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Description

Triggering receptor expressed on myeloid cells 2 (UniProt: Q9NZC2, also known as TREM-2, Triggering receptor expressed on monocytes 2) is encoded by the TREM2 gene (Gene ID: 54209) in human. TREM2 is an Ig-like V-type receptor expressed by populations of myeloid cells in various region of the central nervous system. Its expression is also reported on macrophages and dendritic cells, but not on granulocytes or monocytes. TREM2 is highly expressed in microglia, where it, along with its adaptor protein DAP12, regulates inflammatory cytokine release and phagocytosis of apoptotic neurons. TREM-2 plays a role in chronic inflammations and may stimulate production of constitutive rather than inflammatory chemokines and cytokines. It forms a receptor signaling complex with TYROBP and triggers activation of the immune responses in macrophages and dendritic cells. Apolipoprotein E (ApoE) is reported to function as a high-affinity ligand for TREM-2. ApoE binding is shown to enhance the phagocytosis of apoptotic N2a cells by primary microglia cells. Greatly reduced ApoE binding is seen with Alzheimer s disease-associated TREM2 R47H mutant. TREM2 is produced with a signal peptide sequence (a.a. 1-18), the removal of which yields the mature single-transmembrane (a.a. 175-195) protein with a large extracellular region (a.a. 19-174) that contains the V-type Ig-like domain (a.a. 29-112) and a cytoplasmic tail (a.a. 196-230). The short cytoplasmic tail contains no signaling motifs and relies on its association with the immunoreceptor tyrosine-based activation motif- (ITAM-) containing TYROBP for signal transduction.