Names & Taxonomy
- Uniprot ID:
- O00206
- Entry Name:
- TLR4_HUMAN
- Status:
- reviewed
- Protein Names:
- Toll-like receptor 4 (hToll) (CD antigen CD284)
- Gene Names:
- TLR4
- Gene Names Primary:
- TLR4
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 839
- Sequence:
- MMSASRLAGTLIPAMAFLSCVRPESWEPCVEVVPNITYQCMELNFYKIPDNLPFSTKNLDLSFNPLRHLGSYSFFSFPELQVLDLSRCEIQTIEDGAYQSLSHLSTLILTGNPIQSLALGAFSGLSSLQKLVAVETNLASLENFPIGHLKTLKELNVAHNLIQSFKLPEYFSNLTNLEHLDLSSNKIQSIYCTDLRVLHQMPLLNLSLDLSLNPMNFIQPGAFKEIRLHKLTLRNNFDSLNVMKTCIQGLAGLEVHRLVLGEFRNEGNLEKFDKSALEGLCNLTIEEFRLAYLDYYLDDIIDLFNCLTNVSSFSLVSVTIERVKDFSYNFGWQHLELVNCKFGQFPTLKLKSLKRLTFTSNKGGNAFSEVDLPSLEFLDLSRNGLSFKGCCSQSDFGTTSLKYLDLSFNGVITMSSNFLGLEQLEHLDFQHSNLKQMSEFSVFLSLRNLIYLDISHTHTRVAFNGIFNGLSSLEVLKMAGNSFQENFLPDIFTELRNLTFLDLSQCQLEQLSPTAFNSLSSLQVLNMSHNNFFSLDTFPYKCLNSLQVLDYSLNHIMTSKKQELQHFPSSLAFLNLTQNDFACTCEHQSFLQWIKDQRQLLVEVERMECATPSDKQGMPVLSLNITCQMNKTIIGVSVLSVLVVSVVAVLVYKFYFHLMLLAGCIKYGRGENIYDAFVIYSSQDEDWVRNELVKNLEEGVPPFQLCLHYRDFIPGVAIAANIIHEGFHKSRKVIVVVSQHFIQSRWCIFEYEIAQTWQFLSSRAGIIFIVLQKVEKTLLRQQVELYRLLSRNTYLEWEDSVLGRHIFWRRLRKALLDGKSWNPEGTVGTGCNWQEATSI
- Proteomes:
- UP000005640
Subcellular location
- Subcellular Location:
- Cell membrane
Function
- Function:
- Cooperates with LY96 and CD14 to mediate the innate immune response to bacterial lipopolysaccharide (LPS). Acts via MYD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (PubMed:9237759, PubMed:10835634). Also involved in LPS-independent inflammatory responses triggered by free fatty acids, such as palmitate, and Ni(2+). Responses triggered by Ni(2+) require non-conserved histidines and are, therefore, species-specific (PubMed:20711192). In complex with TLR6, promotes sterile inflammation in monocytes/macrophages in response to oxidized low-density lipoprotein (oxLDL) or amyloid-beta 42. In this context, the initial signal is provided by oxLDL- or amyloid-beta 42-binding to CD36. This event induces the formation of a heterodimer of TLR4 and TLR6, which is rapidly internalized and triggers inflammatory response, leading to the NF-kappa-B-dependent production of CXCL1, CXCL2 and CCL9 cytokines, via MYD88 signaling pathway, and CCL5 cytokine, via TICAM1 signaling pathway, as well as IL1B secretion. Binds electronegative LDL (LDL(-)) and mediates the cytokine release induced by LDL(-) (PubMed:23880187).
- Cross Reference Drug Bank:
- DB01183
- Gene Ontology Go:
- cell surface
cytoplasm
endosome membrane
external side of plasma membrane
integral component of plasma membrane
intrinsic component of plasma membrane
lipopolysaccharide receptor complex
perinuclear region of cytoplasm
plasma membrane
lipopolysaccharide binding
lipopolysaccharide receptor activity
receptor activity
transmembrane signaling receptor activity
activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway
activation of MAPK activity
apoptotic process
astrocyte development
B cell proliferation involved in immune response
cellular response to lipopolysaccharide
cellular response to lipoteichoic acid
cellular response to mechanical stimulus
defense response to bacterium
defense response to Gram-negative bacterium
detection of fungus
detection of lipopolysaccharide
extrinsic apoptotic signaling pathway
I-kappaB kinase/NF-kappaB signaling
I-kappaB phosphorylation
immune response
innate immune response
interferon-gamma production
interleukin-1 beta secretion
intestinal epithelial structure maintenance
lipopolysaccharide-mediated signaling pathway
macrophage activation
MyD88-dependent toll-like receptor signaling pathway
MyD88-independent toll-like receptor signaling pathway
negative regulation of ERK1 and ERK2 cascade
negative regulation of interferon-gamma production
negative regulation of interleukin-17 production
negative regulation of interleukin-23 production
negative regulation of interleukin-6 production
negative regulation of osteoclast differentiation
negative regulation of tumor necrosis factor production
nitric oxide production involved in inflammatory response
positive regulation of B cell proliferation
positive regulation of chemokine production
positive regulation of ERK1 and ERK2 cascade
positive regulation of gene expression
positive regulation of inflammatory response
positive regulation of interferon-alpha production
positive regulation of interferon-beta biosynthetic process
positive regulation of interferon-beta production
positive regulation of interferon-gamma production
positive regulation of interleukin-1 production
positive regulation of interleukin-10 production
positive regulation of interleukin-12 biosynthetic process
positive regulation of interleukin-12 production
positive regulation of interleukin-6 production
positive regulation of interleukin-8 biosynthetic process
positive regulation of interleukin-8 production
positive regulation of JNK cascade
positive regulation of macrophage cytokine production
positive regulation of MHC class II biosynthetic process
positive regulation of NF-kappaB import into nucleus
positive regulation of NF-kappaB transcription factor activity
positive regulation of nitric oxide biosynthetic process
positive regulation of nitric-oxide synthase biosynthetic process
positive regulation of NLRP3 inflammasome complex assembly
positive regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway
positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway
positive regulation of platelet activation
positive regulation of transcription from RNA polymerase II promoter
positive regulation of tumor necrosis factor biosynthetic process
positive regulation of tumor necrosis factor production
programmed cell death
regulation of cytokine secretion
regulation of dendritic cell cytokine production
response to lipopolysaccharide
T-helper 1 type immune response
toll-like receptor 2 signaling pathway
toll-like receptor 3 signaling pathway
toll-like receptor 4 signaling pathway
toll-like receptor signaling pathway
toll-like receptor TLR1:TLR2 signaling pathway
toll-like receptor TLR6:TLR2 signaling pathway
TRIF-dependent toll-like receptor signaling pathway - Gene Ontology Biological Process:
- activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway
activation of MAPK activity
apoptotic process
astrocyte development
B cell proliferation involved in immune response
cellular response to lipopolysaccharide
cellular response to lipoteichoic acid
cellular response to mechanical stimulus
defense response to bacterium
defense response to Gram-negative bacterium
detection of fungus
detection of lipopolysaccharide
extrinsic apoptotic signaling pathway
I-kappaB kinase/NF-kappaB signaling
I-kappaB phosphorylation
immune response
innate immune response
interferon-gamma production
interleukin-1 beta secretion
intestinal epithelial structure maintenance
lipopolysaccharide-mediated signaling pathway
macrophage activation
MyD88-dependent toll-like receptor signaling pathway
MyD88-independent toll-like receptor signaling pathway
negative regulation of ERK1 and ERK2 cascade
negative regulation of interferon-gamma production
negative regulation of interleukin-17 production
negative regulation of interleukin-23 production
negative regulation of interleukin-6 production
negative regulation of osteoclast differentiation
negative regulation of tumor necrosis factor production
nitric oxide production involved in inflammatory response
positive regulation of B cell proliferation
positive regulation of chemokine production
positive regulation of ERK1 and ERK2 cascade
positive regulation of gene expression
positive regulation of inflammatory response
positive regulation of interferon-alpha production
positive regulation of interferon-beta biosynthetic process
positive regulation of interferon-beta production
positive regulation of interferon-gamma production
positive regulation of interleukin-10 production
positive regulation of interleukin-12 biosynthetic process
positive regulation of interleukin-12 production
positive regulation of interleukin-1 production
positive regulation of interleukin-6 production
positive regulation of interleukin-8 biosynthetic process
positive regulation of interleukin-8 production
positive regulation of JNK cascade
positive regulation of macrophage cytokine production
positive regulation of MHC class II biosynthetic process
positive regulation of NF-kappaB import into nucleus
positive regulation of NF-kappaB transcription factor activity
positive regulation of nitric oxide biosynthetic process
positive regulation of nitric-oxide synthase biosynthetic process
positive regulation of NLRP3 inflammasome complex assembly
positive regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway
positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway
positive regulation of platelet activation
positive regulation of transcription from RNA polymerase II promoter
positive regulation of tumor necrosis factor biosynthetic process
positive regulation of tumor necrosis factor production
programmed cell death
regulation of cytokine secretion
regulation of dendritic cell cytokine production
response to lipopolysaccharide
T-helper 1 type immune response
toll-like receptor 2 signaling pathway
toll-like receptor 3 signaling pathway
toll-like receptor 4 signaling pathway
toll-like receptor signaling pathway
toll-like receptor TLR1:TLR2 signaling pathway
toll-like receptor TLR6:TLR2 signaling pathway
TRIF-dependent toll-like receptor signaling pathway - Gene Ontology Molecular Function:
- lipopolysaccharide binding
lipopolysaccharide receptor activity
receptor activity
transmembrane signaling receptor activity - Gene Ontology Cellular Component:
- cell surface
cytoplasm
endosome membrane
external side of plasma membrane
integral component of plasma membrane
intrinsic component of plasma membrane
lipopolysaccharide receptor complex
perinuclear region of cytoplasm
plasma membrane - Keywords:
- 3D-structure
Age-related macular degeneration
Alternative splicing
Cell membrane
Complete proteome
Direct protein sequencing
Disulfide bond
Glycoprotein
Immunity
Inflammatory response
Innate immunity
Leucine-rich repeat
Membrane
Polymorphism
Receptor
Reference proteome
Repeat
Signal
Transmembrane
Transmembrane helix - Interacts With:
- O76552; Q9Y6Y9; Q9NPH5; P58753