of osteoclasts
- term:
id: GO:0045728
label: respiratory burst after phagocytosis
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: respiratory burst after phagocytosis is a plausible downstream immune/inflammatory
consequence of TREM2 signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- term:
id: GO:0045960
label: positive regulation of complement activation, classical pathway
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: positive regulation of complement activation, classical pathway is a plausible
downstream immune/inflammatory consequence of TREM2 signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- term:
id: GO:0048143
label: astrocyte activation
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: astrocyte activation is a plausible downstream immune/inflammatory consequence of TREM2
signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- term:
id: GO:0048678
label: response to axon injury
evidence_type: IEA
original_reference_id: GO_REF:0000120
qualifier: involved_in
review:
summary: response to axon injury is Alzheimer-relevant TREM2 biology, but it is a
context-specific substrate/phenotype rather than the broad core receptor function.
action: KEEP_AS_NON_CORE
reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial
function; do not treat them as disease-progression hypotheses in the core function.
supported_by:
- reference_id: PMID:27477018
supporting_text: β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up
by microglia in a TREM2-dependent fashion.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:0050766
label: positive regulation of phagocytosis
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: positive regulation of phagocytosis is part of TREM2-mediated microglial/myeloid
phagocytic or lipid-response biology.
action: ACCEPT
reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment,
activation, and migration responses.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:0050866
label: negative regulation of cell activation
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: negative regulation of cell activation is a plausible downstream immune/inflammatory
consequence of TREM2 signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- term:
id: GO:0050921
label: positive regulation of chemotaxis
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: positive regulation of chemotaxis is part of TREM2-mediated microglial/myeloid
phagocytic or lipid-response biology.
action: ACCEPT
reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment,
activation, and migration responses.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:0051897
label: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal
transduction is a core downstream consequence of TREM2 receptor signaling.
action: ACCEPT
reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support
calcium/ERK/PI3K-related activation and intracellular signaling.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC
maturation, and DC survival through activation of protein tyrosine kinases and extracellular
signal-regulated kinase.
- reference_id: PMID:32514138
supporting_text: TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis,
processing of neuronal debris, and lipid metabolism.
- term:
id: GO:0051898
label: negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
evidence_type: IEA
original_reference_id: GO_REF:0000120
qualifier: involved_in
review:
summary: negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal
transduction is a core downstream consequence of TREM2 receptor signaling.
action: ACCEPT
reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support
calcium/ERK/PI3K-related activation and intracellular signaling.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC
maturation, and DC survival through activation of protein tyrosine kinases and extracellular
signal-regulated kinase.
- reference_id: PMID:32514138
supporting_text: TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis,
processing of neuronal debris, and lipid metabolism.
- term:
id: GO:0055088
label: lipid homeostasis
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: lipid homeostasis is part of TREM2-mediated microglial/myeloid phagocytic or
lipid-response biology.
action: ACCEPT
reason: TREM2 ligand sensing and phagocytic challenge regulate microglial lipid/cholesterol
handling.
supported_by:
- reference_id: PMID:31902528
supporting_text: TREM2 senses lipids and mediates myelin phagocytosis
- reference_id: PMID:31902528
supporting_text: Our studies identify TREM2 as a key transcriptional regulator of cholesterol
transport and metabolism under conditions of chronic myelin phagocytic activity
- reference_id: PMID:27477018
supporting_text: Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL,
CLU, and APOE in heterologous cells
- term:
id: GO:0060075
label: regulation of resting membrane potential
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: regulation of resting membrane potential is retained as context-specific
TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:0060100
label: positive regulation of phagocytosis, engulfment
evidence_type: IEA
original_reference_id: GO_REF:0000120
qualifier: involved_in
review:
summary: positive regulation of phagocytosis, engulfment is part of TREM2-mediated
microglial/myeloid phagocytic or lipid-response biology.
action: ACCEPT
reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment,
activation, and migration responses.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:0061518
label: microglial cell proliferation
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: microglial cell proliferation is retained as context-specific TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:0061889
label: negative regulation of astrocyte activation
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: negative regulation of astrocyte activation is a plausible downstream
immune/inflammatory consequence of TREM2 signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- term:
id: GO:0070345
label: negative regulation of fat cell proliferation
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: negative regulation of fat cell proliferation is retained as context-specific
TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:0070374
label: positive regulation of ERK1 and ERK2 cascade
evidence_type: IEA
original_reference_id: GO_REF:0000120
qualifier: involved_in
review:
summary: positive regulation of ERK1 and ERK2 cascade is a core downstream consequence of TREM2
receptor signaling.
action: ACCEPT
reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support
calcium/ERK/PI3K-related activation and intracellular signaling.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC
maturation, and DC survival through activation of protein tyrosine kinases and extracellular
signal-regulated kinase.
- reference_id: PMID:32514138
supporting_text: TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis,
processing of neuronal debris, and lipid metabolism.
- term:
id: GO:0070392
label: detection of lipoteichoic acid
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: detection of lipoteichoic acid is electronically inferred pathogen-associated ligand or
defense biology.
action: KEEP_AS_NON_CORE
reason: Retain as non-core because TREM-family receptors participate in myeloid immune sensing,
but the cached human TREM2 evidence reviewed here emphasizes lipids, apoptotic cells, and
microglial phagocytic ligands.
- term:
id: GO:0070891
label: lipoteichoic acid binding
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: enables
review:
summary: lipoteichoic acid binding is electronically inferred pathogen-associated ligand or
defense biology.
action: KEEP_AS_NON_CORE
reason: Retain as non-core because TREM-family receptors participate in myeloid immune sensing,
but the cached human TREM2 evidence reviewed here emphasizes lipids, apoptotic cells, and
microglial phagocytic ligands.
- term:
id: GO:0071223
label: cellular response to lipoteichoic acid
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: cellular response to lipoteichoic acid is electronically inferred pathogen-associated
ligand or defense biology.
action: KEEP_AS_NON_CORE
reason: Retain as non-core because TREM-family receptors participate in myeloid immune sensing,
but the cached human TREM2 evidence reviewed here emphasizes lipids, apoptotic cells, and
microglial phagocytic ligands.
- term:
id: GO:0071224
label: cellular response to peptidoglycan
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: cellular response to peptidoglycan is electronically inferred pathogen-associated
ligand or defense biology.
action: KEEP_AS_NON_CORE
reason: Retain as non-core because TREM-family receptors participate in myeloid immune sensing,
but the cached human TREM2 evidence reviewed here emphasizes lipids, apoptotic cells, and
microglial phagocytic ligands.
- term:
id: GO:0071333
label: cellular response to glucose stimulus
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: cellular response to glucose stimulus is retained as context-specific TREM2-associated
biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:0071456
label: cellular response to hypoxia
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: cellular response to hypoxia is retained as context-specific TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:0071526
label: semaphorin-plexin signaling pathway
evidence_type: IEA
original_reference_id: GO_REF:0000120
qualifier: involved_in
review:
summary: semaphorin-plexin signaling pathway is retained as context-specific TREM2-associated
biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:0071640
label: regulation of macrophage inflammatory protein 1 alpha production
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: regulation of macrophage inflammatory protein 1 alpha production is a plausible
downstream immune/inflammatory consequence of TREM2 signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- term:
id: GO:0097062
label: dendritic spine maintenance
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: dendritic spine maintenance is Alzheimer-relevant TREM2 biology, but it is a
context-specific substrate/phenotype rather than the broad core receptor function.
action: KEEP_AS_NON_CORE
reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial
function; do not treat them as disease-progression hypotheses in the core function.
supported_by:
- reference_id: PMID:27477018
supporting_text: β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up
by microglia in a TREM2-dependent fashion.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:0097242
label: amyloid-beta clearance
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: amyloid-beta clearance is Alzheimer-relevant TREM2 biology, but it is a
context-specific substrate/phenotype rather than the broad core receptor function.
action: KEEP_AS_NON_CORE
reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial
function; do not treat them as disease-progression hypotheses in the core function.
supported_by:
- reference_id: PMID:27477018
supporting_text: β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up
by microglia in a TREM2-dependent fashion.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:0098657
label: import into cell
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: import into cell is retained as context-specific TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:0110089
label: regulation of hippocampal neuron apoptotic process
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: regulation of hippocampal neuron apoptotic process is Alzheimer-relevant TREM2 biology,
but it is a context-specific substrate/phenotype rather than the broad core receptor function.
action: KEEP_AS_NON_CORE
reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial
function; do not treat them as disease-progression hypotheses in the core function.
supported_by:
- reference_id: PMID:27477018
supporting_text: β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up
by microglia in a TREM2-dependent fashion.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:0120035
label: regulation of plasma membrane bounded cell projection organization
evidence_type: IEA
original_reference_id: GO_REF:0000120
qualifier: involved_in
review:
summary: regulation of plasma membrane bounded cell projection organization is retained as
context-specific TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:0150062
label: complement-mediated synapse pruning
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: complement-mediated synapse pruning is Alzheimer-relevant TREM2 biology, but it is a
context-specific substrate/phenotype rather than the broad core receptor function.
action: KEEP_AS_NON_CORE
reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial
function; do not treat them as disease-progression hypotheses in the core function.
supported_by:
- reference_id: PMID:27477018
supporting_text: β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up
by microglia in a TREM2-dependent fashion.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:0150076
label: neuroinflammatory response
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: neuroinflammatory response is a plausible downstream immune/inflammatory consequence of
TREM2 signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- term:
id: GO:0150078
label: positive regulation of neuroinflammatory response
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: positive regulation of neuroinflammatory response is a plausible downstream
immune/inflammatory consequence of TREM2 signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- term:
id: GO:0150079
label: negative regulation of neuroinflammatory response
evidence_type: IEA
original_reference_id: GO_REF:0000120
qualifier: involved_in
review:
summary: negative regulation of neuroinflammatory response is a plausible downstream
immune/inflammatory consequence of TREM2 signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- term:
id: GO:0150094
label: amyloid-beta clearance by cellular catabolic process
evidence_type: IEA
original_reference_id: GO_REF:0000120
qualifier: involved_in
review:
summary: amyloid-beta clearance by cellular catabolic process is Alzheimer-relevant TREM2
biology, but it is a context-specific substrate/phenotype rather than the broad core receptor
function.
action: KEEP_AS_NON_CORE
reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial
function; do not treat them as disease-progression hypotheses in the core function.
supported_by:
- reference_id: PMID:27477018
supporting_text: β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up
by microglia in a TREM2-dependent fashion.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:1900015
label: regulation of cytokine production involved in inflammatory response
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: regulation of cytokine production involved in inflammatory response is a plausible
downstream immune/inflammatory consequence of TREM2 signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- term:
id: GO:1900016
label: negative regulation of cytokine production involved in inflammatory response
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: negative regulation of cytokine production involved in inflammatory response is a
plausible downstream immune/inflammatory consequence of TREM2 signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- term:
id: GO:1900223
label: positive regulation of amyloid-beta clearance
evidence_type: IEA
original_reference_id: GO_REF:0000120
qualifier: involved_in
review:
summary: positive regulation of amyloid-beta clearance is Alzheimer-relevant TREM2 biology, but
it is a context-specific substrate/phenotype rather than the broad core receptor function.
action: KEEP_AS_NON_CORE
reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial
function; do not treat them as disease-progression hypotheses in the core function.
supported_by:
- reference_id: PMID:27477018
supporting_text: β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up
by microglia in a TREM2-dependent fashion.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:1901224
label: positive regulation of non-canonical NF-kappaB signal transduction
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: positive regulation of non-canonical NF-kappaB signal transduction is a plausible
downstream immune/inflammatory consequence of TREM2 signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- term:
id: GO:1901800
label: positive regulation of proteasomal protein catabolic process
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: positive regulation of proteasomal protein catabolic process is retained as
context-specific TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:1902533
label: positive regulation of intracellular signal transduction
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: positive regulation of intracellular signal transduction is a core downstream
consequence of TREM2 receptor signaling.
action: ACCEPT
reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support
calcium/ERK/PI3K-related activation and intracellular signaling.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC
maturation, and DC survival through activation of protein tyrosine kinases and extracellular
signal-regulated kinase.
- reference_id: PMID:32514138
supporting_text: TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis,
processing of neuronal debris, and lipid metabolism.
- term:
id: GO:1903376
label: regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway is
Alzheimer-relevant TREM2 biology, but it is a context-specific substrate/phenotype rather than
the broad core receptor function.
action: KEEP_AS_NON_CORE
reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial
function; do not treat them as disease-progression hypotheses in the core function.
supported_by:
- reference_id: PMID:27477018
supporting_text: β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up
by microglia in a TREM2-dependent fashion.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:1903753
label: negative regulation of p38MAPK cascade
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: negative regulation of p38MAPK cascade is a plausible downstream immune/inflammatory
consequence of TREM2 signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- term:
id: GO:1903980
label: positive regulation of microglial cell activation
evidence_type: IEA
original_reference_id: GO_REF:0000120
qualifier: involved_in
review:
summary: positive regulation of microglial cell activation is part of TREM2-mediated
microglial/myeloid phagocytic or lipid-response biology.
action: ACCEPT
reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment,
activation, and migration responses.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:1904093
label: negative regulation of autophagic cell death
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: negative regulation of autophagic cell death is retained as context-specific
TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:1904141
label: positive regulation of microglial cell migration
evidence_type: IEA
original_reference_id: GO_REF:0000120
qualifier: involved_in
review:
summary: positive regulation of microglial cell migration is part of TREM2-mediated
microglial/myeloid phagocytic or lipid-response biology.
action: ACCEPT
reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment,
activation, and migration responses.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:1904646
label: cellular response to amyloid-beta
evidence_type: IEA
original_reference_id: GO_REF:0000120
qualifier: involved_in
review:
summary: cellular response to amyloid-beta is Alzheimer-relevant TREM2 biology, but it is a
context-specific substrate/phenotype rather than the broad core receptor function.
action: KEEP_AS_NON_CORE
reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial
function; do not treat them as disease-progression hypotheses in the core function.
supported_by:
- reference_id: PMID:27477018
supporting_text: β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up
by microglia in a TREM2-dependent fashion.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:1904951
label: positive regulation of establishment of protein localization
evidence_type: IEA
original_reference_id: GO_REF:0000120
qualifier: involved_in
review:
summary: positive regulation of establishment of protein localization is retained as
context-specific TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:1905291
label: positive regulation of CAMKK-AMPK signaling cascade
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: positive regulation of CAMKK-AMPK signaling cascade is a core downstream consequence of
TREM2 receptor signaling.
action: ACCEPT
reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support
calcium/ERK/PI3K-related activation and intracellular signaling.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC
maturation, and DC survival through activation of protein tyrosine kinases and extracellular
signal-regulated kinase.
- reference_id: PMID:32514138
supporting_text: TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis,
processing of neuronal debris, and lipid metabolism.
- term:
id: GO:1905581
label: positive regulation of low-density lipoprotein particle clearance
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: positive regulation of low-density lipoprotein particle clearance is part of
TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
action: ACCEPT
reason: TREM2 ligand sensing and phagocytic challenge regulate microglial lipid/cholesterol
handling.
supported_by:
- reference_id: PMID:31902528
supporting_text: TREM2 senses lipids and mediates myelin phagocytosis
- reference_id: PMID:31902528
supporting_text: Our studies identify TREM2 as a key transcriptional regulator of cholesterol
transport and metabolism under conditions of chronic myelin phagocytic activity
- reference_id: PMID:27477018
supporting_text: Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL,
CLU, and APOE in heterologous cells
- term:
id: GO:1905805
label: excitatory synapse pruning
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: excitatory synapse pruning is Alzheimer-relevant TREM2 biology, but it is a
context-specific substrate/phenotype rather than the broad core receptor function.
action: KEEP_AS_NON_CORE
reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial
function; do not treat them as disease-progression hypotheses in the core function.
supported_by:
- reference_id: PMID:27477018
supporting_text: β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up
by microglia in a TREM2-dependent fashion.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:1905907
label: negative regulation of amyloid fibril formation
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: negative regulation of amyloid fibril formation is Alzheimer-relevant TREM2 biology,
but it is a context-specific substrate/phenotype rather than the broad core receptor function.
action: KEEP_AS_NON_CORE
reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial
function; do not treat them as disease-progression hypotheses in the core function.
supported_by:
- reference_id: PMID:27477018
supporting_text: β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up
by microglia in a TREM2-dependent fashion.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:1990782
label: protein tyrosine kinase binding
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: enables
review:
summary: protein tyrosine kinase binding is a specific interaction context for TREM2 but not the
main molecular-function term.
action: KEEP_AS_NON_CORE
reason: Retain as non-core because the interaction may be real, while more informative core
terms describe receptor activity and lipid/lipoprotein/aminophospholipid ligand binding.
- term:
id: GO:2001171
label: positive regulation of ATP biosynthetic process
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: positive regulation of ATP biosynthetic process is retained as context-specific
TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:1902533
label: positive regulation of intracellular signal transduction
evidence_type: IDA
original_reference_id: PMID:32514138
qualifier: acts_upstream_of_or_within
review:
summary: positive regulation of intracellular signal transduction is a core downstream
consequence of TREM2 receptor signaling.
action: ACCEPT
reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support
calcium/ERK/PI3K-related activation and intracellular signaling.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC
maturation, and DC survival through activation of protein tyrosine kinases and extracellular
signal-regulated kinase.
- reference_id: PMID:32514138
supporting_text: TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis,
processing of neuronal debris, and lipid metabolism.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: EXP
original_reference_id: PMID:25615530
qualifier: located_in
review:
summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface
receptor role.
action: ACCEPT
reason: Cell-surface/plasma-membrane localization is essential for ligand binding and
DAP12/TYROBP-mediated signal transduction.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is
associated with DAP12.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:27995897
supporting_text: Nasu-Hakola mutations impact protein stability and decrease folded TREM2
surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: EXP
original_reference_id: PMID:28768830
qualifier: located_in
review:
summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface
receptor role.
action: ACCEPT
reason: Cell-surface/plasma-membrane localization is essential for ligand binding and
DAP12/TYROBP-mediated signal transduction.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is
associated with DAP12.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:27995897
supporting_text: Nasu-Hakola mutations impact protein stability and decrease folded TREM2
surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: EXP
original_reference_id: PMID:28923481
qualifier: located_in
review:
summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface
receptor role.
action: ACCEPT
reason: Cell-surface/plasma-membrane localization is essential for ligand binding and
DAP12/TYROBP-mediated signal transduction.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is
associated with DAP12.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:27995897
supporting_text: Nasu-Hakola mutations impact protein stability and decrease folded TREM2
surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
- term:
id: GO:0010468
label: regulation of gene expression
evidence_type: ISS
original_reference_id: PMID:29518356
qualifier: involved_in
review:
summary: regulation of gene expression is retained as context-specific TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:0032675
label: regulation of interleukin-6 production
evidence_type: ISS
original_reference_id: PMID:29518356
qualifier: involved_in
review:
summary: regulation of interleukin-6 production is a plausible downstream immune/inflammatory
consequence of TREM2 signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- term:
id: GO:0043268
label: positive regulation of potassium ion transport
evidence_type: ISS
original_reference_id: PMID:29518356
qualifier: involved_in
review:
summary: positive regulation of potassium ion transport is retained as context-specific
TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:0071640
label: regulation of macrophage inflammatory protein 1 alpha production
evidence_type: ISS
original_reference_id: PMID:29518356
qualifier: involved_in
review:
summary: regulation of macrophage inflammatory protein 1 alpha production is a plausible
downstream immune/inflammatory consequence of TREM2 signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- term:
id: GO:1902533
label: positive regulation of intracellular signal transduction
evidence_type: ISS
original_reference_id: PMID:29518356
qualifier: involved_in
review:
summary: positive regulation of intracellular signal transduction is a core downstream
consequence of TREM2 receptor signaling.
action: ACCEPT
reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support
calcium/ERK/PI3K-related activation and intracellular signaling.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC
maturation, and DC survival through activation of protein tyrosine kinases and extracellular
signal-regulated kinase.
- reference_id: PMID:32514138
supporting_text: TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis,
processing of neuronal debris, and lipid metabolism.
- term:
id: GO:1902533
label: positive regulation of intracellular signal transduction
evidence_type: IDA
original_reference_id: PMID:31902528
qualifier: involved_in
review:
summary: positive regulation of intracellular signal transduction is a core downstream
consequence of TREM2 receptor signaling.
action: ACCEPT
reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support
calcium/ERK/PI3K-related activation and intracellular signaling.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC
maturation, and DC survival through activation of protein tyrosine kinases and extracellular
signal-regulated kinase.
- reference_id: PMID:32514138
supporting_text: TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis,
processing of neuronal debris, and lipid metabolism.
- term:
id: GO:0002116
label: semaphorin receptor complex
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: part_of
review:
summary: semaphorin receptor complex is retained as context-specific TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:0002291
label: T cell activation via T cell receptor contact with antigen bound to MHC molecule on
antigen presenting cell
evidence_type: IDA
original_reference_id: PMID:16715077
qualifier: involved_in
review:
summary: T cell activation via T cell receptor contact with antigen bound to MHC molecule on
antigen presenting cell is a plausible downstream immune/inflammatory consequence of TREM2
signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: IDA
original_reference_id: PMID:16715077
qualifier: is_active_in
review:
summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface
receptor role.
action: ACCEPT
reason: Cell-surface/plasma-membrane localization is essential for ligand binding and
DAP12/TYROBP-mediated signal transduction.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is
associated with DAP12.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:27995897
supporting_text: Nasu-Hakola mutations impact protein stability and decrease folded TREM2
surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
- term:
id: GO:0017154
label: semaphorin receptor activity
evidence_type: IDA
original_reference_id: PMID:16715077
qualifier: contributes_to
review:
summary: semaphorin receptor activity is retained as context-specific TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:0071526
label: semaphorin-plexin signaling pathway
evidence_type: IDA
original_reference_id: PMID:16715077
qualifier: involved_in
review:
summary: semaphorin-plexin signaling pathway is retained as context-specific TREM2-associated
biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:0004888
label: transmembrane signaling receptor activity
evidence_type: IDA
original_reference_id: PMID:29518356
qualifier: enables
review:
summary: TREM2 transmembrane signaling receptor activity is a core plasma-membrane receptor
function coupled to TYROBP/DAP12 signaling.
action: ACCEPT
reason: TREM2 is a myeloid/microglial cell-surface receptor whose ligand engagement drives
intracellular signaling through DAP12/TYROBP-linked kinase pathways.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is
associated with DAP12.
- reference_id: PMID:11602640
supporting_text: TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC
maturation, and DC survival through activation of protein tyrosine kinases and extracellular
signal-regulated kinase.
- reference_id: PMID:32514138
supporting_text: TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis,
processing of neuronal debris, and lipid metabolism.
- term:
id: GO:0004888
label: transmembrane signaling receptor activity
evidence_type: IDA
original_reference_id: PMID:30333625
qualifier: enables
review:
summary: TREM2 transmembrane signaling receptor activity is a core plasma-membrane receptor
function coupled to TYROBP/DAP12 signaling.
action: ACCEPT
reason: TREM2 is a myeloid/microglial cell-surface receptor whose ligand engagement drives
intracellular signaling through DAP12/TYROBP-linked kinase pathways.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is
associated with DAP12.
- reference_id: PMID:11602640
supporting_text: TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC
maturation, and DC survival through activation of protein tyrosine kinases and extracellular
signal-regulated kinase.
- reference_id: PMID:32514138
supporting_text: TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis,
processing of neuronal debris, and lipid metabolism.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: IDA
original_reference_id: PMID:24078628
qualifier: is_active_in
review:
summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface
receptor role.
action: ACCEPT
reason: Cell-surface/plasma-membrane localization is essential for ligand binding and
DAP12/TYROBP-mediated signal transduction.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is
associated with DAP12.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:27995897
supporting_text: Nasu-Hakola mutations impact protein stability and decrease folded TREM2
surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: IDA
original_reference_id: PMID:27477018
qualifier: is_active_in
review:
summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface
receptor role.
action: ACCEPT
reason: Cell-surface/plasma-membrane localization is essential for ligand binding and
DAP12/TYROBP-mediated signal transduction.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is
associated with DAP12.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:27995897
supporting_text: Nasu-Hakola mutations impact protein stability and decrease folded TREM2
surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
- term:
id: GO:0071402
label: cellular response to lipoprotein particle stimulus
evidence_type: IDA
original_reference_id: PMID:27477018
qualifier: involved_in
review:
summary: cellular response to lipoprotein particle stimulus is part of TREM2-mediated
microglial/myeloid phagocytic or lipid-response biology.
action: ACCEPT
reason: TREM2 ligand sensing and phagocytic challenge regulate microglial lipid/cholesterol
handling.
supported_by:
- reference_id: PMID:31902528
supporting_text: TREM2 senses lipids and mediates myelin phagocytosis
- reference_id: PMID:31902528
supporting_text: Our studies identify TREM2 as a key transcriptional regulator of cholesterol
transport and metabolism under conditions of chronic myelin phagocytic activity
- reference_id: PMID:27477018
supporting_text: Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL,
CLU, and APOE in heterologous cells
- term:
id: GO:0097242
label: amyloid-beta clearance
evidence_type: IDA
original_reference_id: PMID:27477018
qualifier: involved_in
review:
summary: amyloid-beta clearance is Alzheimer-relevant TREM2 biology, but it is a
context-specific substrate/phenotype rather than the broad core receptor function.
action: KEEP_AS_NON_CORE
reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial
function; do not treat them as disease-progression hypotheses in the core function.
supported_by:
- reference_id: PMID:27477018
supporting_text: β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up
by microglia in a TREM2-dependent fashion.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:0008013
label: beta-catenin binding
evidence_type: IPI
original_reference_id: PMID:30683932
qualifier: enables
review:
summary: beta-catenin binding is a specific interaction context for TREM2 but not the main
molecular-function term.
action: KEEP_AS_NON_CORE
reason: Retain as non-core because the interaction may be real, while more informative core
terms describe receptor activity and lipid/lipoprotein/aminophospholipid ligand binding.
- term:
id: GO:0051898
label: negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
evidence_type: IMP
original_reference_id: PMID:30683932
qualifier: involved_in
review:
summary: negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal
transduction is a core downstream consequence of TREM2 receptor signaling.
action: ACCEPT
reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support
calcium/ERK/PI3K-related activation and intracellular signaling.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC
maturation, and DC survival through activation of protein tyrosine kinases and extracellular
signal-regulated kinase.
- reference_id: PMID:32514138
supporting_text: TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis,
processing of neuronal debris, and lipid metabolism.
- term:
id: GO:0050921
label: positive regulation of chemotaxis
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: positive regulation of chemotaxis is part of TREM2-mediated microglial/myeloid
phagocytic or lipid-response biology.
action: ACCEPT
reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment,
activation, and migration responses.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:0120035
label: regulation of plasma membrane bounded cell projection organization
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: regulation of plasma membrane bounded cell projection organization is retained as
context-specific TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:1904141
label: positive regulation of microglial cell migration
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: positive regulation of microglial cell migration is part of TREM2-mediated
microglial/myeloid phagocytic or lipid-response biology.
action: ACCEPT
reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment,
activation, and migration responses.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:0010507
label: negative regulation of autophagy
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: negative regulation of autophagy is retained as context-specific TREM2-associated
biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:0032006
label: regulation of TOR signaling
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: regulation of TOR signaling is retained as context-specific TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:0032008
label: positive regulation of TOR signaling
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: positive regulation of TOR signaling is retained as context-specific TREM2-associated
biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:1904093
label: negative regulation of autophagic cell death
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: negative regulation of autophagic cell death is retained as context-specific
TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:1905291
label: positive regulation of CAMKK-AMPK signaling cascade
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: positive regulation of CAMKK-AMPK signaling cascade is a core downstream consequence of
TREM2 receptor signaling.
action: ACCEPT
reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support
calcium/ERK/PI3K-related activation and intracellular signaling.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC
maturation, and DC survival through activation of protein tyrosine kinases and extracellular
signal-regulated kinase.
- reference_id: PMID:32514138
supporting_text: TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis,
processing of neuronal debris, and lipid metabolism.
- term:
id: GO:2001171
label: positive regulation of ATP biosynthetic process
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: positive regulation of ATP biosynthetic process is retained as context-specific
TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:1900223
label: positive regulation of amyloid-beta clearance
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: positive regulation of amyloid-beta clearance is Alzheimer-relevant TREM2 biology, but
it is a context-specific substrate/phenotype rather than the broad core receptor function.
action: KEEP_AS_NON_CORE
reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial
function; do not treat them as disease-progression hypotheses in the core function.
supported_by:
- reference_id: PMID:27477018
supporting_text: β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up
by microglia in a TREM2-dependent fashion.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:0006910
label: phagocytosis, recognition
evidence_type: IMP
original_reference_id: PMID:32514138
qualifier: involved_in
review:
summary: phagocytosis, recognition is part of TREM2-mediated microglial/myeloid phagocytic or
lipid-response biology.
action: ACCEPT
reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment,
activation, and migration responses.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- 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: positive regulation of gene expression is retained as context-specific TREM2-associated
biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:0019216
label: regulation of lipid metabolic process
evidence_type: IMP
original_reference_id: PMID:32514138
qualifier: acts_upstream_of
review:
summary: regulation of lipid metabolic process is part of TREM2-mediated microglial/myeloid
phagocytic or lipid-response biology.
action: ACCEPT
reason: TREM2 ligand sensing and phagocytic challenge regulate microglial lipid/cholesterol
handling.
supported_by:
- reference_id: PMID:31902528
supporting_text: TREM2 senses lipids and mediates myelin phagocytosis
- reference_id: PMID:31902528
supporting_text: Our studies identify TREM2 as a key transcriptional regulator of cholesterol
transport and metabolism under conditions of chronic myelin phagocytic activity
- reference_id: PMID:27477018
supporting_text: Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL,
CLU, and APOE in heterologous cells
- term:
id: GO:0038023
label: signaling receptor activity
evidence_type: IMP
original_reference_id: PMID:32514138
qualifier: enables
review:
summary: TREM2 signaling receptor activity is a core plasma-membrane receptor function coupled
to TYROBP/DAP12 signaling.
action: ACCEPT
reason: TREM2 is a myeloid/microglial cell-surface receptor whose ligand engagement drives
intracellular signaling through DAP12/TYROBP-linked kinase pathways.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is
associated with DAP12.
- reference_id: PMID:11602640
supporting_text: TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC
maturation, and DC survival through activation of protein tyrosine kinases and extracellular
signal-regulated kinase.
- reference_id: PMID:32514138
supporting_text: TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis,
processing of neuronal debris, and lipid metabolism.
- term:
id: GO:0048678
label: response to axon injury
evidence_type: IMP
original_reference_id: PMID:32514138
qualifier: involved_in
review:
summary: response to axon injury is Alzheimer-relevant TREM2 biology, but it is a
context-specific substrate/phenotype rather than the broad core receptor function.
action: KEEP_AS_NON_CORE
reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial
function; do not treat them as disease-progression hypotheses in the core function.
supported_by:
- reference_id: PMID:27477018
supporting_text: β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up
by microglia in a TREM2-dependent fashion.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:0060100
label: positive regulation of phagocytosis, engulfment
evidence_type: IMP
original_reference_id: PMID:32514138
qualifier: acts_upstream_of
review:
summary: positive regulation of phagocytosis, engulfment is part of TREM2-mediated
microglial/myeloid phagocytic or lipid-response biology.
action: ACCEPT
reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment,
activation, and migration responses.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:0071396
label: cellular response to lipid
evidence_type: IMP
original_reference_id: PMID:32514138
qualifier: involved_in
review:
summary: cellular response to lipid is part of TREM2-mediated microglial/myeloid phagocytic or
lipid-response biology.
action: ACCEPT
reason: TREM2 ligand sensing and phagocytic challenge regulate microglial lipid/cholesterol
handling.
supported_by:
- reference_id: PMID:31902528
supporting_text: TREM2 senses lipids and mediates myelin phagocytosis
- reference_id: PMID:31902528
supporting_text: Our studies identify TREM2 as a key transcriptional regulator of cholesterol
transport and metabolism under conditions of chronic myelin phagocytic activity
- reference_id: PMID:27477018
supporting_text: Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL,
CLU, and APOE in heterologous cells
- term:
id: GO:0150079
label: negative regulation of neuroinflammatory response
evidence_type: IMP
original_reference_id: PMID:32514138
qualifier: involved_in
review:
summary: negative regulation of neuroinflammatory response is a plausible downstream
immune/inflammatory consequence of TREM2 signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- term:
id: GO:1900226
label: negative regulation of NLRP3 inflammasome complex assembly
evidence_type: IMP
original_reference_id: PMID:32514138
qualifier: acts_upstream_of_or_within
review:
summary: negative regulation of NLRP3 inflammasome complex assembly is retained as non-core
TREM2-associated biology pending deeper reference-specific adjudication.
action: KEEP_AS_NON_CORE
reason: The annotation is not part of the primary receptor-ligand signaling and phagocytic
microglial function set, but the local evidence was not sufficient to remove it.
- term:
id: GO:0038160
label: CXCL12-activated CXCR4 signaling pathway
evidence_type: IMP
original_reference_id: PMID:33097708
qualifier: acts_upstream_of_or_within_positive_effect
review:
summary: CXCL12-activated CXCR4 signaling pathway is retained as context-specific
TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:0050829
label: defense response to Gram-negative bacterium
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: acts_upstream_of_or_within_positive_effect
review:
summary: defense response to Gram-negative bacterium is electronically inferred
pathogen-associated ligand or defense biology.
action: KEEP_AS_NON_CORE
reason: Retain as non-core because TREM-family receptors participate in myeloid immune sensing,
but the cached human TREM2 evidence reviewed here emphasizes lipids, apoptotic cells, and
microglial phagocytic ligands.
- term:
id: GO:0070269
label: pyroptotic inflammatory response
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: acts_upstream_of_or_within_negative_effect
review:
summary: pyroptotic inflammatory response is a plausible downstream immune/inflammatory
consequence of TREM2 signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- term:
id: GO:1900016
label: negative regulation of cytokine production involved in inflammatory response
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: negative regulation of cytokine production involved in inflammatory response is a
plausible downstream immune/inflammatory consequence of TREM2 signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- term:
id: GO:1900226
label: negative regulation of NLRP3 inflammasome complex assembly
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: acts_upstream_of_or_within
review:
summary: negative regulation of NLRP3 inflammasome complex assembly is retained as non-core
TREM2-associated biology pending deeper reference-specific adjudication.
action: KEEP_AS_NON_CORE
reason: The annotation is not part of the primary receptor-ligand signaling and phagocytic
microglial function set, but the local evidence was not sufficient to remove it.
- term:
id: GO:0150079
label: negative regulation of neuroinflammatory response
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: negative regulation of neuroinflammatory response is a plausible downstream
immune/inflammatory consequence of TREM2 signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- term:
id: GO:1903753
label: negative regulation of p38MAPK cascade
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: negative regulation of p38MAPK cascade is a plausible downstream immune/inflammatory
consequence of TREM2 signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- term:
id: GO:0034144
label: negative regulation of toll-like receptor 4 signaling pathway
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: negative regulation of toll-like receptor 4 signaling pathway is a plausible downstream
immune/inflammatory consequence of TREM2 signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- term:
id: GO:0050866
label: negative regulation of cell activation
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: negative regulation of cell activation is a plausible downstream immune/inflammatory
consequence of TREM2 signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- term:
id: GO:0051897
label: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal
transduction is a core downstream consequence of TREM2 receptor signaling.
action: ACCEPT
reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support
calcium/ERK/PI3K-related activation and intracellular signaling.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC
maturation, and DC survival through activation of protein tyrosine kinases and extracellular
signal-regulated kinase.
- reference_id: PMID:32514138
supporting_text: TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis,
processing of neuronal debris, and lipid metabolism.
- term:
id: GO:0061889
label: negative regulation of astrocyte activation
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: negative regulation of astrocyte activation is a plausible downstream
immune/inflammatory consequence of TREM2 signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- term:
id: GO:0110089
label: regulation of hippocampal neuron apoptotic process
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: regulation of hippocampal neuron apoptotic process is Alzheimer-relevant TREM2 biology,
but it is a context-specific substrate/phenotype rather than the broad core receptor function.
action: KEEP_AS_NON_CORE
reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial
function; do not treat them as disease-progression hypotheses in the core function.
supported_by:
- reference_id: PMID:27477018
supporting_text: β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up
by microglia in a TREM2-dependent fashion.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:1903376
label: regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway is
Alzheimer-relevant TREM2 biology, but it is a context-specific substrate/phenotype rather than
the broad core receptor function.
action: KEEP_AS_NON_CORE
reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial
function; do not treat them as disease-progression hypotheses in the core function.
supported_by:
- reference_id: PMID:27477018
supporting_text: β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up
by microglia in a TREM2-dependent fashion.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:0001786
label: phosphatidylserine binding
evidence_type: IDA
original_reference_id: PMID:31101881
qualifier: enables
review:
summary: TREM2 phosphatidylserine binding is part of its ligand-sensing receptor biology.
action: ACCEPT
reason: Aminophospholipid and anionic lipid recognition is a core TREM2 ligand-sensing function
for apoptotic-cell and debris responses.
supported_by:
- reference_id: PMID:31101881
supporting_text: TREM2-dependent signal transduction in response to apoptotic Neuro2a cells is
mediated by aminophospholipid ligands, phosphatidylserine and phosphatidylethanolamine
- term:
id: GO:0002282
label: microglial cell activation involved in immune response
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: microglial cell activation involved in immune response is part of TREM2-mediated
microglial/myeloid phagocytic or lipid-response biology.
action: ACCEPT
reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment,
activation, and migration responses.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:0007613
label: memory
evidence_type: IDA
original_reference_id: PMID:31462511
qualifier: acts_upstream_of_positive_effect
review:
summary: memory is retained as context-specific TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:0008429
label: phosphatidylethanolamine binding
evidence_type: IDA
original_reference_id: PMID:31101881
qualifier: enables
review:
summary: TREM2 phosphatidylethanolamine binding is part of its ligand-sensing receptor biology.
action: ACCEPT
reason: Aminophospholipid and anionic lipid recognition is a core TREM2 ligand-sensing function
for apoptotic-cell and debris responses.
supported_by:
- reference_id: PMID:31101881
supporting_text: TREM2-dependent signal transduction in response to apoptotic Neuro2a cells is
mediated by aminophospholipid ligands, phosphatidylserine and phosphatidylethanolamine
- term:
id: GO:0034136
label: negative regulation of toll-like receptor 2 signaling pathway
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: negative regulation of toll-like receptor 2 signaling pathway is a plausible downstream
immune/inflammatory consequence of TREM2 signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- term:
id: GO:0034151
label: regulation of toll-like receptor 6 signaling pathway
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: regulation of toll-like receptor 6 signaling pathway is a plausible downstream
immune/inflammatory consequence of TREM2 signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- term:
id: GO:0097062
label: dendritic spine maintenance
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: dendritic spine maintenance is Alzheimer-relevant TREM2 biology, but it is a
context-specific substrate/phenotype rather than the broad core receptor function.
action: KEEP_AS_NON_CORE
reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial
function; do not treat them as disease-progression hypotheses in the core function.
supported_by:
- reference_id: PMID:27477018
supporting_text: β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up
by microglia in a TREM2-dependent fashion.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:0150094
label: amyloid-beta clearance by cellular catabolic process
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: amyloid-beta clearance by cellular catabolic process is Alzheimer-relevant TREM2
biology, but it is a context-specific substrate/phenotype rather than the broad core receptor
function.
action: KEEP_AS_NON_CORE
reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial
function; do not treat them as disease-progression hypotheses in the core function.
supported_by:
- reference_id: PMID:27477018
supporting_text: β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up
by microglia in a TREM2-dependent fashion.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:0150094
label: amyloid-beta clearance by cellular catabolic process
evidence_type: IMP
original_reference_id: PMID:33097708
qualifier: involved_in
review:
summary: amyloid-beta clearance by cellular catabolic process is Alzheimer-relevant TREM2
biology, but it is a context-specific substrate/phenotype rather than the broad core receptor
function.
action: KEEP_AS_NON_CORE
reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial
function; do not treat them as disease-progression hypotheses in the core function.
supported_by:
- reference_id: PMID:27477018
supporting_text: β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up
by microglia in a TREM2-dependent fashion.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:0001774
label: microglial cell activation
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: microglial cell activation is part of TREM2-mediated microglial/myeloid phagocytic or
lipid-response biology.
action: ACCEPT
reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment,
activation, and migration responses.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:0002862
label: negative regulation of inflammatory response to antigenic stimulus
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: negative regulation of inflammatory response to antigenic stimulus is a plausible
downstream immune/inflammatory consequence of TREM2 signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- term:
id: GO:0007613
label: memory
evidence_type: IMP
original_reference_id: PMID:29518357
qualifier: acts_upstream_of_positive_effect
review:
summary: memory is retained as context-specific TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:0034351
label: negative regulation of glial cell apoptotic process
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: negative regulation of glial cell apoptotic process is retained as non-core
TREM2-associated biology pending deeper reference-specific adjudication.
action: KEEP_AS_NON_CORE
reason: The annotation is not part of the primary receptor-ligand signaling and phagocytic
microglial function set, but the local evidence was not sufficient to remove it.
- term:
id: GO:0043124
label: negative regulation of canonical NF-kappaB signal transduction
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: negative regulation of canonical NF-kappaB signal transduction is a plausible
downstream immune/inflammatory consequence of TREM2 signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- term:
id: GO:0050766
label: positive regulation of phagocytosis
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: positive regulation of phagocytosis is part of TREM2-mediated microglial/myeloid
phagocytic or lipid-response biology.
action: ACCEPT
reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment,
activation, and migration responses.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:0050766
label: positive regulation of phagocytosis
evidence_type: IMP
original_reference_id: PMID:29518357
qualifier: involved_in
review:
summary: positive regulation of phagocytosis is part of TREM2-mediated microglial/myeloid
phagocytic or lipid-response biology.
action: ACCEPT
reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment,
activation, and migration responses.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:0051898
label: negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal
transduction is a core downstream consequence of TREM2 receptor signaling.
action: ACCEPT
reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support
calcium/ERK/PI3K-related activation and intracellular signaling.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC
maturation, and DC survival through activation of protein tyrosine kinases and extracellular
signal-regulated kinase.
- reference_id: PMID:32514138
supporting_text: TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis,
processing of neuronal debris, and lipid metabolism.
- term:
id: GO:1900015
label: regulation of cytokine production involved in inflammatory response
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: regulation of cytokine production involved in inflammatory response is a plausible
downstream immune/inflammatory consequence of TREM2 signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- term:
id: GO:0060100
label: positive regulation of phagocytosis, engulfment
evidence_type: IMP
original_reference_id: PMID:33097708
qualifier: involved_in
review:
summary: positive regulation of phagocytosis, engulfment is part of TREM2-mediated
microglial/myeloid phagocytic or lipid-response biology.
action: ACCEPT
reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment,
activation, and migration responses.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:1902227
label: negative regulation of macrophage colony-stimulating factor signaling pathway
evidence_type: IMP
original_reference_id: PMID:33097708
qualifier: involved_in
review:
summary: negative regulation of macrophage colony-stimulating factor signaling pathway is a
plausible downstream immune/inflammatory consequence of TREM2 signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- term:
id: GO:1904141
label: positive regulation of microglial cell migration
evidence_type: IMP
original_reference_id: PMID:33097708
qualifier: involved_in
review:
summary: positive regulation of microglial cell migration is part of TREM2-mediated
microglial/myeloid phagocytic or lipid-response biology.
action: ACCEPT
reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment,
activation, and migration responses.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:1905808
label: positive regulation of synapse pruning
evidence_type: IMP
original_reference_id: PMID:33097708
qualifier: involved_in
review:
summary: positive regulation of synapse pruning is Alzheimer-relevant TREM2 biology, but it is a
context-specific substrate/phenotype rather than the broad core receptor function.
action: KEEP_AS_NON_CORE
reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial
function; do not treat them as disease-progression hypotheses in the core function.
supported_by:
- reference_id: PMID:27477018
supporting_text: β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up
by microglia in a TREM2-dependent fashion.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:0035176
label: social behavior
evidence_type: IMP
original_reference_id: PMID:29752066
qualifier: acts_upstream_of_positive_effect
review:
summary: social behavior is retained as context-specific TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:0045088
label: regulation of innate immune response
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: regulation of innate immune response is a core downstream consequence of TREM2 receptor
signaling.
action: ACCEPT
reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support
calcium/ERK/PI3K-related activation and intracellular signaling.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC
maturation, and DC survival through activation of protein tyrosine kinases and extracellular
signal-regulated kinase.
- reference_id: PMID:32514138
supporting_text: TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis,
processing of neuronal debris, and lipid metabolism.
- term:
id: GO:0045728
label: respiratory burst after phagocytosis
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: respiratory burst after phagocytosis is a plausible downstream immune/inflammatory
consequence of TREM2 signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- term:
id: GO:0045960
label: positive regulation of complement activation, classical pathway
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: positive regulation of complement activation, classical pathway is a plausible
downstream immune/inflammatory consequence of TREM2 signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- term:
id: GO:0061518
label: microglial cell proliferation
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: microglial cell proliferation is retained as context-specific TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:0150062
label: complement-mediated synapse pruning
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: complement-mediated synapse pruning is Alzheimer-relevant TREM2 biology, but it is a
context-specific substrate/phenotype rather than the broad core receptor function.
action: KEEP_AS_NON_CORE
reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial
function; do not treat them as disease-progression hypotheses in the core function.
supported_by:
- reference_id: PMID:27477018
supporting_text: β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up
by microglia in a TREM2-dependent fashion.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:0060100
label: positive regulation of phagocytosis, engulfment
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: positive regulation of phagocytosis, engulfment is part of TREM2-mediated
microglial/myeloid phagocytic or lipid-response biology.
action: ACCEPT
reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment,
activation, and migration responses.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:1905805
label: excitatory synapse pruning
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: excitatory synapse pruning is Alzheimer-relevant TREM2 biology, but it is a
context-specific substrate/phenotype rather than the broad core receptor function.
action: KEEP_AS_NON_CORE
reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial
function; do not treat them as disease-progression hypotheses in the core function.
supported_by:
- reference_id: PMID:27477018
supporting_text: β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up
by microglia in a TREM2-dependent fashion.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:0048678
label: response to axon injury
evidence_type: IMP
original_reference_id: PMID:31235932
qualifier: involved_in
review:
summary: response to axon injury is Alzheimer-relevant TREM2 biology, but it is a
context-specific substrate/phenotype rather than the broad core receptor function.
action: KEEP_AS_NON_CORE
reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial
function; do not treat them as disease-progression hypotheses in the core function.
supported_by:
- reference_id: PMID:27477018
supporting_text: β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up
by microglia in a TREM2-dependent fashion.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:1900223
label: positive regulation of amyloid-beta clearance
evidence_type: IMP
original_reference_id: PMID:31235932
qualifier: involved_in
review:
summary: positive regulation of amyloid-beta clearance is Alzheimer-relevant TREM2 biology, but
it is a context-specific substrate/phenotype rather than the broad core receptor function.
action: KEEP_AS_NON_CORE
reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial
function; do not treat them as disease-progression hypotheses in the core function.
supported_by:
- reference_id: PMID:27477018
supporting_text: β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up
by microglia in a TREM2-dependent fashion.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:0001786
label: phosphatidylserine binding
evidence_type: IDA
original_reference_id: PMID:31902528
qualifier: enables
review:
summary: TREM2 phosphatidylserine binding is part of its ligand-sensing receptor biology.
action: ACCEPT
reason: Aminophospholipid and anionic lipid recognition is a core TREM2 ligand-sensing function
for apoptotic-cell and debris responses.
supported_by:
- reference_id: PMID:31101881
supporting_text: TREM2-dependent signal transduction in response to apoptotic Neuro2a cells is
mediated by aminophospholipid ligands, phosphatidylserine and phosphatidylethanolamine
- term:
id: GO:0010875
label: positive regulation of cholesterol efflux
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: positive regulation of cholesterol efflux is part of TREM2-mediated microglial/myeloid
phagocytic or lipid-response biology.
action: ACCEPT
reason: TREM2 ligand sensing and phagocytic challenge regulate microglial lipid/cholesterol
handling.
supported_by:
- reference_id: PMID:31902528
supporting_text: TREM2 senses lipids and mediates myelin phagocytosis
- reference_id: PMID:31902528
supporting_text: Our studies identify TREM2 as a key transcriptional regulator of cholesterol
transport and metabolism under conditions of chronic myelin phagocytic activity
- reference_id: PMID:27477018
supporting_text: Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL,
CLU, and APOE in heterologous cells
- term:
id: GO:0010887
label: negative regulation of cholesterol storage
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: negative regulation of cholesterol storage is part of TREM2-mediated microglial/myeloid
phagocytic or lipid-response biology.
action: ACCEPT
reason: TREM2 ligand sensing and phagocytic challenge regulate microglial lipid/cholesterol
handling.
supported_by:
- reference_id: PMID:31902528
supporting_text: TREM2 senses lipids and mediates myelin phagocytosis
- reference_id: PMID:31902528
supporting_text: Our studies identify TREM2 as a key transcriptional regulator of cholesterol
transport and metabolism under conditions of chronic myelin phagocytic activity
- reference_id: PMID:27477018
supporting_text: Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL,
CLU, and APOE in heterologous cells
- term:
id: GO:0010891
label: negative regulation of triglyceride storage
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: negative regulation of triglyceride storage is part of TREM2-mediated
microglial/myeloid phagocytic or lipid-response biology.
action: ACCEPT
reason: TREM2 ligand sensing and phagocytic challenge regulate microglial lipid/cholesterol
handling.
supported_by:
- reference_id: PMID:31902528
supporting_text: TREM2 senses lipids and mediates myelin phagocytosis
- reference_id: PMID:31902528
supporting_text: Our studies identify TREM2 as a key transcriptional regulator of cholesterol
transport and metabolism under conditions of chronic myelin phagocytic activity
- reference_id: PMID:27477018
supporting_text: Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL,
CLU, and APOE in heterologous cells
- term:
id: GO:0048678
label: response to axon injury
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: response to axon injury is Alzheimer-relevant TREM2 biology, but it is a
context-specific substrate/phenotype rather than the broad core receptor function.
action: KEEP_AS_NON_CORE
reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial
function; do not treat them as disease-progression hypotheses in the core function.
supported_by:
- reference_id: PMID:27477018
supporting_text: β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up
by microglia in a TREM2-dependent fashion.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:0120146
label: sulfatide binding
evidence_type: IDA
original_reference_id: PMID:31902528
qualifier: enables
review:
summary: TREM2 sulfatide binding is part of its ligand-sensing receptor biology.
action: ACCEPT
reason: Aminophospholipid and anionic lipid recognition is a core TREM2 ligand-sensing function
for apoptotic-cell and debris responses.
supported_by:
- reference_id: PMID:31101881
supporting_text: TREM2-dependent signal transduction in response to apoptotic Neuro2a cells is
mediated by aminophospholipid ligands, phosphatidylserine and phosphatidylethanolamine
- term:
id: GO:0140052
label: cellular response to oxidised low-density lipoprotein particle stimulus
evidence_type: IDA
original_reference_id: PMID:31902528
qualifier: involved_in
review:
summary: cellular response to oxidised low-density lipoprotein particle stimulus is part of
TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
action: ACCEPT
reason: TREM2 ligand sensing and phagocytic challenge regulate microglial lipid/cholesterol
handling.
supported_by:
- reference_id: PMID:31902528
supporting_text: TREM2 senses lipids and mediates myelin phagocytosis
- reference_id: PMID:31902528
supporting_text: Our studies identify TREM2 as a key transcriptional regulator of cholesterol
transport and metabolism under conditions of chronic myelin phagocytic activity
- reference_id: PMID:27477018
supporting_text: Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL,
CLU, and APOE in heterologous cells
- term:
id: GO:1903980
label: positive regulation of microglial cell activation
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: positive regulation of microglial cell activation is part of TREM2-mediated
microglial/myeloid phagocytic or lipid-response biology.
action: ACCEPT
reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment,
activation, and migration responses.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:1904951
label: positive regulation of establishment of protein localization
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: positive regulation of establishment of protein localization is retained as
context-specific TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:1905907
label: negative regulation of amyloid fibril formation
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: negative regulation of amyloid fibril formation is Alzheimer-relevant TREM2 biology,
but it is a context-specific substrate/phenotype rather than the broad core receptor function.
action: KEEP_AS_NON_CORE
reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial
function; do not treat them as disease-progression hypotheses in the core function.
supported_by:
- reference_id: PMID:27477018
supporting_text: β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up
by microglia in a TREM2-dependent fashion.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:0019209
label: kinase activator activity
evidence_type: IMP
original_reference_id: PMID:31902528
qualifier: enables
review:
summary: kinase activator activity is a core downstream consequence of TREM2 receptor signaling.
action: ACCEPT
reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support
calcium/ERK/PI3K-related activation and intracellular signaling.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC
maturation, and DC survival through activation of protein tyrosine kinases and extracellular
signal-regulated kinase.
- reference_id: PMID:32514138
supporting_text: TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis,
processing of neuronal debris, and lipid metabolism.
- term:
id: GO:0010983
label: positive regulation of high-density lipoprotein particle clearance
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: positive regulation of high-density lipoprotein particle clearance is part of
TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
action: ACCEPT
reason: TREM2 ligand sensing and phagocytic challenge regulate microglial lipid/cholesterol
handling.
supported_by:
- reference_id: PMID:31902528
supporting_text: TREM2 senses lipids and mediates myelin phagocytosis
- reference_id: PMID:31902528
supporting_text: Our studies identify TREM2 as a key transcriptional regulator of cholesterol
transport and metabolism under conditions of chronic myelin phagocytic activity
- reference_id: PMID:27477018
supporting_text: Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL,
CLU, and APOE in heterologous cells
- term:
id: GO:0055088
label: lipid homeostasis
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: lipid homeostasis is part of TREM2-mediated microglial/myeloid phagocytic or
lipid-response biology.
action: ACCEPT
reason: TREM2 ligand sensing and phagocytic challenge regulate microglial lipid/cholesterol
handling.
supported_by:
- reference_id: PMID:31902528
supporting_text: TREM2 senses lipids and mediates myelin phagocytosis
- reference_id: PMID:31902528
supporting_text: Our studies identify TREM2 as a key transcriptional regulator of cholesterol
transport and metabolism under conditions of chronic myelin phagocytic activity
- reference_id: PMID:27477018
supporting_text: Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL,
CLU, and APOE in heterologous cells
- term:
id: GO:0070345
label: negative regulation of fat cell proliferation
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: negative regulation of fat cell proliferation is retained as context-specific
TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:1905581
label: positive regulation of low-density lipoprotein particle clearance
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: positive regulation of low-density lipoprotein particle clearance is part of
TREM2-mediated microglial/myeloid phagocytic or lipid-response biology.
action: ACCEPT
reason: TREM2 ligand sensing and phagocytic challenge regulate microglial lipid/cholesterol
handling.
supported_by:
- reference_id: PMID:31902528
supporting_text: TREM2 senses lipids and mediates myelin phagocytosis
- reference_id: PMID:31902528
supporting_text: Our studies identify TREM2 as a key transcriptional regulator of cholesterol
transport and metabolism under conditions of chronic myelin phagocytic activity
- reference_id: PMID:27477018
supporting_text: Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL,
CLU, and APOE in heterologous cells
- term:
id: GO:0044853
label: plasma membrane raft
evidence_type: IDA
original_reference_id: PMID:31413141
qualifier: located_in
review:
summary: TREM2 localization to plasma membrane raft is consistent with its type I cell-surface
receptor role.
action: ACCEPT
reason: Cell-surface/plasma-membrane localization is essential for ligand binding and
DAP12/TYROBP-mediated signal transduction.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is
associated with DAP12.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:27995897
supporting_text: Nasu-Hakola mutations impact protein stability and decrease folded TREM2
surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
- term:
id: GO:0001774
label: microglial cell activation
evidence_type: ISS
original_reference_id: PMID:29518356
qualifier: involved_in
review:
summary: microglial cell activation is part of TREM2-mediated microglial/myeloid phagocytic or
lipid-response biology.
action: ACCEPT
reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment,
activation, and migration responses.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:0048143
label: astrocyte activation
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: astrocyte activation is a plausible downstream immune/inflammatory consequence of TREM2
signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: IMP
original_reference_id: PMID:24990881
qualifier: located_in
review:
summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface
receptor role.
action: ACCEPT
reason: Cell-surface/plasma-membrane localization is essential for ligand binding and
DAP12/TYROBP-mediated signal transduction.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is
associated with DAP12.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:27995897
supporting_text: Nasu-Hakola mutations impact protein stability and decrease folded TREM2
surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: IMP
original_reference_id: PMID:27589997
qualifier: located_in
review:
summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface
receptor role.
action: ACCEPT
reason: Cell-surface/plasma-membrane localization is essential for ligand binding and
DAP12/TYROBP-mediated signal transduction.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is
associated with DAP12.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:27995897
supporting_text: Nasu-Hakola mutations impact protein stability and decrease folded TREM2
surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: IMP
original_reference_id: PMID:28855300
qualifier: located_in
review:
summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface
receptor role.
action: ACCEPT
reason: Cell-surface/plasma-membrane localization is essential for ligand binding and
DAP12/TYROBP-mediated signal transduction.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is
associated with DAP12.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:27995897
supporting_text: Nasu-Hakola mutations impact protein stability and decrease folded TREM2
surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
- term:
id: GO:0060100
label: positive regulation of phagocytosis, engulfment
evidence_type: IMP
original_reference_id: PMID:28855300
qualifier: involved_in
review:
summary: positive regulation of phagocytosis, engulfment is part of TREM2-mediated
microglial/myeloid phagocytic or lipid-response biology.
action: ACCEPT
reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment,
activation, and migration responses.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:1901076
label: positive regulation of engulfment of apoptotic cell
evidence_type: IMP
original_reference_id: PMID:24990881
qualifier: involved_in
review:
summary: positive regulation of engulfment of apoptotic cell is part of TREM2-mediated
microglial/myeloid phagocytic or lipid-response biology.
action: ACCEPT
reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment,
activation, and migration responses.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:1903980
label: positive regulation of microglial cell activation
evidence_type: IMP
original_reference_id: PMID:24990881
qualifier: involved_in
review:
summary: positive regulation of microglial cell activation is part of TREM2-mediated
microglial/myeloid phagocytic or lipid-response biology.
action: ACCEPT
reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment,
activation, and migration responses.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:0030316
label: osteoclast differentiation
evidence_type: IMP
original_reference_id: PMID:12925681
qualifier: involved_in
review:
summary: osteoclast differentiation is retained as context-specific TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
supported_by:
- reference_id: PMID:12925681
supporting_text: loss of function mutations in DAP12 and TREM2 result in an inefficient and
delayed differentiation of osteoclasts
- term:
id: GO:0005886
label: plasma membrane
evidence_type: IMP
original_reference_id: PMID:28855301
qualifier: located_in
review:
summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface
receptor role.
action: ACCEPT
reason: Cell-surface/plasma-membrane localization is essential for ligand binding and
DAP12/TYROBP-mediated signal transduction.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is
associated with DAP12.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:27995897
supporting_text: Nasu-Hakola mutations impact protein stability and decrease folded TREM2
surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
- term:
id: GO:0050714
label: positive regulation of protein secretion
evidence_type: IMP
original_reference_id: PMID:27044754
qualifier: involved_in
review:
summary: positive regulation of protein secretion is retained as context-specific
TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:0043277
label: apoptotic cell clearance
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: apoptotic cell clearance is part of TREM2-mediated microglial/myeloid phagocytic or
lipid-response biology.
action: ACCEPT
reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment,
activation, and migration responses.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:0008289
label: lipid binding
evidence_type: TAS
original_reference_id: PMID:29518356
qualifier: enables
review:
summary: TREM2 lipid binding is part of its ligand-sensing receptor biology.
action: ACCEPT
reason: TREM2 ligand recognition includes lipid-rich particles and supports microglial lipid
handling.
supported_by:
- reference_id: PMID:27477018
supporting_text: we identified a set of lipoprotein particles (including LDL) and
apolipoproteins (including CLU/APOJ and APOE) as ligands
- reference_id: PMID:31902528
supporting_text: TREM2 senses lipids and mediates myelin phagocytosis
- term:
id: GO:0038023
label: signaling receptor activity
evidence_type: ISS
original_reference_id: PMID:29518356
qualifier: enables
review:
summary: TREM2 signaling receptor activity is a core plasma-membrane receptor function coupled
to TYROBP/DAP12 signaling.
action: ACCEPT
reason: TREM2 is a myeloid/microglial cell-surface receptor whose ligand engagement drives
intracellular signaling through DAP12/TYROBP-linked kinase pathways.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is
associated with DAP12.
- reference_id: PMID:11602640
supporting_text: TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC
maturation, and DC survival through activation of protein tyrosine kinases and extracellular
signal-regulated kinase.
- reference_id: PMID:32514138
supporting_text: TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis,
processing of neuronal debris, and lipid metabolism.
- term:
id: GO:0060075
label: regulation of resting membrane potential
evidence_type: ISS
original_reference_id: PMID:29518356
qualifier: involved_in
review:
summary: regulation of resting membrane potential is retained as context-specific
TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:0120035
label: regulation of plasma membrane bounded cell projection organization
evidence_type: IGI
original_reference_id: PMID:29518356
qualifier: involved_in
review:
summary: regulation of plasma membrane bounded cell projection organization is retained as
context-specific TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:1901800
label: positive regulation of proteasomal protein catabolic process
evidence_type: ISS
original_reference_id: PMID:29518356
qualifier: involved_in
review:
summary: positive regulation of proteasomal protein catabolic process is retained as
context-specific TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:1904141
label: positive regulation of microglial cell migration
evidence_type: ISS
original_reference_id: PMID:29518356
qualifier: involved_in
review:
summary: positive regulation of microglial cell migration is part of TREM2-mediated
microglial/myeloid phagocytic or lipid-response biology.
action: ACCEPT
reason: TREM2 is a core microglial/myeloid phagocytic receptor that supports engulfment,
activation, and migration responses.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:1904646
label: cellular response to amyloid-beta
evidence_type: ISS
original_reference_id: PMID:29518356
qualifier: involved_in
review:
summary: cellular response to amyloid-beta is Alzheimer-relevant TREM2 biology, but it is a
context-specific substrate/phenotype rather than the broad core receptor function.
action: KEEP_AS_NON_CORE
reason: Retain amyloid and synapse-pruning annotations as non-core contexts of TREM2 microglial
function; do not treat them as disease-progression hypotheses in the core function.
supported_by:
- reference_id: PMID:27477018
supporting_text: β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up
by microglia in a TREM2-dependent fashion.
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
- term:
id: GO:1990782
label: protein tyrosine kinase binding
evidence_type: ISS
original_reference_id: PMID:29518356
qualifier: enables
review:
summary: protein tyrosine kinase binding is a specific interaction context for TREM2 but not the
main molecular-function term.
action: KEEP_AS_NON_CORE
reason: Retain as non-core because the interaction may be real, while more informative core
terms describe receptor activity and lipid/lipoprotein/aminophospholipid ligand binding.
- term:
id: GO:0001540
label: amyloid-beta binding
evidence_type: IPI
original_reference_id: PMID:29518356
qualifier: enables
review:
summary: TREM2 amyloid-beta binding is part of its ligand-sensing receptor biology.
action: ACCEPT
reason: Amyloid-beta binding is disease-relevant but mechanistically tied to TREM2 ligand uptake
through lipoprotein-associated complexes; retain as part of ligand recognition.
supported_by:
- reference_id: PMID:27477018
supporting_text: β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up
by microglia in a TREM2-dependent fashion.
- term:
id: GO:0044877
label: protein-containing complex binding
evidence_type: IPI
original_reference_id: PMID:29518356
qualifier: enables
review:
summary: Generic protein-containing complex binding annotation for TREM2.
action: MARK_AS_OVER_ANNOTATED
reason: The interaction may be real, but this term is too generic. Specific ligand-binding,
receptor-activity, TYROBP/DAP12 signaling, or phagocytosis annotations are more informative.
- term:
id: GO:0010628
label: positive regulation of gene expression
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: positive regulation of gene expression is retained as context-specific TREM2-associated
biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:0098657
label: import into cell
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: import into cell is retained as context-specific TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:0008035
label: high-density lipoprotein particle binding
evidence_type: IDA
original_reference_id: PMID:27477018
qualifier: enables
review:
summary: TREM2 high-density lipoprotein particle binding is part of its ligand-sensing receptor
biology.
action: ACCEPT
reason: TREM2 recognizes apolipoproteins and lipoprotein particles and promotes their uptake by
microglia or receptor-expressing cells.
supported_by:
- reference_id: PMID:27477018
supporting_text: we identified a set of lipoprotein particles (including LDL) and
apolipoproteins (including CLU/APOJ and APOE) as ligands
- reference_id: PMID:27477018
supporting_text: Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL,
CLU, and APOE in heterologous cells
- term:
id: GO:0030169
label: low-density lipoprotein particle binding
evidence_type: IDA
original_reference_id: PMID:27477018
qualifier: enables
review:
summary: TREM2 low-density lipoprotein particle binding is part of its ligand-sensing receptor
biology.
action: ACCEPT
reason: TREM2 recognizes apolipoproteins and lipoprotein particles and promotes their uptake by
microglia or receptor-expressing cells.
supported_by:
- reference_id: PMID:27477018
supporting_text: we identified a set of lipoprotein particles (including LDL) and
apolipoproteins (including CLU/APOJ and APOE) as ligands
- reference_id: PMID:27477018
supporting_text: Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL,
CLU, and APOE in heterologous cells
- term:
id: GO:0034185
label: apolipoprotein binding
evidence_type: IPI
original_reference_id: PMID:27477018
qualifier: enables
review:
summary: TREM2 apolipoprotein binding is part of its ligand-sensing receptor biology.
action: ACCEPT
reason: TREM2 recognizes apolipoproteins and lipoprotein particles and promotes their uptake by
microglia or receptor-expressing cells.
supported_by:
- reference_id: PMID:27477018
supporting_text: we identified a set of lipoprotein particles (including LDL) and
apolipoproteins (including CLU/APOJ and APOE) as ligands
- reference_id: PMID:27477018
supporting_text: Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL,
CLU, and APOE in heterologous cells
- term:
id: GO:0034186
label: apolipoprotein A-I binding
evidence_type: IPI
original_reference_id: PMID:27477018
qualifier: enables
review:
summary: TREM2 apolipoprotein A-I binding is part of its ligand-sensing receptor biology.
action: ACCEPT
reason: TREM2 recognizes apolipoproteins and lipoprotein particles and promotes their uptake by
microglia or receptor-expressing cells.
supported_by:
- reference_id: PMID:27477018
supporting_text: we identified a set of lipoprotein particles (including LDL) and
apolipoproteins (including CLU/APOJ and APOE) as ligands
- reference_id: PMID:27477018
supporting_text: Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL,
CLU, and APOE in heterologous cells
- term:
id: GO:0034189
label: very-low-density lipoprotein particle binding
evidence_type: IDA
original_reference_id: PMID:27477018
qualifier: enables
review:
summary: TREM2 very-low-density lipoprotein particle binding is part of its ligand-sensing
receptor biology.
action: ACCEPT
reason: TREM2 recognizes apolipoproteins and lipoprotein particles and promotes their uptake by
microglia or receptor-expressing cells.
supported_by:
- reference_id: PMID:27477018
supporting_text: we identified a set of lipoprotein particles (including LDL) and
apolipoproteins (including CLU/APOJ and APOE) as ligands
- reference_id: PMID:27477018
supporting_text: Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL,
CLU, and APOE in heterologous cells
- term:
id: GO:0071813
label: lipoprotein particle binding
evidence_type: IDA
original_reference_id: PMID:27477018
qualifier: enables
review:
summary: TREM2 lipoprotein particle binding is part of its ligand-sensing receptor biology.
action: ACCEPT
reason: TREM2 recognizes apolipoproteins and lipoprotein particles and promotes their uptake by
microglia or receptor-expressing cells.
supported_by:
- reference_id: PMID:27477018
supporting_text: we identified a set of lipoprotein particles (including LDL) and
apolipoproteins (including CLU/APOJ and APOE) as ligands
- reference_id: PMID:27477018
supporting_text: Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL,
CLU, and APOE in heterologous cells
- term:
id: GO:0034241
label: positive regulation of macrophage fusion
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: positive regulation of macrophage fusion is retained as context-specific
TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:0030316
label: osteoclast differentiation
evidence_type: IMP
original_reference_id: PMID:21841309
qualifier: acts_upstream_of_or_within
review:
summary: osteoclast differentiation is retained as context-specific TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
supported_by:
- reference_id: PMID:12925681
supporting_text: loss of function mutations in DAP12 and TREM2 result in an inefficient and
delayed differentiation of osteoclasts
- term:
id: GO:0005543
label: phospholipid binding
evidence_type: IDA
original_reference_id: PMID:27995897
qualifier: enables
review:
summary: TREM2 phospholipid binding is part of its ligand-sensing receptor biology.
action: ACCEPT
reason: Aminophospholipid and anionic lipid recognition is a core TREM2 ligand-sensing function
for apoptotic-cell and debris responses.
supported_by:
- reference_id: PMID:31101881
supporting_text: TREM2-dependent signal transduction in response to apoptotic Neuro2a cells is
mediated by aminophospholipid ligands, phosphatidylserine and phosphatidylethanolamine
- term:
id: GO:0005886
label: plasma membrane
evidence_type: IDA
original_reference_id: PMID:27995897
qualifier: located_in
review:
summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface
receptor role.
action: ACCEPT
reason: Cell-surface/plasma-membrane localization is essential for ligand binding and
DAP12/TYROBP-mediated signal transduction.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is
associated with DAP12.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:27995897
supporting_text: Nasu-Hakola mutations impact protein stability and decrease folded TREM2
surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
- term:
id: GO:0070374
label: positive regulation of ERK1 and ERK2 cascade
evidence_type: IMP
original_reference_id: PMID:27995897
qualifier: involved_in
review:
summary: positive regulation of ERK1 and ERK2 cascade is a core downstream consequence of TREM2
receptor signaling.
action: ACCEPT
reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support
calcium/ERK/PI3K-related activation and intracellular signaling.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC
maturation, and DC survival through activation of protein tyrosine kinases and extracellular
signal-regulated kinase.
- reference_id: PMID:32514138
supporting_text: TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis,
processing of neuronal debris, and lipid metabolism.
- term:
id: GO:0002588
label: positive regulation of antigen processing and presentation of peptide antigen via MHC
class II
evidence_type: IDA
original_reference_id: PMID:11602640
qualifier: involved_in
review:
summary: positive regulation of antigen processing and presentation of peptide antigen via MHC
class II is a plausible downstream immune/inflammatory consequence of TREM2 signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
- term:
id: GO:0016020
label: membrane
evidence_type: IDA
original_reference_id: PMID:11602640
qualifier: located_in
review:
summary: TREM2 localization to membrane is consistent with its type I cell-surface receptor
role.
action: ACCEPT
reason: Cell-surface/plasma-membrane localization is essential for ligand binding and
DAP12/TYROBP-mediated signal transduction.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is
associated with DAP12.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:27995897
supporting_text: Nasu-Hakola mutations impact protein stability and decrease folded TREM2
surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
- term:
id: GO:0050850
label: positive regulation of calcium-mediated signaling
evidence_type: IDA
original_reference_id: PMID:11602640
qualifier: involved_in
review:
summary: positive regulation of calcium-mediated signaling is a core downstream consequence of
TREM2 receptor signaling.
action: ACCEPT
reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support
calcium/ERK/PI3K-related activation and intracellular signaling.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC
maturation, and DC survival through activation of protein tyrosine kinases and extracellular
signal-regulated kinase.
- reference_id: PMID:32514138
supporting_text: TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis,
processing of neuronal debris, and lipid metabolism.
- term:
id: GO:0070374
label: positive regulation of ERK1 and ERK2 cascade
evidence_type: IDA
original_reference_id: PMID:11602640
qualifier: involved_in
review:
summary: positive regulation of ERK1 and ERK2 cascade is a core downstream consequence of TREM2
receptor signaling.
action: ACCEPT
reason: TREM2 signals through DAP12/TYROBP and PLCG2-linked kinase pathways that support
calcium/ERK/PI3K-related activation and intracellular signaling.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC
maturation, and DC survival through activation of protein tyrosine kinases and extracellular
signal-regulated kinase.
- reference_id: PMID:32514138
supporting_text: TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis,
processing of neuronal debris, and lipid metabolism.
- term:
id: GO:0097028
label: dendritic cell differentiation
evidence_type: IDA
original_reference_id: PMID:11602640
qualifier: involved_in
review:
summary: dendritic cell differentiation is retained as context-specific TREM2-associated
biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:0097110
label: scaffold protein binding
evidence_type: IPI
original_reference_id: PMID:11602640
qualifier: enables
review:
summary: scaffold protein binding is a specific interaction context for TREM2 but not the main
molecular-function term.
action: KEEP_AS_NON_CORE
reason: Retain as non-core because the interaction may be real, while more informative core
terms describe receptor activity and lipid/lipoprotein/aminophospholipid ligand binding.
- term:
id: GO:1903078
label: positive regulation of protein localization to plasma membrane
evidence_type: IDA
original_reference_id: PMID:11602640
qualifier: involved_in
review:
summary: positive regulation of protein localization to plasma membrane is retained as
context-specific TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:1903082
label: positive regulation of C-C chemokine receptor CCR7 signaling pathway
evidence_type: IDA
original_reference_id: PMID:11602640
qualifier: involved_in
review:
summary: positive regulation of C-C chemokine receptor CCR7 signaling pathway is retained as
context-specific TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:2000350
label: positive regulation of CD40 signaling pathway
evidence_type: IDA
original_reference_id: PMID:11602640
qualifier: involved_in
review:
summary: positive regulation of CD40 signaling pathway is retained as context-specific
TREM2-associated biology.
action: KEEP_AS_NON_CORE
reason: This annotation reflects a cell-type-specific or downstream phenotype rather than the
core TREM2 receptor-ligand signaling mechanism.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-210289
qualifier: located_in
review:
summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface
receptor role.
action: ACCEPT
reason: Cell-surface/plasma-membrane localization is essential for ligand binding and
DAP12/TYROBP-mediated signal transduction.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is
associated with DAP12.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:27995897
supporting_text: Nasu-Hakola mutations impact protein stability and decrease folded TREM2
surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-210300
qualifier: located_in
review:
summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface
receptor role.
action: ACCEPT
reason: Cell-surface/plasma-membrane localization is essential for ligand binding and
DAP12/TYROBP-mediated signal transduction.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is
associated with DAP12.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:27995897
supporting_text: Nasu-Hakola mutations impact protein stability and decrease folded TREM2
surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-2395412
qualifier: located_in
review:
summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface
receptor role.
action: ACCEPT
reason: Cell-surface/plasma-membrane localization is essential for ligand binding and
DAP12/TYROBP-mediated signal transduction.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is
associated with DAP12.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:27995897
supporting_text: Nasu-Hakola mutations impact protein stability and decrease folded TREM2
surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-2395801
qualifier: located_in
review:
summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface
receptor role.
action: ACCEPT
reason: Cell-surface/plasma-membrane localization is essential for ligand binding and
DAP12/TYROBP-mediated signal transduction.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is
associated with DAP12.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:27995897
supporting_text: Nasu-Hakola mutations impact protein stability and decrease folded TREM2
surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-2396594
qualifier: located_in
review:
summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface
receptor role.
action: ACCEPT
reason: Cell-surface/plasma-membrane localization is essential for ligand binding and
DAP12/TYROBP-mediated signal transduction.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is
associated with DAP12.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:27995897
supporting_text: Nasu-Hakola mutations impact protein stability and decrease folded TREM2
surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-2424480
qualifier: located_in
review:
summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface
receptor role.
action: ACCEPT
reason: Cell-surface/plasma-membrane localization is essential for ligand binding and
DAP12/TYROBP-mediated signal transduction.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is
associated with DAP12.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:27995897
supporting_text: Nasu-Hakola mutations impact protein stability and decrease folded TREM2
surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-2424482
qualifier: located_in
review:
summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface
receptor role.
action: ACCEPT
reason: Cell-surface/plasma-membrane localization is essential for ligand binding and
DAP12/TYROBP-mediated signal transduction.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is
associated with DAP12.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:27995897
supporting_text: Nasu-Hakola mutations impact protein stability and decrease folded TREM2
surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-2424484
qualifier: located_in
review:
summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface
receptor role.
action: ACCEPT
reason: Cell-surface/plasma-membrane localization is essential for ligand binding and
DAP12/TYROBP-mediated signal transduction.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is
associated with DAP12.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:27995897
supporting_text: Nasu-Hakola mutations impact protein stability and decrease folded TREM2
surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-2424486
qualifier: located_in
review:
summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface
receptor role.
action: ACCEPT
reason: Cell-surface/plasma-membrane localization is essential for ligand binding and
DAP12/TYROBP-mediated signal transduction.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is
associated with DAP12.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:27995897
supporting_text: Nasu-Hakola mutations impact protein stability and decrease folded TREM2
surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-2424487
qualifier: located_in
review:
summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface
receptor role.
action: ACCEPT
reason: Cell-surface/plasma-membrane localization is essential for ligand binding and
DAP12/TYROBP-mediated signal transduction.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is
associated with DAP12.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:27995897
supporting_text: Nasu-Hakola mutations impact protein stability and decrease folded TREM2
surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-416725
qualifier: located_in
review:
summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface
receptor role.
action: ACCEPT
reason: Cell-surface/plasma-membrane localization is essential for ligand binding and
DAP12/TYROBP-mediated signal transduction.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is
associated with DAP12.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:27995897
supporting_text: Nasu-Hakola mutations impact protein stability and decrease folded TREM2
surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5696358
qualifier: located_in
review:
summary: TREM2 localization to plasma membrane is consistent with its type I cell-surface
receptor role.
action: ACCEPT
reason: Cell-surface/plasma-membrane localization is essential for ligand binding and
DAP12/TYROBP-mediated signal transduction.
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is
associated with DAP12.
- reference_id: PMID:24990881
supporting_text: missense mutations associated with FTD and FTD-like syndrome reduce TREM2
maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of
TREM2-expressing cells.
- reference_id: PMID:27995897
supporting_text: Nasu-Hakola mutations impact protein stability and decrease folded TREM2
surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand.
- term:
id: GO:0006959
label: humoral immune response
evidence_type: TAS
original_reference_id: PMID:10799849
qualifier: involved_in
review:
summary: humoral immune response is a plausible downstream immune/inflammatory consequence of
TREM2 signaling.
action: KEEP_AS_NON_CORE
reason: TREM2 modulates myeloid and microglial immune responses, but specific
cytokine/TLR/neuroinflammatory outputs are context-dependent and should remain non-core.
supported_by:
- reference_id: PMID:24990881
supporting_text: TREM2 is an innate immune receptor preferentially expressed by microglia and
is involved in inflammation and phagocytosis.
references:
- 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:0000044
title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary
mapping, accompanied by conservative changes to GO terms applied by UniProt
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:10799849
title: 'Cutting edge: inflammatory responses can be triggered by TREM-1, a novel receptor expressed
on neutrophils and monocytes.'
findings: []
- id: PMID:11602640
title: A DAP12-mediated pathway regulates expression of CC chemokine receptor 7 and maturation of
human dendritic cells.
findings: []
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: Cached full-text record directly establishes human TREM2 as a
DAP12-associated cell-surface receptor and supports downstream kinase/ERK
signaling.
- id: PMID:12925681
title: DAP12/TREM2 deficiency results in impaired osteoclast differentiation and osteoporotic
features.
findings: []
- id: PMID:16715077
title: Plexin-A1 and its interaction with DAP12 in immune responses and bone homeostasis.
findings: []
- id: PMID:21841309
title: OSCAR is a collagen receptor that costimulates osteoclastogenesis in DAP12-deficient humans
and mice.
findings: []
- id: PMID:24078628
title: Sequential proteolytic processing of the triggering receptor expressed on myeloid cells-2
(TREM2) protein by ectodomain shedding and γ-secretase-dependent intramembranous cleavage.
findings: []
- id: PMID:24990881
title: TREM2 mutations implicated in neurodegeneration impair cell surface transport and
phagocytosis.
findings: []
- id: PMID:25615530
title: Disease-Associated Mutations of TREM2 Alter the Processing of N-Linked Oligosaccharides in
the Golgi Apparatus.
findings: []
- id: PMID:27044754
title: FRMD4A-cytohesin signaling modulates the cellular release of tau.
findings: []
- id: PMID:27477018
title: TREM2 Binds to Apolipoproteins, Including APOE and CLU/APOJ, and Thereby Facilitates Uptake
of Amyloid-Beta by Microglia.
findings: []
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: Cached abstract directly supports TREM2 binding to
apolipoproteins/lipoprotein particles, including APOE and CLU, and
TREM2-dependent uptake of amyloid-lipoprotein complexes.
- id: PMID:27589997
title: Rare TREM2 variants associated with Alzheimer's disease display reduced cell surface
expression.
findings: []
- id: PMID:27995897
title: Neurodegenerative disease mutations in TREM2 reveal a functional surface and distinct
loss-of-function mechanisms.
findings: []
- id: PMID:28490631
title: A split-luciferase complementation, real-time reporting assay enables monitoring of the
disease-associated transmembrane protein TREM2 in live cells.
findings: []
- id: PMID:28768830
title: Neurodegeneration-associated mutant TREM2 proteins abortively cycle between the ER and
ER-Golgi intermediate compartment.
findings: []
- id: PMID:28855300
title: An Alzheimer-associated TREM2 variant occurs at the ADAM cleavage site and affects shedding
and phagocytic function.
findings: []
- id: PMID:28855301
title: TREM2 shedding by cleavage at the H157-S158 bond is accelerated for the Alzheimer's
disease-associated H157Y variant.
findings: []
- id: PMID:28923481
title: ADAM17 is the main sheddase for the generation of human triggering receptor expressed in
myeloid cells (hTREM2) ectodomain and cleaves TREM2 after Histidine 157.
findings: []
- id: PMID:29518356
title: TREM2 Is a Receptor for β-Amyloid that Mediates Microglial Function.
findings: []
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: Cached record supports TREM2 amyloid-beta receptor activity
and microglial functional consequences; used as Alzheimer-context ligand
evidence.
- id: PMID:29518357
title: Elevated TREM2 Gene Dosage Reprograms Microglia Responsivity and Ameliorates Pathological
Phenotypes in Alzheimer's Disease Models.
findings: []
- id: PMID:29611543
title: Intracellular trafficking of TREM2 is regulated by presenilin 1.
findings: []
- id: PMID:29752066
title: The Microglial Innate Immune Receptor TREM2 Is Required for Synapse Elimination and Normal
Brain Connectivity.
findings: []
- id: PMID:30333625
title: LILRB4 signalling in leukaemia cells mediates T cell suppression and tumour infiltration.
findings: []
- id: PMID:30341064
title: High-affinity interactions and signal transduction between Aβ oligomers and TREM2.
findings: []
- id: PMID:30683932
title: TREM2 acts as a tumor suppressor in hepatocellular carcinoma by targeting the
PI3K/Akt/β-catenin pathway.
findings: []
- id: PMID:31101881
title: Aminophospholipids are signal-transducing TREM2 ligands on apoptotic cells.
findings: []
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: Cached abstract supports phosphatidylserine and
phosphatidylethanolamine as signal-transducing TREM2 ligands on apoptotic
cells.
- id: PMID:31235932
title: TREM2 function impedes tau seeding in neuritic plaques.
findings: []
- id: PMID:31413141
title: The MS4A gene cluster is a key modulator of soluble TREM2 and Alzheimer's disease risk.
findings: []
- id: PMID:31462511
title: Increased soluble TREM2 in cerebrospinal fluid is associated with reduced cognitive and
clinical decline in Alzheimer's disease.
findings: []
- id: PMID:31902528
title: TREM2 Regulates Microglial Cholesterol Metabolism upon Chronic Phagocytic Challenge.
findings: []
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: Cached abstract supports TREM2 lipid/myelin sensing,
microglial phagocytosis, and cholesterol-metabolism adaptation after
chronic phagocytic challenge.
- 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: []
- id: PMID:33097708
title: Gene expression and functional deficits underlie TREM2-knockout microglia responses in
human models of Alzheimer's disease.
findings: []
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: Cached abstract supports human microglial TREM2 loss-of-
function effects on survival, phagocytosis, migration, metabolism, and
inflammatory responses.
- id: Reactome:R-HSA-210289
title: Recruitment of SYK to p-DAP12
findings: []
- id: Reactome:R-HSA-210300
title: Interaction of DAP12 and TREM2
findings: []
- id: Reactome:R-HSA-2395412
title: Phosphorylation of SYK
findings: []
- id: Reactome:R-HSA-2395801
title: Phosphorylation of LAT by p-SYK
findings: []
- id: Reactome:R-HSA-2396594
title: Phosphorylation of SLP-76 by p-SYK
findings: []
- id: Reactome:R-HSA-2424480
title: PI3K phosphorylates PIP2 to PIP3
findings: []
- id: Reactome:R-HSA-2424482
title: p85 regulatory unit of PI3K binds p-6Y-SYK
findings: []
- id: Reactome:R-HSA-2424484
title: Phosphorylation of BTK by p-SYK
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-416725
title: SEMA6D binds to PLXNA1:TREM2:DAP12
findings: []
- id: Reactome:R-HSA-5696358
title: TREM,CD300 binds lipids
findings: []
core_functions:
- molecular_function:
id: GO:0004888
label: transmembrane signaling receptor activity
description: TREM2 is a plasma-membrane myeloid receptor that associates with TYROBP/DAP12 and
transduces ligand binding into intracellular kinase, PLCG2, calcium, ERK, and activation
programs in microglia and other myeloid cells.
directly_involved_in:
- id: GO:0007165
label: signal transduction
- id: GO:0045088
label: regulation of innate immune response
- id: GO:1902533
label: positive regulation of intracellular signal transduction
- id: GO:0050850
label: positive regulation of calcium-mediated signaling
- id: GO:0070374
label: positive regulation of ERK1 and ERK2 cascade
locations:
- id: GO:0005886
label: plasma membrane
supported_by:
- reference_id: PMID:11602640
supporting_text: TREM-2 is a cell surface receptor on human monocyte-derived DCs, which is
associated with DAP12.
- reference_id: PMID:11602640
supporting_text: TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC
maturation, and DC survival through activation of protein tyrosine kinases and extracellular
signal-regulated kinase.
- reference_id: PMID:32514138
supporting_text: TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis, processing
of neuronal debris, and lipid metabolism.
- molecular_function:
id: GO:0008289
label: lipid binding
description: TREM2 recognizes lipid-rich damage and uptake ligands, including aminophospholipids
on apoptotic cells, lipoprotein/apolipoprotein particles, sulfatides, and
amyloid-beta-lipoprotein complexes, enabling microglial phagocytosis, activation, migration, and
lipid handling.
directly_involved_in:
- id: GO:0060100
label: positive regulation of phagocytosis, engulfment
- id: GO:0043277
label: apoptotic cell clearance
- id: GO:1903980
label: positive regulation of microglial cell activation
- id: GO:1904141
label: positive regulation of microglial cell migration
- id: GO:0055088
label: lipid homeostasis
locations:
- id: GO:0005886
label: plasma membrane
supported_by:
- reference_id: PMID:27477018
supporting_text: we identified a set of lipoprotein particles (including LDL) and
apolipoproteins (including CLU/APOJ and APOE) as ligands
- reference_id: PMID:31101881
supporting_text: TREM2-dependent signal transduction in response to apoptotic Neuro2a cells is
mediated by aminophospholipid ligands, phosphatidylserine and phosphatidylethanolamine
- reference_id: PMID:31902528
supporting_text: TREM2 senses lipids and mediates myelin phagocytosis
- reference_id: PMID:33097708
supporting_text: TREM2 deletion reduces microglial survival, impairs phagocytosis of key
substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis
proposed_new_terms: []
suggested_questions:
- question: Which TREM2 ligand classes are normal in-vivo microglial ligands across brain states,
and which are disease-model or injury-specific substrates?
experts:
- microglial biology experts
- GO immune receptor curators
- question: How should TREM2/TYROBP/DAP12 signaling be represented without over-curating every
downstream cytokine, kinase, survival, or metabolic phenotype as a core function?
experts:
- innate immune signaling curators
- microglial signaling experts
- question: Which amyloid-beta, synapse-pruning, and neuroinflammatory annotations reflect evolved
TREM2 biology versus Alzheimer model-stage-specific phenotypes?
experts:
- Alzheimer microglia experts
- GO neuroimmune curators
suggested_experiments:
- description: 'Compare endogenous human TREM2 knock-in and knockout microglia across defined ligands:
apoptotic cells, purified aminophospholipids, APOE/CLU lipoprotein particles, myelin debris, synaptosomes,
and amyloid-beta-lipoprotein complexes.'
hypothesis: TREM2 core ligand sensing can be decomposed into ligand classes with distinct
requirements for TYROBP/DAP12, PLCG2, SYK, and calcium signaling.
experiment_type: ligand-defined microglial uptake and signaling assays
- description: Use in-vivo baseline, injury, demyelination, and amyloid/tau model time courses to
separate normal TREM2-dependent phagocytic functions from disease-stage-specific microglial
states.
hypothesis: Some TREM2 annotations, especially amyloid clearance and synapse pruning, are
context-specific outputs of the same core receptor-phagocytosis program.
experiment_type: time-course in-vivo microglial transcriptomics and functional assays
- description: Quantify cell-surface TREM2, soluble TREM2, and TYROBP-associated signaling after
endogenous AD-risk variant knock-in under non-disease and challenge conditions.
hypothesis: Disease-associated variants alter ligand binding, surface trafficking, or signaling
amplitude without changing the core receptor function category.
experiment_type: endogenous variant knock-in receptor trafficking and signaling