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 PLCΞ³2 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 PLCΞ³2 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 PLCΞ³2 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 PLCΞ³2 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-1Ξ±/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 PLCΞ³2 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-1Ξ±/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 PLCΞ³2 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-1Ξ±/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 PLCΞ³2 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-1Ξ±/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-1Ξ±/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 PLCΞ³2 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-1Ξ±/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 PLCΞ³2 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 Ξ²-amyloid (AΞ²) 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-1Ξ±/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-1Ξ±/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-1Ξ±/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 PLCΞ³2 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 PLCΞ³2 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-1Ξ±/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 PLCΞ³2 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 Ξ²-amyloid (AΞ²) 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-1Ξ±/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 Ξ²-amyloid (AΞ²) 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-1Ξ±/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 Ξ²-amyloid (AΞ²) 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-1Ξ±/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 Ξ²-amyloid (AΞ²) 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-1Ξ±/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 Ξ²-amyloid (AΞ²) 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-1Ξ±/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 Ξ²-amyloid (AΞ²) 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-1Ξ±/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 PLCΞ³2 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 Ξ²-amyloid (AΞ²) 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-1Ξ±/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-1Ξ±/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-1Ξ±/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 Ξ²-amyloid (AΞ²) 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-1Ξ±/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 PLCΞ³2 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 Ξ²-amyloid (AΞ²) 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-1Ξ±/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 Ξ²-amyloid (AΞ²) 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-1Ξ±/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 PLCΞ³2 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 PLCΞ³2 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 Ξ²-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 Ξ²-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 Ξ²-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 Ξ²-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 Ξ²-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 PLCΞ³2 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 PLCΞ³2 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 Ξ²-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 PLCΞ³2 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 PLCΞ³2 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 Ξ²-amyloid (AΞ²) 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-1Ξ±/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 PLCΞ³2 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-1Ξ±/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-1Ξ±/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 PLCΞ³2 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 Ξ²-amyloid (AΞ²) 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-1Ξ±/CXCR4-mediated chemotaxis |
| GO:0006910 phagocytosis, recognition | IMP PMID:32514138 Alzheimer's-associated PLCΞ³2 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-1Ξ±/CXCR4-mediated chemotaxis |
| GO:0010628 positive regulation of gene expression | IMP PMID:32514138 Alzheimer's-associated PLCΞ³2 is a signaling node required fo... | KEEP AS NON CORE | Summary: 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 PLCΞ³2 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 PLCΞ³2 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 PLCΞ³2 to mediate cell survival, phagocytosis, processing of neuronal debris, and lipid metabolism. |
| GO:0048678 response to axon injury | IMP PMID:32514138 Alzheimer's-associated PLCΞ³2 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 Ξ²-amyloid (AΞ²) 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-1Ξ±/CXCR4-mediated chemotaxis |
| GO:0060100 positive regulation of phagocytosis, engulfment | IMP PMID:32514138 Alzheimer's-associated PLCΞ³2 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-1Ξ±/CXCR4-mediated chemotaxis |
| GO:0071396 cellular response to lipid | IMP PMID:32514138 Alzheimer's-associated PLCΞ³2 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 PLCΞ³2 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 PLCΞ³2 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 PLCΞ³2 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 Ξ²-amyloid (AΞ²) 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-1Ξ±/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 Ξ²-amyloid (AΞ²) 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-1Ξ±/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-1Ξ±/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 Ξ²-amyloid (AΞ²) 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-1Ξ±/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 Ξ²-amyloid (AΞ²) 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-1Ξ±/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 Ξ²-amyloid (AΞ²) 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-1Ξ±/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-1Ξ±/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-1Ξ±/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-1Ξ±/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 PLCΞ³2 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-1Ξ±/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-1Ξ±/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 Ξ²-amyloid (AΞ²) 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-1Ξ±/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 PLCΞ³2 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 Ξ²-amyloid (AΞ²) 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-1Ξ±/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-1Ξ±/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 Ξ²-amyloid (AΞ²) 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-1Ξ±/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 Ξ²-amyloid (AΞ²) 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-1Ξ±/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 Ξ²-amyloid (AΞ²) 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-1Ξ±/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 Ξ²-amyloid (AΞ²) 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-1Ξ±/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-1Ξ±/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 Ξ²-amyloid (AΞ²) 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-1Ξ±/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 PLCΞ³2 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 Ξ²-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-1Ξ±/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-1Ξ±/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-1Ξ±/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-1Ξ±/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-1Ξ±/CXCR4-mediated chemotaxis |
| GO:0008289 lipid binding | TAS PMID:29518356 TREM2 Is a Receptor for Ξ²-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 Ξ²-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 PLCΞ³2 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 Ξ²-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 Ξ²-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 Ξ²-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 Ξ²-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-1Ξ±/CXCR4-mediated chemotaxis |
| GO:1904646 cellular response to amyloid-beta | ISS PMID:29518356 TREM2 Is a Receptor for Ξ²-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 Ξ²-amyloid (AΞ²) 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-1Ξ±/CXCR4-mediated chemotaxis |
| GO:1990782 protein tyrosine kinase binding | ISS PMID:29518356 TREM2 Is a Receptor for Ξ²-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 Ξ²-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 Ξ²-amyloid (AΞ²) 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 Ξ²-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 PLCΞ³2 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 PLCΞ³2 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 PLCΞ³2 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. |
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Download this section (compressed HTML)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
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