General Information of the Protein
Protein ID
PT03343
Protein Name
Toll-like receptor 4
Secondarily
Protein Name
hToll
Gene Name
TLR4
Sequence
MMSASRLAGTLIPAMAFLSCVRPESWEPCVEVVPNITYQCMELNFYKIPDNLPFSTKNLDLSFNPLRHLGSYSFFSFPELQVLDLSRCEIQTIEDGAYQSLSHLSTLILTGNPIQSLALGAFSGLSSLQKLVAVETNLASLENFPIGHLKTLKELNVAHNLIQSFKLPEYFSNLTNLEHLDLSSNKIQSIYCTDLRVLHQMPLLNLSLDLSLNPMNFIQPGAFKEIRLHKLTLRNNFDSLNVMKTCIQGLAGLEVHRLVLGEFRNEGNLEKFDKSALEGLCNLTIEEFRLAYLDYYLDDIIDLFNCLTNVSSFSLVSVTIERVKDFSYNFGWQHLELVNCKFGQFPTLKLKSLKRLTFTSNKGGNAFSEVDLPSLEFLDLSRNGLSFKGCCSQSDFGTTSLKYLDLSFNGVITMSSNFLGLEQLEHLDFQHSNLKQMSEFSVFLSLRNLIYLDISHTHTRVAFNGIFNGLSSLEVLKMAGNSFQENFLPDIFTELRNLTFLDLSQCQLEQLSPTAFNSLSSLQVLNMSHNNFFSLDTFPYKCLNSLQVLDYSLNHIMTSKKQELQHFPSSLAFLNLTQNDFACTCEHQSFLQWIKDQRQLLVEVERMECATPSDKQGMPVLSLNITCQMNKTIIGVSVLSVLVVSVVAVLVYKFYFHLMLLAGCIKYGRGENIYDAFVIYSSQDEDWVRNELVKNLEEGVPPFQLCLHYRDFIPGVAIAANIIHEGFHKSRKVIVVVSQHFIQSRWCIFEYEIAQTWQFLSSRAGIIFIVLQKVEKTLLRQQVELYRLLSRNTYLEWEDSVLGRHIFWRRLRKALLDGKSWNPEGTVGTGCNWQEATSI
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Organism
Homo sapiens, Human
Protein Classification
Membrane receptor
>
Toll-like and Il-1 receptors
Function
Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstream signaling pathways (PubMed:16622205, PubMed:10835634, PubMed:15809303, PubMed:17478729, PubMed:20037584, PubMed:20711192, PubMed:23880187, PubMed:27022195, PubMed:17292937, PubMed:29038465). At the plasma membrane, cooperates with LY96 to mediate the innate immune response to bacterial lipopolysaccharide (LPS) (PubMed:27022195). Also involved in LPS-independent inflammatory responses triggered by free fatty acids, such as palmitate, and Ni(2+) (PubMed:20711192). Mechanistically, acts via MYD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (PubMed:9237759, PubMed:10835634, PubMed:27022195, PubMed:21393102). Alternatively, CD14-mediated TLR4 internalization via endocytosis is associated with the initiation of a MYD88-independent signaling via the TICAM1-TBK1-IRF3 axis leading to type I interferon production (PubMed:14517278). In addition to the secretion of proinflammatory cytokines, initiates the activation of NLRP3 inflammasome and formation of a positive feedback loop between autophagy and NF-kappa-B signaling cascade (PubMed:32894580). In complex with TLR6, promotes inflammation in monocytes/macrophages by associating with TLR6 and the receptor CD86 (PubMed:23880187). Upon ligand binding, such as oxLDL or amyloid-beta 42, the TLR4:TLR6 complex is internalized and triggers inflammatory response, leading to NF-kappa-B-dependent production of CXCL1, CXCL2 and CCL9 cytokines, via MYD88 signaling pathway, and CCL5 cytokine, via TICAM1 signaling pathway (PubMed:23880187). In myeloid dendritic cells, vesicular stomatitis virus glycoprotein G but not LPS promotes the activation of IRF7, leading to type I IFN production in a CD14-dependent manner (PubMed:23880187, PubMed:15265881). Required for the migration-promoting effects of ZG16B/PAUF on pancreatic cancer cells.
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Uniprot ID
Primary ID:
O00206

Secondarily ID:
A8K1Y8
A9XLP9
A9XLQ0
A9XLQ1
B4E194
D1CS52
D1CS53
Q5VZI8
Q5VZI9
Q9UK78
Q9UM57
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Ensembl ID
ENSG00000136869
HGNC ID
HGNC:11850
Subcellular Location
Cell membrane
Early endosome
Cell projection
Ruffle
Map of Molecular Bioactivity Related to the Protein
Map of Molecular Bioactivity Related to the Protein

Protein
Cell Line
Compound

Bioactivity Value:

<= 0.1 μM
> 0.1 μM and <= 10 μM
> 10 μM
Imprecise Activity
Table of Molecular Bioactivities Related to the Protein
Cell Line ID: CL000192 , AD-293
Compound ID Compound Name Compound Formula
CP0390128
[(3S,8S,9R,10R,12R,13S,14R,17S)-17-acetyl-3-(2-chloroacetyl)oxy-8,14,17-trihydroxy-10,13-dimethyl-1,2,3,4,7,9,11,12,15,16-decahydrocyclopenta[a]phenanthren-12-yl] 4-hydroxybenzoate
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C30H37ClO9
 1
1
EC50 = 3270 nM
   TI
   LI
   LO
   TS
CP0390129
[(3S,8S,9R,10R,12R,13S,14R,17S)-17-acetyl-8,14,17-trihydroxy-3-[(E)-3-(4-methoxyphenyl)prop-2-enoyl]oxy-10,13-dimethyl-1,2,3,4,7,9,11,12,15,16-decahydrocyclopenta[a]phenanthren-12-yl] (E)-3,4-dimethylpent-2-enoate
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C38H50O9
 1
1
EC50 = 3950 nM
   TI
   LI
   LO
   TS
CP0390127
[(1R)-1-[(3S,8S,9R,10R,12R,13R,14R,17S)-3,8,14,17-tetrahydroxy-10,13-dimethyl-12-[(E)-3-phenylprop-2-enoyl]oxy-1,2,3,4,7,9,11,12,15,16-decahydrocyclopenta[a]phenanthren-17-yl]ethyl] 2-hydroxybenzoate
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C37H44O9
 1
1
EC50 = 4900 nM
   TI
   LI
   LO
   TS
CP0569853
[(1R)-1-[(8S,9R,10R,12R,13R,14R,17S)-8,14,17-trihydroxy-10,13-dimethyl-3-oxo-12-[(E)-3-phenylprop-2-enoyl]oxy-11,12,15,16-tetrahydro-9H-cyclopenta[a]phenanthren-17-yl]ethyl] pyridine-3-carboxylate
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C36H37NO8
 1
1
EC50 = 6350 nM
   TI
   LI
   LO
   TS
CP0569855
[(1R)-1-[(3S,8S,9R,10R,12R,13R,14R,17S)-3-benzoyloxy-8,14,17-trihydroxy-10,13-dimethyl-12-[(E)-3-phenylprop-2-enoyl]oxy-1,2,3,4,7,9,11,12,15,16-decahydrocyclopenta[a]phenanthren-17-yl]ethyl] pyridine-3-carboxylate
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C43H47NO9
 1
1
EC50 = 11080 nM
   TI
   LI
   LO
   TS
CP0558940
[(8S,9R,10R,12R,13S,14R,17S)-17-acetyl-8,14,17-trihydroxy-10,13-dimethyl-3-oxo-2,4,7,9,11,12,15,16-octahydro-1H-cyclopenta[a]phenanthren-12-yl] (E)-3,4-dimethylpent-2-enoate
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C28H40O7
 1
1
EC50 = 11680 nM
   TI
   LI
   LO
   TS
CP0566539
[(3S,8S,9R,10R,12R,13S,14R,17S)-17-acetyl-3-chloro-8,14,17-trihydroxy-10,13-dimethyl-1,2,3,4,7,9,11,12,15,16-decahydrocyclopenta[a]phenanthren-12-yl] (E)-3,4-dimethylpent-2-enoate
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C28H41ClO6
 1
1
EC50 = 12000 nM
   TI
   LI
   LO
   TS
CP0558941
[(1R)-1-[(3S,8S,9R,10R,12R,13R,14R,17S)-8,14,17-trihydroxy-10,13-dimethyl-3-[(E)-3-(4-nitrophenyl)prop-2-enoyl]oxy-12-[(E)-3-phenylprop-2-enoyl]oxy-1,2,3,4,7,9,11,12,15,16-decahydrocyclopenta[a]phenanthren-17-yl]ethyl] pyridine-3-carboxylate
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C45H48N2O11
 1
1
EC50 = 14000 nM
   TI
   LI
   LO
   TS
Biochemical Assays
Compound ID Compound Name Compound Formula
CP0291589
6-(2-Chloro-4-fluoro-phenylsulfamoyl)-cyclohex-1-enecarboxylic acid ethyl ester
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C15H17ClFNO4S
 1
1 IC50 = 3.2 nM
Clinical Information about the Protein
Target 1 ( Toll-like receptor 4 (TLR4) )
Target Type Clinical trial Target
Disease 1 Target-related Disease  1
1 Sepsis [ICD-11: 1G40-1G41]
Clinical Trial Drug(s) 2 Clinical Trial Drugs  2
1 ERITORAN Phase 3
Sepsis
2 Resatorvid Phase 3
Sepsis
Discontinued Drug(s) 1 Discontinued Drug  1
1 CS-4771 Discontinued in Phase 1
Sepsis
Similar Protein(s) and Bioactivity Statistics
50% Identity
Protein ID Protein Name Protein Organism
PT03041 Toll-like receptor 4 Mus musculus, Mouse