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TLR4 toll-like receptor 4 [ Homo sapiens (human) ]

Gene ID: 7099, updated on 26-Aug-2014
Official Symbol
TLR4provided by HGNC
Official Full Name
toll-like receptor 4provided by HGNC
Primary source
HGNC:11850
See related
Ensembl:ENSG00000136869; HPRD:04325; MIM:603030; Vega:OTTHUMG00000021046
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
TOLL; CD284; TLR-4; ARMD10
Summary
The protein encoded by this gene is a member of the Toll-like receptor (TLR) family which plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. They recognize pathogen-associated molecular patterns that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity. The various TLRs exhibit different patterns of expression. This receptor has been implicated in signal transduction events induced by lipopolysaccharide (LPS) found in most gram-negative bacteria. Mutations in this gene have been associated with differences in LPS responsiveness. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]
See TLR4 in Epigenomics, MapViewer
Location:
9q33.1
Exon count:
4
Annotation release Status Assembly Chr Location
106 current GRCh38 (GCF_000001405.26) 9 NC_000009.12 (117704175..117717491)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 9 NC_000009.11 (120466453..120479769)

Chromosome 9 - NC_000009.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC101928797 Neighboring gene ribosomal protein L35a pseudogene 22 Neighboring gene uncharacterized LOC101928826 Neighboring gene tumor protein, translationally-controlled 1 pseudogene 9 Neighboring gene uncharacterized LOC102724929

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Associated conditions

Description Tests
Age-related macular degeneration 10
MedGen: C1969108 OMIM: 611488 GeneReviews: Not available
Compare labs

NHGRI GWAS Catalog

Description
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
NHGRI GWA Catalog

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env The binding of soluble HIV-1 gp120 to TLR2 or TLR4 results in upregulation of the TNF-alpha and IL-8 production through NF-kappaB activation PubMed
env Human primary astrocytes exposed to HIV-1 gp120 has a significant increase in TLR4 protein expression PubMed
Tat tat HIV-1 Tat protein decreases TLR4 protein levels and suppresses C. parvum-induced TLR4 protein expression PubMed
Vpr vpr HIV-1 Vpr-induced IL-6 production depends on the activation of NFkappaB and the involvement of C/EBP-beta, TLR4, and MyD88 PubMed
vpr HIV-1 Vpr potentiates the suppression of Toll-like receptor 4 by glucocorticoids via the glucocorticoid receptor pathway PubMed

Go to the HIV-1, Human Protein Interaction Database

  • Activated TLR4 signalling, organism-specific biosystem (from REACTOME)
    Activated TLR4 signalling, organism-specific biosystemTLR4 is unique among the TLR family in its ability to recruit four adapters to activate two distinct signaling pathways. One pathway is activated by the pair of the adapters Mal or TIRAP (Toll/inter...
  • Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon, organism-specific biosystem (from REACTOME)
    Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon, organism-specific biosystemCell stimulation with viral ds RNA leads to the activation of two IKK-related serine/threonine kinases, TBK1 and IKK-i which directly phosphorylate IRF3 and IRF7 promoting their dimerization and tran...
  • Amoebiasis, organism-specific biosystem (from KEGG)
    Amoebiasis, organism-specific biosystemEntamoeba histolytica, an extracellular protozoan parasite is a human pathogen that invades the intestinal epithelium. Infection occurs on ingestion of contaminated water and food. The pathogenesis o...
  • Amoebiasis, conserved biosystem (from KEGG)
    Amoebiasis, conserved biosystemEntamoeba histolytica, an extracellular protozoan parasite is a human pathogen that invades the intestinal epithelium. Infection occurs on ingestion of contaminated water and food. The pathogenesis o...
  • Chagas disease (American trypanosomiasis), organism-specific biosystem (from KEGG)
    Chagas disease (American trypanosomiasis), organism-specific biosystemTrypanosoma cruzi is an intracellular protozoan parasite that causes Chagas disease. The parasite life cycle involves hematophagous reduviid bugs as vectors. Once parasites enter the host body, they ...
  • Chagas disease (American trypanosomiasis), conserved biosystem (from KEGG)
    Chagas disease (American trypanosomiasis), conserved biosystemTrypanosoma cruzi is an intracellular protozoan parasite that causes Chagas disease. The parasite life cycle involves hematophagous reduviid bugs as vectors. Once parasites enter the host body, they ...
  • Corticotropin-releasing hormone, organism-specific biosystem (from WikiPathways)
    Corticotropin-releasing hormone, organism-specific biosystemCorticotropin-releasing hormone (CRH) is a neuropeptide secreted abundantly in the paraventricular nucleus of the hypothalamus, amygdala, cerebral cortex and cerebellum in the central nervous system ...
  • HIF-1 signaling pathway, organism-specific biosystem (from KEGG)
    HIF-1 signaling pathway, organism-specific biosystemHypoxia-inducible factor 1 (HIF-1) is a transcription factor that functions as a master regulator of oxygen homeostasis. It consists of two subunits: an inducibly-expressed HIF-1alpha subunit and a c...
  • Hepatitis B, organism-specific biosystem (from KEGG)
    Hepatitis B, organism-specific biosystemHepatitis B virus (HBV) is an enveloped virus and contains a partially double-stranded relaxed circular DNA (RC-DNA) genome. After entry into hepatocytes, HBV RC-DNA is transported to the nucleus and...
  • IKK complex recruitment mediated by RIP1, organism-specific biosystem (from REACTOME)
    IKK complex recruitment mediated by RIP1, organism-specific biosystemReceptor-interacting protein 1 (RIP1) mediates the activation of proinflammatory cytokines via intermediate induction of IKK complex in NFkB pathways [Ea et al. 2006]. Poly(I-C) treatment stimulated ...
  • Immune System, organism-specific biosystem (from REACTOME)
    Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
  • Inflammatory bowel disease (IBD), organism-specific biosystem (from KEGG)
    Inflammatory bowel disease (IBD), organism-specific biosystemInflammatory bowel disease (IBD), which includes Crohn disease (CD) and ulcerative colitis (UC), is characterized by chronic inflammation of the gastrointestinal tract due to environmental and geneti...
  • Inflammatory bowel disease (IBD), conserved biosystem (from KEGG)
    Inflammatory bowel disease (IBD), conserved biosystemInflammatory bowel disease (IBD), which includes Crohn disease (CD) and ulcerative colitis (UC), is characterized by chronic inflammation of the gastrointestinal tract due to environmental and geneti...
  • Influenza A, organism-specific biosystem (from KEGG)
    Influenza A, organism-specific biosystemInfluenza is a contagious respiratory disease caused by influenza virus infection. Influenza A virus is responsible for both annual seasonal epidemics and periodic worldwide pandemics. Novel strains ...
  • Influenza A, conserved biosystem (from KEGG)
    Influenza A, conserved biosystemInfluenza is a contagious respiratory disease caused by influenza virus infection. Influenza A virus is responsible for both annual seasonal epidemics and periodic worldwide pandemics. Novel strains ...
  • Innate Immune System, organism-specific biosystem (from REACTOME)
    Innate Immune System, organism-specific biosystemInnate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup
  • Legionellosis, organism-specific biosystem (from KEGG)
    Legionellosis, organism-specific biosystemLegionellosis is a potentially fatal infectious disease caused by the bacterium Legionella pneumophila and other legionella species. Two distinct clinical and epidemiological syndromes are associated...
  • Legionellosis, conserved biosystem (from KEGG)
    Legionellosis, conserved biosystemLegionellosis is a potentially fatal infectious disease caused by the bacterium Legionella pneumophila and other legionella species. Two distinct clinical and epidemiological syndromes are associated...
  • Leishmaniasis, organism-specific biosystem (from KEGG)
    Leishmaniasis, organism-specific biosystemLeishmania is an intracellular protozoan parasite of macrophages that causes visceral, mucosal, and cutaneous diseases. The parasite is transmitted to humans by sandflies, where they survive and prol...
  • Leishmaniasis, conserved biosystem (from KEGG)
    Leishmaniasis, conserved biosystemLeishmania is an intracellular protozoan parasite of macrophages that causes visceral, mucosal, and cutaneous diseases. The parasite is transmitted to humans by sandflies, where they survive and prol...
  • Malaria, organism-specific biosystem (from KEGG)
    Malaria, organism-specific biosystemPlasmodium protozoa are parasites that account for malaria infection. Sporozoite forms of the parasite are injected by mosquito bites under the skin and are carried to the liver where they develop in...
  • Malaria, conserved biosystem (from KEGG)
    Malaria, conserved biosystemPlasmodium protozoa are parasites that account for malaria infection. Sporozoite forms of the parasite are injected by mosquito bites under the skin and are carried to the liver where they develop in...
  • Measles, organism-specific biosystem (from KEGG)
    Measles, organism-specific biosystemMeasles virus (MV) is highly contagious virus that leads infant death worldwide. Humans are the unique natural reservoir for this virus. It causes severe immunosuppression favouring secondary bacteri...
  • Measles, conserved biosystem (from KEGG)
    Measles, conserved biosystemMeasles virus (MV) is highly contagious virus that leads infant death worldwide. Humans are the unique natural reservoir for this virus. It causes severe immunosuppression favouring secondary bacteri...
  • MyD88-independent cascade, organism-specific biosystem (from REACTOME)
    MyD88-independent cascade, organism-specific biosystemMyD88-independent signaling pathway is shared by TLR3 and TLR4 cascades. TIR-domain-containing adapter-inducing interferon-beta (TRIF or TICAM1) is a key adapter molecule in transducing signals from ...
  • MyD88:Mal cascade initiated on plasma membrane, organism-specific biosystem (from REACTOME)
    MyD88:Mal cascade initiated on plasma membrane, organism-specific biosystemThe first known downstream component of TLR4 and TLR2 signaling is the adaptor MyD88. Another adapter MyD88-adaptor-like (Mal; also known as TIR-domain-containing adaptor protein or TIRAP) has also b...
  • NF-kappa B signaling pathway, organism-specific biosystem (from KEGG)
    NF-kappa B signaling pathway, organism-specific biosystemNuclear factor-kappa B (NF-kappa B) is the generic name of a family of transcription factors that function as dimers and regulate genes involved in immunity, inflammation and cell survival. There are...
  • PI3K-Akt signaling pathway, organism-specific biosystem (from KEGG)
    PI3K-Akt signaling pathway, organism-specific biosystemThe phosphatidylinositol 3' -kinase(PI3K)-Akt signaling pathway is activated by many types of cellular stimuli or toxic insults and regulates fundamental cellular functions such as transcription, tra...
  • PI3K-Akt signaling pathway, conserved biosystem (from KEGG)
    PI3K-Akt signaling pathway, conserved biosystemThe phosphatidylinositol 3' -kinase(PI3K)-Akt signaling pathway is activated by many types of cellular stimuli or toxic insults and regulates fundamental cellular functions such as transcription, tra...
  • Pathogenic Escherichia coli infection, organism-specific biosystem (from KEGG)
    Pathogenic Escherichia coli infection, organism-specific biosystemEnteropathogenic E. coli (EPEC) and enterohemorrhagic E. coli (EHEC) are closely related pathogenic strains of Escherichia coli. The hallmark of EPEC/EHEC infections [DS:H00278 H00277] is induction o...
  • Pathogenic Escherichia coli infection, organism-specific biosystem (from WikiPathways)
    Pathogenic Escherichia coli infection, organism-specific biosystemSources: [http://www.genome.jp/kegg/pathway/hsa/hsa05130.html KEGG]
  • Pathogenic Escherichia coli infection, conserved biosystem (from KEGG)
    Pathogenic Escherichia coli infection, conserved biosystemEnteropathogenic E. coli (EPEC) and enterohemorrhagic E. coli (EHEC) are closely related pathogenic strains of Escherichia coli. The hallmark of EPEC/EHEC infections [DS:H00278 H00277] is induction o...
  • Pertussis, organism-specific biosystem (from KEGG)
    Pertussis, organism-specific biosystemPertussis, also known as whooping cough, is an acute respiratory infectious disease caused by a bacteria called Bordetella Pertussis. The characteristic symptoms are paroxysmal cough, inspiratory whe...
  • Pertussis, conserved biosystem (from KEGG)
    Pertussis, conserved biosystemPertussis, also known as whooping cough, is an acute respiratory infectious disease caused by a bacteria called Bordetella Pertussis. The characteristic symptoms are paroxysmal cough, inspiratory whe...
  • Phagosome, organism-specific biosystem (from KEGG)
    Phagosome, organism-specific biosystemPhagocytosis is the process of taking in relatively large particles by a cell, and is a central mechanism in the tissue remodeling, inflammation, and defense against infectious agents. A phagosome is...
  • Phagosome, conserved biosystem (from KEGG)
    Phagosome, conserved biosystemPhagocytosis is the process of taking in relatively large particles by a cell, and is a central mechanism in the tissue remodeling, inflammation, and defense against infectious agents. A phagosome is...
  • Proteoglycans in cancer, organism-specific biosystem (from KEGG)
    Proteoglycans in cancer, organism-specific biosystemMany proteoglycans (PGs) in the tumor microenvironment have been shown to be key macromolecules that contribute to biology of various types of cancer including proliferation, adhesion, angiogenesis a...
  • Proteoglycans in cancer, conserved biosystem (from KEGG)
    Proteoglycans in cancer, conserved biosystemMany proteoglycans (PGs) in the tumor microenvironment have been shown to be key macromolecules that contribute to biology of various types of cancer including proliferation, adhesion, angiogenesis a...
  • Regulation of toll-like receptor signaling pathway, organism-specific biosystem (from WikiPathways)
    Regulation of toll-like receptor signaling pathway, organism-specific biosystem
    Regulation of toll-like receptor signaling pathway
  • Rheumatoid arthritis, organism-specific biosystem (from KEGG)
    Rheumatoid arthritis, organism-specific biosystemRheumatoid arthritis (RA) is a chronic autoimmune joint disease where persistent inflammation affects bone remodeling leading to progressive bone destruction. In RA, abnormal activation of the immune...
  • Rheumatoid arthritis, conserved biosystem (from KEGG)
    Rheumatoid arthritis, conserved biosystemRheumatoid arthritis (RA) is a chronic autoimmune joint disease where persistent inflammation affects bone remodeling leading to progressive bone destruction. In RA, abnormal activation of the immune...
  • Salmonella infection, organism-specific biosystem (from KEGG)
    Salmonella infection, organism-specific biosystemSalmonella infection usually presents as a self-limiting gastroenteritis or the more severe typhoid fever and bacteremia. The common disease-causing Salmonella species in human is a single species, S...
  • Salmonella infection, conserved biosystem (from KEGG)
    Salmonella infection, conserved biosystemSalmonella infection usually presents as a self-limiting gastroenteritis or the more severe typhoid fever and bacteremia. The common disease-causing Salmonella species in human is a single species, S...
  • Spinal Cord Injury, organism-specific biosystem (from WikiPathways)
    Spinal Cord Injury, organism-specific biosystemThis pathway provides an overview of cell types, therapeutic targets, drugs, new proposed targets and pathways implicated in spinal cord injury. Spinal cord injury is a complex multistep process that...
  • TRAF6 mediated induction of TAK1 complex, organism-specific biosystem (from REACTOME)
    TRAF6 mediated induction of TAK1 complex, organism-specific biosystemIn human, together with ubiquitin-conjugating E2-type enzymes UBC13 and UEV1A (also known as UBE2V1), TRAF6 catalyses Lys63-linked ubiquitination. It is believed that auto polyubiquitination and oli...
  • TRIF-mediated TLR3/TLR4 signaling, organism-specific biosystem (from REACTOME)
    TRIF-mediated TLR3/TLR4 signaling, organism-specific biosystemTRIF(TICAM1) was shown to induce IRF3/7 and NF-?B activation and apoptosis through distinct intracellular signaling pathways [Han KJ et al 2004; Kaiser WJ and Offermann MK et al 2005]. TRIF consists...
  • TRIF-mediated programmed cell death, organism-specific biosystem (from REACTOME)
    TRIF-mediated programmed cell death, organism-specific biosystemTLR3 and -4 trigger TRIF-dependent programmed cell death in various human and mouse cells [Kalai M et al 2002; Han KJ et al 2004; Kaiser WJ and Offermann MK 2005; Estornes Y et al 2012; He S et al 20...
  • Toll Like Receptor 2 (TLR2) Cascade, organism-specific biosystem (from REACTOME)
    Toll Like Receptor 2 (TLR2) Cascade, organism-specific biosystemTLR2 is involved in recognition of peptidoglycan from gram-positive bacteria, bacterial lipoproteins, mycoplasma lipoprotein and mycobacterial products. It is quite possible that recognition of at le...
  • Toll Like Receptor 3 (TLR3) Cascade, organism-specific biosystem (from REACTOME)
    Toll Like Receptor 3 (TLR3) Cascade, organism-specific biosystemToll-like receptor 3 (TLR3) as was shown for mammals is expressed on myeloid dendritic cells, respiratory epithelium, macrophages, and appears to play a central role in mediating the antiviral and in...
  • Toll Like Receptor 4 (TLR4) Cascade, organism-specific biosystem (from REACTOME)
    Toll Like Receptor 4 (TLR4) Cascade, organism-specific biosystemToll-like Receptor 4 is a Microbe Associated Molecular Pattern receptor well known for it's sensitivity to Bacterial Lipopolysaccharides (LPS). LPS is assembled within diverse Gram-negative bacteria,...
  • Toll Like Receptor TLR1:TLR2 Cascade, organism-specific biosystem (from REACTOME)
    Toll Like Receptor TLR1:TLR2 Cascade, organism-specific biosystemTLR1 is expressed by monocytes. TLR1 and TLR2 cotranslationally form heterodimeric complexes on the cell surface and in the cytosol. The TLR2:TLR1 complex recognizes Neisserial PorB and Mycobacterial...
  • Toll Like Receptor TLR6:TLR2 Cascade, organism-specific biosystem (from REACTOME)
    Toll Like Receptor TLR6:TLR2 Cascade, organism-specific biosystemTLR2 and TLR4 recognize different bacterial cell wall components. While TLR4 is trained onto Gram-negative lipopolysaccharide components, TLR2 - in combination with TLR6 - plays a major role in recog...
  • Toll-Like Receptors Cascades, organism-specific biosystem (from REACTOME)
    Toll-Like Receptors Cascades, organism-specific biosystemIn human, ten members of the Toll-like receptor (TLR) family (TLR1-TLR10) have been identified (TLR11 has been found in mouse, but not in human). All TLRs have a similar Toll/IL-1 receptor (TIR) doma...
  • Toll-like receptor signaling pathway, organism-specific biosystem (from KEGG)
    Toll-like receptor signaling pathway, organism-specific biosystemSpecific families of pattern recognition receptors are responsible for detecting microbial pathogens and generating innate immune responses. Toll-like receptors (TLRs) are membrane-bound receptors id...
  • Toll-like receptor signaling pathway, organism-specific biosystem (from WikiPathways)
    Toll-like receptor signaling pathway, organism-specific biosystemSpecific families of pattern recognition receptors are responsible for detecting microbial pathogens and generating innate immune responses. Toll-like receptors (TLRs) are membrane-bound receptors id...
  • Toll-like receptor signaling pathway, conserved biosystem (from KEGG)
    Toll-like receptor signaling pathway, conserved biosystemSpecific families of pattern recognition receptors are responsible for detecting microbial pathogens and generating innate immune responses. Toll-like receptors (TLRs) are membrane-bound receptors id...
  • Toxoplasmosis, organism-specific biosystem (from KEGG)
    Toxoplasmosis, organism-specific biosystemToxoplasma gondii is an obligate intracellular parasite that is prevalent worldwide. The tachyzoite form acquired by oral ingestion downmodulates proinflammatory signaling pathways via various mechan...
  • Toxoplasmosis, conserved biosystem (from KEGG)
    Toxoplasmosis, conserved biosystemToxoplasma gondii is an obligate intracellular parasite that is prevalent worldwide. The tachyzoite form acquired by oral ingestion downmodulates proinflammatory signaling pathways via various mechan...
  • Tuberculosis, organism-specific biosystem (from KEGG)
    Tuberculosis, organism-specific biosystemTuberculosis, or TB, is an infectious disease caused by Mycobacterium tuberculosis. One third of the world's population is thought to be infected with TB. About 90% of those infected result in latent...
  • Tuberculosis, conserved biosystem (from KEGG)
    Tuberculosis, conserved biosystemTuberculosis, or TB, is an infectious disease caused by Mycobacterium tuberculosis. One third of the world's population is thought to be infected with TB. About 90% of those infected result in latent...
Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
lipopolysaccharide binding IMP
Inferred from Mutant Phenotype
more info
PubMed 
lipopolysaccharide binding NAS
Non-traceable Author Statement
more info
PubMed 
lipopolysaccharide receptor activity IDA
Inferred from Direct Assay
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
receptor activity TAS
Traceable Author Statement
more info
PubMed 
transmembrane signaling receptor activity NAS
Non-traceable Author Statement
more info
PubMed 
Process Evidence Code Pubs
B cell proliferation involved in immune response IEA
Inferred from Electronic Annotation
more info
 
I-kappaB kinase/NF-kappaB signaling TAS
Traceable Author Statement
more info
 
I-kappaB phosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
MyD88-dependent toll-like receptor signaling pathway TAS
Traceable Author Statement
more info
 
MyD88-independent toll-like receptor signaling pathway TAS
Traceable Author Statement
more info
 
T-helper 1 type immune response NAS
Non-traceable Author Statement
more info
PubMed 
TRIF-dependent toll-like receptor signaling pathway TAS
Traceable Author Statement
more info
 
activation of MAPK activity ISS
Inferred from Sequence or Structural Similarity
more info
 
cellular response to lipopolysaccharide ISS
Inferred from Sequence or Structural Similarity
more info
 
cellular response to lipoteichoic acid IEA
Inferred from Electronic Annotation
more info
 
cellular response to mechanical stimulus IEP
Inferred from Expression Pattern
more info
PubMed 
defense response to Gram-negative bacterium IC
Inferred by Curator
more info
PubMed 
defense response to bacterium TAS
Traceable Author Statement
more info
PubMed 
detection of fungus NAS
Non-traceable Author Statement
more info
PubMed 
detection of lipopolysaccharide IDA
Inferred from Direct Assay
more info
PubMed 
immune response TAS
Traceable Author Statement
more info
PubMed 
innate immune response TAS
Traceable Author Statement
more info
PubMed 
interferon-gamma production IEA
Inferred from Electronic Annotation
more info
 
intestinal epithelial structure maintenance ISS
Inferred from Sequence or Structural Similarity
more info
 
NOT lipopolysaccharide-mediated signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
lipopolysaccharide-mediated signaling pathway IGI
Inferred from Genetic Interaction
more info
PubMed 
macrophage activation IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of ERK1 and ERK2 cascade ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of interferon-gamma production ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of interleukin-17 production ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of interleukin-23 production ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of interleukin-6 production ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of osteoclast differentiation NAS
Non-traceable Author Statement
more info
PubMed 
negative regulation of tumor necrosis factor production ISS
Inferred from Sequence or Structural Similarity
more info
 
nitric oxide production involved in inflammatory response IEA
Inferred from Electronic Annotation
more info
 
positive regulation of B cell proliferation IEA
Inferred from Electronic Annotation
more info
 
positive regulation of ERK1 and ERK2 cascade IEA
Inferred from Electronic Annotation
more info
 
positive regulation of I-kappaB kinase/NF-kappaB signaling IEA
Inferred from Electronic Annotation
more info
 
positive regulation of JNK cascade IEA
Inferred from Electronic Annotation
more info
 
positive regulation of MHC class II biosynthetic process IEA
Inferred from Electronic Annotation
more info
 
positive regulation of NF-kappaB import into nucleus IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of NF-kappaB transcription factor activity IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of chemokine production IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of inflammatory response IC
Inferred by Curator
more info
PubMed 
positive regulation of interferon-alpha production ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of interferon-beta biosynthetic process IEA
Inferred from Electronic Annotation
more info
 
positive regulation of interferon-beta production ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of interferon-gamma production ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of interleukin-1 production ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of interleukin-10 production ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of interleukin-12 biosynthetic process IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of interleukin-12 production ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of interleukin-6 production IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of interleukin-8 biosynthetic process IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of interleukin-8 production IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of macrophage cytokine production IEA
Inferred from Electronic Annotation
more info
 
positive regulation of nitric oxide biosynthetic process IEA
Inferred from Electronic Annotation
more info
 
positive regulation of nitric-oxide synthase biosynthetic process ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway IEA
Inferred from Electronic Annotation
more info
 
positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway IEA
Inferred from Electronic Annotation
more info
 
positive regulation of platelet activation ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
positive regulation of transcription from RNA polymerase II promoter ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of tumor necrosis factor biosynthetic process IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of tumor necrosis factor production ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of cytokine secretion IEA
Inferred from Electronic Annotation
more info
 
response to lipopolysaccharide IC
Inferred by Curator
more info
PubMed 
response to lipopolysaccharide IDA
Inferred from Direct Assay
more info
PubMed 
toll-like receptor 2 signaling pathway TAS
Traceable Author Statement
more info
 
toll-like receptor 3 signaling pathway TAS
Traceable Author Statement
more info
 
toll-like receptor 4 signaling pathway TAS
Traceable Author Statement
more info
 
toll-like receptor TLR1:TLR2 signaling pathway TAS
Traceable Author Statement
more info
 
toll-like receptor TLR6:TLR2 signaling pathway TAS
Traceable Author Statement
more info
 
toll-like receptor signaling pathway TAS
Traceable Author Statement
more info
 
Component Evidence Code Pubs
cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
endosome membrane TAS
Traceable Author Statement
more info
 
external side of plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
integral component of plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
lipopolysaccharide receptor complex IDA
Inferred from Direct Assay
more info
PubMed 
perinuclear region of cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane TAS
Traceable Author Statement
more info
 
Preferred Names
toll-like receptor 4
Names
toll-like receptor 4
hToll
homolog of Drosophila toll

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_011475.1 

    Range
    4994..18310
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_003266.3NP_003257.1  toll-like receptor 4 isoform C

    See proteins identical to NP_003257.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) contains an additional internal exon compared to transcript variant 1. This variant represents translation initiation at a downstream AUG compared to variant 1; the 5'-most initiation codon, as used in variant 1, is associated with a weak Kozak sequence and a truncated ORF that would render the transcript a candidate for nonsense-mediated decay (NMD). Leaky scanning may allow translation initiation at the downstream AUG, which results in an isoform (C) with a shorter N-terminus compared to isoform A.
    Source sequence(s)
    AK226155, BC025294, BC143841, BG622357, DA187988, DA218006
    UniProtKB/Swiss-Prot
    O00206
    Conserved Domains (4) summary
    smart00082
    Location:539585
    Blast Score: 111
    LRRCT; Leucine rich repeat C-terminal domain
    cd00116
    Location:112416
    Blast Score: 106
    LRR_RI; Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 residue sequence motifs present in many proteins that participate in protein-protein interactions and have different functions and cellular locations. LRRs correspond ...
    pfam01582
    Location:636774
    Blast Score: 334
    TIR; TIR domain
    pfam13855
    Location:3898
    Blast Score: 131
    LRR_8; Leucine rich repeat
  2. NM_138554.4NP_612564.1  toll-like receptor 4 isoform A precursor

    See proteins identical to NP_612564.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (A).
    Source sequence(s)
    AK226155, BC117422, BG622357, DA187988, DA218006
    Consensus CDS
    CCDS6818.1
    UniProtKB/Swiss-Prot
    O00206
    Related
    ENSP00000363089, OTTHUMP00000022807, ENST00000355622, OTTHUMT00000055549
    Conserved Domains (4) summary
    smart00082
    Location:579625
    Blast Score: 110
    LRRCT; Leucine rich repeat C-terminal domain
    cd00116
    Location:152456
    Blast Score: 108
    LRR_RI; Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 residue sequence motifs present in many proteins that participate in protein-protein interactions and have different functions and cellular locations. LRRs correspond ...
    pfam01582
    Location:676814
    Blast Score: 336
    TIR; TIR domain
    pfam13855
    Location:78138
    Blast Score: 133
    LRR_8; Leucine rich repeat
  3. NM_138557.2NP_612567.1  toll-like receptor 4 isoform D

    See proteins identical to NP_612567.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) lacks an internal exon compared to transcript variant 1. This variant represents translation initiation at a downstream AUG compared to variant 1; the 5'-most initiation codon, as used in variant 1, is associated with a weak Kozak sequence and a truncated ORF that would render the transcript a candidate for nonsense-mediated decay (NMD). Leaky scanning may allow translation initiation at the downstream AUG, which results in an isoform (D) with a shorter N-terminus compared to isoform A.
    Source sequence(s)
    AK226155, BC025294, BG622357, DA187988, DA218006
    UniProtKB/Swiss-Prot
    O00206
    Conserved Domains (4) summary
    smart00082
    Location:379425
    Blast Score: 110
    LRRCT; Leucine rich repeat C-terminal domain
    cd00116
    Location:27256
    Blast Score: 108
    LRR_RI; Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 residue sequence motifs present in many proteins that participate in protein-protein interactions and have different functions and cellular locations. LRRs correspond ...
    pfam01582
    Location:476614
    Blast Score: 332
    TIR; TIR domain
    pfam13855
    Location:271332
    Blast Score: 113
    LRR_8; Leucine rich repeat

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 106

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38 Primary Assembly

Genomic

  1. NC_000009.12 

    Range
    117704175..117717491
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

  1. AC_000141.1 

    Range
    90084535..90097850
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.1

Genomic

  1. NC_018920.2 

    Range
    120614005..120627323
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_138556.1: Suppressed sequence

    Description
    NM_138556.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein is not supported by current protein homology data.