KARAP/DAP12/TYROBP: three names and a multiplicity of biological functions

Eur J Immunol. 2005 Jun;35(6):1670-7. doi: 10.1002/eji.200425932.


The signaling adaptor protein KARAP/DAP12/TYROBP (killer cell activating receptor-associated protein / DNAX activating protein of 12 kDa / tyrosine kinase binding protein) belongs to the family of transmembrane polypeptides bearing an intracytoplasmic immunoreceptor tyrosine-based activation motif (ITAM). This adaptor, initially characterized in NK cells, is associated with multiple cell-surface activating receptors expressed in both lymphoid and myeloid lineages. We review here the main features of KARAP/DAP12, describing findings from its identification to recently published data, showing its involvement in a broad array of biological functions. KARAP/DAP12 is a wiring component for NK cell anti-viral function (e.g. mouse cytomegalovirus via its association with mouse Ly49H) and NK cell anti-tumoral function (e.g. via its association with mouse NKG2D or human NKp44). KARAP/DAP12 is also involved in inflammatory reactions via its coupling to myeloid receptors, such as the triggering receptors expressed by myeloid cells (TREM) displayed by neutrophils, monocytes/macrophages and dendritic cells. Finally, bone remodeling and brain function are also dependent upon the integrity of KARAP/DAP12 signals, as shown by the analysis of KARAP/DAP12-deficient mice and KARAP/DAP12-deficient Nasu-Hakola patients.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Animals
  • Bone Remodeling
  • Brain / pathology
  • Cell Lineage
  • Dendritic Cells / physiology
  • Humans
  • Killer Cells, Natural / physiology
  • Mast Cells / physiology
  • Membrane Proteins
  • Molecular Sequence Data
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / physiology*


  • Adaptor Proteins, Signal Transducing
  • Membrane Proteins
  • Receptors, Immunologic
  • TYROBP protein, human