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PMID: 1828896 Published · ppublish English Journal Article

Interleukin 1 receptor antagonist is a member of the interleukin 1 gene family: evolution of a cytokine control mechanism.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 88 ·No. 12 ·1991-06-15 ·Pages 5232-6

Eisenberg SP, Brewer MT, Verderber E, Heimdal P, Brandhuber BJ, Thompson RC

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.

MeSH Terms
Amino Acid Sequence Animals Base Sequence Humans Interleukin-1/genetics,metabolism Introns Mice Molecular Sequence Data Multigene Family Mutation Rats Rats, Inbred Strains Receptors, Immunologic/antagonists & inhibitors Receptors, Interleukin-1 Sequence Alignment Sequence Homology, Nucleic Acid
Chemicals
Interleukin-1 Receptors, Immunologic Receptors, Interleukin-1
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Eisenberg S P
Synergen, Boulder, CO 80301.
Brewer M T
Verderber E
Heimdal P
Brandhuber B J
Thompson R C
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.88.12.5232
Published
1991-06-15
Pages
5232-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC51846
Subset
IM
Databases
GENBANK
M63099, M63100, M63101
External Links
PubMed source DOI: 10.1073/pnas.88.12.5232 PMC Full Text View journal details
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