Triggering receptor expressed on myeloid cells 2 (Q9NZC2)

Uniprot ID Q9NZC2
Protein Name Triggering receptor expressed on myeloid cells 2
Gene Name TREM2
Species Homo sapiens (Human)
Signal peptide(a) N Secretome P(b)
Function Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding (PubMed:10799849). Acts as a receptor for amyloid-beta protein 42, a cleavage product of the amyloid-beta precursor protein APP, and mediates its uptake and degradation by microglia (PubMed:27477018, PubMed:29518356). Binding to amyloid-beta 42 mediates microglial activation, proliferation, migration, apoptosis and expression of pro-inflammatory cytokines, such as IL6R and CCL3, and the anti-inflammatory cytokine ARG1 (By similarity). Acts as a receptor for lipoprotein particles such as LDL, VLDL, and HDL and for apolipoproteins such as APOA1, APOA2, APOB, APOE, APOE2, APOE3, APOE4, and CLU and enhances their uptake in microglia (PubMed:27477018). Binds phospholipids (preferably anionic lipids) such as phosphatidylserine, phosphatidylethanolamine, phosphatidylglycerol and sphingomyelin (PubMed:29794134). Regulates microglial proliferation by acting as an upstream regulator of the Wnt/beta-catenin signaling cascade (By similarity). Required for microglial phagocytosis of apoptotic neurons (PubMed:24990881). Also required for microglial activation and phagocytosis of myelin debris after neuronal injury and of neuronal synapses during synapse elimination in the developing brain (By similarity). Regulates microglial chemotaxis and process outgrowth, and also the microglial response to oxidative stress and lipopolysaccharide (By similarity). It suppresses PI3K and NF-kappa-B signaling in response to lipopolysaccharide; thus promoting phagocytosis, suppressing pro-inflammatory cytokine and nitric oxide production, inhibiting apoptosis and increasing expression of IL10 and TGFB (By similarity). During oxidative stress, it promotes anti-apoptotic NF-kappa-B signaling and ERK signaling (By similarity). Plays a role in microglial MTOR activation and metabolism (By similarity). Regulates age-related changes in microglial numbers (PubMed:29752066). Triggers activation of the immune responses in macrophages and dendritic cells (PubMed:10799849). Mediates cytokine-induced formation of multinucleated giant cells which are formed by the fusion of macrophages (By similarity). In dendritic cells, it mediates up-regulation of chemokine receptor CCR7 and dendritic cell maturation and survival (PubMed:11602640). Involved in the positive regulation of osteoclast differentiation (PubMed:12925681). .
GO - Molecular function
  • amyloid-beta binding : IPI:ARUK-UCL
  • apolipoprotein A-I binding : IPI:ARUK-UCL
  • apolipoprotein binding : IPI:ARUK-UCL
  • high-density lipoprotein particle binding : IDA:ARUK-UCL
  • lipid binding : TAS:ARUK-UCL
  • lipopolysaccharide binding : IEA:Ensembl
  • lipoprotein particle binding : IDA:ARUK-UCL
  • lipoteichoic acid binding : IEA:Ensembl
  • low-density lipoprotein particle binding : IDA:ARUK-UCL
  • peptidoglycan binding : IEA:Ensembl
  • phospholipid binding : IDA:UniProtKB
  • protein tyrosine kinase binding : ISS:ARUK-UCL
  • protein-containing complex binding : IPI:ARUK-UCL
  • scaffold protein binding : IPI:BHF-UCL
  • signaling receptor activity : ISS:ARUK-UCL
  • very-low-density lipoprotein particle binding : IDA:ARUK-UCL
GO - Biological process
  • amyloid-beta clearance : IEA:Ensembl
  • apoptotic cell clearance : ISS:UniProtKB
  • astrocyte activation : ISS:ARUK-UCL
  • cellular response to amyloid-beta : ISS:ARUK-UCL
  • cellular response to lipoteichoic acid : IEA:Ensembl
  • cellular response to peptidoglycan : IEA:Ensembl
  • complement-mediated synapse pruning : IEA:Ensembl
  • defense response to bacterium : IEA:Ensembl
  • dendritic cell differentiation : IDA:BHF-UCL
  • detection of lipopolysaccharide : IEA:Ensembl
  • detection of lipoteichoic acid : IEA:Ensembl
  • detection of peptidoglycan : IEA:Ensembl
  • humoral immune response : TAS:ProtInc
  • import into cell : ISS:ARUK-UCL
  • innate immune response : TAS:Reactome
  • microglial cell activation : ISS:ARUK-UCL
  • microglial cell activation involved in immune response : IEA:Ensembl
  • microglial cell proliferation : IEA:Ensembl
  • negative regulation of apoptotic process : IEA:Ensembl
  • negative regulation of autophagic cell death : ISS:ARUK-UCL
  • negative regulation of autophagy : ISS:ARUK-UCL
  • negative regulation of interleukin-1 beta production : IEA:Ensembl
  • negative regulation of tumor necrosis factor production : IEA:Ensembl
  • osteoclast differentiation : IMP:UniProtKB
  • phagocytosis, engulfment : IEA:Ensembl
  • positive regulation of amyloid-beta clearance : ISS:ARUK-UCL
  • positive regulation of antigen processing and presentation of peptide antigen via MHC class II : IDA:BHF-UCL
  • positive regulation of ATP biosynthetic process : ISS:ARUK-UCL
  • positive regulation of C-C chemokine receptor CCR7 signaling pathway : IDA:BHF-UCL
  • positive regulation of calcium-mediated signaling : IDA:BHF-UCL
  • positive regulation of CAMKK-AMPK signaling cascade : ISS:ARUK-UCL
  • positive regulation of CD40 signaling pathway : IDA:BHF-UCL
  • positive regulation of chemotaxis : ISS:ARUK-UCL
  • positive regulation of engulfment of apoptotic cell : IMP:UniProtKB
  • positive regulation of ERK1 and ERK2 cascade : IDA:BHF-UCL
  • positive regulation of gene expression : ISS:ARUK-UCL
  • positive regulation of interleukin-10 production : IEA:Ensembl
  • positive regulation of inward rectifier potassium channel activity : ISS:ARUK-UCL
  • positive regulation of macrophage fusion : ISS:UniProtKB
  • positive regulation of microglial cell activation : IMP:UniProtKB
  • positive regulation of microglial cell migration : ISS:ARUK-UCL
  • positive regulation of mitochondrion organization : ISS:ARUK-UCL
  • positive regulation of NIK/NF-kappaB signaling : IEA:Ensembl
  • positive regulation of osteoclast differentiation : IEA:Ensembl
  • positive regulation of peptidyl-tyrosine phosphorylation : IDA:BHF-UCL
  • positive regulation of phagocytosis, engulfment : IMP:UniProtKB
  • positive regulation of proteasomal protein catabolic process : ISS:ARUK-UCL
  • positive regulation of protein localization to plasma membrane : IDA:BHF-UCL
  • positive regulation of protein phosphorylation : ISS:ARUK-UCL
  • positive regulation of protein secretion : IMP:UniProtKB
  • positive regulation of TOR signaling : ISS:ARUK-UCL
  • regulation of gene expression : ISS:ARUK-UCL
  • regulation of immune response : TAS:Reactome
  • regulation of innate immune response : IEA:Ensembl
  • regulation of interleukin-6 production : ISS:ARUK-UCL
  • regulation of intracellular signal transduction : ISS:ARUK-UCL
  • regulation of macrophage inflammatory protein 1 alpha production : ISS:ARUK-UCL
  • regulation of peptidyl-tyrosine phosphorylation : ISS:ARUK-UCL
  • regulation of plasma membrane bounded cell projection organization : IGI:ARUK-UCL
  • regulation of resting membrane potential : ISS:ARUK-UCL
  • regulation of TOR signaling : ISS:ARUK-UCL
  • response to ischemia : IEA:Ensembl
Back
(a) The Signal peptide D-score cutoff for "YES"(having signal peptide) is 0.45.
(b) Non-classically secreted proteins should obtain an NN-score(Neural Networks score) exceeding the normal threshold of 0.5, but not at the same time be predicted to contain a signal peptide.