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
Gene location (Human)
Chr.	Chromosome 9 (human)
End	117,724,735 bp
Gene location (Mouse)
Chr.	Chromosome 4 (mouse)
End	66,848,521 bp
RNA expression pattern
	Top expressed in
	monocyte; ; Achilles tendon; ; blood; ; bone marrow; ; spongy bone; ; spleen; ; right lung; ; gallbladder; ; bone marrow cells; ; subcutaneous adipose tissue;
	Top expressed in
	aortic valve; ; ascending aorta; ; epithelium of stomach; ; cervix; ; mucous cell of stomach; ; sciatic nerve; ; white adipose tissue; ; calvaria; ; carotid body; ; seminal vesicula;
	More reference expression data
	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
	7099
	21898
	ENSG00000136869
	ENSMUSG00000039005
	O00206
	Q9QUK6
	NM_138557; NM_003266; NM_138554; NM_138556
	NM_021297
	NP_003257; NP_612564; NP_612567
	NP_067272
	Wikidata
View/Edit Human	View/Edit Mouse

Toll-like receptor 4 (TLR4) is a transmembrane protein of approximately 95 kDa that is encoded by the TLR4 gene. TLR4 is also designated as CD284 (cluster of differentiation 284).

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.

TLR4 is expressed in immune cells mainly of myeloid origin, including monocytes, macrophages and dendritic cells (DC). 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.

TLR4 is activated by lipopolysaccharide (LPS), a major component 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) and hyaluronic acid. These compounds are released during tissue injury and can activate TLR4 in non-infectious conditions to induce tissue repair. Apart from LPS and its derivatives, up to 30 natural TLR4 agonists with diverse chemical structures have been postulated. However, besides DAMPs, the others have not demonstrated to be direct activators of TLR4 and could therefore act as chaperones for TLR4 or as promoters of LPS internalization.

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