Domain

Toll/interleukin-1 receptor homology (TIR) domain (IPR000157)

Short name: TIR_dom

Domain relationships

None.

Description

Toll proteins or Toll-like receptors (TLRs) and the interleukin-1 receptor (IL-1R) superfamily are both involved in innate antibacterial and antifungal immunity in insects as well as in mammals. These receptors share a conserved cytoplasmic domain of approximately 200 amino acids, known as the Toll/IL-1R homologous region (TIR). The similarity between TLRs and IL-1Rs is not restricted to sequence homology since these proteins also share a similar signaling pathway. They both induce the activation of a Rel type transcription factor via an adaptor protein and a protein kinase [PMID: 10231569]. Interestingly, MyD88, a cytoplasmic adaptor protein found in mammals, contains a TIR domain associated to a DEATH domain [PMID: 8621445, PMID: 9374458, PMID: 10679407]. Besides the mammalian and Drosophila proteins, a TIR domain is also found in a number of plant cytoplasmic proteins implicated in host defense [Van der Biezen E.A., Jones J.D., Trends Biochem. Sci. 23:454-456(1998)].

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 [PMID: 10671496].

Resolution of the crystal structures of the TIR domains of human Toll-like receptors 1 and 2 has shown that they contain a central five-stranded parallel beta-sheet that is surrounded by a total of five helices on both sides [PMID: 11081518].

GO terms

Biological Process

GO:0007165 signal transduction

Molecular Function

GO:0005515 protein binding

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
Pfam
Pfam
PROSITE profiles
SMART