Toll-like receptor 2
Also known as: TIL4, TLR2
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. May also activate immune cells and promote apoptosis in response to the lipid moiety of lipoproteins. Recognizes mycoplasmal macrophage-activating lipopeptide-2kD (MALP-2), soluble tuberculosis factor (STF), phenol-soluble modulin (PSM) and B.burgdorferi outer surface protein A lipoprotein (OspA-L) cooperatively with TLR6. Stimulation of monocytes in vitro with M.tuberculosis PstS1 induces p38 MAPK and ERK1/2 activation primarily via this receptor, but also partially via TLR4. MAPK activation in response to bacterial peptidoglycan also occurs via this receptor. Acts as a receptor for M.tuberculosis lipoproteins LprA, LprG, LpqH and PstS1, some lipoproteins are dependent on other coreceptors (TLR1, CD14 and/or CD36); the lipoproteins act as agonists to modulate antigen presenting cell functions in response to the pathogen. M.tuberculosis HSP70 (dnaK) but not HSP65 (groEL-2) acts via this protein to stimulate NF-kappa-B expression. Recognizes M.tuberculosis major T-antigen EsxA (ESAT-6) which inhibits downstream MYD88-dependent signaling (shown in mouse) (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. Required for normal uptake of M.tuberculosis, a process that is inhibited by M.tuberculosis LppM (By similarity).
Classification
- Family (Pfam)
- PF00560 LRR_1, PF13855 LRR_8, PF01463 LRRCT, PF01582 TIR
- InterPro
- Cys-rich_flank_reg_C, Leu-rich_rpt, Leu-rich_rpt_typical-subtyp, LRR_dom_sf, TIR_dom, Toll-like_receptor, Toll_tir_struct_dom_sf
- Functional cluster
- Immunoglobulin & Immune-Response Proteins
Experimental structures · PDB · 7
- 1FYW X-ray 3.00A
- 1FYX X-ray 2.80A
- 1O77 X-ray 3.20A
- 2Z7X X-ray 2.10A
- 2Z80 X-ray 1.80A
- 6NIG X-ray 2.35A
- 8AR0 NMR
A predicted model is available from AlphaFold.
Gene Ontology · 59
- GO:0009986 cell surface
- GO:0005737 cytoplasm
- GO:0005794 Golgi apparatus
- GO:0045121 membrane raft
- GO:0030670 phagocytic vesicle membrane
- GO:0005886 plasma membrane
- GO:0044853 plasma membrane raft
- GO:0043235 receptor complex
- GO:0030667 secretory granule membrane
- GO:0035354 Toll-like receptor 1-Toll-like receptor 2 protein complex
- GO:0035355 Toll-like receptor 2-Toll-like receptor 6 protein complex
- GO:0001540 amyloid-beta binding
- GO:0042802 identical protein binding
- GO:0001530 lipopolysaccharide binding
- GO:0001875 lipopolysaccharide immune receptor activity
- GO:0038187 pattern recognition receptor activity
- GO:0042834 peptidoglycan binding
- GO:0044877 protein-containing complex binding
- GO:0038023 signaling receptor activity
- GO:0035325 Toll-like receptor binding
- GO:0004888 transmembrane signaling receptor activity
- GO:0042497 triacyl lipopeptide binding
- GO:0140367 antibacterial innate immune response
- GO:0006915 apoptotic process
- GO:0071221 cellular response to bacterial lipopeptide
- GO:0071726 cellular response to diacyl bacterial lipopeptide
- GO:0071223 cellular response to lipoteichoic acid
- GO:0071727 cellular response to triacyl bacterial lipopeptide
- GO:0071346 cellular response to type II interferon
- GO:0050830 defense response to Gram-positive bacterium
- GO:0051607 defense response to virus
- GO:0042496 detection of diacyl bacterial lipopeptide
- GO:0042495 detection of triacyl bacterial lipopeptide
- GO:0006955 immune response
- GO:0006954 inflammatory response
- GO:0045087 innate immune response
- GO:0007612 learning
- GO:0014005 microglia development
- GO:0050765 negative regulation of phagocytosis
- GO:0051964 negative regulation of synapse assembly
- GO:0043123 positive regulation of canonical NF-kappaB signal transduction
- GO:1903974 positive regulation of cellular response to macrophage colony-stimulating factor stimulus
- GO:0032722 positive regulation of chemokine production
- GO:0010628 positive regulation of gene expression
- GO:0050729 positive regulation of inflammatory response
- GO:0032728 positive regulation of interferon-beta production
- GO:0032735 positive regulation of interleukin-12 production
- GO:0032741 positive regulation of interleukin-18 production
- GO:0032755 positive regulation of interleukin-6 production
- GO:0032757 positive regulation of interleukin-8 production
- GO:1904466 positive regulation of matrix metallopeptidase secretion
- GO:0045944 positive regulation of transcription by RNA polymerase II
- GO:0032760 positive regulation of tumor necrosis factor production
- GO:0030177 positive regulation of Wnt signaling pathway
- GO:0007165 signal transduction
- GO:0034134 toll-like receptor 2 signaling pathway
- GO:0002224 toll-like receptor signaling pathway
- GO:0038123 toll-like receptor TLR1:TLR2 signaling pathway
- GO:0038124 toll-like receptor TLR6:TLR2 signaling pathway
Disease associations
- leprosy, susceptibility to, 3 MONDO:0009518
Drugs targeting this protein · 1
- VB-201 inhibitor
Related proteins · sequence + function similarity
- Toll-like receptor 2 1.00
- Toll-like receptor 2 1.00
- Toll-like receptor 2 1.00
- Toll-like receptor 2 1.00
- Toll-like receptor 2 1.00
- Toll-like receptor 2 0.99
- Toll-like receptor 2 0.98
- Toll-like receptor 2 0.98
- Toll-like receptor 2 0.98
- Toll-like receptor 2 0.98
- Toll-like receptor 2 0.98
- Toll-like receptor 2 0.98
Co-cited proteins · studied together in the literature
- Toll-like receptor 1 8 shared papers
- Toll-like receptor 6 4 shared papers
- Toll-like receptor 5 4 shared papers
- Toll-like receptor 2 4 shared papers
- Cell surface glycolipoprotein MPB83 1 shared papers
- TIR domain-containing adapter molecule 2 2 shared papers
- Toll-like receptor 4 6 shared papers
- Lipoprotein LpqH 3 shared papers
- Phosphate-binding protein PstS 1 3 shared papers
- Staphylococcal superantigen-like 3 1 shared papers
- E3 ubiquitin-protein ligase PPP1R11 1 shared papers
- Toll-like receptor 3 3 shared papers
Literature · 28 cited papers
- Long-lived macrophage reprogramming drives spike protein-mediated inflammasome activation in COVID-19. EMBO Mol. Med. · 2021
- RING finger E3 ligase PPP1R11 regulates TLR2 signaling and innate immunity. Elife · 2016
- TRAM is required for TLR2 endosomal signaling to type I IFN induction. J. Immunol. · 2014
- TMEM59 defines a novel ATG16L1-binding motif that promotes local activation of LC3. EMBO J. · 2013
- Staphylococcal superantigen-like protein 3 binds to the Toll-like receptor 2 extracellular domain and inhibits cytokine production induced by Staphylococcus aureus, cell wall component, or lipopeptides in murine macrophages. Infect. Immun. · 2012
- Functional characterization of naturally occurring genetic variants in the human TLR1-2-6 gene family. Hum. Mutat. · 2011
- Mycobacterium tuberculosis lipoproteins directly regulate human memory CD4(+) T cell activation via Toll-like receptors 1 and 2. Infect. Immun. · 2011
- Non-acylated Mycobacterium bovis glycoprotein MPB83 binds to TLR1/2 and stimulates production of matrix metalloproteinase 9. Biochem. Biophys. Res. Commun. · 2010
- The heterogeneous allelic repertoire of human Toll-Like receptor (TLR) genes. PLoS ONE · 2009
- TLR2 and its co-receptors determine responses of macrophages and dendritic cells to lipoproteins of Mycobacterium tuberculosis. Cell. Immunol. · 2009
- Natural selection in the TLR-related genes in the course of primate evolution. Immunogenetics · 2008
- Crystal structure of the TLR1-TLR2 heterodimer induced by binding of a tri-acylated lipopeptide. Cell · 2007
- … and 16 more in the literature graph