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Isoform 2 of Triggering receptor expressed on myeloid cells 2 AlphaSync

Canonical isoform description: Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding¹. 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^2,3. 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 ARG1^4,5. 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 microglia⁶. Binds phospholipids (preferably anionic lipids) such as phosphatidylserine, phosphatidylethanolamine, phosphatidylglycerol and sphingomyelin (By similarity). Regulates microglial proliferation by acting as an upstream regulator of the Wnt/beta-catenin signaling cascade⁷. Required for microglial phagocytosis of apoptotic neurons⁸. Also required for microglial activation and phagocytosis of myelin debris after neuronal injury and of neuronal synapses during synapse elimination in the developing brain^9,10,11,12. Regulates microglial chemotaxis and process outgrowth, and also the microglial response to oxidative stress and lipopolysaccharide^13,14,15,16. 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 TGFB¹⁷. During oxidative stress, it promotes anti-apoptotic NF-kappa-B signaling and ERK signaling¹⁸. Plays a role in microglial MTOR activation and metabolism¹⁹. Regulates age-related changes in microglial numbers^20,21,22. Triggers activation of the immune responses in macrophages and dendritic cells. Mediates cytokine-induced formation of multinucleated giant cells which are formed by the fusion of macrophages²³. In dendritic cells, receptor of SEMA6D with PLEXNA1 as coreceptor and mediates up-regulation of chemokine receptor CCR7 and dendritic cell maturation and survival²⁴. Involved in the positive regulation of osteoclast differentiation²⁵.

AlphaFold DB , UniProt , Accession Q99NH8-2 (canonical: Q99NH8), Species MOUSE (Mus musculus, Mouse), Gene Trem2, Length 249 aa.