Toll - interleukin 1 - resistance
ショウジョウバエで、Tollタンパク質は発生（dorso-ventral polarity）に重要な役割をもつ。加えて、Tollファミリーのタンパク質は細菌や真菌に対する自然免疫に中心的な役割を果たす。1型の膜貫通受容体で、細胞内の200アミノ酸残基（Toll/IL-1R homologous region; TIR）はインターロイキン1受容体と相同性がある。
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).
Toll様受容体（TLRs）とIL-1Rの類似点はアミノ酸配列の相同性のみならず、シグナル伝達経路も共有している。どちらもRelタイプの転写因子をアダプタータンパク質とタンパク質キナーゼを介して活性化する。興味深いことに、哺乳動物にみられる細胞質に存在するアダプタータンパク質のMyD88はTIRドメインをもっておりDEATHドメインと相互作用する。哺乳動物、ショウジョウバエに加えて、TIRドメインは植物でも宿主の防御機構として含まれている。MyD88と同様にこれらは細胞質に局在する。
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)].
http://smart.embl-heidelberg.de/smart/do_annotation.pl?DOMAIN=TIR&BLAST=DUMMY
