TIR

Toll - interleukin 1 - resistance
TIR
SMART accession number:SM00255
Description:
Interpro abstract (IPR000157):

In Drosophila melanogaster the Toll protein is involved in establishment of dorso-ventral polarity in the embryo. In addition, members of the Toll family play a key role in innate antibacterial and antifungal immunity in insects as well as in mammals. These proteins are type-I transmembrane receptors that share an intracellular 200 residue domain with the interleukin-1 receptor (IL-1R), the Toll/IL-1R homologous region (TIR). The similarity between Toll-like receptors (LTRs) and IL-1R is not restricted to sequence homology since these proteins also share a similar signalling pathway. They both induce the activation of a Rel type transcription factor via an adaptor protein and a protein kinase [(PUBMED:8621445)]. Interestingly, MyD88, a cytoplasmic adaptor protein found in mammals, contains a TIR domain associated to a DEATH domain (see IPR000488) [(PUBMED:8621445), (PUBMED:9374458), (PUBMED:10679407)]. Besides the mammalian and Drosophila melanogaster proteins, a TIR domain is also found in a number of plant proteins implicated in host defence [(PUBMED:9868361)]. As MyD88, these proteins are cytoplasmic.

Site directed mutagenesis and deletion analysis have shown that the TIR domain is essential for Toll and IL-1R activities. Sequence analysis have revealed the presence of three highly conserved regions among the different members of the family: box 1 (FDAFISY), box 2 (GYKLC-RD-PG), and box 3 (a conserved W surrounded by basic residues). It has been proposed that boxes 1 and 2 are involved in the binding of proteins involved in signalling, whereas box 3 is primarily involved in directing localization of receptor, perhaps through interactions with cytoskeletal elements [(PUBMED:10671496)].

GO process:signal transduction (GO:0007165)
GO component:intracellular (GO:0005622)
GO function:protein binding (GO:0005515)
Family alignment:
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There are 1622 TIR domains in 1557 proteins in SMART's nrdb database.

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