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 the central nervous system and periphery. TREM2 is highly expressed in microglia, where it, along with its adaptor protein DAP12, regulates inflammatory cytokine release and phagocytosis of apoptotic neurons. Apolipoprotein E (apoE) is reported to function as a high-affinity TREM2 ligand. ApoE binding enhances the phagocytosis of apoptotic N2a cells by primary microglia cells, and greatly reduced ApoE binding is seen with AD-associated TREM2 R47H mutatant. 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. TREM2 gene mutations and polymorphisms are linked to several neurological disorders, including Alzheimer's disease (AD), frontotemporal dementia (FTD), Parkinson's disease (PD), and Nasu-Hakola disease (a.k.a. PLOSL or polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy).
Synonyms: Triggering receptor expressed on myeloid cells 2, TREM-2, Triggering receptor expressed on monocytes 2
Application: Research Sub CategoryNeuroinflammation & Pain
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