LMPD Database

New search | Record Overview | Ontology/Pathway Information | Domain Information | UniProt Annotations | Related Proteins
LMP012574

UniProt Annotations

Entry Information
Gene Nametoll-like receptor 4
Protein EntryTLR4_RAT
UniProt IDQ9QX05
SpeciesRat
Comments
Comment typeDescription
DomainThe TIR domain mediates interaction with NOX4
FunctionCooperates 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 free fatty acids, such as palmitate. In complex with TLR6, promotes sterile inflammation in monocytes/macrophages in response to oxidized low- density lipoprotein (oxLDL) or amyloid-beta 42. In this context, the initial signal is provided by oxLDL- or amyloid-beta 42- binding to CD36. This event induces the formation of a heterodimer of TLR4 and TLR6, which is rapidly internalized and triggers inflammatory response, leading to the NF-kappa-B-dependent production of CXCL1, CXCL2 and CCL9 cytokines, via MYD88 signaling pathway, and CCL5 cytokine, via TICAM1 signaling pathway, as well as IL1B secretion
SimilarityBelongs to the Toll-like receptor family
SimilarityContains 16 LRR (leucine-rich) repeats
SimilarityContains 1 LRRCT domain
SimilarityContains 1 TIR domain. {ECO:0000255|PROSITE- ProRule:PRU00204}.
Subcellular LocationCell membrane ; Single-pass type I membrane protein . Note=Upon complex formation with CD36 and TLR6, internalized through dynamin-dependent endocytosis
SubunitBelongs 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 and HSP90B1; this interaction 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