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    TLR4 toll-like receptor 4 [ Homo sapiens ]

    Gene ID: 7099, updated on 20-May-2012
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    Summary

    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]
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    Genomic context

    Location :
    9q33.1
    Sequence :
    Chromosome: 9; NC_000009.11 (120466460..120479768)
    See TLR4 in Epigenomics, MapViewer

    Chromosome 9 - NC_000009.11Genomic Context describing neighboring genes Neighboring gene astrotactin 2 Neighboring gene small nucleolar RNA, H/ACA box 70C (retrotransposed) Neighboring gene ribosomal protein L10 pseudogene 3 Neighboring gene ribosomal protein L35a pseudogene 22 Neighboring gene tumor protein, translationally-controlled 1 pseudogene Neighboring gene deleted in bladder cancer 1

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    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
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    Bibliography

    Related articles in PubMed

    1. Polymorphisms of the TLR2 and TLR4 genes are associated with risk of gastric cancer in a Brazilian population. de Oliveira JG, et al. World J Gastroenterol, 2012 Mar 21. PMID 22468087.
    2. [CARD15 and TLR4 genes polymorphisms in atopic bronchial asthma]. Voron'ko OE, et al. Mol Biol (Mosk), 2011 Sep-Oct. PMID 22393779.
    3. Cytokine and chemokine modification by Toll-like receptor polymorphisms is associated with nasopharyngeal carcinoma. Yang ZH, et al. Cancer Sci, 2012 Apr. PMID 22320262.
    4. Mannose-binding lectin and Toll-like receptor polymorphisms and Chagas disease in Chile. Weitzel T, et al. Am J Trop Med Hyg, 2012 Feb. PMID 22302853.
    5. Polymorphism of the TLR4 gene reduces the risk of hepatitis C virus-induced hepatocellular carcinoma. Agúndez JA, et al. Oncology, 2012. PMID 22286521.

    See all (1175) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. Our data suggest that TLR4 T399I modify cytokines and chemokines patterns and play a role in the development of NPC.
      Title: Cytokine and chemokine modification by Toll-like receptor polymorphisms is associated with nasopharyngeal carcinoma.
    2. Data indicate that TLR2 -196 to -174 del and TLR4+896G may increase the risk of gastric cancer in a Brazilian population.
      Title: Polymorphisms of the TLR2 and TLR4 genes are associated with risk of gastric cancer in a Brazilian population.
    3. TLR4(1196C>T) variant was associated with protection from melioidosis when compared with non-hospitalized controls.
      Title: Toll-like receptor 4 region genetic variants are associated with susceptibility to melioidosis.
    4. Chemerin enhanced expression of TLR4 and induced release of CCL2 in synovial fibroblasts.
      Title: Chemerin induces CCL2 and TLR4 in synovial fibroblasts of patients with rheumatoid arthritis and osteoarthritis.
    5. The expression of TLR4 may be closely associated with the course of gallbladder carcinoma.
      Title: TLR4 expression in normal gallbladder, chronic cholecystitis and gallbladder carcinoma.
    6. The stimulation of HK-2 infected with HBV by LPS may upregulate the expression of TLR4 and reduce the copies of HBV DNA.
      Title: [The expression and role of Toll receptor 4 in renal tubular epithelial cells in hepatitis B virus infection].
    7. No TLR4 polymorphisms were detected in Korean subjects.
      Title: Association between toll-like receptors/CD14 gene polymorphisms and inflammatory bowel disease in Korean population.
    8. MLK4 is a negative regulator of TLR4 signaling.
      Title: MLK4 has negative effect on TLR4 signaling.
    9. Our results demonstrate increased expression of TLR4 and TLR9 on lung CD8(+) T cells in COPD. CD8(+) T cells exposed to CSC increased TLR4 and TLR9 levels and increased cytokine production.
      Title: Cigarette smoke increases TLR4 and TLR9 expression and induces cytokine production from CD8(+) T cells in chronic obstructive pulmonary disease.
    10. In acute coronary syndromes, MRP8 and MRP8/14 complex are specific ligands of TLR4, which induce the release of TNFalpha and probably other pro-inflammatory agents from monocytes
      Title: Myeloid related proteins activate Toll-like receptor 4 in human acute coronary syndromes.
    Submit: New GeneRIF Correction See all (907)
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    Phenotypes

    Review eQTL and phenotype association data in this region using PheGenI

    Colorectal cancer, susceptibility to

    Endotoxin hyporesponsiveness

    Longevity, susceptibility to

    Macular degeneration, age-related, 10

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    HIV-1 protein interactions

    Protein Gene Interaction Pubs
    Vpr 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

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    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    O00206 O95999 BCL10    HPRD  PubMed  
    O00206 Q06187 BTK    HPRD  PubMed  
    O00206 P08571 CD14    HPRD  PubMed  
    O00206 MGC40499 CNPY4    HPRD  PubMed  
    O00206 O15263 DEFB4A    HPRD  PubMed  
    O00206 P09429 HMGB1    HPRD  PubMed  
    O00206 P14625 HSP90B1    HPRD  PubMed  
    O00206 P51617 IRAK1    HPRD  PubMed  
    O00206 O43187 IRAK2    HPRD  PubMed  
    O00206 Q9Y6Y9 LY96    HPRD  PubMed  
    O00206 Q9UPT6 MAPK8IP3    HPRD  PubMed  
    O00206 Q99836 MYD88    HPRD  PubMed  
    O00206 Q9NPH5 NOX4    HPRD  PubMed  
    O00206 O43353 RIPK2    HPRD  PubMed  
    O00206 TRIAD3 RNF216    HPRD  PubMed  
    O00206 Q6IA17 SIGIRR    HPRD  PubMed  
    O00206 P43405 SYK    HPRD  PubMed  
    O00206 Toll like receptor adaptor molecule 2 TICAM2    HPRD  PubMed  
    O00206 P58753 TIRAP    HPRD  PubMed  
    O00206 Q15399 TLR1    HPRD  PubMed  
    O00206 O60602 TLR5    HPRD  PubMed  
    O00206 Q9H0E2 TOLLIP    HPRD  PubMed  
    BioGRID:112954 BioGRID:119446 ECSIT    BioGRID  PubMed Phenotypic Suppression 
    BioGRID:112954 BioGRID:109544 HSPA8    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:112954 BioGRID:109863 IRAK1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:112954 BioGRID:119322 IRAK4    BioGRID  PubMed Affinity Capture-Western 
    NP_056179.1 LY96    BIND  PubMed MD-2 interacts with TLR4 
    BioGRID:112954 BioGRID:117170 LY96    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:112954 BioGRID:110700 MYD88    BioGRID  PubMed Affinity Capture-Western; PCA; Phenotypic Suppression; Reconstituted Complex; Two-hybrid 
    BioGRID:112954 BioGRID:111523 PPP4C    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:112954 BioGRID:111576 PRKCZ    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:112954 BioGRID:119981 RNF216    BioGRID  PubMed Two-hybrid 
    BioGRID:112954 BioGRID:121873 SIGIRR    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:112954 BioGRID:112592 SRC    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:112954 BioGRID:125352 STK11IP    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:112954 BioGRID:115563 STUB1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:112954 BioGRID:118878 TBK1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:112954 BioGRID:131694 TICAM2    BioGRID  PubMed Affinity Capture-MS; PCA 
    BioGRID:112954 BioGRID:125325 TIRAP    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western; PCA; Phenotypic Suppression; Reconstituted Complex 
    BioGRID:112954 BioGRID:112951 TLR1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:112954 BioGRID:119978 TOLLIP    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:112954 BioGRID:113039 TRAF3    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:112954 BioGRID:113041 TRAF6    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:112954 BioGRID:126654 TRIM69    BioGRID  PubMed Affinity Capture-Western 
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    General gene information

    Markers

    Genotypes

    Homology

    Pathways from BioSystems

    • 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 ...
    • 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). RIP1 was shown to be dispensabl...
    • IRAK2 mediated activation of TAK1 complex, organism-specific biosystem (from REACTOME)
      IRAK2 mediated activation of TAK1 complex, organism-specific biosystemAlthough IRAK-1 was originally thought to be a key mediator of TRAF6 activation in the IL1R/TLR signaling (Dong W et al. 2006), recent studies showed that IRAK-2, but not IRAK-1, led to TRAF6 polyubi...
    • 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...
    • 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 cascade initiated on plasma membrane, organism-specific biosystem (from REACTOME)
      MyD88 cascade initiated on plasma membrane, organism-specific biosystemMammalian myeloid differentiation factor 88 (MyD88) is Toll/interleukin (IL)-1 (TIR)-domain containing adapter protein which plays crucial role in TLR signaling. All TLRs, with only one exception of...
    • MyD88-independent cascade initiated on plasma membrane, organism-specific biosystem (from REACTOME)
      MyD88-independent cascade initiated on plasma membrane, organism-specific biosystemThe MyD88-independent signaling route utilizes TRAM and TRIF adapters, that are essential for production of both type 1 interferons(IFNs) and pro-inflammatory cytokines. TRAM is thought to bridge bet...
    • 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...
    • NFkB and MAP kinases activation mediated by TLR4 signaling repertoire, organism-specific biosystem (from REACTOME)
      NFkB and MAP kinases activation mediated by TLR4 signaling repertoire, organism-specific biosystemMitogen activated protein kinase (MAPK) cascade, one of the most ancient and evolutionarily conserved signaling pathways, is involved in many processes of immune responses. The MAP kinases cascade tr...
    • 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, 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...
    • 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...
    • 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...
    • Toll Like Receptor 10 (TLR10) Cascade, organism-specific biosystem (from REACTOME)
      Toll Like Receptor 10 (TLR10) Cascade, organism-specific biosystemLittle is known about TLR10 ligands. It has been established that the receptor homodimerizes upon binding and signals in an MyD88-dependent manner (Hasan U et al 2005; Nyman T et al 2008). It may als...
    • 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 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 5 (TLR5) Cascade, organism-specific biosystem (from REACTOME)
      Toll Like Receptor 5 (TLR5) Cascade, organism-specific biosystemTLR5 is the receptor for flagellin, the protein that forms bacterial flagella. Unlike most other Pathogen-Associated Molecular Patterns (PAMPs), flagellin does not undergo any posttranslational modif...
    • 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 Receptor Cascades, organism-specific biosystem (from REACTOME)
      Toll Receptor 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...

    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 
    phosphatidylinositol 3-kinase binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    receptor activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    transmembrane signaling receptor activity NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    I-kappaB kinase/NF-kappaB cascade 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 
    Toll 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 
    immunoglobulin mediated immune response IEA
    Inferred from Electronic Annotation
    more info
    		  
    innate immune response TAS
    Traceable Author Statement
    more info
    		 PubMed 
    innate immune response-activating signal transduction IEA
    Inferred from Electronic Annotation
    more info
    		  
    intestinal epithelial structure maintenance ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    lipopolysaccharide-mediated signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    macrophage activation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    microglial cell activation involved in immune response IEA
    Inferred from Electronic Annotation
    more info
    		  
    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
    		  
    pathogen-associated molecular pattern dependent induction by symbiont of host innate immune response IEA
    Inferred from Electronic Annotation
    more info
    		  
    positive regulation of B cell proliferation IEA
    Inferred from Electronic Annotation
    more info
    		  
    positive regulation of DNA binding 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 cascade 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 apoptotic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    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 peptidyl-tyrosine phosphorylation 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 sensory perception of pain IEA
    Inferred from Electronic Annotation
    more info
    		  
    response to activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    response to ethanol IEA
    Inferred from Electronic Annotation
    more info
    		  
    response to fatty acid IEA
    Inferred from Electronic Annotation
    more info
    		  
    response to hypoxia IEA
    Inferred from Electronic Annotation
    more info
    		  
    response to insulin stimulus 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 
    response to oxidative stress IEA
    Inferred from Electronic Annotation
    more info
    		  
    response to progesterone stimulus IEA
    Inferred from Electronic Annotation
    more info
    		  
    response to toxin IEA
    Inferred from Electronic Annotation
    more info
    		  
    signal transduction IEA
    Inferred from Electronic Annotation
    more info
    		  
    skeletal muscle contraction IEA
    Inferred from Electronic Annotation
    more info
    		  
    toll-like receptor 1 signaling pathway TAS
    Traceable Author Statement
    more info
    		  
    toll-like receptor 2 signaling pathway TAS
    Traceable Author Statement
    more info
    		  
    toll-like receptor 4 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 
    external side of plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    integral to plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    intracellular IEA
    Inferred from Electronic Annotation
    more info
    		  
    lipopolysaccharide receptor complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    membrane raft IEA
    Inferred from Electronic Annotation
    more info
    		  
    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
    		  
    Help top of page

    General protein information

    Preferred Names
    toll-like receptor 4
    Names
    toll-like receptor 4
    hToll
    homolog of Drosophila toll
    Help top of page

    NCBI Reference Sequences (RefSeq)

    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 RefSeqGene

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

    mRNA and Protein(s)

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

      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
      PLN00113
      Location:7 – 492
      Blast Score: 164
      PLN00113; leucine-rich repeat receptor-like protein kinase; Provisional
      smart00082
      Location:539 – 585
      Blast Score: 108
      LRRCT; Leucine rich repeat C-terminal domain
      cl15309
      Location:332 – 541
      Blast Score: 95
      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 ...
      cl15770
      Location:636 – 773
      Blast Score: 324
      TIR_2; TIR domain

    2. NM_138554.4 → NP_612564.1  toll-like receptor 4 isoform A precursor

      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/TrEMBL
      D1CS53
      UniProtKB/Swiss-Prot
      O00206
      Related
      ENSP00000363089, OTTHUMP00000022807, ENST00000355622, OTTHUMT00000055549
      Conserved Domains (4) summary
      PLN00113
      Location:47 – 532
      Blast Score: 165
      PLN00113; leucine-rich repeat receptor-like protein kinase; Provisional
      smart00082
      Location:579 – 625
      Blast Score: 107
      LRRCT; Leucine rich repeat C-terminal domain
      cl15309
      Location:372 – 581
      Blast Score: 96
      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 ...
      cl15770
      Location:676 – 813
      Blast Score: 326
      TIR_2; TIR domain

    3. NM_138557.2 → NP_612567.1  toll-like receptor 4 isoform D

      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:379 – 425
      Blast Score: 108
      LRRCT; Leucine rich repeat C-terminal domain
      cl15309
      Location:172 – 381
      Blast Score: 97
      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 ...
      pfam13855
      Location:272 – 332
      Blast Score: 110
      LRR_8; Leucine rich repeat
      cl15770
      Location:476 – 613
      Blast Score: 324
      TIR_2; TIR domain

    RefSeqs of Annotated Genomes: Build 37.3

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

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000009.11 Reference GRCh37.p5 Primary Assembly

      Range
      120466460..120479768
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000141.1 Alternate HuRef

      Range
      90084542..90097849
      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.
    Help top of page

    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AF172171.1 AAF89753.1
    genomic AF177765.1 AAF05316.1
    genomic AF177766.1 AAF07823.1
    genomic AL160272.16 CAH72618.1
      CAH72619.1
    genomic CH471090.1 EAW87448.1
      EAW87449.1
      EAW87451.1
    genomic DQ018108.1 AAY82268.1
    genomic DQ018109.1 AAY82269.1
    genomic FB700885.1 CAS02255.1
    genomic GM869034.1 CAT16978.1
    mRNA AA598398.1 None
    mRNA AB445638.1 BAG55035.1
    mRNA AK226155.1 None
    mRNA AK290053.1 BAF82742.1
    mRNA AK293068.1 BAF85757.1
    mRNA AK303730.1 BAG64706.1
    mRNA AL710219.1 None
    mRNA BC025294.1 None
    mRNA BC117422.1 AAI17423.1
    mRNA BC143841.1 None
    mRNA BG622357.1 None
    mRNA DA126770.1 None
    mRNA DA187988.1 None
    mRNA DA218006.1 None
    mRNA U69193.1 None
    mRNA U88880.1 AAC34135.1
    mRNA U93091.1 AAC80227.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    O00206.2 GenPept UniProtKB/Swiss-Prot:O00206
    Help top of page

    Additional Links

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
    Medical
    Molecular Biology Databases
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