UniprotKB/SwissProt ID: Q9QUK6 (Q9QUK6)
Gene Name:
Tlr4
Organism: Mus musculus (Mouse)
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 (PubMed:20133493, PubMed:9851930, PubMed:9989976). At the plasma membrane, cooperates with LY96 to mediate the innate immune response to bacterial lipopolysaccharide (LPS) (PubMed:20133493, PubMed:9851930, PubMed:9989976). 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 (PubMed:24380872). 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 (By similarity) (Microbial infection) Required for the virulence of fungus C.neoformans var. grubii serotype A (strain KN99) CPL1 (PubMed:35896747). Independently of Ly96/Md2, activated by CPL1 which results in a type 2 inflammation response characterized by Arg1/arginase-1 induction in interstitial macrophages (PubMed:35896747) (Microbial infection) Mediates activation of bone marrow-derived dendritic cells and macrophages, and production of pro-inflammatory cytokines, such as IL12 (IL12B/IL12A), triggered by Toxoplasma gondii micronemal protein 4 (MIC4) and micronemal protein 1 (MIC1) (PubMed:31226171). Mediates production of anti-inflammatory cytokine IL10 triggered by Toxoplasma gondii micronemal protein 4 (MIC4) and micronemal protein 1 (MIC1) in murine bone marrow-derived macrophages (PubMed:33912181)
Other Modifications: View all modification sites in dbPTM
Protein Subcellular Localization: Cell membrane. Early endosome. Cell projection, ruffle
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