ID TREM2_MOUSE Reviewed; 227 AA.
AC Q99NH8; Q8CGK4; Q8CIA6; Q99NH9; Q9JL34;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 27-MAR-2024, entry version 163.
DE RecName: Full=Triggering receptor expressed on myeloid cells 2;
DE Short=TREM-2;
DE AltName: Full=Triggering receptor expressed on monocytes 2;
DE Flags: Precursor;
GN Name=Trem2; Synonyms=Trem2a, Trem2b, Trem2c;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=10799849; DOI=10.4049/jimmunol.164.10.4991;
RA Bouchon A., Dietrich J., Colonna M.;
RT "Inflammatory responses can be triggered by TREM-1, a novel receptor
RT expressed on neutrophils and monocytes.";
RL J. Immunol. 164:4991-4995(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, AND
RP INTERACTION WITH TYROBP/DAP12.
RC STRAIN=BALB/cJ; TISSUE=Macrophage;
RX PubMed=11241283;
RX DOI=10.1002/1521-4141(200103)31:3<783::aid-immu783>3.0.co;2-u;
RA Daws M.R., Lanier L.L., Seaman W.E., Ryan J.C.;
RT "Cloning and characterization of a novel mouse myeloid DAP12-associated
RT receptor family.";
RL Eur. J. Immunol. 31:783-791(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=12472885; DOI=10.1046/j.1471-4159.2002.01243.x;
RA Schmid C.D., Sautkulis L.N., Danielson P.E., Cooper J., Hasel K.W.,
RA Hilbush B.S., Sutcliffe J.G., Carson M.J.;
RT "Heterogeneous expression of the triggering receptor expressed on myeloid
RT cells-2 on adult murine microglia.";
RL J. Neurochem. 83:1309-1320(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Spinal cord;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT TRP-78.
RC STRAIN=Czech II, and FVB/N; TISSUE=Lung, and Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=15728241; DOI=10.1084/jem.20041611;
RA Takahashi K., Rochford C.D., Neumann H.;
RT "Clearance of apoptotic neurons without inflammation by microglial
RT triggering receptor expressed on myeloid cells-2.";
RL J. Exp. Med. 201:647-657(2005).
RN [7]
RP FUNCTION.
RX PubMed=16418779; DOI=10.1359/jbmr.051016;
RA Humphrey M.B., Daws M.R., Spusta S.C., Niemi E.C., Torchia J.A.,
RA Lanier L.L., Seaman W.E., Nakamura M.C.;
RT "TREM2, a DAP12-associated receptor, regulates osteoclast differentiation
RT and function.";
RL J. Bone Miner. Res. 21:237-245(2006).
RN [8]
RP FUNCTION.
RX PubMed=18957693; DOI=10.1126/scisignal.1159665;
RA Helming L., Tomasello E., Kyriakides T.R., Martinez F.O., Takai T.,
RA Gordon S., Vivier E.;
RT "Essential role of DAP12 signaling in macrophage programming into a fusion-
RT competent state.";
RL Sci. Signal. 1:RA11-RA11(2008).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, AND PROTEOLYTIC PROCESSING.
RX PubMed=24990881; DOI=10.1126/scitranslmed.3009093;
RA Kleinberger G., Yamanishi Y., Suarez-Calvet M., Czirr E., Lohmann E.,
RA Cuyvers E., Struyfs H., Pettkus N., Wenninger-Weinzierl A., Mazaheri F.,
RA Tahirovic S., Lleo A., Alcolea D., Fortea J., Willem M., Lammich S.,
RA Molinuevo J.L., Sanchez-Valle R., Antonell A., Ramirez A., Heneka M.T.,
RA Sleegers K., van der Zee J., Martin J.J., Engelborghs S.,
RA Demirtas-Tatlidede A., Zetterberg H., Van Broeckhoven C., Gurvit H.,
RA Wyss-Coray T., Hardy J., Colonna M., Haass C.;
RT "TREM2 mutations implicated in neurodegeneration impair cell surface
RT transport and phagocytosis.";
RL Sci. Transl. Med. 6:243RA86-243RA86(2014).
RN [10]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=25631124; DOI=10.1007/s00401-015-1388-1;
RA Cantoni C., Bollman B., Licastro D., Xie M., Mikesell R., Schmidt R.,
RA Yuede C.M., Galimberti D., Olivecrona G., Klein R.S., Cross A.H., Otero K.,
RA Piccio L.;
RT "TREM2 regulates microglial cell activation in response to demyelination in
RT vivo.";
RL Acta Neuropathol. 129:429-447(2015).
RN [11]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=27477018; DOI=10.1016/j.neuron.2016.06.015;
RA Yeh F.L., Wang Y., Tom I., Gonzalez L.C., Sheng M.;
RT "TREM2 Binds to Apolipoproteins, Including APOE and CLU/APOJ, and Thereby
RT Facilitates Uptake of Amyloid-Beta by Microglia.";
RL Neuron 91:328-340(2016).
RN [12]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=28802038; DOI=10.1016/j.cell.2017.07.023;
RA Ulland T.K., Song W.M., Huang S.C., Ulrich J.D., Sergushichev A.,
RA Beatty W.L., Loboda A.A., Zhou Y., Cairns N.J., Kambal A., Loginicheva E.,
RA Gilfillan S., Cella M., Virgin H.W., Unanue E.R., Wang Y., Artyomov M.N.,
RA Holtzman D.M., Colonna M.;
RT "TREM2 Maintains Microglial Metabolic Fitness in Alzheimer's Disease.";
RL Cell 170:649-663(2017).
RN [13]
RP FUNCTION, TISSUE SPECIFICITY, AND MUTAGENESIS OF THR-66.
RX PubMed=28559417; DOI=10.15252/embj.201796516;
RA Kleinberger G., Brendel M., Mracsko E., Wefers B., Groeneweg L., Xiang X.,
RA Focke C., Deussing M., Suarez-Calvet M., Mazaheri F., Parhizkar S.,
RA Pettkus N., Wurst W., Feederle R., Bartenstein P., Mueggler T.,
RA Arzberger T., Knuesel I., Rominger A., Haass C.;
RT "The FTD-like syndrome causing TREM2 T66M mutation impairs microglia
RT function, brain perfusion, and glucose metabolism.";
RL EMBO J. 36:1837-1853(2017).
RN [14]
RP TISSUE SPECIFICITY, AND PROTEOLYTIC PROCESSING.
RX PubMed=28855301; DOI=10.15252/emmm.201707673;
RA Thornton P., Sevalle J., Deery M.J., Fraser G., Zhou Y., Staahl S.,
RA Franssen E.H., Dodd R.B., Qamar S., Gomez Perez-Nievas B., Nicol L.S.,
RA Eketjaell S., Revell J., Jones C., Billinton A., St George-Hyslop P.H.,
RA Chessell I., Crowther D.C.;
RT "TREM2 shedding by cleavage at the H157-S158 bond is accelerated for the
RT Alzheimer's disease-associated H157Y variant.";
RL EMBO Mol. Med. 9:1366-1378(2017).
RN [15]
RP FUNCTION.
RX PubMed=28483841; DOI=10.15252/embr.201743922;
RA Mazaheri F., Snaidero N., Kleinberger G., Madore C., Daria A., Werner G.,
RA Krasemann S., Capell A., Truembach D., Wurst W., Brunner B., Bultmann S.,
RA Tahirovic S., Kerschensteiner M., Misgeld T., Butovsky O., Haass C.;
RT "TREM2 deficiency impairs chemotaxis and microglial responses to neuronal
RT injury.";
RL EMBO Rep. 18:1186-1198(2017).
RN [16]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=28077724; DOI=10.1523/jneurosci.2459-16.2017;
RA Zheng H., Jia L., Liu C.C., Rong Z., Zhong L., Yang L., Chen X.F.,
RA Fryer J.D., Wang X., Zhang Y.W., Xu H., Bu G.;
RT "TREM2 Promotes Microglial Survival by Activating Wnt/beta-Catenin
RT Pathway.";
RL J. Neurosci. 37:1772-1784(2017).
RN [17]
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION BY OXYGEN-GLUCOSE DEPRIVATION
RP AND ISCHEMIA.
RX PubMed=28592261; DOI=10.1186/s13041-017-0296-9;
RA Wu R., Li X., Xu P., Huang L., Cheng J., Huang X., Jiang J., Wu L.J.,
RA Tang Y.;
RT "TREM2 protects against cerebral ischemia/reperfusion injury.";
RL Mol. Brain 10:20-20(2017).
RN [18]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=29752066; DOI=10.1016/j.immuni.2018.04.016;
RA Filipello F., Morini R., Corradini I., Zerbi V., Canzi A., Michalski B.,
RA Erreni M., Markicevic M., Starvaggi-Cucuzza C., Otero K., Piccio L.,
RA Cignarella F., Perrucci F., Tamborini M., Genua M., Rajendran L., Menna E.,
RA Vetrano S., Fahnestock M., Paolicelli R.C., Matteoli M.;
RT "The Microglial Innate Immune Receptor TREM2 Is Required for Synapse
RT Elimination and Normal Brain Connectivity.";
RL Immunity 48:979-991(2018).
RN [19]
RP TISSUE SPECIFICITY, AND MUTAGENESIS OF ARG-47.
RX PubMed=29794134; DOI=10.1074/jbc.ra118.002352;
RA Sudom A., Talreja S., Danao J., Bragg E., Kegel R., Min X., Richardson J.,
RA Zhang Z., Sharkov N., Marcora E., Thibault S., Bradley J., Wood S.,
RA Lim A.C., Chen H., Wang S., Foltz I.N., Sambashivan S., Wang Z.;
RT "Molecular basis for the loss-of-function effects of the Alzheimer's
RT disease-associated R47H variant of the immune receptor TREM2.";
RL J. Biol. Chem. 293:12634-12646(2018).
RN [20]
RP FUNCTION, AND MUTAGENESIS OF ARG-47.
RX PubMed=29859094; DOI=10.1186/s13024-018-0262-8;
RA Cheng-Hathaway P.J., Reed-Geaghan E.G., Jay T.R., Casali B.T.,
RA Bemiller S.M., Puntambekar S.S., von Saucken V.E., Williams R.Y.,
RA Karlo J.C., Moutinho M., Xu G., Ransohoff R.M., Lamb B.T., Landreth G.E.;
RT "The Trem2 R47H variant confers loss-of-function-like phenotypes in
RT Alzheimer's disease.";
RL Mol. Neurodegener. 13:29-29(2018).
RN [21]
RP FUNCTION, AND INTERACTION WITH TYROBP.
RX PubMed=29518356; DOI=10.1016/j.neuron.2018.01.031;
RA Zhao Y., Wu X., Li X., Jiang L.L., Gui X., Liu Y., Sun Y., Zhu B.,
RA Pina-Crespo J.C., Zhang M., Zhang N., Chen X., Bu G., An Z., Huang T.Y.,
RA Xu H.;
RT "TREM2 Is a Receptor for beta-Amyloid that Mediates Microglial Function.";
RL Neuron 97:1023-1031(2018).
RN [22]
RP FUNCTION.
RX PubMed=30232263; DOI=10.1073/pnas.1811411115;
RA Sayed F.A., Telpoukhovskaia M., Kodama L., Li Y., Zhou Y., Le D.,
RA Hauduc A., Ludwig C., Gao F., Clelland C., Zhan L., Cooper Y.A.,
RA Davalos D., Akassoglou K., Coppola G., Gan L.;
RT "Differential effects of partial and complete loss of TREM2 on microglial
RT injury response and tauopathy.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:10172-10177(2018).
RN [23]
RP FUNCTION.
RX PubMed=29663649; DOI=10.1002/cbin.10975;
RA Li C., Zhao B., Lin C., Gong Z., An X.;
RT "TREM2 inhibits inflammatory responses in mouse microglia by suppressing
RT the PI3K/NF-kappaB signaling.";
RL Cell Biol. Int. 43:360-372(2019).
RN [24]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=30548312; DOI=10.1002/glia.23563;
RA Linnartz-Gerlach B., Bodea L.G., Klaus C., Ginolhac A., Halder R.,
RA Sinkkonen L., Walter J., Colonna M., Neumann H.;
RT "TREM2 triggers microglial density and age-related neuronal loss.";
RL Glia 67:539-550(2019).
CC -!- FUNCTION: Forms a receptor signaling complex with TYROBP which mediates
CC signaling and cell activation following ligand binding
CC (PubMed:11241283). Acts as a receptor for amyloid-beta protein 42, a
CC cleavage product of the amyloid-beta precursor protein APP, and
CC mediates its uptake and degradation by microglia (PubMed:27477018,
CC PubMed:29518356). Binding to amyloid-beta 42 mediates microglial
CC activation, proliferation, migration, apoptosis and expression of pro-
CC inflammatory cytokines, such as IL6R and CCL3, and the anti-
CC inflammatory cytokine ARG1 (PubMed:27477018, PubMed:29518356). Acts as
CC a receptor for lipoprotein particles such as LDL, VLDL, and HDL and for
CC apolipoproteins such as APOA1, APOA2, APOB, APOE, APOE2, APOE3, APOE4,
CC and CLU and enhances their uptake in microglia (PubMed:27477018). Binds
CC phospholipids (preferably anionic lipids) such as phosphatidylserine,
CC phosphatidylethanolamine, phosphatidylglycerol and sphingomyelin (By
CC similarity). Regulates microglial proliferation by acting as an
CC upstream regulator of the Wnt/beta-catenin signaling cascade
CC (PubMed:28077724). Required for microglial phagocytosis of apoptotic
CC neurons (PubMed:24990881). Also required for microglial activation and
CC phagocytosis of myelin debris after neuronal injury and of neuronal
CC synapses during synapse elimination in the developing brain
CC (PubMed:15728241, PubMed:28592261, PubMed:29752066, PubMed:25631124).
CC Regulates microglial chemotaxis and process outgrowth, and also the
CC microglial response to oxidative stress and lipopolysaccharide
CC (PubMed:30232263, PubMed:29663649, PubMed:28483841, PubMed:29859094).
CC It suppresses PI3K and NF-kappa-B signaling in response to
CC lipopolysaccharide; thus promoting phagocytosis, suppressing pro-
CC inflammatory cytokine and nitric oxide production, inhibiting apoptosis
CC and increasing expression of IL10 and TGFB (PubMed:29663649). During
CC oxidative stress, it promotes anti-apoptotic NF-kappa-B signaling and
CC ERK signaling (PubMed:28592261). Plays a role in microglial MTOR
CC activation and metabolism (PubMed:28802038). Regulates age-related
CC changes in microglial numbers (PubMed:30548312, PubMed:29752066,
CC PubMed:25631124). Triggers activation of the immune responses in
CC macrophages and dendritic cells (By similarity). Mediates cytokine-
CC induced formation of multinucleated giant cells which are formed by the
CC fusion of macrophages (PubMed:18957693). In dendritic cells, it
CC mediates up-regulation of chemokine receptor CCR7 and dendritic cell
CC maturation and survival (By similarity). Involved in the positive
CC regulation of osteoclast differentiation (PubMed:16418779).
CC {ECO:0000250|UniProtKB:Q9NZC2, ECO:0000269|PubMed:11241283,
CC ECO:0000269|PubMed:15728241, ECO:0000269|PubMed:16418779,
CC ECO:0000269|PubMed:18957693, ECO:0000269|PubMed:24990881,
CC ECO:0000269|PubMed:25631124, ECO:0000269|PubMed:27477018,
CC ECO:0000269|PubMed:28077724, ECO:0000269|PubMed:28483841,
CC ECO:0000269|PubMed:28592261, ECO:0000269|PubMed:28802038,
CC ECO:0000269|PubMed:29518356, ECO:0000269|PubMed:29663649,
CC ECO:0000269|PubMed:29752066, ECO:0000269|PubMed:29859094,
CC ECO:0000269|PubMed:30232263, ECO:0000269|PubMed:30548312}.
CC -!- SUBUNIT: Monomer (By similarity). After ectodomain shedding, the
CC extracellular domain oligomerizes, which is enhanced and stabilized by
CC binding of phosphatidylserine (By similarity). Interacts with
CC TYROBP/DAP12 (PubMed:11241283, PubMed:29518356). Interaction with
CC TYROBP is required for stabilization of the TREM2 C-terminal fragment
CC (TREM2-CTF) which is produced by proteolytic processing (By
CC similarity). {ECO:0000250|UniProtKB:Q9NZC2,
CC ECO:0000269|PubMed:11241283, ECO:0000269|PubMed:29518356}.
CC -!- INTERACTION:
CC Q99NH8; P70206: Plxna1; NbExp=4; IntAct=EBI-15982016, EBI-771260;
CC Q99NH8; PRO_0000000092 [P05067]: APP; Xeno; NbExp=2; IntAct=EBI-15982016, EBI-821758;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane
CC {ECO:0000269|PubMed:24990881}; Single-pass type I membrane protein
CC {ECO:0000255}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Secreted {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q99NH8-1; Sequence=Displayed;
CC Name=2; Synonyms=svTREM-2b;
CC IsoId=Q99NH8-2; Sequence=VSP_010794;
CC -!- TISSUE SPECIFICITY: Expressed in the brain, specifically in microglia
CC (at protein level) (PubMed:15728241, PubMed:28802038, PubMed:28855301,
CC PubMed:28077724, PubMed:28592261, PubMed:29794134, PubMed:29752066,
CC PubMed:27477018, PubMed:28559417). Expressed in macrophages (at protein
CC level) (PubMed:11241283, PubMed:28802038, PubMed:28559417). Expressed
CC at higher levels in the CNS, heart and lung than in lymph nodes or in
CC other non-lymphoid tissues such as kidney, liver and testis
CC (PubMed:12472885). In the CNS not all microglia express TREM2
CC (PubMed:12472885). Brain regions with an incomplete blood-brain barrier
CC had the lowest percentages of TREM2 expressing microglia, whereas the
CC lateral entorhinal and cingulate cortex had the highest percentages
CC (PubMed:12472885). {ECO:0000269|PubMed:11241283,
CC ECO:0000269|PubMed:12472885, ECO:0000269|PubMed:15728241,
CC ECO:0000269|PubMed:27477018, ECO:0000269|PubMed:28077724,
CC ECO:0000269|PubMed:28559417, ECO:0000269|PubMed:28592261,
CC ECO:0000269|PubMed:28802038, ECO:0000269|PubMed:28855301,
CC ECO:0000269|PubMed:29752066, ECO:0000269|PubMed:29794134}.
CC -!- INDUCTION: Expression is increased during oxygen-glucose deprivation,
CC reaching the highest expression level 12 hours after reoxygenation.
CC Expression is also increased by ischemia, where maximum expression is
CC reached 7 days after ischemic conditions.
CC {ECO:0000269|PubMed:28592261}.
CC -!- PTM: Undergoes ectodomain shedding through proteolytic cleavage by
CC ADAM10 and ADAM17 to produce a transmembrane segment, the TREM2 C-
CC terminal fragment (TREM2-CTF), which is subsequently cleaved by gamma-
CC secretase. {ECO:0000269|PubMed:24990881, ECO:0000269|PubMed:28855301}.
CC -!- DISRUPTION PHENOTYPE: Mice exhibit a strong increase in self-grooming
CC behavior, defective social behavior, and some sensorimotor defects
CC (PubMed:25631124, PubMed:29752066). Aged mice show decreases in age-
CC related neuronal loss and increases in synaptic density in the
CC substantia nigra and the hippocampus (PubMed:30548312). They also
CC exhibit a decrease in the connectivity between the retrosplenial
CC cortices, subiculum, hippocampus and anterior cingulate, as a result of
CC defective synaptic growth thus impairing their function
CC (PubMed:29752066). {ECO:0000269|PubMed:25631124,
CC ECO:0000269|PubMed:29752066, ECO:0000269|PubMed:30548312}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF69825.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF213458; AAF69825.1; ALT_FRAME; mRNA.
DR EMBL; AY024348; AAK01465.1; -; mRNA.
DR EMBL; AY024349; AAK01466.1; -; mRNA.
DR EMBL; AY187009; AAO06114.1; -; mRNA.
DR EMBL; AK039477; BAC30362.1; -; mRNA.
DR EMBL; BC032959; AAH32959.1; -; mRNA.
DR EMBL; BC033485; AAH33485.1; -; mRNA.
DR EMBL; BC052784; AAH52784.1; -; mRNA.
DR CCDS; CCDS28865.1; -. [Q99NH8-1]
DR CCDS; CCDS70825.1; -. [Q99NH8-2]
DR RefSeq; NP_001259007.1; NM_001272078.1. [Q99NH8-2]
DR RefSeq; NP_112544.1; NM_031254.3. [Q99NH8-1]
DR AlphaFoldDB; Q99NH8; -.
DR SMR; Q99NH8; -.
DR DIP; DIP-59896N; -.
DR IntAct; Q99NH8; 3.
DR STRING; 10090.ENSMUSP00000108863; -.
DR GlyCosmos; Q99NH8; 2 sites, No reported glycans.
DR GlyGen; Q99NH8; 2 sites.
DR iPTMnet; Q99NH8; -.
DR PhosphoSitePlus; Q99NH8; -.
DR MaxQB; Q99NH8; -.
DR PaxDb; 10090-ENSMUSP00000024791; -.
DR PeptideAtlas; Q99NH8; -.
DR ProteomicsDB; 298212; -. [Q99NH8-1]
DR ProteomicsDB; 298213; -. [Q99NH8-2]
DR Antibodypedia; 2280; 788 antibodies from 39 providers.
DR DNASU; 83433; -.
DR Ensembl; ENSMUST00000024791.15; ENSMUSP00000024791.9; ENSMUSG00000023992.15. [Q99NH8-1]
DR Ensembl; ENSMUST00000113237.4; ENSMUSP00000108863.4; ENSMUSG00000023992.15. [Q99NH8-2]
DR GeneID; 83433; -.
DR KEGG; mmu:83433; -.
DR UCSC; uc008cxj.2; mouse. [Q99NH8-1]
DR UCSC; uc008cxk.2; mouse. [Q99NH8-2]
DR AGR; MGI:1913150; -.
DR CTD; 54209; -.
DR MGI; MGI:1913150; Trem2.
DR VEuPathDB; HostDB:ENSMUSG00000023992; -.
DR eggNOG; ENOG502S4HV; Eukaryota.
DR GeneTree; ENSGT00470000042297; -.
DR HOGENOM; CLU_076120_0_0_1; -.
DR InParanoid; Q99NH8; -.
DR OMA; KWREKSW; -.
DR OrthoDB; 5000573at2759; -.
DR PhylomeDB; Q99NH8; -.
DR TreeFam; TF334441; -.
DR Reactome; R-MMU-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR Reactome; R-MMU-2172127; DAP12 interactions.
DR Reactome; R-MMU-2424491; DAP12 signaling.
DR Reactome; R-MMU-416700; Other semaphorin interactions.
DR BioGRID-ORCS; 83433; 5 hits in 79 CRISPR screens.
DR PRO; PR:Q99NH8; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q99NH8; Protein.
DR Bgee; ENSMUSG00000023992; Expressed in white adipose tissue and 71 other cell types or tissues.
DR Genevisible; Q99NH8; MM.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0044853; C:plasma membrane raft; ISO:MGI.
DR GO; GO:0001540; F:amyloid-beta binding; ISO:MGI.
DR GO; GO:0034186; F:apolipoprotein A-I binding; ISO:MGI.
DR GO; GO:0034185; F:apolipoprotein binding; ISO:MGI.
DR GO; GO:0008013; F:beta-catenin binding; ISO:MGI.
DR GO; GO:0008035; F:high-density lipoprotein particle binding; ISO:MGI.
DR GO; GO:0019209; F:kinase activator activity; ISS:ARUK-UCL.
DR GO; GO:0001530; F:lipopolysaccharide binding; IDA:BHF-UCL.
DR GO; GO:0071813; F:lipoprotein particle binding; ISO:MGI.
DR GO; GO:0070891; F:lipoteichoic acid binding; IDA:BHF-UCL.
DR GO; GO:0030169; F:low-density lipoprotein particle binding; ISO:MGI.
DR GO; GO:0042834; F:peptidoglycan binding; IDA:BHF-UCL.
DR GO; GO:0008429; F:phosphatidylethanolamine binding; ISO:MGI.
DR GO; GO:0001786; F:phosphatidylserine binding; ISS:ARUK-UCL.
DR GO; GO:0005543; F:phospholipid binding; ISS:UniProtKB.
DR GO; GO:1990782; F:protein tyrosine kinase binding; IPI:ARUK-UCL.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0097110; F:scaffold protein binding; ISO:MGI.
DR GO; GO:0038023; F:signaling receptor activity; IMP:ARUK-UCL.
DR GO; GO:0120146; F:sulfatide binding; ISS:ARUK-UCL.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; ISS:MGI.
DR GO; GO:0034189; F:very-low-density lipoprotein particle binding; ISO:MGI.
DR GO; GO:0097242; P:amyloid-beta clearance; IMP:UniProtKB.
DR GO; GO:0150094; P:amyloid-beta clearance by cellular catabolic process; IMP:ARUK-UCL.
DR GO; GO:0043277; P:apoptotic cell clearance; IMP:UniProtKB.
DR GO; GO:0048143; P:astrocyte activation; IGI:ARUK-UCL.
DR GO; GO:1904646; P:cellular response to amyloid-beta; IGI:ARUK-UCL.
DR GO; GO:0071333; P:cellular response to glucose stimulus; ISO:MGI.
DR GO; GO:0071456; P:cellular response to hypoxia; ISO:MGI.
DR GO; GO:0071396; P:cellular response to lipid; ISO:MGI.
DR GO; GO:0071223; P:cellular response to lipoteichoic acid; IDA:BHF-UCL.
DR GO; GO:0140052; P:cellular response to oxidised low-density lipoprotein particle stimulus; ISO:MGI.
DR GO; GO:0071224; P:cellular response to peptidoglycan; IDA:BHF-UCL.
DR GO; GO:0150062; P:complement-mediated synapse pruning; IMP:UniProtKB.
DR GO; GO:0038160; P:CXCL12-activated CXCR4 signaling pathway; ISS:ARUK-UCL.
DR GO; GO:0042742; P:defense response to bacterium; IMP:UniProtKB.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IMP:ARUK-UCL.
DR GO; GO:0097028; P:dendritic cell differentiation; ISO:MGI.
DR GO; GO:0097062; P:dendritic spine maintenance; IMP:ARUK-UCL.
DR GO; GO:0032497; P:detection of lipopolysaccharide; IDA:BHF-UCL.
DR GO; GO:0070392; P:detection of lipoteichoic acid; IDA:BHF-UCL.
DR GO; GO:0032499; P:detection of peptidoglycan; IDA:BHF-UCL.
DR GO; GO:1905805; P:excitatory synapse pruning; IMP:ARUK-UCL.
DR GO; GO:0098657; P:import into cell; IGI:ARUK-UCL.
DR GO; GO:0045087; P:innate immune response; IC:BHF-UCL.
DR GO; GO:0055088; P:lipid homeostasis; IMP:ARUK-UCL.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IC:BHF-UCL.
DR GO; GO:0007613; P:memory; ISO:MGI.
DR GO; GO:0001774; P:microglial cell activation; IMP:UniProtKB.
DR GO; GO:0002282; P:microglial cell activation involved in immune response; IMP:UniProtKB.
DR GO; GO:0061518; P:microglial cell proliferation; IMP:UniProtKB.
DR GO; GO:1905907; P:negative regulation of amyloid fibril formation; IMP:ARUK-UCL.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0061889; P:negative regulation of astrocyte activation; IDA:ARUK-UCL.
DR GO; GO:1904093; P:negative regulation of autophagic cell death; IGI:ARUK-UCL.
DR GO; GO:0010507; P:negative regulation of autophagy; IMP:ARUK-UCL.
DR GO; GO:0043124; P:negative regulation of canonical NF-kappaB signal transduction; IMP:ARUK-UCL.
DR GO; GO:0050866; P:negative regulation of cell activation; IDA:ARUK-UCL.
DR GO; GO:0010887; P:negative regulation of cholesterol storage; IMP:ARUK-UCL.
DR GO; GO:1900016; P:negative regulation of cytokine production involved in inflammatory response; IMP:ARUK-UCL.
DR GO; GO:0070345; P:negative regulation of fat cell proliferation; IMP:ARUK-UCL.
DR GO; GO:0034351; P:negative regulation of glial cell apoptotic process; IMP:ARUK-UCL.
DR GO; GO:0002862; P:negative regulation of inflammatory response to antigenic stimulus; IMP:ARUK-UCL.
DR GO; GO:0032691; P:negative regulation of interleukin-1 beta production; IMP:UniProtKB.
DR GO; GO:1902227; P:negative regulation of macrophage colony-stimulating factor signaling pathway; ISS:ARUK-UCL.
DR GO; GO:0150079; P:negative regulation of neuroinflammatory response; IDA:ARUK-UCL.
DR GO; GO:1900226; P:negative regulation of NLRP3 inflammasome complex assembly; IMP:ARUK-UCL.
DR GO; GO:1903753; P:negative regulation of p38MAPK cascade; IMP:ARUK-UCL.
DR GO; GO:0051898; P:negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IMP:ARUK-UCL.
DR GO; GO:0010891; P:negative regulation of sequestering of triglyceride; IMP:ARUK-UCL.
DR GO; GO:0034136; P:negative regulation of toll-like receptor 2 signaling pathway; IMP:ARUK-UCL.
DR GO; GO:0034144; P:negative regulation of toll-like receptor 4 signaling pathway; IDA:ARUK-UCL.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IMP:UniProtKB.
DR GO; GO:0150076; P:neuroinflammatory response; IMP:UniProtKB.
DR GO; GO:0030316; P:osteoclast differentiation; ISO:MGI.
DR GO; GO:0006911; P:phagocytosis, engulfment; IDA:MGI.
DR GO; GO:0006910; P:phagocytosis, recognition; ISO:MGI.
DR GO; GO:1900223; P:positive regulation of amyloid-beta clearance; IMP:ARUK-UCL.
DR GO; GO:0002588; P:positive regulation of antigen processing and presentation of peptide antigen via MHC class II; ISO:MGI.
DR GO; GO:2001171; P:positive regulation of ATP biosynthetic process; IMP:ARUK-UCL.
DR GO; GO:1903082; P:positive regulation of C-C chemokine receptor CCR7 signaling pathway; ISO:MGI.
DR GO; GO:0050850; P:positive regulation of calcium-mediated signaling; ISO:MGI.
DR GO; GO:1905291; P:positive regulation of CAMKK-AMPK signaling cascade; IGI:ARUK-UCL.
DR GO; GO:2000350; P:positive regulation of CD40 signaling pathway; ISO:MGI.
DR GO; GO:0050921; P:positive regulation of chemotaxis; IGI:ARUK-UCL.
DR GO; GO:0010875; P:positive regulation of cholesterol efflux; IMP:ARUK-UCL.
DR GO; GO:0045960; P:positive regulation of complement activation, classical pathway; IMP:ARUK-UCL.
DR GO; GO:1901076; P:positive regulation of engulfment of apoptotic cell; ISO:MGI.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:UniProtKB.
DR GO; GO:1904951; P:positive regulation of establishment of protein localization; IMP:ARUK-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IGI:ARUK-UCL.
DR GO; GO:0010983; P:positive regulation of high-density lipoprotein particle clearance; IMP:ARUK-UCL.
DR GO; GO:0032733; P:positive regulation of interleukin-10 production; IMP:UniProtKB.
DR GO; GO:1901980; P:positive regulation of inward rectifier potassium channel activity; IMP:ARUK-UCL.
DR GO; GO:1905581; P:positive regulation of low-density lipoprotein particle clearance; IMP:ARUK-UCL.
DR GO; GO:0034241; P:positive regulation of macrophage fusion; IMP:UniProtKB.
DR GO; GO:1903980; P:positive regulation of microglial cell activation; IDA:ARUK-UCL.
DR GO; GO:1904141; P:positive regulation of microglial cell migration; IMP:UniProtKB.
DR GO; GO:0010822; P:positive regulation of mitochondrion organization; IMP:ARUK-UCL.
DR GO; GO:0150078; P:positive regulation of neuroinflammatory response; IMP:UniProtKB.
DR GO; GO:1901224; P:positive regulation of non-canonical NF-kappaB signal transduction; IMP:UniProtKB.
DR GO; GO:0045672; P:positive regulation of osteoclast differentiation; IMP:UniProtKB.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISO:MGI.
DR GO; GO:0050766; P:positive regulation of phagocytosis; IMP:ARUK-UCL.
DR GO; GO:0060100; P:positive regulation of phagocytosis, engulfment; IMP:UniProtKB.
DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IMP:ARUK-UCL.
DR GO; GO:1901800; P:positive regulation of proteasomal protein catabolic process; IMP:ARUK-UCL.
DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; ISO:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IGI:ARUK-UCL.
DR GO; GO:0050714; P:positive regulation of protein secretion; ISO:MGI.
DR GO; GO:1905808; P:positive regulation of synapse pruning; ISS:ARUK-UCL.
DR GO; GO:0032008; P:positive regulation of TOR signaling; IGI:ARUK-UCL.
DR GO; GO:0070269; P:pyroptosis; IMP:ARUK-UCL.
DR GO; GO:1900015; P:regulation of cytokine production involved in inflammatory response; IMP:ARUK-UCL.
DR GO; GO:0010468; P:regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0110089; P:regulation of hippocampal neuron apoptotic process; IMP:ARUK-UCL.
DR GO; GO:0045088; P:regulation of innate immune response; IMP:UniProtKB.
DR GO; GO:0032675; P:regulation of interleukin-6 production; IGI:ARUK-UCL.
DR GO; GO:1902531; P:regulation of intracellular signal transduction; IGI:ARUK-UCL.
DR GO; GO:0019216; P:regulation of lipid metabolic process; ISO:MGI.
DR GO; GO:0071640; P:regulation of macrophage inflammatory protein 1 alpha production; IGI:ARUK-UCL.
DR GO; GO:1903376; P:regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway; IMP:ARUK-UCL.
DR GO; GO:0050730; P:regulation of peptidyl-tyrosine phosphorylation; IGI:ARUK-UCL.
DR GO; GO:0120035; P:regulation of plasma membrane bounded cell projection organization; IMP:UniProtKB.
DR GO; GO:0060075; P:regulation of resting membrane potential; IMP:ARUK-UCL.
DR GO; GO:0034151; P:regulation of toll-like receptor 6 signaling pathway; IMP:ARUK-UCL.
DR GO; GO:0032006; P:regulation of TOR signaling; IMP:ARUK-UCL.
DR GO; GO:0045728; P:respiratory burst after phagocytosis; IMP:ARUK-UCL.
DR GO; GO:0048678; P:response to axon injury; IMP:ARUK-UCL.
DR GO; GO:0002931; P:response to ischemia; IMP:UniProtKB.
DR GO; GO:0035176; P:social behavior; IMP:ARUK-UCL.
DR Gene3D; 2.60.40.10; Immunoglobulins; 1.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR013106; Ig_V-set.
DR PANTHER; PTHR16423:SF11; IG-LIKE DOMAIN-CONTAINING PROTEIN; 1.
DR PANTHER; PTHR16423; TREM-LIKE TRANSCRIPT PROTEIN; 1.
DR Pfam; PF07686; V-set; 1.
DR SMART; SM00409; IG; 1.
DR SUPFAM; SSF48726; Immunoglobulin; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Disulfide bond; Glycoprotein;
KW Immunoglobulin domain; Lipid-binding; Membrane; Receptor;
KW Reference proteome; Secreted; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..227
FT /note="Triggering receptor expressed on myeloid cells 2"
FT /id="PRO_0000014988"
FT TOPO_DOM 19..171
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 172..192
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 193..227
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 29..112
FT /note="Ig-like V-type"
FT BINDING 67
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-L-serine"
FT /ligand_id="ChEBI:CHEBI:57262"
FT /evidence="ECO:0000250|UniProtKB:Q9NZC2"
FT BINDING 88
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-L-serine"
FT /ligand_id="ChEBI:CHEBI:57262"
FT /evidence="ECO:0000250|UniProtKB:Q9NZC2"
FT SITE 157..158
FT /note="Cleavage of ectodomain"
FT /evidence="ECO:0000269|PubMed:28855301"
FT CARBOHYD 20
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 79
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:Q9NZC2"
FT DISULFID 36..110
FT /evidence="ECO:0000250|UniProtKB:Q9NZC2"
FT DISULFID 51..60
FT /evidence="ECO:0000250|UniProtKB:Q9NZC2"
FT VAR_SEQ 162..227
FT /note="NQETSFPPTSILLLLACVLLSKFLAASILWAVARGRQKPGTPVVRGLDCGQD
FT AGHQLQILTGPGGT -> QVSSCGSPLAYHLPPLSKESRDLLPTHLHSSPPGLRSPEQV
FT SCSQHPLGCGQGQAEAGNTCGQRAGLWPRCWAPTSDPHWTRRYVREF (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:12472885"
FT /id="VSP_010794"
FT VARIANT 78
FT /note="R -> W (in strain: FVB/N)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT MUTAGEN 47
FT /note="R->H: Decreases myeloid cell immune response.
FT Reduces expression levels."
FT /evidence="ECO:0000269|PubMed:29794134,
FT ECO:0000269|PubMed:29859094"
FT MUTAGEN 66
FT /note="T->M: Macrophages exhibit increased apoptosis,
FT reduced proliferation, and reduced phagocytosis.
FT Macrophages also exhibit increased inflammatory cytokine
FT secretion. Microglia demonstrate reduced immune activity.
FT Also decreases cerebral blood flow and reduces cerebral
FT glucose metabolism."
FT /evidence="ECO:0000269|PubMed:28559417"
FT CONFLICT 105
FT /note="A -> S (in Ref. 2; AAK01465 and 5; AAH32959)"
FT /evidence="ECO:0000305"
FT CONFLICT 118
FT /note="A -> R (in Ref. 1; AAF69825)"
FT /evidence="ECO:0000305"
FT CONFLICT 122
FT /note="Q -> K (in Ref. 2; AAK01465 and 5; AAH32959)"
FT /evidence="ECO:0000305"
FT CONFLICT 148
FT /note="S -> E (in Ref. 2; AAK01465 and 5; AAH32959)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 227 AA; 24527 MW; 740EEA8D90BF9773 CRC64;
MGPLHQFLLL LITALSQALN TTVLQGMAGQ SLRVSCTYDA LKHWGRRKAW CRQLGEEGPC
QRVVSTHGVW LLAFLKKRNG STVIADDTLA GTVTITLKNL QAGDAGLYQC QSLRGREAEV
LQKVLVEVLE DPLDDQDAGD LWVPEESSSF EGAQVEHSTS RNQETSFPPT SILLLLACVL
LSKFLAASIL WAVARGRQKP GTPVVRGLDC GQDAGHQLQI LTGPGGT
//
