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].

NameOMIM IDEnsembl IDHGNC IDPHARMGKB IDMap Location
toll like receptor 4MIM:603030Ensembl:ENSG00000136869HGNC:HGNC:11850PA365529q33.1

GO terms in TLR4


Term TypeEvidence TypeGO Term IDGO Des.
MFIBAGO:0001530lipopolysaccharide binding
MFIMPGO:0001530lipopolysaccharide binding
MFNASGO:0001530lipopolysaccharide binding
MFIBAGO:0001875lipopolysaccharide receptor activity
MFIDAGO:0001875lipopolysaccharide receptor activity
MFNASGO:0004888transmembrane signaling receptor activity
MFIPIGO:0005102signaling receptor binding
MFIPIGO:0005515protein binding
MFTASGO:0038023signaling receptor activity
MFIPIGO:0042802identical protein binding
MFIPIGO:0046982protein heterodimerization activity
CCIPIGO:0005622intracellular
CCIDAGO:0005737cytoplasm
CCIEAGO:0005769early endosome
CCIDAGO:0005886plasma membrane
CCTASGO:0005886plasma membrane
CCIBAGO:0005887integral component of plasma membrane
CCIDAGO:0005887integral component of plasma membrane
CCIDAGO:0009897external side of plasma membrane
CCIDAGO:0009986cell surface
CCTASGO:0010008endosome membrane
CCIDAGO:0031226intrinsic component of plasma membrane
CCIPIGO:0043235receptor complex
CCIDAGO:0046696lipopolysaccharide receptor complex
CCIDAGO:0048471perinuclear region of cytoplasm
BPISSGO:0000187activation of MAPK activity
BPIBAGO:0002224toll-like receptor signaling pathway
BPTASGO:0002224toll-like receptor signaling pathway
BPISSGO:0002755MyD88-dependent toll-like receptor signaling pathway
BPTASGO:0002755MyD88-dependent toll-like receptor signaling pathway
BPTASGO:0002756MyD88-independent toll-like receptor signaling pathway
BPIBAGO:0006954inflammatory response
BPTASGO:0006955immune response
BPTASGO:0007249I-kappaB kinase/NF-kappaB signaling
BPIDAGO:0007252I-kappaB phosphorylation
BPISSGO:0010572positive regulation of platelet activation
BPIMPGO:0010628positive regulation of gene expression
BPISSGO:0010628positive regulation of gene expression
BPNASGO:0016046detection of fungus
BPIDAGO:0031663lipopolysaccharide-mediated signaling pathway
BPIGIGO:0031663lipopolysaccharide-mediated signaling pathway
BPICGO:0032496response to lipopolysaccharide
BPIDAGO:0032496response to lipopolysaccharide
BPIDAGO:0032497detection of lipopolysaccharide
BPISSGO:0032689negative regulation of interferon-gamma production
BPISSGO:0032700negative regulation of interleukin-17 production
BPISSGO:0032707negative regulation of interleukin-23 production
BPISSGO:0032715negative regulation of interleukin-6 production
BPISSGO:0032720negative regulation of tumor necrosis factor production
BPIDAGO:0032722positive regulation of chemokine production
BPISSGO:0032727positive regulation of interferon-alpha production
BPISSGO:0032728positive regulation of interferon-beta production
BPISSGO:0032729positive regulation of interferon-gamma production
BPISSGO:0032732positive regulation of interleukin-1 production
BPISSGO:0032733positive regulation of interleukin-10 production
BPISSGO:0032735positive regulation of interleukin-12 production
BPIDAGO:0032755positive regulation of interleukin-6 production
BPIDAGO:0032757positive regulation of interleukin-8 production
BPISSGO:0032760positive regulation of tumor necrosis factor production
BPTASGO:0034128negative regulation of MyD88-independent toll-like receptor signaling pathway
BPTASGO:0034142toll-like receptor 4 signaling pathway
BPISSGO:0035666TRIF-dependent toll-like receptor signaling pathway
BPTASGO:0035666TRIF-dependent toll-like receptor signaling pathway
BPNASGO:0042088T-helper 1 type immune response
BPIMPGO:0042116macrophage activation
BPIDAGO:0042535positive regulation of tumor necrosis factor biosynthetic process
BPTASGO:0042742defense response to bacterium
BPISSGO:0043032positive regulation of macrophage activation
BPIDAGO:0045084positive regulation of interleukin-12 biosynthetic process
BPTASGO:0045087innate immune response
BPIDAGO:0045416positive regulation of interleukin-8 biosynthetic process
BPISSGO:0045429positive regulation of nitric oxide biosynthetic process
BPNASGO:0045671negative regulation of osteoclast differentiation
BPISSGO:0045944positive regulation of transcription by RNA polymerase II
BPISSGO:0050702interleukin-1 beta secretion
BPIDAGO:0050718positive regulation of interleukin-1 beta secretion
BPICGO:0050729positive regulation of inflammatory response
BPIBAGO:0050829defense response to Gram-negative bacterium
BPICGO:0050829defense response to Gram-negative bacterium
BPIDAGO:0051092positive regulation of NF-kappaB transcription factor activity
BPIGIGO:0051092positive regulation of NF-kappaB transcription factor activity
BPISSGO:0051770positive regulation of nitric-oxide synthase biosynthetic process
BPISSGO:0060729intestinal epithelial structure maintenance
BPTASGO:0070266necroptotic process
BPISSGO:0070373negative regulation of ERK1 and ERK2 cascade
BPIDAGO:0071222cellular response to lipopolysaccharide
BPISSGO:0071222cellular response to lipopolysaccharide
BPIEPGO:0071260cellular response to mechanical stimulus
BPIDAGO:0071346cellular response to interferon-gamma
BPTASGO:0097190apoptotic signaling pathway
BPISSGO:0140052cellular response to oxidised low-density lipoprotein particle stimulus
BPISSGO:1900017positive regulation of cytokine production involved in inflammatory response
BPISSGO:1900227positive regulation of NLRP3 inflammasome complex assembly
BPIDAGO:1901224positive regulation of NIK/NF-kappaB signaling
BPISSGO:1903223positive regulation of oxidative stress-induced neuron death
BPISSGO:1903428positive regulation of reactive oxygen species biosynthetic process
BPIDAGO:1903974positive regulation of cellular response to macrophage colony-stimulating factor stimulus
BPIGIGO:1904646cellular response to amyloid-beta

Gene expression in normal tissue: TLR4

Gene-model tissue-cancer distribution: Bubble Plot

Gene-drug pathway distribution

Pathways in TLR4


DatabasePathway IDPathway Des.
reactomeR-HSA-109581Apoptosis
reactomeR-HSA-1236974ER-Phagosome pathway
reactomeR-HSA-1236975Antigen processing-Cross presentation
reactomeR-HSA-1280218Adaptive Immune System
reactomeR-HSA-140534via Death Receptors in the presence of ligand
reactomeR-HSA-1643685Disease
reactomeR-HSA-166016Toll Like Receptor 4 (TLR4) Cascade
reactomeR-HSA-166058MyD88:Mal cascade initiated on plasma membrane
reactomeR-HSA-166166MyD88-independent TLR4 cascade
reactomeR-HSA-168138Toll Like Receptor 9 (TLR9) Cascade
reactomeR-HSA-168164Toll Like Receptor 3 (TLR3) Cascade
reactomeR-HSA-168179Toll Like Receptor TLR1:TLR2 Cascade
reactomeR-HSA-168181Toll Like Receptor 7/8 (TLR7/8) Cascade
reactomeR-HSA-168188Toll Like Receptor TLR6:TLR2 Cascade
reactomeR-HSA-168249Innate Immune System
reactomeR-HSA-168256Immune System
reactomeR-HSA-168898Toll-Like Receptors Cascades
reactomeR-HSA-181438Toll Like Receptor 2 (TLR2) Cascade
reactomeR-HSA-2562578TRIF-mediated programmed cell death
reactomeR-HSA-5260271Diseases of Immune System
reactomeR-HSA-5357769Caspase activation via extrinsic apoptotic signalling pathway
reactomeR-HSA-5357801Programmed Cell Death
reactomeR-HSA-5602358Diseases associated with the TLR signaling cascade
reactomeR-HSA-5602498MyD88 deficiency (TLR2/4)
reactomeR-HSA-5603041IRAK4 deficiency (TLR2/4)
reactomeR-HSA-5686938Regulation of TLR by endogenous ligand
reactomeR-HSA-9014325TICAM1,TRAF6-dependent induction of TAK1 complex
reactomeR-HSA-936964Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon
reactomeR-HSA-937041IKK complex recruitment mediated by RIP1
reactomeR-HSA-937061TRIF(TICAM1)-mediated TLR4 signaling
reactomeR-HSA-937072TRAF6-mediated induction of TAK1 complex within TLR4 complex
reactomeR-HSA-975138TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation
reactomeR-HSA-975155MyD88 dependent cascade initiated on endosome
reactomeR-HSA-975163IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation
reactomeR-HSA-983169Class I MHC mediated antigen processing & presentation
biocartagsk3pathwayinactivation of gsk3 by akt causes accumulation of b-catenin in alveolar macrophages
biocartanfkbpathwaynf-kb signaling pathway
biocartatollpathwaytoll-like receptor pathway
kegghsa04064NF-kappa B signaling pathway - Homo sapiens (human)
kegghsa04066HIF-1 signaling pathway - Homo sapiens (human)
kegghsa04145Phagosome - Homo sapiens (human)
kegghsa04151PI3K-Akt signaling pathway - Homo sapiens (human)
kegghsa04217Necroptosis - Homo sapiens (human)
kegghsa04620Toll-like receptor signaling pathway - Homo sapiens (human)
kegghsa04621NOD-like receptor signaling pathway - Homo sapiens (human)
kegghsa05130Pathogenic Escherichia coli infection - Homo sapiens (human)
kegghsa05132Salmonella infection - Homo sapiens (human)
kegghsa05133Pertussis - Homo sapiens (human)
kegghsa05134Legionellosis - Homo sapiens (human)
kegghsa05140Leishmaniasis - Homo sapiens (human)
kegghsa05142Chagas disease (American trypanosomiasis) - Homo sapiens (human)
kegghsa05144Malaria - Homo sapiens (human)
kegghsa05145Toxoplasmosis - Homo sapiens (human)
kegghsa05146Amoebiasis - Homo sapiens (human)
kegghsa05152Tuberculosis - Homo sapiens (human)
kegghsa05161Hepatitis B - Homo sapiens (human)
kegghsa05162Measles - Homo sapiens (human)
kegghsa05164Influenza A - Homo sapiens (human)
kegghsa05205Proteoglycans in cancer - Homo sapiens (human)
kegghsa05321Inflammatory bowel disease (IBD) - Homo sapiens (human)
kegghsa05323Rheumatoid arthritis - Homo sapiens (human)
pidtoll_endogenous_pathwayEndogenous TLR signaling
wikipathwaysWP1449Regulation of toll-like receptor signaling pathway
wikipathwaysWP2272Pathogenic Escherichia coli infection
wikipathwaysWP2355Corticotropin-releasing hormone signaling pathway
wikipathwaysWP2431Spinal Cord Injury
wikipathwaysWP2572Primary Focal Segmental Glomerulosclerosis FSGS
wikipathwaysWP3851TLR4 Signaling and Tolerance
wikipathwaysWP3858Toll-like Receptor Signaling
wikipathwaysWP3877Simplified Depiction of MYD88 Distinct Input-Output Pathway
wikipathwaysWP3890Nanomaterial induced inflammasome activation
wikipathwaysWP3926ApoE and miR-146 in inflammation and atherosclerosis
wikipathwaysWP4136Fibrin Complement Receptor 3 Signaling Pathway
wikipathwaysWP4172PI3K-Akt Signaling Pathway
wikipathwaysWP4180Ebola Virus Pathway on Host
wikipathwaysWP4217Ebola Virus Pathway on Host
wikipathwaysWP75Toll-like Receptor Signaling Pathway

Gene-Drug: Aster Plot


Drug IDDrug NameModel Num.
iGMDRD263AACOCF31
iGMDRD353PD03259011
iGMDRD42Vorinostat3
iGMDRD322FK 8663
iGMDRD100Zebularine3
iGMDRD871BRD63683
iGMDRD188Piperlongumine3
iGMDRD414MST-3123
iGMDRD329Merck603
iGMDRD577BIX012944
iGMDRD6AM-5802
iGMDRD434BMS-5369244
iGMDRD441TW 373
iGMDRD8012,4-dideoxy-DC-45-A21
iGMDRD513BML-2593
iGMDRD138PX 126
iGMDRD202Curcumin3
iGMDRD280CYTOCHALASIN B1
iGMDRD85Ursolic acid1
iGMDRD314Tanespimycin1
iGMDRD152179324-69-74
iGMDRD61Kinetin riboside4
iGMDRD427ABT7372
iGMDRD701NVP-AUY9223
iGMDRD79Gemcitabine3
iGMDRD84Lovastatin acid3

Gene in drug-gene network: Network Plot

Gene-drug targets distribution

Gene Structure: PDB

Models in TLR4

​​​​