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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
Chromosomal Location of Human Ortholog: 9q33.1
Cellular Component: cell surface; cytoplasm; endosome membrane; external side of plasma membrane; integral to plasma membrane; intrinsic to plasma membrane; lipopolysaccharide receptor complex; perinuclear region of cytoplasm; plasma membrane
Molecular Function: lipopolysaccharide binding; lipopolysaccharide receptor activity; protein binding; receptor activity; transmembrane receptor activity
Biological Process: activation of MAPK activity; activation of NF-kappaB transcription factor; astrocyte development; B cell proliferation during immune response; defense response to bacterium; defense response to Gram-negative bacterium; detection of fungus; detection of lipopolysaccharide; I-kappaB kinase/NF-kappaB cascade; I-kappaB phosphorylation; immune response; inflammatory response; innate immune response; interferon-gamma production; interleukin-1 beta secretion; lipopolysaccharide-mediated signaling pathway; macrophage activation; MyD88-dependent toll-like receptor signaling pathway; MyD88-independent toll-like receptor signaling pathway; 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 MyD88-independent toll-like receptor signaling pathway; negative regulation of osteoclast differentiation; negative regulation of tumor necrosis factor production; positive regulation of B cell proliferation; positive regulation of chemokine production; 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 MHC class II biosynthetic process; positive regulation of NF-kappaB import into nucleus; positive regulation of nitric oxide biosynthetic process; positive regulation of nitric-oxide synthase biosynthetic process; positive regulation of transcription from RNA polymerase II promoter; positive regulation of tumor necrosis factor biosynthetic process; positive regulation of tumor necrosis factor production; production of nitric oxide during acute inflammatory response; regulation of cytokine secretion; regulation of dendritic cell cytokine production; response to lipopolysaccharide; T-helper 1 type immune response; toll-like receptor 4 signaling pathway; toll-like receptor signaling pathway
Disease: Macular Degeneration, Age-related, 10
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


 LTP 

LTP: 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.


 HTP 

HTP: 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 Y551‑p NSLQVLDySLNHIMT
2 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
C549 YSLSTLDCSFNRIET
Y672 YSRGESIYDAFVIYS
Y678 IYDAFVIYSSQNEDW
S728 IQEGFHKSRKVIVVV
S736 RKVIVVVSRHFIQSR
S788 VELYRLLSRNTYLEW
N798 TYLEWEDNPLGRHIF
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