Computational Identification, Cloning, and Characterization of IL-1R9, a Novel Interleukin-1 Receptor-like Gene Encoded over an Unusually Large Interval of Human Chromosome Xq22.2–q22.3

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• 作者：Sana ; Theodore R. ; Debets ; Reno ; Timans ; Jackie C. ; Bazan ; J. Fernando ; Kastelein ; Robert A.
• 刊名：Genomics
• 出版年：2000
• 出版时间：October 15, 2000
• 年：2000
• 卷：69
• 期：2
• 页码：252-262
• 全文大小：727 K

文摘

The Interleukin-1 receptor (IL-1R) and Toll signaling pathways share the evolutionarily conserved Toll homology domain (THD), which is a critical component in the signaling cascade of the host defense responses to infection and inflammation. Our initial genomic database searches uncovered a novel THD signature sequence between DNA markers DXS87 and DXS366. The feasibility of subsequently applying a coordinated computational approach, including various exon-finding programs, homology-based searches, and receptor profile searches, in revealing the exons encoding this novel IL-1R family member is described. IL-1R9 shows restricted expression in fetal brain and is highly homologous to IL1RAPL (A. Carrie et al., 1999 Nat. Genet. 23: 25–31), which is reportedly involved in nonsyndromic X-linked mental retardation. These genes are scattered over separate genomic intervals in excess of 1.0 Mb and encode receptors with extended C-terminal tails. In our functional NF-κB reporter assays, IL1RAPL, IL-1R9, or versions lacking the extended C-terminal sequences failed in responding either to IL-1 directly or to IL-18 when various permutations of IL-18R ectodomain chimeras were fused to their cytoplasmic domains. Evolutionary sequence analyses reinforce our conclusion that these novel orphan receptors probably form a functionally distinct subset of the IL-1R superfamily.