Toll Interleukin 1 Receptor Domain Containing Adaptor Protein (TIRAP)

TIRAP is a TIR adaptor protein involved in the TLR4 signaling pathway of the immune system. It activates NF-kappa-B, MAPK1, MAPK3 and JNK, which then results in cytokine secretion and the inflammatory response. Alternative splicing of this gene results in several transcript variants; however, not all variants have been fully described. MAL, unlike MYD88, does not interact with IRAK1  and is not inhibited by the dominant-negative N-terminal region of IRAK1; however, like MYD88, MAL does, through its TIR domain, interact with and is inhibited in NFKB activation by the dominant-negative form of IRAK2. A dominant-negative form of MAL inhibits TLR4 or lipopolysaccharide activation of NFKB, but not NFKB activation by IL1R1 or IL18R. Immunoprecipitation analysis showed that TLR4 and MAL are constitutively associated.