TLR2

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. This protein is a cell-surface protein that can form heterodimers with other TLR family members to recognize conserved molecules derived from microorganisms known as pathogen-associated molecular patterns (PAMPs). Activation of TLRs by PAMPs leads to an up-regulation of signaling pathways to modulate the host's inflammatory response. This gene is also thought to promote apoptosis in response to bacterial lipoproteins. This gene has been implicated in the pathogenesis of several autoimmune diseases. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

TLR2 Toll Like Receptor 2

Cooperates with LY96 to mediate the innate immune response to bacterial lipoproteins and other microbial cell wall components. Cooperates with TLR1 or TLR6 to mediate the innate immune response to bacterial lipoproteins or lipopeptides. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (By similarity) (PubMed:15690042).
May also promote apoptosis in response to lipoproteins (By similarity).
Forms activation clusters composed of several receptors depending on the ligand, these clusters trigger signaling from the cell surface and subsequently are targeted to the Golgi in a lipid-raft dependent pathway. Forms the cluster TLR2:TLR6:CD14:CD36 in response to diacylated lipopeptides and TLR2:TLR1:CD14 in response to triacylated lipopeptides (By similarity).
Recognizes M.tuberculosis major T-antigen EsxA (ESAT-6) which inhibits downstream MYD88-dependent signaling (PubMed:17486091).
Acts as the major receptor for M.tuberculosis lipoproteins LprA, LprG, LpqH and PhoS1 (pstS1), in conjunction with TLR1 and for some but not all lipoproteins CD14 and/or CD36. The lipoproteins act as agonists to modulate antigen presenting cell functions in response to the pathogen (PubMed:19362712).
Recombinant MPT83 from M.tuberculosis stimulates secretion of cytokines (TNF-alpha, IL-6 and IL-12p40) by mouse macrophage cell lines in a TLR2-dependent fashion, which leads to increased host innate immunity responses against the bacterium (PubMed:22174456).
Lung macrophages which express low levels of TLR2 respond poorly to stimulation by M.tuberculosis LpqH (PubMed:19362712).
Required for normal uptake of M.tuberculosis, a process that is inhibited by M.tuberculosis LppM (PubMed:27220037).
Interacts with TICAM2 (By similarity).

Biological Process cell activationSource:MGI
Biological Process cell surface pattern recognition receptor signaling pathwaySource:MGI1 Publication
Biological Process cellular response to bacterial lipopeptideSource:MGI1 Publication
Biological Process cellular response to diacyl bacterial lipopeptideSource:UniProtKB
Biological Process cellular response to interferon-gammaSource:MGI
Biological Process cellular response to lipoteichoic acidSource:MGI1 Publication
Biological Process cellular response to peptidoglycanSource:MGI1 Publication
Biological Process cellular response to triacyl bacterial lipopeptideSource:UniProtKB
Biological Process central nervous system myelin formationSource:MGI
Biological Process defense responseSource:MGI1 Publication
Biological Process defense response to Gram-positive bacteriumSource:MGI3 Publications
Biological Process detection of diacyl bacterial lipopeptideSource:MGI
Biological Process detection of triacyl bacterial lipopeptideSource:MGI
Biological Process ERK1 and ERK2 cascadeSource:MGI1 Publication
Biological Process I-kappaB phosphorylationSource:MGI
Biological Process inflammatory responseSource:MGI
Biological Process innate immune responseSource:BHF-UCL1 Publication
Biological Process learningSource:ARUK-UCL1 Publication
Biological Process leukocyte migrationSource:MGI1 Publication
Biological Process leukotriene metabolic processSource:MGI
Biological Process microglia developmentSource:ARUK-UCL1 Publication
Biological Process microglial cell activationSource:MGI
Biological Process MyD88-dependent toll-like receptor signaling pathwaySource:MGI1 Publication
Biological Process negative regulation of actin filament polymerizationSource:ARUK-UCL1 Publication
Biological Process negative regulation of cell population proliferationSource:MGI
Biological Process negative regulation of interleukin-12 productionSource:MGI1 Publication
Biological Process negative regulation of interleukin-17 productionSource:MGI1 Publication
Biological Process negative regulation of phagocytosisSource:ARUK-UCL1 Publication
Biological Process negative regulation of synapse assemblySource:ARUK-UCL1 Publication
Biological Process neutrophil migrationSource:MGI1 Publication
Biological Process NIK/NF-kappaB signalingSource:MGI1 Publication
Biological Process nitric oxide biosynthetic processSource:MGI2 Publications
Biological Process nitric oxide metabolic processSource:MGI
Biological Process positive regulation of cellular response to macrophage colony-stimulating factor stimulusSource:MGI
Biological Process positive regulation of chemokine productionSource:MGI1 Publication
Biological Process positive regulation of cytokine productionSource:MGI1 Publication
Biological Process positive regulation of ERK1 and ERK2 cascadeSource:MGI1 Publication
Biological Process positive regulation of gene expressionSource:MGI
Biological Process positive regulation of inflammatory responseSource:ARUK-UCL1 Publication
Biological Process positive regulation of interferon-beta productionSource:BHF-UCL1 Publication
Biological Process positive regulation of interleukin-1 beta productionSource:ARUK-UCL1 Publication
Biological Process positive regulation of interleukin-10 productionSource:MGI
Biological Process positive regulation of interleukin-12 productionSource:BHF-UCL1 Publication
Biological Process positive regulation of interleukin-18 productionSource:BHF-UCL1 Publication
Biological Process positive regulation of interleukin-6 productionSource:BHF-UCL1 Publication
Biological Process positive regulation of interleukin-8 productionSource:MGI
Biological Process positive regulation of leukocyte migrationSource:MGI1 Publication
Biological Process positive regulation of macrophage cytokine productionSource:MGI1 Publication
Biological Process positive regulation of matrix metallopeptidase secretionSource:MGI
Biological Process positive regulation of neutrophil migrationSource:MGI1 Publication
Biological Process positive regulation of NF-kappaB transcription factor activitySource:MGI
Biological Process positive regulation of NIK/NF-kappaB signalingSource:MGI1 Publication
Biological Process positive regulation of nitric oxide biosynthetic processSource:MGI2 Publications
Biological Process positive regulation of nitric-oxide synthase biosynthetic processSource:BHF-UCL1 Publication
Biological Process positive regulation of oligodendrocyte differentiationSource:MGI
Biological Process positive regulation of toll-like receptor signaling pathwaySource:MGI
Biological Process positive regulation of transcription by RNA polymerase IISource:BHF-UCL1 Publication
Biological Process positive regulation of tumor necrosis factor productionSource:BHF-UCL1 Publication
Biological Process positive regulation of Wnt signaling pathwaySource:MGI
Biological Process positive regulation of xenophagySource:MGI1 Publication
Biological Process regulation of dendritic cell cytokine productionSource:MGI1 Publication
Biological Process response to bacterial lipoproteinSource:MGI
Biological Process response to bacteriumSource:MGI1 Publication
Biological Process response to fatty acidSource:MGI
Biological Process response to molecule of fungal originSource:MGI1 Publication
Biological Process response to peptidoglycanSource:MGI2 Publications
Biological Process toll-like receptor 2 signaling pathwaySource:InterPro
Biological Process toll-like receptor signaling pathwaySource:MGI
Biological Process toll-like receptor TLR6:TLR2 signaling pathwaySource:MGI
Biological Process xenophagySource:MGI1 Publication

Cell membrane
Cytoplasmic vesicle, phagosome membrane
Membrane raft
Does not reside in lipid rafts before stimulation but accumulates increasingly in the raft upon the presence of the microbial ligand. In response to diacylated lipoproteins, TLR2:TLR6 heterodimers are recruited in lipid rafts, this recruitment determine the intracellular targeting to the Golgi apparatus. Triacylated lipoproteins induce the same mechanism for TLR2:TLR1 heterodimers.

Extracellular: 25-587
Helical: 588-608
Cytoplasmic: 609-784

Ubiquitinated at Lys-754 by PPP1R11, leading to its degradation. Deubiquitinated by USP2.
Glycosylation of Asn-442 is critical for secretion of the N-terminal ectodomain of TLR2.