Protein detail
TLR4
Toll-like receptor 4 (hToll) (CD antigen CD284)
Protein symbol TLR4 | UniProt ID | EVMP score 0.50 |
Frequency 2 | Transmembrane count 1 | Protein classification CD markersFDA approved drug targetsHuman disease related genesPredicted intracellular proteinsPredicted membrane proteinsTransporters |
EVMP score: annotation confidence score.
Extremely high >= 0.85High >= 0.70Medium >= 0.55Low >= 0.40
Basic Information
Protein Names
Toll-like receptor 4 (hToll) (CD antigen CD284)
Protein Class
CD markersFDA approved drug targetsHuman disease related genesPredicted intracellular proteinsPredicted membrane proteinsTransporters
Protein Function
- Predicted intracellular proteins
- CD markers
- Transporters:Accessory Factors Involved in Transport
- FDA approved drug targets:Small molecule drugs
- Human disease related genes:Nervous system diseases:Eye disease
Transmembrane
632..652; Helical
Transmembrane Count
1
Ensembl
Entrez Gene Symbol
Gene Synonym
ARMD10CD284hTollTLR-4
Gene Description
Toll like receptor 4
Chromosome
9
Position
117704175-117724735
Frequency
2
EVMP Score
0.50
Fluorescence & Localization
Tissue SpecificintestineCell SpecificEnteric stem cellsSecretome LocationIntracellular and membraneSecretome FunctionReceptor
Function & Pathway
Protein Function
- Predicted intracellular proteins
- CD markers
- Transporters:Accessory Factors Involved in Transport
- FDA approved drug targets:Small molecule drugs
- Human disease related genes:Nervous system diseases:Eye disease
Cellular Component
- GO:0001726 ruffle
- GO:0001891 phagocytic cup
- GO:0005737 cytoplasm
- GO:0005769 early endosome
- GO:0005886 plasma membrane
- GO:0009897 external side of plasma membrane
- GO:0009986 cell surface
- GO:0010008 endosome membrane
- GO:0043235 receptor complex
- GO:0046696 lipopolysaccharide receptor complex
- GO:0048471 perinuclear region of cytoplasm
Molecular Function
- GO:0001530 lipopolysaccharide binding
- GO:0001540 amyloid-beta binding
- GO:0001875 lipopolysaccharide immune receptor activity
- GO:0004888 transmembrane signaling receptor activity
- GO:0005102 signaling receptor binding
- GO:0005515 protein binding
- GO:0038023 signaling receptor activity
- GO:0042802 identical protein binding
- GO:0046982 protein heterodimerization activity
- GO:0061809 NAD+ nucleotidase, cyclic ADP-ribose generating
Biological Process
KEGG
- hsa04064 NF-kappa B signaling pathway
- KEGG:hsa04066 HIF-1 signaling pathway
- KEGG:hsa04145 Phagosome
- KEGG:hsa04151 PI3K-Akt signaling pathway
- KEGG:hsa04217 Necroptosis
- KEGG:hsa04613 Neutrophil extracellular trap formation
- KEGG:hsa04620 Toll-like receptor signaling pathway
- KEGG:hsa04621 NOD-like receptor signaling pathway
- KEGG:hsa04936 Alcoholic liver disease
- KEGG:hsa05130 Pathogenic Escherichia coli infection
- KEGG:hsa05131 Shigellosis
- KEGG:hsa05132 Salmonella infection
- KEGG:hsa05133 Pertussis
- KEGG:hsa05134 Legionellosis
- KEGG:hsa05135 Yersinia infection
- KEGG:hsa05140 Leishmaniasis
- KEGG:hsa05142 Chagas disease
- KEGG:hsa05144 Malaria
- KEGG:hsa05145 Toxoplasmosis
- KEGG:hsa05146 Amoebiasis
- KEGG:hsa05152 Tuberculosis
- KEGG:hsa05161 Hepatitis B
- KEGG:hsa05162 Measles
- KEGG:hsa05164 Influenza A
- KEGG:hsa05170 Human immunodeficiency virus 1 infection
- KEGG:hsa05171 Coronavirus disease
- KEGG:hsa05205 Proteoglycans in cancer
- KEGG:hsa05235 PD-L1 expression and PD-1 checkpoint pathway in cancer
- KEGG:hsa05321 Inflammatory bowel disease
- KEGG:hsa05323 Rheumatoid arthritis
- KEGG:hsa05417 Lipid and atherosclerosis
Reactome
- R-hsa-936964 activation of irf3 irf7 mediated by tbk1 ikk ikbke
- R-hsa-1280218 adaptive immune system
- R-hsa-1236975 antigen processing cross presentation
- R-hsa-109581 apoptosis
- R-hsa-140534 caspase activation via death receptors in the presence of ligand
- R-hsa-5357769 caspase activation via extrinsic apoptotic signalling pathway
- R-hsa-8953897 cellular responses to stimuli
- R-hsa-983169 class i mhc mediated antigen processing presentation
- R-hsa-9918481 dengue virus host interactions
- R-hsa-9839923 dengue virus infection
- R-hsa-5260271 diseases of immune system
- R-hsa-9707616 heme signaling
- R-hsa-937041 ikk complex recruitment mediated by rip1
- R-hsa-5663205 infectious disease
- R-hsa-168249 innate immune system
- R-hsa-5603041 irak4 deficiency tlr2 4
- R-hsa-166166 myd88 independent tlr4 cascade
- R-hsa-5357801 programmed cell death
- R-hsa-9824878 regulation of tbk1 ikk ikbke mediated activation of irf3 irf7
- R-hsa-5686938 regulation of tlr by endogenous ligand
- R-hsa-9820952 respiratory syncytial virus infection pathway
- R-hsa-9820960 respiratory syncytial virus rsv attachment and entry
- R-hsa-9833110 rsv host interactions
- R-hsa-168138 toll like receptor 9 tlr9 cascade
- R-hsa-168898 toll like receptor cascades
- R-hsa-168179 toll like receptor tlr1 tlr2 cascade
- R-hsa-937072 traf6 mediated induction of tak1 complex within tlr4 complex
- R-hsa-2562578 trif mediated programmed cell death
- R-hsa-9824446 viral infection pathways
Canonical Pathways
M8 Pid endothelin pathway
Mediation Categories
Clinical-translation mediationFusion and delivery mediationImmune mediationMetabolism mediationReceptor-signaling mediation
Relations & Evidence
Enzyme-Mediated Modification
1 record.
| Substrate Gene Symbol | Enzyme Gene Symbol | Enzyme UniProt ID | Residue Type | Residue Offset | Modification | Database | References |
|---|---|---|---|---|---|---|---|
| TLR4 | PRKD1 | Q15139 | S | 790 | phosphorylation | PhosphoSite_MIMPMIMPProtMapperPhosphoSitePhosphoSite_ProtMapper |
Ligand-Receptor Signaling
62 records.
| Category | Parent | Database | Transmitter | Receiver | Secreted | Plasma Membrane (Transmembrane) | Plasma Membrane (Peripheral) |
|---|---|---|---|---|---|---|---|
| toll | receptor | HPMR | No | Yes | No | Yes | No |
| til_toll | receptor | HPMR | No | Yes | No | Yes | No |
| toll | receptor | Surfaceome | No | Yes | No | Yes | No |
| innate_immune | receptor | ICELLNET | No | Yes | No | Yes | No |
| innate_immune_tlr | receptor | ICELLNET | No | Yes | No | Yes | No |
| receptor | receptor | OmniPath | No | Yes | No | Yes | No |
| extracellular | extracellular | HPMR | No | No | No | Yes | No |
| extracellular | extracellular | DGIdb | No | No | No | Yes | No |
| extracellular | extracellular | OmniPath | No | No | No | Yes | No |
| intracellular | intracellular | LOCATE | No | No | No | Yes | No |
Regulatory Interaction Network
11 records.
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Protein Complex Composition
4 records.
| Component Name | Component Gene Symbols | Component UniProt ID | Stoichiometry | Database | Database IDs | References |
|---|---|---|---|---|---|---|
| TLR4-TLR6 toll-like receptor complex | TLR4TLR6 | O00206Q9Y2C9 | 1:1 | ComplexPortal | intact:EBI-12685429 | 34180006147552922003758433576548 |
| TLR4 | O00206 | 4 | PDB | PDB:2z66 | ||
| FADDGALEIRAK4MYD88TLR4TLR5TRAF6 | O00206O60602Q13158Q14376Q99836Q9NWZ3Q9Y4K3 | 1:1:1:1:1:1:1 | NetworkBlastCompleat | Compleat:HC5512 | ||
| HMGB1HSPA8MAXMNTTLR4 | O00206P09429P11142P61244Q99583 | 1:1:1:1:1 | NetworkBlastCompleat | Compleat:HC8934 |
Sequence, Structure & Domains
Sequences
Length
839
Mass
95,680
Sequence
MMSASRLAGTLIPAMAFLSCVRPESWEPCVEVVPNITYQCMELNFYKIPDNLPFSTKNLDLSFNPLRHLGSYSFFSFPELQVLDLSRCEIQTIEDGAYQSLSHLSTLILTGNPIQSLALGAFSGLSSLQKLVAVETNLASLENFPIGHLKTLKELNVAHNLIQSFKLPEYFSNLTNLEHLDLSSNKIQSIYCTDLRVLHQMPLLNLSLDLSLNPMNFIQPGAFKEIRLHKLTLRNNFDSLNVMKTCIQGLAGLEVHRLVLGEFRNEGNLEKFDKSALEGLCNLTIEEFRLAYLDYYLDDIIDLFNCLTNVSSFSLVSVTIERVKDFSYNFGWQHLELVNCKFGQFPTLKLKSLKRLTFTSNKGGNAFSEVDLPSLEFLDLSRNGLSFKGCCSQSDFGTTSLKYLDLSFNGVITMSSNFLGLEQLEHLDFQHSNLKQMSEFSVFLSLRNLIYLDISHTHTRVAFNGIFNGLSSLEVLKMAGNSFQENFLPDIFTELRNLTFLDLSQCQLEQLSPTAFNSLSSLQVLNMSHNNFFSLDTFPYKCLNSLQVLDYSLNHIMTSKKQELQHFPSSLAFLNLTQNDFACTCEHQSFLQWIKDQRQLLVEVERMECATPSDKQGMPVLSLNITCQMNKTIIGVSVLSVLVVSVVAVLVYKFYFHLMLLAGCIKYGRGENIYDAFVIYSSQDEDWVRNELVKNLEEGVPPFQLCLHYRDFIPGVAIAANIIHEGFHKSRKVIVVVSQHFIQSRWCIFEYEIAQTWQFLSSRAGIIFIVLQKVEKTLLRQQVELYRLLSRNTYLEWEDSVLGRHIFWRRLRKALLDGKSWNPEGTVGTGCNWQEATSI
Alternative Products
Event=Alternative splicing; Named isoforms=3; Name=1; IsoId=O00206-1; Sequence=Displayed; Name=2; IsoId=O00206-2; Sequence=VSP_035794; Name=3; IsoId=O00206-3; Sequence=VSP_035793
Alternative Sequence
1..200; Missing (in isoform 3); 1..40; Missing (in isoform 2)
3D Structural Models
Turn
34..36; 71..76; 95..100; 119..124; 145..148; 220..225; 249..252; 274..277; 301..304; 438..445; 464..469; 513..518
Helix
141..143; 169..173; 192..195; 196..199; 242..248; 278..282; 305..307; 324..327; 393..396; 484..486; 538..540; 585..587; 588..596; 597..600; 604..606; 613..615; 620..622; 630..662
Beta Strand
29..33; 37..39; 50..52; 58..60; 81..84; 106..108; 115..117; 130..132; 154..156; 179..181; 206..209; 227..235; 254..262; 283..292; 295..298; 311..317; 319..322; 333..339; 341..344; 355..360; 377..379; 387..392; 403..405; 410..419; 426..428; 432..437; 451..453; 475..477; 500..502; 524..526; 548..550; 560..563; 573..575; 608..612; 617..619; 627..629
3D Structure
Electron microscopy (3); NMR spectroscopy (2); X-ray crystallography (10)
Domain & Motif Annotations
Repeat
55..76; LRR 1; 79..100; LRR 2; 103..124; LRR 3; 127..148; LRR 4; 151..172; LRR 5; 176..199; LRR 6; 205..225; LRR 7; 227..247; LRR 8; 331..351; LRR 9; 352..373; LRR 10; 374..394; LRR 11; 400..422; LRR 12; 423..444; LRR 13; 448..456; LRR 14; 472..495; LRR 15; 497..518; LRR 16; 521..542; LRR 17; 545..565; LRR 18
Domain (CC)
The TIR domain mediates interaction with NOX4..
Domain (FT)
579..629; LRRCT; 672..815; TIR
Protein Families
Toll-like receptor family
Sequence Similarities
Belongs to the Toll-like receptor family.
Clinical Relevance
Disease Involvement
Age-related macular degenerationFDA approved drug targets
Related Diseases
Biomarker
Preregistration; Phase 1; Phase 2; Investigative; Phase 3
Drug Targets
FDA approved drug targetsClinical trial target
Drugs
Interaction Protein
ENSG00000150455ENSG00000154589ENSG00000172936ENSG00000243414
Interaction Count
4
Interaction Dataset
intact_biogrid