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.
Subunit:
Homodimer. Also forms heterodimers with MyD88. Binds to TLR4 and IRAK2 via their respective TIR domains. Binds to BMX, PKR and TBK1. Does not interact with IRAK1, nor TLR9.
Subcellular Location:
Cytoplasm.
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 modifications:
Phosphorylated by IRAK1 and IRAK4. Also phosphorylated by BTK.
Polyubiquitinated. Polyubiquitination follows phosphorylation by BTK and leads to TIRAP degradation.
Similarity:
Contains 1 TIR domain.
SWISS:
P58753
Gene ID:
11929
Database links:
Entrez Gene: 11929 Human
Entrez Gene: 117149 Mouse
Entrez Gene: 136127 Rat
GenBank: AF378129 Human
GenBank: AF378130 Human
Omim: 606252 Human
SwissProt: P58753 Human
SwissProt: Q99JY1 Mouse
Unigene: 537126 Human
Unigene: 23987 Mouse
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