Toll-Like Receptor 4 (TLR4) Antibody – Mouse Monoclonal

The protein encoded by this 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 (PAMPs) 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 is most abundantly expressed in placenta, and in myelomonocytic subpopulation of the leukocytes. It has been implicated in signal transduction events induced by lipopolysaccharide (LPS) found in most gram-negative bacteria. Mutations in this gene have been associated with differences in LPS responsiveness. Also, several transcript variants of this gene have been found, but the protein coding potential of most of them is uncertain. [provided by RefSeq]

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. Also involved in LPS-independent inflammatory responses triggered by Ni2+. These responses require non-conserved histidines and are, therefore, species-specific. Ref.15

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. Ref.14

Subcellular location: Membrane; Single-pass type I membrane protein.

Tissue specificity: Highly expressed in placenta, spleen and peripheral blood leukocytes. Detected in monocytes, macrophages, dendritic cells and several types of T-cells.

Domain: The TIR domain mediates interaction with NOX4.

Post-translational modification: 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. Ref.13 Ref.16 Ref.17

Polymorphism: Allele TLR4*B (Gly-299, Ile-399) is associated with a blunted response to inhaled LPS.

Involvement in disease: Genetic variation in TLR4 is associated with age-related macular degeneration type 10 (ARMD10) [

MIM:611488]. ARMD is 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.

Miscellaneous: His-456 and His-458 are found in TLR4 of human and several other primate species and may be responsible for inflammatory responses triggered by nickel (Ni2+). Ni2+ may cross-link the two receptor monomers through specific histidines, triggering the formation of a dimer that structurally resembles that induced by LPS. This process may be the basis for the development of contact allergy to Ni2+. A mouse model of contact allergy to Ni2+ in which TLR4-deficient mice expresses human TLR4 has been proposed.

Sequence similarities: Belongs to the Toll-like receptor family.Contains 18 LRR (leucine-rich) repeats.Contains 1 LRRCT domain.Contains 1 TIR domain.