TIRAP: an adapter protein involved in the TLR4 signaling pathway in the innate immune response. Acts via IRAK2 and TRAF-6, leading to the activation of NF-kappa-B, ERK1, ERK2 and JNK, resulting in cytokine secretion and the inflammatory response. Homodimerizes. Also forms heterodimers with MyD88. Binds to TLR4 and IRAK2 via their respective TIR domains. Binds to PKR and TBK1. Does not interact with IRAK1, nor TLR9. Genetic variations in TIRAP can influence susceptibility or resistance to infectious diseases, including invasive pneumococcal disease, malaria and tuberculosis. Three isoforms of the human protein are produced by alternative splicing.
Protein type: Adaptor/scaffold
Chromosomal Location of Human Ortholog: 11q24.2
Cellular Component: cytoplasm; cytosol; endocytic vesicle; intercellular bridge; nucleoplasm; plasma membrane
Molecular Function: phosphatidylinositol-4,5-bisphosphate binding; protein binding; protein binding, bridging; protein heterodimerization activity; protein homodimerization activity; protein kinase C binding
Biological Process: activation of NF-kappaB transcription factor; cell surface receptor linked signal transduction; defense response to Gram-positive bacterium; inflammatory response; innate immune response; MyD88-dependent toll-like receptor signaling pathway; myeloid cell differentiation; positive regulation of B cell proliferation; positive regulation of I-kappaB kinase/NF-kappaB cascade; positive regulation of interleukin-12 production; positive regulation of interleukin-15 production; positive regulation of interleukin-6 biosynthetic process; positive regulation of interleukin-8 production; positive regulation of JNK cascade; positive regulation of toll-like receptor 2 signaling pathway; positive regulation of toll-like receptor 3 signaling pathway; positive regulation of toll-like receptor 4 signaling pathway; positive regulation of tumor necrosis factor production; regulation of innate immune response; regulation of interferon-beta production; response to lipopolysaccharide; toll-like receptor 2 signaling pathway; toll-like receptor 4 signaling pathway; toll-like receptor signaling pathway
Disease: Bacteremia, Susceptibility To, 1; Invasive Pneumococcal Disease, Recurrent Isolated, 1; Malaria, Susceptibility To; Mycobacterium Tuberculosis, Susceptibility To
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