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Gene Review

Tyrobp  -  TYRO protein tyrosine kinase binding protein

Mus musculus

Synonyms: DAP12, DNAX-activation protein 12, Dap12, KAR-associated protein, KARAP, ...
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Disease relevance of Tyrobp


Psychiatry related information on Tyrobp

  • Deletions in the DAP12 gene in humans result in Nasu-Hakola disease, characterized by a combination of bone fractures and psychotic symptoms similar to schizophrenia, rapidly progressing to presenile dementia [6].

High impact information on Tyrobp


Chemical compound and disease context of Tyrobp


Biological context of Tyrobp


Anatomical context of Tyrobp

  • Natural killer (NK) cells express multiple activating receptors that initiate signaling cascades through DAP10- or immunoreceptor tyrosine-based activation motif-containing adapters, including DAP12 and FcRgamma [11].
  • Unexpectedly, DAP12-deficient macrophages produced higher concentrations of inflammatory cytokines in response to a variety of pathogenic stimuli [2].
  • DAP12 is a signaling adaptor containing an immunoreceptor tyrosine-based activation motif (ITAM) that pairs with receptors on myeloid cells and natural killer cells [2].
  • The aim of this study was to clarify the role of DAP12 signaling during osteoclast development [3].
  • In addition, we identify microglial cells and oligodendrocytes as the major Dap12/Trem2-producing cells in the CNS and, consequently, as the predominant cell types involved in PLOSL pathogenesis [12].

Associations of Tyrobp with chemical compounds

  • Ten other transcripts elevated in both mouse models are associated with macrophage functions, including complement C4, the three subunits of complement C1q, lysozyme M, cathepsins S and Z, cytochrome b558 small subunit, macrophage-specific protein 1, and DAP12 [13].

Physical interactions of Tyrobp


Regulatory relationships of Tyrobp


Other interactions of Tyrobp


Analytical, diagnostic and therapeutic context of Tyrobp


  1. Combined natural killer cell and dendritic cell functional deficiency in KARAP/DAP12 loss-of-function mutant mice. Tomasello, E., Desmoulins, P.O., Chemin, K., Guia, S., Cremer, H., Ortaldo, J., Love, P., Kaiserlian, D., Vivier, E. Immunity (2000) [Pubmed]
  2. Enhanced Toll-like receptor responses in the absence of signaling adaptor DAP12. Hamerman, J.A., Tchao, N.K., Lowell, C.A., Lanier, L.L. Nat. Immunol. (2005) [Pubmed]
  3. The signaling adapter protein DAP12 regulates multinucleation during osteoclast development. Humphrey, M.B., Ogasawara, K., Yao, W., Spusta, S.C., Daws, M.R., Lane, N.E., Lanier, L.L., Nakamura, M.C. J. Bone Miner. Res. (2004) [Pubmed]
  4. DAP12-deficient mice fail to develop autoimmunity due to impaired antigen priming. Bakker, A.B., Hoek, R.M., Cerwenka, A., Blom, B., Lucian, L., McNeil, T., Murray, R., Phillips, L.H., Sedgwick, J.D., Lanier, L.L. Immunity (2000) [Pubmed]
  5. DAP12 (KARAP) amplifies inflammation and increases mortality from endotoxemia and septic peritonitis. Turnbull, I.R., McDunn, J.E., Takai, T., Townsend, R.R., Cobb, J.P., Colonna, M. J. Exp. Med. (2005) [Pubmed]
  6. Osteopetrosis and thalamic hypomyelinosis with synaptic degeneration in DAP12-deficient mice. Kaifu, T., Nakahara, J., Inui, M., Mishima, K., Momiyama, T., Kaji, M., Sugahara, A., Koito, H., Ujike-Asai, A., Nakamura, A., Kanazawa, K., Tan-Takeuchi, K., Iwasaki, K., Yokoyama, W.M., Kudo, A., Fujiwara, M., Asou, H., Takai, T. J. Clin. Invest. (2003) [Pubmed]
  7. Toward the identification of a tolerogenic signature in IDO-competent dendritic cells. Orabona, C., Puccetti, P., Vacca, C., Bicciato, S., Luchini, A., Fallarino, F., Bianchi, R., Velardi, E., Perruccio, K., Velardi, A., Bronte, V., Fioretti, M.C., Grohmann, U. Blood (2006) [Pubmed]
  8. Clearance of apoptotic neurons without inflammation by microglial triggering receptor expressed on myeloid cells-2. Takahashi, K., Rochford, C.D., Neumann, H. J. Exp. Med. (2005) [Pubmed]
  9. A DAP12-mediated pathway regulates expression of CC chemokine receptor 7 and maturation of human dendritic cells. Bouchon, A., Hernández-Munain, C., Cella, M., Colonna, M. J. Exp. Med. (2001) [Pubmed]
  10. Plexin-A1 and its interaction with DAP12 in immune responses and bone homeostasis. Takegahara, N., Takamatsu, H., Toyofuku, T., Tsujimura, T., Okuno, T., Yukawa, K., Mizui, M., Yamamoto, M., Prasad, D.V., Suzuki, K., Ishii, M., Terai, K., Moriya, M., Nakatsuji, Y., Sakoda, S., Sato, S., Akira, S., Takeda, K., Inui, M., Takai, T., Ikawa, M., Okabe, M., Kumanogoh, A., Kikutani, H. Nat. Cell Biol. (2006) [Pubmed]
  11. Differential requirements for Vav proteins in DAP10- and ITAM-mediated NK cell cytotoxicity. Cella, M., Fujikawa, K., Tassi, I., Kim, S., Latinis, K., Nishi, S., Yokoyama, W., Colonna, M., Swat, W. J. Exp. Med. (2004) [Pubmed]
  12. Dap12 and Trem2, molecules involved in innate immunity and neurodegeneration, are co-expressed in the CNS. Kiialainen, A., Hovanes, K., Paloneva, J., Kopra, O., Peltonen, L. Neurobiol. Dis. (2005) [Pubmed]
  13. Activated microglia in cortex of mouse models of mucopolysaccharidoses I and IIIB. Ohmi, K., Greenberg, D.S., Rajavel, K.S., Ryazantsev, S., Li, H.H., Neufeld, E.F. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  14. High dose M-CSF partially rescues the Dap12-/- osteoclast phenotype. Faccio, R., Zou, W., Colaianni, G., Teitelbaum, S.L., Ross, F.P. J. Cell. Biochem. (2003) [Pubmed]
  15. Aberrant DAP12 signaling in the 129 strain of mice: implications for the analysis of gene-targeted mice. McVicar, D.W., Winkler-Pickett, R., Taylor, L.S., Makrigiannis, A., Bennett, M., Anderson, S.K., Ortaldo, J.R. J. Immunol. (2002) [Pubmed]
  16. NKG2D triggers cytotoxicity in mouse NK cells lacking DAP12 or Syk family kinases. Zompi, S., Hamerman, J.A., Ogasawara, K., Schweighoffer, E., Tybulewicz, V.L., Di Santo, J.P., Lanier, L.L., Colucci, F. Nat. Immunol. (2003) [Pubmed]
  17. T cells gene-engineered with DAP12 mediate effector function in an NKG2D-dependent and major histocompatibility complex-independent manner. Teng, M.W., Kershaw, M.H., Hayakawa, Y., Cerutti, L., Jane, S.M., Darcy, P.K., Smyth, M.J. J. Biol. Chem. (2005) [Pubmed]
  18. The immunomodulatory adapter proteins DAP12 and Fc receptor gamma-chain (FcRgamma) regulate development of functional osteoclasts through the Syk tyrosine kinase. Mócsai, A., Humphrey, M.B., Van Ziffle, J.A., Hu, Y., Burghardt, A., Spusta, S.C., Majumdar, S., Lanier, L.L., Lowell, C.A., Nakamura, M.C. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  19. IL-4 confers NK stimulatory capacity to murine dendritic cells: a signaling pathway involving KARAP/DAP12-triggering receptor expressed on myeloid cell 2 molecules. Terme, M., Tomasello, E., Maruyama, K., Crépineau, F., Chaput, N., Flament, C., Marolleau, J.P., Angevin, E., Wagner, E.F., Salomon, B., Lemonnier, F.A., Wakasugi, H., Colonna, M., Vivier, E., Zitvogel, L. J. Immunol. (2004) [Pubmed]
  20. Characterization of the CD200 receptor family in mice and humans and their interactions with CD200. Wright, G.J., Cherwinski, H., Foster-Cuevas, M., Brooke, G., Puklavec, M.J., Bigler, M., Song, Y., Jenmalm, M., Gorman, D., McClanahan, T., Liu, M.R., Brown, M.H., Sedgwick, J.D., Phillips, J.H., Barclay, A.N. J. Immunol. (2003) [Pubmed]
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