The Interleukin 1 receptor family (IL1R) comprises at least eleven members including IL1 RI (IL1R1), IL1 RII (IL1 R2), IL1 RAcP (IL1 R3), ST2 (T1/IL-1 R4), IL-18 Rα (IL1 Rrp/IL1 R5), IL1 Rrp2 (IL1 RL2/IL1 R6), IL18 Rβ (AcPL/IL1 R7), IL1RAPL1 (TIGIRR2/IL1 R8), and IL1 RAPL2 (TIGIRR1/IL1 R9) (1). All family members possess three immunoglobulin (Ig)like domains in their extracellular region. Most members also have an intracellular TIR (Tolllike receptor/IL1 receptor signaling)
domain that is also conserved in the Tolllike receptor family. Related proteins, SIGIRR (single Ig domaincontaining IL1 Rrelated molecule) and IL18BP, differ from the other members by having only one Ig domain (1). IL1 receptor accessory proteinlike 2 (IL1 RAPL2) is alternately known as IL1 R9 and three immunoglobulin domain containing IL1 receptorrelated molecule 1 (TIGIRR1) and is expressed in the brain (2). Its sequence predicts an 686 amino acid (aa) residue type I transmembrane glycoprotein with a 17 aa signal peptide, a 339 aa extracellular region containing three Iglike domains, an 18 aa transmembrane domain and a 312 aa cytoplasmic tail (3). By comparison to other IL1 receptor family proteins, IL1 RAPL2 has a Cterminal cytoplasmic extension beyond the TIR domain that is found in IL1RAPL1 and SIGIRR but not other family members (3). Human and mouse IL1 RAPL2 share approximately 95% aa sequence identity. Human IL-1 RAPL2 is most homologous (63%) to IL1RAPL1, a receptor protein that is highly expressed in hippocampus and is involved in Xlinked mental retardation (4, 5). Genes for both have been localized to human chromosome Xq22. A ligand for IL1 RAPL2 has not been identified.