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Protein Page:
TLR4 (human)

Overview
TLR4 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. Also involved in LPS- independent inflammatory responses triggered by Ni(2+). These responses require non-conserved histidines and are, therefore, species-specific. Belongs to the lipopolysaccharide (LPS) receptor, a multi-protein complex containing at least CD14, LY96 and TLR4. Binding to bacterial LPS leads to homodimerization. Interacts with LY96 via the extracellular domain. Interacts with MYD88 and TIRAP via their respective TIR domains. Interacts with NOX4. Interacts with CNPY3. Interacts with HSP90B1. The interaction with both CNPY3 and HSP90B1 is required for proper folding in the endoplasmic reticulum. Highly expressed in placenta, spleen and peripheral blood leukocytes. Detected in monocytes, macrophages, dendritic cells and several types of T-cells. Belongs to the Toll-like receptor family. 3 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: Receptor, misc.; Membrane protein, integral
Cellular Component: perinuclear region of cytoplasm; integral to plasma membrane; cytoplasm; plasma membrane; lipopolysaccharide receptor complex; endosome membrane; external side of plasma membrane
Molecular Function: protein binding; transmembrane receptor activity; lipopolysaccharide binding; lipopolysaccharide receptor activity; receptor activity
Biological Process: I-kappaB kinase/NF-kappaB cascade; positive regulation of nitric oxide biosynthetic process; activation of MAPK activity; positive regulation of NF-kappaB import into nucleus; response to lipopolysaccharide; toll-like receptor 3 signaling pathway; positive regulation of interleukin-10 production; activation of NF-kappaB transcription factor; positive regulation of interferon-beta production; negative regulation of interleukin-6 production; positive regulation of B cell proliferation; toll-like receptor 4 signaling pathway; positive regulation of interferon-alpha production; T-helper 1 type immune response; positive regulation of I-kappaB kinase/NF-kappaB cascade; production of nitric oxide during acute inflammatory response; positive regulation of interleukin-8 biosynthetic process; positive regulation of interleukin-6 production; positive regulation of tumor necrosis factor production; positive regulation of chemokine production; toll-like receptor 2 signaling pathway; negative regulation of interleukin-23 production; macrophage activation; detection of lipopolysaccharide; defense response to bacterium; positive regulation of transcription from RNA polymerase II promoter; I-kappaB phosphorylation; positive regulation of nitric-oxide synthase biosynthetic process; negative regulation of osteoclast differentiation; regulation of cytokine secretion; positive regulation of interleukin-12 production; positive regulation of JNK cascade; defense response to Gram-negative bacterium; positive regulation of interleukin-8 production; positive regulation of MHC class II biosynthetic process; negative regulation of interferon-gamma production; lipopolysaccharide-mediated signaling pathway; interferon-gamma production; B cell proliferation during immune response; positive regulation of tumor necrosis factor biosynthetic process; detection of fungus; MyD88-independent toll-like receptor signaling pathway; negative regulation of tumor necrosis factor production; MyD88-dependent toll-like receptor signaling pathway; positive regulation of interferon-gamma production; positive regulation of interleukin-12 biosynthetic process; negative regulation of interleukin-17 production; positive regulation of interferon-beta biosynthetic process; toll-like receptor signaling pathway; innate immune response; immune response; positive regulation of interleukin-1 production; positive regulation of inflammatory response
Reference #:  O00206 (UniProtKB)
Alt. Names/Synonyms: ARMD10; CD284; homolog of Drosophila toll; hToll; TLR4; TOLL; Toll-like receptor 4
Gene Symbols: TLR4
Molecular weight: 95,680 Da
Basal Isoelectric point: 5.88  Predict pI for various phosphorylation states
CST Pathways:  NF-kB Signaling  |  Toll-Like Receptor Signaling
Select Structure to View Below

TLR4

Protein Structure Not Found.


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Sites Implicated In
transcription, induced: Y674‑p, Y680‑p
molecular association, regulation: Y674‑p, Y680‑p
phosphorylation: Y674‑p, Y680‑p

Modification Sites and Domains  

Modification Sites in Parent Protein, Orthologs, and Isoforms  
 

Show Multiple Sequence Alignment


 SS 

SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.


 MS 

MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.


       human

 
1 0 T175-p PEYFSNLtNLEHLDL
0 1 E376 EVDLPSLEFLDLSRN
0 1 F377 VDLPSLEFLDLSRNG
0 1 S381 SLEFLDLSRNGLSFK
0 1 Y551-p NSLQVLDySLNHIMT
1 0 Y674-p YGRGENIyDAFVIyS
1 0 Y680-p IyDAFVIySSQDEDW
0 1 S730-p IHEGFHKsRKVIVVV
0 1 S738-p RKVIVVVsQHFIQSR
1 0 S790-p VELYRLLsRNTYLEW
0 1 S800-p TYLEWEDsVLGRHIF
  mouse

 
T174 PAYFSNLTNLVHVDL
S374-p KVALPSLsyLDLsRN
Y375-p VALPSLsyLDLsRNA
S379-p SLsyLDLsRNALSFS
C549 YSLSTLDCSFNRIET
Y672 YSRGESIYDAFVIYS
Y678 IYDAFVIYSSQNEDW
S728 IQEGFHKSRKVIVVV
S736 RKVIVVVSRHFIQSR
S788 VELYRLLSRNTYLEW
N798 TYLEWEDNPLGRHIF
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