The Toll-like receptor (TLR) family in mammals comprises a family of transmembrane proteins characterized by multiple copies of leucine rich repeats in the extracellular domain and IL-1 receptor motif in the cytoplasmic domain. Like its counterparts in Drosophila, TLRs signal through adaptor molecules. The TLR family is a phylogenetically conserved mediator of innate immunity that is essential for microbial recognition. Ten human homologs of TLRs (TLR1-10) have been described. TIRAP (TIR domain-containing adaptor protein) is an adaptor protein used by TLR4. Blocking TIRAP inhibits TLR4-mediated signaling events, including DC maturation and cytokine production.
Function: Adapter involved in TLR2 and TLR4 signaling pathways in the innate immune response. Acts via IRAK2 and TRAF-6, leading to the activation of NF-kappa-B, MAPK1, MAPK3 and JNK, and resulting in cytokine secretion and the inflammatory response. Positively regulates the production of TNF-alpha and interleukin-6.
Tissue specificity: Highly expressed in liver, kidney, spleen, skeletal muscle and heart. Also detected in peripheral blood leukocytes, lung, placenta, small intestine, thymus, colon and brain.
Post-translational modification: Phosphorylated by IRAK1 and IRAK4. Also phosphorylated by BTK.
Sequence similarities: Contains 1 TIR domain.