Aliases for TLR4 Gene
External Ids for TLR4 Gene
Previous GeneCards Identifiers for TLR4 Gene
The protein encoded by this gene is a member of the Toll-like receptor (TLR) family which plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. They recognize pathogen-associated molecular patterns that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity. The various TLRs exhibit different patterns of expression. This receptor has been implicated in signal transduction events induced by lipopolysaccharide (LPS) found in most gram-negative bacteria. Mutations in this gene have been associated with differences in LPS responsiveness. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]
GeneCards Summary for TLR4 Gene
TLR4 (Toll-Like Receptor 4) is a Protein Coding gene. Diseases associated with TLR4 include macular degeneration, age-related, 10 and behcet's disease. Among its related pathways are PI3K-Akt signaling pathway and Proteoglycans in cancer. GO annotations related to this gene include receptor activity and lipopolysaccharide binding. An important paralog of this gene is TLR6.
UniProtKB/Swiss-Prot for TLR4 Gene
Cooperates with LY96 and CD14 to mediate the innate immune response to bacterial lipopolysaccharide (LPS). Acts via MYD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Also involved in LPS-independent inflammatory responses triggered by free fatty acids, such as palmitate, and Ni(2+). Responses triggered by Ni(2+) require non-conserved histidines and are, therefore, species-specific. In complex with TLR6, promotes sterile inflammation in monocytes/macrophages in response to oxidized low-density lipoprotein (oxLDL) or amyloid-beta 42. In this context, the initial signal is provided by oxLDL- or amyloid-beta 42-binding to CD36. This event induces the formation of a heterodimer of TLR4 and TLR6, which is rapidly internalized and triggers inflammatory response, leading to the NF-kappa-B-dependent production of CXCL1, CXCL2 and CCL9 cytokines, via MYD88 signaling pathway, and CCL5 cytokine, via TICAM1 signaling pathway, as well as IL1B secretion.
Toll-like receptors (TLRs) are single transmembrane cell-surface receptors, which have a key role in the innate immune system. TLRs generally exist as homodimers (although TLR2-TLR6 heterodimers have been reported) and are found on immune cells such as macrophages, B lymphocytes and mast cells. Toll-like receptors are activated by molecules associated with biological threat and are highly specific towards evolutionary conserved entities on microbes, such as bacterial cell-surface lipopolysaccharides, flagella and unmethylated CpG islands. It has been suggested that some toll-like receptors may have endogenous ligands, such as Hsp60 and fibrinogen, and this has promoted speculation that endogenous toll-like receptor activators may have a pathological role in autoimmune disease. Activation of toll-like receptors initiates downstream signaling cascades, initially via the adapter molecules MyD88, Trap, Trif and Tram, which converge on the PI 3-K and NF-kappaB pathways and regulate intracellular kinases and gene expression. This can stimulate an inflammatory and/or antigen-specific immune response. The signaling cascade coupled to toll-like receptor activation is very similar to that of interleukin-1 receptor (IL-1R) activation.