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Protein

Triggering receptor expressed on myeloid cells 2

Gene

TREM2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Forms a receptor signaling complex with TYROBP and triggers activation of the immune responses in macrophages and dendritic cells. May have a role in chronic inflammations and may stimulate production of constitutive rather than inflammatory chemokines and cytokines.1 Publication

GO - Molecular functioni

  • lipopolysaccharide binding Source: Ensembl
  • lipoteichoic acid binding Source: Ensembl
  • peptidoglycan binding Source: Ensembl
  • phospholipid binding Source: UniProtKB
  • scaffold protein binding Source: BHF-UCL
  • signaling receptor activity Source: ProtInc

GO - Biological processi

  • cellular response to lipoteichoic acid Source: Ensembl
  • cellular response to peptidoglycan Source: Ensembl
  • dendritic cell differentiation Source: BHF-UCL
  • detection of lipopolysaccharide Source: Ensembl
  • detection of lipoteichoic acid Source: Ensembl
  • detection of peptidoglycan Source: Ensembl
  • humoral immune response Source: ProtInc
  • innate immune response Source: Reactome
  • osteoclast differentiation Source: MGI
  • phagocytosis, engulfment Source: Ensembl
  • positive regulation of antigen processing and presentation of peptide antigen via MHC class II Source: BHF-UCL
  • positive regulation of calcium-mediated signaling Source: BHF-UCL
  • positive regulation of C-C chemokine receptor CCR7 signaling pathway Source: BHF-UCL
  • positive regulation of CD40 signaling pathway Source: BHF-UCL
  • positive regulation of ERK1 and ERK2 cascade Source: BHF-UCL
  • positive regulation of peptidyl-tyrosine phosphorylation Source: BHF-UCL
  • positive regulation of protein localization to plasma membrane Source: BHF-UCL
  • regulation of immune response Source: Reactome

Keywordsi

Molecular functionReceptor

Enzyme and pathway databases

ReactomeiR-HSA-198933 Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-2172127 DAP12 interactions
R-HSA-2424491 DAP12 signaling
R-HSA-416700 Other semaphorin interactions

Names & Taxonomyi

Protein namesi
Recommended name:
Triggering receptor expressed on myeloid cells 2
Short name:
TREM-2
Alternative name(s):
Triggering receptor expressed on monocytes 2
Gene namesi
Name:TREM2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000095970.16
HGNCiHGNC:17761 TREM2
MIMi605086 gene
neXtProtiNX_Q9NZC2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini19 – 174ExtracellularSequence analysisAdd BLAST156
Transmembranei175 – 195HelicalSequence analysisAdd BLAST21
Topological domaini196 – 230CytoplasmicSequence analysisAdd BLAST35

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Involvement in diseasei

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionRecessively inherited disease characterized by a combination of psychotic symptoms rapidly progressing to presenile dementia and bone cysts restricted to wrists and ankles. PLOSL has a global distribution, although most of the patients have been diagnosed in Finland and Japan, with an estimated population prevalence of 2x10(-6) in the Finns.
See also OMIM:221770
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_019334134D → G in PLOSL. 1 PublicationCorresponds to variant dbSNP:rs28939079EnsemblClinVar.1
Natural variantiVAR_019335186K → N in PLOSL. 1 PublicationCorresponds to variant dbSNP:rs28937876EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi38Y → C: Increases protein aggregation; decreases cell membrane localization; protein is secreted. 1 Publication1
Mutagenesisi47R → H: Decreases binding to NA2 and THP-1 cells; induces small conformational change; no change in thermal stability; no effect on cell membrane localization. 1 Publication1
Mutagenesisi62R → H: Does not change protein structure; no change in thermal stability; no effect on cell membrane localization. 1 Publication1
Mutagenesisi66T → M: Increases protein aggregation; decreases cell membrane localization; protein is secreted. 1 Publication1
Mutagenesisi68N → K: No effect on cell membrane localization. 1 Publication1
Mutagenesisi76R → D: Decreases binding to THP-1 cells. 1 Publication1
Mutagenesisi77R → D: Decreases binding to THP-1 cells. 1 Publication1
Mutagenesisi87D → N: No effect on cell membrane localization. 1 Publication1
Mutagenesisi126V → G: Increases protein aggregation; decreases cell membrane localization; protein is secreted. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi54209
GeneReviewsiTREM2
MalaCardsiTREM2
MIMi221770 phenotype
OpenTargetsiENSG00000095970
Orphaneti803 Amyotrophic lateral sclerosis
275864 Behavioral variant of frontotemporal dementia
2770 Nasu-Hakola disease
100070 Progressive non-fluent aphasia
100069 Semantic dementia
PharmGKBiPA38468

Polymorphism and mutation databases

DMDMi50401689

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 18Sequence analysisAdd BLAST18
ChainiPRO_000001498719 – 230Triggering receptor expressed on myeloid cells 2Add BLAST212

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi20N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi36 ↔ 110Combined sources1 Publication
Disulfide bondi51 ↔ 60Combined sources1 Publication
Glycosylationi79N-linked (GlcNAc...) asparagineCombined sources1 Publication1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ9NZC2
PeptideAtlasiQ9NZC2
PRIDEiQ9NZC2

PTM databases

iPTMnetiQ9NZC2
PhosphoSitePlusiQ9NZC2

Expressioni

Tissue specificityi

Expressed on macrophages and dendritic cells but not on granulocytes or monocytes. In the CNS strongest expression seen in the basal ganglia, corpus callosum, medulla oblongata and spinal cord.2 Publications

Gene expression databases

BgeeiENSG00000095970
CleanExiHS_TREM2
ExpressionAtlasiQ9NZC2 baseline and differential
GenevisibleiQ9NZC2 HS

Organism-specific databases

HPAiHPA010917
HPA012571

Interactioni

Subunit structurei

Monomer (PubMed:27995897). Interacts with TYROBP/DAP12 (By similarity).By similarity1 Publication

GO - Molecular functioni

  • scaffold protein binding Source: BHF-UCL

Protein-protein interaction databases

IntActiQ9NZC2, 1 interactor
STRINGi9606.ENSP00000362205

Structurei

Secondary structure

1230
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi22 – 27Combined sources6
Beta strandi32 – 37Combined sources6
Turni40 – 45Combined sources6
Beta strandi47 – 53Combined sources7
Turni55 – 57Combined sources3
Beta strandi60 – 65Combined sources6
Helixi70 – 72Combined sources3
Beta strandi77 – 79Combined sources3
Beta strandi82 – 87Combined sources6
Turni88 – 91Combined sources4
Beta strandi92 – 99Combined sources8
Beta strandi106 – 114Combined sources9
Beta strandi117 – 129Combined sources13

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5ELIX-ray3.10A/B19-133[»]
5UD7X-ray2.20A/B/C/D/E/F19-174[»]
5UD8X-ray1.80A/B19-130[»]
ProteinModelPortaliQ9NZC2
SMRiQ9NZC2
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini29 – 112Ig-like V-typeAdd BLAST84

Keywords - Domaini

Immunoglobulin domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IXBY Eukaryota
ENOG410YZ1S LUCA
GeneTreeiENSGT00470000042297
HOGENOMiHOG000118075
HOVERGENiHBG058623
InParanoidiQ9NZC2
KOiK14378
OMAiWAAAWHG
OrthoDBiEOG091G0LFM
PhylomeDBiQ9NZC2
TreeFamiTF334441

Family and domain databases

Gene3Di2.60.40.10, 1 hit
InterProiView protein in InterPro
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR013106 Ig_V-set
PfamiView protein in Pfam
PF07686 V-set, 1 hit
SUPFAMiSSF48726 SSF48726, 1 hit

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9NZC2-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MEPLRLLILL FVTELSGAHN TTVFQGVAGQ SLQVSCPYDS MKHWGRRKAW
60 70 80 90 100
CRQLGEKGPC QRVVSTHNLW LLSFLRRWNG STAITDDTLG GTLTITLRNL
110 120 130 140 150
QPHDAGLYQC QSLHGSEADT LRKVLVEVLA DPLDHRDAGD LWFPGESESF
160 170 180 190 200
EDAHVEHSIS RSLLEGEIPF PPTSILLLLA CIFLIKILAA SALWAAAWHG
210 220 230
QKPGTHPPSE LDCGHDPGYQ LQTLPGLRDT
Length:230
Mass (Da):25,447
Last modified:October 1, 2000 - v1
Checksum:iC894AA210F708AF7
GO
Isoform 2 (identifier: Q9NZC2-2) [UniParc]FASTAAdd to basket
Also known as: TREM-2V

The sequence of this isoform differs from the canonical sequence as follows:
     162-230: SLLEGEIPFP...LQTLPGLRDT → AERHVKEDDG...FSWTLEAGTG

Note: No experimental confirmation available.1 Publication
Show »
Length:219
Mass (Da):24,328
Checksum:i9C9B1E89807967EA
GO
Isoform 3 (identifier: Q9NZC2-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     162-230: SLLEGEIPFP...LQTLPGLRDT → PSQGSHLPSC...WTEARDTSTQ

Note: No experimental confirmation available.
Show »
Length:222
Mass (Da):24,669
Checksum:i9E842B1CC1C35718
GO

Sequence cautioni

The sequence BAB78736 differs from that shown. Reason: Erroneous initiation.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06132996T → K Does not change protein structure; changes protein stability; increases binding to THP-1 cells. 1 PublicationCorresponds to variant dbSNP:rs2234253EnsemblClinVar.1
Natural variantiVAR_06133096T → R. Corresponds to variant dbSNP:rs2234253EnsemblClinVar.1
Natural variantiVAR_019334134D → G in PLOSL. 1 PublicationCorresponds to variant dbSNP:rs28939079EnsemblClinVar.1
Natural variantiVAR_033625157H → Y Polymorphism; may be associated with an increased risk for late-onset Alzheimer disease. 1 PublicationCorresponds to variant dbSNP:rs2234255EnsemblClinVar.1
Natural variantiVAR_019335186K → N in PLOSL. 1 PublicationCorresponds to variant dbSNP:rs28937876EnsemblClinVar.1
Natural variantiVAR_077696192A → T1 PublicationCorresponds to variant dbSNP:rs150277350Ensembl.1
Natural variantiVAR_033626211L → P. Corresponds to variant dbSNP:rs2234256EnsemblClinVar.1
Isoform 2 (identifier: Q9NZC2-2)
Natural varianti183S → C1 PublicationCorresponds to variant dbSNP:rs200820365Ensembl.1
Natural varianti200W → C1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_010792162 – 230SLLEG…GLRDT → AERHVKEDDGRKSPGEVPPG TSPACILATWPPGLLVLLWQ ETTLPEHCFSWTLEAGTG in isoform 2. 1 PublicationAdd BLAST69
Alternative sequenceiVSP_010793162 – 230SLLEG…GLRDT → PSQGSHLPSCLSKEPLGRRN PLPTHFHPSPPGLHLSHQDS SSQRPLGCSLAWTEARDTST Q in isoform 3. 1 PublicationAdd BLAST69

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF213457 mRNA Translation: AAF69824.1
AB062787 mRNA Translation: BAB78736.1 Different initiation.
BC032362 mRNA Translation: AAH32362.1
CCDSiCCDS4852.1 [Q9NZC2-1]
CCDS64422.1 [Q9NZC2-2]
RefSeqiNP_001258750.1, NM_001271821.1 [Q9NZC2-2]
NP_061838.1, NM_018965.3 [Q9NZC2-1]
UniGeneiHs.435295

Genome annotation databases

EnsembliENST00000338469; ENSP00000342651; ENSG00000095970 [Q9NZC2-2]
ENST00000373113; ENSP00000362205; ENSG00000095970 [Q9NZC2-1]
ENST00000373122; ENSP00000362214; ENSG00000095970 [Q9NZC2-3]
GeneIDi54209
KEGGihsa:54209
UCSCiuc003opy.4 human [Q9NZC2-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTREM2_HUMAN
AccessioniPrimary (citable) accession number: Q9NZC2
Secondary accession number(s): Q8N5H8, Q8WYN6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: October 1, 2000
Last modified: May 23, 2018
This is version 141 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

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