TREM2
entrez
54209
canonical
uniprot
Q9NZC2
canonical
ensembl
ENSG00000095970
resolver
ensp
ENSP00000342651
resolver
ensp
ENSP00000362205
resolver
genesymbol
TREM2
resolver
hgnc
HGNC:17761
resolver
uniprot
A6NDG2
resolver
uniprot
Q5TCX1
resolver
uniprot
Q8N5H8
resolver
uniprot
Q8WYN6
resolver
uniprot_entry
Q5TCX1_HUMAN
resolver
uniprot_entry
TREM2_HUMAN
resolver
uniprot_sec
A6NDG2
resolver
uniprot_sec
Q8N5H8
resolver
uniprot_sec
Q8WYN6
resolver
amino_acid_sequence
MEPLRLLILLFVTELSGAHNTTVFQGVAGQSLQVSCPYDSMKHWGRRKAWCRQLGEKGPCQRVVSTHNLWLLSFLRRWNGSTAITDDTLGGTLTITLRNLQPHDAGLYQCQSLHGSEADTLRKVLVEVLADPLDHRDAGDLWFPGESESFEDAHVEHSISRSLLEGEIPFPPTSILLLLACIFLIKILAASALWAAAWHGQKPGTHPPSELDCGHDPGYQLQTLPGLRDT
uniprot
proteins
disease_involvement
DISEASE: Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2 (PLOSL2) [MIM:618193]: 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. {ECO:0000269|PubMed:12080485, ECO:0000269|PubMed:12754369, ECO:0000269|PubMed:12925681, ECO:0000269|PubMed:15883308, ECO:0000269|PubMed:23399524, ECO:0000269|PubMed:25615530, ECO:0000269|PubMed:27995897, ECO:0000269|PubMed:28768830, ECO:0000269|PubMed:28923481, ECO:0000269|PubMed:29142083}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Alzheimer disease 17 (AD17) [MIM:615080]: A late-onset form of Alzheimer disease. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituents of these plaques are neurotoxic amyloid-beta protein 40 and amyloid-beta protein 42, that are produced by the proteolysis of the transmembrane APP protein. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products, such as C31, are also implicated in neuronal death. {ECO:0000269|PubMed:23150908, ECO:0000269|PubMed:24899047, ECO:0000269|PubMed:27589997, ECO:0000269|PubMed:38899702}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding (PubMed:10799849). 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 (By similarity). 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 (PubMed:29794134). Regulates microglial proliferation by acting as an upstream regulator of the Wnt/beta-catenin signaling cascade (By similarity). 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 (By similarity). Regulates microglial chemotaxis and process outgrowth, and also the microglial response to oxidative stress and lipopolysaccharide (By similarity). 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 (By similarity). During oxidative stress, it promotes anti-apoptotic NF-kappa-B signaling and ERK signaling (By similarity). Plays a role in microglial MTOR activation and metabolism (By similarity). Regulates age-related changes in microglial numbers (PubMed:29752066). Triggers activation of the immune responses in macrophages and dendritic cells (PubMed:10799849). Mediates cytokine-induced formation of multinucleated giant cells which are formed by the fusion of macrophages (By similarity). 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:11602640). Involved in the positive regulation of osteoclast differentiation (PubMed:12925681). {ECO:0000250|UniProtKB:Q99NH8, ECO:0000269|PubMed:10799849, ECO:0000269|PubMed:11602640, ECO:0000269|PubMed:12925681, ECO:0000269|PubMed:24990881, ECO:0000269|PubMed:27477018, ECO:0000269|PubMed:29518356, ECO:0000269|PubMed:29752066, ECO:0000269|PubMed:29794134}.
uniprot
proteins
mass_dalton
25447
uniprot
proteins
mutagenesis
MUTAGEN 20; /note="N->D: Loss of glycosylation."; /evidence="ECO:0000269|PubMed:29794134"; MUTAGEN 36; /note="C->A: Loss of proteolytic cleavage by ADAM10 and ectodomain shedding. Decreases protein maturation and cell membrane localization."; /evidence="ECO:0000269|PubMed:24990881"; MUTAGEN 48; /note="K->M: Loss of LDL, CLU and APOE binding."; /evidence="ECO:0000269|PubMed:27477018"; MUTAGEN 60; /note="C->A: Loss of proteolytic cleavage by ADAM10 and ectodomain shedding. Decreases protein maturation and cell membrane localization."; /evidence="ECO:0000269|PubMed:24990881"; MUTAGEN 68; /note="N->K: No effect on cell membrane localization."; /evidence="ECO:0000269|PubMed:27995897"; MUTAGEN 76; /note="R->D: Decreases binding to THP-1 cells."; /evidence="ECO:0000269|PubMed:27995897"; MUTAGEN 77; /note="R->D: Decreases binding to THP-1 cells."; /evidence="ECO:0000269|PubMed:27995897
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:24078628, ECO:0000269|PubMed:24990881, ECO:0000269|PubMed:28855300, ECO:0000269|PubMed:28855301, ECO:0000269|PubMed:28923481}.
uniprot
proteins
pubmed
10799849
uniprot
proteins
pubmed
11602640
uniprot
proteins
pubmed
12080485
uniprot
proteins
pubmed
12754369
uniprot
proteins
pubmed
12925681
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15883308
uniprot
proteins
pubmed
18957693
uniprot
proteins
pubmed
23150908
uniprot
proteins
pubmed
23399524
uniprot
proteins
pubmed
24078628
uniprot
proteins
pubmed
24899047
uniprot
proteins
pubmed
24990881
uniprot
proteins
pubmed
25615530
uniprot
proteins
pubmed
25957402
uniprot
proteins
pubmed
27067662
uniprot
proteins
pubmed
27477018
uniprot
proteins
pubmed
27589997
uniprot
proteins
pubmed
27995897
uniprot
proteins
pubmed
28768830
uniprot
proteins
pubmed
28802038
uniprot
proteins
pubmed
28855300
uniprot
proteins
pubmed
28855301
uniprot
proteins
pubmed
28923481
uniprot
proteins
pubmed
29142083
uniprot
proteins
pubmed
29518356
uniprot
proteins
pubmed
29752066
uniprot
proteins
pubmed
29794134
uniprot
proteins
pubmed
30442540
uniprot
proteins
pubmed
38899702
uniprot
proteins
sequence_length
230
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane {ECO:0000269|PubMed:24078628, ECO:0000269|PubMed:24990881, ECO:0000269|PubMed:25615530, ECO:0000269|PubMed:27589997, ECO:0000269|PubMed:27995897, ECO:0000269|PubMed:28768830, ECO:0000269|PubMed:28855300, ECO:0000269|PubMed:28855301, ECO:0000269|PubMed:28923481}; Single-pass type I membrane protein {ECO:0000255}.; SUBCELLULAR LOCATION: [Isoform 2]: Secreted {ECO:0000305}.; SUBCELLULAR LOCATION: [Isoform 3]: Secreted {ECO:0000305}.
uniprot
proteins
transmembrane_region
TRANSMEM 175..195; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins