|Homo sapiens Gene: TLR4|
|Last Modified||2014-10-13 [Report errors or provide feedback]|
|Gene Name||toll-like receptor 4|
|Synonyms||ARMD10; CD284; TLR-4; TOLL;|
toll-like receptor 4
toll-like receptor 4
|Useful resources||Stemformatics EHFPI ImmGen|
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.
TLR4 binding to microbial ligands can be inhibited by CD180 and its helper molecule, LY86, via direct interactions with the TLR4 signalling complex.
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.
TLR4-TLR6-Cd36 activation is a common molecular mechanism by which atherogenic lipids and amyloid-beta stimulate sterile inflammation.
TLR4 dimerize and enable rapid signal transduction against LPS stimulation on membrane-associated CD14-expressing cells.
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.
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.
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)
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)
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)
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.
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)
TLR4 on dendritic cell surfaces binds to HSPA14 and induces a robust Th1 response via the MAPK and NFkB signalling pathways. (Demonstrated in mouse)
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)
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)
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)
TLR4 translocates to membrane lipid rafts in a ceramide-dependent manner in Helicobacter pylori infected gastric epithelial cells.
TLR4 is involved in cell-cell contact signalling between activated apoptotic lymphocytes and dendritic cells (DC) during the maturation of DCs.
Synthetic triacylated lipid A-molecules have the potent ability to selectively antagonize TLR4 and inhibit anti-bacterial immunity.
The poxviral protein A46 directly inhibits TLR4 signalling by disrupting receptor complex formation.
A human TLR4 polymorphism (D299G/T399I) impairs TLR4::LY96 dimerization and results in a dampened host response to bacterial lipids.
TLR4 is an important regulator of wound inflammation and is essential for early skin wound healing. (Demonstrated in mice)
TIR domain-contaning protein from Brucella melitensis, TcpB, disrupts the receptor-adaptor interaction between TLR4 and TIRAP.
ECSIT binds to MAP3K7 and TRAF6 to form a complex that plays a pivotal role in activating TLR4-mediated NF-kB signalling.
The TLR4/S100A8 axis is important in the activation of monocytes.
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.
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.
PELI3 is involved in endotoxin tolerance and functions as a negative regulator of TLR2/4 signalling.
|InnateDB Annotation from Orthologs|
[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.
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]
|Genomic Location||Chromosome 9:117704332-117716871|
|Number of Interactions||
This gene and/or its encoded proteins are associated with 91 experimentally validated interaction(s) in this database.
They are also associated with 38 interaction(s) predicted by orthology.
Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon pathway
Toll Like Receptor TLR1:TLR2 Cascade pathway
TRIF-mediated programmed cell death pathway
Toll Like Receptor TLR6:TLR2 Cascade pathway
Innate Immune System pathway
IKK complex recruitment mediated by RIP1 pathway
Toll Like Receptor 3 (TLR3) Cascade pathway
Toll Like Receptor 2 (TLR2) Cascade pathway
Toll-Like Receptors Cascades pathway
TRAF6 mediated induction of TAK1 complex pathway
Immune System pathway
MyD88-independent cascade pathway
MyD88:Mal cascade initiated on plasma membrane pathway
Toll Like Receptor 4 (TLR4) Cascade pathway
Activated TLR4 signalling pathway
TRIF-mediated TLR3/TLR4 signaling pathway
Toll-like receptor signaling pathway pathway
Pathogenic Escherichia coli infection pathway
Chagas disease (American trypanosomiasis) pathway
Toll-like receptor signaling pathway pathway
Endogenous TLR signaling
|UniProt Splice Variant|
|RefSeq||NM_003266 NM_138554 NM_138557|
|EMBL||AB445638 AF172169 AF172170 AF172171 AF177765 AF177766 AK290053 AK293068 AK303730 AL160272 BC117422 CH471090 DQ018107 DQ018108 DQ018109 EF535831 EF535832 EF535833 GQ903698 GQ903701 GQ903702 JQ480854 JQ480855 JQ480856 JQ480857 JQ480859 JQ480860 JQ480861 JQ480862 JQ480863 JQ480864 JQ480865 JQ480866 JQ480867 JQ480868 JQ480871 JQ480872 JQ480873 JQ480874 JQ480875 JQ480877 JQ480878 JQ480879 JQ480880 JQ480881 JQ480882 JQ480884 JQ480886 JQ480887 JQ480888 JQ480889 JQ480890 JQ480893 JQ480894 JQ480895 JQ480896 JQ480897 JQ480898 JQ480899 JQ480900 JQ480901 JQ480903 JQ480904 JQ480905 JQ480906 JQ480907 JQ480908 JQ480909 JQ480912 JQ480914 JQ480915 JQ480916 JQ480918 JQ480919 JQ480921 JQ480925 JQ480926 JQ480927 JQ480928 JQ480929 JQ480930 JQ480931 JQ480933 JQ480934 JQ480935 JQ480936 JQ480939 JQ480940 JQ480941 JQ480942 JQ480943 JQ480944 JQ480946 JQ480947 JQ480948 JQ480949 JQ480950 JQ480952 JQ480954 JQ480955 JQ480956 JQ480958 JQ480960 JQ480961 JQ480964 JQ480965 JQ480969 JQ480970 JQ480971 JQ480972 JQ480973 JQ480976 JQ480978 JQ480979 JQ480980 JQ480982 JQ480984 JQ480985 JQ480986 JQ480989 JQ480991 JQ480992 JQ480993 JQ480994 JQ480998 JQ481001 JQ481002 JQ481006 JQ481007 JQ481008 JQ481009 JQ481012 JQ481013 JQ481015 JQ481016 JQ481017 JQ481018 JQ481019 JQ481022 JQ481023 JQ481024 JQ481025 JQ481026 JQ481028 JQ481029 JQ481030 JQ481031 JQ481032 JQ481033 JQ481034 JQ481035 JQ481037 JQ481038 JQ481039 JQ481040 JQ481041 JQ481042 JQ481043 JQ481044 JQ481045 JQ481046 JQ481048 JQ481049 JQ481050 JQ481051 JQ481052 JQ481053 JQ481054 JQ481055 JQ481056 JQ481057 JQ481058 JQ481059 JQ481060 JQ481061 JQ481063 JQ481065 JQ481066 JQ481067 JQ481068 JQ481069 JQ481070 JQ481071 JQ481072 JQ481073 JQ481074 JQ481076 JQ481078 JQ481080 JQ481083 JQ481086 JQ481088 JQ481089 JQ481091 JQ481092 JQ481093 JQ481094 JQ481095 JQ481096 JQ481098 JQ481099 JQ481100 JQ481101 JQ481103 JQ481107 JQ481108 JQ481109 JQ481112 JQ481113 JQ481114 JQ481115 JQ481117 JQ481119 JQ481121 JQ481124 JQ481125 JQ481129 JQ481130 JQ481131 JQ481133 JQ481135 JQ481136 JQ481137 JQ481138 JQ481139 JQ481140 JQ481141 JQ481142 JQ481143 JQ481144 JQ481145 JQ481146 JQ481147 JQ481148 JQ481149 JQ481150 JQ481151 JQ481152 JQ481153 JQ481154 JQ481155 JQ481156 JQ481160 JQ481161 JQ481162 JQ481164 JQ481165 JQ481166 JQ481167 JQ481168 JQ481169 JQ481171 JQ481172 JQ481173 JQ481174 JQ481175 JQ481176 JQ481177 JQ481178 JQ481179 JQ481180 JQ481181 JQ481183 JQ481184 JQ481185 JQ481186 JQ481187 JQ481189 JQ481190 JQ481191 JQ481192 JQ481193 JQ481194 JQ481195 JQ481196 JQ481197 JQ481198 JQ481199 JQ481200 JQ481201 JQ481202 JQ481203 JQ481204 JQ481205 JQ481206 JQ481207 JQ481208 JQ481209 JQ481210 JQ481211 JQ481212 JQ481213 JQ481215 JQ481218 JQ481219 JQ481220 JQ481221 JQ481222 JQ481224 JQ481225 JQ481226 JQ481228 JQ481231 JQ481234 JQ481235 JQ481237 JQ481238 JQ481239 JQ481240 JQ481241 U88880 U93091|
|GenPept||AAC34135 AAC80227 AAF05316 AAF07823 AAF89753 AAI17423 AAY82267 AAY82268 AAY82269 ABU41662 ABU41663 ABU41664 ACX46980 ACX46983 ACX46984 AFX71930 AFX71931 AFX71932 AFX71933 AFX71935 AFX71936 AFX71937 AFX71938 AFX71939 AFX71940 AFX71941 AFX71942 AFX71943 AFX71944 AFX71947 AFX71948 AFX71949 AFX71950 AFX71951 AFX71953 AFX71954 AFX71955 AFX71956 AFX71957 AFX71958 AFX71960 AFX71962 AFX71963 AFX71964 AFX71965 AFX71966 AFX71969 AFX71970 AFX71971 AFX71972 AFX71973 AFX71974 AFX71975 AFX71976 AFX71977 AFX71979 AFX71980 AFX71981 AFX71982 AFX71983 AFX71984 AFX71985 AFX71988 AFX71990 AFX71991 AFX71992 AFX71994 AFX71995 AFX71997 AFX72001 AFX72002 AFX72003 AFX72004 AFX72005 AFX72006 AFX72007 AFX72009 AFX72010 AFX72011 AFX72012 AFX72015 AFX72016 AFX72017 AFX72018 AFX72019 AFX72020 AFX72022 AFX72023 AFX72024 AFX72025 AFX72026 AFX72028 AFX72030 AFX72031 AFX72032 AFX72034 AFX72036 AFX72037 AFX72040 AFX72041 AFX72045 AFX72046 AFX72047 AFX72048 AFX72049 AFX72052 AFX72054 AFX72055 AFX72056 AFX72058 AFX72060 AFX72061 AFX72062 AFX72065 AFX72067 AFX72068 AFX72069 AFX72070 AFX72074 AFX72077 AFX72078 AFX72082 AFX72083 AFX72084 AFX72085 AFX72088 AFX72089 AFX72091 AFX72092 AFX72093 AFX72094 AFX72095 AFX72098 AFX72099 AFX72100 AFX72101 AFX72102 AFX72104 AFX72105 AFX72106 AFX72107 AFX72108 AFX72109 AFX72110 AFX72111 AFX72113 AFX72114 AFX72115 AFX72116 AFX72117 AFX72118 AFX72119 AFX72120 AFX72121 AFX72122 AFX72124 AFX72125 AFX72126 AFX72127 AFX72128 AFX72129 AFX72130 AFX72131 AFX72132 AFX72133 AFX72134 AFX72135 AFX72136 AFX72137 AFX72139 AFX72141 AFX72142 AFX72143 AFX72144 AFX72145 AFX72146 AFX72147 AFX72148 AFX72149 AFX72150 AFX72152 AFX72154 AFX72156 AFX72159 AFX72162 AFX72164 AFX72165 AFX72167 AFX72168 AFX72169 AFX72170 AFX72171 AFX72172 AFX72174 AFX72175 AFX72176 AFX72177 AFX72179 AFX72183 AFX72184 AFX72185 AFX72188 AFX72189 AFX72190 AFX72191 AFX72193 AFX72195 AFX72197 AFX72200 AFX72201 AFX72205 AFX72206 AFX72207 AFX72209 AFX72211 AFX72212 AFX72213 AFX72214 AFX72215 AFX72216 AFX72217 AFX72218 AFX72219 AFX72220 AFX72221 AFX72222 AFX72223 AFX72224 AFX72225 AFX72226 AFX72227 AFX72228 AFX72229 AFX72230 AFX72231 AFX72232 AFX72236 AFX72237 AFX72238 AFX72240 AFX72241 AFX72242 AFX72243 AFX72244 AFX72245 AFX72247 AFX72248 AFX72249 AFX72250 AFX72251 AFX72252 AFX72253 AFX72254 AFX72255 AFX72256 AFX72257 AFX72259 AFX72260 AFX72261 AFX72262 AFX72263 AFX72265 AFX72266 AFX72267 AFX72268 AFX72269 AFX72270 AFX72271 AFX72272 AFX72273 AFX72274 AFX72275 AFX72276 AFX72277 AFX72278 AFX72279 AFX72280 AFX72281 AFX72282 AFX72283 AFX72284 AFX72285 AFX72286 AFX72287 AFX72288 AFX72289 AFX72291 AFX72294 AFX72295 AFX72296 AFX72297 AFX72298 AFX72300 AFX72301 AFX72302 AFX72304 AFX72307 AFX72310 AFX72311 AFX72313 AFX72314 AFX72315 AFX72316 AFX72317 BAF82742 BAF85757 BAG55035 BAG64706 CAH72618 CAH72619 EAW87448 EAW87451|
|RNA Seq Atlas||7099|