TREM2 His Tag Protein, Human

TREM-2 (Triggering Receptor Expressed on Myeloid cells-2) is a 35 kDa type I transmembrane member of the TREM family and Ig superfamily. Mature human TREM-2 consists of a 156 amino acid (aa) extracellular domain (ECD) with one V-type Ig-like domain, a 21 aa transmembrane (TM) domain, and a 35 aa cytoplasmic tail. Soluble forms of the TREM-2 ECD are generated by alternative splicing or proteolytic cleavage, and the cytoplasmic domain can be liberated by gamma-Secretase mediated intramembrane cleavage. A positively charged lysine within the transmembrane segment allows association with the signal adapter protein, DAP12 and inhibition of macrophage activation. TREM-2 is expressed on macrophages, immature myeloid dendritic cells, osteoclasts, microglia, and adipocytes. It promotes the differentiation and function of osteoclasts, the production of inflammatory cytokines by adipocytes, insulin resistance, and the phagocytic clearance of bacteria. In the CNS, TREM-2 binds to ApoE, ApoA1, and ApoB and mediates the clearance of apoptotic neurons, amyloid plaques, and cell debris following demyelination. TREM-2 also interacts with and modifies signaling through Plexin A1 on dendritic cells and osteoclasts. Mutations in TREM-2 or DAP12 are associated with the development of Alzheimer's disease and Nasu-Hakola disease (NHD/PLOSL) which is characterized by presenile dementia and bone cysts. Soluble TREM-2 is elevated in cerebrospinal fluid of patients with active multiple sclerosis (MS), and TREM-2 blockade exacerbates disease symptoms in the experimental EAE model of MS.