Evolution of the IL17 receptor family in chordates: a new subfamily IL17REL

Abstract

The human interleukin 17 receptor (IL17R) family plays a critical role in inflammatory responses and contributes to the pathology of many autoimmune diseases. So far, five members, IL17RA to IL17RE, have been identified. Recently, some IL17R genes have been identified in non-mammalian species, such as zebrafish IL17RD; however, there are no reports on the evolutionary history of this complex gene family through comparative phylogenetic approaches. Here, we concentrated on the IL17R evolution in chordates. There are two IL17Rs in the genome of the basal chordate amphioxus: IL17RA and IL17RD. After two rounds of whole genome duplications, these two IL17R genes expanded into five early vertebrate IL17R genes, IL17RA to IL17RE. IL17RA and IL17RD are found in most vertebrates, whereas the other three, IL17RB, ILR17RC, and IL17RE, underwent some loss in vertebrates during evolution. Our sequence and structure analyses reveal functional similarities and distinctions between the different IL17Rs. Based on similarity searches for IL17R-like proteins within chordate sequences, a group of IL17RE-like (IL17REL) proteins were identified from mammalians to lower vertebrates. In silico and expression analyses on the novel IL17RELs showed that this group of receptors is highly conserved across species, indicating that IL17REL may represent a unique subfamily of IL17Rs.

Cloning and Characterization of Rainbow Trout Interleukin-17A/F2 (IL-17A/F2) and IL-17 Receptor A: Expression during Infection and Bioactivity of Recombinant IL-17A/F2

“…According to analysis of the phylogenetic relationship between the various IL-17R protein family members, trout IL-17RA clustered with the other piscine and homeotherm IL-17RA molecules. Multiple alignment of this protein sequence with those of other vertebrate IL-17RA molecules revealed a high degree of conservation within the extracellular and intracellular SEFIR domains, which are characteristic of the IL-17RA family (18,24,25). Several conserved cysteines, eight of which are potentially involved in disulfide bridge formation, as seen in mammalian molecules (64), were also present in trout IL-17RA.…”

“…Several conserved cysteines, eight of which are potentially involved in disulfide bridge formation, as seen in mammalian molecules (64), were also present in trout IL-17RA. Two putative FNIII domains which are known to be crucial in the binding of the ligand to its receptor (25) were also identified within the extracellular domain of trout IL-17RA.…”

“…Members of the IL-17R family include five molecules (IL-17RA to E) known to possess particular features not present in other receptor families (1,24). Most recently, a new member of this family (IL-17RE-like, or IL-17REL) has also been characterized (25). IL-17 cytokines mediate intracellular signaling through activation of the adaptor protein ACT1, tumor necrosis factor (TNF) receptor-associated factor (TRAF)-6, and transcription nuclear factor (NF)-B (7,24).…”

Evolution of prokaryotic homologues of the eukaryotic SEFIR protein domain

“…In 2003, a SEFIR protein was observed in bacterium Staphylococcus hominis (Novatchkova et al, 2003), and later, we found that SEFIR proteins are widely distributed in metazoans (Wu et al, 2011a(Wu et al, , 2011b. Nevertheless, little information about the prokaryotic SEFIR homologues has been reported so far.…”

“…However, it is unknown whether the sequences of the signal peptides were cleaved or the proteins do not possess a signal peptide inherently. Chordate CIKSs and IL17Rs contain two TRAF (tumor necrosis factor receptor-associated factor) binding sites: TRAF2 and TRAF6 binding sites (Gaffen, 2009;Li, 2008;Wu et al, 2011aWu et al, , 2011b. TRAF binding sites are also present in prokaryotic SEFIR proteins.…”