Toll interacting protein, also known as TOLLIP, is an inhibitory adaptor protein that in humans is encoded by the TOLLIP gene. [5] [6] [7]
It is an inhibitory adaptor protein within Toll-like receptors (TLR). [8] The TLR pathway is a part of the innate immune system that recognizes structurally conserved molecular patterns of microbial pathogens, leading to an inflammatory immune response.
Tollip interacts with cellular and subcellular membrane compartments such as endosome and lysosome through its C2 domain binding with phosphoinositides. [9] By coordinating organelle communications, Tollip can contribute to the fusion of endo-lysosome and autophagosome. Mice with Tollip deletion exhibit elevated risks for inflammatory diseases such as atherosclerosis and neurodegeneration. [10]
Polymorphisms in TLR genes have been implicated in various diseases like atopic dermatitis. [11] Recently, variations in the TOLLIP gene have been associated with tuberculosis and idiopathic pulmonary fibrosis. [12] [13]
TOLLIP has been shown to interact with TOM1, [14] TLR 2, [15] TLR 4 [15] and IL1RAP. [7]
Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. They are single-spanning receptors usually expressed on sentinel cells such as macrophages and dendritic cells, that recognize structurally conserved molecules derived from microbes. Once these microbes have reached physical barriers such as the skin or intestinal tract mucosa, they are recognized by TLRs, which activate immune cell responses. The TLRs include TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10, TLR11, TLR12, and TLR13. Humans lack genes for TLR11, TLR12 and TLR13 and mice lack a functional gene for TLR10. The receptors TLR1, TLR2, TLR4, TLR5, TLR6, and TLR10 are located on the cell membrane, whereas TLR3, TLR7, TLR8, and TLR9 are located in intracellular vesicles.
Myeloid differentiation primary response 88 (MYD88) is a protein that, in humans, is encoded by the MYD88 gene. originally discovered in the laboratory of Dan A. Liebermann as a Myeloid differentiation primary response gene.
Toll-like receptor 2 also known as TLR2 is a protein that in humans is encoded by the TLR2 gene. TLR2 has also been designated as CD282. TLR2 is one of the toll-like receptors and plays a role in the immune system. TLR2 is a membrane protein, a receptor, which is expressed on the surface of certain cells and recognizes foreign substances and passes on appropriate signals to the cells of the immune system.
TIR domain containing adaptor molecule 1 is an adapter in responding to activation of toll-like receptors (TLRs). It mediates the rather delayed cascade of two TLR-associated signaling cascades, where the other one is dependent upon a MyD88 adapter.
Toll-like receptor 4 (TLR4), also designated as CD284, is a key activator of the innate immune response and plays a central role in the fight against bacterial infections. TLR4 is a transmembrane protein of approximately 95 kDa that is encoded by the TLR4 gene.
Lymphocyte antigen 96, also known as "Myeloid Differentiation factor 2 (MD-2)," is a protein that in humans is encoded by the LY96 gene.
TNF receptor-associated factor 1 is a protein that in humans is encoded by the TRAF1 gene.
AP-2 complex subunit mu is a protein that in humans is encoded by the AP2M1 gene.
Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) is a protein receptor that in humans is encoded by the NOD1 gene. It recognizes bacterial molecules and stimulates an immune reaction.
Interleukin-1 receptor-associated kinase 1 (IRAK-1) is an enzyme in humans encoded by the IRAK1 gene. IRAK-1 plays an important role in the regulation of the expression of inflammatory genes by immune cells, such as monocytes and macrophages, which in turn help the immune system in eliminating bacteria, viruses, and other pathogens. IRAK-1 is part of the IRAK family consisting of IRAK-1, IRAK-2, IRAK-3, and IRAK-4, and is activated by inflammatory molecules released by signaling pathways during pathogenic attack. IRAK-1 is classified as a kinase enzyme, which regulates pathways in both innate and adaptive immune systems.
Arrestin, beta 1, also known as ARRB1, is a protein which in humans is encoded by the ARRB1 gene.
Interleukin 1 receptor, type I (IL1R1) also known as CD121a, is an interleukin receptor. IL1R1 also denotes its human gene.
Interleukin-1 receptor accessory protein is a protein that in humans is encoded by the IL1RAP gene.
Sorting nexin-9 is a protein that in humans is encoded by the SNX9 gene.
E3 ubiquitin-protein ligase RNF216 is an enzyme that in humans is encoded by the RNF216 gene.
Target of Myb protein 1 is a protein that in humans is encoded by the TOM1 gene.
Receptor-interacting serine/threonine-protein kinase 3 is an enzyme that is encoded by the RIPK3 gene in humans.
Single Ig IL-1-related receptor (SIGIRR), also called Toll/Interleukin-1 receptor 8 (TIR8) or Interleukin-1 receptor 8 (IL-1R8), is transmembrane protein encoded by gene SIGIRR, which modulate inflammation, immune response, and tumorigenesis of colonic epithelial cells.
The toll-interleukin-1 receptor (TIR) homology domain is an intracellular signaling domain found in MyD88, SARM1, interleukin-1 receptors, toll receptors and many plant R proteins. It contains three highly conserved regions, and mediates protein-protein interactions between the toll-like receptors (TLRs) and signal-transduction components. TIR-like motifs are also found in plant proteins where they are involved in resistance to disease and in bacteria where they are associated with virulence. When activated, TIR domains recruit cytoplasmic adaptor proteins MyD88 (UniProt Q99836) and TOLLIP (toll-interacting protein, UniProt Q9H0E2). In turn, these associate with various kinases to set off signaling cascades. Some TIR domains have also been found to have intrinsic NAD+ cleavage activity, such as in SARM1. In the case of SARM1, the TIR NADase activity leads to the production of Nam, ADPR and cADPR and the activation of downstream pathways involved in Wallerian degeneration and neuron death.
Interleukin 17 receptor D is a protein that in humans is encoded by the IL17RD gene.