Open AccessInterleukin 1 receptor antagonist is a member of the interleukin 1 gene family: evolution of a cytokine control mechanism.
Author(s) -
Stephen P. Eisenberg,
Michael K. Brewer,
Evie L. Verderber,
P Heimdal,
Barbara J. Brandhuber,
Robert C. Thompson
Publication year - 1991
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.88.12.5232
Subject(s) - interleukin 12 receptor, beta 1 subunit , interleukin 1 receptor antagonist , gene , biology , gene duplication , interleukin 1 receptor, type i , genetics , exon , gene family , receptor antagonist , interleukin 1 receptor, type ii , interleukin 10 receptor, alpha subunit , alpha (finance) , microbiology and biotechnology , interleukin 21 receptor , receptor , interleukin , cytokine , gene expression , antagonist , interleukin 5 , g alpha subunit , protein subunit , medicine , construct validity , nursing , patient satisfaction
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.