Human interleukin-36 receptor antagonist IL-36Ra; previously IL-1F5 and also named FIL-1δ (delta), IL- 1HY1, IL- 1H3, and IL-1L1 is a member of the IL- 1 family of proteins. IL- 1 family members include IL-1 beta, IL-1 alpha, IL-1ra, IL- 18 and IL-1F5-F10. All family members show a 12 beta -strand, beta -trefoil configuration, and all family members are believed to have
arisen from a common ancestral gene that underwent multiple duplications . The human IL- 36Ra/IL- 1F5 gene is in closest proximity to the gene for IL-1ra and is likely a relatively recent duplication of the IL-1ra gene. IL-36Ra/IL-1F5 is synthesized as a 155 amino acid (aa) protein that contains no signal sequence, no prosegment and no potential N-linked glycosylation site(s). Nevertheless, it appears to be secreted as a 17 kDa monomer. There is an alternate start site that potentially gives rise to an alternate splice form. The
translated product, however, has a premature stop codon, resulting in a truncated 16 aa peptide. Human to mouse, full length IL-1F5 has 90% aa identity. Within the family, IL-36Ra/IL-1F5 is 50% aa identical to IL-1ra, and 32%, 31%, 35%, 37%, 32% and 42% aa identical to IL-1 beta, IL-36 alpha /IL- 1F6, IL- 37/IL- 1F7, IL- 36 beta /IL- 1F8, IL- 36 gamma /IL- 1F9 and IL- 1F10, respectively. Cells reported to expressIL- 36Ra/IL- 1F5 include monocytes, B cells, dendritic cells/Langerhans cells, keratinocytes, and gastric fundus Parietal and Chief cells. The receptor for IL-36Ra/IL-1F5 has not been positively identified. Indirect evidence suggests it is IL-1 Rrp2 and/or IL-1 RAcP. In either case, activity association with receptor binding is also unclear. It was initially reported to be an antagonist of IL- 36 gamma /IL- 1F9 activity. This would be consistent with its hypothesized relationship to IL- 1ra. Studies, however, find IL-36Ra/IL-1F5 antagonist activity difficult to demonstrate.
