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Protein

Triggering receptor expressed on myeloid cells 2

Gene

TREM2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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

GO - Molecular functioni

  1. lipopolysaccharide binding Source: Ensembl
  2. receptor activity Source: ProtInc
  3. scaffold protein binding Source: BHF-UCL

GO - Biological processi

  1. axon guidance Source: Reactome
  2. dendritic cell differentiation Source: BHF-UCL
  3. humoral immune response Source: ProtInc
  4. innate immune response Source: Reactome
  5. positive regulation of antigen processing and presentation of peptide antigen via MHC class II Source: BHF-UCL
  6. positive regulation of calcium-mediated signaling Source: BHF-UCL
  7. positive regulation of C-C chemokine receptor CCR7 signaling pathway Source: BHF-UCL
  8. positive regulation of CD40 signaling pathway Source: BHF-UCL
  9. positive regulation of ERK1 and ERK2 cascade Source: BHF-UCL
  10. positive regulation of peptidyl-tyrosine phosphorylation Source: BHF-UCL
  11. positive regulation of protein localization to plasma membrane Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Enzyme and pathway databases

ReactomeiREACT_147694. DAP12 interactions.
REACT_147814. DAP12 signaling.
REACT_19200. 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
ProteomesiUP000005640: Chromosome 6

Organism-specific databases

HGNCiHGNC:17761. TREM2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini19 – 174156ExtracellularSequence AnalysisAdd
BLAST
Transmembranei175 – 19521HelicalSequence AnalysisAdd
BLAST
Topological domaini196 – 23035CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. extracellular region Source: UniProtKB-SubCell
  2. integral component of membrane Source: BHF-UCL
  3. intracellular membrane-bounded organelle Source: HPA
  4. plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Involvement in diseasei

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy1 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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti134 – 1341D → G in PLOSL. 1 Publication
VAR_019334
Natural varianti186 – 1861K → N in PLOSL. 1 Publication
VAR_019335

Keywords - Diseasei

Disease mutation

Organism-specific databases

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1818Sequence AnalysisAdd
BLAST
Chaini19 – 230212Triggering receptor expressed on myeloid cells 2PRO_0000014987Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi20 – 201N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi36 ↔ 110Sequence Analysis
Disulfide bondi51 ↔ 60Sequence Analysis
Glycosylationi79 – 791N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ9NZC2.
PRIDEiQ9NZC2.

PTM databases

PhosphoSiteiQ9NZC2.

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

BgeeiQ9NZC2.
CleanExiHS_TREM2.
ExpressionAtlasiQ9NZC2. baseline and differential.
GenevestigatoriQ9NZC2.

Organism-specific databases

HPAiHPA010917.
HPA012571.

Interactioni

Subunit structurei

Interacts with TYROBP/DAP12.By similarity

Protein-protein interaction databases

STRINGi9606.ENSP00000362205.

Structurei

3D structure databases

ProteinModelPortaliQ9NZC2.
SMRiQ9NZC2. Positions 26-110.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini29 – 11284Ig-like V-typeAdd
BLAST

Sequence similaritiesi

Keywords - Domaini

Immunoglobulin domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG42611.
GeneTreeiENSGT00470000042297.
HOGENOMiHOG000118075.
HOVERGENiHBG058623.
InParanoidiQ9NZC2.
KOiK14378.
OMAiACIFLIK.
OrthoDBiEOG7B8S4S.
PhylomeDBiQ9NZC2.
TreeFamiTF334441.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
InterProiIPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR013106. Ig_V-set.
[Graphical view]
PfamiPF07686. V-set. 1 hit.
[Graphical view]
SMARTiSM00409. IG. 1 hit.
[Graphical view]

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. Align

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.

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 BAB78736.1 differs from that shown. Reason: Erroneous initiation. Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti96 – 961T → K.
Corresponds to variant rs2234253 [ dbSNP | Ensembl ].
VAR_061329
Natural varianti96 – 961T → R.
Corresponds to variant rs2234253 [ dbSNP | Ensembl ].
VAR_061330
Natural varianti134 – 1341D → G in PLOSL. 1 Publication
VAR_019334
Natural varianti157 – 1571H → Y.
Corresponds to variant rs2234255 [ dbSNP | Ensembl ].
VAR_033625
Natural varianti186 – 1861K → N in PLOSL. 1 Publication
VAR_019335
Natural varianti211 – 2111L → P.
Corresponds to variant rs2234256 [ dbSNP | Ensembl ].
VAR_033626

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei162 – 23069SLLEG…GLRDT → AERHVKEDDGRKSPGEVPPG TSPACILATWPPGLLVLLWQ ETTLPEHCFSWTLEAGTG in isoform 2. 1 PublicationVSP_010792Add
BLAST
Alternative sequencei162 – 23069SLLEG…GLRDT → PSQGSHLPSCLSKEPLGRRN PLPTHFHPSPPGLHLSHQDS SSQRPLGCSLAWTEARDTST Q in isoform 3. 1 PublicationVSP_010793Add
BLAST

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.3. human. [Q9NZC2-1]
uc003opz.3. human. [Q9NZC2-3]
uc010jxl.2. human. [Q9NZC2-2]

Polymorphism databases

DMDMi50401689.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ9NZC2.
SMRiQ9NZC2. Positions 26-110.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000362205.

PTM databases

PhosphoSiteiQ9NZC2.

Polymorphism databases

DMDMi50401689.

Proteomic databases

PaxDbiQ9NZC2.
PRIDEiQ9NZC2.

Protocols and materials databases

DNASUi54209.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000338469; ENSP00000342651; ENSG00000095970. [Q9NZC2-2]
ENST00000373113; ENSP00000362205; ENSG00000095970. [Q9NZC2-1]
ENST00000373122; ENSP00000362214; ENSG00000095970. [Q9NZC2-3]
GeneIDi54209.
KEGGihsa:54209.
UCSCiuc003opy.3. human. [Q9NZC2-1]
uc003opz.3. human. [Q9NZC2-3]
uc010jxl.2. human. [Q9NZC2-2]

Organism-specific databases

CTDi54209.
GeneCardsiGC06M041126.
GeneReviewsiTREM2.
HGNCiHGNC:17761. TREM2.
HPAiHPA010917.
HPA012571.
MIMi221770. phenotype.
605086. gene.
neXtProtiNX_Q9NZC2.
Orphaneti803. Amyotrophic lateral sclerosis.
275864. Behavioral variant of frontotemporal dementia.
2770. Nasu-Hakola disease.
100070. Progressive non-fluent aphasia.
100069. Semantic dementia.
PharmGKBiPA38468.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG42611.
GeneTreeiENSGT00470000042297.
HOGENOMiHOG000118075.
HOVERGENiHBG058623.
InParanoidiQ9NZC2.
KOiK14378.
OMAiACIFLIK.
OrthoDBiEOG7B8S4S.
PhylomeDBiQ9NZC2.
TreeFamiTF334441.

Enzyme and pathway databases

ReactomeiREACT_147694. DAP12 interactions.
REACT_147814. DAP12 signaling.
REACT_19200. Other semaphorin interactions.

Miscellaneous databases

GeneWikiiTREM2.
GenomeRNAii54209.
NextBioi56542.
PROiQ9NZC2.
SOURCEiSearch...

Gene expression databases

BgeeiQ9NZC2.
CleanExiHS_TREM2.
ExpressionAtlasiQ9NZC2. baseline and differential.
GenevestigatoriQ9NZC2.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
InterProiIPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR013106. Ig_V-set.
[Graphical view]
PfamiPF07686. V-set. 1 hit.
[Graphical view]
SMARTiSM00409. IG. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Inflammatory responses can be triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes."
    Bouchon A., Dietrich J., Colonna M.
    J. Immunol. 164:4991-4995(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY.
  2. "Identification of a novel variant of triggering receptor, TREM-2V, by mRNA differential display."
    Begum N.A., Tsukasa S.
    Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
    Tissue: Brain.
  4. "Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype."
    Paloneva J., Manninen T., Christman G., Hovanes K., Mandelin J., Adolfsson R., Bianchin M., Bird T., Miranda R., Salmaggi A., Tranebjaerg L., Konttinen Y., Peltonen L.
    Am. J. Hum. Genet. 71:656-662(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, VARIANTS PLOSL GLY-134 AND ASN-186.

Entry informationi

Entry nameiTREM2_HUMAN
AccessioniPrimary (citable) accession number: Q9NZC2
Secondary accession number(s): Q8N5H8, Q8WYN6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: October 1, 2000
Last modified: February 4, 2015
This is version 117 of the entry and version 1 of the sequence. [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

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. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.