IL1RAP

Interleukin-1 Receptor Accessory Protein (IL1RAP) is a protein that in humans is encoded by the IL1RAP gene. This protein is an essential part of the interleukin 1 receptor complex, which mediates the biological responses to interleukin 1 alpha (IL-1α) and interleukin 1 beta (IL-1β) cytokines. IL1RAP is crucial for the proper functioning of the immune system, playing a significant role in the regulation of immune and inflammatory responses.

Function

IL1RAP, together with the Interleukin-1 receptor, type I (IL1R1), forms a receptor complex necessary for the IL-1 signal transduction. Upon binding of IL-1α or IL-1β to IL1R1, IL1RAP is recruited to form a high-affinity receptor complex. This interaction initiates a series of intracellular signaling pathways, leading to the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and other transcription factors that regulate the expression of various inflammatory genes.

Clinical Significance

Alterations in the expression or function of IL1RAP have been associated with several diseases, including autoimmune diseases, rheumatoid arthritis, and various forms of cancer. Due to its role in promoting inflammation, IL1RAP is considered a potential therapeutic target. Inhibitors of IL1RAP are being explored for the treatment of inflammatory and autoimmune conditions, as well as for cancer immunotherapy.

Gene

The IL1RAP gene is located on human chromosome 3 and consists of multiple exons that encode the IL1RAP protein. Variants and mutations within the IL1RAP gene may influence the susceptibility to diseases by affecting the protein's expression or function.

Structure

IL1RAP is a transmembrane protein that contains three extracellular immunoglobulin-like domains, a single transmembrane domain, and a short cytoplasmic tail. Its structure is critical for mediating the interaction with IL1R1 and the subsequent activation of downstream signaling pathways.

Therapeutic Applications

Given its central role in inflammation and immune regulation, targeting IL1RAP has therapeutic potential in treating various diseases. Monoclonal antibodies and small molecule inhibitors that block the interaction between IL1RAP and IL1R1 are under investigation. These therapeutic agents aim to reduce pathological inflammation and modulate the immune response in diseases where IL1RAP signaling is implicated.

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