Q99NH8 (TREM2_MOUSE) 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
Synonyms:	Trem2a, Trem2b, Trem2c

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	227 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.2
Subunit structure	Interacts with TYROBP/DAP12. Ref.2
Subcellular location	Isoform 1: Cell membrane; Single-pass type I membrane protein Potential. Isoform 2: Secreted Potential.
Tissue specificity	Expressed at higher levels in the CNS, heart and lung than in lymph nodes or in other non-lymphoid tissues such as kidney, liver and testis. In the CNS not all microglia express TREM2. Brain regions with an incomplete blood-brain barrier had the lowest percentages of TREM2 expressing microglia, whereas the lateral entorhinal and cingulate cortex had the highest percentages. Ref.2 Ref.3
Sequence similarities	Contains 1 Ig-like V-type (immunoglobulin-like) domain.
Sequence caution	The sequence AAF69825.1 differs from that shown. Reason: Frameshift at positions 70 and 78.

Ontologies

Keywords
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Alternative splicing
Domain	Immunoglobulin domain Signal Transmembrane Transmembrane helix
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Cellular_component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	bacterial cell surface binding Inferred from direct assay PubMed 19079182. Source: MGI lipopolysaccharide binding Inferred from direct assay PubMed 19079182. Source: MGI transmembrane signaling receptor activity Inferred from sequence or structural similarity Ref.1. Source: MGI
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q99NH8-1)

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: Q99NH8-2)

Also known as: svTREM-2b;

The sequence of this isoform differs from the canonical sequence as follows:
     162-227: NQETSFPPTS...LQILTGPGGT → QVSSCGSPLA...HWTRRYVREF

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 18	18	Potential
	Chain	19 – 227	209	Triggering receptor expressed on myeloid cells 2		PRO_0000014988
Regions
	Topological domain	19 – 171	153	Extracellular Potential
	Transmembrane	172 – 192	21	Helical; Potential
	Topological domain	193 – 227	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 – 227	66	NQETS…GPGGT → QVSSCGSPLAYHLPPLSKES RDLLPTHLHSSPPGLRSPEQ VSCSQHPLGCGQGQAEAGNT CGQRAGLWPRCWAPTSDPHW TRRYVREF in isoform 2.		VSP_010794
	Natural variant	78	1	R → W in strain: FVB/N. Ref.5
Experimental info
	Sequence conflict	105	1	A → S in AAK01465. Ref.2
	Sequence conflict	105	1	A → S in AAH32959. Ref.5
	Sequence conflict	118	1	A → R in AAF69825. Ref.1
	Sequence conflict	122	1	Q → K in AAK01465. Ref.2
	Sequence conflict	122	1	Q → K in AAH32959. Ref.5
	Sequence conflict	148	1	S → E in AAK01465. Ref.2
	Sequence conflict	148	1	S → E in AAH32959. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 1, 2001. Version 1. Checksum: 740EEA8D90BF9773	FASTA	227	24,527
	10 20 30 40 50 60 MGPLHQFLLL LITALSQALN TTVLQGMAGQ SLRVSCTYDA LKHWGRRKAW CRQLGEEGPC 70 80 90 100 110 120 QRVVSTHGVW LLAFLKKRNG STVIADDTLA GTVTITLKNL QAGDAGLYQC QSLRGREAEV 130 140 150 160 170 180 LQKVLVEVLE DPLDDQDAGD LWVPEESSSF EGAQVEHSTS RNQETSFPPT SILLLLACVL 190 200 210 220 LSKFLAASIL WAVARGRQKP GTPVVRGLDC GQDAGHQLQI LTGPGGT
	Isoform 2 (svTREM-2b) [UniParc]. Checksum: 99D0BC9909FDA704	FASTA	249	27,304
	10 20 30 40 50 60 MGPLHQFLLL LITALSQALN TTVLQGMAGQ SLRVSCTYDA LKHWGRRKAW CRQLGEEGPC 70 80 90 100 110 120 QRVVSTHGVW LLAFLKKRNG STVIADDTLA GTVTITLKNL QAGDAGLYQC QSLRGREAEV 130 140 150 160 170 180 LQKVLVEVLE DPLDDQDAGD LWVPEESSSF EGAQVEHSTS RQVSSCGSPL AYHLPPLSKE 190 200 210 220 230 240 SRDLLPTHLH SSPPGLRSPE QVSCSQHPLG CGQGQAEAGN TCGQRAGLWP RCWAPTSDPH WTRRYVREF

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).
[2]	"Cloning and characterization of a novel mouse myeloid DAP12-associated receptor family." Daws M.R., Lanier L.L., Seaman W.E., Ryan J.C. Eur. J. Immunol. 31:783-791(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH TYROBP/DAP12. Strain: BALB/c. Tissue: Macrophage.
[3]	"Heterogeneous expression of the triggering receptor expressed on myeloid cells-2 on adult murine microglia." Schmid C.D., Sautkulis L.N., Danielson P.E., Cooper J., Hasel K.W., Hilbush B.S., Sutcliffe J.G., Carson M.J. J. Neurochem. 83:1309-1320(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY. Strain: C57BL/6J. Tissue: Brain.
[4]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Strain: C57BL/6J. Tissue: Spinal cord.
[5]	"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 1), VARIANT TRP-78. Strain: Czech II and FVB/N. Tissue: Lung and Mammary gland.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF213458 mRNA. Translation: AAF69825.1. Frameshift. AY024348 mRNA. Translation: AAK01465.1. AY024349 mRNA. Translation: AAK01466.1. AY187009 mRNA. Translation: AAO06114.1. AK039477 mRNA. Translation: BAC30362.1. BC032959 mRNA. Translation: AAH32959.1. BC033485 mRNA. Translation: AAH33485.1. BC052784 mRNA. Translation: AAH52784.1.
IPI	IPI00387519. IPI00407589.
RefSeq	NP_001259007.1. NM_001272078.1. NP_112544.1. NM_031254.3.
UniGene	Mm.261623.
3D structure databases
ProteinModelPortal	Q99NH8.
SMR	Q99NH8. Positions 26-110.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-59896N.
PTM databases
PhosphoSite	Q99NH8.
Proteomic databases
PaxDb	Q99NH8.
PRIDE	Q99NH8.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000024791; ENSMUSP00000024791; ENSMUSG00000023992. ENSMUST00000113237; ENSMUSP00000108863; ENSMUSG00000023992.
GeneID	83433.
KEGG	mmu:83433.
UCSC	uc008cxj.1. mouse. uc008cxk.1. mouse.
Organism-specific databases
CTD	54209.
MGI	MGI:1913150. Trem2.
Phylogenomic databases
eggNOG	NOG42611.
GeneTree	ENSGT00470000042297.
HOGENOM	HOG000118075.
HOVERGEN	HBG058623.
KO	K14378.
OrthoDB	EOG4CVG89.
Gene expression databases
Bgee	Q99NH8.
CleanEx	MM_TREM2.
Genevestigator	Q99NH8.
GermOnline	ENSMUSG00000023992. Mus musculus.
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
NextBio	350558.
SOURCE	Search...

Entry information

Entry name

TREM2_MOUSE

Accession

Primary (citable) accession number: Q99NH8
Secondary accession number(s): Q8CGK4 , Q8CIA6, Q99NH9, Q9JL34

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2004
Last sequence update:	June 1, 2001
Last modified:	May 29, 2013
This is version 92 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program