Interleukin-1 receptor-associated kinase-like 2 (IRAK2) is a critical mediator of TLR/IL1-R signalling [, ]. It is required for production of pro-inflammatory cytokines [, ].All IRAKs are multidomain proteins, consisting of a conserved N-terminal death domain (DD) and a central kinase domain (KD). The DD is a protein interaction motif implicated in binding to the adaptor protein MyD88 []. IRAK2 lacks an active kinase domain, as a critical residue in the kinase domain has changed [].
This family represents Protein K7 from Orthopoxvirus. K7 is Bcl-2-like protein which, through its interaction with the DEAD box RNA helicase DDX3X/DDX3, prevents TBK1/IKKepsilon-mediated IRF3 activation []. It contributes to virulence by binding to the host TRAF6 and IRAK2 and preventing host NF-kappa-B activation and affects the acute immune response to infection [, , ]. In vaccinia virus, this protein has been related to the increase in cellular histone methylation during infection [].
This entry represents the death domain found in interleukin-1 receptor-associated kinase-like 2 (IRAK2) []. 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 [, ].Interleukin-1 receptor-associated kinases (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 death domain (DD) and a C-terminal kinase domain [, , , ].Death domains (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 [].
