TLR4 Products

Antibodies
Antibody Packs
TLR4 Antibody Pack
TLR4 Antibody Pack
NBP2-31096
Applications: WB, Flow, IHC, B/N
ELISA Kits
Human TLR4 ELISA Kit (Colorim ...
Human TLR4 ELISA Kit (Colorimetric)
NBP2-76569
Species: Hu
Applications: ELISA
Mouse TLR4 ELISA Kit (Colorim ...
Mouse TLR4 ELISA Kit (Colorimetric)
NBP2-76570
Species: Mu
Applications: ELISA
Human TLR4 ELISA Kit (Chemilu ...
Human TLR4 ELISA Kit (Chemilumines...
NBP2-76637
Species: Hu
Applications: ELISA
Inhibitors
TLR4 Inhibitor Peptide Set
TLR4 Inhibitor Peptide Set
NBP2-26244
Species: Hu, Mu, Rt
Applications: Flow, Func, In vitro, B/N
TLR4 Inhibitor
TLR4 Inhibitor
NBP2-31230
Species: Hu, Mu
Applications: In vitro
Lysates
TLR4 Overexpression Lysate
TLR4 Overexpression Lysate
NBP2-05647
Species: Hu
Applications: WB
Proteins
Recombinant Human TLR4 Protei ...
Recombinant Human TLR4 Protein, CF
1478-TR
Species: Hu
Applications: Bioactivity
Formulation Catalog # Availability Price  
Recombinant Mouse TLR4 Fc Chi ...
Recombinant Mouse TLR4 Fc Chimera ...
9149-TR
Species: Mu
Applications: Bioactivity
Formulation Catalog # Availability Price  
TLR4 Antibody Blocking Peptid ...
TLR4 Antibody Blocking Peptide
NBP2-24821PEP
Species: Hu
Applications: AC

Description

TLR4 (Toll-like receptor 4) is a type-1 transmembrane glycoprotein that is a pattern recognition receptor (PRR) belonging to the TLR family (1-3). TLR4 is expressed in many tissues and is most abundantly expressed in the placenta, spleen, and peripheral blood leukocytes (1). Human TLR4 is synthesized as a 839 amino acid (aa) protein containing a signal sequence (1-23 aa), an extracellular domain (ECD) (24-631 aa), a transmembrane domain (632-652 aa), and Toll/interleukin-1 receptor (TIR) cytoplasmic domain (652-839 aa) with a theoretical molecular weight of 95 kDa (3, 4). The ECD contains 21 leucine-rich repeats (LRRs) and has a horseshoe-shaped structure (3, 4). TLR4 requires binding with the co-receptor myeloid differentiation protein 2 (MD2) largely via hydrophilic interactions for proper ligand sensing and signaling (2-4). In general, the TLR family plays a role in activation of innate immunity and responds to a variety of pathogen-associated molecular patterns (PAMPs) (5). TLR4 is specifically responsive to lipopolysaccharide (LPS), which is found on the outer-membrane of most ram-negative bacteria (3-5). Activation of TLR4 requires binding of a ligand, such as LPS to MD2, followed by MD2-LPS complex binding to TLR4, resulting in a partial complex (TLR4-MD2/LPS) (3, 5). To become fully active, two partial complexes must dimerize thereby allowing the TIR domains of TLR4 to bind other adapter molecular and initiate signaling, triggering an inflammatory response and cytokine production (3, 5).

TLR4 signaling occurs through two distinct pathways: The MyD88 (myeloid differentiation primary response gene 88)-dependent pathway and the MyD88-independent (TRIF-dependent, TIR domain-containing adaptor inducing IFN-beta) pathway (3, 5-7). The MyD88-dependent pathway occurs mainly at the plasma membrane and involves the binding of MyD88-adaptor-like (MAL) protein followed by a signaling cascade that results in the activation of transcription factors including nuclear factor-kappaB (NF-kappaB) that promote the secretion of inflammatory molecules and increased phagocytosis (5-7). Conversely, the MyD88-independent pathway occurs after TLR4-MD2 complex internalization in the endosomal compartment. This pathway involves the binding of adapter proteins TRIF and TRIF-related adaptor molecule (TRAM), a signaling activation cascade resulting in IFN regulatory factor 3 (IRF3) translocation into the nucleus, and secretion of interferon-beta (INF-beta) genes and increased phagocytosis (5-7).

Given its expression on immune-related cells and its role in inflammation, TLR4 activation can contribute to various diseases (6-8). For instance, several studies have found that TLR4 activation is associated with neurodegeneration and several central nervous system (CNS) pathologies, including Alzheimer's disease, Parkinson's disease, and Huntington's disease (6, 7). Furthermore, TLR4 mutations have been shown to lead to higher rates of infections and increased susceptibility to sepsis (7-8). One potential therapeutic approach aimed at targeting TLR4 and neuroinflammation is polyphenolic compounds which include flavonoids and phenolic acids and alcohols (8).

Alternative names for TLR4 includes 76B357.1, ARMD10, CD284 antigen, CD284, EC 3.2.2.6, homolog of Drosophila toll, hToll, toll like receptor 4 protein, TOLL, toll-like receptor 4.

References

1. Vaure, C., & Liu, Y. (2014). A comparative review of toll-like receptor 4 expression and functionality in different animal species. Frontiers in immunology. https://doi.org/10.3389/fimmu.2014.00316

2. Park, B. S., & Lee, J. O. (2013). Recognition of lipopolysaccharide pattern by TLR4 complexes. Experimental & molecular medicine. https://doi.org/10.1038/emm.2013.97

3. Krishnan, J., Anwar, M.A., & Choi, S. (2016) TLR4 (Toll-Like Receptor 4). In: Choi S. (eds) Encyclopedia of Signaling Molecules. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6438-9_592-1

4. Botos, I., Segal, D. M., & Davies, D. R. (2011). The structural biology of Toll-like receptors. Structure. https://doi.org/10.1016/j.str.2011.02.004

5. Lu, Y. C., Yeh, W. C., & Ohashi, P. S. (2008). LPS/TLR4 signal transduction pathway. Cytokine. https://doi.org/10.1016/j.cyto.2008.01.006

6. Leitner, G. R., Wenzel, T. J., Marshall, N., Gates, E. J., & Klegeris, A. (2019). Targeting toll-like receptor 4 to modulate neuroinflammation in central nervous system disorders. Expert opinion on therapeutic targets. https://doi.org/10.1080/14728222.2019.1676416

7. Molteni, M., Gemma, S., & Rossetti, C. (2016). The Role of Toll-Like Receptor 4 in Infectious and Noninfectious Inflammation. Mediators of inflammation. https://doi.org/10.1155/2016/6978936

8. Rahimifard, M., Maqbool, F., Moeini-Nodeh, S., Niaz, K., Abdollahi, M., Braidy, N., Nabavi, S. M., & Nabavi, S. F. (2017). Targeting the TLR4 signaling pathway by polyphenols: A novel therapeutic strategy for neuroinflammation. Ageing research reviews. https://doi.org/10.1016/j.arr.2017.02.004

Bioinformatics

Entrez Human
Mouse
Rat
Uniprot Human
Human
Human
Mouse
Product By Gene ID 7099
Alternate Names
  • CD_antigen: CD284
  • EC 3.2.2.6
  • EC:3.2.2.6
  • homolog of Drosophila toll
  • hToll
  • TLR4
  • TLR-4
  • toll like receptor 4 protein
  • ARMD10
  • CD284 antigen
  • CD284
  • TOLL
  • toll-like receptor 4

Research Areas for TLR4

Find related products by research area and learn more about each of the different research areas below.

Adaptive Immunity
Cytokine Research
Immunology
Innate Immunity
Signal Transduction
Toll-Like Receptors

Bioinformatics Tool for TLR4

Discover related pathways, diseases and genes to TLR4. Need help? Read the Bioinformatics Tool Guide for instructions on using this tool.
 
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Related TLR4 Blog Posts

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Stimulator of interferon genes (STING), also known as TMEM173, promotes the production of the interferon’s IFN-alpha and IFN-beta.  STING possesses three functional domains: a cytoplasmic C-terminal tail, a central globular domain, and four N-...    Read more.
TRIF/TICAM1 and mitochondrial dynamics in the innate immune response
TRIF, also known as toll like receptor adaptor molecule 1 or TICAM1, is known for its role in invading foreign pathogens as part of our innate immune response. TRIF/TICAM1 is a TIR-domain adaptor protein (toll/interleukin-1 receptor) that interacts...    Read more.
The role of TLR4 in breast cancer
Toll like receptors (TLRs) are highly conserved proteins that are first known for their role in pathogen recognition and immune response activation.  In order to elicit the necessary immune response in reaction to a foreign pathogen, TLRs trigger cy...    Read more.
cIAP2 - balancing cell death and cell survival
The inhibitor of apoptosis proteins (IAPs) are important regulators of cell death and inflammation. The cellular inhibitor of apoptosis protein 2 (cIAP2) contains three Baculovirus IAP repeat (BIR) domains, a Ubiquitin associated (UBA) domain, and...    Read more.
TLR4 - A Guardian of Innate Immunity
Toll-like receptor 4 (TLR4) belongs to the family of Toll-like receptors (TLR), and plays a main role in pathogen recognition and innate immunity system activation. The TLR family members are highly conserved proteins that all contain a high degree of...    Read more.
IRAK4: The "master IRAK" critical for initiating immune responses
IRAK4, also known as Interleukin-1 receptor-associated kinase 4, is a serine/threonine-protein kinase that plays a critical role in initiating innate and adaptive immune responses against foreign pathogens. It activates NF-kappaB in both Toll-like rec...    Read more.
TLR4: Playing Roles in Apoptosis and Autoimmunity
TLR4 (Toll-like receptor 4) is a member of the Toll-like receptor (TLR) family that plays a key role in pathogen recognition and activation of innate immunity. Scientists have found that TLRs are highly conserved from Drosophila to humans, with a high...    Read more.
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