SIGIRR
Description
The SIGIRR (single Ig and TIR domain containing) is a protein-coding gene located on chromosome 11.
SIGIRR (Single Ig IL-1-related receptor), also known as Toll/Interleukin-1 receptor 8 (TIR8) or Interleukin-1 receptor 8 (IL-1R8), is a transmembrane protein encoded by the SIGIRR gene. It plays a role in modulating inflammation, immune response, and tumorigenesis of colonic epithelial cells.
The human SIGIRR gene is located on chromosome 11 and consists of 10 exons spanning approximately 11,700 base pairs. In mice, the gene is found on chromosome 7 and has 9 exons spanning about 9,400 base pairs.
SIGIRR is a 410 amino acid protein with a unique structure compared to other members of the IL-1 receptor family. It has only one immunoglobulin (Ig) domain in its N-terminal extracellular region, unlike the three Ig domains found in other members. Following the Ig domain is a transmembrane domain that anchors the protein to the plasma membrane. The intracellular region contains a TIR domain and a 95-amino acid C-terminal tail, absent in other IL-1 receptor family members. The TIR domain of SIGIRR has a distinct structure, lacking the amino acids Ser447 and Tyr536, which are crucial for IL-1R1 signaling. Instead, SIGIRR has Cys222 and Leu305 in its structure.
SIGIRR acts as a negative regulator of the Toll-like and IL-1R receptor signaling pathways. It inhibits the assembly of signaling complexes at the TLR4 receptor, likely through a TIR-TIR domain interaction with TLR4. SIGIRR's extracellular domain interferes with the formation of the Il1R1 and IL1RAP heterodimer.
SIGIRR is also known as IL-1R8, TIR8.
Associated Diseases
- hyper-IgE recurrent infection syndrome 5, autosomal recessive
- inflammatory bowel disease 30
- severe combined immunodeficiency due to CARD11 deficiency
- immunodeficiency 37
- cystic fibrosis
