lmmol · Proteins

Toll-like receptor 4

UniProt O00206 Organism Homo sapiens Gene TLR4

Also known as: TLR4

Function

Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstream signaling pathways. At the plasma membrane, cooperates with LY96 to mediate the innate immune response to bacterial lipopolysaccharide (LPS). Also involved in LPS-independent inflammatory responses triggered by free fatty acids, such as palmitate, and Ni(2+). Mechanistically, acts via MYD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Alternatively, CD14-mediated TLR4 internalization via endocytosis is associated with the initiation of a MYD88-independent signaling via the TICAM1-TBK1-IRF3 axis leading to type I interferon production. In addition to the secretion of proinflammatory cytokines, initiates the activation of NLRP3 inflammasome and formation of a positive feedback loop between autophagy and NF-kappa-B signaling cascade. In complex with TLR6, promotes inflammation in monocytes/macrophages by associating with TLR6 and the receptor CD86. Upon ligand binding, such as oxLDL or amyloid-beta 42, the TLR4:TLR6 complex is internalized and triggers inflammatory response, leading to NF-kappa-B-dependent production of CXCL1, CXCL2 and CCL9 cytokines, via MYD88 signaling pathway, and CCL5 cytokine, via TICAM1 signaling pathway. In myeloid dendritic cells, vesicular stomatitis virus glycoprotein G but not LPS promotes the activation of IRF7, leading to type I IFN production in a CD14-dependent manner. Required for the migration-promoting effects of ZG16B/PAUF on pancreatic cancer cells.

Classification

Family (Pfam)
PF12799 LRR_4, PF13516 LRR_6, PF13855 LRR_8, PF01582 TIR
InterPro
Cys-rich_flank_reg_C, Leu-rich_rpt, Leu-rich_rpt_4, Leu-rich_rpt_typical-subtyp, LRR_dom_sf, TIR_dom, Toll-like_receptor, Toll_tir_struct_dom_sf
Functional cluster
Immunoglobulin-Domain Cell Adhesion Proteins

Experimental structures · PDB · 15

A predicted model is available from AlphaFold.

Gene Ontology · 76

Drugs targeting this protein · 2

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Literature · 49 cited papers

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