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TREM2

Function

The protein expressed by gene TREM2 forms a receptor signaling complex with TYROBP, facilitating signaling and cell activation upon ligand binding. It serves as a receptor for amyloid-beta protein 42, mediating its uptake and degradation by microglia, and also acts as a receptor for lipoprotein particles such as LDL, VLDL, HDL, and various apolipoproteins, enhancing their uptake in microglia. TREM2 binds phospholipids, preferably anionic lipids, and is necessary for microglial phagocytosis of apoptotic neurons. It regulates changes in microglial numbers with age and activates immune responses in macrophages and dendritic cells, where it plays a role in chemokine receptor CCR7 up-regulation, as well as dendritic cell maturation and survival. Additionally, TREM2 is involved in positively regulating osteoclast differentiation. This supplementary information is collated from multiple sources and compiled automatically.

Involvement in disease

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2

PLOSL2

An autosomal recessive disease characterized by presenile frontal dementia with leukoencephalopathy and basal ganglia calcification. In most cases the disorder first manifests in early adulthood as pain and swelling in ankles and feet, followed by bone fractures. Neurologic symptoms manifest in the fourth decade of life as a frontal lobe syndrome with loss of judgment, euphoria, and disinhibition. Progressive decline in other cognitive domains begins to develop at about the same time. The disorder culminates in a profound dementia and death by age 50 years.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

Undergoes ectodomain shedding through proteolytic cleavage by ADAM10 and ADAM17 to produce a transmembrane segment, the TREM2 C-terminal fragment (TREM2-CTF), which is subsequently cleaved by gamma-secretase.

Tissue Specificity

Expressed in the brain, specifically in microglia and in the fusiform gyrus (at protein level) (PubMed:27477018, PubMed:28802038, PubMed:28855300, PubMed:29752066). Expressed on macrophages and dendritic cells but not on granulocytes or monocytes (PubMed:10799849, PubMed:28855301). In the CNS strongest expression seen in the basal ganglia, corpus callosum, medulla oblongata and spinal cord (PubMed:12080485).

Cellular localization

Alternative names

Triggering receptor expressed on myeloid cells 2, TREM-2, Triggering receptor expressed on monocytes 2, TREM2

swissprot:Q9NZC2 omim:605086 entrezGene:54209

Other research areas