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

Genomics. 2000 Oct 15;69(2):252-62. doi: 10.1006/geno.2000.6328.


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-kappaB 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Cloning, Molecular
  • Evolution, Molecular
  • Humans
  • In Situ Hybridization, Fluorescence
  • Interleukin-1 / metabolism
  • Molecular Sequence Data
  • NF-kappa B / metabolism
  • Polymerase Chain Reaction
  • Receptors, Interleukin-1 / genetics*
  • Receptors, Interleukin-1 / metabolism
  • Receptors, Interleukin-1 Type I
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Software
  • X Chromosome*


  • Interleukin-1
  • NF-kappa B
  • Receptors, Interleukin-1
  • Receptors, Interleukin-1 Type I

Associated data

  • GENBANK/AF212016