Triggering receptor expressed on myeloid cells 2

<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

Sites

<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

• amyloid-beta binding Source: ARUK-UCL <p>Inferred from Physical Interaction</p> <p>Covers physical interactions between the gene product of interest and another molecule (or ion, or complex).</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ipi">GO evidence code guide</a></p> Inferred from physical interactionⁱ
  • Ref.22

    "TREM2 Is a Receptor for beta-Amyloid that Mediates Microglial Function."
    Zhao Y., Wu X., Li X., Jiang L.L., Gui X., Liu Y., Sun Y., Zhu B., Pina-Crespo J.C., Zhang M., Zhang N., Chen X., Bu G., An Z., Huang T.Y., Xu H.
    Neuron 97:1023-1031(2018) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, CHARACTERIZATION OF VARIANTS HIS-47 AND HIS-62.
• apolipoprotein A-I binding Source: ARUK-UCLInferred from physical interactionⁱ
  • Ref.15

    "TREM2 Binds to Apolipoproteins, Including APOE and CLU/APOJ, and Thereby Facilitates Uptake of Amyloid-Beta by Microglia."
    Yeh F.L., Wang Y., Tom I., Gonzalez L.C., Sheng M.
    Neuron 91:328-340(2016) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, TISSUE SPECIFICITY, CHARACTERIZATION OF VARIANTS CYS-38; HIS-47; HIS-62; MET-66 AND ASN-87, MUTAGENESIS OF LYS-48.
• apolipoprotein binding Source: ARUK-UCLInferred from physical interactionⁱ
  • Ref.15

    "TREM2 Binds to Apolipoproteins, Including APOE and CLU/APOJ, and Thereby Facilitates Uptake of Amyloid-Beta by Microglia."
    Yeh F.L., Wang Y., Tom I., Gonzalez L.C., Sheng M.
    Neuron 91:328-340(2016) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, TISSUE SPECIFICITY, CHARACTERIZATION OF VARIANTS CYS-38; HIS-47; HIS-62; MET-66 AND ASN-87, MUTAGENESIS OF LYS-48.
• high-density lipoprotein particle binding Source: ARUK-UCL <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ
  • Ref.15

    "TREM2 Binds to Apolipoproteins, Including APOE and CLU/APOJ, and Thereby Facilitates Uptake of Amyloid-Beta by Microglia."
    Yeh F.L., Wang Y., Tom I., Gonzalez L.C., Sheng M.
    Neuron 91:328-340(2016) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, TISSUE SPECIFICITY, CHARACTERIZATION OF VARIANTS CYS-38; HIS-47; HIS-62; MET-66 AND ASN-87, MUTAGENESIS OF LYS-48.
• kinase activator activity Source: ARUK-UCL <p>Inferred from Mutant Phenotype</p> <p>Describes annotations that are concluded from looking at variations or changes in a gene product such as mutations or abnormal levels and includes techniques such as knockouts, overexpression, anti-sense experiments and use of specific protein inhibitors.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#imp">GO evidence code guide</a></p> Inferred from mutant phenotypeⁱ
  • "TREM2 Regulates Microglial Cholesterol Metabolism upon Chronic Phagocytic Challenge."
    Nugent A.A., Lin K., van Lengerich B., Lianoglou S., Przybyla L., Davis S.S., Llapashtica C., Wang J., Kim D.J., Xia D., Lucas A., Baskaran S., Haddick P.C.G., Lenser M., Earr T.K., Shi J., Dugas J.C., Andreone B.J.

    , Logan T., Solanoy H.O., Chen H., Srivastava A., Poda S.B., Sanchez P.E., Watts R.J., Sandmann T., Astarita G., Lewcock J.W., Monroe K.M., Di Paolo G.
    Neuron 105:837-854.e9(2020) [PubMed] [Europe PMC] [Abstract]
• lipid binding Source: ARUK-UCL <p>Traceable Author Statement</p> <p>Used for information from review articles where the original experiments are traceable through that article and also for information from text books or dictionaries.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#tas">GO evidence code guide</a></p> Traceable author statementⁱ
  • Ref.22

    "TREM2 Is a Receptor for beta-Amyloid that Mediates Microglial Function."
    Zhao Y., Wu X., Li X., Jiang L.L., Gui X., Liu Y., Sun Y., Zhu B., Pina-Crespo J.C., Zhang M., Zhang N., Chen X., Bu G., An Z., Huang T.Y., Xu H.
    Neuron 97:1023-1031(2018) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, CHARACTERIZATION OF VARIANTS HIS-47 AND HIS-62.
• lipopolysaccharide binding Source: Ensembl
• lipoprotein particle binding Source: ARUK-UCLInferred from direct assayⁱ
  • Ref.15

    "TREM2 Binds to Apolipoproteins, Including APOE and CLU/APOJ, and Thereby Facilitates Uptake of Amyloid-Beta by Microglia."
    Yeh F.L., Wang Y., Tom I., Gonzalez L.C., Sheng M.
    Neuron 91:328-340(2016) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, TISSUE SPECIFICITY, CHARACTERIZATION OF VARIANTS CYS-38; HIS-47; HIS-62; MET-66 AND ASN-87, MUTAGENESIS OF LYS-48.
• lipoteichoic acid binding Source: Ensembl
• low-density lipoprotein particle binding Source: ARUK-UCLInferred from direct assayⁱ
  • Ref.15

    "TREM2 Binds to Apolipoproteins, Including APOE and CLU/APOJ, and Thereby Facilitates Uptake of Amyloid-Beta by Microglia."
    Yeh F.L., Wang Y., Tom I., Gonzalez L.C., Sheng M.
    Neuron 91:328-340(2016) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, TISSUE SPECIFICITY, CHARACTERIZATION OF VARIANTS CYS-38; HIS-47; HIS-62; MET-66 AND ASN-87, MUTAGENESIS OF LYS-48.
• peptidoglycan binding Source: Ensembl
• phosphatidylethanolamine binding Source: ARUK-UCLInferred from direct assayⁱ
  • "Aminophospholipids are signal-transducing TREM2 ligands on apoptotic cells."
    Shirotani K., Hori Y., Yoshizaki R., Higuchi E., Colonna M., Saito T., Hashimoto S., Saito T., Saido T.C., Iwata N.
    Sci Rep 9:7508-7508(2019) [PubMed] [Europe PMC] [Abstract]
• phosphatidylserine binding Source: ARUK-UCLInferred from direct assayⁱ
  • "Aminophospholipids are signal-transducing TREM2 ligands on apoptotic cells."
    Shirotani K., Hori Y., Yoshizaki R., Higuchi E., Colonna M., Saito T., Hashimoto S., Saito T., Saido T.C., Iwata N.
    Sci Rep 9:7508-7508(2019) [PubMed] [Europe PMC] [Abstract]
  • "TREM2 Regulates Microglial Cholesterol Metabolism upon Chronic Phagocytic Challenge."
    Nugent A.A., Lin K., van Lengerich B., Lianoglou S., Przybyla L., Davis S.S., Llapashtica C., Wang J., Kim D.J., Xia D., Lucas A., Baskaran S., Haddick P.C.G., Lenser M., Earr T.K., Shi J., Dugas J.C., Andreone B.J.

    , Logan T., Solanoy H.O., Chen H., Srivastava A., Poda S.B., Sanchez P.E., Watts R.J., Sandmann T., Astarita G., Lewcock J.W., Monroe K.M., Di Paolo G.
    Neuron 105:837-854.e9(2020) [PubMed] [Europe PMC] [Abstract]
• phospholipid binding Source: UniProtKBInferred from direct assayⁱ
  • Ref.23

    "Neurodegenerative disease mutations in TREM2 reveal a functional surface and distinct loss-of-function mechanisms."
    Kober D.L., Alexander-Brett J.M., Karch C.M., Cruchaga C., Colonna M., Holtzman M.J., Brett T.J.
    Elife 5:E20391-E20391(2016) [PubMed] [Europe PMC] [Abstract]

    Cited for: X-RAY CRYSTALLOGRAPHY (3.10 ANGSTROMS) OF 19-133, DISULFIDE BONDS, SUBUNIT, SUBCELLULAR LOCATION, MUTAGENESIS OF ASN-68; ARG-76 AND ARG-77, GLYCOSYLATION AT ASN-79, CHARACTERIZATION OF VARIANTS CYS-38; HIS-47; HIS-62; MET-66; ASN-87 AND LYS-96, CHARACTERIZATION OF VARIANT PLOSL2 GLY-126.
• protein-containing complex binding Source: ARUK-UCLInferred from physical interactionⁱ
  • Ref.22

    "TREM2 Is a Receptor for beta-Amyloid that Mediates Microglial Function."
    Zhao Y., Wu X., Li X., Jiang L.L., Gui X., Liu Y., Sun Y., Zhu B., Pina-Crespo J.C., Zhang M., Zhang N., Chen X., Bu G., An Z., Huang T.Y., Xu H.
    Neuron 97:1023-1031(2018) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, CHARACTERIZATION OF VARIANTS HIS-47 AND HIS-62.
• protein tyrosine kinase binding Source: ARUK-UCL <p>Inferred from Sequence or Structural Similarity<br />Used for any analysis based on sequence alignment, structure comparison, or evaluation of sequence features such as composition.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#iss">GO evidence code guide</a></p> Inferred from sequence or structural similarityⁱ
  • Ref.22

    "TREM2 Is a Receptor for beta-Amyloid that Mediates Microglial Function."
    Zhao Y., Wu X., Li X., Jiang L.L., Gui X., Liu Y., Sun Y., Zhu B., Pina-Crespo J.C., Zhang M., Zhang N., Chen X., Bu G., An Z., Huang T.Y., Xu H.
    Neuron 97:1023-1031(2018) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, CHARACTERIZATION OF VARIANTS HIS-47 AND HIS-62.
• scaffold protein binding Source: BHF-UCLInferred from physical interactionⁱ
  • Ref.4

    "A DAP12-mediated pathway regulates expression of CC chemokine receptor 7 and maturation of human dendritic cells."
    Bouchon A., Hernandez-Munain C., Cella M., Colonna M.
    J. Exp. Med. 194:1111-1122(2001) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, INTERACTION WITH TYROBP.
• signaling receptor activity Source: ARUK-UCLInferred from mutant phenotypeⁱ
  • "Alzheimer's-associated PLCgamma2 is a signaling node required for both TREM2 function and the inflammatory response in human microglia."
    Andreone B.J., Przybyla L., Llapashtica C., Rana A., Davis S.S., van Lengerich B., Lin K., Shi J., Mei Y., Astarita G., Di Paolo G., Sandmann T., Monroe K.M., Lewcock J.W.
    Nat Neurosci 23:927-938(2020) [PubMed] [Europe PMC] [Abstract]
• sulfatide binding Source: ARUK-UCLInferred from direct assayⁱ
  • "TREM2 Regulates Microglial Cholesterol Metabolism upon Chronic Phagocytic Challenge."
    Nugent A.A., Lin K., van Lengerich B., Lianoglou S., Przybyla L., Davis S.S., Llapashtica C., Wang J., Kim D.J., Xia D., Lucas A., Baskaran S., Haddick P.C.G., Lenser M., Earr T.K., Shi J., Dugas J.C., Andreone B.J.

    , Logan T., Solanoy H.O., Chen H., Srivastava A., Poda S.B., Sanchez P.E., Watts R.J., Sandmann T., Astarita G., Lewcock J.W., Monroe K.M., Di Paolo G.
    Neuron 105:837-854.e9(2020) [PubMed] [Europe PMC] [Abstract]
• transmembrane signaling receptor activity Source: GO_Central <p>Inferred from Biological aspect of Ancestor</p> <p>A type of phylogenetic evidence whereby an aspect of a descendent is inferred through the characterization of an aspect of a ancestral gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#iba">GO evidence code guide</a></p> Inferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief Bioinform 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• very-low-density lipoprotein particle binding Source: ARUK-UCLInferred from direct assayⁱ
  • Ref.15

    "TREM2 Binds to Apolipoproteins, Including APOE and CLU/APOJ, and Thereby Facilitates Uptake of Amyloid-Beta by Microglia."
    Yeh F.L., Wang Y., Tom I., Gonzalez L.C., Sheng M.
    Neuron 91:328-340(2016) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, TISSUE SPECIFICITY, CHARACTERIZATION OF VARIANTS CYS-38; HIS-47; HIS-62; MET-66 AND ASN-87, MUTAGENESIS OF LYS-48.

GO - Biological processⁱ

• amyloid-beta clearance by cellular catabolic process Source: ARUK-UCLInferred from mutant phenotypeⁱ
  • "Gene expression and functional deficits underlie TREM2-knockout microglia responses in human models of Alzheimer's disease."
    McQuade A., Kang Y.J., Hasselmann J., Jairaman A., Sotelo A., Coburn M., Shabestari S.K., Chadarevian J.P., Fote G., Tu C.H., Danhash E., Silva J., Martinez E., Cotman C., Prieto G.A., Thompson L.M., Steffan J.S., Smith I.

    , Davtyan H., Cahalan M., Cho H., Blurton-Jones M.
    Nat Commun 11:5370-5370(2020) [PubMed] [Europe PMC] [Abstract]
• apoptotic cell clearance Source: UniProtKB
• astrocyte activation Source: ARUK-UCL
• cellular response to amyloid-beta Source: ARUK-UCLInferred from sequence or structural similarityⁱ
  • Ref.22

    "TREM2 Is a Receptor for beta-Amyloid that Mediates Microglial Function."
    Zhao Y., Wu X., Li X., Jiang L.L., Gui X., Liu Y., Sun Y., Zhu B., Pina-Crespo J.C., Zhang M., Zhang N., Chen X., Bu G., An Z., Huang T.Y., Xu H.
    Neuron 97:1023-1031(2018) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, CHARACTERIZATION OF VARIANTS HIS-47 AND HIS-62.
• cellular response to glucose stimulus Source: Ensembl
• cellular response to hypoxia Source: Ensembl
• cellular response to lipid Source: ARUK-UCLInferred from mutant phenotypeⁱ
  • "Alzheimer's-associated PLCgamma2 is a signaling node required for both TREM2 function and the inflammatory response in human microglia."
    Andreone B.J., Przybyla L., Llapashtica C., Rana A., Davis S.S., van Lengerich B., Lin K., Shi J., Mei Y., Astarita G., Di Paolo G., Sandmann T., Monroe K.M., Lewcock J.W.
    Nat Neurosci 23:927-938(2020) [PubMed] [Europe PMC] [Abstract]
• cellular response to lipoteichoic acid Source: Ensembl
• cellular response to oxidised low-density lipoprotein particle stimulus Source: ARUK-UCLInferred from direct assayⁱ
  • "TREM2 Regulates Microglial Cholesterol Metabolism upon Chronic Phagocytic Challenge."
    Nugent A.A., Lin K., van Lengerich B., Lianoglou S., Przybyla L., Davis S.S., Llapashtica C., Wang J., Kim D.J., Xia D., Lucas A., Baskaran S., Haddick P.C.G., Lenser M., Earr T.K., Shi J., Dugas J.C., Andreone B.J.

    , Logan T., Solanoy H.O., Chen H., Srivastava A., Poda S.B., Sanchez P.E., Watts R.J., Sandmann T., Astarita G., Lewcock J.W., Monroe K.M., Di Paolo G.
    Neuron 105:837-854.e9(2020) [PubMed] [Europe PMC] [Abstract]
• cellular response to peptidoglycan Source: Ensembl
• complement-mediated synapse pruning Source: ARUK-UCL
• CXCL12-activated CXCR4 signaling pathway Source: ARUK-UCLInferred from mutant phenotypeⁱ
  • "Gene expression and functional deficits underlie TREM2-knockout microglia responses in human models of Alzheimer's disease."
    McQuade A., Kang Y.J., Hasselmann J., Jairaman A., Sotelo A., Coburn M., Shabestari S.K., Chadarevian J.P., Fote G., Tu C.H., Danhash E., Silva J., Martinez E., Cotman C., Prieto G.A., Thompson L.M., Steffan J.S., Smith I.

    , Davtyan H., Cahalan M., Cho H., Blurton-Jones M.
    Nat Commun 11:5370-5370(2020) [PubMed] [Europe PMC] [Abstract]
• defense response to Gram-negative bacterium Source: ARUK-UCL
• dendritic cell differentiation Source: BHF-UCLInferred from direct assayⁱ
  • Ref.4

    "A DAP12-mediated pathway regulates expression of CC chemokine receptor 7 and maturation of human dendritic cells."
    Bouchon A., Hernandez-Munain C., Cella M., Colonna M.
    J. Exp. Med. 194:1111-1122(2001) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, INTERACTION WITH TYROBP.
• dendritic spine maintenance Source: ARUK-UCL
• detection of lipopolysaccharide Source: Ensembl
• detection of lipoteichoic acid Source: Ensembl
• detection of peptidoglycan Source: Ensembl
• excitatory synapse pruning Source: ARUK-UCL
• humoral immune response Source: ProtIncTraceable author statementⁱ
  • Ref.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.
• import into cell Source: ARUK-UCL
• lipid homeostasis Source: ARUK-UCL
• memory Source: ARUK-UCLInferred from direct assayⁱ
  • "Increased soluble TREM2 in cerebrospinal fluid is associated with reduced cognitive and clinical decline in Alzheimer's disease."
    Ewers M., Franzmeier N., Suarez-Calvet M., Morenas-Rodriguez E., Caballero M.A.A., Kleinberger G., Piccio L., Cruchaga C., Deming Y., Dichgans M., Trojanowski J.Q., Shaw L.M., Weiner M.W., Haass C.
    Sci Transl Med 11:eaav6221-eaav6221(2019) [PubMed] [Europe PMC] [Abstract]
• microglial cell activation Source: ARUK-UCLInferred from sequence or structural similarityⁱ
  • Ref.22

    "TREM2 Is a Receptor for beta-Amyloid that Mediates Microglial Function."
    Zhao Y., Wu X., Li X., Jiang L.L., Gui X., Liu Y., Sun Y., Zhu B., Pina-Crespo J.C., Zhang M., Zhang N., Chen X., Bu G., An Z., Huang T.Y., Xu H.
    Neuron 97:1023-1031(2018) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, CHARACTERIZATION OF VARIANTS HIS-47 AND HIS-62.
• microglial cell activation involved in immune response Source: ARUK-UCL
• microglial cell proliferation Source: ARUK-UCL
• negative regulation of amyloid fibril formation Source: ARUK-UCL
• negative regulation of astrocyte activation Source: ARUK-UCL
• negative regulation of autophagic cell death Source: ARUK-UCL
• negative regulation of autophagy Source: ARUK-UCL
• negative regulation of cell activation Source: ARUK-UCL
• negative regulation of cholesterol storage Source: ARUK-UCL
• negative regulation of cytokine production involved in inflammatory response Source: ARUK-UCL
• negative regulation of fat cell proliferation Source: ARUK-UCL
• negative regulation of glial cell apoptotic process Source: ARUK-UCL
• negative regulation of I-kappaB kinase/NF-kappaB signaling Source: ARUK-UCL
• negative regulation of inflammatory response to antigenic stimulus Source: ARUK-UCL
• negative regulation of interleukin-1 beta production Source: Ensembl
• negative regulation of macrophage colony-stimulating factor signaling pathway Source: ARUK-UCLInferred from mutant phenotypeⁱ
  • "Gene expression and functional deficits underlie TREM2-knockout microglia responses in human models of Alzheimer's disease."
    McQuade A., Kang Y.J., Hasselmann J., Jairaman A., Sotelo A., Coburn M., Shabestari S.K., Chadarevian J.P., Fote G., Tu C.H., Danhash E., Silva J., Martinez E., Cotman C., Prieto G.A., Thompson L.M., Steffan J.S., Smith I.

    , Davtyan H., Cahalan M., Cho H., Blurton-Jones M.
    Nat Commun 11:5370-5370(2020) [PubMed] [Europe PMC] [Abstract]
• negative regulation of neuroinflammatory response Source: ARUK-UCLInferred from mutant phenotypeⁱ
  • "Alzheimer's-associated PLCgamma2 is a signaling node required for both TREM2 function and the inflammatory response in human microglia."
    Andreone B.J., Przybyla L., Llapashtica C., Rana A., Davis S.S., van Lengerich B., Lin K., Shi J., Mei Y., Astarita G., Di Paolo G., Sandmann T., Monroe K.M., Lewcock J.W.
    Nat Neurosci 23:927-938(2020) [PubMed] [Europe PMC] [Abstract]
• negative regulation of NLRP3 inflammasome complex assembly Source: ARUK-UCLInferred from mutant phenotypeⁱ
  • "Alzheimer's-associated PLCgamma2 is a signaling node required for both TREM2 function and the inflammatory response in human microglia."
    Andreone B.J., Przybyla L., Llapashtica C., Rana A., Davis S.S., van Lengerich B., Lin K., Shi J., Mei Y., Astarita G., Di Paolo G., Sandmann T., Monroe K.M., Lewcock J.W.
    Nat Neurosci 23:927-938(2020) [PubMed] [Europe PMC] [Abstract]
• negative regulation of p38MAPK cascade Source: ARUK-UCL
• negative regulation of phosphatidylinositol 3-kinase signaling Source: ARUK-UCL
• negative regulation of sequestering of triglyceride Source: ARUK-UCL
• negative regulation of toll-like receptor 2 signaling pathway Source: ARUK-UCL
• negative regulation of toll-like receptor 4 signaling pathway Source: ARUK-UCL
• negative regulation of tumor necrosis factor production Source: Ensembl
• osteoclast differentiation Source: UniProtKBInferred from mutant phenotypeⁱ
  • Ref.7

    "DAP12/TREM2 deficiency results in impaired osteoclast differentiation and osteoporotic features."
    Paloneva J., Mandelin J., Kiialainen A., Bohling T., Prudlo J., Hakola P., Haltia M., Konttinen Y.T., Peltonen L.
    J. Exp. Med. 198:669-675(2003) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, INVOLVEMENT IN PLOSL2, VARIANT PLOSL2 14-GLU--THR-230 DEL, CHARACTERIZATION OF VARIANT PLOSL2 14-GLU--THR-230 DEL.
• phagocytosis, engulfment Source: Ensembl
• phagocytosis, recognition Source: ARUK-UCLInferred from mutant phenotypeⁱ
  • "Alzheimer's-associated PLCgamma2 is a signaling node required for both TREM2 function and the inflammatory response in human microglia."
    Andreone B.J., Przybyla L., Llapashtica C., Rana A., Davis S.S., van Lengerich B., Lin K., Shi J., Mei Y., Astarita G., Di Paolo G., Sandmann T., Monroe K.M., Lewcock J.W.
    Nat Neurosci 23:927-938(2020) [PubMed] [Europe PMC] [Abstract]
• positive regulation of amyloid-beta clearance Source: ARUK-UCLInferred from mutant phenotypeⁱ
  • "TREM2 function impedes tau seeding in neuritic plaques."
    Leyns C.E.G., Gratuze M., Narasimhan S., Jain N., Koscal L.J., Jiang H., Manis M., Colonna M., Lee V.M.Y., Ulrich J.D., Holtzman D.M.
    Nat Neurosci 22:1217-1222(2019) [PubMed] [Europe PMC] [Abstract]
• positive regulation of antigen processing and presentation of peptide antigen via MHC class II Source: BHF-UCLInferred from direct assayⁱ
  • Ref.4

    "A DAP12-mediated pathway regulates expression of CC chemokine receptor 7 and maturation of human dendritic cells."
    Bouchon A., Hernandez-Munain C., Cella M., Colonna M.
    J. Exp. Med. 194:1111-1122(2001) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, INTERACTION WITH TYROBP.
• positive regulation of ATP biosynthetic process Source: ARUK-UCL
• positive regulation of calcium-mediated signaling Source: BHF-UCLInferred from direct assayⁱ
  • Ref.4

    "A DAP12-mediated pathway regulates expression of CC chemokine receptor 7 and maturation of human dendritic cells."
    Bouchon A., Hernandez-Munain C., Cella M., Colonna M.
    J. Exp. Med. 194:1111-1122(2001) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, INTERACTION WITH TYROBP.
• positive regulation of CAMKK-AMPK signaling cascade Source: ARUK-UCL
• positive regulation of C-C chemokine receptor CCR7 signaling pathway Source: BHF-UCLInferred from direct assayⁱ
  • Ref.4

    "A DAP12-mediated pathway regulates expression of CC chemokine receptor 7 and maturation of human dendritic cells."
    Bouchon A., Hernandez-Munain C., Cella M., Colonna M.
    J. Exp. Med. 194:1111-1122(2001) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, INTERACTION WITH TYROBP.
• positive regulation of CD40 signaling pathway Source: BHF-UCLInferred from direct assayⁱ
  • Ref.4

    "A DAP12-mediated pathway regulates expression of CC chemokine receptor 7 and maturation of human dendritic cells."
    Bouchon A., Hernandez-Munain C., Cella M., Colonna M.
    J. Exp. Med. 194:1111-1122(2001) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, INTERACTION WITH TYROBP.
• positive regulation of chemotaxis Source: ARUK-UCL
• positive regulation of cholesterol efflux Source: ARUK-UCL
• positive regulation of complement activation, classical pathway Source: ARUK-UCL
• positive regulation of engulfment of apoptotic cell Source: UniProtKBInferred from mutant phenotypeⁱ
  • Ref.12

    "TREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis."
    Kleinberger G., Yamanishi Y., Suarez-Calvet M., Czirr E., Lohmann E., Cuyvers E., Struyfs H., Pettkus N., Wenninger-Weinzierl A., Mazaheri F., Tahirovic S., Lleo A., Alcolea D., Fortea J., Willem M., Lammich S., Molinuevo J.L., Sanchez-Valle R.

    , Antonell A., Ramirez A., Heneka M.T., Sleegers K., van der Zee J., Martin J.J., Engelborghs S., Demirtas-Tatlidede A., Zetterberg H., Van Broeckhoven C., Gurvit H., Wyss-Coray T., Hardy J., Colonna M., Haass C.
    Sci. Transl. Med. 6:243RA86-243RA86(2014) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, SUBCELLULAR LOCATION, PROTEOLYTIC PROCESSING, CHARACTERIZATION OF VARIANTS CYS-38; HIS-47 AND MET-66, MUTAGENESIS OF CYS-36 AND CYS-60.
• positive regulation of ERK1 and ERK2 cascade Source: BHF-UCLInferred from direct assayⁱ
  • Ref.4

    "A DAP12-mediated pathway regulates expression of CC chemokine receptor 7 and maturation of human dendritic cells."
    Bouchon A., Hernandez-Munain C., Cella M., Colonna M.
    J. Exp. Med. 194:1111-1122(2001) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, INTERACTION WITH TYROBP.
• positive regulation of establishment of protein localization Source: ARUK-UCL
• positive regulation of gene expression Source: ARUK-UCLInferred from mutant phenotypeⁱ
  • "Alzheimer's-associated PLCgamma2 is a signaling node required for both TREM2 function and the inflammatory response in human microglia."
    Andreone B.J., Przybyla L., Llapashtica C., Rana A., Davis S.S., van Lengerich B., Lin K., Shi J., Mei Y., Astarita G., Di Paolo G., Sandmann T., Monroe K.M., Lewcock J.W.
    Nat Neurosci 23:927-938(2020) [PubMed] [Europe PMC] [Abstract]
• positive regulation of high-density lipoprotein particle clearance Source: ARUK-UCL
• positive regulation of interleukin-10 production Source: Ensembl
• positive regulation of inward rectifier potassium channel activity Source: ARUK-UCLInferred from sequence or structural similarityⁱ
  • Ref.22

    "TREM2 Is a Receptor for beta-Amyloid that Mediates Microglial Function."
    Zhao Y., Wu X., Li X., Jiang L.L., Gui X., Liu Y., Sun Y., Zhu B., Pina-Crespo J.C., Zhang M., Zhang N., Chen X., Bu G., An Z., Huang T.Y., Xu H.
    Neuron 97:1023-1031(2018) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, CHARACTERIZATION OF VARIANTS HIS-47 AND HIS-62.
• positive regulation of kinase activity Source: ARUK-UCLInferred from direct assayⁱ
  • "TREM2 Regulates Microglial Cholesterol Metabolism upon Chronic Phagocytic Challenge."
    Nugent A.A., Lin K., van Lengerich B., Lianoglou S., Przybyla L., Davis S.S., Llapashtica C., Wang J., Kim D.J., Xia D., Lucas A., Baskaran S., Haddick P.C.G., Lenser M., Earr T.K., Shi J., Dugas J.C., Andreone B.J.

    , Logan T., Solanoy H.O., Chen H., Srivastava A., Poda S.B., Sanchez P.E., Watts R.J., Sandmann T., Astarita G., Lewcock J.W., Monroe K.M., Di Paolo G.
    Neuron 105:837-854.e9(2020) [PubMed] [Europe PMC] [Abstract]
• positive regulation of low-density lipoprotein particle clearance Source: ARUK-UCL
• positive regulation of macrophage fusion Source: UniProtKB
• positive regulation of microglial cell activation Source: UniProtKBInferred from mutant phenotypeⁱ
  • Ref.12

    "TREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis."
    Kleinberger G., Yamanishi Y., Suarez-Calvet M., Czirr E., Lohmann E., Cuyvers E., Struyfs H., Pettkus N., Wenninger-Weinzierl A., Mazaheri F., Tahirovic S., Lleo A., Alcolea D., Fortea J., Willem M., Lammich S., Molinuevo J.L., Sanchez-Valle R.

    , Antonell A., Ramirez A., Heneka M.T., Sleegers K., van der Zee J., Martin J.J., Engelborghs S., Demirtas-Tatlidede A., Zetterberg H., Van Broeckhoven C., Gurvit H., Wyss-Coray T., Hardy J., Colonna M., Haass C.
    Sci. Transl. Med. 6:243RA86-243RA86(2014) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, SUBCELLULAR LOCATION, PROTEOLYTIC PROCESSING, CHARACTERIZATION OF VARIANTS CYS-38; HIS-47 AND MET-66, MUTAGENESIS OF CYS-36 AND CYS-60.
• positive regulation of microglial cell migration Source: ARUK-UCLInferred from mutant phenotypeⁱ
  • "Gene expression and functional deficits underlie TREM2-knockout microglia responses in human models of Alzheimer's disease."
    McQuade A., Kang Y.J., Hasselmann J., Jairaman A., Sotelo A., Coburn M., Shabestari S.K., Chadarevian J.P., Fote G., Tu C.H., Danhash E., Silva J., Martinez E., Cotman C., Prieto G.A., Thompson L.M., Steffan J.S., Smith I.

    , Davtyan H., Cahalan M., Cho H., Blurton-Jones M.
    Nat Commun 11:5370-5370(2020) [PubMed] [Europe PMC] [Abstract]
• positive regulation of mitochondrion organization Source: ARUK-UCL
• positive regulation of NIK/NF-kappaB signaling Source: Ensembl
• positive regulation of osteoclast differentiation Source: Ensembl
• positive regulation of peptidyl-tyrosine phosphorylation Source: BHF-UCLInferred from direct assayⁱ
  • Ref.4

    "A DAP12-mediated pathway regulates expression of CC chemokine receptor 7 and maturation of human dendritic cells."
    Bouchon A., Hernandez-Munain C., Cella M., Colonna M.
    J. Exp. Med. 194:1111-1122(2001) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, INTERACTION WITH TYROBP.
• positive regulation of phagocytosis Source: ARUK-UCLInferred from mutant phenotypeⁱ
  • "Elevated TREM2 Gene Dosage Reprograms Microglia Responsivity and Ameliorates Pathological Phenotypes in Alzheimer's Disease Models."
    Lee C.Y.D., Daggett A., Gu X., Jiang L.L., Langfelder P., Li X., Wang N., Zhao Y., Park C.S., Cooper Y., Ferando I., Mody I., Coppola G., Xu H., Yang X.W.
    Neuron 97:1032-1048.e5(2018) [PubMed] [Europe PMC] [Abstract]
• positive regulation of phagocytosis, engulfment Source: UniProtKBInferred from mutant phenotypeⁱ
  • Ref.17

    "An Alzheimer-associated TREM2 variant occurs at the ADAM cleavage site and affects shedding and phagocytic function."
    Schlepckow K., Kleinberger G., Fukumori A., Feederle R., Lichtenthaler S.F., Steiner H., Haass C.
    EMBO Mol. Med. 9:1356-1365(2017) [PubMed] [Europe PMC] [Abstract]

    Cited for: SUBCELLULAR LOCATION, PROTEOLYTIC PROCESSING, CHARACTERIZATION OF VARIANT TYR-157.
• positive regulation of phosphatidylinositol 3-kinase signaling Source: ARUK-UCL
• positive regulation of proteasomal protein catabolic process Source: ARUK-UCLInferred from sequence or structural similarityⁱ
  • Ref.22

    "TREM2 Is a Receptor for beta-Amyloid that Mediates Microglial Function."
    Zhao Y., Wu X., Li X., Jiang L.L., Gui X., Liu Y., Sun Y., Zhu B., Pina-Crespo J.C., Zhang M., Zhang N., Chen X., Bu G., An Z., Huang T.Y., Xu H.
    Neuron 97:1023-1031(2018) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, CHARACTERIZATION OF VARIANTS HIS-47 AND HIS-62.
• positive regulation of protein localization to plasma membrane Source: BHF-UCLInferred from direct assayⁱ
  • Ref.4

    "A DAP12-mediated pathway regulates expression of CC chemokine receptor 7 and maturation of human dendritic cells."
    Bouchon A., Hernandez-Munain C., Cella M., Colonna M.
    J. Exp. Med. 194:1111-1122(2001) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, INTERACTION WITH TYROBP.
• positive regulation of protein phosphorylation Source: ARUK-UCLInferred from sequence or structural similarityⁱ
  • Ref.22

    "TREM2 Is a Receptor for beta-Amyloid that Mediates Microglial Function."
    Zhao Y., Wu X., Li X., Jiang L.L., Gui X., Liu Y., Sun Y., Zhu B., Pina-Crespo J.C., Zhang M., Zhang N., Chen X., Bu G., An Z., Huang T.Y., Xu H.
    Neuron 97:1023-1031(2018) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, CHARACTERIZATION OF VARIANTS HIS-47 AND HIS-62.
• positive regulation of protein secretion Source: UniProtKBInferred from mutant phenotypeⁱ
  • "FRMD4A-cytohesin signaling modulates the cellular release of tau."
    Yan X., Nykaenen N.P., Brunello C.A., Haapasalo A., Hiltunen M., Uronen R.L., Huttunen H.J.
    J. Cell Sci. 129:2003-2015(2016) [PubMed] [Europe PMC] [Abstract]
• positive regulation of synapse pruning Source: ARUK-UCLInferred from mutant phenotypeⁱ
  • "Gene expression and functional deficits underlie TREM2-knockout microglia responses in human models of Alzheimer's disease."
    McQuade A., Kang Y.J., Hasselmann J., Jairaman A., Sotelo A., Coburn M., Shabestari S.K., Chadarevian J.P., Fote G., Tu C.H., Danhash E., Silva J., Martinez E., Cotman C., Prieto G.A., Thompson L.M., Steffan J.S., Smith I.

    , Davtyan H., Cahalan M., Cho H., Blurton-Jones M.
    Nat Commun 11:5370-5370(2020) [PubMed] [Europe PMC] [Abstract]
• positive regulation of TOR signaling Source: ARUK-UCL
• pyroptosis Source: ARUK-UCL
• regulation of cytokine production involved in inflammatory response Source: ARUK-UCL
• regulation of gene expression Source: ARUK-UCLInferred from sequence or structural similarityⁱ
  • Ref.22

    "TREM2 Is a Receptor for beta-Amyloid that Mediates Microglial Function."
    Zhao Y., Wu X., Li X., Jiang L.L., Gui X., Liu Y., Sun Y., Zhu B., Pina-Crespo J.C., Zhang M., Zhang N., Chen X., Bu G., An Z., Huang T.Y., Xu H.
    Neuron 97:1023-1031(2018) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, CHARACTERIZATION OF VARIANTS HIS-47 AND HIS-62.
• regulation of hippocampal neuron apoptotic process Source: ARUK-UCL
• regulation of innate immune response Source: ARUK-UCL
• regulation of interleukin-6 production Source: ARUK-UCLInferred from sequence or structural similarityⁱ
  • Ref.22

    "TREM2 Is a Receptor for beta-Amyloid that Mediates Microglial Function."
    Zhao Y., Wu X., Li X., Jiang L.L., Gui X., Liu Y., Sun Y., Zhu B., Pina-Crespo J.C., Zhang M., Zhang N., Chen X., Bu G., An Z., Huang T.Y., Xu H.
    Neuron 97:1023-1031(2018) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, CHARACTERIZATION OF VARIANTS HIS-47 AND HIS-62.
• regulation of intracellular signal transduction Source: ARUK-UCLInferred from sequence or structural similarityⁱ
  • Ref.22

    "TREM2 Is a Receptor for beta-Amyloid that Mediates Microglial Function."
    Zhao Y., Wu X., Li X., Jiang L.L., Gui X., Liu Y., Sun Y., Zhu B., Pina-Crespo J.C., Zhang M., Zhang N., Chen X., Bu G., An Z., Huang T.Y., Xu H.
    Neuron 97:1023-1031(2018) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, CHARACTERIZATION OF VARIANTS HIS-47 AND HIS-62.
• regulation of lipid metabolic process Source: ARUK-UCLInferred from mutant phenotypeⁱ
  • "Alzheimer's-associated PLCgamma2 is a signaling node required for both TREM2 function and the inflammatory response in human microglia."
    Andreone B.J., Przybyla L., Llapashtica C., Rana A., Davis S.S., van Lengerich B., Lin K., Shi J., Mei Y., Astarita G., Di Paolo G., Sandmann T., Monroe K.M., Lewcock J.W.
    Nat Neurosci 23:927-938(2020) [PubMed] [Europe PMC] [Abstract]
• regulation of macrophage inflammatory protein 1 alpha production Source: ARUK-UCLInferred from sequence or structural similarityⁱ
  • Ref.22

    "TREM2 Is a Receptor for beta-Amyloid that Mediates Microglial Function."
    Zhao Y., Wu X., Li X., Jiang L.L., Gui X., Liu Y., Sun Y., Zhu B., Pina-Crespo J.C., Zhang M., Zhang N., Chen X., Bu G., An Z., Huang T.Y., Xu H.
    Neuron 97:1023-1031(2018) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, CHARACTERIZATION OF VARIANTS HIS-47 AND HIS-62.
• regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway Source: ARUK-UCL
• regulation of peptidyl-tyrosine phosphorylation Source: ARUK-UCLInferred from sequence or structural similarityⁱ
  • Ref.22

    "TREM2 Is a Receptor for beta-Amyloid that Mediates Microglial Function."
    Zhao Y., Wu X., Li X., Jiang L.L., Gui X., Liu Y., Sun Y., Zhu B., Pina-Crespo J.C., Zhang M., Zhang N., Chen X., Bu G., An Z., Huang T.Y., Xu H.
    Neuron 97:1023-1031(2018) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, CHARACTERIZATION OF VARIANTS HIS-47 AND HIS-62.
• regulation of plasma membrane bounded cell projection organization Source: ARUK-UCL <p>Inferred from Genetic Interaction</p> <p>Used to describe "traditional" genetic interactions such as suppressors and synthetic lethals as well as other techniques such as functional complementation, rescue experiments, or inferences about a gene drawn from the phenotype of a mutation in a different gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#igi">GO evidence code guide</a></p> Inferred from genetic interactionⁱ
  • Ref.22

    "TREM2 Is a Receptor for beta-Amyloid that Mediates Microglial Function."
    Zhao Y., Wu X., Li X., Jiang L.L., Gui X., Liu Y., Sun Y., Zhu B., Pina-Crespo J.C., Zhang M., Zhang N., Chen X., Bu G., An Z., Huang T.Y., Xu H.
    Neuron 97:1023-1031(2018) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, CHARACTERIZATION OF VARIANTS HIS-47 AND HIS-62.
• regulation of resting membrane potential Source: ARUK-UCLInferred from sequence or structural similarityⁱ
  • Ref.22

    "TREM2 Is a Receptor for beta-Amyloid that Mediates Microglial Function."
    Zhao Y., Wu X., Li X., Jiang L.L., Gui X., Liu Y., Sun Y., Zhu B., Pina-Crespo J.C., Zhang M., Zhang N., Chen X., Bu G., An Z., Huang T.Y., Xu H.
    Neuron 97:1023-1031(2018) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, CHARACTERIZATION OF VARIANTS HIS-47 AND HIS-62.
• regulation of toll-like receptor 6 signaling pathway Source: ARUK-UCL
• regulation of TOR signaling Source: ARUK-UCL
• respiratory burst after phagocytosis Source: ARUK-UCL
• response to axon injury Source: ARUK-UCLInferred from mutant phenotypeⁱ
  • "TREM2 function impedes tau seeding in neuritic plaques."
    Leyns C.E.G., Gratuze M., Narasimhan S., Jain N., Koscal L.J., Jiang H., Manis M., Colonna M., Lee V.M.Y., Ulrich J.D., Holtzman D.M.
    Nat Neurosci 22:1217-1222(2019) [PubMed] [Europe PMC] [Abstract]
  • "Alzheimer's-associated PLCgamma2 is a signaling node required for both TREM2 function and the inflammatory response in human microglia."
    Andreone B.J., Przybyla L., Llapashtica C., Rana A., Davis S.S., van Lengerich B., Lin K., Shi J., Mei Y., Astarita G., Di Paolo G., Sandmann T., Monroe K.M., Lewcock J.W.
    Nat Neurosci 23:927-938(2020) [PubMed] [Europe PMC] [Abstract]
• response to ischemia Source: Ensembl
• social behavior Source: ARUK-UCLInferred from mutant phenotypeⁱ
  • Ref.21

    "The Microglial Innate Immune Receptor TREM2 Is Required for Synapse Elimination and Normal Brain Connectivity."
    Filipello F., Morini R., Corradini I., Zerbi V., Canzi A., Michalski B., Erreni M., Markicevic M., Starvaggi-Cucuzza C., Otero K., Piccio L., Cignarella F., Perrucci F., Tamborini M., Genua M., Rajendran L., Menna E., Vetrano S.

    , Fahnestock M., Paolicelli R.C., Matteoli M.
    Immunity 48:979-991(2018) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, TISSUE SPECIFICITY.

<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

Enzyme and pathway databases

Protein family/group databases

<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

Organism-specific databases

<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

• UniProt annotation
• GO - Cellular component

Topology

Keywords - Cellular componentⁱ

<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

Mutagenesis

Keywords - Diseaseⁱ

Organism-specific databases

Miscellaneous databases

Genetic variation databases

<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

Amino acid modifications

<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

Sites

Keywords - PTMⁱ

Proteomic databases

PTM databases

<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

Gene expression databases

Organism-specific databases

<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

<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

GO - Molecular functionⁱ

• apolipoprotein A-I binding Source: ARUK-UCLInferred from physical interactionⁱ
  • Ref.15

    "TREM2 Binds to Apolipoproteins, Including APOE and CLU/APOJ, and Thereby Facilitates Uptake of Amyloid-Beta by Microglia."
    Yeh F.L., Wang Y., Tom I., Gonzalez L.C., Sheng M.
    Neuron 91:328-340(2016) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, TISSUE SPECIFICITY, CHARACTERIZATION OF VARIANTS CYS-38; HIS-47; HIS-62; MET-66 AND ASN-87, MUTAGENESIS OF LYS-48.
• apolipoprotein binding Source: ARUK-UCLInferred from physical interactionⁱ
  • Ref.15

    "TREM2 Binds to Apolipoproteins, Including APOE and CLU/APOJ, and Thereby Facilitates Uptake of Amyloid-Beta by Microglia."
    Yeh F.L., Wang Y., Tom I., Gonzalez L.C., Sheng M.
    Neuron 91:328-340(2016) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, TISSUE SPECIFICITY, CHARACTERIZATION OF VARIANTS CYS-38; HIS-47; HIS-62; MET-66 AND ASN-87, MUTAGENESIS OF LYS-48.
• protein tyrosine kinase binding Source: ARUK-UCLInferred from sequence or structural similarityⁱ
  • Ref.22

    "TREM2 Is a Receptor for beta-Amyloid that Mediates Microglial Function."
    Zhao Y., Wu X., Li X., Jiang L.L., Gui X., Liu Y., Sun Y., Zhu B., Pina-Crespo J.C., Zhang M., Zhang N., Chen X., Bu G., An Z., Huang T.Y., Xu H.
    Neuron 97:1023-1031(2018) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, CHARACTERIZATION OF VARIANTS HIS-47 AND HIS-62.
• scaffold protein binding Source: BHF-UCLInferred from physical interactionⁱ
  • Ref.4

    "A DAP12-mediated pathway regulates expression of CC chemokine receptor 7 and maturation of human dendritic cells."
    Bouchon A., Hernandez-Munain C., Cella M., Colonna M.
    J. Exp. Med. 194:1111-1122(2001) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, INTERACTION WITH TYROBP.
• very-low-density lipoprotein particle binding Source: ARUK-UCLInferred from direct assayⁱ
  • Ref.15

    "TREM2 Binds to Apolipoproteins, Including APOE and CLU/APOJ, and Thereby Facilitates Uptake of Amyloid-Beta by Microglia."
    Yeh F.L., Wang Y., Tom I., Gonzalez L.C., Sheng M.
    Neuron 91:328-340(2016) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, TISSUE SPECIFICITY, CHARACTERIZATION OF VARIANTS CYS-38; HIS-47; HIS-62; MET-66 AND ASN-87, MUTAGENESIS OF LYS-48.

Protein-protein interaction databases

Miscellaneous databases

<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

3D structure databases

<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

Keywords - Domainⁱ

Phylogenomic databases

Family and domain databases

<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.

        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                       

        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 RAERHVKEDD GRKSPGEVPP GTSPACILAT WPPGLLVLLW 
       210 
QETTLPEHCF SWTLEAGTG                                   

        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 RPSQGSHLPS CLSKEPLGRR NPLPTHFHPS PPGLHLSHQD 
       210        220 
SSSQRPLGCS LAWTEARDTS TQ                               

<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

Natural variant