title: Identification and characterization of SIGIRR, a molecule representing a novel subtype of the IL-1R superfamily.
abstract: 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.
authors.affiliation: Immunex Corporation, Seattle, WA 98101, USA.
authors.forename: E
authors.initials: E
authors.lastname: Thomassen
authors.forename: B R
authors.initials: BR
authors.lastname: Renshaw
authors.forename: J E
authors.initials: JE
authors.lastname: Sims
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000937:Antigen-Antibody Reactions; D015153:Blotting, Western; D002460:Cell Line; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D012333:RNA, Messenger / Q000096:biosynthesis; D017472:Receptors, Interleukin-1 / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology
chemical_list: D007136:Immunoglobulins; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1