A novel member of the interleukin 1 receptor (IL-1R) superfamily, SIGIRR (single Ig IL-1R-related molecule) was identified in mouse and human. Although it shows the typical conserved motifs that characterize the IL-1R and Toll superfamily, it is structurally and functionally distinct from both. SIGIRR has only one Ig domain in its extracellular portion whereas the IL-1R family contains three Ig folds. An unusually long cytoplasmic domain is reminiscent of the structure of drosophila Toll, yet the SIGIRR peptide sequence is more closely related to IL-1RI. The human SIGIRR gene maps to 11p15. 5 and thus is not located in the same cluster on chromosome 2 that is known to contain four members of the IL-1R family. It failed to bind to the known IL-1-family members and, when co-expressed with the IL-1RI, had no effect on the binding of IL-1 and on subsequent nuclear factor kappaB (NFkappaB) activation. A chimera, in which the SIGIRR intracellular domain was fused to the IL-1R extracellular domain, did not activate NFkappaB unlike similar fusion proteins of other IL-1R related molecules. We conclude that the SIGIRR protein represents a novel subtype of the IL-1R superfamily.
Copyright 1999 Academic Press.