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UniProtKB - Q9NZC2 (TREM2_HUMAN)

Entry version 161 (02 Dec 2020)
Sequence version 1 (01 Oct 2000)
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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

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

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, it 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).By similarity8 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei67Phospholipid1 Publication1
Binding sitei68Phospholipid; via amide nitrogen1 Publication1
Binding sitei77Phospholipid1 Publication1
Binding sitei88Phospholipid1 Publication1

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionReceptor
LigandLipid-binding

Enzyme and pathway databases

Pathway Commons web resource for biological pathway data

More...PathwayCommonsi		Q9NZC2

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-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

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Triggering receptor expressed on myeloid cells 2
Short name:
TREM-2
Alternative name(s):
Triggering receptor expressed on monocytes 2
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:TREM2
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 6

Organism-specific databases

Eukaryotic Pathogen and Host Database Resources

More...EuPathDBi		HostDB:ENSG00000095970.16

Human Gene Nomenclature Database

More...HGNCi		HGNC:17761, TREM2

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		605086, gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_Q9NZC2

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>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 & Seán O’Donoghue; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.<p><a href='/help/topo_dom' target='_top'>More...</a></p>Topological domaini19 – 174ExtracellularSequence analysisAdd BLAST156
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>Transmembranei175 – 195HelicalSequence analysisAdd BLAST21
Topological domaini196 – 230CytoplasmicSequence analysisAdd BLAST35

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2 (PLOSL2)9 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn 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.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_08167614 – 230Missing in PLOSL2; results in decreased osteoclast differentiation; no TREM2 transcripts can be detected in patient cells homozygous for the variant. 1 PublicationAdd BLAST217
Natural variantiVAR_08167733 – 230Missing in PLOSL2; no protein detected by Wester blot. 5 PublicationsAdd BLAST198
Natural variantiVAR_08167844 – 230Missing in PLOSL2. 1 PublicationAdd BLAST187
Natural variantiVAR_08167978 – 230Missing in PLOSL2. 1 PublicationAdd BLAST153
Natural variantiVAR_081680126V → G in PLOSL2; results in defective protein maturation; increases protein aggregation; decreases cell membrane localization. 3 PublicationsCorresponds to variant dbSNP:rs121908402EnsemblClinVar.1
Natural variantiVAR_019334134D → G in PLOSL2; unknown pathological significance; decreased protein level. 2 PublicationsCorresponds to variant dbSNP:rs28939079EnsemblClinVar.1
Natural variantiVAR_019335186K → N in PLOSL2; unknown pathological significance; increased localization at the cell membrane. 2 PublicationsCorresponds to variant dbSNP:rs28937876EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi20N → D: Loss of glycosylation. 1 Publication1
Mutagenesisi36C → A: Loss of proteolytic cleavage by ADAM10 and ectodomain shedding. Decreases protein maturation and cell membrane localization. 1 Publication1
Mutagenesisi48K → M: Loss of LDL, CLU and APOE binding. 1 Publication1
Mutagenesisi60C → A: Loss of proteolytic cleavage by ADAM10 and ectodomain shedding. Decreases protein maturation and cell membrane localization. 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

Keywords - Diseasei

Disease mutation, Neurodegeneration

Organism-specific databases

DisGeNET

More...DisGeNETi		54209

GeneReviews a resource of expert-authored, peer-reviewed disease descriptions.

More...GeneReviewsi		TREM2

MalaCards human disease database

More...MalaCardsi		TREM2
MIMi618193, phenotype

NIAGADS Genomics Database

More...NIAGADSi		ENSG00000095970

Open Targets

More...OpenTargetsi		ENSG00000095970

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...Orphaneti		803, Amyotrophic lateral sclerosis
275864, Behavioral variant of frontotemporal dementia
1020, Early-onset autosomal dominant Alzheimer disease
2770, Nasu-Hakola disease
238616, NON RARE IN EUROPE: Alzheimer disease
100070, Progressive non-fluent aphasia
100069, Semantic dementia

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA38468

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		Q9NZC2, Tbio

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		TREM2

Domain mapping of disease mutations (DMDM)

More...DMDMi		50401689

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section denotes the presence of an N-terminal signal peptide.<p><a href='/help/signal' target='_top'>More...</a></p>Signal peptidei1 – 18Sequence analysisAdd BLAST18
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_000001498719 – 230Triggering receptor expressed on myeloid cells 2Add BLAST212

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>Glycosylationi20N-linked (GlcNAc...) asparagineCombined sources1 Publication1
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi36 ↔ 110Combined sources2 Publications
Disulfide bondi51 ↔ 60Combined sources2 Publications
Glycosylationi79N-linked (GlcNAc...) asparagineCombined sources2 Publications1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

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.4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections ('Function', 'PTM / Processing', 'Pathology and Biotech') according to its content.<p><a href='/help/site' target='_top'>More...</a></p>Sitei157 – 158Cleavage of ectodomain2 Publications2

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		Q9NZC2

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		Q9NZC2

PaxDb, a database of protein abundance averages across all three domains of life

More...PaxDbi		Q9NZC2

PeptideAtlas

More...PeptideAtlasi		Q9NZC2

PRoteomics IDEntifications database

More...PRIDEi		Q9NZC2

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		83358 [Q9NZC2-1]
83359 [Q9NZC2-2]
83360 [Q9NZC2-3]

PTM databases

GlyGen: Computational and Informatics Resources for Glycoscience

More...GlyGeni		Q9NZC2, 2 sites

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		Q9NZC2

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...PhosphoSitePlusi		Q9NZC2

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Expressed in the brain, specifically in microglia and in the fusiform gyrus (at protein level) (PubMed:28802038, PubMed:28855300, PubMed:27477018, PubMed:29752066). Expressed on macrophages and dendritic cells but not on granulocytes or monocytes (PubMed:10799849, PubMed:28855301). In the CNS strongest expression seen in the basal ganglia, corpus callosum, medulla oblongata and spinal cord (PubMed:12080485).7 Publications

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000095970, Expressed in substantia nigra and 155 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		Q9NZC2, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		Q9NZC2, HS

Organism-specific databases

Human Protein Atlas

More...HPAi		ENSG00000095970, Tissue enhanced (adipose tissue, brain, lung)

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Monomer (PubMed:27995897). After ectodomain shedding, the extracellular domain oligomerizes, which is enhanced and stabilized by binding of phosphatidylserine (PubMed:29794134).

Interacts with TYROBP/DAP12 (PubMed:11602640, PubMed:25957402). Interaction with TYROBP is required for stabilization of the TREM2 C-terminal fragment (TREM2-CTF) which is produced by proteolytic processing (PubMed:25957402).

4 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Hide details

GO - Molecular functioni

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...BioGRIDi		119925, 9 interactors

Protein interaction database and analysis system

More...IntActi		Q9NZC2, 6 interactors

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000362205

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		Q9NZC2, protein

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1230
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...SMRi		Q9NZC2

Database of comparative protein structure models

More...ModBasei		Search...

Protein Data Bank in Europe - Knowledge Base

More...PDBe-KBi		Search...

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family%5Fand%5Fdomains%5Fsection">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini29 – 112Ig-like V-typeAdd BLAST84

Keywords - Domaini

Immunoglobulin domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		ENOG502S4HV, Eukaryota

Ensembl GeneTree

More...GeneTreei		ENSGT00470000042297

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...HOGENOMi		CLU_076120_0_0_1

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		Q9NZC2

Identification of Orthologs from Complete Genome Data

More...OMAi		AWHGQKQ

Database for complete collections of gene phylogenies

More...PhylomeDBi		Q9NZC2

TreeFam database of animal gene trees

More...TreeFami		TF334441

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

More...Gene3Di		2.60.40.10, 1 hit

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR036179, Ig-like_dom_sf
IPR013783, Ig-like_fold
IPR013106, Ig_V-set

Pfam protein domain database

More...Pfami		View protein in Pfam
PF07686, V-set, 1 hit

Superfamily database of structural and functional annotation

More...SUPFAMi		SSF48726, SSF48726, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (3)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 <p>This subsection of the 'Sequence' section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform. This section is only present in reviewed entries, i.e. in UniProtKB/Swiss-Prot.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: Q9NZC2-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali 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
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> 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

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

Show »
Length:222
Mass (Da):24,669
Checksum:i9E842B1CC1C35718
GO

<p>This subsection of the 'Sequence' section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

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

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_08167614 – 230Missing in PLOSL2; results in decreased osteoclast differentiation; no TREM2 transcripts can be detected in patient cells homozygous for the variant. 1 PublicationAdd BLAST217
Natural variantiVAR_08181227V → M Found in patients with late onset Alzheimer disease; unknown pathological significance; no effect on cell membrane localization. 1 PublicationCorresponds to variant dbSNP:rs768745050Ensembl.1
Natural variantiVAR_08181328A → V Found in patients with late onset Alzheimer disease; unknown pathological significance; increases cell membrane localization. 1 PublicationCorresponds to variant dbSNP:rs2234252Ensembl.1
Natural variantiVAR_08181431S → F Found in patients with late onset Alzheimer disease; unknown pathological significance; decreases cell membrane localization. 1 PublicationCorresponds to variant dbSNP:rs746216516Ensembl.1
Natural variantiVAR_08167733 – 230Missing in PLOSL2; no protein detected by Wester blot. 5 PublicationsAdd BLAST198
Natural variantiVAR_08181538Y → C Results in defective protein maturation and trafficking; loss of proteolytic cleavage by ADAM10 and ectodomain shedding; increases protein aggregation; decreases cell membrane localization; decreased phagocytosis; loss of LDL, CLU and APOE binding; greatly decreases LDL and CLU uptake into cells. 6 PublicationsCorresponds to variant dbSNP:rs797044603EnsemblClinVar.1
Natural variantiVAR_08167844 – 230Missing in PLOSL2. 1 PublicationAdd BLAST187
Natural variantiVAR_08181647R → C Found in patients with late onset Alzheimer disease; unknown pathological significance; decreases cell membrane localization. 1 PublicationCorresponds to variant dbSNP:rs753325601Ensembl.1
Natural variantiVAR_08181747R → H Found in patients with late onset Alzheimer disease; unknown pathological significance; no effect on cell membrane localization; no effect on autophagy in microglia; no effect on phagocystosis, including amyloid plaque clearance by microglia; reduces ectodomain shedding caused by proteolytic cleavage by ADAM10, while also reducing the oligomerization of the extracellular domain after shedding; decreases binding to and uptake of LDL and CLU into cells; decreases binding to APOE, phospholipids and oligomeric APP cleavage product beta-amyloid peptide 42. 9 PublicationsCorresponds to variant dbSNP:rs75932628EnsemblClinVar.1
Natural variantiVAR_08181862R → H Does not affect protein structure; no effect on cell membrane localization; increases autophagy in microglia; decreases LDL, CLU and APOE binding; decreases LDL uptake into cells; no effect on CLU uptake into cells; decreases the uptake of APP-LDL complex in macrophages; decreases binding to oligomeric APP cleavage product beta-amyloid peptide 42. 4 PublicationsCorresponds to variant dbSNP:rs143332484EnsemblClinVar.1
Natural variantiVAR_08181966T → M Results in defective protein maturation and trafficking; loss of proteolytic cleavage by ADAM10 and ectodomain shedding; increases protein aggregation; decreases cell membrane localization; decreases phagocytosis; loss of LDL, CLU and APOE binding; greatly decreases LDL and CLU uptake into cells. 5 PublicationsCorresponds to variant dbSNP:rs201258663EnsemblClinVar.1
Natural variantiVAR_08167978 – 230Missing in PLOSL2. 1 PublicationAdd BLAST153
Natural variantiVAR_08182087D → N Polymorphism; decreases LDL, CLU and APOE binding; decreases LDL and CLU uptake into cells; no effect on cell membrane localization. 3 PublicationsCorresponds to variant dbSNP:rs142232675EnsemblClinVar.1
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_081680126V → G in PLOSL2; results in defective protein maturation; increases protein aggregation; decreases cell membrane localization. 3 PublicationsCorresponds to variant dbSNP:rs121908402EnsemblClinVar.1
Natural variantiVAR_081821130A → S Polymorphism; no effect on protein expression and maturation. 1 Publication1
Natural variantiVAR_019334134D → G in PLOSL2; unknown pathological significance; decreased protein level. 2 PublicationsCorresponds to variant dbSNP:rs28939079EnsemblClinVar.1
Natural variantiVAR_081822136R → Q Found in patients with Alzheimer disease; unknown pathological significance; slightly decreases cell membrane localization. 1 PublicationCorresponds to variant dbSNP:rs149622783EnsemblClinVar.1
Natural variantiVAR_081823136R → W Found in patients with Alzheimer disease; unknown pathological significance; decreases cell membrane localization. 1 PublicationCorresponds to variant dbSNP:rs772641807Ensembl.1
Natural variantiVAR_081824151E → K Found in patients with late onset Alzheimer disease; unknown pathological significance; decreases cell membrane localization. 1 PublicationCorresponds to variant dbSNP:rs79011726Ensembl.1
Natural variantiVAR_033625157H → Y Polymorphism; may be associated with an increased risk for late-onset Alzheimer disease; accelerates ectodomain shedding but does not alter the cleavage site; decreases cell membrane localization; decreases phagocytosis. 3 PublicationsCorresponds to variant dbSNP:rs2234255EnsemblClinVar.1
Natural variantiVAR_081825162S → R Polymorphism; no effect on protein expression and maturation. 1 PublicationCorresponds to variant dbSNP:rs371702633Ensembl.1
Natural variantiVAR_019335186K → N in PLOSL2; unknown pathological significance; increased localization at the cell membrane. 2 PublicationsCorresponds 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
Natural variantiVAR_081826223T → I Polymorphism; affects protein maturation. 1 PublicationCorresponds to variant dbSNP:rs138355759EnsemblClinVar.1
Isoform 2 (identifier: Q9NZC2-2)
Natural variantiVAR_082839183S → C1 PublicationCorresponds to variant dbSNP:rs200820365Ensembl.1
Natural variantiVAR_082840200W → C1 PublicationCorresponds to variant dbSNP:rs1391283629Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>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:

EMBL nucleotide sequence database

More...EMBLi

GenBank nucleotide sequence database

More...GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...DDBJi
Links Updated
AF213457 mRNA Translation: AAF69824.1
AB062787 mRNA Translation: BAB78736.1 Different initiation.
BC032362 mRNA Translation: AAH32362.1

The Consensus CDS (CCDS) project

More...CCDSi		CCDS4852.1 [Q9NZC2-1]
CCDS64422.1 [Q9NZC2-2]

NCBI Reference Sequences

More...RefSeqi		NP_001258750.1, NM_001271821.1 [Q9NZC2-2]
NP_061838.1, NM_018965.3 [Q9NZC2-1]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000338469; ENSP00000342651; ENSG00000095970 [Q9NZC2-2]
ENST00000373113; ENSP00000362205; ENSG00000095970 [Q9NZC2-1]
ENST00000373122; ENSP00000362214; ENSG00000095970 [Q9NZC2-3]

Database of genes from NCBI RefSeq genomes

More...GeneIDi		54209

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:54209

UCSC genome browser

More...UCSCi		uc003opy.4, human [Q9NZC2-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>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]

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...PDBei

Protein Data Bank RCSB

More...RCSB PDBi

Protein Data Bank Japan

More...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[»]
6B8OX-ray2.20A/B/C/D/E/F19-174[»]
SMRiQ9NZC2
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGRIDi119925, 9 interactors
IntActiQ9NZC2, 6 interactors
STRINGi9606.ENSP00000362205

PTM databases

GlyGeniQ9NZC2, 2 sites
iPTMnetiQ9NZC2
PhosphoSitePlusiQ9NZC2

Polymorphism and mutation databases

BioMutaiTREM2
DMDMi50401689

Proteomic databases

jPOSTiQ9NZC2
MassIVEiQ9NZC2
PaxDbiQ9NZC2
PeptideAtlasiQ9NZC2
PRIDEiQ9NZC2
ProteomicsDBi83358 [Q9NZC2-1]
83359 [Q9NZC2-2]
83360 [Q9NZC2-3]

Protocols and materials databases

Antibodypedia a portal for validated antibodies

More...Antibodypediai		2280, 555 antibodies

The DNASU plasmid repository

More...DNASUi		54209

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]

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		54209
DisGeNETi54209
EuPathDBiHostDB:ENSG00000095970.16

GeneCards: human genes, protein and diseases

More...GeneCardsi		TREM2
GeneReviewsiTREM2
HGNCiHGNC:17761, TREM2
HPAiENSG00000095970, Tissue enhanced (adipose tissue, brain, lung)
MalaCardsiTREM2
MIMi605086, gene
618193, phenotype
neXtProtiNX_Q9NZC2
NIAGADSiENSG00000095970
OpenTargetsiENSG00000095970
Orphaneti803, Amyotrophic lateral sclerosis
275864, Behavioral variant of frontotemporal dementia
1020, Early-onset autosomal dominant Alzheimer disease
2770, Nasu-Hakola disease
238616, NON RARE IN EUROPE: Alzheimer disease
100070, Progressive non-fluent aphasia
100069, Semantic dementia
PharmGKBiPA38468

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiENOG502S4HV, Eukaryota
GeneTreeiENSGT00470000042297
HOGENOMiCLU_076120_0_0_1
InParanoidiQ9NZC2
OMAiAWHGQKQ
PhylomeDBiQ9NZC2
TreeFamiTF334441

Enzyme and pathway databases

PathwayCommonsiQ9NZC2
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

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...BioGRID-ORCSi		54209, 4 hits in 838 CRISPR screens

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...ChiTaRSi		TREM2, human

The Gene Wiki collection of pages on human genes and proteins

More...GeneWikii		TREM2

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...GenomeRNAii		54209
PharosiQ9NZC2, Tbio

Protein Ontology

More...PROi		PR:Q9NZC2
RNActiQ9NZC2, protein

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000095970, Expressed in substantia nigra and 155 other tissues
ExpressionAtlasiQ9NZC2, baseline and differential
GenevisibleiQ9NZC2, HS

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

ProtoNet; Automatic hierarchical classification of proteins

More...ProtoNeti		Search...

MobiDB: a database of protein disorder and mobility annotations

More...MobiDBi		Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiTREM2_HUMAN
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: Q9NZC2
Secondary accession number(s): Q8N5H8, Q8WYN6
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: October 1, 2000
Last modified: December 2, 2020
This is version 161 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>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.

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Reference proteome

Documents

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