TLR4
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].
| Name | OMIM ID | Ensembl ID | HGNC ID | PHARMGKB ID | Map Location |
|---|---|---|---|---|---|
| toll like receptor 4 | MIM:603030 | Ensembl:ENSG00000136869 | HGNC:HGNC:11850 | PA36552 | 9q33.1 |
GO terms in TLR4
| Term Type | Evidence Type | GO Term ID | GO Des. |
|---|---|---|---|
| MF | IBA | GO:0001530 | lipopolysaccharide binding |
| MF | IMP | GO:0001530 | lipopolysaccharide binding |
| MF | NAS | GO:0001530 | lipopolysaccharide binding |
| MF | IBA | GO:0001875 | lipopolysaccharide receptor activity |
| MF | IDA | GO:0001875 | lipopolysaccharide receptor activity |
| MF | NAS | GO:0004888 | transmembrane signaling receptor activity |
| MF | IPI | GO:0005102 | signaling receptor binding |
| MF | IPI | GO:0005515 | protein binding |
| MF | TAS | GO:0038023 | signaling receptor activity |
| MF | IPI | GO:0042802 | identical protein binding |
| MF | IPI | GO:0046982 | protein heterodimerization activity |
| CC | IPI | GO:0005622 | intracellular |
| CC | IDA | GO:0005737 | cytoplasm |
| CC | IEA | GO:0005769 | early endosome |
| CC | IDA | GO:0005886 | plasma membrane |
| CC | TAS | GO:0005886 | plasma membrane |
| CC | IBA | GO:0005887 | integral component of plasma membrane |
| CC | IDA | GO:0005887 | integral component of plasma membrane |
| CC | IDA | GO:0009897 | external side of plasma membrane |
| CC | IDA | GO:0009986 | cell surface |
| CC | TAS | GO:0010008 | endosome membrane |
| CC | IDA | GO:0031226 | intrinsic component of plasma membrane |
| CC | IPI | GO:0043235 | receptor complex |
| CC | IDA | GO:0046696 | lipopolysaccharide receptor complex |
| CC | IDA | GO:0048471 | perinuclear region of cytoplasm |
| BP | ISS | GO:0000187 | activation of MAPK activity |
| BP | IBA | GO:0002224 | toll-like receptor signaling pathway |
| BP | TAS | GO:0002224 | toll-like receptor signaling pathway |
| BP | ISS | GO:0002755 | MyD88-dependent toll-like receptor signaling pathway |
| BP | TAS | GO:0002755 | MyD88-dependent toll-like receptor signaling pathway |
| BP | TAS | GO:0002756 | MyD88-independent toll-like receptor signaling pathway |
| BP | IBA | GO:0006954 | inflammatory response |
| BP | TAS | GO:0006955 | immune response |
| BP | TAS | GO:0007249 | I-kappaB kinase/NF-kappaB signaling |
| BP | IDA | GO:0007252 | I-kappaB phosphorylation |
| BP | ISS | GO:0010572 | positive regulation of platelet activation |
| BP | IMP | GO:0010628 | positive regulation of gene expression |
| BP | ISS | GO:0010628 | positive regulation of gene expression |
| BP | NAS | GO:0016046 | detection of fungus |
| BP | IDA | GO:0031663 | lipopolysaccharide-mediated signaling pathway |
| BP | IGI | GO:0031663 | lipopolysaccharide-mediated signaling pathway |
| BP | IC | GO:0032496 | response to lipopolysaccharide |
| BP | IDA | GO:0032496 | response to lipopolysaccharide |
| BP | IDA | GO:0032497 | detection of lipopolysaccharide |
| BP | ISS | GO:0032689 | negative regulation of interferon-gamma production |
| BP | ISS | GO:0032700 | negative regulation of interleukin-17 production |
| BP | ISS | GO:0032707 | negative regulation of interleukin-23 production |
| BP | ISS | GO:0032715 | negative regulation of interleukin-6 production |
| BP | ISS | GO:0032720 | negative regulation of tumor necrosis factor production |
| BP | IDA | GO:0032722 | positive regulation of chemokine production |
| BP | ISS | GO:0032727 | positive regulation of interferon-alpha production |
| BP | ISS | GO:0032728 | positive regulation of interferon-beta production |
| BP | ISS | GO:0032729 | positive regulation of interferon-gamma production |
| BP | ISS | GO:0032732 | positive regulation of interleukin-1 production |
| BP | ISS | GO:0032733 | positive regulation of interleukin-10 production |
| BP | ISS | GO:0032735 | positive regulation of interleukin-12 production |
| BP | IDA | GO:0032755 | positive regulation of interleukin-6 production |
| BP | IDA | GO:0032757 | positive regulation of interleukin-8 production |
| BP | ISS | GO:0032760 | positive regulation of tumor necrosis factor production |
| BP | TAS | GO:0034128 | negative regulation of MyD88-independent toll-like receptor signaling pathway |
| BP | TAS | GO:0034142 | toll-like receptor 4 signaling pathway |
| BP | ISS | GO:0035666 | TRIF-dependent toll-like receptor signaling pathway |
| BP | TAS | GO:0035666 | TRIF-dependent toll-like receptor signaling pathway |
| BP | NAS | GO:0042088 | T-helper 1 type immune response |
| BP | IMP | GO:0042116 | macrophage activation |
| BP | IDA | GO:0042535 | positive regulation of tumor necrosis factor biosynthetic process |
| BP | TAS | GO:0042742 | defense response to bacterium |
| BP | ISS | GO:0043032 | positive regulation of macrophage activation |
| BP | IDA | GO:0045084 | positive regulation of interleukin-12 biosynthetic process |
| BP | TAS | GO:0045087 | innate immune response |
| BP | IDA | GO:0045416 | positive regulation of interleukin-8 biosynthetic process |
| BP | ISS | GO:0045429 | positive regulation of nitric oxide biosynthetic process |
| BP | NAS | GO:0045671 | negative regulation of osteoclast differentiation |
| BP | ISS | GO:0045944 | positive regulation of transcription by RNA polymerase II |
| BP | ISS | GO:0050702 | interleukin-1 beta secretion |
| BP | IDA | GO:0050718 | positive regulation of interleukin-1 beta secretion |
| BP | IC | GO:0050729 | positive regulation of inflammatory response |
| BP | IBA | GO:0050829 | defense response to Gram-negative bacterium |
| BP | IC | GO:0050829 | defense response to Gram-negative bacterium |
| BP | IDA | GO:0051092 | positive regulation of NF-kappaB transcription factor activity |
| BP | IGI | GO:0051092 | positive regulation of NF-kappaB transcription factor activity |
| BP | ISS | GO:0051770 | positive regulation of nitric-oxide synthase biosynthetic process |
| BP | ISS | GO:0060729 | intestinal epithelial structure maintenance |
| BP | TAS | GO:0070266 | necroptotic process |
| BP | ISS | GO:0070373 | negative regulation of ERK1 and ERK2 cascade |
| BP | IDA | GO:0071222 | cellular response to lipopolysaccharide |
| BP | ISS | GO:0071222 | cellular response to lipopolysaccharide |
| BP | IEP | GO:0071260 | cellular response to mechanical stimulus |
| BP | IDA | GO:0071346 | cellular response to interferon-gamma |
| BP | TAS | GO:0097190 | apoptotic signaling pathway |
| BP | ISS | GO:0140052 | cellular response to oxidised low-density lipoprotein particle stimulus |
| BP | ISS | GO:1900017 | positive regulation of cytokine production involved in inflammatory response |
| BP | ISS | GO:1900227 | positive regulation of NLRP3 inflammasome complex assembly |
| BP | IDA | GO:1901224 | positive regulation of NIK/NF-kappaB signaling |
| BP | ISS | GO:1903223 | positive regulation of oxidative stress-induced neuron death |
| BP | ISS | GO:1903428 | positive regulation of reactive oxygen species biosynthetic process |
| BP | IDA | GO:1903974 | positive regulation of cellular response to macrophage colony-stimulating factor stimulus |
| BP | IGI | GO:1904646 | cellular response to amyloid-beta |
Gene expression in normal tissue: TLR4
Gene-model tissue-cancer distribution: Bubble Plot
Gene-drug pathway distribution
Pathways in TLR4
| Database | Pathway ID | Pathway Des. |
|---|---|---|
| reactome | R-HSA-109581 | Apoptosis |
| reactome | R-HSA-1236974 | ER-Phagosome pathway |
| reactome | R-HSA-1236975 | Antigen processing-Cross presentation |
| reactome | R-HSA-1280218 | Adaptive Immune System |
| reactome | R-HSA-140534 | via Death Receptors in the presence of ligand |
| reactome | R-HSA-1643685 | Disease |
| reactome | R-HSA-166016 | Toll Like Receptor 4 (TLR4) Cascade |
| reactome | R-HSA-166058 | MyD88:Mal cascade initiated on plasma membrane |
| reactome | R-HSA-166166 | MyD88-independent TLR4 cascade |
| reactome | R-HSA-168138 | Toll Like Receptor 9 (TLR9) Cascade |
| reactome | R-HSA-168164 | Toll Like Receptor 3 (TLR3) Cascade |
| reactome | R-HSA-168179 | Toll Like Receptor TLR1:TLR2 Cascade |
| reactome | R-HSA-168181 | Toll Like Receptor 7/8 (TLR7/8) Cascade |
| reactome | R-HSA-168188 | Toll Like Receptor TLR6:TLR2 Cascade |
| reactome | R-HSA-168249 | Innate Immune System |
| reactome | R-HSA-168256 | Immune System |
| reactome | R-HSA-168898 | Toll-Like Receptors Cascades |
| reactome | R-HSA-181438 | Toll Like Receptor 2 (TLR2) Cascade |
| reactome | R-HSA-2562578 | TRIF-mediated programmed cell death |
| reactome | R-HSA-5260271 | Diseases of Immune System |
| reactome | R-HSA-5357769 | Caspase activation via extrinsic apoptotic signalling pathway |
| reactome | R-HSA-5357801 | Programmed Cell Death |
| reactome | R-HSA-5602358 | Diseases associated with the TLR signaling cascade |
| reactome | R-HSA-5602498 | MyD88 deficiency (TLR2/4) |
| reactome | R-HSA-5603041 | IRAK4 deficiency (TLR2/4) |
| reactome | R-HSA-5686938 | Regulation of TLR by endogenous ligand |
| reactome | R-HSA-9014325 | TICAM1,TRAF6-dependent induction of TAK1 complex |
| reactome | R-HSA-936964 | Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon |
| reactome | R-HSA-937041 | IKK complex recruitment mediated by RIP1 |
| reactome | R-HSA-937061 | TRIF(TICAM1)-mediated TLR4 signaling |
| reactome | R-HSA-937072 | TRAF6-mediated induction of TAK1 complex within TLR4 complex |
| reactome | R-HSA-975138 | TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation |
| reactome | R-HSA-975155 | MyD88 dependent cascade initiated on endosome |
| reactome | R-HSA-975163 | IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation |
| reactome | R-HSA-983169 | Class I MHC mediated antigen processing & presentation |
| biocarta | gsk3pathway | inactivation of gsk3 by akt causes accumulation of b-catenin in alveolar macrophages |
| biocarta | nfkbpathway | nf-kb signaling pathway |
| biocarta | tollpathway | toll-like receptor pathway |
| kegg | hsa04064 | NF-kappa B signaling pathway - Homo sapiens (human) |
| kegg | hsa04066 | HIF-1 signaling pathway - Homo sapiens (human) |
| kegg | hsa04145 | Phagosome - Homo sapiens (human) |
| kegg | hsa04151 | PI3K-Akt signaling pathway - Homo sapiens (human) |
| kegg | hsa04217 | Necroptosis - Homo sapiens (human) |
| kegg | hsa04620 | Toll-like receptor signaling pathway - Homo sapiens (human) |
| kegg | hsa04621 | NOD-like receptor signaling pathway - Homo sapiens (human) |
| kegg | hsa05130 | Pathogenic Escherichia coli infection - Homo sapiens (human) |
| kegg | hsa05132 | Salmonella infection - Homo sapiens (human) |
| kegg | hsa05133 | Pertussis - Homo sapiens (human) |
| kegg | hsa05134 | Legionellosis - Homo sapiens (human) |
| kegg | hsa05140 | Leishmaniasis - Homo sapiens (human) |
| kegg | hsa05142 | Chagas disease (American trypanosomiasis) - Homo sapiens (human) |
| kegg | hsa05144 | Malaria - Homo sapiens (human) |
| kegg | hsa05145 | Toxoplasmosis - Homo sapiens (human) |
| kegg | hsa05146 | Amoebiasis - Homo sapiens (human) |
| kegg | hsa05152 | Tuberculosis - Homo sapiens (human) |
| kegg | hsa05161 | Hepatitis B - Homo sapiens (human) |
| kegg | hsa05162 | Measles - Homo sapiens (human) |
| kegg | hsa05164 | Influenza A - Homo sapiens (human) |
| kegg | hsa05205 | Proteoglycans in cancer - Homo sapiens (human) |
| kegg | hsa05321 | Inflammatory bowel disease (IBD) - Homo sapiens (human) |
| kegg | hsa05323 | Rheumatoid arthritis - Homo sapiens (human) |
| pid | toll_endogenous_pathway | Endogenous TLR signaling |
| wikipathways | WP1449 | Regulation of toll-like receptor signaling pathway |
| wikipathways | WP2272 | Pathogenic Escherichia coli infection |
| wikipathways | WP2355 | Corticotropin-releasing hormone signaling pathway |
| wikipathways | WP2431 | Spinal Cord Injury |
| wikipathways | WP2572 | Primary Focal Segmental Glomerulosclerosis FSGS |
| wikipathways | WP3851 | TLR4 Signaling and Tolerance |
| wikipathways | WP3858 | Toll-like Receptor Signaling |
| wikipathways | WP3877 | Simplified Depiction of MYD88 Distinct Input-Output Pathway |
| wikipathways | WP3890 | Nanomaterial induced inflammasome activation |
| wikipathways | WP3926 | ApoE and miR-146 in inflammation and atherosclerosis |
| wikipathways | WP4136 | Fibrin Complement Receptor 3 Signaling Pathway |
| wikipathways | WP4172 | PI3K-Akt Signaling Pathway |
| wikipathways | WP4180 | Ebola Virus Pathway on Host |
| wikipathways | WP4217 | Ebola Virus Pathway on Host |
| wikipathways | WP75 | Toll-like Receptor Signaling Pathway |
Gene-Drug: Aster Plot
| Drug ID | Drug Name | Model Num. |
|---|---|---|
| iGMDRD263 | AACOCF3 | 1 |
| iGMDRD353 | PD0325901 | 1 |
| iGMDRD42 | Vorinostat | 3 |
| iGMDRD322 | FK 866 | 3 |
| iGMDRD100 | Zebularine | 3 |
| iGMDRD871 | BRD6368 | 3 |
| iGMDRD188 | Piperlongumine | 3 |
| iGMDRD414 | MST-312 | 3 |
| iGMDRD329 | Merck60 | 3 |
| iGMDRD577 | BIX01294 | 4 |
| iGMDRD6 | AM-580 | 2 |
| iGMDRD434 | BMS-536924 | 4 |
| iGMDRD441 | TW 37 | 3 |
| iGMDRD801 | 2,4-dideoxy-DC-45-A2 | 1 |
| iGMDRD513 | BML-259 | 3 |
| iGMDRD138 | PX 12 | 6 |
| iGMDRD202 | Curcumin | 3 |
| iGMDRD280 | CYTOCHALASIN B | 1 |
| iGMDRD85 | Ursolic acid | 1 |
| iGMDRD314 | Tanespimycin | 1 |
| iGMDRD152 | 179324-69-7 | 4 |
| iGMDRD61 | Kinetin riboside | 4 |
| iGMDRD427 | ABT737 | 2 |
| iGMDRD701 | NVP-AUY922 | 3 |
| iGMDRD79 | Gemcitabine | 3 |
| iGMDRD84 | Lovastatin acid | 3 |
Gene in drug-gene network: Network Plot
Gene-drug targets distribution
Gene Structure: PDB
Models in TLR4
CLASSFICATION
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