Toll-like receptor 4; hToll; CD284 (TLR4)

Function

• cooperates with LY96 & CD14 to mediate the innate immune response to bacterial lipopolysaccharide (LPS) or lipid A
• acts via MyD88, TIRAP & TRAF6
• NF-kappa-B activation
• cytokine secretion
• inflammatory response
• may attenuate allergic response
  • TLR4 stimulation reduces allergen induced IL-13
• component of lipopolysaccharide receptor (LPS receptor)
• interacts with MyD88, TIRAP, NOX4
• interacts with LY96 via the extracellular domain

Structure

• N-glycosylated
  • glycosylation of Asn-526 & Asn-575 appears to be necessary for the expression of TLR4 on the cell surface & the LPS-response
  • mutants lacking 2 or more other N-glycosylation sites are deficient in interaction with LPS
• TIR domain mediates interaction with NOX4
• belongs to the Toll-like receptor family
• contains 21 LRR repeats (leucine-rich repeats)
• contains 1 TIR domain

Compartment

membrane

Alternative splicing

named isoforms=3

Expression

• expressed in placenta, spleen, peripheral blood leukocytes > monocytes, macrophages, dendritic cells, T-cells

Pathology

• genetic variation in TLR4 is associated with age-related macular degeneration type 10

Polymorphism

• allele TLR4*B (Gly-299, Ile-399) associated with blunted response to inhaled LPS

Pharmacology

• ibudilast inhibits Toll-like receptor 4 allegedly targeting neuroinflammation
• ApToll is a DNA oligonucleotide antagonist at toll-like receptor 4 & an investigational agent for treatment of ischemic stroke in combination with endovascular thrombectomy

More general terms

• toll-like receptor
• leucine-rich repeat-containing protein (LRRC)
• glycoprotein
• CD antigen

Additional terms

• Toll/interleukin-1 receptor domain-containing adapter protein; TIR domain-containing adapter protein; adaptor protein Wyatt; MyD88 adapter-like protein (TIRAP, MAL)

Component of

• lipopolysaccharide (LPS) receptor

Database

• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:7099
• OMIM: https://mirror.omim.org/entry/603030
• OMIM: https://mirror.omim.org/entry/611488
• UniProt: http://www.uniprot.org/uniprot/O00206.html
• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=7099