Fig. 8

Orthologous components of the TLR signaling cascade in Aplysia californica and other animals. Immune genes of interest were extracted from a custom InterProScan annotation of the Aplysia californcia RefSeq predicted protein models (AplCal, GCF_000002075.1) and publicly available InterPro annotations of proteins from the UniprotKB data base for Biomphalaria glabrata (Bglab, UP000076420_IPS), Crassosteraea gigas (Cgig, UP000005408), Nematostella vectensis (Nvect, UP000001593), Drosophila melanogaster (Dromel, UP000000803), Strongylocentrotus purpuratus (Spurp, UP000007110), and human (Hs, UP000005640) based on InterPro domains detailed in supplementary data Supplemental File SFile5. Results were further refined using sequence similarity search among listed proteomes and predicted protein models using OrthoFinder and BLASTP. Columns of the table represent a single species, while rows represent proteins known to play key roles in TLR signaling in mammals. Proteins are grouped according to their functional roles in TLR signaling: TLR receptors, Adapter proteins like MyD88, E3 Ubiquitin ligases, Kinase signaling complexes and components, and Transcription factors and associated proteins. Numbers in each cell represent the number of protein hits to each protein type, and thus differ from gene level numbers present in the main text. Note that hits are to Uniprot KB proteomes and as such differ from previously reported numbers for C. gigas and S. purpuratus which used predicted gene models. Aplysia protein numbers for major components are broadly similar to other animals, although TLRs appear to be highly diversified compared to mammals and arthropods, but still fewer in number than in S. purpuratus and previously reported numbers for C. gigas (83 genes vs the 18 identified proteins with out methods in Uniprot KB). Similarly, TLR/Interleukin-1 receptor domain (TIR) containing adapters are much more diverse in Aplysia compared to human, but again less diverse than that of S. purpuratus and C. gigas. Toll-like receptor (TLR); Myeloid differentiation primary response protein (MyD88); NAD(+) hydrolase SARM1 (SARM); TIR domain-containing adapter molecule 1 (TRIF/TICAM1); TIR domain-containing adapter molecule 2 (TRAM/TICAM2); Toll/interleukin-1 receptor domain-containing adapter protein (TIRAP/Mal); Armadillo fold and TIR domain containing proteins (ARM-TIR); Epidermal growth factor and TIR domain containing proteins (EGF-TIR); Imunoglobulin and TIR domain containing proteins (IG-TIR); Orphan TIR proteins (OrTIR); Evolutionarily conserved signaling intermediate in Toll pathway (ECSIT); Toll-interacting protein (TOLLIP); TNF receptor-associated factors (TRAF); E3 ubiquitin ligase Pellino (Pellino); E3 ubiquitin-protein ligase RNF31 (HOIP); RanBP-type and C3HC4-type zinc finger-containing protein 1 RBCK1 (HOIL1); Sharpin (SHARPIN); Interleukin-1 receptor-associated kinase 1 (IRAK); TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 (TAB1); TGF-beta-activated kinase 1 and MAP3K7-binding protein 2/3 (TAB2/3); MAP3K7/TGF-beta-activated kinase 1 (TAK1); Inhibitor of nuclear factor kappa-B kinase subunit alpha (IKK); NF-kappa-B essential modulator (IKKg/NEMO); p38 MAPK/ MAPK14 (p38); Mitogen-activated protein kinase 8 (JNK); Inhibitor of NFkB (IkB); Major Vault Protein (MVP); Nuclear factor kB (NFkB); Activating protein 1 family (AP-1); Activating protein 1 JUN (JUN)