Toll-like receptor 4

TLR4
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4G8A, 2Z62, 2Z63, 2Z65, 2Z66, 3FXI, 3UL7, 3UL8, 3UL9, 3ULA
Identifiers
Aliases	TLR4, ARMD10, CD284, TLR-4, TOLL, toll like receptor 4
External IDs	OMIM: 603030; MGI: 96824; HomoloGene: 41317; GeneCards: TLR4; OMA:TLR4 - orthologs
Gene location (Human) Chr. Chromosome 9 (human)[1] Band 9q33.1 Start 117,704,175 bp[1] End 117,724,735 bp[1]
Gene location (Mouse) Chr. Chromosome 4 (mouse)[2] Band 4 C1|4 34.66 cM Start 66,745,821 bp[2] End 66,848,521 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in monocyte Achilles tendon blood bone marrow trabecular bone spleen granulocyte right lung gallbladder bone marrow cells Top expressed in lumbar spinal ganglion aortic valve ascending aorta granulocyte decidua epithelium of stomach stroma of bone marrow endothelial cell of lymphatic vessel cervix mucous cell of stomach More reference expression data BioGPS More reference expression data
Gene ontology Molecular function lipopolysaccharide immune receptor activity lipopolysaccharide binding protein binding transmembrane signaling receptor activity Cellular component cytoplasm membrane perinuclear region of cytoplasm cell surface integral component of membrane plasma membrane endosome membrane intrinsic component of plasma membrane integral component of plasma membrane lipopolysaccharide receptor complex external side of plasma membrane Biological process positive regulation of MHC class II biosynthetic process positive regulation of JNK cascade TRIF-dependent toll-like receptor signaling pathway cellular response to mechanical stimulus positive regulation of interleukin-8 production positive regulation of ERK1 and ERK2 cascade T-helper 1 type immune response positive regulation of platelet activation positive regulation of interleukin-1 production positive regulation of stress-activated MAPK cascade positive regulation of NLRP3 inflammasome complex assembly positive regulation of interleukin-12 production positive regulation of interferon-alpha production I-kappaB phosphorylation positive regulation of nitric-oxide synthase biosynthetic process positive regulation of B cell proliferation defense response to bacterium positive regulation of interleukin-6 production activation of innate immune response positive regulation of tumor necrosis factor production negative regulation of tumor necrosis factor production innate immune response negative regulation of interleukin-17 production I-kappaB kinase/NF-kappaB signaling positive regulation of interferon-beta production positive regulation of inflammatory response toll-like receptor 4 signaling pathway positive regulation of macrophage cytokine production positive regulation of interleukin-10 production immune system process astrocyte development intestinal epithelial structure maintenance positive regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway response to lipopolysaccharide cellular response to lipoteichoic acid positive regulation of NF-kappaB transcription factor activity immune response negative regulation of interleukin-23 production regulation of inflammatory response positive regulation of chemokine production lipopolysaccharide-mediated signaling pathway detection of fungus positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway negative regulation of interferon-gamma production response to bacterium negative regulation of osteoclast differentiation B cell proliferation involved in immune response positive regulation of nitric oxide biosynthetic process negative regulation of interleukin-6 production positive regulation of interferon-gamma production nitric oxide production involved in inflammatory response MyD88-dependent toll-like receptor signaling pathway regulation of dendritic cell cytokine production positive regulation of gene expression negative regulation of ERK1 and ERK2 cascade positive regulation of I-kappaB kinase/NF-kappaB signaling macrophage activation detection of lipopolysaccharide cellular response to lipopolysaccharide positive regulation of lymphocyte proliferation positive regulation of transcription by RNA polymerase II MyD88-independent toll-like receptor signaling pathway signal transduction inflammatory response defense response to Gram-negative bacterium toll-like receptor signaling pathway necroptosis apoptotic signaling pathway negative regulation of MyD88-independent toll-like receptor signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7099 21898 Ensembl ENSG00000136869 ENSMUSG00000039005 UniProt O00206 Q9QUK6 RefSeq (mRNA) NM_138557 NM_003266 NM_138554 NM_138556 NM_021297 RefSeq (protein) NP_003257 NP_612564 NP_612567 NP_067272 Location (UCSC) Chr 9: 117.7 – 117.72 Mb Chr 4: 66.75 – 66.85 Mb PubMed search [3] [4]
Wikidata
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Toll-like receptor 4 (TLR4), also designated as CD284 (cluster of differentiation 284), 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.

TLR4 belongs to the toll-like receptor family which is representative of the pattern recognition receptors (PRR), so named for their ability to recognize evolutionarily conserved components of microorganisms (bacteria, viruses, fungi and parasites) called pathogen-associated molecular patterns (PAMPs). The recognition of a PAMP by a PRR triggers rapid activation of the innate immunity essential to fight infectious diseases.^[5]

TLR4 is expressed in immune cells mainly of myeloid origin, including monocytes, macrophages and dendritic cells (DC).^[5] It is also expressed at a lower level on some non-immune cells, including epithelium, endothelium, placental cells and beta cells in Langerhans islets. Most myeloid cells express also high amounts of plasma membrane-anchored CD14, which facilitates the activation of TLR4 by LPS and controls the subsequent internalization of the LPS-activated TLR4 important for receptor signaling and degradation.^[6][7]

The main ligands for TLR4 are lipopolysaccharides (LPS), the major components of the outer membrane of Gram-negative bacteria and some Gram-positive bacteria. TLR4 can also be activated by endogenous compounds called damage-associated molecular patterns (DAMPs), including high mobility group box protein 1 (HMGB1), S100 proteins, or histones. These compounds are released during tissue injury and by dying or necrotic cells.^{[8][9][10][11][12]}