Bos taurus Gene: TLR4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Summary | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
InnateDB Gene | IDBG-638758.3 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Last Modified | 2014-10-13 [Report errors or provide feedback] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Gene Symbol | TLR4 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Gene Name | toll-like receptor 4 precursor | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Synonyms | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Species | Bos taurus | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Ensembl Gene | ENSBTAG00000006240 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Encoded Proteins |
toll-like receptor 4 precursor
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Protein Structure | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Useful resources | Stemformatics EHFPI ImmGen | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
InnateDB Annotation from Orthologs | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Summary |
[Homo sapiens] TLR4 is activated by LPS and this recognition activates the Src family kinases, Src, Fyn and Yes, which in turn contribute to tyrosine phosphorylation of Zonula adherens proteins to open the endothelial paracellular pathway.
[Homo sapiens] TLR4 binding to microbial ligands can be inhibited by CD180 and its helper molecule, LY86, via direct interactions with the TLR4 signalling complex.
[Homo sapiens] TLR4 is involved in lipopolysaccharide (LPS) signaling and serves as a cell-surface co-receptor for CD14, leading to LPS-mediated NF-kappaB activation and subsequent cellular events.
[Homo sapiens] TLR4-TLR6-Cd36 activation is a common molecular mechanism by which atherogenic lipids and amyloid-beta stimulate sterile inflammation.
[Homo sapiens] TLR4 dimerize and enable rapid signal transduction against LPS stimulation on membrane-associated CD14-expressing cells.
[Homo sapiens] TLR4 and TLR9 have both non-redundant and cooperative roles in lung innate responses during Gram-negative bacterial pneumonia and are both critical for IL-17 driven antibacterial host response.
[Homo sapiens] TLR4 mediates LPS-induced muscle catabolism via coordinate activation of the ubiquitin-proteasome and the autophagy-lysosomal pathways. TLR4 activation by LPS induces C2C12 myotube atrophy via up-regulating autophagosome formation and the expression of ubiquitin ligase atrogin-1/MAFbx and MuRF1.
[Homo sapiens] TLR4 transfection of eukaryotic host cells using bacterial vectors, or bactofection, was shown to reduce E. coli colonization in the kidney and the bladder in an animal model of urinary tract infection. (Demonstrated in murine model)
[Homo sapiens] TLR4 is involved in the transmission of ER stress from tumour cells to macrophages, promoting a pro-inflammatory program in the tumour microenvironment, thus facilitating tumour progression. (Demonstrated in murine model)
[Homo sapiens] TLR4 deficient murine macrophages results in the complete abrogation of TNF-alpha production during Leishmania panamensis infection. The endosomal TLR4 plays a crucial role in the activation of host macrophages and controlling the early stages of parasitic infection. (Demonstrated in murine model)
[Homo sapiens] Epithelial TLR4 activation facilitates the transcytosis of non-cytolytic uropathogenic E. coli across intact collecting duct cell layers to invade the renal interstitium in experimental urinary tract infections.
[Homo sapiens] TLR4:LY96 functions as intracellular LPS sensor and triggers a unique set of LPS responses upon recognition of phagocytosed bacteria in macrophages. (Demonstrated in murine model)
[Homo sapiens] TLR4 on dendritic cell surfaces binds to HSPA14 and induces a robust Th1 response via the MAPK and NFkB signalling pathways. (Demonstrated in mouse)
[Homo sapiens] TLR4 recognizes Clostridium difficile surface layer proteins and induces the maturation of dendritic cells to activate the innate and adaptive immune response. (Demonstrated in mouse)
[Homo sapiens] TLR4 and HSPD1 mediate myocardial ischemia-activated innate immune signalling, which plays an important role in mediating apoptosis and inflammation during ischemia/reperfusion (I/R). (Demonstrated in murine model)
[Homo sapiens] TLR4 and TLR2 are crucial for in vivo recognition of Chlamydia pneumoniae. Tlr4/2 double-deficient mice were unable to control pneumonia caused by C. pneumoniae. (Demonstrated in mice)
[Homo sapiens] TLR4 translocates to membrane lipid rafts in a ceramide-dependent manner in Helicobacter pylori infected gastric epithelial cells.
[Homo sapiens] TLR4 is involved in cell-cell contact signalling between activated apoptotic lymphocytes and dendritic cells (DC) during the maturation of DCs.
[Homo sapiens] Synthetic triacylated lipid A-molecules have the potent ability to selectively antagonize TLR4 and inhibit anti-bacterial immunity.
[Homo sapiens] The poxviral protein A46 directly inhibits TLR4 signalling by disrupting receptor complex formation.
[Homo sapiens] A human TLR4 polymorphism (D299G/T399I) impairs TLR4::LY96 dimerization and results in a dampened host response to bacterial lipids.
[Homo sapiens] TLR4 is an important regulator of wound inflammation and is essential for early skin wound healing. (Demonstrated in mice)
[Homo sapiens] TIR domain-contaning protein from Brucella melitensis, TcpB, disrupts the receptor-adaptor interaction between TLR4 and TIRAP.
[Homo sapiens] ECSIT binds to MAP3K7 and TRAF6 to form a complex that plays a pivotal role in activating TLR4-mediated NF-kB signalling.
[Homo sapiens] The TLR4/S100A8 axis is important in the activation of monocytes.
[Homo sapiens] Endotoxin tolerance re-programs TLR4 signalling via suppression of PELI1, a positive regulator of MyD88- and TIR domain-containing adapter inducing IFN-β (TRIF)-dependent signalling that promotes K63-linked polyubiquitination of IRAK1, TBK1, and TAK1.
[Homo sapiens] H. pylori infection induces the expression and activation of components of NLRP3 inflammasomes in neutrophils and this activation is independent of a functional type IV secretion system, TLR2 and TLR4.
[Homo sapiens] PELI3 is involved in endotoxin tolerance and functions as a negative regulator of TLR2/4 signalling.
[Mus musculus] Signaling crosstalk during sequential Tlr4 and Tlr9 activation amplifies the inflammatory response of mouse macrophages.
[Mus musculus] Tlr4 and Tlr2 activate murine macrophages and this activation is negatively regulated by a Lyn/PI3K module and promoted by SHIP1.
[Mus musculus] Tlr4 transfection of eukaryotic host cells using bacterial vectors, or bactofection, was shown to reduce E. coli colonization in the kidney and the bladder in an animal model of urinary tract infection.
[Mus musculus] Tlr4 is involved in the transmission of ER stress from tumour cells to macrophages, promoting a pro-inflammatory program in the tumour microenvironment, thus facilitating tumour progression.
[Mus musculus] Tlr4 deficient murine macrophages results in the complete abrogation of TNF-alpha production during Leishmania panamensis infection. The endosomal Tlr4 plays a cruical role in the activation of host macrophages and controlling the early stages of parasitic infection.
[Mus musculus] Epithelial Tlr4 activation facilitates the transcytosis of non-cytolytic uropathogenic E. coli across intact collecting duct cell layers to invade the renal interstitium in experimental urinary tract infections.
[Mus musculus] Tlr4:Ly96 functions as intracellular LPS sensor and triggers a unique set of LPS responses upon recognition of phagocytosed bacteria in macrophages.
[Mus musculus] Tlr4 on dendritic cell surfaces binds to Hspa14 and induces a robust Th1 response via the MAPK and NFkB signalling pathways.
[Mus musculus] Tlr4 recognizes Clostridium difficile surface layer proteins and induces the maturation of dendritic cells to activate the innate and adaptive immune response.
[Mus musculus] Tlr4 and Hspd1 mediate myocardial ischemia-activated innate immune signalling, which plays an important role in mediating apoptosis and inflammation during ischemia/reperfusion (I/R).
[Mus musculus] Tlr4 and Tlr2 are crucial for in vivo recognition of Chlamydia pneumoniae. Tlr4/2 double-deficient mice were unable to control pneumonia caused by C. pneumoniae.
[Mus musculus] Tlr4 translocates to membrane lipid rafts in a ceramide-dependent manner in Helicobacter pylori infected gastric epithelial cells. (Demonstrated in human)
[Mus musculus] Tlr4 is involved in cell-cell contact signalling between activated apoptotic lymphocytes and dendritic cells (DC) during the maturation of DCs. (Demonstrated in human)
[Mus musculus] Synthetic triacylated lipid A-molecules have the potent ability to selectively antagonize Tlr4 and inhibit anti-bacterial immunity. (Demonstrated in human)
[Mus musculus] The poxviral protein A46 directly inhibits Tlr4 signalling by disrupting receptor complex formation. (Demonstrated in human)
[Mus musculus] A human TLR4 polymorphism (D299G/T399I) impairs TLR4::LY96 dimerization and results in a dampened host response to bacterial lipids. (Demonstrated in human)
[Mus musculus] Tlr4 is an important regulator of wound inflammation and is essential for early skin wound healing.
[Mus musculus] Milk oligosaccharide sialyl(α2,3)lactose modulates mucosal immunity by inducing inflammation through TLR4 signaling
[Mus musculus] Itgam (Cd11b) fine tunes the balance between adaptive and innate immune responses initiated by LPS by modulating the trafficking and signalling functions of Tlr4 in a cell-type-specific manner.
[Mus musculus] Nod1 and Nod2 synergize with Tlr4 in dendritic cells to increase IL12 production and enhance invariant natural killer T (iNKT) cell activation, and are important regulators of the IFN gamma response by iNKT cells during S. typhimurium and L. monocytogenes infections.
[Mus musculus] Rab8a interacts with Pik3cg to regulate Akt signalling generated by surface Tlr4.
[Mus musculus] High-potency Tlr4 agonists can act as clinically useful vaccine adjuvants by selectively activating Ticam1-dependent immunostimulatory signalling events and only weakly activating potentially harmful Myd88-dependent inflammatory responses.
[Mus musculus] Myd88 and Ticam1 pathways differently regulate Tlr4-induced immune responses in B cells.
[Mus musculus] Autophagy causes PELI3 degradation during Tlr4-signalling, subsequently inhibiting Il1b expression and impairing the hyperinflammatory phase during sepsis.
[Mus musculus] Tmem126a upregulates genes involved in antigen presentation; such as Icam1, MHC II, Cd86 and Cd40, via the Tlr4 signal transduction pathway.
[Mus musculus] Ticam1 but not Myd88 signalling is critical for the Trl4 protective adjuvant effect in neonates; where Ticam1(-/-) but not Myd88(-/-) neonates are highly susceptible to Escherichia coli peritonitis and bacteremia.
[Mus musculus] Wdfy1 is a crucial adaptor protein in the Tlr3/4 signalling pathway. Wdfy1 interacts with Tlr3 and Tlr4 and mediates the recruitment of Ticam1 to these receptors.
[Mus musculus] Lipopolysaccharide-mediated myeloid Anpep (CD13) expression governs internalization of Tlr4 and negatively regulates Tlr4 signalling, thereby balancing the innate response by maintaining the inflammatory equilibrium critical to innate immune regulation.
[Mus musculus] Psen2 deficiency is paralleled by reduced transcription of Tlr4 mRNA and loss of LPS-induced Tlr4 mRNA transcription regulation.
[Mus musculus] Peli3 is involved in endotoxin tolerance and functions as a negative regulator of Tlr2/4 signalling.
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Entrez Gene | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Summary |
This gene does not have any Entrez summary - the following is the summary from its human ortholog ENSG00000136869:
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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Gene Information | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Type | Protein coding | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Genomic Location | Chromosome 8:108828899-108839910 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Strand | Forward strand | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Band | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Transcripts |
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Interactions | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Number of Interactions |
This gene and/or its encoded proteins are associated with 0 experimentally validated interaction(s) in this database.
They are also associated with 77 interaction(s) predicted by orthology.
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Gene Ontology | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Molecular Function |
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Biological Process |
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Cellular Component |
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Orthologs | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Species
Homo sapiens
Mus musculus
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Gene ID
Gene Order
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Pathway Predictions based on Human Orthology Data | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
NETPATH | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
REACTOME |
TRAF6 mediated induction of TAK1 complex pathway
IKK complex recruitment mediated by RIP1 pathway
Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon pathway
TRIF-mediated programmed cell death pathway
MyD88-independent cascade pathway
Toll Like Receptor 3 (TLR3) Cascade pathway
MyD88:Mal cascade initiated on plasma membrane pathway
Toll Like Receptor TLR1:TLR2 Cascade pathway
Toll Like Receptor TLR6:TLR2 Cascade pathway
Toll Like Receptor 4 (TLR4) Cascade pathway
Innate Immune System pathway
Toll Like Receptor 2 (TLR2) Cascade pathway
Toll-Like Receptors Cascades pathway
Immune System pathway
Activated TLR4 signalling pathway
TRIF-mediated TLR3/TLR4 signaling pathway
Toll Like Receptor 3 (TLR3) Cascade pathway
Toll Like Receptor 2 (TLR2) Cascade pathway
Innate Immune System pathway
Toll Like Receptor TLR1:TLR2 Cascade pathway
TRAF6 mediated induction of TAK1 complex pathway
Immune System pathway
Toll Like Receptor TLR6:TLR2 Cascade pathway
Toll-Like Receptors Cascades pathway
TRIF-mediated programmed cell death pathway
Activated TLR4 signalling pathway
IKK complex recruitment mediated by RIP1 pathway
MyD88-independent cascade pathway
MyD88:Mal cascade initiated on plasma membrane pathway
TRIF-mediated TLR3/TLR4 signaling pathway
Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon pathway
Toll Like Receptor 4 (TLR4) Cascade pathway
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KEGG |
Pathogenic Escherichia coli infection pathway
Toll-like receptor signaling pathway pathway
Leishmaniasis pathway
Amoebiasis pathway
Malaria pathway
Chagas disease (American trypanosomiasis) pathway
Toxoplasmosis pathway
Phagosome pathway
Toll-like receptor signaling pathway pathway
Leishmaniasis pathway
Amoebiasis pathway
Malaria pathway
Phagosome pathway
Toxoplasmosis pathway
Chagas disease (American trypanosomiasis) pathway
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INOH |
Toll-like receptor signaling pathway pathway
Toll-like receptor signaling pathway pathway
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PID NCI |
Endogenous TLR signaling
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Cross-References | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
SwissProt | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
TrEMBL | Q56GY6 Q6WCD5 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
UniProt Splice Variant | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Entrez Gene | 281536 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
UniGene | Bt.9030 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
RefSeq | NM_174198 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
HUGO | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
OMIM | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
CCDS | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
HPRD | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
IMGT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
EMBL | AY297040 AY957625 DAAA02024656 DQ839567 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
GenPept | AAQ62700 AAX56982 ABH09760 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
RNA Seq Atlas | 281536 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||