SIGIRR

single immunoglobulin and toll-interleukin 1 receptor (TIR) domain

SIGIRR is a member of the Toll-like receptor-interleukin 1 receptor superfamily. Members of this family are defined by the presence of an intracellular Toll-IL-1R (TIR) domain. The Toll-like receptors (TLRs) are signaling molecules that recognize different microbial products during infection and serve as an important link between the innate and adaptive immune responses. SIGIRR was originally identified through database analysis and was shown to have only one Ig domain as opposed to the normal three Ig folds seen in the TIR family. Similar to ST2, another TIR family member, it has been shown to negatively regulate IL-1 receptor and Toll-like receptor signaling. However, SIGIRR inhibits TLR-IL-1R signaling by dimerizing with TLR4, TLR5, TLR9, and IL-1R. It also associates with the down-stream TLR signaling proteins IRAK and TRAF6 in an IL-1-dependent fashion.

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