Single immunoglobulin interleukin-1 receptor-related receptor (SIGIRR)

Single immunoglobulin interleukin-1 receptor-related receptor (SIGIRR) is a member of the interleukin-1 receptor (IL-1R) family and Toll/interleukin-1 receptor (TIR) superfamily, structurally characterized by a single extracellular immunoglobulin domain, a transmembrane region, a TIR domain, and a unique carboxy-terminal tail[1][2][3][4]. SIGIRR functions as a negative regulator of both TLR and IL-1R signaling pathways, inhibiting signaling that leads to inflammation, autoimmunity, and tumor-associated immune responses[1][2][3][4]. It achieves this by interfering with receptor dimerization, sequestration of adaptor proteins, and attenuation of downstream signaling events like NF-κB, JNK, and mTOR activation[1][2][3][4]. SIGIRR is broadly expressed in epithelial, immune, and lymphoid tissues, and plays a key physiological role in limiting excessive immune responses while maintaining immune homeostasis. Downregulation or loss of SIGIRR leads to exacerbated immune and inflammatory diseases and is implicated in the development of inflammation-associated cancers[1][2][3][4]. No approved drugs are currently known to directly target SIGIRR[3][4].

Other names

Interleukin-1 receptor 8 (IL-1R8)TIR8Single Ig IL-1-related receptorSingle Ig IL-1R-related moleculeSingle immunoglobulin domain-containing IL-1R-related proteinToll/interleukin-1 receptor 8Single immunoglobulin domain IL1R1 relatedUNQ301/PRO342

Negative regulation of TLR and IL-1R signaling via interference in receptor-proximal signaling and prevention of dimerization of signaling complexes Sequestration of TIR domain-containing adaptor molecules (e.g., MyD88) Disruption of signaling complex formation at both extracellular and cytoplasmic levels