This entry represents one repeat unit found in CD180 from mammals. CD180 may cooperate with MD-1 and TLR4 to mediate the innate immune response to bacterial lipopolysaccharide (LPS) in B-cells [].
TIR domain-containing adapter molecule 1 (TICAM1) is involved in innate immunity against invading pathogens. It is an adapter used by TLR3 and TLR4 (through TICAM2) to mediate NF-kappa-B and interferon-regulatory factor (IRF) activation, and to induce apoptosis [, ].
This entry represents mitogen-activated protein kinase kinase kinase 8 (MAP3K8 or COT or TPL2) (), which plays a role in the cell cycle. MAP3K8 is required for TLR4 activation of the MEK/ERK pathway. MAP3K8 is able to activate NF-kappa-B 1 (NFKB1) by stimulating proteasome-mediated proteolysis of NF-kappa-B 1/p105 []. MAP3K8 forms a ternary complex with NFKB1 and TNIP2 []. MAP3K8 is recruited to the CD40 complex via a mechanism dependent on TRAF-binding sites in CD40 [].
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 [].
This entry includes coiled-coil and C2 domain-containing protein 1A/B (CC2D1A/B, also known as Freud-1/2). CC2D1A is involved in many pathways, including nuclear factor kappaB, PDK1/Akt, cAMP/PKA, Notch and bone morphogenetic protein []. It is a calcium-regulated repressor of serotonine receptor 5-HT1A and dopamine-D2 receptor expression [, ]. CC2D1B binds to the 5-HT1A DRE and represses the human 5-HT1A receptor gene to regulate its expression in non-serotonergic cells and neurons [].CC2D1A and CC2D1B have also been shown to interact with the CHMP4 family of proteins, the major subunit of the ESCRT-III complex. They may regulate degradation and signaling of EGFR and TLR4 [].CC2D1A and CC2D1B share conserved domains, including several DM14 domains that are specific to this protein family, a C-terminal helix-loop-helix domain, and a C2 domain. The CC2D1A C2 domain is thought to be calcium insensitive and it lacks several acidic residues that mediate calcium binding of the PKC C2 domain. In addition, it contains a poly-basic insert that is not present in calcium-dependent C2 domains and may function as a nuclear localization signal []. The CC2D1B C2 domain appears to be essential for its DNA binding and repressor function; it may mediate protein-protein interactions []. Mutations in the CC2D1A gene has been linked to nonsyndromic mental retardation [, ].
