Fig. 1.

Simplified reference TLR signaling pathway projected onto putative homologs in Trichoplax sp. H2. True Toll-like receptors are absent but many components of the downstream signaling cascade are present. Support for the presence and homologous function of pathway components is indicated by filled boxes and superscript letters, where 1: is supported by domain composition, 2: is supported by KEGG annotation, 3: is supported by two of either EggNOG OG, OrthoMCL OG or best Swiss-Prot hit, 4: is supported by phylogenetic validation. Uncertainty regarding homology because of missing domains is indicated by a red outline. For example, Trichoplax possesses several IRAK-like genes but all are lacking the DD of true IRAK genes. In the case of the identified NF-κB-like protein, an RHD and ANK repeats are present but a DD is absent. Question marks denote unknown down- or upstream signaling components: Since true Toll-like receptors are absent and a bipartite receptor (extracellular LRR, intracellular TIR/SEFIR) is hypothetical, the recognition part in TLR signaling remains speculative. Similarly, some of the identified TIR domain containing (TIR-DC) proteins may function in TLR signaling as alternative adaptor molecules, but their upstream input as well as their targets have yet to be identified. The function of the missing IκBα ortholog may be fulfilled by other placozoan ANK containing proteins. The MyD88-independent pathway has been omitted since it is assumed to have emerged in chordates. See also Additional files 1, 2 and 3