Death domain of Interleukin 1 Receptor Associated Kinase-1
Death Domain (DD) of Interleukin-1 Receptor-Associated Kinase 1 (IRAK1). IRAKs are essential components of innate immunity and inflammation in mammals and other vertebrates. They are involved in signal transduction pathways involving IL-1 and IL-18 receptors, Toll-like receptors, nuclear factor-kappaB (NF-kB), and mitogen-activated protein kinases (MAPKs). IRAKs contain an N-terminal DD domain and a C-terminal kinase domain. IRAK1 is an active kinase and also plays adaptor functions. It binds to the MyD88-IRAK4 complex via its DD, which facilitates its phosphorylation by IRAK4, activating it for further auto-phosphorylation. Hyper-phosphorylated IRAK1 forms a cytosolic complex with TRAF6, leading to the activation of NF-kB and MAPK pathways. IRAK1 is involved in autoimmunity and may be associated with lupus pathogenesis. DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN. They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes.
Feature 1:putative IRAK1-IRAK4 interaction site [polypeptide binding site]
Evidence:
Comment:Based on the observed interaction between IRAK2 and IRAK4 within the Myddosome complex.
Comment:MyD88, IRAK4, and IRAK2 form the Myddosome complex which is assembled in a stepwise manner. MyD88 first recruits IRAK4, then the MyD88-IRAK4 complex recruits the substrates IRAK2 or IRAK1.
Jiyao W et al.(2023). "The conserved domain database in 2023.",