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The Interleukin 1 receptor family (IL-1R) comprises at least eleven members including IL-1 RI (IL-1R1), IL-1 RII (IL-1 R2), IL-1 RAcP (IL-1 R3), ST2 (T1/IL‑1 R4), IL‑18 R alpha (IL-1 Rrp/IL-1 R5), IL-1 Rrp2 (IL-1 RL2/IL-1 R6), IL-18 R beta (AcPL/IL-1 R7), IL-1RAPL1 (TIGIRR-2/IL-1 R8), and IL-1 RAPL2 (TIGIRR-1/IL-1 R9) (1). All family members possess three immunoglobulin (Ig)-like domains in their extracellular region. Most members also have an intracellular TIR (Toll-like receptor/IL-1 receptor signaling) domain that is also conserved in the Toll-like receptor family. Related proteins, SIGIRR (single Ig domain-containing IL-1 R-related molecule) and IL-18BP, differ from the other members by having only one Ig domain (1). IL-1 receptor accessory protein-like 2 (IL-1 RAPL2) is alternately known as IL-1 R9 and three immunoglobulin domain containing IL-1 receptor-related molecule 1 (TIGIRR-1) 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 Ig-like domains, an 18 aa transmembrane domain and a 312 aa cytoplasmic tail (3). By comparison to other IL-1 receptor family proteins, IL-1 RAPL2 has a C-terminal cytoplasmic extension beyond the TIR domain that is found in IL-1RAPL1 and SIGIRR but not other family members (3). Human and mouse IL-1 RAPL2 share approximately 95% aa sequence identity. Human IL‑1 RAPL2 is most homologous (63%) to IL-1RAPL1, a receptor protein that is highly expressed in hippocampus and is involved in X-linked mental retardation (4, 5). Genes for both have been localized to human chromosome Xq22. A ligand for IL-1 RAPL2 has not been identified (1).

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