The STIR-domain superfamily in signal transduction, development and immunity

Trends Biochem Sci. 2003 May;28(5):226-9. doi: 10.1016/S0968-0004(03)00067-7.


We have identified a conserved sequence segment in transmembrane receptors (including SEFs, IL17Rs) and soluble factors (including CIKS/ACT1) in eukaryotes and bacteria - the SEFIR domain. This sequence domain is part of the new STIR domain superfamily comprising also the TIR domain known to mediate TIR-TIR homotypic interactions. In TOLL/IL1R-like pathways, the cytoplasmically localized TIR domain of a receptor and the TIR domain of a soluble adaptor interact physically and activate signalling. The similarity between the SEFIR and TIR domains involves the conserved boxes 1 and 2 of the TIR domain that are implicated in homotypic dimerization, but there is no sequence similarity between SEFIR domains and the TIR sequence box 3. By analogy, we suggest that SEFIR-domain proteins function as signalling components of Toll/IL-1R-similar pathways and that their SEFIR domain mediates physical protein-protein interactions between pathway components.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Humans
  • Immunity*
  • Membrane Glycoproteins / metabolism
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • Proteins / chemistry*
  • Proteins / immunology
  • Proteins / metabolism*
  • Receptors, Cell Surface / metabolism
  • Receptors, Interleukin / chemistry*
  • Receptors, Interleukin-1 / metabolism
  • Receptors, Interleukin-17
  • Recombinant Proteins / chemistry*
  • Signal Transduction*
  • Toll-Like Receptors


  • IL17RA protein, human
  • Membrane Glycoproteins
  • Proteins
  • Receptors, Cell Surface
  • Receptors, Interleukin
  • Receptors, Interleukin-1
  • Receptors, Interleukin-17
  • Recombinant Proteins
  • Toll-Like Receptors