TLR4 — Toll like receptor 4
TLR4 belongs to a gene co-expression module in 3 of 28 SCUBA cell types. Each module groups genes that rise and fall together in that cell type; the genes it shares a module with are its closest co-expression partners there.
TLR4's module in each cell type
| Cell type | Module | Shares the module with | |
|---|---|---|---|
| Macrophages | Myeloid Innate Signaling Innate immunity | ADCY7, ARHGAP18, BMP2K, C3AR1, C6orf62, CD46, CD84, CLTC +34 more | View in SCUBA |
| Monocytes | Macrophage Innate Activation Innate immunity | DMXL2, FGL2, HSD17B4, KCTD12, MPEG1, PTPRC, SAMHD1, VPS35 +1 more | View in SCUBA |
| Neutrophils | TLR Lipid Signaling Innate immunity | DGAT2, IFNAR1, LILRB3, MBOAT7, NOTCH1, PPP1R3B, STEAP4, TLR1 +1 more |
About the gene
| Synonyms | ARMD10, CD284, hToll, TLR-4 |
|---|---|
| Chromosome | 9: 117704175-117724735 |
| Predicted location | Intracellular, Membrane |
| Essential gene | No |
| Protein class | CD markers, FDA approved drug targets, Human disease related genes, Predicted intracellular proteins, Predicted membrane proteins, Transporters |
| Molecular function | Receptor |
| Biological process | Immunity, Inflammatory response, Innate immunity |
Function
Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstream signaling pathways. At the plasma membrane, cooperates with LY96 to mediate the innate immune response to bacterial lipopolysaccharide (LPS). Also involved in LPS-independent inflammatory responses triggered by free fatty acids, such as palmitate, and Ni(2+). Mechanistically, acts via MYD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Alternatively, CD14- mediated TLR4 internalization via endocytosis is associated with the initiation of a MYD88-independent signaling via the TICAM1-TBK1-IRF3 axis leading to type I interferon production. In addition to the secretion of proinflammatory cytokines, initiates the activation of NLRP3 inflammasome and formation of a positive feedback loop between autophagy and NF-kappa-B signaling cascade. In complex with TLR6, promotes inflammation in monocytes/macrophages by associating with TLR6 and the receptor CD86. Upon ligand binding, such as oxLDL or amyloid-beta 42, the TLR4:TLR6 complex is internalized and triggers inflammatory response, leading to NF-kappa-B-dependent production of CXCL1, CXCL2 and CCL9 cytokines, via MYD88 signaling pathway, and CCL5 cytokine, via TICAM1 signaling pathway. In myeloid dendritic cells, vesicular stomatitis virus glycoprotein G but not LPS promotes the activation of IRF7, leading to type I IFN production in a CD14- dependent manner. Required for the migration-promoting effects of ZG16B/PAUF on pancreatic cancer cells.
Human Protein Atlas · Open Targets · UniProt
Gene annotation from the Human Protein Atlas and UniProt; see sources & licences.