IL1RAP
Description
The IL1RAP (interleukin 1 receptor accessory protein) is a protein-coding gene located on chromosome 3.
Interleukin-1 receptor accessory protein is a protein that in humans is encoded by the IL1RAP gene. Interleukin 1 induces synthesis of acute phase and proinflammatory proteins during infection, tissue damage, or stress, by forming a complex at the cell membrane with an interleukin 1 receptor and an accessory protein. This gene encodes an interleukin 1 receptor accessory protein. Alternative splicing of this gene results in two transcript variants encoding two different isoforms, one membrane-bound and one soluble.
IL1RAP acts as a coreceptor for IL1RL2 in the IL-36 signaling system and for IL1R1 in the IL-1 signaling system. It forms a high-affinity complex with IL1R1 and IL1B, mediating IL-1-dependent activation of NF-kappa-B and other pathways. This complex recruits adapter molecules like TOLLIP, MYD88, and IRAK1/2 via TIR domains. IL1RAP also recruits TOLLIP to the signaling complex. It does not bind to interleukin-1 alone, and binding of IL1RN to IL1R1 prevents complex formation. IL1RAP interacts with the decoy receptor IL1R2, modulating cellular responses. It acts as a coreceptor for IL1RL1 in the IL-33 signaling system. IL1RAP can induce pre- and postsynaptic differentiation of neurons by binding to PTPRD. It may contribute to IL1B-mediated costimulation of IFNG production in Th1 cells. IL1RAP associates with secreted IL1R2 and increases its affinity for IL1B, potentially being the main mechanism for neutralizing IL1B by secreted receptors. It also enhances the inhibitory effect of secreted IL1R1 on IL-33 signaling. However, IL1RAP is unable to mediate canonical IL-1 signaling. IL1RAP is required for Src phosphorylation by IL1B and may be involved in IL1B-potentiated NMDA-induced calcium influx in neurons. The IL-36 receptor complex is a heterodimer of IL1RL2 and IL1RAP, while the IL-1 receptor complex is a heterodimer of IL1R1 and IL1RAP. IL1RAP associates with IL1R2 to form a non-signaling complex. Isoform 4 interacts with IL1R1 in an IL-1-dependent manner. IL1RAP interacts with IL-33-bound IL1RL1 to form a minimal signaling complex. It also interacts with KIT, independently of KITLG/SCF stimulation. A mast cell-specific KITLG/SCF-induced IL-33 signaling complex contains IL1RL1, IL1RAP, KIT, and MYD88. IL1RAP interacts with PTPRD via its first immunoglobulin domain, inducing pre- and postsynaptic differentiation of neurons.
IL1RAP is also known as C3orf13, IL-1RAcP, IL1R3.
