The SEFIR domain (after SEFs and IL17Rs) is a conserved sequence segmentidentified in transmembrane receptors (including SEFs, IL17Rs) and solublefactors (including CIKS/ACT1) in eukaryotes and bacteria. In addition to theSEFIR sequence homology, SEFs and IL17Rs share the same architecture. Theirextracellular regions are sequentially divergent but appear structurallysimilar to a tandem fibronectin 3 (FN3)-like domain arrangement. A singletransmembrane region is followed by a high-complexity sequence regioninvolving the SEFIR domain and a C-terminal tail that is enriched with polarresidues and, sometimes, with low complexity regions [].The SEFIR domain is related to the TIR domain. The SEFIRdomain is similar to the TIR domain in length and secondary structure. Thesimilarity between the SEFIR and TIR domains involves the conserved boxes 1and 2 of the TIR domain that are implicated in homotypic dimerization, butthere is no sequence similarity between SEFIR domains and the TIR sequence box3 [].Proteins containing this domain also includes TRAF3IP2 from humans. TRAF3IP2 is a U-box E3 ubiquitin ligase for IL-17 signaling []. A mutation (T536I) located in the SEFIR domain, abolished the homotypic interaction of ACT1 with IL-17 receptors, with no effect on homodimerization [].
