Toll-like receptor 2 (TLR2, CD282) is a single-pass type I transmembrane pattern recognition receptor of the innate immune system. It is expressed mainly on monocytes, macrophages, dendritic cells and other myeloid cells, and also on epithelial cells such as keratinocytes. Its leucine-rich-repeat ectodomain recognizes microbial lipoproteins and lipopeptides, lipoteichoic acid and other cell-wall components of Gram-positive bacteria, mycobacteria, mycoplasma and fungi. TLR2 acts as a heterodimer: with TLR1 it responds to triacylated lipopeptides and with TLR6 to diacylated lipopeptides. A pocket in TLR2 holds the two ester-linked acyl chains, and in the TLR1 complex the amide-linked chain enters a channel in TLR1, so ligand binding bridges the two ectodomains and brings their cytoplasmic TIR domains together. The TIR dimer recruits the adaptors TIRAP/Mal and MyD88, leading to NF-kappaB and MAP kinase activation and production of inflammatory cytokines and chemokines such as IL-8, IL-6 and TNF. CD14, CD36 and LBP assist ligand delivery. TLR2 signals from the cell surface, where ligand-bound heterodimers gather in lipid rafts, and it is also recruited to phagosomes. Endogenous molecules such as aggregated amyloid-beta also engage TLR2. Variation in TLR2 influences susceptibility to mycobacterial infection, including leprosy.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001530 lipopolysaccharide binding | IDA PMID:11274165 Lipopolysaccharide is in close proximity to each of the prot... | UNDECIDED | Summary: Direct lipopolysaccharide binding by TLR2, from a photo-crosslinking study of the LPS receptor complex. Reason: The cached abstract reports that LPS cross-linked specifically to TLR4 and MD-2 (with CD14); it does not state that TLR2 was cross-linked, and the full text is not cached. Other cached papers argue against TLR2 being an LPS receptor: soluble TLR2 ectodomain binds LPS very weakly, TLR2 does not respond to pure protein-free LPS without MD-2, and LPS responses attributed to TLR2 in keratinocytes were ascribed to contaminating non-LPS components. The curator may have seen TLR2 used as a comparator in the full text; I cannot verify what was shown. Supporting Evidence: PMID:11274165 Here we show that LPS is cross-linked specifically to TLR4 and MD-2 only when co-expressed with CD14 PMID:11986301 In contrast, sTLR2 exhibited a very weak binding to lipopolysaccharide PMID:11521063 TLR2 without MD-2 does not respond to pure protein-free endotoxic LPS, ReLPS, and lipid A PMID:12443841 might be mediated by TLR2-dependent recognition of non-LPS bacterial components contaminating in commercial LPS preparations |
| GO:0001540 amyloid-beta binding | IDA PMID:22198949 TLR2 is a primary receptor for Alzheimer's amyloid Ξ² peptide... | KEEP AS NON CORE | Summary: TLR2 binds aggregated amyloid-beta 42 directly (surface plasmon resonance and pull-down) and mediates A-beta-triggered microglial inflammatory activation. Reason: Direct binding is shown and TLR2 expression confers A-beta responsiveness on HEK293 cells, so the MF is supported. A-beta is an endogenous danger-associated ligand, not the core microbial-lipoprotein recognition role, so kept as non-core. Supporting Evidence: PMID:22198949 demonstrate a direct interaction between TLR2 and the aggregated 42-aa form of human AΞ² (AΞ²42) PMID:22198949 we observed that TLR2 expression enabled HEK293 cells to respond to AΞ²42 |
| GO:0001540 amyloid-beta binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Amyloid-beta binding transferred from mouse Tlr2 by sequence similarity. Reason: Consistent with the direct human evidence (PMID:22198949); non-core for the same reason as the IDA row. Supporting Evidence: PMID:22198949 demonstrate a direct interaction between TLR2 and the aggregated 42-aa form of human AΞ² (AΞ²42) |
| GO:0001875 lipopolysaccharide immune receptor activity | IDA PMID:16880211 Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 ... | MODIFY | Summary: TLR2 contributes, as part of the TLR2:TLR1 and TLR2:TLR6 heterodimers, to a cell-surface receptor activity for bacterial lipopeptides. The cited study examines those heterodimers and their lipopeptide ligands, not LPS. Reason: The contributes_to receptor claim is sound - TLR2 forms pre-existing heterodimers with TLR1 and TLR6 that are activated at the cell surface - but GO:0001875 is defined as combining with lipopolysaccharide. The TLR2 heterodimers recognise triacylated (with TLR1) and diacylated (with TLR6) lipopeptides; LPS is sensed by TLR4/MD-2, and TLR2 does not respond to pure LPS without MD-2. This row appears to be the GAF export of GO-CAMs 5fb9cc0600000727 (TLR1-TLR2 complex) and 5fce9b7300000030 (TLR2-TLR6 complex), whose own ligands are triacyl lipopeptide, diacyl lipopeptide and a bacteriocin (same reference, curator and date); GO has no lipopeptide-specific immune receptor term. Generalised to pattern recognition receptor activity, keeping contributes_to, consistent with the matching rows on TLR1 and TLR6. Proposed replacements: pattern recognition receptor activity Supporting Evidence: PMID:16880211 Our data show that TLR2 forms heterodimers with TLR1 and TLR6 and that these heterodimer pre-exist and are not induced by the ligand PMID:16880211 Activation occurs at the cell surface, and the observed trafficking is independent of signaling PMID:19931471 Toll-like receptor 2 (TLR2) initiates potent immune responses by recognizing diacylated and triacylated lipopeptides. Its ligand specificity is controlled by whether it heterodimerizes with TLR1 or TLR6. PMID:11521063 TLR2 without MD-2 does not respond to pure protein-free endotoxic LPS, ReLPS, and lipid A PMID:11521063 MD-2 enables TLR2 to respond to non-activating LPS, ReLPS, and lipid A |
| GO:0001875 lipopolysaccharide immune receptor activity | TAS PMID:11518816 Toll-like receptors as sensors of pathogens. | REMOVE | Summary: Traceable author statement that TLR2 has lipopolysaccharide immune receptor activity. Reason: The cited review itself assigns LPS recognition to TLR4 and describes TLR2 as mediating responses to Gram-positive bacteria and yeast, so it does not support the statement. Pure, protein-free LPS does not signal through TLR2 without MD-2, and TLR2 responses to commercial LPS were attributed to contaminating components. TLR2 is a lipopeptide/lipoprotein receptor, not an LPS receptor. Supporting Evidence: PMID:11518816 Mammalian TLR4 is the signal-transducing receptor activated by the bacterial lipopolysaccharide PMID:11518816 TLR2 mediates the host response to Gram-positive bacteria and yeast PMID:11521063 TLR2 without MD-2 does not respond to pure protein-free endotoxic LPS, ReLPS, and lipid A PMID:12443841 might be mediated by TLR2-dependent recognition of non-LPS bacterial components contaminating in commercial LPS preparations |
| GO:0002224 toll-like receptor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: TLR2 participates in toll-like receptor signaling as the ligand-binding, TIR-bearing receptor of TLR2/1 and TLR2/6 heterodimers. Reason: Phylogenetically placed IBA consistent with abundant experimental evidence. More specific TLR1:TLR2 and TLR6:TLR2 pathway terms are also annotated. Supporting Evidence: PMID:11521063 Therefore, TLR2 is a functional receptor for both Gram-positive and Gram-negative bacteria and it induces activation of IL-8 PMID:16893894 This resulted in the identification of four residues crucial for TLR2/1 signaling: Arg-748, Phe-749, Leu-752, and Arg-753 |
| GO:0002224 toll-like receptor signaling pathway | IDA PMID:16893894 Structural and functional evidence for the role of the TLR2 ... | ACCEPT | Summary: Mutagenesis of the TLR2 TIR DD loop defines residues required for TLR2/1 signaling. Reason: Direct evidence that TLR2 is a signaling component. The more specific GO:0038123 would also fit. Supporting Evidence: PMID:16893894 This resulted in the identification of four residues crucial for TLR2/1 signaling: Arg-748, Phe-749, Leu-752, and Arg-753 |
| GO:0002224 toll-like receptor signaling pathway | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based assignment of toll-like receptor signaling pathway. Reason: Correct for this canonical TLR. Supporting Evidence: PMID:11521063 Therefore, TLR2 is a functional receptor for both Gram-positive and Gram-negative bacteria and it induces activation of IL-8 |
| GO:0004888 transmembrane signaling receptor activity | IDA PMID:20406817 Identification of Drosophila Yin and PEPT2 as evolutionarily... | ACCEPT | Summary: TLR2 (with TLR6) contributes to transmembrane signaling receptor activity in response to Staphylococcus aureus in transfected HEK293T cells. Reason: Correct but general. TLR2 supplies the ligand-binding pocket and a TIR domain to the TLR2/1 and TLR2/6 heterodimeric receptors, so contributes_to fits. The more informative MF, pattern recognition receptor activity (GO:0038187), is also annotated. Supporting Evidence: PMID:20406817 However, when coexpressed with TLR2/6, NOD2 enhanced NFkB activation, indicating that although NOD2 is insufficient for full activation, it synergized with TLR2/6 to increase cytokine response PMID:10384090 Heterologous expression of human TLR2, but not TLR4, in fibroblasts conferred responsiveness to Staphylococcus aureus and Streptococcus pneumoniae as evidenced by inducible translocation of NF-kappaB |
| GO:0004888 transmembrane signaling receptor activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based assignment of transmembrane signaling receptor activity. Reason: TLR2 is a single-pass type I transmembrane receptor; the term is general but correct for an electronic mapping. Supporting Evidence: PMID:10384090 Heterologous expression of human TLR2, but not TLR4, in fibroblasts conferred responsiveness to Staphylococcus aureus and Streptococcus pneumoniae as evidenced by inducible translocation of NF-kappaB |
| GO:0005515 protein binding | IPI PMID:11441107 Cooperation of Toll-like receptor 2 and 6 for cellular activ... | REMOVE | Summary: Tollip co-immunoprecipitates with TLR2 in HEK293 cells. Reason: Generic protein binding is uninformative. The interaction is reported, but removal does not mean it is false; it does not identify a molecular function of TLR2 that is not better captured by other terms (pattern recognition receptor activity, lipopeptide binding, Toll-like receptor binding). Supporting Evidence: PMID:11441107 we show that Toll-interacting protein (Tollip) coimmunoprecipitates with TLR2 and TLR4 using HEK 293 cells |
| GO:0005515 protein binding | IPI PMID:12594264 The 19-kDa Mycobacterium tuberculosis protein induces macrop... | REMOVE | Summary: Mycobacterium tuberculosis 19-kDa lipoprotein LpqH acts through TLR2. Reason: Generic protein binding is uninformative. The interaction is reported, but removal does not mean it is false; it does not identify a molecular function of TLR2 that is not better captured by other terms (pattern recognition receptor activity, lipopeptide binding, Toll-like receptor binding). Supporting Evidence: PMID:12594264 this effect of p19 is Toll-like receptor (TLR)-2-mediated because preincubation of either THP-1 cells or TLR-2-expressing CHO cells with anti-TLR-2 mAb inhibited apoptosis induced by p19 |
| GO:0005515 protein binding | IPI PMID:15657077 TRIP6 is a RIP2-associated common signaling component of mul... | REMOVE | Summary: TRIP6 interacts with TLR2 in overexpression assays. Reason: Generic protein binding is uninformative. The interaction is reported, but removal does not mean it is false; it does not identify a molecular function of TLR2 that is not better captured by other terms (pattern recognition receptor activity, lipopeptide binding, Toll-like receptor binding). Supporting Evidence: PMID:15657077 TRIP6 also interacts with TRAF2, a protein that is crucially involved in TNF signaling, as well as the IL-1 receptor, TLR2 and Nod1 |
| GO:0005515 protein binding | IPI PMID:15728506 Human TLR10 is a functional receptor, expressed by B cells a... | MODIFY | Summary: TLR10 heterodimerizes with TLR2. Reason: Generic protein binding; the cited paper shows TLR2 pairing with another Toll-like receptor, which is the informative Toll-like receptor binding (GO:0035325). Heterodimerization with TLR1 or TLR6 is how TLR2 acquires ligand specificity. Proposed replacements: Toll-like receptor binding Supporting Evidence: PMID:15728506 We have shown that TLR10 was not only able to homodimerize but also heterodimerized with TLRs 1 and 2 PMID:19931471 Its ligand specificity is controlled by whether it heterodimerizes with TLR1 or TLR6 |
| GO:0005515 protein binding | IPI PMID:16293622 Localization of TLR2 and MyD88 to Chlamydia trachomatis incl... | REMOVE | Summary: TLR2 and MyD88 co-localize at the chlamydial inclusion. Reason: Generic protein binding is uninformative. The interaction is reported, but removal does not mean it is false; it does not identify a molecular function of TLR2 that is not better captured by other terms (pattern recognition receptor activity, lipopeptide binding, Toll-like receptor binding). Supporting Evidence: PMID:16293622 both TLR2 and MyD88 co-localize with the intracellular chlamydial inclusion |
| GO:0005515 protein binding | IPI PMID:16622205 The mycobacterial 38-kilodalton glycolipoprotein antigen act... | REMOVE | Summary: Mycobacterial 38-kDa PstS1 lipoprotein acts via TLR2. Reason: Generic protein binding is uninformative. The interaction is reported, but removal does not mean it is false; it does not identify a molecular function of TLR2 that is not better captured by other terms (pattern recognition receptor activity, lipopeptide binding, Toll-like receptor binding). Supporting Evidence: PMID:16622205 neutralizing antibodies for Toll-like receptor 2 (TLR2) or TLR4 significantly reduced the ERK1/2 and p38 activation induced by the 38-kDa protein |
| GO:0005515 protein binding | IPI PMID:16880211 Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 ... | REMOVE | Summary: TLR2 associates with TLR6, CD14 and CD36 in ligand-induced receptor clusters. Reason: Generic protein binding is uninformative. The interaction is reported, but removal does not mean it is false; it does not identify a molecular function of TLR2 that is not better captured by other terms (pattern recognition receptor activity, lipopeptide binding, Toll-like receptor binding). Supporting Evidence: PMID:16880211 Our data show that TLR2 forms heterodimers with TLR1 and TLR6 and that these heterodimer pre-exist and are not induced by the ligand |
| GO:0005515 protein binding | IPI PMID:16880211 Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 ... | REMOVE | Summary: TLR2 associates with TLR1 and CD14 in receptor clusters. Reason: Generic protein binding is uninformative. The interaction is reported, but removal does not mean it is false; it does not identify a molecular function of TLR2 that is not better captured by other terms (pattern recognition receptor activity, lipopeptide binding, Toll-like receptor binding). Supporting Evidence: PMID:16880211 Our data show that TLR2 forms heterodimers with TLR1 and TLR6 and that these heterodimer pre-exist and are not induced by the ligand |
| GO:0005515 protein binding | IPI PMID:17095513 Execution of macrophage apoptosis by PE_PGRS33 of Mycobacter... | REMOVE | Summary: M. tuberculosis PE_PGRS33 acts via TLR2. Reason: Generic protein binding is uninformative. The interaction is reported, but removal does not mean it is false; it does not identify a molecular function of TLR2 that is not better captured by other terms (pattern recognition receptor activity, lipopeptide binding, Toll-like receptor binding). Supporting Evidence: PMID:17095513 PE_PGRS33, a surface exposed protein, elicits TNF-alpha release from macrophages in a TLR2 (Toll-like receptor 2)-dependent manner |
| GO:0005515 protein binding | IPI PMID:17126326 Extracellular heat shock protein 70 mediates heat stress-ind... | REMOVE | Summary: Hsp70 induces TLR2 association with EGFR in A431 cells. Reason: Generic protein binding is uninformative. The interaction is reported, but removal does not mean it is false; it does not identify a molecular function of TLR2 that is not better captured by other terms (pattern recognition receptor activity, lipopeptide binding, Toll-like receptor binding). Supporting Evidence: PMID:17126326 Both heat stress and pure Hsp70 stimulate activation of TLR2/4 and their association with EGFR |
| GO:0005515 protein binding | IPI PMID:17126326 Extracellular heat shock protein 70 mediates heat stress-ind... | REMOVE | Summary: Interaction with MyD88 reported in an Hsp70/EGFR transactivation study. Reason: Generic protein binding is uninformative. The interaction is reported, but removal does not mean it is false; it does not identify a molecular function of TLR2 that is not better captured by other terms (pattern recognition receptor activity, lipopeptide binding, Toll-like receptor binding). Supporting Evidence: PMID:17126326 Both heat stress and pure Hsp70 stimulate activation of TLR2/4 and their association with EGFR |
| GO:0005515 protein binding | IPI PMID:18765807 Pathogen induction of CXCR4/TLR2 cross-talk impairs host def... | REMOVE | Summary: Porphyromonas gingivalis fimbriae induce TLR2-CXCR4 co-association. Reason: Generic protein binding is uninformative. The interaction is reported, but removal does not mean it is false; it does not identify a molecular function of TLR2 that is not better captured by other terms (pattern recognition receptor activity, lipopeptide binding, Toll-like receptor binding). Supporting Evidence: PMID:18765807 Here, we have identified CXC-chemokine receptor 4 (CXCR4) as a TLR2-associated receptor interacting with Pg-fimbriae |
| GO:0005515 protein binding | IPI PMID:19509286 A TIR domain variant of MyD88 adapter-like (Mal)/TIRAP resul... | MODIFY | Summary: TIRAP/Mal co-immunoprecipitates with TLR2. Reason: Generic protein binding; the partner is a TIR-domain adaptor (MyD88 or TIRAP) recruited through TIR-TIR interaction with the TLR2 cytoplasmic domain, so TIR domain binding (GO:0070976) is the informative MF. Proposed replacements: TIR domain binding Supporting Evidence: PMID:19509286 As expected, wild type Mal interacted with the receptors TLR2 PMID:19509286 It is thought that Mal acts as a bridging adapter between the receptor (TLR2 or TLR4) and MyD88 and, thus, physically interacts with both |
| GO:0005515 protein binding | IPI PMID:19880448 The PPE18 of Mycobacterium tuberculosis interacts with TLR2 ... | REMOVE | Summary: M. tuberculosis PPE18 binds the TLR2 LRR 11-15 region. Reason: Generic protein binding is uninformative. The interaction is reported, but removal does not mean it is false; it does not identify a molecular function of TLR2 that is not better captured by other terms (pattern recognition receptor activity, lipopeptide binding, Toll-like receptor binding). Supporting Evidence: PMID:19880448 The recombinant PPE18 was found to specifically interact with the TLR2 leading to an early and sustained activation of p38 MAPK, which is critical for IL-10 induction |
| GO:0005515 protein binding | IPI PMID:20067962 Increased toll-like receptor (TLR) activation and TLR ligand... | MODIFY | Summary: TLR6 co-immunoprecipitates with TLR2 from human monocytes. Reason: Generic protein binding; the cited paper shows TLR2 pairing with another Toll-like receptor, which is the informative Toll-like receptor binding (GO:0035325). Heterodimerization with TLR1 or TLR6 is how TLR2 acquires ligand specificity. Proposed replacements: Toll-like receptor binding Supporting Evidence: PMID:20067962 immunoprecipitated with TLR2 or TLR4 antibody overnight at 4Β°C as reported previously (3) and blotted with TLR6 PMID:19931471 Its ligand specificity is controlled by whether it heterodimerizes with TLR1 or TLR6 |
| GO:0005515 protein binding | IPI PMID:20802527 Pancreatic adenocarcinoma upregulated factor promotes metast... | REMOVE | Summary: PAUF associates with a CXCR4-TLR2 complex. Reason: Generic protein binding is uninformative. The interaction is reported, but removal does not mean it is false; it does not identify a molecular function of TLR2 that is not better captured by other terms (pattern recognition receptor activity, lipopeptide binding, Toll-like receptor binding). Supporting Evidence: PMID:20802527 We also identify PAUF as an endogenous ligand of Toll-like receptor 2 (TLR2) and TLR4 by screening extracellular domain receptor pools |
| GO:0005515 protein binding | IPI PMID:20802527 Pancreatic adenocarcinoma upregulated factor promotes metast... | REMOVE | Summary: PAUF (ZG16B) binds TLR2 as a ligand. Reason: Generic protein binding is uninformative. The interaction is reported, but removal does not mean it is false; it does not identify a molecular function of TLR2 that is not better captured by other terms (pattern recognition receptor activity, lipopeptide binding, Toll-like receptor binding). Supporting Evidence: PMID:20802527 We also identify PAUF as an endogenous ligand of Toll-like receptor 2 (TLR2) and TLR4 by screening extracellular domain receptor pools |
| GO:0005515 protein binding | IPI PMID:23155421 Isolated Toll-like receptor transmembrane domains are capabl... | MODIFY | Summary: Isolated TLR2 transmembrane domain interacts with the TLR1 transmembrane domain. Reason: Generic protein binding; the cited paper shows TLR2 pairing with another Toll-like receptor, which is the informative Toll-like receptor binding (GO:0035325). Heterodimerization with TLR1 or TLR6 is how TLR2 acquires ligand specificity. Proposed replacements: Toll-like receptor binding Supporting Evidence: PMID:23155421 The TLR2 transmembrane domain demonstrated strong heterotypic interactions in bacterial membranes with its known interaction partners, TLR1 and TLR6, as well as with a proposed interaction partner, TLR10 PMID:19931471 Its ligand specificity is controlled by whether it heterodimerizes with TLR1 or TLR6 |
| GO:0005515 protein binding | IPI PMID:23155421 Isolated Toll-like receptor transmembrane domains are capabl... | MODIFY | Summary: Isolated TLR2 transmembrane domain interacts with the TLR10 transmembrane domain. Reason: Generic protein binding; the cited paper shows TLR2 pairing with another Toll-like receptor, which is the informative Toll-like receptor binding (GO:0035325). Heterodimerization with TLR1 or TLR6 is how TLR2 acquires ligand specificity. Proposed replacements: Toll-like receptor binding Supporting Evidence: PMID:23155421 The TLR2 transmembrane domain demonstrated strong heterotypic interactions in bacterial membranes with its known interaction partners, TLR1 and TLR6, as well as with a proposed interaction partner, TLR10 PMID:19931471 Its ligand specificity is controlled by whether it heterodimerizes with TLR1 or TLR6 |
| GO:0005515 protein binding | IPI PMID:23155421 Isolated Toll-like receptor transmembrane domains are capabl... | MODIFY | Summary: Isolated TLR2 transmembrane domain interacts with the TLR6 transmembrane domain. Reason: Generic protein binding; the cited paper shows TLR2 pairing with another Toll-like receptor, which is the informative Toll-like receptor binding (GO:0035325). Heterodimerization with TLR1 or TLR6 is how TLR2 acquires ligand specificity. Proposed replacements: Toll-like receptor binding Supporting Evidence: PMID:23155421 The TLR2 transmembrane domain demonstrated strong heterotypic interactions in bacterial membranes with its known interaction partners, TLR1 and TLR6, as well as with a proposed interaction partner, TLR10 PMID:19931471 Its ligand specificity is controlled by whether it heterodimerizes with TLR1 or TLR6 |
| GO:0005515 protein binding | IPI PMID:23376921 TMEM59 defines a novel ATG16L1-binding motif that promotes l... | REMOVE | Summary: TLR2 carries an ATG16L1-binding motif and interacts with ATG16L1. Reason: Generic protein binding is uninformative. The interaction is reported, but removal does not mean it is false; it does not identify a molecular function of TLR2 that is not better captured by other terms (pattern recognition receptor activity, lipopeptide binding, Toll-like receptor binding). Supporting Evidence: PMID:23376921 Since the ATG161-binding motif is present in proteins involved in the cellular response to bacterial invasion (NOD2, TLR2 and TMEM59) |
| GO:0005515 protein binding | IPI PMID:24658140 The mammalian-membrane two-hybrid assay (MaMTH) for probing ... | REMOVE | Summary: TLR2-EGFR interaction detected in a mammalian membrane two-hybrid screen. Reason: Generic protein binding is uninformative. The interaction is reported, but removal does not mean it is false; it does not identify a molecular function of TLR2 that is not better captured by other terms (pattern recognition receptor activity, lipopeptide binding, Toll-like receptor binding). |
| GO:0005515 protein binding | IPI PMID:29990310 Selective disruption of TLR2-MyD88 interaction inhibits infl... | MODIFY | Summary: TLR2 TIR domain associates with MyD88. Reason: Generic protein binding; the partner is a TIR-domain adaptor (MyD88 or TIRAP) recruited through TIR-TIR interaction with the TLR2 cytoplasmic domain, so TIR domain binding (GO:0070976) is the informative MF. Proposed replacements: TIR domain binding Supporting Evidence: PMID:29990310 Induction of TLR2 activation depends on its association with the adapter protein MyD88 PMID:29990310 we applied a rigid-body, protein-protein interaction tool to model the interaction between the TLR-interacting domain (TIR) of TLR2 and MyD88 |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | REMOVE | Summary: TLR2-EGFR interaction detected in a large-scale EGFR network study. Reason: Generic protein binding is uninformative. The interaction is reported, but removal does not mean it is false; it does not identify a molecular function of TLR2 that is not better captured by other terms (pattern recognition receptor activity, lipopeptide binding, Toll-like receptor binding). |
| GO:0005737 cytoplasm | IDA PMID:19740627 Cultured human melanocytes express functional toll-like rece... | KEEP AS NON CORE | Summary: TLR2 protein detected in cultured human melanocytes by immunofluorescence. Reason: Not wrong (TLR2 is found on intracellular membranes such as Golgi and phagosomes, which are within the cytoplasm) but uninformative; the principal location is the plasma membrane. Supporting Evidence: PMID:19740627 Ample amounts of TLRs 2-4, 7 and 9 were confirmed at protein level |
| GO:0005794 Golgi apparatus | IDA PMID:16880211 Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 ... | KEEP AS NON CORE | Summary: Ligand-activated TLR2 clusters are trafficked to the Golgi apparatus. Reason: Direct evidence, but Golgi targeting is post-activation trafficking that is independent of signaling; signaling occurs at the cell surface. Supporting Evidence: PMID:16880211 All TLR2 receptor clusters accumulate in lipid rafts and are targeted to the Golgi apparatus PMID:16880211 Activation occurs at the cell surface, and the observed trafficking is independent of signaling |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: TLR2 is active at the plasma membrane. Reason: IBA consistent with experimental evidence. TLR2 is a single-pass type I plasma membrane receptor; activation occurs at the cell surface. Supporting Evidence: PMID:16880211 Activation occurs at the cell surface, and the observed trafficking is independent of signaling |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | ACCEPT | Summary: Plasma membrane localization from immunofluorescence curation. Reason: TLR2 is a single-pass type I plasma membrane receptor; activation occurs at the cell surface. Supporting Evidence: PMID:16880211 Activation occurs at the cell surface, and the observed trafficking is independent of signaling |
| GO:0005886 plasma membrane | IDA PMID:11274165 Lipopolysaccharide is in close proximity to each of the prot... | ACCEPT | Summary: Plasma membrane localization of transfected TLR2 in HEK293 cells. Reason: TLR2 is a single-pass type I plasma membrane receptor; activation occurs at the cell surface. Supporting Evidence: PMID:16880211 Activation occurs at the cell surface, and the observed trafficking is independent of signaling |
| GO:0005886 plasma membrane | IDA PMID:16880211 Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 ... | ACCEPT | Summary: TLR2/1 and TLR2/6 heterodimers are active at the cell surface. Reason: TLR2 is a single-pass type I plasma membrane receptor; activation occurs at the cell surface. Supporting Evidence: PMID:16880211 Activation occurs at the cell surface, and the observed trafficking is independent of signaling |
| GO:0005886 plasma membrane | IDA PMID:19509287 Modulation of TLR2 protein expression by miR-105 in human or... | ACCEPT | Summary: Cell-surface TLR2 in human oral keratinocytes. Reason: TLR2 is a single-pass type I plasma membrane receptor; activation occurs at the cell surface. Supporting Evidence: PMID:19509287 This confirmed that miR-105 up-regulation suppressed TLR-2 protein expression on the cell surface |
| GO:0005886 plasma membrane | IDA PMID:19740627 Cultured human melanocytes express functional toll-like rece... | ACCEPT | Summary: TLR2 at the surface of human melanocytes. Reason: TLR2 is a single-pass type I plasma membrane receptor; activation occurs at the cell surface. Supporting Evidence: PMID:19740627 Ample amounts of TLRs 2-4, 7 and 9 were confirmed at protein level |
| GO:0005886 plasma membrane | IDA PMID:20406817 Identification of Drosophila Yin and PEPT2 as evolutionarily... | ACCEPT | Summary: TLR2/6 at the plasma membrane in transfected cells. Reason: TLR2 is a single-pass type I plasma membrane receptor; activation occurs at the cell surface. Supporting Evidence: PMID:16880211 Activation occurs at the cell surface, and the observed trafficking is independent of signaling |
| GO:0005886 plasma membrane | NAS PMID:16893894 Structural and functional evidence for the role of the TLR2 ... | ACCEPT | Summary: Plasma membrane location stated in a TLR2/1 signaling paper. Reason: TLR2 is a single-pass type I plasma membrane receptor; activation occurs at the cell surface. Supporting Evidence: PMID:16880211 Activation occurs at the cell surface, and the observed trafficking is independent of signaling |
| GO:0005886 plasma membrane | NAS PMID:33576548 Structural and functional understanding of the toll-like rec... | ACCEPT | Summary: Review statement that TLR2 is a cell-membrane TLR. Reason: TLR2 is a single-pass type I plasma membrane receptor; activation occurs at the cell surface. Supporting Evidence: PMID:33576548 One group is composed of TLR1, TLR2, TLR4, TLR5, TLR6 and poorly characterized TLR10, which are localized to cell membranes and predominantly recognize bacterial components such as lipids, lipoproteins, and proteins |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-166072 | ACCEPT | Summary: Reactome places TLR2 at the plasma membrane in its TLR2 signaling reactions. Reason: Consistent with experimental evidence. TLR2 is a single-pass type I plasma membrane receptor; activation occurs at the cell surface. Supporting Evidence: PMID:16880211 Activation occurs at the cell surface, and the observed trafficking is independent of signaling |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-166082 | ACCEPT | Summary: Reactome places TLR2 at the plasma membrane in its TLR2 signaling reactions. Reason: Consistent with experimental evidence. TLR2 is a single-pass type I plasma membrane receptor; activation occurs at the cell surface. Supporting Evidence: PMID:16880211 Activation occurs at the cell surface, and the observed trafficking is independent of signaling |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-166091 | ACCEPT | Summary: Reactome places TLR2 at the plasma membrane in its TLR2 signaling reactions. Reason: Consistent with experimental evidence. TLR2 is a single-pass type I plasma membrane receptor; activation occurs at the cell surface. Supporting Evidence: PMID:16880211 Activation occurs at the cell surface, and the observed trafficking is independent of signaling |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-166119 | ACCEPT | Summary: Reactome places TLR2 at the plasma membrane in its TLR2 signaling reactions. Reason: Consistent with experimental evidence. TLR2 is a single-pass type I plasma membrane receptor; activation occurs at the cell surface. Supporting Evidence: PMID:16880211 Activation occurs at the cell surface, and the observed trafficking is independent of signaling |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-166284 | ACCEPT | Summary: Reactome places TLR2 at the plasma membrane in its TLR2 signaling reactions. Reason: Consistent with experimental evidence. TLR2 is a single-pass type I plasma membrane receptor; activation occurs at the cell surface. Supporting Evidence: PMID:16880211 Activation occurs at the cell surface, and the observed trafficking is independent of signaling |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-166286 | ACCEPT | Summary: Reactome places TLR2 at the plasma membrane in its TLR2 signaling reactions. Reason: Consistent with experimental evidence. TLR2 is a single-pass type I plasma membrane receptor; activation occurs at the cell surface. Supporting Evidence: PMID:16880211 Activation occurs at the cell surface, and the observed trafficking is independent of signaling |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-166362 | ACCEPT | Summary: Reactome places TLR2 at the plasma membrane in its TLR2 signaling reactions. Reason: Consistent with experimental evidence. TLR2 is a single-pass type I plasma membrane receptor; activation occurs at the cell surface. Supporting Evidence: PMID:16880211 Activation occurs at the cell surface, and the observed trafficking is independent of signaling |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-166363 | ACCEPT | Summary: Reactome places TLR2 at the plasma membrane in its TLR2 signaling reactions. Reason: Consistent with experimental evidence. TLR2 is a single-pass type I plasma membrane receptor; activation occurs at the cell surface. Supporting Evidence: PMID:16880211 Activation occurs at the cell surface, and the observed trafficking is independent of signaling |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-168950 | ACCEPT | Summary: Reactome places TLR2 at the plasma membrane in its TLR2 signaling reactions. Reason: Consistent with experimental evidence. TLR2 is a single-pass type I plasma membrane receptor; activation occurs at the cell surface. Supporting Evidence: PMID:16880211 Activation occurs at the cell surface, and the observed trafficking is independent of signaling |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-168951 | ACCEPT | Summary: Reactome places TLR2 at the plasma membrane in its TLR2 signaling reactions. Reason: Consistent with experimental evidence. TLR2 is a single-pass type I plasma membrane receptor; activation occurs at the cell surface. Supporting Evidence: PMID:16880211 Activation occurs at the cell surface, and the observed trafficking is independent of signaling |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-1974676 | ACCEPT | Summary: Reactome places TLR2 at the plasma membrane in its TLR2 signaling reactions. Reason: Consistent with experimental evidence. TLR2 is a single-pass type I plasma membrane receptor; activation occurs at the cell surface. Supporting Evidence: PMID:16880211 Activation occurs at the cell surface, and the observed trafficking is independent of signaling |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2201316 | ACCEPT | Summary: Reactome places TLR2 at the plasma membrane in its TLR2 signaling reactions. Reason: Consistent with experimental evidence. TLR2 is a single-pass type I plasma membrane receptor; activation occurs at the cell surface. Supporting Evidence: PMID:16880211 Activation occurs at the cell surface, and the observed trafficking is independent of signaling |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2201322 | ACCEPT | Summary: Reactome places TLR2 at the plasma membrane in its TLR2 signaling reactions. Reason: Consistent with experimental evidence. TLR2 is a single-pass type I plasma membrane receptor; activation occurs at the cell surface. Supporting Evidence: PMID:16880211 Activation occurs at the cell surface, and the observed trafficking is independent of signaling |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2262775 | ACCEPT | Summary: Reactome places TLR2 at the plasma membrane in its TLR2 signaling reactions. Reason: Consistent with experimental evidence. TLR2 is a single-pass type I plasma membrane receptor; activation occurs at the cell surface. Supporting Evidence: PMID:16880211 Activation occurs at the cell surface, and the observed trafficking is independent of signaling |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2262777 | ACCEPT | Summary: Reactome places TLR2 at the plasma membrane in its TLR2 signaling reactions. Reason: Consistent with experimental evidence. TLR2 is a single-pass type I plasma membrane receptor; activation occurs at the cell surface. Supporting Evidence: PMID:16880211 Activation occurs at the cell surface, and the observed trafficking is independent of signaling |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2559414 | ACCEPT | Summary: Reactome places TLR2 at the plasma membrane in its TLR2 signaling reactions. Reason: Consistent with experimental evidence. TLR2 is a single-pass type I plasma membrane receptor; activation occurs at the cell surface. Supporting Evidence: PMID:16880211 Activation occurs at the cell surface, and the observed trafficking is independent of signaling |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5432814 | ACCEPT | Summary: Reactome places TLR2 at the plasma membrane in its TLR2 signaling reactions. Reason: Consistent with experimental evidence. TLR2 is a single-pass type I plasma membrane receptor; activation occurs at the cell surface. Supporting Evidence: PMID:16880211 Activation occurs at the cell surface, and the observed trafficking is independent of signaling |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5602353 | ACCEPT | Summary: Reactome places TLR2 at the plasma membrane in its TLR2 signaling reactions. Reason: Consistent with experimental evidence. TLR2 is a single-pass type I plasma membrane receptor; activation occurs at the cell surface. Supporting Evidence: PMID:16880211 Activation occurs at the cell surface, and the observed trafficking is independent of signaling |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5602383 | ACCEPT | Summary: Reactome places TLR2 at the plasma membrane in its TLR2 signaling reactions. Reason: Consistent with experimental evidence. TLR2 is a single-pass type I plasma membrane receptor; activation occurs at the cell surface. Supporting Evidence: PMID:16880211 Activation occurs at the cell surface, and the observed trafficking is independent of signaling |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5602606 | ACCEPT | Summary: Reactome places TLR2 at the plasma membrane in its TLR2 signaling reactions. Reason: Consistent with experimental evidence. TLR2 is a single-pass type I plasma membrane receptor; activation occurs at the cell surface. Supporting Evidence: PMID:16880211 Activation occurs at the cell surface, and the observed trafficking is independent of signaling |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6798743 | ACCEPT | Summary: Reactome places TLR2 at the plasma membrane in its TLR2 signaling reactions. Reason: Consistent with experimental evidence. TLR2 is a single-pass type I plasma membrane receptor; activation occurs at the cell surface. Supporting Evidence: PMID:16880211 Activation occurs at the cell surface, and the observed trafficking is independent of signaling |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-937022 | ACCEPT | Summary: Reactome places TLR2 at the plasma membrane in its TLR2 signaling reactions. Reason: Consistent with experimental evidence. TLR2 is a single-pass type I plasma membrane receptor; activation occurs at the cell surface. Supporting Evidence: PMID:16880211 Activation occurs at the cell surface, and the observed trafficking is independent of signaling |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-937059 | ACCEPT | Summary: Reactome places TLR2 at the plasma membrane in its TLR2 signaling reactions. Reason: Consistent with experimental evidence. TLR2 is a single-pass type I plasma membrane receptor; activation occurs at the cell surface. Supporting Evidence: PMID:16880211 Activation occurs at the cell surface, and the observed trafficking is independent of signaling |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-937079 | ACCEPT | Summary: Reactome places TLR2 at the plasma membrane in its TLR2 signaling reactions. Reason: Consistent with experimental evidence. TLR2 is a single-pass type I plasma membrane receptor; activation occurs at the cell surface. Supporting Evidence: PMID:16880211 Activation occurs at the cell surface, and the observed trafficking is independent of signaling |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9637638 | ACCEPT | Summary: Reactome places TLR2 at the plasma membrane in its TLR2 signaling reactions. Reason: Consistent with experimental evidence. TLR2 is a single-pass type I plasma membrane receptor; activation occurs at the cell surface. Supporting Evidence: PMID:16880211 Activation occurs at the cell surface, and the observed trafficking is independent of signaling |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9637641 | ACCEPT | Summary: Reactome places TLR2 at the plasma membrane in its TLR2 signaling reactions. Reason: Consistent with experimental evidence. TLR2 is a single-pass type I plasma membrane receptor; activation occurs at the cell surface. Supporting Evidence: PMID:16880211 Activation occurs at the cell surface, and the observed trafficking is independent of signaling |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9755368 | ACCEPT | Summary: Reactome places TLR2 at the plasma membrane in its TLR2 signaling reactions. Reason: Consistent with experimental evidence. TLR2 is a single-pass type I plasma membrane receptor; activation occurs at the cell surface. Supporting Evidence: PMID:16880211 Activation occurs at the cell surface, and the observed trafficking is independent of signaling |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9836256 | ACCEPT | Summary: Reactome places TLR2 at the plasma membrane in its TLR2 signaling reactions. Reason: Consistent with experimental evidence. TLR2 is a single-pass type I plasma membrane receptor; activation occurs at the cell surface. Supporting Evidence: PMID:16880211 Activation occurs at the cell surface, and the observed trafficking is independent of signaling |
| GO:0006955 immune response | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based immune response. Reason: General but correct; TLR2 initiates innate immune responses. Supporting Evidence: PMID:19931471 Toll-like receptor 2 (TLR2) initiates potent immune responses by recognizing diacylated and triacylated lipopeptides |
| GO:0007165 signal transduction | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro TIR-domain-based signal transduction. Reason: General but correct. Supporting Evidence: PMID:16893894 This resulted in the identification of four residues crucial for TLR2/1 signaling: Arg-748, Phe-749, Leu-752, and Arg-753 |
| GO:0007612 learning | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Learning, transferred from mouse Tlr2. Reason: Presumably reflects a behavioural phenotype of Tlr2-deficient mice. TLR2 does not execute a step of learning; any effect is an indirect consequence of neuroinflammatory signaling. Not transferred with confidence to human. |
| GO:0009986 cell surface | IDA PMID:12443841 Expression of functional Toll-like receptor 2 on human epide... | ACCEPT | Summary: Functional TLR2 on the surface of human epidermal keratinocytes. Reason: TLR2 is a single-pass type I plasma membrane receptor; activation occurs at the cell surface. Supporting Evidence: PMID:12443841 Although CD14 and TLR2 mRNA were expressed in cultured NHEK, only TLR2 was detected on the cell surface |
| GO:0010628 positive regulation of gene expression | IMP PMID:23817958 Proinflammatory stimuli induce galectin-9 in human mesenchym... | KEEP AS NON CORE | Summary: TLR2 ligands induce galectin-9 in mesenchymal stromal cells. Reason: Induction of target genes is a downstream output of TLR2 signaling; the term is very general. Retained as non-core. Supporting Evidence: PMID:23817958 ligands of the Toll-like receptors (TLRs) TLR2, TLR3, and TLR4 elicited similar induction of galectin-9 in activated PBMCs |
| GO:0014005 microglia development | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Microglia development, transferred from mouse Tlr2. Reason: TLR2 is an activating receptor on microglia; there is no cached evidence that it performs a step in microglial development, and such a claim is likely an interpretation of an activation phenotype. |
| GO:0016020 membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Membrane (electronic). Reason: Correct but general; TLR2 is a type I transmembrane protein. Supporting Evidence: PMID:16880211 Activation occurs at the cell surface, and the observed trafficking is independent of signaling |
| GO:0016020 membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Membrane, from mouse Tlr2. Reason: Correct but general. Supporting Evidence: PMID:16880211 Activation occurs at the cell surface, and the observed trafficking is independent of signaling |
| GO:0030177 positive regulation of Wnt signaling pathway | IMP PMID:16601243 The Wingless homolog WNT5A and its receptor Frizzled-5 regul... | MARK AS OVER ANNOTATED | Summary: Microbial stimulation induces WNT5A expression via TLR signaling. Reason: The paper shows WNT5A transcription requires TLR/NF-kappaB signaling; that is induction of a Wnt ligand gene, not regulation of the Wnt signaling pathway by TLR2. The term over-states the evidence. Supporting Evidence: PMID:16601243 The expression of WNT5A required Toll-like receptor signaling and NF-kappaB activation |
| GO:0030667 secretory granule membrane | TAS Reactome:R-HSA-6798743 | KEEP AS NON CORE | Summary: TLR2 is found in neutrophil secretory granule membranes (Reactome neutrophil degranulation). Reason: Reflects proteomic detection in granule membranes delivered to the surface on degranulation. Plausible but not the functional location. |
| GO:0030670 phagocytic vesicle membrane | IEA GO_REF:0000044 | ACCEPT | Summary: TLR2 is recruited to phagosome membranes. Reason: TLR2 and TLR6 are recruited to macrophage phagosomes where they sample phagosome contents. Supporting Evidence: PMID:11095740 TLR6 and TLR2 both are recruited to the macrophage phagosome, where they recognize peptidoglycan, a Gram-positive pathogen component |
| GO:0031663 lipopolysaccharide-mediated signaling pathway | IEA GO_REF:0000108 | REMOVE | Summary: LPS-mediated signaling pathway, inferred from the lipopolysaccharide immune receptor activity annotation. Reason: Derived mechanically from GO:0001875, which is not supported for TLR2 (the TAS row is removed and the IDA row is modified to pattern recognition receptor activity, because the TLR2 heterodimers recognise lipopeptides). LPS signaling is mediated by TLR4/MD-2; TLR2 does not respond to pure LPS without MD-2. Removed, consistent with the same inferred row on TLR1 and TLR6. Supporting Evidence: PMID:11521063 TLR2 without MD-2 does not respond to pure protein-free endotoxic LPS, ReLPS, and lipid A |
| GO:0032722 positive regulation of chemokine production | IDA PMID:19740627 Cultured human melanocytes express functional toll-like rece... | KEEP AS NON CORE | Summary: TLR2 ligand stimulation of melanocytes induces chemokines. Reason: Cytokine and chemokine induction is the downstream output of TLR2 signaling; TLR2 regulates it through the pathway rather than directly. Kept as non-core. Supporting Evidence: PMID:19740627 Stimulation of melanocytes with TLRs ligands resulted in the release of cytokines (IL-8 and IL-6) and the mRNA accumulation of chemokines (CCL2, CCL3 and CCL5) |
| GO:0032728 positive regulation of interferon-beta production | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Positive regulation of interferon-beta production, from mouse Tlr2. Reason: Transferred from mouse. IFN-beta induction is not a general TLR2 output and is likely cell-type restricted; kept as non-core. Cytokine and chemokine induction is the downstream output of TLR2 signaling; TLR2 regulates it through the pathway rather than directly. Kept as non-core. |
| GO:0032735 positive regulation of interleukin-12 production | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Positive regulation of IL-12 production, from mouse Tlr2. Reason: Cytokine and chemokine induction is the downstream output of TLR2 signaling; TLR2 regulates it through the pathway rather than directly. Kept as non-core. |
| GO:0032741 positive regulation of interleukin-18 production | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Positive regulation of IL-18 production, from mouse Tlr2. Reason: Cytokine and chemokine induction is the downstream output of TLR2 signaling; TLR2 regulates it through the pathway rather than directly. Kept as non-core. |
| GO:0032755 positive regulation of interleukin-6 production | IDA PMID:19740627 Cultured human melanocytes express functional toll-like rece... | KEEP AS NON CORE | Summary: TLR2 ligand stimulation of melanocytes induces IL-6. Reason: Cytokine and chemokine induction is the downstream output of TLR2 signaling; TLR2 regulates it through the pathway rather than directly. Kept as non-core. Supporting Evidence: PMID:19740627 Stimulation of melanocytes with TLRs ligands resulted in the release of cytokines (IL-8 and IL-6) and the mRNA accumulation of chemokines (CCL2, CCL3 and CCL5) |
| GO:0032755 positive regulation of interleukin-6 production | IGI PMID:28078022 MiR-19 suppresses fibroblast-like synoviocytes cytokine rele... | KEEP AS NON CORE | Summary: miR-19 targeting of TLR2 reduces IL-6 release from synoviocytes. Reason: Cytokine and chemokine induction is the downstream output of TLR2 signaling; TLR2 regulates it through the pathway rather than directly. Kept as non-core. Supporting Evidence: PMID:28078022 Transfection of miR-19 mimic or miR-19 inhibitor obviously suppressed or increased TLR2 expression, and reduced or promoted release of cytokines IL-6 and MMP-3 in FLS, respectively |
| GO:0032757 positive regulation of interleukin-8 production | IDA PMID:17128265 Maintenance of colonic homeostasis by distinctive apical TLR... | KEEP AS NON CORE | Summary: IL-8 production upstream role, from a study of TLR9 polarity in intestinal epithelial cells using TLR2-deficient mice as comparators. Reason: The cached abstract uses TLR2-deficient mice only as a comparator; the curator presumably saw TLR2-dependent IL-8 in the full text. TLR2-dependent IL-8 induction is well established elsewhere, so kept as non-core. Supporting Evidence: PMID:17128265 IECs in TLR9-deficient mice, when compared with wild-type and TLR2-deficient mice, display a lower NF-kappaB activation threshold PMID:11521063 Therefore, TLR2 is a functional receptor for both Gram-positive and Gram-negative bacteria and it induces activation of IL-8 |
| GO:0032757 positive regulation of interleukin-8 production | IDA PMID:19740627 Cultured human melanocytes express functional toll-like rece... | KEEP AS NON CORE | Summary: TLR2 ligands induce IL-8 from melanocytes. Reason: Cytokine and chemokine induction is the downstream output of TLR2 signaling; TLR2 regulates it through the pathway rather than directly. Kept as non-core. Supporting Evidence: PMID:19740627 Stimulation of melanocytes with TLRs ligands resulted in the release of cytokines (IL-8 and IL-6) and the mRNA accumulation of chemokines (CCL2, CCL3 and CCL5) |
| GO:0032757 positive regulation of interleukin-8 production | IGI PMID:22198949 TLR2 is a primary receptor for Alzheimer's amyloid Ξ² peptide... | KEEP AS NON CORE | Summary: TLR2 mediates A-beta-induced IL-8. Reason: Cytokine and chemokine induction is the downstream output of TLR2 signaling; TLR2 regulates it through the pathway rather than directly. Kept as non-core. Supporting Evidence: PMID:22198949 we observed that TLR2 expression enabled HEK293 cells to respond to AΞ²42 |
| GO:0032760 positive regulation of tumor necrosis factor production | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Positive regulation of TNF production, from mouse Tlr2. Reason: Cytokine and chemokine induction is the downstream output of TLR2 signaling; TLR2 regulates it through the pathway rather than directly. Kept as non-core. Supporting Evidence: PMID:17095513 PE_PGRS33, a surface exposed protein, elicits TNF-alpha release from macrophages in a TLR2 (Toll-like receptor 2)-dependent manner |
| GO:0034134 toll-like receptor 2 signaling pathway | IDA PMID:17128265 Maintenance of colonic homeostasis by distinctive apical TLR... | ACCEPT | Summary: TLR2 signaling pathway. Reason: TLR2 is by definition the receptor of this pathway. The cited paper is primarily about TLR9 in intestinal epithelium, but the term is core for TLR2 and is supported by many cached papers. Supporting Evidence: PMID:11521063 Therefore, TLR2 is a functional receptor for both Gram-positive and Gram-negative bacteria and it induces activation of IL-8 PMID:16893894 This resulted in the identification of four residues crucial for TLR2/1 signaling: Arg-748, Phe-749, Leu-752, and Arg-753 |
| GO:0035325 Toll-like receptor binding | IPI PMID:16880211 Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 ... | ACCEPT | Summary: TLR2 binds TLR1 and TLR6 to form preformed heterodimers. Reason: Heterodimerization with TLR1 or TLR6 is intrinsic to TLR2 function and determines its ligand specificity. Supporting Evidence: PMID:16880211 Our data show that TLR2 forms heterodimers with TLR1 and TLR6 and that these heterodimer pre-exist and are not induced by the ligand PMID:19931471 Its ligand specificity is controlled by whether it heterodimerizes with TLR1 or TLR6 |
| GO:0035354 Toll-like receptor 1-Toll-like receptor 2 protein complex | IDA PMID:16880211 Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 ... | ACCEPT | Summary: TLR1-TLR2 heterodimer. Reason: Core complex. Supporting Evidence: PMID:16880211 Our data show that TLR2 forms heterodimers with TLR1 and TLR6 and that these heterodimer pre-exist and are not induced by the ligand |
| GO:0035354 Toll-like receptor 1-Toll-like receptor 2 protein complex | IDA PMID:17889651 Crystal structure of the TLR1-TLR2 heterodimer induced by bi... | ACCEPT | Summary: Crystal structure of the TLR1-TLR2-Pam3CSK4 heterodimer. Reason: Core complex. Supporting Evidence: PMID:17889651 Binding of the tri-acylated lipopeptide, Pam(3)CSK(4), induced the formation of an "m" shaped heterodimer of the TLR1 and TLR2 ectodomains |
| GO:0035354 Toll-like receptor 1-Toll-like receptor 2 protein complex | IPI PMID:17889651 Crystal structure of the TLR1-TLR2 heterodimer induced by bi... | ACCEPT | Summary: TLR1-TLR2 heterodimer (structural). Reason: Core complex. Supporting Evidence: PMID:17889651 Binding of the tri-acylated lipopeptide, Pam(3)CSK(4), induced the formation of an "m" shaped heterodimer of the TLR1 and TLR2 ectodomains |
| GO:0035355 Toll-like receptor 2-Toll-like receptor 6 protein complex | IDA PMID:16880211 Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 ... | ACCEPT | Summary: TLR2-TLR6 heterodimer. Reason: Core complex. Supporting Evidence: PMID:16880211 Our data show that TLR2 forms heterodimers with TLR1 and TLR6 and that these heterodimer pre-exist and are not induced by the ligand |
| GO:0035355 Toll-like receptor 2-Toll-like receptor 6 protein complex | IDA PMID:19931471 Recognition of lipopeptide patterns by Toll-like receptor 2-... | ACCEPT | Summary: Crystal structure of TLR2-TLR6-diacyl lipopeptide. Reason: Core complex. Supporting Evidence: PMID:19931471 We have determined the crystal structures of TLR2-TLR6-diacylated lipopeptide, TLR2-lipoteichoic acid, and TLR2-PE-DTPA complexes |
| GO:0035355 Toll-like receptor 2-Toll-like receptor 6 protein complex | IPI PMID:23155421 Isolated Toll-like receptor transmembrane domains are capabl... | ACCEPT | Summary: TLR2 and TLR6 transmembrane domains interact. Reason: Core complex; consistent with structural data. Supporting Evidence: PMID:23155421 The TLR2 transmembrane domain demonstrated strong heterotypic interactions in bacterial membranes with its known interaction partners, TLR1 and TLR6, as well as with a proposed interaction partner, TLR10 |
| GO:0038023 signaling receptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Signaling receptor activity (IBA). Reason: Correct and appropriately general for the TLR family node; pattern recognition receptor activity is the more specific term. Supporting Evidence: PMID:10384090 Heterologous expression of human TLR2, but not TLR4, in fibroblasts conferred responsiveness to Staphylococcus aureus and Streptococcus pneumoniae as evidenced by inducible translocation of NF-kappaB |
| GO:0038123 toll-like receptor TLR1:TLR2 signaling pathway | IDA PMID:16880211 Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 ... | ACCEPT | Summary: TLR1:TLR2 signaling pathway. Reason: Core pathway. Supporting Evidence: PMID:16880211 Our data show that TLR2 forms heterodimers with TLR1 and TLR6 and that these heterodimer pre-exist and are not induced by the ligand PMID:17889651 We propose that formation of the TLR1-TLR2 heterodimer brings the intracellular TIR domains close to each other to promote dimerization and initiate signaling |
| GO:0038124 toll-like receptor TLR6:TLR2 signaling pathway | IDA PMID:16880211 Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 ... | ACCEPT | Summary: TLR6:TLR2 signaling pathway. Reason: Core pathway. Supporting Evidence: PMID:16880211 Our data show that TLR2 forms heterodimers with TLR1 and TLR6 and that these heterodimer pre-exist and are not induced by the ligand PMID:11441107 Dominant negative constructs of TLR2 or TLR6 inhibit the responses of STF and OspA-L as well as PSM in TLR2-transfected HMEC |
| GO:0038124 toll-like receptor TLR6:TLR2 signaling pathway | IDA PMID:20406817 Identification of Drosophila Yin and PEPT2 as evolutionarily... | ACCEPT | Summary: TLR2/6 signaling synergizes with NOD2 in response to S. aureus. Reason: Core pathway. Supporting Evidence: PMID:20406817 However, when coexpressed with TLR2/6, NOD2 enhanced NFkB activation, indicating that although NOD2 is insufficient for full activation, it synergized with TLR2/6 to increase cytokine response |
| GO:0038124 toll-like receptor TLR6:TLR2 signaling pathway | IDA PMID:23626692 Divergent roles of amino acid residues inside and outside th... | ACCEPT | Summary: TIR residues required for TLR2/6 responsiveness. Reason: Core pathway. Note that this paper carries a 2024 expression of concern; the conclusion is supported independently (PMID:11441107, PMID:19931471). Supporting Evidence: PMID:23626692 The responsiveness of human TLR2/2, TLR2/1 or TLR2/6 was completely lost when 663L and 688N were replaced with the corresponding amino acid residues in the TLR3 TIR domain, respectively PMID:11441107 Dominant negative constructs of TLR2 or TLR6 inhibit the responses of STF and OspA-L as well as PSM in TLR2-transfected HMEC |
| GO:0038187 pattern recognition receptor activity | IDA PMID:10384090 Cutting edge: recognition of Gram-positive bacterial cell wa... | ACCEPT | Summary: TLR2 confers responsiveness to Gram-positive bacteria and their cell-wall components. Reason: Core MF: TLR2 directly binds microbial lipopeptides and other PAMPs and signals across the membrane. Supporting Evidence: PMID:10384090 Heterologous expression of human TLR2, but not TLR4, in fibroblasts conferred responsiveness to Staphylococcus aureus and Streptococcus pneumoniae as evidenced by inducible translocation of NF-kappaB PMID:19931471 Toll-like receptor 2 (TLR2) initiates potent immune responses by recognizing diacylated and triacylated lipopeptides |
| GO:0042495 detection of triacyl bacterial lipopeptide | IDA PMID:19931471 Recognition of lipopeptide patterns by Toll-like receptor 2-... | ACCEPT | Summary: Detection of triacyl bacterial lipopeptide by TLR2-TLR1. Reason: Core process; structural and functional evidence. Supporting Evidence: PMID:19931471 Toll-like receptor 2 (TLR2) initiates potent immune responses by recognizing diacylated and triacylated lipopeptides |
| GO:0042496 detection of diacyl bacterial lipopeptide | IDA PMID:19931471 Recognition of lipopeptide patterns by Toll-like receptor 2-... | ACCEPT | Summary: Detection of diacyl bacterial lipopeptide by TLR2-TLR6. Reason: Core process. Supporting Evidence: PMID:19931471 Toll-like receptor 2 (TLR2) initiates potent immune responses by recognizing diacylated and triacylated lipopeptides |
| GO:0042497 triacyl lipopeptide binding | IBA GO_REF:0000033 | ACCEPT | Summary: Triacyl lipopeptide binding (IBA). Reason: The TLR2 lipid pocket binds the two ester-bound chains of triacyl lipopeptides. Supporting Evidence: PMID:17889651 the two ester-bound lipid chains are inserted into a pocket in TLR2, while the amide-bound lipid chain is inserted into a hydrophobic channel in TLR1 |
| GO:0042497 triacyl lipopeptide binding | IDA PMID:17889651 Crystal structure of the TLR1-TLR2 heterodimer induced by bi... | ACCEPT | Summary: TLR2 binds the ester-bound acyl chains of Pam3CSK4. Reason: Core MF, directly shown by crystal structure. Supporting Evidence: PMID:17889651 the two ester-bound lipid chains are inserted into a pocket in TLR2, while the amide-bound lipid chain is inserted into a hydrophobic channel in TLR1 |
| GO:0042802 identical protein binding | IPI PMID:23155421 Isolated Toll-like receptor transmembrane domains are capabl... | KEEP AS NON CORE | Summary: Isolated TLR2 transmembrane domains self-associate. Reason: Homotypic TMD association in bacterial membranes; TLR2 homodimers are reported but the physiological signaling unit is the TLR1 or TLR6 heterodimer. Supporting Evidence: PMID:23155421 All TLR transmembrane domains showed strong homotypic interaction potential file:human/TLR2/TLR2-deep-research-falcon.md The formation and functionality of TLR2 homodimers remains controversial in the field |
| GO:0042834 peptidoglycan binding | IDA PMID:11986301 The extracellular toll-like receptor 2 domain directly binds... | ACCEPT | Summary: The TLR2 ectodomain binds S. aureus peptidoglycan. Reason: Direct binding shown with soluble ectodomain. Supporting Evidence: PMID:11986301 sTLR2 bound avidly to insoluble PGN (iPGN) from Staphylococcus aureus coated onto microtiter wells in a concentration-dependent manner PMID:11986301 we conclude that the extracellular TLR2 domain directly binds to PGN |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IDA PMID:19740627 Cultured human melanocytes express functional toll-like rece... | ACCEPT | Summary: TLR2 ligation activates NF-kappaB. Reason: NF-kappaB activation is the principal output of TLR2 signaling. Supporting Evidence: PMID:19740627 Triggering of TLRs in melanocytes resulted in the up-regulation of phosphorylated IkappaBalpha and in the nucleus translocation of NF-kappaBp65 PMID:10384090 Heterologous expression of human TLR2, but not TLR4, in fibroblasts conferred responsiveness to Staphylococcus aureus and Streptococcus pneumoniae as evidenced by inducible translocation of NF-kappaB |
| GO:0043235 signaling receptor complex | IBA GO_REF:0000033 | ACCEPT | Summary: Signaling receptor complex (IBA). Reason: TLR2 functions in heterodimeric receptor complexes. Supporting Evidence: PMID:16880211 Our data show that TLR2 forms heterodimers with TLR1 and TLR6 and that these heterodimer pre-exist and are not induced by the ligand |
| GO:0043235 signaling receptor complex | IEA GO_REF:0000117 | ACCEPT | Summary: Signaling receptor complex (ARBA). Reason: Correct. Supporting Evidence: PMID:16880211 Our data show that TLR2 forms heterodimers with TLR1 and TLR6 and that these heterodimer pre-exist and are not induced by the ligand |
| GO:0043235 signaling receptor complex | IPI PMID:23155421 Isolated Toll-like receptor transmembrane domains are capabl... | ACCEPT | Summary: Signaling receptor complex (ComplexPortal). Reason: Correct. Supporting Evidence: PMID:23155421 The TLR2 transmembrane domain demonstrated strong heterotypic interactions in bacterial membranes with its known interaction partners, TLR1 and TLR6, as well as with a proposed interaction partner, TLR10 |
| GO:0044853 plasma membrane raft | IDA PMID:16880211 Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 ... | ACCEPT | Summary: Ligand-stimulated TLR2 heterodimers are recruited to plasma membrane rafts. Reason: Direct evidence. Supporting Evidence: PMID:16880211 Upon stimulation by the specific ligand, these heterodimers are recruited within lipid rafts |
| GO:0044877 protein-containing complex binding | IPI PMID:22198949 TLR2 is a primary receptor for Alzheimer's amyloid Ξ² peptide... | KEEP AS NON CORE | Summary: TLR2 binds aggregated amyloid-beta 42 (ComplexPortal entity). Reason: Duplicates the amyloid-beta binding annotation at a less informative level; non-core. Supporting Evidence: PMID:22198949 demonstrate a direct interaction between TLR2 and the aggregated 42-aa form of human AΞ² (AΞ²42) |
| GO:0045087 innate immune response | NAS PMID:11095740 The repertoire for pattern recognition of pathogens by the i... | ACCEPT | Summary: Innate immune response. Reason: Core process. Supporting Evidence: PMID:11095740 We show that the cytoplasmic domain of TLR2 can form functional pairs with TLR6 or TLR1, and this interaction leads to cytokine induction |
| GO:0045087 innate immune response | NAS PMID:33576548 Structural and functional understanding of the toll-like rec... | ACCEPT | Summary: Innate immune response (review). Reason: Core process. Supporting Evidence: PMID:33576548 One group is composed of TLR1, TLR2, TLR4, TLR5, TLR6 and poorly characterized TLR10, which are localized to cell membranes and predominantly recognize bacterial components such as lipids, lipoproteins, and proteins |
| GO:0045087 innate immune response | TAS PMID:15356140 Microglia initiate central nervous system innate and adaptiv... | ACCEPT | Summary: Innate immune response. Reason: Core process; the cited paper is on mouse microglia but the term is well supported for human TLR2. Supporting Evidence: PMID:15356140 stimulation of quiescent microglia with various TLR agonists, including LPS (TLR4), peptidoglycan (TLR2) PMID:10384090 Heterologous expression of human TLR2, but not TLR4, in fibroblasts conferred responsiveness to Staphylococcus aureus and Streptococcus pneumoniae as evidenced by inducible translocation of NF-kappaB |
| GO:0045121 membrane raft | IDA PMID:16880211 Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 ... | ACCEPT | Summary: Membrane raft. Reason: Direct evidence. Supporting Evidence: PMID:16880211 Upon stimulation by the specific ligand, these heterodimers are recruited within lipid rafts |
| GO:0045121 membrane raft | IEA GO_REF:0000044 | ACCEPT | Summary: Membrane raft (UniProt subcellular location). Reason: Consistent with PMID:16880211. Supporting Evidence: PMID:16880211 Upon stimulation by the specific ligand, these heterodimers are recruited within lipid rafts |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:12594207 Lipoteichoic acid (LTA) of Streptococcus pneumoniae and Stap... | MARK AS OVER ANNOTATED | Summary: Upstream of RNA polymerase II transcription in response to lipoteichoic acid. Reason: Transcriptional induction is a distal output of TLR2 signaling via NF-kappaB; the term is too indirect to describe TLR2's role. Supporting Evidence: PMID:12594207 Human embryonic kidney (HEK) 293/CD14 cells and Chinese hamster ovary (CHO) cells were responsive to LTA only after transfection with TLR-2 |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Positive regulation of Pol II transcription, from mouse Tlr2. Reason: Indirect downstream output; see above. |
| GO:0050729 positive regulation of inflammatory response | IDA PMID:19740627 Cultured human melanocytes express functional toll-like rece... | KEEP AS NON CORE | Summary: TLR2 ligation of melanocytes induces pro-inflammatory mediators. Reason: Cytokine and chemokine induction is the downstream output of TLR2 signaling; TLR2 regulates it through the pathway rather than directly. Kept as non-core. Supporting Evidence: PMID:19740627 Stimulation of melanocytes with TLRs ligands resulted in the release of cytokines (IL-8 and IL-6) and the mRNA accumulation of chemokines (CCL2, CCL3 and CCL5) |
| GO:0050729 positive regulation of inflammatory response | IGI PMID:28078022 MiR-19 suppresses fibroblast-like synoviocytes cytokine rele... | KEEP AS NON CORE | Summary: Increased TLR2 in RA synoviocytes enhances cytokine release. Reason: Cytokine and chemokine induction is the downstream output of TLR2 signaling; TLR2 regulates it through the pathway rather than directly. Kept as non-core. Supporting Evidence: PMID:28078022 Transfection of miR-19 mimic or miR-19 inhibitor obviously suppressed or increased TLR2 expression, and reduced or promoted release of cytokines IL-6 and MMP-3 in FLS, respectively |
| GO:0050765 negative regulation of phagocytosis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Negative regulation of phagocytosis, from mouse Tlr2. Reason: TLR2 deficiency enhanced A-beta phagocytosis in microglia/macrophages; a context-specific, indirect effect. Supporting Evidence: PMID:22198949 TLR2 deficiency reduced AΞ²42-triggered inflammatory activation but enhanced AΞ² phagocytosis in cultured microglia and macrophages |
| GO:0050830 defense response to Gram-positive bacterium | IDA PMID:11521063 Role of MD-2 in TLR2- and TLR4-mediated recognition of Gram-... | ACCEPT | Summary: TLR2 is a functional receptor for Gram-positive bacteria and induces IL-8. Reason: Core process. Supporting Evidence: PMID:11521063 Therefore, TLR2 is a functional receptor for both Gram-positive and Gram-negative bacteria and it induces activation of IL-8 |
| GO:0051607 defense response to virus | IEP PMID:32634389 Chikungunya virus infection induces differential inflammator... | MARK AS OVER ANNOTATED | Summary: Expression of TLRs in monocytes and macrophages changes after chikungunya virus infection. Reason: The row is an expression-pattern annotation from a study in which chikungunya virus infection changed the expression of Toll-like receptors in monocytes and macrophages, so it records a real expression response. A change in expression after infection shows that TLR2 is regulated in that setting, not that it takes part in antiviral defence, and the paper itself states that the functional role of the receptors was not determined. The term over-reads expression data; nothing refutes it, so it is marked as an over-annotation rather than removed. Supporting Evidence: PMID:32634389 However, additional studies are required to determine the functional role of TLRs in monocytes and MDMs |
| GO:0051964 negative regulation of synapse assembly | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Negative regulation of synapse assembly, from mouse Tlr2. Reason: No cached evidence that TLR2 performs a step in synapse assembly; likely an indirect neuroinflammatory effect. |
| GO:0071221 cellular response to bacterial lipopeptide | TAS PMID:15356140 Microglia initiate central nervous system innate and adaptiv... | ACCEPT | Summary: Cellular response to bacterial lipopeptide. Reason: Core process. Supporting Evidence: PMID:19931471 Toll-like receptor 2 (TLR2) initiates potent immune responses by recognizing diacylated and triacylated lipopeptides |
| GO:0071223 cellular response to lipoteichoic acid | IDA PMID:12594207 Lipoteichoic acid (LTA) of Streptococcus pneumoniae and Stap... | ACCEPT | Summary: TLR2 is required for cellular responses to LTA. Reason: LTA signals via TLR2 (with LBP and CD14). Supporting Evidence: PMID:12594207 Human embryonic kidney (HEK) 293/CD14 cells and Chinese hamster ovary (CHO) cells were responsive to LTA only after transfection with TLR-2 |
| GO:0071223 cellular response to lipoteichoic acid | IMP PMID:26649771 Expression of Beta-Defensin 131 Promotes an Innate Immune Re... | ACCEPT | Summary: TLR2 knockdown reduces LTA-induced DEFB131 expression. Reason: Consistent with TLR2 as the LTA receptor. Supporting Evidence: PMID:26649771 We found that DEFB131 expression was induced by LTA stimulation |
| GO:0071346 cellular response to type II interferon | IDA PMID:11672593 Toll-like receptor 2 and 4 surface expressions on human mono... | MARK AS OVER ANNOTATED | Summary: IFN-gamma up-regulates TLR2 surface expression on monocytes. Reason: The paper shows TLR2 is a target of IFN-gamma (an expression response), not that TLR2 carries out the cellular response to IFN-gamma. Supporting Evidence: PMID:11672593 IFN-gamma up-regulated both TLR2 and TLR4, but enhanced the surface expression, on human peripheral blood monocytes of TLR4 more than that of TLR2 |
| GO:0071726 cellular response to diacyl bacterial lipopeptide | IDA PMID:16880211 Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 ... | ACCEPT | Summary: Cellular response to diacyl bacterial lipopeptide. Reason: Core process. Supporting Evidence: PMID:16880211 Our data show that TLR2 forms heterodimers with TLR1 and TLR6 and that these heterodimer pre-exist and are not induced by the ligand PMID:19931471 Toll-like receptor 2 (TLR2) initiates potent immune responses by recognizing diacylated and triacylated lipopeptides |
| GO:0071726 cellular response to diacyl bacterial lipopeptide | IDA PMID:19931471 Recognition of lipopeptide patterns by Toll-like receptor 2-... | ACCEPT | Summary: Cellular response to diacyl bacterial lipopeptide (structural and functional). Reason: Core process. Supporting Evidence: PMID:19931471 Toll-like receptor 2 (TLR2) initiates potent immune responses by recognizing diacylated and triacylated lipopeptides |
| GO:0071727 cellular response to triacyl bacterial lipopeptide | IDA PMID:16880211 Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 ... | ACCEPT | Summary: Cellular response to triacyl bacterial lipopeptide. Reason: Core process. Supporting Evidence: PMID:16880211 Our data show that TLR2 forms heterodimers with TLR1 and TLR6 and that these heterodimer pre-exist and are not induced by the ligand PMID:19931471 Toll-like receptor 2 (TLR2) initiates potent immune responses by recognizing diacylated and triacylated lipopeptides |
| GO:0071727 cellular response to triacyl bacterial lipopeptide | IDA PMID:19931471 Recognition of lipopeptide patterns by Toll-like receptor 2-... | ACCEPT | Summary: Cellular response to triacyl bacterial lipopeptide (structural and functional). Reason: Core process. Supporting Evidence: PMID:19931471 Toll-like receptor 2 (TLR2) initiates potent immune responses by recognizing diacylated and triacylated lipopeptides |
| GO:0140367 antibacterial innate immune response | IDA PMID:20406817 Identification of Drosophila Yin and PEPT2 as evolutionarily... | ACCEPT | Summary: TLR2/6 recognition of S. aureus in antibacterial innate immunity. Reason: Core process. Supporting Evidence: PMID:20406817 However, when coexpressed with TLR2/6, NOD2 enhanced NFkB activation, indicating that although NOD2 is insufficient for full activation, it synergized with TLR2/6 to increase cytokine response PMID:10384090 Heterologous expression of human TLR2, but not TLR4, in fibroblasts conferred responsiveness to Staphylococcus aureus and Streptococcus pneumoniae as evidenced by inducible translocation of NF-kappaB |
| GO:1903974 positive regulation of cellular response to macrophage colony-stimulating factor stimulus | IDA PMID:11672593 Toll-like receptor 2 and 4 surface expressions on human mono... | MARK AS OVER ANNOTATED | Summary: M-CSF up-regulates TLR2 surface expression on monocytes. Reason: TLR2 is the regulated target here; the paper does not show TLR2 regulating the cellular response to M-CSF. Supporting Evidence: PMID:11672593 M-CSF up-regulated both TLR2 and TLR4 surface expression on human peripheral blood monocytes |
| GO:1904466 positive regulation of matrix metallopeptidase secretion | IGI PMID:28078022 MiR-19 suppresses fibroblast-like synoviocytes cytokine rele... | MARK AS OVER ANNOTATED | Summary: miR-19 targeting of TLR2 reduces MMP-3 release from synoviocytes. Reason: An indirect downstream consequence of TLR2 signaling levels; TLR2 does not act in MMP secretion itself. Supporting Evidence: PMID:28078022 Transfection of miR-19 mimic or miR-19 inhibitor obviously suppressed or increased TLR2 expression, and reduced or promoted release of cytokines IL-6 and MMP-3 in FLS, respectively |
| GO:0042498 diacyl lipopeptide binding | IDA PMID:19931471 Recognition of lipopeptide patterns by Toll-like receptor 2-... | NEW | Summary: TLR2 binds diacylated lipopeptide in the TLR2-TLR6 heterodimer crystal structure. Reason: Triacyl lipopeptide binding is annotated but its diacyl counterpart is not, although the TLR2-TLR6-diacyl lipopeptide crystal structure shows direct binding, with the ester-linked acyl chains in the TLR2 pocket. This is a molecular function from direct structural evidence, not a process claim. Supporting Evidence: PMID:19931471 We have determined the crystal structures of TLR2-TLR6-diacylated lipopeptide, TLR2-lipoteichoic acid, and TLR2-PE-DTPA complexes PMID:17889651 the two ester-bound lipid chains are inserted into a pocket in TLR2, while the amide-bound lipid chain is inserted into a hydrophobic channel in TLR1 |
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Download this section (compressed HTML)Q: Does human TLR2 bind LPS in any physiological setting, or do TLR2 responses to LPS preparations reflect contaminating lipoproteins or MD-2-dependent effects? The GO:0001530 and GO:0001875 rows depend on this.
Q: Is TLR2 recognition of peptidoglycan direct, or due to lipoproteins that co-purify with peptidoglycan preparations?
Q: Do TLR2 homodimers signal physiologically in human cells, or is the signaling unit always a heterodimer with TLR1, TLR6 or TLR10?
Q: Should the mouse-derived ISS annotations to neural and behavioural processes (learning, microglia development, synapse assembly) be propagated to human TLR2 at all?
Experiment: Binding assays with highly purified, lipoprotein-free LPS and peptidoglycan against soluble TLR2 ectodomain, with and without MD-2 and CD14, to settle whether these are direct TLR2 ligands.
Experiment: Signaling assays in TLR1/TLR6/TLR10 triple-deficient human myeloid cells to test whether TLR2 alone can respond to lipoteichoic acid or other agonists.
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