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TLR2

Domain

Ester-bound lipid substrates are bound through a crevice formed between the LRR 11 and LRR 12.

The ATG16L1-binding motif mediates interaction with ATG16L1.

The TIR domain mediates NAD(+) hydrolase (NADase) activity. Self-association of TIR domains is required for NADase activity.

Function

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).

Post-translational modifications

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.

Sequence similarities

Belongs to the Toll-like receptor family.

Tissue specificity

Detected in a macrophage cell line, smooth muscle, lung, spleen, thymus, brain and adipose tissue. Cell surface expression detected in lung alveolar macrophages, dendritic macrophages and at lower levels in lung macrophages (at protein level) (PubMed:19362712).

Cellular localization

  • Cell membrane
  • Single-pass type I membrane protein
  • Cytoplasmic vesicle
  • Phagosome membrane
  • Single-pass type I membrane protein
  • 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.

Alternative names

  • Toll-like receptor 2
  • Tlr2

Target type

Proteins

Primary research area

Immunology & Infectious Disease

Other research areas

  • Immuno-oncology

Molecular weight

89449Da