TYRO protein tyrosine kinase binding protein (TYROBP)

TYRO protein tyrosine kinase binding protein (TYROBP), also known as DAP12, is a transmembrane adapter protein encoded by the TYROBP gene on human chromosome 19. It contains an immunoreceptor tyrosine-based activation motif (ITAM) in its cytoplasmic domain and serves as a crucial signaling adapter in various immune cell types including natural killer cells, neutrophils, monocytes, dendritic cells, and microglia. TYROBP non-covalently associates with multiple activating receptors, including members of the killer cell immunoglobulin-like receptor (KIR) family, TREM2, TREM1, CD300 family receptors, and others. Upon receptor engagement, TYROBP becomes tyrosine-phosphorylated, recruiting kinases like SYK and ZAP-70 to propagate activation signals. Beyond immune function, TYROBP plays important roles in bone modeling through osteoclast regulation and brain development through myelination. Pathological mutations in TYROBP cause polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL or Nasu-Hakola disease), a rare autosomal recessive disorder characterized by early-onset dementia and bone cysts. The protein's partnership with TREM2 has drawn particular attention in neurodegenerative disease research, as both proteins are implicated in microglial function and neuroinflammation.

Other names

DAP12 (DNAX-Activation Protein 12)KARAP (Killer-Activating Receptor-Associated Protein)Transmembrane Immune Signaling Adaptor TYROBPKiller cell activating receptor associated protein

TYROBP functions through non-covalent association with activating receptors on immune cell surfaces. Upon ligand binding to associated receptors, TYROBP undergoes tyrosine phosphorylation in its ITAM domain, which then recruits and activates tyrosine kinases such as ZAP-70 and SYK, leading to downstream cell activation and immune responses.