Death domain of Interleukin 1 Receptor Associated Kinase-2
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 (TLRs), nuclear factor-kappaB (NF-kB), and mitogen-activated protein kinases (MAPKs). IRAKs contain an N-terminal DD domain and a C-terminal kinase domain. IRAK2 is an essential component of several signaling pathways, including NF-kappaB and the IL-1 signaling pathways. It is an inactive kinase that participates in septic shock mediated by TLR4 and TLR9. It plays a redundant role with IRAK1 in early NF-kB and MAPK responses, and remains present at later stages whereas IRAK1 disappears. 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:IRAK2-IRAK4 interaction site [polypeptide binding site]
Evidence:
Structure:3MOP; Four IRAK2 DDs interact with four IRAK4 DDs within the Myddosome complex; contacts at 4A.
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.",