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FLASH GENE
Symbol TREM2 contributors: mct/ - updated : 03-05-2016
HGNC name triggering receptor expressed on myeloid cells 2
HGNC id 17761
Corresponding disease
PLOSL2 polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2
Location 6p21.1      Physical location : 41.126.245 - 41.130.922
Synonym name triggering receptor expressed on monocytes 2
Synonym symbol(s) Trem2a, Trem2b, Trem2c
DNA
TYPE functioning gene
SPECIAL FEATURE component of a cluster
STRUCTURE 4.69 kb     5 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
Physical map
LOC389388 6 LOC389388 KIAA1246 6p21.1 LOC389388 UNC5CL 6p21.1 unc-5 homolog C (C. elegans)-like BZRPL1 6p21.1 benzodiazapine receptor (peripheral)-like 1 APOBEC2 6p21 apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 2 C6orf130 6p21.1 chromosome 6 open reading frame 130 NFYA 6p21.3 nuclear transcription factor Y, alpha LOC221442 6p21.1 hypothetical protein LOC221442 TREML1 6p21.1 triggering receptor expressed on myeloid cells-like 1 TREM2 6p21.1 triggering receptor expressed on myeloid cells 2 C6orf76 6p21.1 chromosome 6 open reading frame 76 LOC285852 6p21.1 hypothetical protein LOC285852 TREM1 6p21.1 triggering receptor expressed on myeloid cells 1 NCR2 6p21.1 natural cytotoxicity triggering receptor 2 FOXP4 6p21.1 forkhead box P4 MDFI 6p21 MyoD family inhibitor TFEB 6p21 transcription factor EB PGC 6p22-p12 progastricsin (pepsinogen C) FRS3 6p21.1 fibroblast growth factor receptor substrate 3 C6orf49 6p21.31 chromosome 6 open reading frame 49 MGC20741 6p21 ubiquitin specific protease 49 USP49 6p12.1 ubiquitin specific protease 49 BYSL 6p21.1 bystin-like CCND3 6p21 cyclin D3
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
5 - 1059 25.4 230 - 2001 11602640
five exons
4 - 882 - 219 - 2001 11602640
EXPRESSION
Type restricted
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Nervousbrain     Homo sapiens
Reproductivefemale systemuteruscervix  
 female systemuterus   
Respiratorylung    
Urinarykidney    
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connectiveadipose   
cells
SystemCellPubmedSpeciesStageRna symbol
Blood/Hematopoieticmyelocyte Homo sapiens
Lymphoid/Immunemacrophage Homo sapiens
Nervousglia Homo sapiens
Nervousneuron
Skeletonosteoclast Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
HOMOLOGY
interspecies ortholog to murine Trem2c-pending
homolog to drosophila CG2304
homolog to C.elegans Y119C1B.5
Homologene
FAMILY
  • family of cell membrane expressed innate immune receptors
  • CATEGORY immunity/defense , receptor nuclear
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    basic FUNCTION
  • playing a role in chronic inflammatory response
  • playing a critical role in the differentiation of mononuclear myeloid precursors into functional multinucleated osteoclasts
  • regulates osteoclast multinucleation as well as resorption and migration of mature osteoclast
  • delivers intracellular signals through the adaptor TYROBP to regulate myeloid cell function both within and outside the immune system
  • expressed on newly differentiated and alternatively activated macrophages and functions to restrain macrophage activation
  • TYROBP and TREM2, with SYK are required for the cytokine-induced formation of giant cells
  • its signaling is an important pathway to promote healing of wounds in the colon where stem cell replacement is necessary
  • TREM2, triggering receptor expressed on myeloid cell-2, negatively regulates TLR responses in dendritic cells
  • regulates the rate of osteoclastogenesis, providing a mechanism for the bone pathology in Nasu-Hakola disease (PLOSL2)
  • TREM2 signaling has been shown to enhance the proliferation of osteoclast precursors via a phosphatidylinositol 3-kinase-mediated activation of AKT1
  • ITAM molecules, FCER1G, TREM2 and TYROBP play an important role in osteoclast development and activity
  • is responsible for an unexpectedly high number of dementia cases
  • TREM2 and its signaling adaptor protein TYROBP/DAP12 play important roles in signal transduction in dendritic cells, osteoclasts, tissue macrophages, and microglia
  • involved in the anti-inflammatory response and osteoclast development
  • promotes adipogenesis and diet-induced obesity by upregulating adipogenic regulators in conjunction with inhibiting the WNT10B/CTNNB1 signaling pathway
  • key regulator of microglia activation in response to tissue damage
  • is required for promoting microglial expansion during aging and microglial response to insults of the white matter
  • TREM2 and TYROBP—possess the ability to modulate critical cellular functions via crosstalk with diverse signaling pathways
  • microglial receptor that recognizes changes in the lipid microenvironment, which may occur during APP accumulation and neuronal degeneration in Alzheimer disease (AD)
  • TREM2 protects from AD by enabling microglia to surround and alter APP plaque structure, thereby limiting neuritic damage
  • microglial receptor, involved in innate immunity
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS development , immunity/defense , inflammation
    text humoral defense mechanism
    PATHWAY
    metabolism
    signaling signal transduction
    a component
  • TREM2-TYROBP signals regulate both osteoclasts formation and function
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • associating with its ligand TYROBP and triggering immune responses of macrophges and dendritic cells and associates with TYROBP in osteoclasts
  • interacts with endogenous ligands on neurons (
  • HSPD1 is the only TREM2-binding protein exposed at the surface of neuroblastoma N2A cells and astrocytes
  • HSPD1 was found to stimulate the best known TREM2-dependent process, phagocytosis
  • LAT2 is a critical, LAT-independent regulator of TREM2 signaling and macrophage development capable of controlling subsequent inflammatory responses
  • interaction with HCST, a signaling adaptor molecule that play a key role in the TREM2- and TYROBP-dependent recruitment of PI3K to the signaling complex
  • OSCAR and TREM2 are essential receptors that pair with adaptor molecules Fc receptor common gamma chain (FCR1G) and TYROBP respectively to induce calcium signalling
  • TYROBP/TREM2 activation plays an important role in activation and differentiation of osteoclasts, brain and bone homeostasis and inhibition of the toll-like receptor (TLR) signaling in macrophages and dendritic cells
  • TREM2 is a TYROBP-associated receptor expressed in microglia, macrophages, and other myeloid-derived cells
  • cell & other
    REGULATION
    inhibited by FKBP3 (both TREM2 and OSCAR were inhibited by FKBP3 in the late stage of osteoclast formation)
    ASSOCIATED DISORDERS
    corresponding disease(s) PLOSL2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --other  
    in Cerebrospinal fluid soluble TREM2 correlates with aging
    constitutional       loss of function
    alters acute macrophage distribution and improves recovery after Traumatic brain injury (TBI)
    Susceptibility to late-onset Alzheimer disease (AD)
    Variant & Polymorphism other rs75932628 (encoding R47H), showed highly significant association with Alzheimer disease
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Trem2-deficient (TREM2(-/-)) mice had defective clearance of myelin debris and more axonal pathology, resulting in impaired clinical performances compared to wild-type (WT) mice