Q9NZC2 (TREM2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Triggering receptor expressed on myeloid cells 2
Short name=TREM-2

Alternative name(s):
Triggering receptor expressed on monocytes 2

Gene names

Name:

TREM2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	230 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.1
Subunit structure	Interacts with TYROBP/DAP12 By similarity.
Subcellular location	Isoform 1: Cell membrane; Single-pass type I membrane protein Potential. Isoform 2: Secreted Potential. Isoform 3: Secreted Potential.
Tissue specificity	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. Ref.1 Ref.4
Involvement in disease	Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) [MIM:221770]: Recessively 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.4
Sequence similarities	Contains 1 Ig-like V-type (immunoglobulin-like) domain.
Sequence caution	The sequence BAB78736.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Immunoglobulin domain Signal Transmembrane Transmembrane helix
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	axon guidance Traceable author statement. Source: Reactome humoral immune response Traceable author statement Ref.1. Source: ProtInc
Cellular_component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Traceable author statement. Source: Reactome
Molecular_function	receptor activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9NZC2-1)

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.

Isoform 2 (identifier: Q9NZC2-2)

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.

Isoform 3 (identifier: Q9NZC2-3)

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

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 18	18	Potential
	Chain	19 – 230	212	Triggering receptor expressed on myeloid cells 2		PRO_0000014987
Regions
	Topological domain	19 – 174	156	Extracellular Potential
	Transmembrane	175 – 195	21	Helical; Potential
	Topological domain	196 – 230	35	Cytoplasmic Potential
	Domain	29 – 112	84	Ig-like V-type
Amino acid modifications
	Glycosylation	20	1	N-linked (GlcNAc...) Potential
	Glycosylation	79	1	N-linked (GlcNAc...) Potential
	Disulfide bond	36 ↔ 110		Potential
	Disulfide bond	51 ↔ 60		Potential
Natural variations
	Alternative sequence	162 – 230	69	SLLEG…GLRDT → AERHVKEDDGRKSPGEVPPG TSPACILATWPPGLLVLLWQ ETTLPEHCFSWTLEAGTG in isoform 2.		VSP_010792
	Alternative sequence	162 – 230	69	SLLEG…GLRDT → PSQGSHLPSCLSKEPLGRRN PLPTHFHPSPPGLHLSHQDS SSQRPLGCSLAWTEARDTST Q in isoform 3.		VSP_010793
	Natural variant	96	1	T → K. Corresponds to variant rs2234253 [ dbSNP | Ensembl ].		VAR_061329
	Natural variant	96	1	T → R. Corresponds to variant rs2234253 [ dbSNP | Ensembl ].		VAR_061330
	Natural variant	134	1	D → G in PLOSL. Ref.4		VAR_019334
	Natural variant	157	1	H → Y. Corresponds to variant rs2234255 [ dbSNP | Ensembl ].		VAR_033625
	Natural variant	186	1	K → N in PLOSL. Ref.4		VAR_019335
	Natural variant	211	1	L → P. Corresponds to variant rs2234256 [ dbSNP | Ensembl ].		VAR_033626

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: C894AA210F708AF7	FASTA	230	25,447
	10 20 30 40 50 60 MEPLRLLILL FVTELSGAHN TTVFQGVAGQ SLQVSCPYDS MKHWGRRKAW CRQLGEKGPC 70 80 90 100 110 120 QRVVSTHNLW LLSFLRRWNG STAITDDTLG GTLTITLRNL QPHDAGLYQC QSLHGSEADT 130 140 150 160 170 180 LRKVLVEVLA DPLDHRDAGD LWFPGESESF EDAHVEHSIS RSLLEGEIPF PPTSILLLLA 190 200 210 220 230 CIFLIKILAA SALWAAAWHG QKPGTHPPSE LDCGHDPGYQ LQTLPGLRDT
	Isoform 2 (TREM-2V) [UniParc]. Checksum: 9C9B1E89807967EA	FASTA	219	24,328
	10 20 30 40 50 60 MEPLRLLILL FVTELSGAHN TTVFQGVAGQ SLQVSCPYDS MKHWGRRKAW CRQLGEKGPC 70 80 90 100 110 120 QRVVSTHNLW LLSFLRRWNG STAITDDTLG GTLTITLRNL QPHDAGLYQC QSLHGSEADT 130 140 150 160 170 180 LRKVLVEVLA DPLDHRDAGD LWFPGESESF EDAHVEHSIS RAERHVKEDD GRKSPGEVPP 190 200 210 GTSPACILAT WPPGLLVLLW QETTLPEHCF SWTLEAGTG
	Isoform 3 [UniParc]. Checksum: 9E842B1CC1C35718	FASTA	222	24,669
	10 20 30 40 50 60 MEPLRLLILL FVTELSGAHN TTVFQGVAGQ SLQVSCPYDS MKHWGRRKAW CRQLGEKGPC 70 80 90 100 110 120 QRVVSTHNLW LLSFLRRWNG STAITDDTLG GTLTITLRNL QPHDAGLYQC QSLHGSEADT 130 140 150 160 170 180 LRKVLVEVLA DPLDHRDAGD LWFPGESESF EDAHVEHSIS RPSQGSHLPS CLSKEPLGRR 190 200 210 220 NPLPTHFHPS PPGLHLSHQD SSSQRPLGCS LAWTEARDTS TQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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.
[5]	Erratum 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. 72:225-225(2003)
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF213457 mRNA. Translation: AAF69824.1. AB062787 mRNA. Translation: BAB78736.1. Different initiation. BC032362 mRNA. Translation: AAH32362.1.
IPI	IPI00103749. IPI00384361. IPI00429125.
RefSeq	NP_001258750.1. NM_001271821.1. NP_061838.1. NM_018965.3.
UniGene	Hs.435295.
3D structure databases
ProteinModelPortal	Q9NZC2.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000362205.
PTM databases
PhosphoSite	Q9NZC2.
Polymorphism databases
DMDM	50401689.
Proteomic databases
PaxDb	Q9NZC2.
PRIDE	Q9NZC2.
Protocols and materials databases
DNASU	54209.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000338469; ENSP00000342651; ENSG00000095970. ENST00000373113; ENSP00000362205; ENSG00000095970. ENST00000373122; ENSP00000362214; ENSG00000095970.
GeneID	54209.
KEGG	hsa:54209.
UCSC	uc003opy.2. human. uc003opz.2. human. uc010jxl.1. human.
Organism-specific databases
CTD	54209.
GeneCards	GC06M041126.
HGNC	HGNC:17761. TREM2.
HPA	HPA010917. HPA012571.
MIM	221770. phenotype. 605086. gene.
neXtProt	NX_Q9NZC2.
Orphanet	2770. Polycystic lipomembranous osteodysplasia - sclerosing leukoencephalopathy.
PharmGKB	PA38468.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG42611.
HOGENOM	HOG000118075.
HOVERGEN	HBG058623.
KO	K14378.
OMA	ACIFLIK.
OrthoDB	EOG4CVG89.
Enzyme and pathway databases
Reactome	REACT_111045. Developmental Biology. REACT_6900. Immune System.
Gene expression databases
ArrayExpress	Q9NZC2.
Bgee	Q9NZC2.
CleanEx	HS_TREM2.
Genevestigator	Q9NZC2.
GermOnline	ENSG00000095970. Homo sapiens.
Family and domain databases
Gene3D	2.60.40.10. 1 hit.
InterPro	IPR013783. Ig-like_fold. IPR003599. Ig_sub. IPR013106. Ig_V-set. [Graphical view]
Pfam	PF07686. V-set. 1 hit. [Graphical view]
SMART	SM00409. IG. 1 hit. [Graphical view]
PROSITE	PS50835. IG_LIKE. False negative. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	54209.
NextBio	56542.
SOURCE	Search...

Entry information

Entry name

TREM2_HUMAN

Accession

Primary (citable) accession number: Q9NZC2
Secondary accession number(s): Q8N5H8, Q8WYN6

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2004
Last sequence update:	October 1, 2000
Last modified:	May 1, 2013
This is version 101 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.