The STIR-domain superfamily in signal transduction, development and immunity.
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.
Novatchkova
Maria
M
Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, A-1030 Vienna, Austria. novatchkova@imp.univie.ac.at
Leibbrandt
Andreas
A
Werzowa
Johannes
J
Neubüser
Annette
A
Eisenhaber
Frank
F
D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D007109:Immunity; D008562:Membrane Glycoproteins / Q000378:metabolism; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D018123:Receptors, Interleukin / Q000737:chemistry*; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D053722:Receptors, Interleukin-17; D011994:Recombinant Proteins / Q000737:chemistry*; D015398:Signal Transduction; D051193:Toll-Like Receptors
C109985:IL17RA protein, human; D008562:Membrane Glycoproteins; D011506:Proteins; D011956:Receptors, Cell Surface; D018123:Receptors, Interleukin; D017472:Receptors, Interleukin-1; D053722:Receptors, Interleukin-17; D011994:Recombinant Proteins; D051193:Toll-Like Receptors