Tlr4 - toll-like receptor 4 Gene

Also Known as Lps; Ly87; Ran/M1; Rasl2-8

Species: Mus musculus

Gene Type: protein coding

Gene ID: 21898

About Tlr4

Chromosome 4: 66,745,821-66,848,521 forward strand.GRCm39:CM000997.3

This gene has 4 transcripts (splice variants), 127 orthologues, 23 paralogues and is associated with 133 phenotypes. Broad expression in bladder adult (RPKM 2.), subcutaneous fat pad adult (RPKM 1.2) and 2 other tissues.

Summary

This gene belongs to the evolutionarily-conserved Toll-like Receptor family, whose members are type-1 transmembrane proteins that are involved in innate immunity. Toll-like receptors are characterized by an extracellular leucine-rich repeat domain that functions in ligand recognition and an intracellular toll/interleukin-1 receptor-like domain that is crucial for signal transduction. The receptor encoded by this gene mediates the innate immune response to Bacterial lipopolysaccharide, a major component of the outer membrane of Gram-negative bacteria, through synthesis of pro-inflammatory cytokines and chemokines. In addition, this protein can recognize Other pathogens from Gram-negative and Gram-positive bacteria as well as viral components. Mice deficient in this gene display a number of immune response-related phenotypes including hyporesponsiveness to Bacterial lipopolysaccharide and increased levels of respiratory syncytial virus compared to controls. [provided by RefSeq, Sep 2015]

Tlr4 Products (1)

mRNA	Protein	Name
NM_021297.3	NP_067272.1	toll-like receptor 4 precursor

Gene Ontology

Molecular Function
Biological Process
Cellular Component

Molecular Function GO Annotation	Evidence	References	Source
enables lipopolysaccharide immune receptor activity	IDA IDA: Inferred from direct assay	16260493	MGI
enables protein binding	IPI IPI: Inferred from physical interaction	17803912	MGI

Biological Process GO Annotation	Evidence	References	Source
acts upstream of B cell proliferation	IMP IMP: Inferred from mutant phenotype	10549626	MGI
acts upstream of or within B cell proliferation involved in immune response	IMP IMP: Inferred from mutant phenotype	10880523	MGI
acts upstream of ERK1 and ERK2 cascade	IDA IDA: Inferred from direct assay	18261938	MGI
acts upstream of or within I-kappaB phosphorylation	IMP IMP: Inferred from mutant phenotype	18820689	MGI
acts upstream of JNK cascade	IDA IDA: Inferred from direct assay	16260493	MGI
acts upstream of JNK cascade	IGI IGI: Inferred from genetic interaction	16260493	MGI
acts upstream of MHC class II biosynthetic process	IMP IMP: Inferred from mutant phenotype	10549626	MGI
involved in MyD88-dependent toll-like receptor signaling pathway	IGI IGI: Inferred from genetic interaction	20037584	MGI
involved in TRIF-dependent toll-like receptor signaling pathway	IGI IGI: Inferred from genetic interaction	20037584	MGI
acts upstream of or within activation of innate immune response	IMP IMP: Inferred from mutant phenotype	15661922	MGI
acts upstream of or within astrocyte development	IMP IMP: Inferred from mutant phenotype	22577135	MGI
acts upstream of or within cellular response to lipopolysaccharide	IDA IDA: Inferred from direct assay	10880523	MGI
involved in cellular response to lipopolysaccharide	IDA IDA: Inferred from direct assay	28096568	MGI
acts upstream of or within cellular response to lipopolysaccharide	IMP IMP: Inferred from mutant phenotype	10880523	MGI
involved in cellular response to lipopolysaccharide	IMP IMP: Inferred from mutant phenotype	20051628	MGI
acts upstream of or within cellular response to lipoteichoic acid	IMP IMP: Inferred from mutant phenotype	10549626	MGI
involved in cellular response to oxidised low-density lipoprotein particle stimulus	IGI IGI: Inferred from genetic interaction	20037584	MGI
involved in cellular response to platelet-derived growth factor stimulus	IMP IMP: Inferred from mutant phenotype	21880694	MGI
acts upstream of or within defense response to Gram-negative bacterium	IMP IMP: Inferred from mutant phenotype	15661922	MGI
involved in detection of lipopolysaccharide	IDA IDA: Inferred from direct assay	28098138	MGI
acts upstream of or within gene expression	IMP IMP: Inferred from mutant phenotype	18509511	MGI
acts upstream of or within inflammatory response	IMP IMP: Inferred from mutant phenotype	18509511	MGI
involved in inflammatory response	IMP IMP: Inferred from mutant phenotype	21880694	MGI
acts upstream of interferon-beta production	IMP IMP: Inferred from mutant phenotype	15661922	MGI
acts upstream of interleukin-10 production	IDA IDA: Inferred from direct assay	21609717	MGI
acts upstream of interleukin-6 production	IDA IDA: Inferred from direct assay	18261938	MGI
acts upstream of interleukin-6 production	IMP IMP: Inferred from mutant phenotype	10549626	MGI
involved in intestinal epithelial structure maintenance	IMP IMP: Inferred from mutant phenotype	20051628	MGI
involved in lipopolysaccharide-mediated signaling pathway	IDA IDA: Inferred from direct assay	28098138	MGI
acts upstream of or within lipopolysaccharide-mediated signaling pathway	IGI IGI: Inferred from genetic interaction	10880523	MGI
acts upstream of lymphocyte proliferation	IMP IMP: Inferred from mutant phenotype	10607756	MGI
acts upstream of macrophage cytokine production	IDA IDA: Inferred from direct assay	18261938	MGI
acts upstream of macrophage cytokine production	IMP IMP: Inferred from mutant phenotype	10549626	MGI
acts upstream of or within microglia differentiation	IMP IMP: Inferred from mutant phenotype	18509511	MGI
involved in negative regulation of ERK1 and ERK2 cascade	IMP IMP: Inferred from mutant phenotype	20051628	MGI
involved in negative regulation of cold-induced thermogenesis	IMP IMP: Inferred from mutant phenotype	26370079	MGI
involved in negative regulation of interleukin-17 production	IMP IMP: Inferred from mutant phenotype	18203139	MGI
involved in negative regulation of interleukin-23 production	IMP IMP: Inferred from mutant phenotype	18203139	MGI
involved in negative regulation of interleukin-6 production	IMP IMP: Inferred from mutant phenotype	18203139	MGI
involved in negative regulation of tumor necrosis factor production	IMP IMP: Inferred from mutant phenotype	20051628	MGI
involved in negative regulation of type II interferon production	IMP IMP: Inferred from mutant phenotype	20051628	MGI
acts upstream of or within neurogenesis	IMP IMP: Inferred from mutant phenotype	18509511	MGI
acts upstream of nitric oxide biosynthetic process	IMP IMP: Inferred from mutant phenotype	10549626	MGI
acts upstream of or within nitric oxide production involved in inflammatory response	IMP IMP: Inferred from mutant phenotype	10623794	MGI
acts upstream of nucleotide-binding oligomerization domain containing 1 signaling pathway	IDA IDA: Inferred from direct assay	18261938	MGI
acts upstream of nucleotide-binding oligomerization domain containing 2 signaling pathway	IDA IDA: Inferred from direct assay	18261938	MGI
acts upstream of or within positive regulation of B cell proliferation	IMP IMP: Inferred from mutant phenotype	10549626	MGI
acts upstream of or within positive regulation of ERK1 and ERK2 cascade	IDA IDA: Inferred from direct assay	18261938	MGI
acts upstream of or within positive regulation of JNK cascade	IDA IDA: Inferred from direct assay	16260493	MGI
acts upstream of or within positive regulation of JNK cascade	IGI IGI: Inferred from genetic interaction	16260493	MGI
acts upstream of positive regulation of MAP kinase activity	IMP IMP: Inferred from mutant phenotype	20051628	MGI
acts upstream of or within positive regulation of MHC class II biosynthetic process	IMP IMP: Inferred from mutant phenotype	10549626	MGI
involved in positive regulation of NF-kappaB transcription factor activity	IMP IMP: Inferred from mutant phenotype	29038465	MGI
involved in positive regulation of NLRP3 inflammasome complex assembly	IDA IDA: Inferred from direct assay	23812099	MGI
acts upstream of or within positive regulation of canonical NF-kappaB signal transduction	IDA IDA: Inferred from direct assay	19734906	MGI
involved in positive regulation of canonical NF-kappaB signal transduction	IDA IDA: Inferred from direct assay	16260493	MGI
involved in positive regulation of chemokine production	IDA IDA: Inferred from direct assay	15356140	MGI
involved in positive regulation of cytokine production involved in inflammatory response	IGI IGI: Inferred from genetic interaction	20037584	MGI
involved in positive regulation of extrinsic apoptotic signaling pathway	IGI IGI: Inferred from genetic interaction	20037584	MGI
involved in positive regulation of gene expression	IGI IGI: Inferred from genetic interaction	20037584	MGI
acts upstream of or within positive regulation of gene expression	IMP IMP: Inferred from mutant phenotype	21880694	MGI
involved in positive regulation of gene expression	IMP IMP: Inferred from mutant phenotype	20037584	MGI
involved in positive regulation of inflammatory response	IGI IGI: Inferred from genetic interaction	20037584	MGI
involved in positive regulation of interferon-alpha production	IDA IDA: Inferred from direct assay	15356140	MGI
involved in positive regulation of interferon-beta production	IDA IDA: Inferred from direct assay	15356140	MGI
acts upstream of or within positive regulation of interferon-beta production	IMP IMP: Inferred from mutant phenotype	15661922	MGI
involved in positive regulation of interleukin-1 beta production	IDA IDA: Inferred from direct assay	23812099	MGI
involved in positive regulation of interleukin-1 production	IDA IDA: Inferred from direct assay	15356140	MGI
acts upstream of or within positive regulation of interleukin-10 production	IDA IDA: Inferred from direct assay	21609717	MGI
involved in positive regulation of interleukin-10 production	IDA IDA: Inferred from direct assay	15356140	MGI
involved in positive regulation of interleukin-12 production	IDA IDA: Inferred from direct assay	15356140	MGI
acts upstream of or within positive regulation of interleukin-6 production	IDA IDA: Inferred from direct assay	18261938	MGI
involved in positive regulation of interleukin-6 production	IDA IDA: Inferred from direct assay	15356140	MGI
acts upstream of or within positive regulation of interleukin-6 production	IMP IMP: Inferred from mutant phenotype	10549626	MGI
acts upstream of or within positive regulation of lymphocyte proliferation	IMP IMP: Inferred from mutant phenotype	10607756	MGI
involved in positive regulation of macrophage activation	IGI IGI: Inferred from genetic interaction	20037584	MGI
acts upstream of or within positive regulation of macrophage cytokine production	IDA IDA: Inferred from direct assay	18261938	MGI
acts upstream of or within positive regulation of macrophage cytokine production	IMP IMP: Inferred from mutant phenotype	10549626	MGI
involved in positive regulation of nitric oxide biosynthetic process	IGI IGI: Inferred from genetic interaction	20037584	MGI
acts upstream of or within positive regulation of nitric oxide biosynthetic process	IMP IMP: Inferred from mutant phenotype	10549626	MGI
involved in positive regulation of nitric-oxide synthase biosynthetic process	IDA IDA: Inferred from direct assay	15356140	MGI
acts upstream of or within positive regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway	IDA IDA: Inferred from direct assay	18261938	MGI
acts upstream of or within positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway	IDA IDA: Inferred from direct assay	18261938	MGI
involved in positive regulation of platelet activation	IMP IMP: Inferred from mutant phenotype	16514062	MGI
involved in positive regulation of reactive oxygen species biosynthetic process	IMP IMP: Inferred from mutant phenotype	20037584	MGI
acts upstream of or within positive regulation of smooth muscle cell migration	IMP IMP: Inferred from mutant phenotype	21880694	MGI
acts upstream of or within positive regulation of smooth muscle cell proliferation	IMP IMP: Inferred from mutant phenotype	21880694	MGI
acts upstream of or within positive regulation of stress-activated MAPK cascade	IDA IDA: Inferred from direct assay	18261938	MGI
involved in positive regulation of transcription by RNA polymerase II	IDA IDA: Inferred from direct assay	15356140	MGI
acts upstream of or within positive regulation of tumor necrosis factor production	IDA IDA: Inferred from direct assay	18261938	MGI
involved in positive regulation of tumor necrosis factor production	IDA IDA: Inferred from direct assay	15356140	MGI
acts upstream of or within positive regulation of tumor necrosis factor production	IMP IMP: Inferred from mutant phenotype	10549626	MGI
involved in positive regulation of type II interferon production	IMP IMP: Inferred from mutant phenotype	18203139	MGI
acts upstream of or within regulation of dendritic cell cytokine production	IDA IDA: Inferred from direct assay	19047410	MGI
involved in regulation of inflammatory response	IMP IMP: Inferred from mutant phenotype	18203139	MGI
acts upstream of or within response to bacterium	IMP IMP: Inferred from mutant phenotype	11294571	MGI
acts upstream of or within response to lipopolysaccharide	IGI IGI: Inferred from genetic interaction	11489994	MGI
acts upstream of or within response to lipopolysaccharide	IMP IMP: Inferred from mutant phenotype	10229796	MGI
acts upstream of stress-activated MAPK cascade	IDA IDA: Inferred from direct assay	18261938	MGI
acts upstream of or within toll-like receptor 4 signaling pathway	IDA IDA: Inferred from direct assay	25549946	MGI
involved in toll-like receptor 4 signaling pathway	IDA IDA: Inferred from direct assay	28098138	MGI
acts upstream of tumor necrosis factor production	IDA IDA: Inferred from direct assay	18261938	MGI
acts upstream of tumor necrosis factor production	IMP IMP: Inferred from mutant phenotype	10549626	MGI
acts upstream of or within type II interferon production	IGI IGI: Inferred from genetic interaction	11489994	MGI
involved in wound healing involved in inflammatory response	IMP IMP: Inferred from mutant phenotype	21880694	MGI

Cellular Component GO Annotation	Evidence	References	Source
located in plasma membrane	IDA IDA: Inferred from direct assay	25549946	MGI
part of receptor complex	IDA IDA: Inferred from direct assay	28098138	MGI

EXP: Inferred from Experiment IDA: Inferred from direct assay IPI: Inferred from physical interaction IMP: Inferred from mutant phenotype IGI: Inferred from genetic interaction IEP: Inferred from expression pattern

Tlr4 Protein Structure

PLN00113

LRR_RI

PPP1R42

LRR_RI

TIR

0
200
400
600
835 a.a.

Protein Preferred Names	Protein Names
toll-like receptor 4	Toll like receptor 4 lipopolysaccharide response

Tlr4 Protein-protein interaction Information

Type	Protein Name	Protein ID	Interactor	Interactor Species	Interactor ID	Detection Method	References
Intra	Tlr4	Q9QUK6	Ly96	Mus musculus	Q9JHF9	Comig Non-Denat Gel	22532668
Intra	Tlr4	Q9QUK6	Ly96	Mus musculus	Q9JHF9	GMS	22532668
Intra	Tlr4	Q9QUK6	Ly96	Mus musculus	Q9JHF9	X-Ray Diffraction	22532668
Intra	Tlr4	Q9QUK6	Ly96	Mus musculus	Q9JHF9	GMS	21857663
Intra	Tlr4	Q9QUK6	Ly96	Mus musculus	Q9JHF9	SAXS	22532668
Intra	Tlr4	Q9QUK6	Tradd	Mus musculus	Q3U0V2	Anti Bait CoIP	18719121
Intra	Tlr4	Q9QUK6	Tradd	Mus musculus	Q3U0V2	Anti Tag CoIP	18719121
Intra	Tlr4	Q9QUK6	Myd88	Mus musculus	P22366	Anti Bait CoIP	23023391

Cross: Cross-species interaction Intra: Intraspecies interaction

Related Agents

Approval
Clinical Phase
Pre-clinical Phase

Approval

Bioactive Molecules (6)

Cat. No.	Product Name	Effect	Purity	Rare Diseases
HY-108910	Chymotrypsin	Inhibitor	/	Unkown
HY-N0680	Thiamine hydrochloride	Inhibitor	99.97%	Unkown
HY-14806B	Teneligliptin hydrobromide hydrate	Inhibitor	99.97%	Unkown
HY-130320	Monophosphoryl lipid A	Agonist	99.87%	Unkown
HY-W105835	Magnesium citrate	Modulator	98.0%	Unkown
HY-107352	Fosfenopril	Inhibitor	99.85%	Unkown

Clinical Phase

Bioactive Molecules (6)

Cat. No.	Product Name	Effect	Purity	Phase
HY-D1056	Lipopolysaccharides, from E. coli O55:B5	Activator	/	Phase 4
HY-N8277	Kdo2-Lipid A ammonium	Activator	99.00%	Phase 4
HY-165632	Creatine ethyl ester	Activator	/	Phase 4
HY-11109	Resatorvid	Inhibitor	99.95%	Phase 3
HY-14750	Rabeximod		/	Phase 2
HY-165386	TU-100	Inhibitor	/	Phase 2

Pre-clinical Phase

Bioactive Molecules (80)

Cat. No.	Product Name	Effect	Purity	Rare Diseases
HY-107575	TLR4-IN-C34	Inhibitor	99.94%	Unkown
HY-N0703	Schaftoside	Inhibitor	99.70%	Unkown
HY-P1439	RS 09	Agonist	99.88%	Unkown
HY-116213	Sparstolonin B	Antagonist	99.94%	Unkown
HY-N0108	Physcion	Inhibitor	99.40%	Unkown
HY-N6673	Okanin	Inhibitor	99.98%	Unkown
HY-N6612	D-Glucuronic acid	Agonist	98.0%	Unkown
HY-125171	IAXO-102	Antagonist	98.0%	Unkown
HY-N1346	Robinin	Inhibitor	99.96%	Unkown
HY-N0774	Isofraxidin	Inhibitor	99.94%	Unkown
HY-N7700A	Guluronic acid sodium	Inhibitor	98.0%	Unkown
HY-P1439A	RS 09 TFA	Agonist	99.87%	Unkown
HY-159069	Zymosan (ZM), 95%	Activator	96.11%	Unkown
HY-Y0278	Chloranil	Inducer	98%	Unkown
HY-U00435	Neoseptin 3	Agonist	99.21%	Unkown
HY-18325	AN-3485	Inhibitor	97.38%	Unkown
HY-P10227	Xelafaslatide	Inhibitor	99.88%	Unkown
HY-N2345	Procyanidin B3	Inhibitor	99.92%	Unkown
HY-N2110	Phellopterin	Inhibitor	99.94%	Unkown
HY-103483	MD2-IN-1	Inhibitor	99.88%	Unkown
HY-128598	MD2-TLR4-IN-1	Inhibitor	98.16%	Unkown
HY-W082785A	L6H21	Inhibitor	99.19%	Unkown
HY-N1508	Ecliptasaponin A	Inhibitor	99.81%	Unkown
HY-N2055	Kaempferol 3-O-sophoroside	Inhibitor	99.41%	Unkown
HY-N0726	Dracorhodin perchlorate	Modulator	99.02%	Unkown
HY-124750	NecroX-7	Inhibitor	99.69%	Unkown
HY-P10208A	RKH acetate	Antagonist	99.79%	Unkown
HY-108910A	Chymotrypsin (MS grade)	Inhibitor	/	Unkown
HY-N0392	Polygalasaponin F	Inhibitor	99.85%	Unkown
HY-101318	β-Funaltrexamine hydrochloride	Inhibitor	99.07%	Unkown
HY-135042	CAY10614	Antagonist	98.87%	Unkown
HY-N4093	Astringin	Inhibitor	99.54%	Unkown
HY-129440	N-(p-Coumaroyl) Serotonin	Inhibitor	99.03%	Unkown
HY-175222	GlcNAc-MurNAc	Inhibitor	95.37%	Unkown
HY-N7627	Regaloside C	Chemical	99.62%	Unkown
HY-126154	L48H37	Inhibitor	97.13%	Unkown
HY-146195	MAPK-IN-1	Inhibitor	98.11%	Unkown
HY-175674	NGI-235		99.70%	Unkown
HY-NP192	Sericin	Inhibitor	0%	Unkown
HY-168710	TLR4/NF-κB-IN-1	Inhibitor	99.92%	Unkown
HY-N6928	Mogroside III-E	Inhibitor	99.30%	Unkown
HY-N0320	Salvianolic acid D	Inhibitor	95.15%	Unkown
HY-N8284	Tomentosin	Inhibitor	98.95%	Unkown
HY-W012837	Benzylmethyl ether		98.70%	Unkown
HY-N3097	Pellitorine	Inhibitor	99.84%	Unkown
HY-P10897	SjDX5-271	Inhibitor	98.90%	Unkown
HY-145245	TLR4-IN-C34-C2-amide-C6-OH	Inhibitor	99.62%	Unkown
HY-178037	TLR9 antagonist 1	Antagonist	/	Unkown
HY-N12378	β-Patchoulene	Inhibitor	96.88%	Unkown
HY-179474	TSI-13-57	Inhibitor	98.73%	Unkown
HY-N7700	Guluronic acid	Inhibitor	98.90%	Unkown
HY-W041608	Methylchloroisothiazolinone	Activator	/	Unkown
HY-179646	CIAC101	Antagonist	/	Unkown
HY-146560	Xanthine oxidase-IN-6	Inhibitor	/	Unkown
HY-145253	Tri(TLR4-IN-C34-C2-amide-PEG1)-amide-C3-COOH	Inhibitor	/	Unkown
HY-182034	GAP214	Agonist	/	Unkown
HY-N8903	Mumefural	Inhibitor	95.17%	Unkown
HY-169057	BI1543673	Inhibitor	/	Unkown
HY-186062	HCN-IN-1	Inhibitor	/	Unkown
HY-N17383	Ligusticum cycloprolactam	Inhibitor	/	Unkown
HY-173388A	rel-TLR4-IN-2	Inhibitor	/	Unkown
HY-P11442	Lytx-Pa2a	Inhibitor	/	Unkown
HY-183573	PTPRO-IN-1	Inhibitor	/	Unkown
HY-176755	CCL-34	Activator	/	Unkown
HY-N19847	LYRM03	Inhibitor	/	Unkown
HY-P11580	Pap12-6-10	Inhibitor	/	Unkown
HY-179036	APG-7		/	Unkown
HY-P11093	Papiliocin	Inhibitor	/	Unkown
HY-176837	NOD2/TLR4 agonist-1	Agonist	/	Unkown
HY-174465	TLR4L 10	Ligand	/	Unkown
HY-129684	IAXO-101 iodide	Inhibitor	/	Unkown
HY-162004	NF-κB-IN-14	Inhibitor	/	Unkown
HY-145255	Tri(TLR4-IN-C34-C2-amide-C3-amide-PEG1)-amide-C3-COOH	Inhibitor	/	Unkown
HY-N6612A	D-Glucuronic acid sodium salt monohydrate	Agonist	98.0%	Unkown
HY-160938	β-Funaltrexamine	Inhibitor	/	Unkown
HY-P11250	HVF18-a3-d	Inhibitor	/	Unkown
HY-180336	LM9	Inhibitor	/	Unkown
HY-N16021	4A-MPLA ammonium	Agonist	/	Unkown
HY-W127601	Lard oil	Activator	/	Unkown
HY-N7697C	Chitohexaose hexahydrochloride	Inhibitor	95.0%	Unkown

Orthologs Information

Species	Symbol	Source	ID
Homo sapiens	Tlr4	NCBI	NCBI:7099