Evolution of prokaryotic homologues of the eukaryotic SEFIR protein domain

Abstract SEF/IL17 receptor (SEFIR) domains are mainly found in IL17 receptors (IL17Rs) and their adaptor proteins CIKS (connection to IKK and SAPK/JNK), which exert a host defense role in numbers of infectious diseases and promote inflammatory pathology in autoimmunity. Exploring the evolutionary pathway of SEFIR domains will provide further insight into their functions. Here, we have identified 84 SEFIR domain-containing proteins from more than 1400 prokaryotic genomes. As most SEFIR domain-containing bacterial genomes possess a single SEFIR encoding gene and the SEFIR protein domain forms homodimeric complexes like the Toll/IL1 receptor (TIR) domain, the single bacterial SEFIR proteins may receive binding partners from other organisms. Through comparative and phylogenetic sequence analyses, we show that bacterial SEFIR domain is more similar to that of vertebrate CIKS than IL17R, and it possibly emerges via a lateral gene transfer (LGT) from animals. In addition, our secondary and three-dimensional structural predictions of SEFIR domains reveal that human and pathogenic bacterial SEFIR domains share similar structural and electrostatic features. Our findings provide important clues for further experimental researches on determining the functions of SEFIR proteins in pathogenic prokaryotes.