The fish-specific domain upstream of the NACHT domain. (a) Alignment of a representative subset of the Fisna domain (the region upstream of the NACHT domain that is shared by all of the novel fish NLR proteins. The group names on the right refer to the subdivision of the Danio rerio groups according to similarities in the NACHT-domain and the Fisna domain (also see Figure 15) or indicate which species form the group. Peptide motifs with similarity to Nod2 and Nod3 are underlined. (b) Hidden Markov model (HMM) logo representing the consensus sequence of the Fisna domain in all three fish species. The logo has been generated using the software HMMER [58,59] and visualized using the HMM-Logo web server [60,61]. Peptide sequences from human Nod2 and Nod3 with similarity to short stretches of the Fisna consensus, color coded to highlight conserved residues, are listed underneath, as are stretches from the regions upstream of the NACHT domain present in 140 sea urchin NLR proteins. NLR, nucleotide-binding domain/NACHT domain and leucine rich repeat containing family; Nod, nucleotide oligomerization domain containing protein.