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TLR4 / TLR-4  Protein, Antibody, ELISA Kit, cDNA Clone

Expression host: Baculovirus-Insect Cells  
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10146-H08B-50
10146-H08B-100
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100 µg 
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TLR4 / TLR-4 Related Area

TLR4 / TLR-4 Related Pathways

TLR4 / TLR-4 Summary & Protein Information

TLR4 / TLR-4 Background

Gene Summary: The protein encoded by TLR4 gene is a member of the Toll-like receptor (TLR) family which plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. They recognize pathogen-associated molecular patterns that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity. The various TLRs exhibit different patterns of expression. This receptor has been implicated in signal transduction events induced by lipopolysaccharide (LPS) found in most gram-negative bacteria. Mutations in TLR4 gene have been associated with differences in LPS responsiveness. Multiple transcript variants encoding different isoforms have been found for TLR4 gene. [provided by RefSeq, Jan 2012]
General information above from NCBI
Subunit structure: 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 (By similarity). Interacts with HSP90B1. The interaction with both CNPY3 and HSP90B1 is required for proper folding in the endoplasmic reticulum. Interacts with MLK4; this interaction leads to negative regulation of TLR4 signaling. Interacts with CD36, following CD36 stimulation by oxLDL or amyloid-beta 42, and forms a heterodimer with TLR6. The trimeric complex is internalized and triggers inflammatory response. LYN kinase activity facilitates TLR4-TLR6 heterodimerization and signal initiation. {ECO:0000250, ECO:0000269|PubMed:15356101, ECO:0000269|PubMed:19252480, ECO:0000269|PubMed:20037584, ECO:0000269|PubMed:20865800, ECO:0000269|PubMed:21602844}.
Domain: The TIR domain mediates interaction with NOX4.
Subcellular location: Cell membrane; Single-pass type I membrane protein. Note=Upon complex formation with CD36 and TLR6, internalized through dynamin-dependent endocytosis. {ECO:0000269|PubMed:20037584}.
Tissue specificity: Highly expressed in placenta, spleen and peripheral blood leukocytes. Detected in monocytes, macrophages, dendritic cells and several types of T-cells.
Post-translational: N-glycosylated. Glycosylation of Asn-526 and Asn-575 seems to be necessary for the expression of TLR4 on the cell surface and the LPS-response. Likewise, mutants lacking two or more of the other N-glycosylation sites were deficient in interaction with LPS. {ECO:0000269|PubMed:11706042, ECO:0000269|PubMed:17803912, ECO:0000269|PubMed:19252480, ECO:0000269|PubMed:22363519}.
Involvement in disease: DISEASE: Macular degeneration, age-related, 10 (ARMD10) [MIM:611488]: A form of age-related macular degeneration, a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
Sequence similarity: Belongs to the Toll-like receptor family. {ECO:0000305}.; Contains 18 LRR (leucine-rich) repeats. {ECO:0000305}.; Contains 1 LRRCT domain. {ECO:0000305}.; Contains 1 TIR domain. {ECO:0000255|PROSITE-ProRule:PRU00204}.
General information above from UniProt

TLR4, also known as TLR-4, is a member of the Toll-like receptor (TLR) family, which plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. They recognize pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity. TLR4 is most abundantly expressed in placenta, and in myelomonocytic subpopulation of the leukocytes. TLR 4 has also been designated as CD284 (cluster of differentiation 284). It has been implicated in signal transduction events induced by lipopolysaccharide (LPS) found in most gram-negative bacteria. TLR4 Cooperates with LY96 and CD14 to mediate the innate immune response to bacterial lipopolysaccharide (LPS). It acts via MYD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. It is also involved in LPS-independent inflammatory responses triggered by Ni(2+).

TLR4 / TLR-4 Alternative Name

ARMD10,CD284,TLR-4,TOLL, [human]
Lps,Ly87,Ran/M1,Rasl2-8,RP24-209H15.1, [mouse]

TLR4 / TLR-4 Related Studies

  • Re, Fabio, et al. (2002) Monomeric recombinant MD-2 binds toll-like receptor 4 tightly and confers lipopolysaccharide responsiveness. J Biol Chem. 277(26):23427-32.
  • Shimazu, R, et al. (1999) MD-2, a Molecule that Confers Lipopolysaccharide Responsiveness on Toll-like Receptor 4. J Exp Med. 189(11):1777-82.
  • Blanco, A M, et al. (2005) Involvement of TLR4/type I IL-1 receptor signaling in the induction of inflammatory mediators and cell death induced by ethanol in cultured astrocytes. Journal of immunology. 175(10):6893-9.
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