Toll-like receptor (IPR017241)

Short name: Toll-like_receptor

Family relationships


This entry represents toll-like receptors (TLRs), which are key regulators of immune responses. They recognise pathogen-associated molecular patterns (PAMPs) such as bacterial lipopeptides (TLR1/2/6), bacterial flagellin (TLR5), and lipopolysaccharide (TLR4) [PMID: 16675322]. In higher vertebrates, TLRs are essential not only for sensing microbes by the innate immune system, but also for inducing adaptive immune system responses mediated by B and T cells [PMID: 9039775].

TLRs are expressed at the cell membrane and in subcellular compartments such as the endosome. TLRs are type-I transmembrane proteins with extracellular leucine-rich repeat (LRR) motifs and an intracellular Toll/interleukin-1 receptor (TIR) domain. Members of the TLR family contribute both to cell-cell interactions and to signalling, linking extracellular signals to specific gene-expression programmes [PMID: 18227810, PMID: 16822173]. Binding of ligands to the extracellular domains causes rearrangement of the receptor complexes and triggers the recruitment of specific adaptor proteins to the intracellular TIR domain, leading to nuclear factor-kappa B (NF-kappaB) activation and initiation of both innate and adaptive immune responses. Signalling by TLRs involves five adaptor proteins known as MyD88, MAL, TRIF, TRAM and SARM [PMID: 17457343].

TLRs form homodimers or heterodimers induced by the binding of ligands to residues in the LRRs of distinct receptor chains. In mice and humans combined there are 13 paralogous TLRs; 10 in humans and 12 in mice. TLR10 is only present in humans, and TLR11-13 are only present in mice [PMID: 21741580]. This entry represents some toll-like receptors, which includes TLR1, TLR2, TLR4, TLR6 and TLR10.

In Drosophila, the Toll receptor plays a role in development as well as immunity [PMID: 12888789, PMID: 11135568]. Toll is a component of the extracellular signaling pathway that establishes the dorsal-ventral pathway of the embryo [PMID: 2449285]. Three proteases; ndl, gd and snk process easter to create active easter. Active easter defines cell identities along the dorsal-ventral continuum by activating the Spz ligand for the Tl receptor in the ventral region of the embryo [PMID: 12872120]. Toll promotes heterophilic cellular adhesion [PMID: 2124970]. The Drosophila Toll receptor is essential in initiating innate immune defenses to fungi and Gram-positive bacteria in adult flies [PMID: 12888789]. Spz C-106 in the hemolymph controls expression of the antifungal peptide Drosomycin (Drs) by acting as a ligand of Tl and inducing an intracellular signaling pathway [PMID: 8808632].

GO terms

Biological Process

GO:0006955 immune response
GO:0002224 toll-like receptor signaling pathway

Molecular Function

GO:0004888 transmembrane signaling receptor activity

Cellular Component

GO:0016021 integral component of membrane

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.