Identification and characterization of SIGIRR, a molecule representing a novel subtype of the IL-1R superfamily

A novel member of the interleukin 1 receptor (IL-1R) superfamily, SIGIRR (s ingle Ig IL-1R-related molecule) was identified in mouse and human. Althoug h it shows the typical conserved motifs that characterize the IL-1R and Tol l superfamily, it is structurally and functionally distinct from both. SIGI RR has only one Ig domain in its extracellular portion whereas the IL-1R fa mily contains three Ig folds, An unusually long cytoplasmic domain is remin iscent 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 a nd 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 I L-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 kappa B (NF kappa B) activation, A chimera, in which the SIGIRR intracellular domain was fused t o the IL-1R extracellular domain, did not activate NF kappa B unlike simila r fusion proteins of other IL-1R related molecules. We conclude that the SI GIRR protein represents a novel subtype of the IL-1R superfamily, (C) 1999 Academic Press.