TLR1 is a type I transmembrane pattern recognition receptor of the Toll-like receptor family, expressed widely and most highly in leukocytes, spleen, thymus and ovary. Its leucine-rich-repeat ectodomain pairs with TLR2 to form a heterodimeric receptor at the plasma membrane that recognises triacylated bacterial lipopeptides and lipoproteins, such as the mycobacterial 19-kDa lipoprotein and synthetic Pam3CSK4: the two ester-linked acyl chains insert into a pocket in TLR2 and the amide-linked chain into a hydrophobic channel in TLR1, bridging the two ectodomains. Ligand-induced dimerisation juxtaposes the cytoplasmic TIR domains, which recruit TIRAP and MYD88 and lead through IRAK and TRAF6 to NF-kappaB activation and proinflammatory cytokine production. Activated TLR1:TLR2 complexes accumulate in lipid rafts and are then trafficked to the Golgi; TLR1 is also recruited to phagosomes. TLR1 polymorphisms, including the common I602S allele that impairs surface expression, influence susceptibility to leprosy.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001774 microglial cell activation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Electronic ortholog transfer (rat) of microglial cell activation. Reason: TLR1 acts as the lipopeptide-selecting co-receptor of TLR2. Microglial activation is a downstream cellular outcome of TLR2-subfamily signaling; TLR1 enhanced TLR2-dependent Abeta42-triggered inflammatory activation, but this is not a microglia-specific role of TLR1 and the process is several steps removed from its receptor activity. Supporting Evidence: PMID:22198949 TLR2-mediated AΞ²42-triggered inflammatory activation was enhanced by TLR1 and suppressed by TLR6 |
| GO:0001875 lipopolysaccharide immune receptor activity | IDA PMID:16880211 Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 ... | MODIFY | Summary: Curator IDA (the same evidence also underlies GO-CAM 5fb9cc0600000727) that TLR1 contributes to an immune receptor activity of the TLR1:TLR2 heterodimer. Reason: The contributes_to receptor claim is well founded - TLR1 and TLR2 form a pre-existing heterodimer that is activated at the cell surface by triacylated lipopeptide - but GO:0001875 is defined as combining with lipopolysaccharide. TLR1:TLR2 binds triacyl lipopeptides (the amide-linked acyl chain sits in a TLR1 channel), not LPS. The parent GO:0038187 pattern recognition receptor activity captures the activity without the wrong ligand. 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: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:0002224 toll-like receptor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for TLR signaling pathway at the TLR node PTN002808083. Reason: TLR1 is a bona fide TLR whose TIR domain signals via MyD88 as the TLR1:TLR2 heterodimer; the IBA is at an appropriate level, with the more specific TLR1:TLR2 pathway term captured separately. Supporting Evidence: PMID:12077222 Macrophages from TLR1-deficient (TLR1(-/-)) mice showed impaired proinflammatory cytokine production in response to the 19-kDa lipoprotein and a synthetic triacylated lipopeptide PMID:11081518 the conserved surface patch may mediate interactions with the down-stream MyD88 adapter molecule |
| GO:0002224 toll-like receptor signaling pathway | IDA PMID:16893894 Structural and functional evidence for the role of the TLR2 ... | ACCEPT | Summary: IDA from TIR-domain mutagenesis: TLR1 BB-loop mutants reduce Pam3CSK4-driven NF-kappaB activation. Reason: Directly shows TLR1 TIR-domain residues are required for signaling. The experiment tests the TLR1:TLR2 heterodimer, so the specific GO:0038123 toll-like receptor TLR1:TLR2 signaling pathway (already annotated by IDA) is the most precise description; the general term is correct. Supporting Evidence: PMID:16893894 As expected, in vitro functional studies involving TLR1 G676A and TLR1 G676L resulted in reduced PAM(3)CSK(4) mediated NF-kappaB activation |
| GO:0002224 toll-like receptor signaling pathway | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA for TLR signaling pathway. Reason: Correct general process for a TLR; consistent with experimental data. Supporting Evidence: PMID:12077222 Macrophages from TLR1-deficient (TLR1(-/-)) mice showed impaired proinflammatory cytokine production in response to the 19-kDa lipoprotein and a synthetic triacylated lipopeptide |
| GO:0004888 transmembrane signaling receptor activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO (IPR017241 Toll-like receptor family) mapping to transmembrane signaling receptor activity. Reason: TLR1 is a type I transmembrane receptor whose ectodomain binds the ligand and whose TIR domain recruits adaptors; correct though general (PRR activity is the more informative core term). 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 PMID:11081518 the conserved surface patch may mediate interactions with the down-stream MyD88 adapter molecule |
| GO:0004888 transmembrane signaling receptor activity | NAS PMID:11081518 Structural basis for signal transduction by the Toll/interle... | ACCEPT | Summary: NAS from the TLR1/TLR2 TIR-domain crystal structure paper. Reason: Consistent with structural and functional evidence of TIR-mediated signaling by TLR1. Supporting Evidence: PMID:11081518 Here we report the crystal structures of the TIR domains of human TLR1 and TLR2 PMID:11081518 the conserved surface patch may mediate interactions with the down-stream MyD88 adapter molecule |
| GO:0005515 protein binding | IPI PMID:15728506 Human TLR10 is a functional receptor, expressed by B cells a... | MODIFY | Summary: IPI: TLR1 co-immunoprecipitates with TLR10 in transfected cells. Reason: Protein binding is uninformative. The paper reports TLR10 heterodimerisation with TLR1 (and TLR2); the specific GO:0035325 Toll-like receptor binding describes this. Physiological relevance of the TLR1:TLR10 pair is unclear (overexpression), so this is not a core function. 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 |
| GO:0005515 protein binding | IPI PMID:16880211 Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 ... | MODIFY | Summary: IPI: TLR1 associates with TLR2 (and CD14 in the activation cluster) at the cell surface. Reason: The informative content is heterodimerisation with TLR2, captured by GO:0035663 Toll-like receptor 2 binding (already on TLR1 by IPI/IBA). Proposed replacements: Toll-like receptor 2 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:23155421 Isolated Toll-like receptor transmembrane domains are capabl... | MODIFY | Summary: IPI: isolated TLR1 and TLR2 transmembrane-domain peptides interact (ToxR assay and FRET in micelles). Reason: Supports TLR1-TLR2 association, consistent with the full-length heterodimer; the informative term is Toll-like receptor 2 binding. Proposed replacements: Toll-like receptor 2 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 |
| GO:0005515 protein binding | IPI PMID:23155421 Isolated Toll-like receptor transmembrane domains are capabl... | REMOVE | Summary: IPI: TLR1 and TLR10 transmembrane domains interact in a bacterial ToxR reporter. Reason: Protein binding is uninformative and the evidence is an isolated-TMD assay in E. coli membranes; the TLR1-TLR10 pairing is represented (as Toll-like receptor binding) from the co-immunoprecipitation paper. 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:0005515 protein binding | IPI PMID:23155421 Isolated Toll-like receptor transmembrane domains are capabl... | REMOVE | Summary: IPI: TLR1 and TLR6 transmembrane domains interact in a bacterial ToxR reporter. Reason: Protein binding is uninformative; an isolated-TMD interaction between TLR1 and TLR6 in E. coli membranes has no established functional counterpart for the full-length receptors, which each pair with TLR2. 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:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: IPI from the BioPlex 3.0 AP-MS interactome: TLR1 co-purifies with TLR6. Reason: High-throughput co-purification; protein binding is uninformative and no functional TLR1:TLR6 receptor is known. Supporting Evidence: PMID:33961781 Through affinity-purification mass spectrometry, we have created two proteome-scale, cell-line-specific interaction networks |
| GO:0005794 Golgi apparatus | IDA PMID:16880211 Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 ... | KEEP AS NON CORE | Summary: IDA: ligand-activated TLR2:TLR1 clusters are targeted to the Golgi apparatus. Reason: Post-activation trafficking destination; the paper states signaling occurs at the cell surface and trafficking is independent of signaling. 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:0005794 Golgi apparatus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt subcellular-location mapping to Golgi apparatus. Reason: Same basis as the IDA row (PMID:16880211); a post-activation location. Supporting Evidence: PMID:16880211 All TLR2 receptor clusters accumulate in lipid rafts and are targeted to the Golgi apparatus |
| GO:0005886 plasma membrane | EXP PMID:16880211 Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 ... | ACCEPT | Summary: EXP: TLR1 localizes to the cell surface. Reason: TLR1:TLR2 heterodimers pre-exist and are activated at the cell surface. 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 |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for plasma membrane (is_active_in) across cell-surface TLRs. Reason: TLR1 acts at the plasma membrane. Supporting Evidence: PMID:16880211 Activation occurs at the cell surface, and the observed trafficking is independent of signaling |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping (cell membrane). Reason: Consistent with experimental data. 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: NAS: plasma membrane. Reason: Consistent with experimental localization. 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: NAS from a TLR structural review. Reason: Review groups TLR1 with the cell-membrane TLRs that recognise bacterial lipids and lipoproteins. 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 PMID:9435236 A family of human receptors structurally related to Drosophi... | ACCEPT | Summary: TAS from the original cloning of TLRs 1-5. Reason: TLR1 is a type I transmembrane receptor at the cell surface; consistent with later experiments. Supporting Evidence: PMID:9435236 Five human Toll-like receptors--named TLRs 1-5--are probably the direct homologs of the fly molecule |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-166072 | ACCEPT | Summary: Reactome places TLR1 (as the TLR1:TLR2 heterodimer) at the plasma membrane in its TLR2-subfamily signaling reactions. Reason: Plasma membrane localization of TLR1 is experimentally established; the TLR1:TLR2 heterodimer pre-exists at, and is activated 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 TLR1 (as the TLR1:TLR2 heterodimer) at the plasma membrane in its TLR2-subfamily signaling reactions. Reason: Plasma membrane localization of TLR1 is experimentally established; the TLR1:TLR2 heterodimer pre-exists at, and is activated 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 TLR1 (as the TLR1:TLR2 heterodimer) at the plasma membrane in its TLR2-subfamily signaling reactions. Reason: Plasma membrane localization of TLR1 is experimentally established; the TLR1:TLR2 heterodimer pre-exists at, and is activated 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 TLR1 (as the TLR1:TLR2 heterodimer) at the plasma membrane in its TLR2-subfamily signaling reactions. Reason: Plasma membrane localization of TLR1 is experimentally established; the TLR1:TLR2 heterodimer pre-exists at, and is activated 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 TLR1 (as the TLR1:TLR2 heterodimer) at the plasma membrane in its TLR2-subfamily signaling reactions. Reason: Plasma membrane localization of TLR1 is experimentally established; the TLR1:TLR2 heterodimer pre-exists at, and is activated 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 TLR1 (as the TLR1:TLR2 heterodimer) at the plasma membrane in its TLR2-subfamily signaling reactions. Reason: Plasma membrane localization of TLR1 is experimentally established; the TLR1:TLR2 heterodimer pre-exists at, and is activated 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 TLR1 (as the TLR1:TLR2 heterodimer) at the plasma membrane in its TLR2-subfamily signaling reactions. Reason: Plasma membrane localization of TLR1 is experimentally established; the TLR1:TLR2 heterodimer pre-exists at, and is activated 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 TLR1 (as the TLR1:TLR2 heterodimer) at the plasma membrane in its TLR2-subfamily signaling reactions. Reason: Plasma membrane localization of TLR1 is experimentally established; the TLR1:TLR2 heterodimer pre-exists at, and is activated 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 TLR1 (as the TLR1:TLR2 heterodimer) at the plasma membrane in its TLR2-subfamily signaling reactions. Reason: Plasma membrane localization of TLR1 is experimentally established; the TLR1:TLR2 heterodimer pre-exists at, and is activated 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 TLR1 (as the TLR1:TLR2 heterodimer) at the plasma membrane in its TLR2-subfamily signaling reactions. Reason: Plasma membrane localization of TLR1 is experimentally established; the TLR1:TLR2 heterodimer pre-exists at, and is activated 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 TLR1 (as the TLR1:TLR2 heterodimer) at the plasma membrane in its TLR2-subfamily signaling reactions. Reason: Plasma membrane localization of TLR1 is experimentally established; the TLR1:TLR2 heterodimer pre-exists at, and is activated 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 TLR1 (as the TLR1:TLR2 heterodimer) at the plasma membrane in its TLR2-subfamily signaling reactions. Reason: Plasma membrane localization of TLR1 is experimentally established; the TLR1:TLR2 heterodimer pre-exists at, and is activated 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 TLR1 (as the TLR1:TLR2 heterodimer) at the plasma membrane in its TLR2-subfamily signaling reactions. Reason: Plasma membrane localization of TLR1 is experimentally established; the TLR1:TLR2 heterodimer pre-exists at, and is activated 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 TLR1 (as the TLR1:TLR2 heterodimer) at the plasma membrane in its TLR2-subfamily signaling reactions. Reason: Plasma membrane localization of TLR1 is experimentally established; the TLR1:TLR2 heterodimer pre-exists at, and is activated 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 TLR1 (as the TLR1:TLR2 heterodimer) at the plasma membrane in its TLR2-subfamily signaling reactions. Reason: Plasma membrane localization of TLR1 is experimentally established; the TLR1:TLR2 heterodimer pre-exists at, and is activated 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 TLR1 (as the TLR1:TLR2 heterodimer) at the plasma membrane in its TLR2-subfamily signaling reactions. Reason: Plasma membrane localization of TLR1 is experimentally established; the TLR1:TLR2 heterodimer pre-exists at, and is activated 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 TLR1 (as the TLR1:TLR2 heterodimer) at the plasma membrane in its TLR2-subfamily signaling reactions. Reason: Plasma membrane localization of TLR1 is experimentally established; the TLR1:TLR2 heterodimer pre-exists at, and is activated 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 TLR1 (as the TLR1:TLR2 heterodimer) at the plasma membrane in its TLR2-subfamily signaling reactions. Reason: Plasma membrane localization of TLR1 is experimentally established; the TLR1:TLR2 heterodimer pre-exists at, and is activated 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 TLR1 (as the TLR1:TLR2 heterodimer) at the plasma membrane in its TLR2-subfamily signaling reactions. Reason: Plasma membrane localization of TLR1 is experimentally established; the TLR1:TLR2 heterodimer pre-exists at, and is activated 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 TLR1 (as the TLR1:TLR2 heterodimer) at the plasma membrane in its TLR2-subfamily signaling reactions. Reason: Plasma membrane localization of TLR1 is experimentally established; the TLR1:TLR2 heterodimer pre-exists at, and is activated 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 TLR1 (as the TLR1:TLR2 heterodimer) at the plasma membrane in its TLR2-subfamily signaling reactions. Reason: Plasma membrane localization of TLR1 is experimentally established; the TLR1:TLR2 heterodimer pre-exists at, and is activated 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 TLR1 (as the TLR1:TLR2 heterodimer) at the plasma membrane in its TLR2-subfamily signaling reactions. Reason: Plasma membrane localization of TLR1 is experimentally established; the TLR1:TLR2 heterodimer pre-exists at, and is activated 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 TLR1 (as the TLR1:TLR2 heterodimer) at the plasma membrane in its TLR2-subfamily signaling reactions. Reason: Plasma membrane localization of TLR1 is experimentally established; the TLR1:TLR2 heterodimer pre-exists at, and is activated 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 | KEEP AS NON CORE | Summary: InterPro2GO mapping to immune response. Reason: Correct but very general; innate immune response and the TLR1:TLR2 pathway capture the role more precisely. Supporting Evidence: PMID:12077222 Macrophages from TLR1-deficient (TLR1(-/-)) mice showed impaired proinflammatory cytokine production in response to the 19-kDa lipoprotein and a synthetic triacylated lipopeptide |
| GO:0007165 signal transduction | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro2GO (TIR domain) mapping to signal transduction. Reason: Correct but uninformative parent of the TLR signaling pathway terms. Supporting Evidence: PMID:11081518 the conserved surface patch may mediate interactions with the down-stream MyD88 adapter molecule |
| GO:0016020 membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA: membrane. Reason: Correct; TLR1 is a single-pass membrane protein. Supporting Evidence: PMID:16880211 Activation occurs at the cell surface, and the observed trafficking is independent of signaling |
| GO:0016020 membrane | NAS PMID:11081518 Structural basis for signal transduction by the Toll/interle... | ACCEPT | Summary: NAS: membrane. Reason: Correct. Supporting Evidence: PMID:11081518 Here we report the crystal structures of the TIR domains of human TLR1 and TLR2 |
| GO:0030670 phagocytic vesicle membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt subcellular-location mapping (by similarity to mouse) to phagocytic vesicle membrane. Reason: TLR1 is recruited to macrophage phagosomes together with TLR2 and TLR6; signaling from phagosomes is plausible but the primary site of activation is the cell surface. Supporting Evidence: PMID:11095740 Finally, we show that TLR6, TLR2, and TLR1 are recruited to macrophage phagosomes |
| GO:0031663 lipopolysaccharide-mediated signaling pathway | IEA GO_REF:0000108 | REMOVE | Summary: IEA inferred (GO_REF:0000108) from the lipopolysaccharide immune receptor activity annotation. Reason: Derived automatically from GO:0001875, which is itself a mis-fit for TLR1 (the TLR1:TLR2 ligand is triacyl lipopeptide, not LPS). There is no evidence that TLR1 participates in LPS signaling. 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 PMID:12077222 We report here that TLR1 associates with TLR2 and recognizes the native mycobacterial 19-kDa lipoprotein along with TLR2 |
| GO:0032493 response to bacterial lipoprotein | IEA GO_REF:0000107 | ACCEPT | Summary: Electronic ortholog transfer (rat) of response to bacterial lipoprotein. Reason: TLR1 with TLR2 recognises mycobacterial lipoprotein; TLR1-deficient macrophages respond poorly. Supporting Evidence: PMID:12077222 We report here that TLR1 associates with TLR2 and recognizes the native mycobacterial 19-kDa lipoprotein along with TLR2 PMID:12077222 Macrophages from TLR1-deficient (TLR1(-/-)) mice showed impaired proinflammatory cytokine production in response to the 19-kDa lipoprotein and a synthetic triacylated lipopeptide |
| GO:0032755 positive regulation of interleukin-6 production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Electronic ortholog transfer (mouse Tlr1) of positive regulation of IL-6 production. Reason: Cytokine induction is a downstream outcome of TLR1:TLR2 signaling (impaired in Tlr1-/- macrophages), not a direct activity of TLR1. Supporting Evidence: PMID:12077222 Macrophages from TLR1-deficient (TLR1(-/-)) mice showed impaired proinflammatory cytokine production in response to the 19-kDa lipoprotein and a synthetic triacylated lipopeptide |
| GO:0032755 positive regulation of interleukin-6 production | ISS PMID:12077222 Cutting edge: role of Toll-like receptor 1 in mediating immu... | KEEP AS NON CORE | Summary: ISS from mouse Tlr1 knockout: positive regulation of IL-6 production. Reason: Downstream outcome of TLR1:TLR2 signaling. Supporting Evidence: PMID:12077222 Macrophages from TLR1-deficient (TLR1(-/-)) mice showed impaired proinflammatory cytokine production in response to the 19-kDa lipoprotein and a synthetic triacylated lipopeptide |
| 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: IGI: TLR1 co-expression enhances TLR2-dependent Abeta42-triggered inflammatory (IL-8) responses. Reason: Downstream cytokine output of TLR2 heterodimer signaling; TLR1 acts as co-receptor. Supporting Evidence: PMID:22198949 TLR2-mediated AΞ²42-triggered inflammatory activation was enhanced by TLR1 and suppressed by TLR6 |
| GO:0032760 positive regulation of tumor necrosis factor production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Electronic ortholog transfer (mouse Tlr1) of positive regulation of TNF production. Reason: Downstream outcome of TLR1:TLR2 signaling. Supporting Evidence: PMID:12077222 Macrophages from TLR1-deficient (TLR1(-/-)) mice showed impaired proinflammatory cytokine production in response to the 19-kDa lipoprotein and a synthetic triacylated lipopeptide |
| GO:0032760 positive regulation of tumor necrosis factor production | ISS PMID:12077222 Cutting edge: role of Toll-like receptor 1 in mediating immu... | KEEP AS NON CORE | Summary: ISS from mouse Tlr1: positive regulation of TNF production. Reason: Downstream outcome of TLR1:TLR2 signaling. Supporting Evidence: PMID:12077222 Macrophages from TLR1-deficient (TLR1(-/-)) mice showed impaired proinflammatory cytokine production in response to the 19-kDa lipoprotein and a synthetic triacylated lipopeptide |
| GO:0034137 positive regulation of toll-like receptor 2 signaling pathway | IGI PMID:22198949 TLR2 is a primary receptor for Alzheimer's amyloid Ξ² peptide... | KEEP AS NON CORE | Summary: IGI: TLR1 enhances TLR2-mediated Abeta42-triggered signaling. Reason: TLR1 is a co-receptor within the TLR2 heterodimer rather than a regulator external to the pathway; the experimental observation is accepted as reported, but the core process for TLR1 is GO:0038123 TLR1:TLR2 signaling pathway. Supporting Evidence: PMID:22198949 TLR2-mediated AΞ²42-triggered inflammatory activation was enhanced by TLR1 and suppressed by TLR6 |
| GO:0035354 Toll-like receptor 1-Toll-like receptor 2 protein complex | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA: part of TLR1-TLR2 protein complex. Reason: The TLR1:TLR2 heterodimer is established structurally and biochemically. 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 | IDA PMID:16880211 Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 ... | ACCEPT | Summary: IDA: TLR1-TLR2 heterodimer at the cell surface. Reason: Core complex membership. 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: IDA: crystal structure of the TLR1-TLR2-Pam3CSK4 complex. Reason: Core complex membership. 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: IPI: TLR1-TLR2 heterodimer induced by triacyl lipopeptide. Reason: Core complex membership. 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:0035663 Toll-like receptor 2 binding | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA: Toll-like receptor 2 binding (TLR1/TLR6/TLR10 clade node). Reason: TLR1 directly binds TLR2 to form the heterodimeric receptor. 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 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:0035663 Toll-like receptor 2 binding | IPI PMID:16880211 Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 ... | ACCEPT | Summary: IPI: TLR1 binds TLR2. Reason: Direct, functionally essential interaction. 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:0038023 signaling receptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA: signaling receptor activity. Reason: Correct general MF for a TLR; PRR activity is the informative child. 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: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: IDA: toll-like receptor TLR1:TLR2 signaling pathway. Reason: Core process: activation of the TLR1:TLR2 heterodimer at the cell surface by triacylated lipopeptide. Supporting Evidence: PMID:16880211 Activation occurs at the cell surface, and the observed trafficking is independent of signaling PMID:12077222 Macrophages from TLR1-deficient (TLR1(-/-)) mice showed impaired proinflammatory cytokine production in response to the 19-kDa lipoprotein and a synthetic triacylated lipopeptide |
| GO:0042116 macrophage activation | NAS PMID:11607792 IFNs activate toll-like receptor gene expression in viral in... | MARK AS OVER ANNOTATED | Summary: NAS citing a paper on interferon induction of TLR mRNA in virus-infected macrophages. Reason: The cited paper measures regulation of TLR1 mRNA by interferons, not a role of TLR1 in macrophage activation. TLR1:TLR2 signaling does drive cytokine output in macrophages, but this general cellular-activation term is better represented by the specific TLR1:TLR2 pathway. Supporting Evidence: PMID:11607792 Viral infection enhanced TLR1, TLR2, TLR3, and TLR7 mRNA expression 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:0042495 detection of triacyl bacterial lipopeptide | IDA PMID:19931471 Recognition of lipopeptide patterns by Toll-like receptor 2-... | ACCEPT | Summary: IDA: detection of triacyl bacterial lipopeptide. Reason: Core process: TLR1 provides the channel that accommodates the amide-linked acyl chain of triacyl lipopeptides, and the TLR1 vs TLR6 partner determines TLR2 ligand specificity. Supporting Evidence: PMID:19931471 Its ligand specificity is controlled by whether it heterodimerizes with TLR1 or TLR6 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 file:human/TLR1/TLR1-deep-research-falcon.md Two lipid chains of the ligand bind the hydrophobic pocket of TLR2, while the third, amide-linked chain fits into the hydrophobic channel of TLR1 |
| GO:0042802 identical protein binding | IPI PMID:23155421 Isolated Toll-like receptor transmembrane domains are capabl... | MARK AS OVER ANNOTATED | Summary: IPI: TLR1 transmembrane-domain homotypic interaction in bacterial membranes. Reason: Isolated-TMD self-association in an E. coli ToxR reporter; the functional TLR1 receptor is a TLR1:TLR2 heterodimer, and no TLR1 homodimer function is known. Supporting Evidence: PMID:23155421 All TLR transmembrane domains showed strong homotypic interaction |
| GO:0043235 signaling receptor complex | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA IEA: signaling receptor complex. Reason: TLR1 is part of the TLR1:TLR2 receptor complex (the more specific GO:0035354 is also annotated). 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:0043235 signaling receptor complex | IPI PMID:23155421 Isolated Toll-like receptor transmembrane domains are capabl... | ACCEPT | Summary: IPI: TMD-mediated oligomerization supports signaling receptor complex. Reason: True as a general statement (TLR1 is part of the TLR1:TLR2 receptor complex); the specific TLR1-TLR2 complex term is also annotated with stronger evidence. 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: IDA: TLR2:TLR1 heterodimers are recruited to plasma membrane rafts upon ligand stimulation. Reason: Direct observation of ligand-induced raft recruitment. Supporting Evidence: PMID:16880211 Upon stimulation by the specific ligand, these heterodimers are recruited within lipid rafts |
| GO:0045087 innate immune response | NAS PMID:11095740 The repertoire for pattern recognition of pathogens by the i... | ACCEPT | Summary: NAS: innate immune response (TLR cooperation paper). Reason: TLR1 is a pattern recognition receptor of innate immunity acting with TLR2. 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: NAS: innate immune response (structural review). Reason: Correct. Supporting Evidence: PMID:33576548 Tollβlike receptors (TLRs) are patternβrecognition receptors of the innate immune system that are activated when conserved molecular signatures on microbial or host molecules |
| GO:0045121 membrane raft | IDA PMID:16880211 Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 ... | ACCEPT | Summary: IDA: membrane raft. Reason: Direct observation. 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: UniProt subcellular-location mapping: membrane raft. Reason: Consistent with IDA. Supporting Evidence: PMID:16880211 Upon stimulation by the specific ligand, these heterodimers are recruited within lipid rafts |
| GO:0071723 lipopeptide binding | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA: lipopeptide binding. Reason: TLR1 contacts the lipopeptide directly in the TLR1-TLR2-Pam3CSK4 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:0071723 lipopeptide binding | IEA GO_REF:0000107 | ACCEPT | Summary: Electronic ortholog transfer (rat) of lipopeptide binding. Reason: Correct. Structural evidence further identifies the ligand class: the amide-bound acyl chain of triacylated lipopeptides inserts into the TLR1 channel, so GO:0042497 triacyl lipopeptide binding is recorded as a core function. 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:0071727 cellular response to triacyl bacterial lipopeptide | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA: cellular response to triacyl bacterial lipopeptide. Reason: Core role of TLR1. Supporting Evidence: PMID:12077222 Macrophages from TLR1-deficient (TLR1(-/-)) mice showed impaired proinflammatory cytokine production in response to the 19-kDa lipoprotein and a synthetic triacylated lipopeptide |
| 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: IDA: cellular response to triacyl bacterial lipopeptide. Reason: Core role of TLR1. Supporting Evidence: PMID:16880211 Upon stimulation by the specific ligand, these heterodimers are recruited within lipid rafts |
| GO:0071727 cellular response to triacyl bacterial lipopeptide | IDA PMID:19931471 Recognition of lipopeptide patterns by Toll-like receptor 2-... | ACCEPT | Summary: IDA: cellular response to triacyl bacterial lipopeptide (TLR2 heterodimer structures). Reason: Core role of TLR1; TLR1 pairing confers triacyl specificity on TLR2. Supporting Evidence: PMID:19931471 Its ligand specificity is controlled by whether it heterodimerizes with TLR1 or TLR6 |
| GO:0042497 triacyl lipopeptide binding | IDA PMID:17889651 Crystal structure of the TLR1-TLR2 heterodimer induced by bi... | NEW | Summary: Crystal structure of TLR1-TLR2 with Pam3CSK4 shows the amide-bound acyl chain inserted into a hydrophobic channel in TLR1. Reason: Direct structural evidence that TLR1 itself contacts and binds triacylated lipopeptide; more precise than the existing lipopeptide binding annotations. The TLR6 channel is blocked, which is why TLR1 confers triacyl specificity on TLR2. 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 PMID:19931471 First, the lipid channel of TLR6 is blocked by two phenylalanines |
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Download this section (compressed HTML)Q: GO:0001875 lipopolysaccharide immune receptor activity is currently used (contributes_to) for TLR1 and in GO-CAM 5fb9cc0600000727 for the TLR1:TLR2 complex, whose ligand is triacyl lipopeptide. Should these be moved to GO:0038187 pattern recognition receptor activity, or should GO add a lipopeptide-specific immune receptor activity term parallel to the LPS term?
Q: Is the TLR1:TLR10 heterodimer observed on overexpression formed at endogenous levels in B cells, and does it compete with TLR1:TLR2 for ligand or partner?
Experiment: Quantify endogenous TLR1:TLR2 vs TLR10:TLR2 vs TLR1:TLR10 complexes in primary human B cells and monocytes by proximity ligation or co-immunoprecipitation with and without Pam3CSK4, and measure how the ratio changes the NF-kappaB response.
Hypothesis: TLR10 competes with TLR1 for TLR2 and ligand, tuning the TLR1:TLR2 response in cells where both are expressed.
Type: co-immunoprecipitation / proximity ligation assay
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