TREM2 triggering receptor expressed on myeloid cells 2 [ Homo sapiens (human) ]

Gene ID: 54209, updated on 11-Apr-2024

Summary

Official Symbol: TREM2provided by HGNC
Official Full Name: triggering receptor expressed on myeloid cells 2provided by HGNC
Primary source: HGNC:HGNC:17761
See related: Ensembl:ENSG00000095970 MIM:605086; AllianceGenome:HGNC:17761
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: PLOSL2; TREM-2; Trem2a; Trem2b; Trem2c
Summary: This gene encodes a membrane protein that forms a receptor signaling complex with the TYRO protein tyrosine kinase binding protein. The encoded protein functions in immune response and may be involved in chronic inflammation by triggering the production of constitutive inflammatory cytokines. Defects in this gene are a cause of polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Nov 2012]
Expression: Broad expression in brain (RPKM 11.5), lung (RPKM 7.7) and 14 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 6p21.1

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (41158508..41163116, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (40987077..40991685, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (41126246..41130854, complement)

Chromosome 6 - NC_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Dynamic pathological analysis reveals a protective role against skin fibrosis for TREM2-dependent macrophages.
Title: Dynamic pathological analysis reveals a protective role against skin fibrosis for TREM2-dependent macrophages.
TREM2 in Alzheimer's disease: Structure, function, therapeutic prospects, and activation challenges.
Title: TREM2 in Alzheimer's disease: Structure, function, therapeutic prospects, and activation challenges.
TREM2 mediates phagocytosis in glioblastoma.
Title: TREM2 mediates phagocytosis in glioblastoma.
Effect of triggering receptor expressed on myeloid cells 2-associated alterations on lipid metabolism in macrophages in the development of non-alcoholic fatty liver disease.
Title: Effect of triggering receptor expressed on myeloid cells 2-associated alterations on lipid metabolism in macrophages in the development of non-alcoholic fatty liver disease.
TREM-2: friend or foe in infectious diseases?
Title: TREM-2: friend or foe in infectious diseases?
TREM-2 Drives Development of Multiple Sclerosis by Promoting Pathogenic Th17 Polarization.
Title: TREM-2 Drives Development of Multiple Sclerosis by Promoting Pathogenic Th17 Polarization.
Soluble TREM2 triggers microglial dysfunction in neuromyelitis optica spectrum disorders.
Title: Soluble TREM2 triggers microglial dysfunction in neuromyelitis optica spectrum disorders.
14-3-3 [Formula: see text]-reported early synaptic injury in Alzheimer's disease is independently mediated by sTREM2.
Title: 14-3-3 [Formula: see text]-reported early synaptic injury in Alzheimer's disease is independently mediated by sTREM2.
Computational saturation mutagenesis to explore the effect of pathogenic mutations on extra-cellular domains of TREM2 associated with Alzheimer's and Nasu-Hakola disease.
Title: Computational saturation mutagenesis to explore the effect of pathogenic mutations on extra-cellular domains of TREM2 associated with Alzheimer's and Nasu-Hakola disease.
Serum soluble TREM2 is an independent biomarker associated with coronary heart disease.
Title: Serum soluble TREM2 is an independent biomarker associated with coronary heart disease.

Submit: New GeneRIF Correction See all GeneRIFs (318)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2 MedGen: C4748657 OMIM: 618193 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Genome-wide association and population genetic analysis of C-reactive protein in African American and Hispanic American women. EBI GWAS Catalog EBI GWAS CatalogPubMed
Variant of TREM2 associated with the risk of Alzheimer's disease. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope transmembrane glycoprotein gp41	env	A synthetic peptide corresponding to the immunosuppressive domain (amino acids 574-592) of HIV-1 gp41 downregulates the expression of triggering receptor expressed on myeloid cells 2 (TREM2) in peptide-treated PBMCs	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables amyloid-beta binding	IPI Inferred from Physical Interaction more info	PubMed
enables apolipoprotein A-I binding	IPI Inferred from Physical Interaction more info	PubMed
enables apolipoprotein binding	IPI Inferred from Physical Interaction more info	PubMed
enables beta-catenin binding	IPI Inferred from Physical Interaction more info	PubMed
enables high-density lipoprotein particle binding	IDA Inferred from Direct Assay more info	PubMed
enables kinase activator activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables lipid binding	TAS Traceable Author Statement more info	PubMed
enables lipopolysaccharide binding	IEA Inferred from Electronic Annotation more info
enables lipoprotein particle binding	IDA Inferred from Direct Assay more info	PubMed
enables lipoteichoic acid binding	IEA Inferred from Electronic Annotation more info
enables low-density lipoprotein particle binding	IDA Inferred from Direct Assay more info	PubMed
enables peptidoglycan binding	IEA Inferred from Electronic Annotation more info
enables phosphatidylethanolamine binding	IDA Inferred from Direct Assay more info	PubMed
enables phosphatidylserine binding	IDA Inferred from Direct Assay more info	PubMed
enables phospholipid binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein tyrosine kinase binding	ISS Inferred from Sequence or Structural Similarity more info	PubMed
enables protein-containing complex binding	IPI Inferred from Physical Interaction more info	PubMed
enables scaffold protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables signaling receptor activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables signaling receptor activity	ISS Inferred from Sequence or Structural Similarity more info	PubMed
enables sulfatide binding	IDA Inferred from Direct Assay more info	PubMed
enables transmembrane signaling receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables transmembrane signaling receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables very-low-density lipoprotein particle binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
acts_upstream_of_or_within_positive_effect CXCL12-activated CXCR4 signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in amyloid-beta clearance by cellular catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in amyloid-beta clearance by cellular catabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in apoptotic cell clearance	ISS Inferred from Sequence or Structural Similarity more info
involved_in astrocyte activation	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to amyloid-beta	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in cellular response to glucose stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to hypoxia	IEA Inferred from Electronic Annotation more info
involved_in cellular response to lipid	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to lipoteichoic acid	IEA Inferred from Electronic Annotation more info
involved_in cellular response to oxidised low-density lipoprotein particle stimulus	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to peptidoglycan	IEA Inferred from Electronic Annotation more info
involved_in complement-mediated synapse pruning	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within_positive_effect defense response to Gram-negative bacterium	ISS Inferred from Sequence or Structural Similarity more info
involved_in dendritic cell differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in dendritic spine maintenance	ISS Inferred from Sequence or Structural Similarity more info
involved_in detection of lipopolysaccharide	IEA Inferred from Electronic Annotation more info
involved_in detection of lipoteichoic acid	IEA Inferred from Electronic Annotation more info
involved_in detection of peptidoglycan	IEA Inferred from Electronic Annotation more info
involved_in excitatory synapse pruning	ISS Inferred from Sequence or Structural Similarity more info
involved_in humoral immune response	TAS Traceable Author Statement more info
involved_in import into cell	ISS Inferred from Sequence or Structural Similarity more info
involved_in lipid homeostasis	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_positive_effect memory	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_positive_effect memory	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in microglial cell activation	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in microglial cell activation involved in immune response	ISS Inferred from Sequence or Structural Similarity more info
involved_in microglial cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within negative regulation of NLRP3 inflammasome complex assembly	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within negative regulation of NLRP3 inflammasome complex assembly	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of amyloid fibril formation	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of astrocyte activation	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of autophagic cell death	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of autophagy	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of canonical NF-kappaB signal transduction	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of cell activation	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of cholesterol storage	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of cytokine production involved in inflammatory response	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of fat cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of glial cell apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of inflammatory response to antigenic stimulus	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of interleukin-1 beta production	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of macrophage colony-stimulating factor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of neuroinflammatory response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of neuroinflammatory response	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of p38MAPK cascade	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of sequestering of triglyceride	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of toll-like receptor 2 signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of toll-like receptor 4 signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of tumor necrosis factor production	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within osteoclast differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in osteoclast differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in phagocytosis, engulfment	IEA Inferred from Electronic Annotation more info
involved_in phagocytosis, recognition	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of ATP biosynthetic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of C-C chemokine receptor CCR7 signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of CAMKK-AMPK signaling cascade	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of CD40 signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of ERK1 and ERK2 cascade	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of ERK1 and ERK2 cascade	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of ERK1 and ERK2 cascade	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of TOR signaling	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of amyloid-beta clearance	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of amyloid-beta clearance	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of antigen processing and presentation of peptide antigen via MHC class II	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of calcium-mediated signaling	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of calcium-mediated signaling	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of chemotaxis	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of cholesterol efflux	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of complement activation, classical pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of engulfment of apoptotic cell	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of establishment of protein localization	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within positive regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of gene expression	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of high-density lipoprotein particle clearance	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of interleukin-10 production	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of inward rectifier potassium channel activity	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in positive regulation of kinase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of low-density lipoprotein particle clearance	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of macrophage fusion	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of microglial cell activation	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of microglial cell activation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of microglial cell activation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of microglial cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of microglial cell migration	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in positive regulation of non-canonical NF-kappaB signal transduction	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of osteoclast differentiation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within positive regulation of peptidyl-tyrosine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of peptidyl-tyrosine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of phagocytosis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of phagocytosis	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of phagocytosis, engulfment	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of positive regulation of phagocytosis, engulfment	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of phagocytosis, engulfment	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of phagocytosis, engulfment	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of proteasomal protein catabolic process	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in positive regulation of protein localization to plasma membrane	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of protein phosphorylation	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in positive regulation of protein secretion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of synapse pruning	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within_negative_effect pyroptosis	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of TOR signaling	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of cytokine production involved in inflammatory response	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of gene expression	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in regulation of hippocampal neuron apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of innate immune response	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of interleukin-6 production	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in regulation of intracellular signal transduction	ISS Inferred from Sequence or Structural Similarity more info	PubMed
acts_upstream_of regulation of lipid metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of macrophage inflammatory protein 1 alpha production	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of peptidyl-tyrosine phosphorylation	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of peptidyl-tyrosine phosphorylation	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in regulation of plasma membrane bounded cell projection organization	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of plasma membrane bounded cell projection organization	IGI Inferred from Genetic Interaction more info	PubMed
involved_in regulation of plasma membrane bounded cell projection organization	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of resting membrane potential	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in regulation of toll-like receptor 6 signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in respiratory burst after phagocytosis	ISS Inferred from Sequence or Structural Similarity more info
involved_in response to axon injury	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to axon injury	ISS Inferred from Sequence or Structural Similarity more info
involved_in response to ischemia	IEA Inferred from Electronic Annotation more info
acts_upstream_of_positive_effect social behavior	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
is_active_in cell surface	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular region	IEA Inferred from Electronic Annotation more info
located_in membrane	IDA Inferred from Direct Assay more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IMP Inferred from Mutant Phenotype more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
located_in plasma membrane raft	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: triggering receptor expressed on myeloid cells 2

Names: triggering receptor expressed on monocytes 2; triggering receptor expressed on myeloid cells 2a

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_011561.1 RefSeqGene

Range

4999..9679

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_631

mRNA and Protein(s)

NM_001271821.2 → NP_001258750.1 triggering receptor expressed on myeloid cells 2 precursor isoform 2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2), alternately referred to as TREM-2V, lacks a 3' coding exon which results in a frameshift, compared to variant 1. The resulting isoform (2) is shorter compared to isoform 1.

Source sequence(s)

AB062787

Consensus CDS

CCDS64422.1

UniProtKB/Swiss-Prot

Q9NZC2

Related

ENSP00000342651.4, ENST00000338469.3

Conserved Domains (1) summary

cl11960
Location:23 → 128

Ig; Immunoglobulin domain
NM_018965.4 → NP_061838.1 triggering receptor expressed on myeloid cells 2 precursor isoform 1 precursor

See identical proteins and their annotated locations for NP_061838.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AF213457, BC032362

Consensus CDS

CCDS4852.1

UniProtKB/Swiss-Prot

Q8N5H8, Q8WYN6, Q9NZC2

UniProtKB/TrEMBL

A6NDG2, Q5TCX1

Related

ENSP00000362205.3, ENST00000373113.8

Conserved Domains (2) summary

smart00410
Location:26 → 111

IG_like; Immunoglobulin like

cl11960
Location:23 → 128

Ig; Immunoglobulin domain