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TLR4 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 Ni(2+). These responses require non-conserved histidines and are, therefore, species-specific. Belongs to the lipopolysaccharide (LPS) receptor, a multi-protein complex containing at least CD14, LY96 and TLR4. Binding to bacterial LPS leads to homodimerization. Interacts with LY96 via the extracellular domain. Interacts with MYD88 and TIRAP via their respective TIR domains. Interacts with NOX4. Interacts with CNPY3. Interacts with HSP90B1. The interaction with both CNPY3 and HSP90B1 is required for proper folding in the endoplasmic reticulum. Highly expressed in placenta, spleen and peripheral blood leukocytes. Detected in monocytes, macrophages, dendritic cells and several types of T-cells. Belongs to the Toll-like receptor family. 3 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: Membrane protein, integral; Receptor, misc.
Chromosomal Location of Human Ortholog: 4 C1|4 34.66 cM
Cellular Component: cell surface; cytoplasm; external side of plasma membrane; integral to plasma membrane; intracellular; intrinsic to plasma membrane; lipid raft; lipopolysaccharide receptor complex; perinuclear region of cytoplasm; plasma membrane; receptor complex
Molecular Function: lipopolysaccharide binding; lipopolysaccharide receptor activity; phosphoinositide 3-kinase binding; protein binding; protein heterodimerization activity; receptor activity; receptor binding
Biological Process: activation of innate immune response; activation of MAPK activity; activation of NF-kappaB transcription factor; astrocyte development; B cell proliferation during immune response; defense response to Gram-negative bacterium; detection of lipopolysaccharide; I-kappaB phosphorylation; innate immune response; innate immune response-activating signal transduction; interferon-gamma production; interleukin-1 beta secretion; leukotriene metabolic process; lipopolysaccharide-mediated signaling pathway; macrophage activation; microglial cell activation; MyD88-dependent toll-like receptor signaling pathway; negative regulation of interferon-gamma production; negative regulation of interleukin-17 production; negative regulation of interleukin-23 production; negative regulation of interleukin-6 production; negative regulation of tumor necrosis factor production; positive regulation of apoptosis; positive regulation of B cell proliferation; positive regulation of chemokine production; positive regulation of DNA binding; positive regulation of I-kappaB kinase/NF-kappaB cascade; positive regulation of inflammatory response; positive regulation of interferon-alpha production; positive regulation of interferon-beta biosynthetic process; positive regulation of interferon-beta production; positive regulation of interferon-gamma production; positive regulation of interleukin-1 beta secretion; positive regulation of interleukin-1 production; positive regulation of interleukin-10 production; positive regulation of interleukin-12 biosynthetic process; positive regulation of interleukin-12 production; positive regulation of interleukin-6 production; positive regulation of interleukin-8 biosynthetic process; positive regulation of interleukin-8 production; positive regulation of JNK cascade; positive regulation of lymphocyte proliferation; positive regulation of MHC class II biosynthetic process; positive regulation of NF-kappaB import into nucleus; positive regulation of nitric oxide biosynthetic process; positive regulation of nitric-oxide synthase biosynthetic process; positive regulation of peptidyl-tyrosine phosphorylation; positive regulation of stress-activated MAPK cascade; positive regulation of transcription factor activity; positive regulation of transcription from RNA polymerase II promoter; positive regulation of tumor necrosis factor biosynthetic process; positive regulation of tumor necrosis factor production; production of nitric oxide during acute inflammatory response; regulation of dendritic cell cytokine production; regulation of inflammatory response; regulation of sensory perception of pain; response to bacterium; response to ethanol; response to lipopolysaccharide; response to oxidative stress; toll-like receptor signaling pathway
Reference #:  Q9QUK6 (UniProtKB)
Alt. Names/Synonyms: lipopolysaccharide response; Lps; Ly87; OTTMUSP00000000296; Ran/M1; Rasl2-8; Tlr4; Toll-like receptor 4
Gene Symbols: Tlr4
Molecular weight: 95,519 Da
Basal Isoelectric point: 6.12  Predict pI for various phosphorylation states
CST Pathways:  NF-kB Signaling  |  Toll-Like Receptor Signaling
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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