Trem2
entrez
83433
canonical
uniprot
Q99NH8
canonical
ensembl
ENSMUSG00000023992
resolver
ensp
ENSMUSP00000024791
resolver
ensp
ENSMUSP00000108863
resolver
genesymbol
Trem2
resolver
genesymbol_syn
Trem2a
resolver
genesymbol_syn
Trem2b
resolver
genesymbol_syn
Trem2c
resolver
uniprot
Q8CGK4
resolver
uniprot
Q8CIA6
resolver
uniprot
Q99NH9
resolver
uniprot
Q9JL34
resolver
uniprot_entry
TREM2_MOUSE
resolver
uniprot_sec
Q8CGK4
resolver
uniprot_sec
Q8CIA6
resolver
uniprot_sec
Q99NH9
resolver
uniprot_sec
Q9JL34
resolver
amino_acid_sequence
MGPLHQFLLLLITALSQALNTTVLQGMAGQSLRVSCTYDALKHWGRRKAWCRQLGEEGPCQRVVSTHGVWLLAFLKKRNGSTVIADDTLAGTVTITLKNLQAGDAGLYQCQSLRGREAEVLQKVLVEVLEDPLDDQDAGDLWVPEESSSFEGAQVEHSTSRNQETSFPPTSILLLLACVLLSKFLAASILWAVARGRQKPGTPVVRGLDCGQDAGHQLQILTGPGGT
uniprot
proteins
function
FUNCTION: Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding (PubMed:11241283). 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 (PubMed:27477018, PubMed:29518356). 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 (PubMed:27477018, PubMed:29518356). 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 microglia (PubMed:27477018). 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 cascade (PubMed:28077724). Required for microglial phagocytosis of apoptotic neurons (PubMed:24990881). Also required for microglial activation and phagocytosis of myelin debris after neuronal injury and of neuronal synapses during synapse elimination in the developing brain (PubMed:15728241, PubMed:25631124, PubMed:28592261, PubMed:29752066). Regulates microglial chemotaxis and process outgrowth, and also the microglial response to oxidative stress and lipopolysaccharide (PubMed:28483841, PubMed:29663649, PubMed:29859094, PubMed:30232263). 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 TGFB (PubMed:29663649). During oxidative stress, it promotes anti-apoptotic NF-kappa-B signaling and ERK signaling (PubMed:28592261). Plays a role in microglial MTOR activation and metabolism (PubMed:28802038). Regulates age-related changes in microglial numbers (PubMed:25631124, PubMed:29752066, PubMed:30548312). 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 macrophages (PubMed:18957693). In dendritic cells, receptor of SEMA6D with PLEXNA1 as coreceptor and mediates up-regulation of chemokine receptor CCR7 and dendritic cell maturation and survival (PubMed:16715077). Involved in the positive regulation of osteoclast differentiation (PubMed:16418779). {ECO:0000250|UniProtKB:Q9NZC2, ECO:0000269|PubMed:11241283, ECO:0000269|PubMed:15728241, ECO:0000269|PubMed:16418779, ECO:0000269|PubMed:16715077, ECO:0000269|PubMed:18957693, ECO:0000269|PubMed:24990881, ECO:0000269|PubMed:25631124, ECO:0000269|PubMed:27477018, ECO:0000269|PubMed:28077724, ECO:0000269|PubMed:28483841, ECO:0000269|PubMed:28592261, ECO:0000269|PubMed:28802038, ECO:0000269|PubMed:29518356, ECO:0000269|PubMed:29663649, ECO:0000269|PubMed:29752066, ECO:0000269|PubMed:29859094, ECO:0000269|PubMed:30232263, ECO:0000269|PubMed:30548312}.
uniprot
proteins
mass_dalton
24527
uniprot
proteins
mutagenesis
MUTAGEN 47; /note="R->H: Decreases myeloid cell immune response. Reduces expression levels."; /evidence="ECO:0000269|PubMed:29794134, ECO:0000269|PubMed:29859094"; MUTAGEN 66; /note="T->M: Macrophages exhibit increased apoptosis, reduced proliferation, and reduced phagocytosis. Macrophages also exhibit increased inflammatory cytokine secretion. Microglia demonstrate reduced immune activity. Also decreases cerebral blood flow and reduces cerebral glucose metabolism."; /evidence="ECO:0000269|PubMed:28559417
uniprot
proteins
post_translational_modification
PTM: 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. {ECO:0000269|PubMed:24990881, ECO:0000269|PubMed:28855301}.
uniprot
proteins
pubmed
10799849
uniprot
proteins
pubmed
11241283
uniprot
proteins
pubmed
12472885
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15728241
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
16418779
uniprot
proteins
pubmed
16715077
uniprot
proteins
pubmed
18957693
uniprot
proteins
pubmed
24990881
uniprot
proteins
pubmed
25631124
uniprot
proteins
pubmed
27477018
uniprot
proteins
pubmed
28077724
uniprot
proteins
pubmed
28483841
uniprot
proteins
pubmed
28559417
uniprot
proteins
pubmed
28592261
uniprot
proteins
pubmed
28802038
uniprot
proteins
pubmed
28855301
uniprot
proteins
pubmed
29518356
uniprot
proteins
pubmed
29663649
uniprot
proteins
pubmed
29752066
uniprot
proteins
pubmed
29794134
uniprot
proteins
pubmed
29859094
uniprot
proteins
pubmed
30232263
uniprot
proteins
pubmed
30548312
uniprot
proteins
sequence_length
227
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane {ECO:0000269|PubMed:16715077, ECO:0000269|PubMed:24990881}; Single-pass type I membrane protein {ECO:0000255}.; SUBCELLULAR LOCATION: [Isoform 2]: Secreted {ECO:0000305}.
uniprot
proteins
transmembrane_region
TRANSMEM 172..192; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins