title: Interleukin 1 receptor antagonist is a member of the interleukin 1 gene family: evolution of a cytokine control mechanism.
abstract: Interleukin 1 receptor antagonist (IL-1ra) is a protein that binds to the IL-1 receptor and blocks the binding of both IL-1 alpha and -beta without inducing a signal of its own. Human IL-1ra has some sequence identity to human IL-1 beta, but the evolutionary relationship between these proteins has been unclear. We show that the genes for human, mouse, and rat IL-1ra are similar to the genes for IL-1 alpha and IL-1 beta in intron-exon organization, indicating that gene duplication events were important in the creation of this gene family. Furthermore, an analysis of sequence comparisons and mutation rates for IL-1 alpha, IL-1 beta, and IL-1ra suggests that the duplication giving rise to the IL-1ra gene was an early event in the evolution of the gene family. Comparisons between the mature sequences for IL-1ra, IL-1 alpha, and IL-1 beta suggest that IL-1ra has a beta-stranded structure like to IL-1 alpha and IL-1 beta, consistent with the three proteins being related. The N-terminal sequences of IL-1ra appear to be derived from a region of the genome different than those of IL-1 alpha and IL-1 beta, thus explaining their different modes of biosynthesis and suggesting an explanation for their different biological activities.
authors.affiliation: Synergen, Boulder, CO 80301.
authors.forename: S P
authors.initials: SP
authors.lastname: Eisenberg
authors.forename: M T
authors.initials: MT
authors.lastname: Brewer
authors.forename: E
authors.initials: E
authors.lastname: Verderber
authors.forename: P
authors.initials: P
authors.lastname: Heimdal
authors.forename: B J
authors.initials: BJ
authors.lastname: Brandhuber
authors.forename: R C
authors.initials: RC
authors.lastname: Thompson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics* / Q000378:metabolism; D007438:Introns; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D009154:Mutation; D051381:Rats; D011919:Rats, Inbred Strains; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D017472:Receptors, Interleukin-1; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid
chemical_list: D007375:Interleukin-1; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1