CD14 is a leucine-rich-repeat glycoprotein expressed mainly by monocytes and macrophages (weakly by granulocytes). It exists as a glycosylphosphatidylinositol-anchored protein on the outer leaflet of the plasma membrane, concentrated in lipid rafts, and as a soluble form in plasma and other body fluids produced by release of the anchored protein or secretion of an anchor-less form. Its bent LRR solenoid carries an amino-terminal hydrophobic pocket that binds acylated microbial molecules. CD14 accepts monomeric bacterial lipopolysaccharide (LPS) from LPS-binding protein (LBP) and transfers it to the TLR4-MD-2 complex, forming with TLR4 and MD-2 the LPS receptor complex; it similarly delivers di- and triacylated lipopeptides to TLR2-TLR6 and TLR2-TLR1 heterodimers and binds lipoteichoic acid and peptidoglycan. Because it lacks a transmembrane and cytoplasmic domain, CD14 does not itself transmit signals across the membrane, but it greatly sensitises cells to low ligand concentrations. Membrane CD14 is also required for LPS-induced TLR4 dimerization and for Syk/PLCgamma2-dependent endocytosis of TLR4, which enables TRIF-dependent interferon production from endosomes. Soluble CD14 confers LPS responsiveness on CD14-negative cells such as epithelial and endothelial cells. CD14 also binds apoptotic cells and mediates their recognition and clearance by macrophages without triggering inflammation. Mice lacking CD14 are resistant to endotoxic shock.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001530 lipopolysaccharide binding | IBA GO_REF:0000033 | ACCEPT | Summary: CD14 binds monomeric LPS (1-2 molecules per CD14) in an N-terminal hydrophobic pocket; LPS is loaded onto CD14 by LBP. Reason: Direct LPS binding by soluble and membrane CD14 is one of the best-established biochemical properties of the protein (sucrose gradient binding, cross-linking, crystal structure of the ligand pocket) and is the basis of its carrier function. The IBA and IDA rows agree. Supporting Evidence: PMID:7537731 LBP catalyzes LPS binding to sCD14 PMID:7537731 Complexes of LPS with sCD14 do not form large aggregates, consisting of only 1-2 LPS bound to a single sCD14 even at high multiples of LPS to sCD14 PMID:11274165 LPS is cross-linked specifically to TLR4 and MD-2 only when co-expressed with CD14 PMID:23264655 The structure reveals a bent solenoid typical of leucine-rich repeat proteins with an amino-terminal pocket that presumably binds acylated ligands including LPS |
| GO:0001530 lipopolysaccharide binding | IDA PMID:12594207 Lipoteichoic acid (LTA) of Streptococcus pneumoniae and Stap... | ACCEPT | Summary: CD14 binds monomeric LPS (1-2 molecules per CD14) in an N-terminal hydrophobic pocket; LPS is loaded onto CD14 by LBP. Reason: Direct LPS binding by soluble and membrane CD14 is one of the best-established biochemical properties of the protein (sucrose gradient binding, cross-linking, crystal structure of the ligand pocket) and is the basis of its carrier function. The IBA and IDA rows agree. Supporting Evidence: PMID:7537731 LBP catalyzes LPS binding to sCD14 PMID:7537731 Complexes of LPS with sCD14 do not form large aggregates, consisting of only 1-2 LPS bound to a single sCD14 even at high multiples of LPS to sCD14 PMID:11274165 LPS is cross-linked specifically to TLR4 and MD-2 only when co-expressed with CD14 PMID:23264655 The structure reveals a bent solenoid typical of leucine-rich repeat proteins with an amino-terminal pocket that presumably binds acylated ligands including LPS |
| GO:0001819 positive regulation of cytokine production | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetically inferred positive regulation of cytokine production. Reason: Cytokine production is a downstream output of TLR signalling to which CD14 contributes as a ligand carrier; correct but indirect. Supporting Evidence: PMID:1698311 CD14, a differentiation antigen of monocytes, was found to bind complexes of LPS and LBP, and blockade of CD14 with monoclonal antibodies prevented synthesis of TNF-alpha by whole blood incubated with LPS PMID:23880187 CD14 and TLR4 mediate cytokine release induced by LDL(-) in human monocytes |
| GO:0001847 opsonin receptor activity | TAS PMID:2402637 Structure and function of lipopolysaccharide binding protein... | MARK AS OVER ANNOTATED | Summary: Traceable-author statement from a paper on the structure of LBP; LBP-LPS complexes bind monocytes. Reason: The cited abstract concerns LBP and does not name CD14. CD14 does bind LBP-LPS complexes, but the opsonin receptor term requires transmitting a signal across the membrane, which GPI-anchored CD14 cannot do on its own. Its activity toward LBP-loaded ligands is better captured by LPS binding and molecular carrier activity. Supporting Evidence: PMID:2402637 LBP may control the response to LPS under physiologic conditions by forming high-affinity complexes with LPS that bind to monocytes and macrophages, which then secrete tumor necrosis factor PMID:1698311 CD14, a differentiation antigen of monocytes, was found to bind complexes of LPS and LBP, and blockade of CD14 with monoclonal antibodies prevented synthesis of TNF-alpha by whole blood incubated with LPS |
| GO:0001875 lipopolysaccharide immune receptor activity | IDA PMID:15294986 Lipopolysaccharide binding protein binds to triacylated and ... | MODIFY | Summary: CD14 binds LPS and is part of the LPS receptor complex, but it is GPI-anchored and hands LPS on to TLR4-MD-2, which transmits the signal across the membrane. Reason: GO:0001875 is defined as combining with LPS and transmitting the signal across the cell membrane. CD14 has no transmembrane or cytoplasmic domain and its LPS-specific role is ligand extraction and transfer to TLR4-MD-2, after which the signal-transducing receptor is TLR4 (with MD-2). The cited abstract (about LBP and lipopeptides) supports CD14 as a ligand acceptor in receptor complexes. The curator-built GO-CAMs represent this activity of CD14 as molecular carrier activity; the LPS-binding aspect is captured by GO:0001530. The evidence is not disputed, only the term: replace with molecular carrier activity. Proposed replacements: molecular carrier activity Supporting Evidence: PMID:15294986 we were able to show that LBP transfers lipopeptides to CD14 on human monocytes using FACS analysis PMID:27986454 Subsequently, the single LPS molecule bound to CD14 was transferred to TLR4-MD2 in a TLR4-dependent manner PMID:2462937 all monocyte CD14 is joined to the plasma membrane by a phosphatidylinositol phospholipid |
| GO:0002237 response to molecule of bacterial origin | IEA GO_REF:0000107 | ACCEPT | Summary: response to molecule of bacterial origin (ortholog transfer). Reason: CD14 mediates responses to bacterial LPS, lipopeptides and LTA; Cd14-deficient mice resist Gram-negative shock and show reduced bacteraemia. Supporting Evidence: PMID:8612135 CD14-deficient mice were found to be highly resistant to shock induced by either live Gram-negative bacteria or LPS PMID:8612135 CD14-deficient mice also showed dramatically reduced levels of bacteremia |
| GO:0002752 cell surface pattern recognition receptor signaling pathway | IDA PMID:15294986 Lipopolysaccharide binding protein binds to triacylated and ... | ACCEPT | Summary: CD14 enhances TLR2-dependent responses to di- and triacylated lipopeptides by accepting ligand from LBP and presenting it to TLR2 heterodimers. Reason: CD14 performs the ligand-delivery step of cell-surface PRR signalling for both TLR4 and TLR2 heterodimers. Supporting Evidence: PMID:15294986 Activation of Chinese hamster ovary cells transfected with TLR-2 by both lipopeptides was enhanced by cotransfection of CD14 PMID:15294986 we were able to show that LBP transfers lipopeptides to CD14 on human monocytes using FACS analysis PMID:23430250 either LBP or sCD14 can drive ternary complex formation and TLR activation by acting as mobile carriers of triacylated lipopeptides or lipoproteins |
| GO:0005515 protein binding | IPI PMID:16880211 Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 ... | MODIFY | Summary: Interaction of CD14 with TLR2 heterodimers (TLR2/TLR6, TLR2/TLR1) and CD36 in lipid rafts after lipopeptide stimulation. Reason: Protein binding is uninformative. The partners are Toll-like receptors, and the functional context (CD14 as ligand-delivering co-receptor for TLR2 heterodimers) is well supported; Toll-like receptor binding is the informative MF supported by this interaction evidence. Proposed replacements: Toll-like receptor binding Supporting Evidence: PMID:16880211 Upon stimulation by the specific ligand, these heterodimers are recruited within lipid rafts PMID:15294986 Activation of Chinese hamster ovary cells transfected with TLR-2 by both lipopeptides was enhanced by cotransfection of CD14 |
| GO:0005515 protein binding | IPI PMID:16880211 Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 ... | MODIFY | Summary: Interaction of CD14 with TLR2 heterodimers (TLR2/TLR6, TLR2/TLR1) and CD36 in lipid rafts after lipopeptide stimulation. Reason: Protein binding is uninformative. The partners are Toll-like receptors, and the functional context (CD14 as ligand-delivering co-receptor for TLR2 heterodimers) is well supported; Toll-like receptor binding is the informative MF supported by this interaction evidence. Proposed replacements: Toll-like receptor binding Supporting Evidence: PMID:16880211 Upon stimulation by the specific ligand, these heterodimers are recruited within lipid rafts PMID:15294986 Activation of Chinese hamster ovary cells transfected with TLR-2 by both lipopeptides was enhanced by cotransfection of CD14 |
| GO:0005515 protein binding | IPI PMID:20860622 DIP2 disco-interacting protein 2 homolog A (Drosophila) is a... | REMOVE | Summary: Binding of CD14 to follistatin-like 1 (FSTL1/FRP), reported as an endogenous TLR4 agonist. Reason: Generic protein binding is uninformative. The interaction is real in the cited work, but it reflects FSTL1 acting as a ligand presented via CD14 to TLR4, which does not warrant a more specific MF for CD14 beyond its existing ligand-binding and carrier terms. Supporting Evidence: PMID:20860622 molecular interaction analyses using Biacore demonstrated that FRP bound to DIP2A and CD14 |
| GO:0005515 protein binding | IPI PMID:22265692 Follistatin-related protein/follistatin-like 1 evokes an inn... | REMOVE | Summary: Binding of CD14 to follistatin-like 1 (FSTL1/FRP), reported as an endogenous TLR4 agonist. Reason: Generic protein binding is uninformative. The interaction is real in the cited work, but it reflects FSTL1 acting as a ligand presented via CD14 to TLR4, which does not warrant a more specific MF for CD14 beyond its existing ligand-binding and carrier terms. Supporting Evidence: PMID:22265692 Recombinant FRP induced interleukin 6 or interleukin 8 production from target cells in a CD14- and TLR4-dependent manner |
| GO:0005515 protein binding | IPI PMID:25965346 SP-R210 (Myo18A) Isoforms as Intrinsic Modulators of Macroph... | REMOVE | Summary: Co-immunoprecipitation of CD14 with the SP-R210S isoform of MYO18A in macrophages. Reason: Generic protein binding is uninformative and the interaction does not define a molecular function of CD14; the removal does not dispute the reported association. Supporting Evidence: PMID:25965346 These studies revealed a novel physical association between SP-R210S, CD14, and SR-A leading to an enhanced response to LPS |
| GO:0005576 extracellular region | EXP PMID:25497142 27-Hydroxycholesterol up-regulates CD14 and predisposes mono... | ACCEPT | Summary: Secretion of soluble CD14 by THP-1 monocytic cells. Reason: Secreted CD14 is well documented. Supporting Evidence: PMID:25497142 Treatment with 27OHChol also resulted in the enhanced secretion of MMP-9 and soluble CD14 (sCD14) |
| GO:0005576 extracellular region | EXP PMID:2779588 Structural relationship between the soluble and membrane-bou... | ACCEPT | Summary: Soluble CD14 isolated from urine and serum. Reason: Soluble CD14 occurs in serum and urine. Supporting Evidence: PMID:2779588 The soluble form occurring in serum and in supernatants of cultured monocytes thus probably arises by phospholipase-mediated cleaving off the cell surface antigen |
| GO:0005576 extracellular region | HDA PMID:16502470 Human colostrum: identification of minor proteins in the aqu... | ACCEPT | Summary: CD14 detected in human colostrum by proteomics. Reason: Soluble CD14 is an abundant body-fluid protein; consistent with other evidence for extracellular sCD14. |
| GO:0005576 extracellular region | IDA PMID:23430250 Human lipopolysaccharide-binding protein (LBP) and CD14 inde... | ACCEPT | Summary: Soluble CD14 functions extracellularly as a mobile lipopeptide carrier for TLR1/TLR2. Reason: Direct functional evidence that sCD14 acts in the extracellular milieu. Supporting Evidence: PMID:23430250 either LBP or sCD14 can drive ternary complex formation and TLR activation by acting as mobile carriers of triacylated lipopeptides or lipoproteins |
| GO:0005576 extracellular region | IDA PMID:7537731 Lipopolysaccharide binding protein-mediated complexation of ... | ACCEPT | Summary: Soluble CD14 binds LPS delivered by LBP in solution. Reason: Direct evidence for the extracellular ligand-binding activity of sCD14. Supporting Evidence: PMID:7537731 LBP catalyzes LPS binding to sCD14 |
| GO:0005576 extracellular region | IEA GO_REF:0000044 | ACCEPT | Summary: Soluble/secreted CD14 is extracellular (UniProt subcellular location mapping). Reason: Consistent with experimental evidence for soluble CD14. Supporting Evidence: PMID:2779588 The soluble form occurring in serum and in supernatants of cultured monocytes thus probably arises by phospholipase-mediated cleaving off the cell surface antigen PMID:3385210 the CD14-expressing neuroglioma cell line, which had been transfected with a single CD14 cDNA, released a soluble form of CD14 into the supernatant |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-166041 | ACCEPT | Summary: Reactome places the CD14-containing complex (Reactome:R-HSA-166041) in the extracellular region, reflecting soluble CD14 or the extracellular face of the receptor complex. Reason: Soluble CD14 in serum and culture supernatants is well documented, and all of CD14 lies on the extracellular side of the membrane. Supporting Evidence: PMID:2779588 The soluble form occurring in serum and in supernatants of cultured monocytes thus probably arises by phospholipase-mediated cleaving off the cell surface antigen |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-166072 | ACCEPT | Summary: Reactome places the CD14-containing complex (Reactome:R-HSA-166072) in the extracellular region, reflecting soluble CD14 or the extracellular face of the receptor complex. Reason: Soluble CD14 in serum and culture supernatants is well documented, and all of CD14 lies on the extracellular side of the membrane. Supporting Evidence: PMID:2779588 The soluble form occurring in serum and in supernatants of cultured monocytes thus probably arises by phospholipase-mediated cleaving off the cell surface antigen |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-166082 | ACCEPT | Summary: Reactome places the CD14-containing complex (Reactome:R-HSA-166082) in the extracellular region, reflecting soluble CD14 or the extracellular face of the receptor complex. Reason: Soluble CD14 in serum and culture supernatants is well documented, and all of CD14 lies on the extracellular side of the membrane. Supporting Evidence: PMID:2779588 The soluble form occurring in serum and in supernatants of cultured monocytes thus probably arises by phospholipase-mediated cleaving off the cell surface antigen |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-166091 | ACCEPT | Summary: Reactome places the CD14-containing complex (Reactome:R-HSA-166091) in the extracellular region, reflecting soluble CD14 or the extracellular face of the receptor complex. Reason: Soluble CD14 in serum and culture supernatants is well documented, and all of CD14 lies on the extracellular side of the membrane. Supporting Evidence: PMID:2779588 The soluble form occurring in serum and in supernatants of cultured monocytes thus probably arises by phospholipase-mediated cleaving off the cell surface antigen |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-166119 | ACCEPT | Summary: Reactome places the CD14-containing complex (Reactome:R-HSA-166119) in the extracellular region, reflecting soluble CD14 or the extracellular face of the receptor complex. Reason: Soluble CD14 in serum and culture supernatants is well documented, and all of CD14 lies on the extracellular side of the membrane. Supporting Evidence: PMID:2779588 The soluble form occurring in serum and in supernatants of cultured monocytes thus probably arises by phospholipase-mediated cleaving off the cell surface antigen |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-166284 | ACCEPT | Summary: Reactome places the CD14-containing complex (Reactome:R-HSA-166284) in the extracellular region, reflecting soluble CD14 or the extracellular face of the receptor complex. Reason: Soluble CD14 in serum and culture supernatants is well documented, and all of CD14 lies on the extracellular side of the membrane. Supporting Evidence: PMID:2779588 The soluble form occurring in serum and in supernatants of cultured monocytes thus probably arises by phospholipase-mediated cleaving off the cell surface antigen |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-166286 | ACCEPT | Summary: Reactome places the CD14-containing complex (Reactome:R-HSA-166286) in the extracellular region, reflecting soluble CD14 or the extracellular face of the receptor complex. Reason: Soluble CD14 in serum and culture supernatants is well documented, and all of CD14 lies on the extracellular side of the membrane. Supporting Evidence: PMID:2779588 The soluble form occurring in serum and in supernatants of cultured monocytes thus probably arises by phospholipase-mediated cleaving off the cell surface antigen |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-166362 | ACCEPT | Summary: Reactome places the CD14-containing complex (Reactome:R-HSA-166362) in the extracellular region, reflecting soluble CD14 or the extracellular face of the receptor complex. Reason: Soluble CD14 in serum and culture supernatants is well documented, and all of CD14 lies on the extracellular side of the membrane. Supporting Evidence: PMID:2779588 The soluble form occurring in serum and in supernatants of cultured monocytes thus probably arises by phospholipase-mediated cleaving off the cell surface antigen |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-166363 | ACCEPT | Summary: Reactome places the CD14-containing complex (Reactome:R-HSA-166363) in the extracellular region, reflecting soluble CD14 or the extracellular face of the receptor complex. Reason: Soluble CD14 in serum and culture supernatants is well documented, and all of CD14 lies on the extracellular side of the membrane. Supporting Evidence: PMID:2779588 The soluble form occurring in serum and in supernatants of cultured monocytes thus probably arises by phospholipase-mediated cleaving off the cell surface antigen |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-169719 | ACCEPT | Summary: Reactome places the CD14-containing complex (Reactome:R-HSA-169719) in the extracellular region, reflecting soluble CD14 or the extracellular face of the receptor complex. Reason: Soluble CD14 in serum and culture supernatants is well documented, and all of CD14 lies on the extracellular side of the membrane. Supporting Evidence: PMID:2779588 The soluble form occurring in serum and in supernatants of cultured monocytes thus probably arises by phospholipase-mediated cleaving off the cell surface antigen |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2201293 | ACCEPT | Summary: Reactome places the CD14-containing complex (Reactome:R-HSA-2201293) in the extracellular region, reflecting soluble CD14 or the extracellular face of the receptor complex. Reason: Soluble CD14 in serum and culture supernatants is well documented, and all of CD14 lies on the extracellular side of the membrane. Supporting Evidence: PMID:2779588 The soluble form occurring in serum and in supernatants of cultured monocytes thus probably arises by phospholipase-mediated cleaving off the cell surface antigen |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2201316 | ACCEPT | Summary: Reactome places the CD14-containing complex (Reactome:R-HSA-2201316) in the extracellular region, reflecting soluble CD14 or the extracellular face of the receptor complex. Reason: Soluble CD14 in serum and culture supernatants is well documented, and all of CD14 lies on the extracellular side of the membrane. Supporting Evidence: PMID:2779588 The soluble form occurring in serum and in supernatants of cultured monocytes thus probably arises by phospholipase-mediated cleaving off the cell surface antigen |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2201322 | ACCEPT | Summary: Reactome places the CD14-containing complex (Reactome:R-HSA-2201322) in the extracellular region, reflecting soluble CD14 or the extracellular face of the receptor complex. Reason: Soluble CD14 in serum and culture supernatants is well documented, and all of CD14 lies on the extracellular side of the membrane. Supporting Evidence: PMID:2779588 The soluble form occurring in serum and in supernatants of cultured monocytes thus probably arises by phospholipase-mediated cleaving off the cell surface antigen |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2262775 | ACCEPT | Summary: Reactome places the CD14-containing complex (Reactome:R-HSA-2262775) in the extracellular region, reflecting soluble CD14 or the extracellular face of the receptor complex. Reason: Soluble CD14 in serum and culture supernatants is well documented, and all of CD14 lies on the extracellular side of the membrane. Supporting Evidence: PMID:2779588 The soluble form occurring in serum and in supernatants of cultured monocytes thus probably arises by phospholipase-mediated cleaving off the cell surface antigen |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2262777 | ACCEPT | Summary: Reactome places the CD14-containing complex (Reactome:R-HSA-2262777) in the extracellular region, reflecting soluble CD14 or the extracellular face of the receptor complex. Reason: Soluble CD14 in serum and culture supernatants is well documented, and all of CD14 lies on the extracellular side of the membrane. Supporting Evidence: PMID:2779588 The soluble form occurring in serum and in supernatants of cultured monocytes thus probably arises by phospholipase-mediated cleaving off the cell surface antigen |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2559414 | ACCEPT | Summary: Reactome places the CD14-containing complex (Reactome:R-HSA-2559414) in the extracellular region, reflecting soluble CD14 or the extracellular face of the receptor complex. Reason: Soluble CD14 in serum and culture supernatants is well documented, and all of CD14 lies on the extracellular side of the membrane. Supporting Evidence: PMID:2779588 The soluble form occurring in serum and in supernatants of cultured monocytes thus probably arises by phospholipase-mediated cleaving off the cell surface antigen |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2559439 | ACCEPT | Summary: Reactome places the CD14-containing complex (Reactome:R-HSA-2559439) in the extracellular region, reflecting soluble CD14 or the extracellular face of the receptor complex. Reason: Soluble CD14 in serum and culture supernatants is well documented, and all of CD14 lies on the extracellular side of the membrane. Supporting Evidence: PMID:2779588 The soluble form occurring in serum and in supernatants of cultured monocytes thus probably arises by phospholipase-mediated cleaving off the cell surface antigen |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5602353 | ACCEPT | Summary: Reactome places the CD14-containing complex (Reactome:R-HSA-5602353) in the extracellular region, reflecting soluble CD14 or the extracellular face of the receptor complex. Reason: Soluble CD14 in serum and culture supernatants is well documented, and all of CD14 lies on the extracellular side of the membrane. Supporting Evidence: PMID:2779588 The soluble form occurring in serum and in supernatants of cultured monocytes thus probably arises by phospholipase-mediated cleaving off the cell surface antigen |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5602383 | ACCEPT | Summary: Reactome places the CD14-containing complex (Reactome:R-HSA-5602383) in the extracellular region, reflecting soluble CD14 or the extracellular face of the receptor complex. Reason: Soluble CD14 in serum and culture supernatants is well documented, and all of CD14 lies on the extracellular side of the membrane. Supporting Evidence: PMID:2779588 The soluble form occurring in serum and in supernatants of cultured monocytes thus probably arises by phospholipase-mediated cleaving off the cell surface antigen |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5602606 | ACCEPT | Summary: Reactome places the CD14-containing complex (Reactome:R-HSA-5602606) in the extracellular region, reflecting soluble CD14 or the extracellular face of the receptor complex. Reason: Soluble CD14 in serum and culture supernatants is well documented, and all of CD14 lies on the extracellular side of the membrane. Supporting Evidence: PMID:2779588 The soluble form occurring in serum and in supernatants of cultured monocytes thus probably arises by phospholipase-mediated cleaving off the cell surface antigen |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-8869694 | ACCEPT | Summary: Reactome places the CD14-containing complex (Reactome:R-HSA-8869694) in the extracellular region, reflecting soluble CD14 or the extracellular face of the receptor complex. Reason: Soluble CD14 in serum and culture supernatants is well documented, and all of CD14 lies on the extracellular side of the membrane. Supporting Evidence: PMID:2779588 The soluble form occurring in serum and in supernatants of cultured monocytes thus probably arises by phospholipase-mediated cleaving off the cell surface antigen |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-937022 | ACCEPT | Summary: Reactome places the CD14-containing complex (Reactome:R-HSA-937022) in the extracellular region, reflecting soluble CD14 or the extracellular face of the receptor complex. Reason: Soluble CD14 in serum and culture supernatants is well documented, and all of CD14 lies on the extracellular side of the membrane. Supporting Evidence: PMID:2779588 The soluble form occurring in serum and in supernatants of cultured monocytes thus probably arises by phospholipase-mediated cleaving off the cell surface antigen |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-937059 | ACCEPT | Summary: Reactome places the CD14-containing complex (Reactome:R-HSA-937059) in the extracellular region, reflecting soluble CD14 or the extracellular face of the receptor complex. Reason: Soluble CD14 in serum and culture supernatants is well documented, and all of CD14 lies on the extracellular side of the membrane. Supporting Evidence: PMID:2779588 The soluble form occurring in serum and in supernatants of cultured monocytes thus probably arises by phospholipase-mediated cleaving off the cell surface antigen |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-937079 | ACCEPT | Summary: Reactome places the CD14-containing complex (Reactome:R-HSA-937079) in the extracellular region, reflecting soluble CD14 or the extracellular face of the receptor complex. Reason: Soluble CD14 in serum and culture supernatants is well documented, and all of CD14 lies on the extracellular side of the membrane. Supporting Evidence: PMID:2779588 The soluble form occurring in serum and in supernatants of cultured monocytes thus probably arises by phospholipase-mediated cleaving off the cell surface antigen |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9836227 | ACCEPT | Summary: Reactome places the CD14-containing complex (Reactome:R-HSA-9836227) in the extracellular region, reflecting soluble CD14 or the extracellular face of the receptor complex. Reason: Soluble CD14 in serum and culture supernatants is well documented, and all of CD14 lies on the extracellular side of the membrane. Supporting Evidence: PMID:2779588 The soluble form occurring in serum and in supernatants of cultured monocytes thus probably arises by phospholipase-mediated cleaving off the cell surface antigen |
| GO:0005794 Golgi apparatus | IDA PMID:16880211 Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 ... | KEEP AS NON CORE | Summary: After ligand stimulation TLR2 receptor clusters, including CD14, are trafficked to the Golgi apparatus. Reason: Golgi localisation is a transient, ligand-induced trafficking destination (and the biosynthetic route of any secreted glycoprotein), not where CD14 acts. Supporting Evidence: PMID:16880211 All TLR2 receptor clusters accumulate in lipid rafts and are targeted to the Golgi apparatus |
| GO:0005794 Golgi apparatus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: After ligand stimulation TLR2 receptor clusters, including CD14, are trafficked to the Golgi apparatus. Reason: Golgi localisation is a transient, ligand-induced trafficking destination (and the biosynthetic route of any secreted glycoprotein), not where CD14 acts. 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:1698311 CD14, a receptor for complexes of lipopolysaccharide (LPS) a... | ACCEPT | Summary: Cell-surface CD14 on monocytes binds LPS-LBP complexes. Reason: Membrane CD14 is the cell-surface acceptor of LPS-LBP complexes. Supporting Evidence: PMID:1698311 CD14, a differentiation antigen of monocytes, was found to bind complexes of LPS and LBP, and blockade of CD14 with monoclonal antibodies prevented synthesis of TNF-alpha by whole blood incubated with LPS |
| GO:0005886 plasma membrane | EXP PMID:2462937 Monocyte antigen CD14 is a phospholipid anchored membrane pr... | ACCEPT | Summary: CD14 is a GPI-anchored plasma membrane protein on monocytes. Reason: PI-PLC release and absence from PNH monocytes demonstrate GPI anchoring to the plasma membrane. Supporting Evidence: PMID:2462937 all monocyte CD14 is joined to the plasma membrane by a phosphatidylinositol phospholipid |
| GO:0005886 plasma membrane | EXP PMID:3385210 The monocyte differentiation antigen, CD14, is anchored to t... | ACCEPT | Summary: CD14 is a GPI-anchored plasma membrane protein on monocytes. Reason: PI-PLC release and absence from PNH monocytes demonstrate GPI anchoring to the plasma membrane. Supporting Evidence: PMID:3385210 Treatment of monocytes as well as a CD14-expressing neuroglioma cell line with PI-phospholipase C removed CD14 from the cell surface |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular location mapping (cell membrane, GPI-anchor). Reason: Supported by experimental evidence. Supporting Evidence: PMID:2462937 all monocyte CD14 is joined to the plasma membrane by a phosphatidylinositol phospholipid |
| GO:0005886 plasma membrane | TAS PMID:9548256 Human CD14 mediates recognition and phagocytosis of apoptoti... | ACCEPT | Summary: CD14 on the macrophage surface recognises apoptotic cells. Reason: Plasma membrane localisation is correct. Supporting Evidence: PMID:9548256 the glycosylphosphatidylinositol-linked plasma-membrane glycoprotein CD14 on the surface of human macrophages is important for the recognition and clearance of apoptotic cells |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-166038 | ACCEPT | Summary: Reactome places membrane CD14 in the plasma membrane in the TLR reaction Reactome:R-HSA-166038. Reason: Membrane CD14 is GPI-anchored in the plasma membrane where it transfers ligands to TLR4 and TLR2 heterodimers. Supporting Evidence: PMID:2462937 all monocyte CD14 is joined to the plasma membrane by a phosphatidylinositol phospholipid |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-166041 | ACCEPT | Summary: Reactome places membrane CD14 in the plasma membrane in the TLR reaction Reactome:R-HSA-166041. Reason: Membrane CD14 is GPI-anchored in the plasma membrane where it transfers ligands to TLR4 and TLR2 heterodimers. Supporting Evidence: PMID:2462937 all monocyte CD14 is joined to the plasma membrane by a phosphatidylinositol phospholipid |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-166072 | ACCEPT | Summary: Reactome places membrane CD14 in the plasma membrane in the TLR reaction Reactome:R-HSA-166072. Reason: Membrane CD14 is GPI-anchored in the plasma membrane where it transfers ligands to TLR4 and TLR2 heterodimers. Supporting Evidence: PMID:2462937 all monocyte CD14 is joined to the plasma membrane by a phosphatidylinositol phospholipid |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-166082 | ACCEPT | Summary: Reactome places membrane CD14 in the plasma membrane in the TLR reaction Reactome:R-HSA-166082. Reason: Membrane CD14 is GPI-anchored in the plasma membrane where it transfers ligands to TLR4 and TLR2 heterodimers. Supporting Evidence: PMID:2462937 all monocyte CD14 is joined to the plasma membrane by a phosphatidylinositol phospholipid |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-166091 | ACCEPT | Summary: Reactome places membrane CD14 in the plasma membrane in the TLR reaction Reactome:R-HSA-166091. Reason: Membrane CD14 is GPI-anchored in the plasma membrane where it transfers ligands to TLR4 and TLR2 heterodimers. Supporting Evidence: PMID:2462937 all monocyte CD14 is joined to the plasma membrane by a phosphatidylinositol phospholipid |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-166119 | ACCEPT | Summary: Reactome places membrane CD14 in the plasma membrane in the TLR reaction Reactome:R-HSA-166119. Reason: Membrane CD14 is GPI-anchored in the plasma membrane where it transfers ligands to TLR4 and TLR2 heterodimers. Supporting Evidence: PMID:2462937 all monocyte CD14 is joined to the plasma membrane by a phosphatidylinositol phospholipid |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-166284 | ACCEPT | Summary: Reactome places membrane CD14 in the plasma membrane in the TLR reaction Reactome:R-HSA-166284. Reason: Membrane CD14 is GPI-anchored in the plasma membrane where it transfers ligands to TLR4 and TLR2 heterodimers. Supporting Evidence: PMID:2462937 all monocyte CD14 is joined to the plasma membrane by a phosphatidylinositol phospholipid |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-166286 | ACCEPT | Summary: Reactome places membrane CD14 in the plasma membrane in the TLR reaction Reactome:R-HSA-166286. Reason: Membrane CD14 is GPI-anchored in the plasma membrane where it transfers ligands to TLR4 and TLR2 heterodimers. Supporting Evidence: PMID:2462937 all monocyte CD14 is joined to the plasma membrane by a phosphatidylinositol phospholipid |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-166362 | ACCEPT | Summary: Reactome places membrane CD14 in the plasma membrane in the TLR reaction Reactome:R-HSA-166362. Reason: Membrane CD14 is GPI-anchored in the plasma membrane where it transfers ligands to TLR4 and TLR2 heterodimers. Supporting Evidence: PMID:2462937 all monocyte CD14 is joined to the plasma membrane by a phosphatidylinositol phospholipid |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-166363 | ACCEPT | Summary: Reactome places membrane CD14 in the plasma membrane in the TLR reaction Reactome:R-HSA-166363. Reason: Membrane CD14 is GPI-anchored in the plasma membrane where it transfers ligands to TLR4 and TLR2 heterodimers. Supporting Evidence: PMID:2462937 all monocyte CD14 is joined to the plasma membrane by a phosphatidylinositol phospholipid |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-168950 | ACCEPT | Summary: Reactome places membrane CD14 in the plasma membrane in the TLR reaction Reactome:R-HSA-168950. Reason: Membrane CD14 is GPI-anchored in the plasma membrane where it transfers ligands to TLR4 and TLR2 heterodimers. Supporting Evidence: PMID:2462937 all monocyte CD14 is joined to the plasma membrane by a phosphatidylinositol phospholipid |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-168951 | ACCEPT | Summary: Reactome places membrane CD14 in the plasma membrane in the TLR reaction Reactome:R-HSA-168951. Reason: Membrane CD14 is GPI-anchored in the plasma membrane where it transfers ligands to TLR4 and TLR2 heterodimers. Supporting Evidence: PMID:2462937 all monocyte CD14 is joined to the plasma membrane by a phosphatidylinositol phospholipid |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2201293 | ACCEPT | Summary: Reactome places membrane CD14 in the plasma membrane in the TLR reaction Reactome:R-HSA-2201293. Reason: Membrane CD14 is GPI-anchored in the plasma membrane where it transfers ligands to TLR4 and TLR2 heterodimers. Supporting Evidence: PMID:2462937 all monocyte CD14 is joined to the plasma membrane by a phosphatidylinositol phospholipid |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2201316 | ACCEPT | Summary: Reactome places membrane CD14 in the plasma membrane in the TLR reaction Reactome:R-HSA-2201316. Reason: Membrane CD14 is GPI-anchored in the plasma membrane where it transfers ligands to TLR4 and TLR2 heterodimers. Supporting Evidence: PMID:2462937 all monocyte CD14 is joined to the plasma membrane by a phosphatidylinositol phospholipid |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2201322 | ACCEPT | Summary: Reactome places membrane CD14 in the plasma membrane in the TLR reaction Reactome:R-HSA-2201322. Reason: Membrane CD14 is GPI-anchored in the plasma membrane where it transfers ligands to TLR4 and TLR2 heterodimers. Supporting Evidence: PMID:2462937 all monocyte CD14 is joined to the plasma membrane by a phosphatidylinositol phospholipid |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2262775 | ACCEPT | Summary: Reactome places membrane CD14 in the plasma membrane in the TLR reaction Reactome:R-HSA-2262775. Reason: Membrane CD14 is GPI-anchored in the plasma membrane where it transfers ligands to TLR4 and TLR2 heterodimers. Supporting Evidence: PMID:2462937 all monocyte CD14 is joined to the plasma membrane by a phosphatidylinositol phospholipid |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2262777 | ACCEPT | Summary: Reactome places membrane CD14 in the plasma membrane in the TLR reaction Reactome:R-HSA-2262777. Reason: Membrane CD14 is GPI-anchored in the plasma membrane where it transfers ligands to TLR4 and TLR2 heterodimers. Supporting Evidence: PMID:2462937 all monocyte CD14 is joined to the plasma membrane by a phosphatidylinositol phospholipid |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2559414 | ACCEPT | Summary: Reactome places membrane CD14 in the plasma membrane in the TLR reaction Reactome:R-HSA-2559414. Reason: Membrane CD14 is GPI-anchored in the plasma membrane where it transfers ligands to TLR4 and TLR2 heterodimers. Supporting Evidence: PMID:2462937 all monocyte CD14 is joined to the plasma membrane by a phosphatidylinositol phospholipid |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2559439 | ACCEPT | Summary: Reactome places membrane CD14 in the plasma membrane in the TLR reaction Reactome:R-HSA-2559439. Reason: Membrane CD14 is GPI-anchored in the plasma membrane where it transfers ligands to TLR4 and TLR2 heterodimers. Supporting Evidence: PMID:2462937 all monocyte CD14 is joined to the plasma membrane by a phosphatidylinositol phospholipid |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2559464 | ACCEPT | Summary: Reactome places membrane CD14 in the plasma membrane in the TLR reaction Reactome:R-HSA-2559464. Reason: Membrane CD14 is GPI-anchored in the plasma membrane where it transfers ligands to TLR4 and TLR2 heterodimers. Supporting Evidence: PMID:2462937 all monocyte CD14 is joined to the plasma membrane by a phosphatidylinositol phospholipid |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2559468 | ACCEPT | Summary: Reactome places membrane CD14 in the plasma membrane in the TLR reaction Reactome:R-HSA-2559468. Reason: Membrane CD14 is GPI-anchored in the plasma membrane where it transfers ligands to TLR4 and TLR2 heterodimers. Supporting Evidence: PMID:2462937 all monocyte CD14 is joined to the plasma membrane by a phosphatidylinositol phospholipid |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5602353 | ACCEPT | Summary: Reactome places membrane CD14 in the plasma membrane in the TLR reaction Reactome:R-HSA-5602353. Reason: Membrane CD14 is GPI-anchored in the plasma membrane where it transfers ligands to TLR4 and TLR2 heterodimers. Supporting Evidence: PMID:2462937 all monocyte CD14 is joined to the plasma membrane by a phosphatidylinositol phospholipid |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5602383 | ACCEPT | Summary: Reactome places membrane CD14 in the plasma membrane in the TLR reaction Reactome:R-HSA-5602383. Reason: Membrane CD14 is GPI-anchored in the plasma membrane where it transfers ligands to TLR4 and TLR2 heterodimers. Supporting Evidence: PMID:2462937 all monocyte CD14 is joined to the plasma membrane by a phosphatidylinositol phospholipid |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5602606 | ACCEPT | Summary: Reactome places membrane CD14 in the plasma membrane in the TLR reaction Reactome:R-HSA-5602606. Reason: Membrane CD14 is GPI-anchored in the plasma membrane where it transfers ligands to TLR4 and TLR2 heterodimers. Supporting Evidence: PMID:2462937 all monocyte CD14 is joined to the plasma membrane by a phosphatidylinositol phospholipid |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6798743 | ACCEPT | Summary: Reactome places membrane CD14 in the plasma membrane in the TLR reaction Reactome:R-HSA-6798743. Reason: Membrane CD14 is GPI-anchored in the plasma membrane where it transfers ligands to TLR4 and TLR2 heterodimers. Supporting Evidence: PMID:2462937 all monocyte CD14 is joined to the plasma membrane by a phosphatidylinositol phospholipid |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-937022 | ACCEPT | Summary: Reactome places membrane CD14 in the plasma membrane in the TLR reaction Reactome:R-HSA-937022. Reason: Membrane CD14 is GPI-anchored in the plasma membrane where it transfers ligands to TLR4 and TLR2 heterodimers. Supporting Evidence: PMID:2462937 all monocyte CD14 is joined to the plasma membrane by a phosphatidylinositol phospholipid |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-937059 | ACCEPT | Summary: Reactome places membrane CD14 in the plasma membrane in the TLR reaction Reactome:R-HSA-937059. Reason: Membrane CD14 is GPI-anchored in the plasma membrane where it transfers ligands to TLR4 and TLR2 heterodimers. Supporting Evidence: PMID:2462937 all monocyte CD14 is joined to the plasma membrane by a phosphatidylinositol phospholipid |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-937079 | ACCEPT | Summary: Reactome places membrane CD14 in the plasma membrane in the TLR reaction Reactome:R-HSA-937079. Reason: Membrane CD14 is GPI-anchored in the plasma membrane where it transfers ligands to TLR4 and TLR2 heterodimers. Supporting Evidence: PMID:2462937 all monocyte CD14 is joined to the plasma membrane by a phosphatidylinositol phospholipid |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9836227 | ACCEPT | Summary: Reactome places membrane CD14 in the plasma membrane in the TLR reaction Reactome:R-HSA-9836227. Reason: Membrane CD14 is GPI-anchored in the plasma membrane where it transfers ligands to TLR4 and TLR2 heterodimers. Supporting Evidence: PMID:2462937 all monocyte CD14 is joined to the plasma membrane by a phosphatidylinositol phospholipid |
| GO:0006898 receptor-mediated endocytosis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred receptor-mediated endocytosis. Reason: CD14 is required for, and drives via Syk/PLCgamma2, the LPS-induced endocytosis of TLR4; the more precise statement is regulation of endocytosis (GO:0045807). Supporting Evidence: PMID:22078883 the plasma membrane localized Pattern Recognition Receptor (PRR) CD14 is required for the microbe-induced endocytosis of TLR4 |
| GO:0006909 phagocytosis | TAS PMID:9548256 Human CD14 mediates recognition and phagocytosis of apoptoti... | MODIFY | Summary: CD14 on macrophages recognises apoptotic cells and triggers their phagocytosis. Reason: Correct but general; the evidence is specifically about recognition and clearance of apoptotic cells, which apoptotic cell clearance captures. Proposed replacements: apoptotic cell clearance Supporting Evidence: PMID:9548256 Here we show that apoptotic cells interact with CD14, triggering phagocytosis of the apoptotic cells PMID:9548256 the glycosylphosphatidylinositol-linked plasma-membrane glycoprotein CD14 on the surface of human macrophages is important for the recognition and clearance of apoptotic cells |
| GO:0006915 apoptotic process | TAS PMID:9548256 Human CD14 mediates recognition and phagocytosis of apoptoti... | REMOVE | Summary: Traceable-author statement from a study of CD14-mediated recognition of apoptotic cells. Reason: The cited study shows CD14 on macrophages recognising and clearing apoptotic cells; CD14 does not execute or regulate apoptosis of the cell it resides in. The relevant process is apoptotic cell clearance. Supporting Evidence: PMID:9548256 Here we show that apoptotic cells interact with CD14, triggering phagocytosis of the apoptotic cells |
| GO:0007166 cell surface receptor signaling pathway | TAS PMID:8798531 CD14 is a cell-activating receptor for bacterial peptidoglyc... | MODIFY | Summary: CD14 confers responsiveness to peptidoglycan and LPS (NF-kappaB activation) in transfected 70Z/3 cells. Reason: Correct but very general. The signalling CD14 contributes to is initiated by microbial ligands at cell-surface PRRs, so the more informative term is cell surface pattern recognition receptor signaling pathway, which is also supported by IDA. Proposed replacements: cell surface pattern recognition receptor signaling pathway Supporting Evidence: PMID:8798531 Both peptidoglycan- and endotoxin-induced activation of NF-kappaB were inhibited by anti-CD14 mAb |
| GO:0009617 response to bacterium | IEA GO_REF:0000107 | ACCEPT | Summary: response to bacterium (ortholog transfer). Reason: CD14 mediates responses to bacterial LPS, lipopeptides and LTA; Cd14-deficient mice resist Gram-negative shock and show reduced bacteraemia. Supporting Evidence: PMID:8612135 CD14-deficient mice were found to be highly resistant to shock induced by either live Gram-negative bacteria or LPS PMID:8612135 CD14-deficient mice also showed dramatically reduced levels of bacteremia |
| GO:0009897 external side of plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: CD14 is GPI-anchored in the outer leaflet of the plasma membrane. Reason: External side of the plasma membrane is the most precise location for GPI-anchored membrane CD14; the IBA, IDA and IEA rows agree. Supporting Evidence: PMID:3385210 Treatment of monocytes as well as a CD14-expressing neuroglioma cell line with PI-phospholipase C removed CD14 from the cell surface PMID:2462937 all monocyte CD14 is joined to the plasma membrane by a phosphatidylinositol phospholipid |
| GO:0009897 external side of plasma membrane | IDA PMID:3385210 The monocyte differentiation antigen, CD14, is anchored to t... | ACCEPT | Summary: CD14 is GPI-anchored in the outer leaflet of the plasma membrane. Reason: External side of the plasma membrane is the most precise location for GPI-anchored membrane CD14; the IBA, IDA and IEA rows agree. Supporting Evidence: PMID:3385210 Treatment of monocytes as well as a CD14-expressing neuroglioma cell line with PI-phospholipase C removed CD14 from the cell surface PMID:2462937 all monocyte CD14 is joined to the plasma membrane by a phosphatidylinositol phospholipid |
| GO:0009897 external side of plasma membrane | IEA GO_REF:0000107 | ACCEPT | Summary: CD14 is GPI-anchored in the outer leaflet of the plasma membrane. Reason: External side of the plasma membrane is the most precise location for GPI-anchored membrane CD14; the IBA, IDA and IEA rows agree. Supporting Evidence: PMID:3385210 Treatment of monocytes as well as a CD14-expressing neuroglioma cell line with PI-phospholipase C removed CD14 from the cell surface PMID:2462937 all monocyte CD14 is joined to the plasma membrane by a phosphatidylinositol phospholipid |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-166168 | KEEP AS NON CORE | Summary: Reactome places CD14 with internalised TLR4:MD-2:LPS on the endosome membrane (Reactome:R-HSA-166168). Reason: CD14 drives LPS-induced endocytosis of TLR4 and delivers it to endosomes for TRIF signalling, so CD14 plausibly accompanies the complex into endosomes. Its primary site of action is the plasma membrane. Supporting Evidence: PMID:22078883 the plasma membrane localized Pattern Recognition Receptor (PRR) CD14 is required for the microbe-induced endocytosis of TLR4 PMID:22078883 This cascade begins with CD14 transporting LPS to TLR4, and culminates with CD14 delivering TLR4 to the endosomal signaling machinery that is needed to induce IFN expression file:human/CD14/CD14-deep-research-falcon.md Following ligand engagement, CD14 facilitates internalization of the TLR4/MD-2 complex from the plasma membrane into early endosomes |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-166175 | KEEP AS NON CORE | Summary: Reactome places CD14 with internalised TLR4:MD-2:LPS on the endosome membrane (Reactome:R-HSA-166175). Reason: CD14 drives LPS-induced endocytosis of TLR4 and delivers it to endosomes for TRIF signalling, so CD14 plausibly accompanies the complex into endosomes. Its primary site of action is the plasma membrane. Supporting Evidence: PMID:22078883 the plasma membrane localized Pattern Recognition Receptor (PRR) CD14 is required for the microbe-induced endocytosis of TLR4 PMID:22078883 This cascade begins with CD14 transporting LPS to TLR4, and culminates with CD14 delivering TLR4 to the endosomal signaling machinery that is needed to induce IFN expression file:human/CD14/CD14-deep-research-falcon.md Following ligand engagement, CD14 facilitates internalization of the TLR4/MD-2 complex from the plasma membrane into early endosomes |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-166245 | KEEP AS NON CORE | Summary: Reactome places CD14 with internalised TLR4:MD-2:LPS on the endosome membrane (Reactome:R-HSA-166245). Reason: CD14 drives LPS-induced endocytosis of TLR4 and delivers it to endosomes for TRIF signalling, so CD14 plausibly accompanies the complex into endosomes. Its primary site of action is the plasma membrane. Supporting Evidence: PMID:22078883 the plasma membrane localized Pattern Recognition Receptor (PRR) CD14 is required for the microbe-induced endocytosis of TLR4 PMID:22078883 This cascade begins with CD14 transporting LPS to TLR4, and culminates with CD14 delivering TLR4 to the endosomal signaling machinery that is needed to induce IFN expression file:human/CD14/CD14-deep-research-falcon.md Following ligand engagement, CD14 facilitates internalization of the TLR4/MD-2 complex from the plasma membrane into early endosomes |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-166271 | KEEP AS NON CORE | Summary: Reactome places CD14 with internalised TLR4:MD-2:LPS on the endosome membrane (Reactome:R-HSA-166271). Reason: CD14 drives LPS-induced endocytosis of TLR4 and delivers it to endosomes for TRIF signalling, so CD14 plausibly accompanies the complex into endosomes. Its primary site of action is the plasma membrane. Supporting Evidence: PMID:22078883 the plasma membrane localized Pattern Recognition Receptor (PRR) CD14 is required for the microbe-induced endocytosis of TLR4 PMID:22078883 This cascade begins with CD14 transporting LPS to TLR4, and culminates with CD14 delivering TLR4 to the endosomal signaling machinery that is needed to induce IFN expression file:human/CD14/CD14-deep-research-falcon.md Following ligand engagement, CD14 facilitates internalization of the TLR4/MD-2 complex from the plasma membrane into early endosomes |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-168915 | KEEP AS NON CORE | Summary: Reactome places CD14 with internalised TLR4:MD-2:LPS on the endosome membrane (Reactome:R-HSA-168915). Reason: CD14 drives LPS-induced endocytosis of TLR4 and delivers it to endosomes for TRIF signalling, so CD14 plausibly accompanies the complex into endosomes. Its primary site of action is the plasma membrane. Supporting Evidence: PMID:22078883 the plasma membrane localized Pattern Recognition Receptor (PRR) CD14 is required for the microbe-induced endocytosis of TLR4 PMID:22078883 This cascade begins with CD14 transporting LPS to TLR4, and culminates with CD14 delivering TLR4 to the endosomal signaling machinery that is needed to induce IFN expression file:human/CD14/CD14-deep-research-falcon.md Following ligand engagement, CD14 facilitates internalization of the TLR4/MD-2 complex from the plasma membrane into early endosomes |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-168921 | KEEP AS NON CORE | Summary: Reactome places CD14 with internalised TLR4:MD-2:LPS on the endosome membrane (Reactome:R-HSA-168921). Reason: CD14 drives LPS-induced endocytosis of TLR4 and delivers it to endosomes for TRIF signalling, so CD14 plausibly accompanies the complex into endosomes. Its primary site of action is the plasma membrane. Supporting Evidence: PMID:22078883 the plasma membrane localized Pattern Recognition Receptor (PRR) CD14 is required for the microbe-induced endocytosis of TLR4 PMID:22078883 This cascade begins with CD14 transporting LPS to TLR4, and culminates with CD14 delivering TLR4 to the endosomal signaling machinery that is needed to induce IFN expression file:human/CD14/CD14-deep-research-falcon.md Following ligand engagement, CD14 facilitates internalization of the TLR4/MD-2 complex from the plasma membrane into early endosomes |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-2201293 | KEEP AS NON CORE | Summary: Reactome places CD14 with internalised TLR4:MD-2:LPS on the endosome membrane (Reactome:R-HSA-2201293). Reason: CD14 drives LPS-induced endocytosis of TLR4 and delivers it to endosomes for TRIF signalling, so CD14 plausibly accompanies the complex into endosomes. Its primary site of action is the plasma membrane. Supporting Evidence: PMID:22078883 the plasma membrane localized Pattern Recognition Receptor (PRR) CD14 is required for the microbe-induced endocytosis of TLR4 PMID:22078883 This cascade begins with CD14 transporting LPS to TLR4, and culminates with CD14 delivering TLR4 to the endosomal signaling machinery that is needed to induce IFN expression file:human/CD14/CD14-deep-research-falcon.md Following ligand engagement, CD14 facilitates internalization of the TLR4/MD-2 complex from the plasma membrane into early endosomes |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-2201338 | KEEP AS NON CORE | Summary: Reactome places CD14 with internalised TLR4:MD-2:LPS on the endosome membrane (Reactome:R-HSA-2201338). Reason: CD14 drives LPS-induced endocytosis of TLR4 and delivers it to endosomes for TRIF signalling, so CD14 plausibly accompanies the complex into endosomes. Its primary site of action is the plasma membrane. Supporting Evidence: PMID:22078883 the plasma membrane localized Pattern Recognition Receptor (PRR) CD14 is required for the microbe-induced endocytosis of TLR4 PMID:22078883 This cascade begins with CD14 transporting LPS to TLR4, and culminates with CD14 delivering TLR4 to the endosomal signaling machinery that is needed to induce IFN expression file:human/CD14/CD14-deep-research-falcon.md Following ligand engagement, CD14 facilitates internalization of the TLR4/MD-2 complex from the plasma membrane into early endosomes |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-2213017 | KEEP AS NON CORE | Summary: Reactome places CD14 with internalised TLR4:MD-2:LPS on the endosome membrane (Reactome:R-HSA-2213017). Reason: CD14 drives LPS-induced endocytosis of TLR4 and delivers it to endosomes for TRIF signalling, so CD14 plausibly accompanies the complex into endosomes. Its primary site of action is the plasma membrane. Supporting Evidence: PMID:22078883 the plasma membrane localized Pattern Recognition Receptor (PRR) CD14 is required for the microbe-induced endocytosis of TLR4 PMID:22078883 This cascade begins with CD14 transporting LPS to TLR4, and culminates with CD14 delivering TLR4 to the endosomal signaling machinery that is needed to induce IFN expression file:human/CD14/CD14-deep-research-falcon.md Following ligand engagement, CD14 facilitates internalization of the TLR4/MD-2 complex from the plasma membrane into early endosomes |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-2559568 | KEEP AS NON CORE | Summary: Reactome places CD14 with internalised TLR4:MD-2:LPS on the endosome membrane (Reactome:R-HSA-2559568). Reason: CD14 drives LPS-induced endocytosis of TLR4 and delivers it to endosomes for TRIF signalling, so CD14 plausibly accompanies the complex into endosomes. Its primary site of action is the plasma membrane. Supporting Evidence: PMID:22078883 the plasma membrane localized Pattern Recognition Receptor (PRR) CD14 is required for the microbe-induced endocytosis of TLR4 PMID:22078883 This cascade begins with CD14 transporting LPS to TLR4, and culminates with CD14 delivering TLR4 to the endosomal signaling machinery that is needed to induce IFN expression file:human/CD14/CD14-deep-research-falcon.md Following ligand engagement, CD14 facilitates internalization of the TLR4/MD-2 complex from the plasma membrane into early endosomes |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-2562541 | KEEP AS NON CORE | Summary: Reactome places CD14 with internalised TLR4:MD-2:LPS on the endosome membrane (Reactome:R-HSA-2562541). Reason: CD14 drives LPS-induced endocytosis of TLR4 and delivers it to endosomes for TRIF signalling, so CD14 plausibly accompanies the complex into endosomes. Its primary site of action is the plasma membrane. Supporting Evidence: PMID:22078883 the plasma membrane localized Pattern Recognition Receptor (PRR) CD14 is required for the microbe-induced endocytosis of TLR4 PMID:22078883 This cascade begins with CD14 transporting LPS to TLR4, and culminates with CD14 delivering TLR4 to the endosomal signaling machinery that is needed to induce IFN expression file:human/CD14/CD14-deep-research-falcon.md Following ligand engagement, CD14 facilitates internalization of the TLR4/MD-2 complex from the plasma membrane into early endosomes |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-2562564 | KEEP AS NON CORE | Summary: Reactome places CD14 with internalised TLR4:MD-2:LPS on the endosome membrane (Reactome:R-HSA-2562564). Reason: CD14 drives LPS-induced endocytosis of TLR4 and delivers it to endosomes for TRIF signalling, so CD14 plausibly accompanies the complex into endosomes. Its primary site of action is the plasma membrane. Supporting Evidence: PMID:22078883 the plasma membrane localized Pattern Recognition Receptor (PRR) CD14 is required for the microbe-induced endocytosis of TLR4 PMID:22078883 This cascade begins with CD14 transporting LPS to TLR4, and culminates with CD14 delivering TLR4 to the endosomal signaling machinery that is needed to induce IFN expression file:human/CD14/CD14-deep-research-falcon.md Following ligand engagement, CD14 facilitates internalization of the TLR4/MD-2 complex from the plasma membrane into early endosomes |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-2569057 | KEEP AS NON CORE | Summary: Reactome places CD14 with internalised TLR4:MD-2:LPS on the endosome membrane (Reactome:R-HSA-2569057). Reason: CD14 drives LPS-induced endocytosis of TLR4 and delivers it to endosomes for TRIF signalling, so CD14 plausibly accompanies the complex into endosomes. Its primary site of action is the plasma membrane. Supporting Evidence: PMID:22078883 the plasma membrane localized Pattern Recognition Receptor (PRR) CD14 is required for the microbe-induced endocytosis of TLR4 PMID:22078883 This cascade begins with CD14 transporting LPS to TLR4, and culminates with CD14 delivering TLR4 to the endosomal signaling machinery that is needed to induce IFN expression file:human/CD14/CD14-deep-research-falcon.md Following ligand engagement, CD14 facilitates internalization of the TLR4/MD-2 complex from the plasma membrane into early endosomes |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-450358 | KEEP AS NON CORE | Summary: Reactome places CD14 with internalised TLR4:MD-2:LPS on the endosome membrane (Reactome:R-HSA-450358). Reason: CD14 drives LPS-induced endocytosis of TLR4 and delivers it to endosomes for TRIF signalling, so CD14 plausibly accompanies the complex into endosomes. Its primary site of action is the plasma membrane. Supporting Evidence: PMID:22078883 the plasma membrane localized Pattern Recognition Receptor (PRR) CD14 is required for the microbe-induced endocytosis of TLR4 PMID:22078883 This cascade begins with CD14 transporting LPS to TLR4, and culminates with CD14 delivering TLR4 to the endosomal signaling machinery that is needed to induce IFN expression file:human/CD14/CD14-deep-research-falcon.md Following ligand engagement, CD14 facilitates internalization of the TLR4/MD-2 complex from the plasma membrane into early endosomes |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-5362486 | KEEP AS NON CORE | Summary: Reactome places CD14 with internalised TLR4:MD-2:LPS on the endosome membrane (Reactome:R-HSA-5362486). Reason: CD14 drives LPS-induced endocytosis of TLR4 and delivers it to endosomes for TRIF signalling, so CD14 plausibly accompanies the complex into endosomes. Its primary site of action is the plasma membrane. Supporting Evidence: PMID:22078883 the plasma membrane localized Pattern Recognition Receptor (PRR) CD14 is required for the microbe-induced endocytosis of TLR4 PMID:22078883 This cascade begins with CD14 transporting LPS to TLR4, and culminates with CD14 delivering TLR4 to the endosomal signaling machinery that is needed to induce IFN expression file:human/CD14/CD14-deep-research-falcon.md Following ligand engagement, CD14 facilitates internalization of the TLR4/MD-2 complex from the plasma membrane into early endosomes |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-5362500 | KEEP AS NON CORE | Summary: Reactome places CD14 with internalised TLR4:MD-2:LPS on the endosome membrane (Reactome:R-HSA-5362500). Reason: CD14 drives LPS-induced endocytosis of TLR4 and delivers it to endosomes for TRIF signalling, so CD14 plausibly accompanies the complex into endosomes. Its primary site of action is the plasma membrane. Supporting Evidence: PMID:22078883 the plasma membrane localized Pattern Recognition Receptor (PRR) CD14 is required for the microbe-induced endocytosis of TLR4 PMID:22078883 This cascade begins with CD14 transporting LPS to TLR4, and culminates with CD14 delivering TLR4 to the endosomal signaling machinery that is needed to induce IFN expression file:human/CD14/CD14-deep-research-falcon.md Following ligand engagement, CD14 facilitates internalization of the TLR4/MD-2 complex from the plasma membrane into early endosomes |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-936947 | KEEP AS NON CORE | Summary: Reactome places CD14 with internalised TLR4:MD-2:LPS on the endosome membrane (Reactome:R-HSA-936947). Reason: CD14 drives LPS-induced endocytosis of TLR4 and delivers it to endosomes for TRIF signalling, so CD14 plausibly accompanies the complex into endosomes. Its primary site of action is the plasma membrane. Supporting Evidence: PMID:22078883 the plasma membrane localized Pattern Recognition Receptor (PRR) CD14 is required for the microbe-induced endocytosis of TLR4 PMID:22078883 This cascade begins with CD14 transporting LPS to TLR4, and culminates with CD14 delivering TLR4 to the endosomal signaling machinery that is needed to induce IFN expression file:human/CD14/CD14-deep-research-falcon.md Following ligand engagement, CD14 facilitates internalization of the TLR4/MD-2 complex from the plasma membrane into early endosomes |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-936951 | KEEP AS NON CORE | Summary: Reactome places CD14 with internalised TLR4:MD-2:LPS on the endosome membrane (Reactome:R-HSA-936951). Reason: CD14 drives LPS-induced endocytosis of TLR4 and delivers it to endosomes for TRIF signalling, so CD14 plausibly accompanies the complex into endosomes. Its primary site of action is the plasma membrane. Supporting Evidence: PMID:22078883 the plasma membrane localized Pattern Recognition Receptor (PRR) CD14 is required for the microbe-induced endocytosis of TLR4 PMID:22078883 This cascade begins with CD14 transporting LPS to TLR4, and culminates with CD14 delivering TLR4 to the endosomal signaling machinery that is needed to induce IFN expression file:human/CD14/CD14-deep-research-falcon.md Following ligand engagement, CD14 facilitates internalization of the TLR4/MD-2 complex from the plasma membrane into early endosomes |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-936952 | KEEP AS NON CORE | Summary: Reactome places CD14 with internalised TLR4:MD-2:LPS on the endosome membrane (Reactome:R-HSA-936952). Reason: CD14 drives LPS-induced endocytosis of TLR4 and delivers it to endosomes for TRIF signalling, so CD14 plausibly accompanies the complex into endosomes. Its primary site of action is the plasma membrane. Supporting Evidence: PMID:22078883 the plasma membrane localized Pattern Recognition Receptor (PRR) CD14 is required for the microbe-induced endocytosis of TLR4 PMID:22078883 This cascade begins with CD14 transporting LPS to TLR4, and culminates with CD14 delivering TLR4 to the endosomal signaling machinery that is needed to induce IFN expression file:human/CD14/CD14-deep-research-falcon.md Following ligand engagement, CD14 facilitates internalization of the TLR4/MD-2 complex from the plasma membrane into early endosomes |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-936985 | KEEP AS NON CORE | Summary: Reactome places CD14 with internalised TLR4:MD-2:LPS on the endosome membrane (Reactome:R-HSA-936985). Reason: CD14 drives LPS-induced endocytosis of TLR4 and delivers it to endosomes for TRIF signalling, so CD14 plausibly accompanies the complex into endosomes. Its primary site of action is the plasma membrane. Supporting Evidence: PMID:22078883 the plasma membrane localized Pattern Recognition Receptor (PRR) CD14 is required for the microbe-induced endocytosis of TLR4 PMID:22078883 This cascade begins with CD14 transporting LPS to TLR4, and culminates with CD14 delivering TLR4 to the endosomal signaling machinery that is needed to induce IFN expression file:human/CD14/CD14-deep-research-falcon.md Following ligand engagement, CD14 facilitates internalization of the TLR4/MD-2 complex from the plasma membrane into early endosomes |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-937029 | KEEP AS NON CORE | Summary: Reactome places CD14 with internalised TLR4:MD-2:LPS on the endosome membrane (Reactome:R-HSA-937029). Reason: CD14 drives LPS-induced endocytosis of TLR4 and delivers it to endosomes for TRIF signalling, so CD14 plausibly accompanies the complex into endosomes. Its primary site of action is the plasma membrane. Supporting Evidence: PMID:22078883 the plasma membrane localized Pattern Recognition Receptor (PRR) CD14 is required for the microbe-induced endocytosis of TLR4 PMID:22078883 This cascade begins with CD14 transporting LPS to TLR4, and culminates with CD14 delivering TLR4 to the endosomal signaling machinery that is needed to induce IFN expression file:human/CD14/CD14-deep-research-falcon.md Following ligand engagement, CD14 facilitates internalization of the TLR4/MD-2 complex from the plasma membrane into early endosomes |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-937075 | KEEP AS NON CORE | Summary: Reactome places CD14 with internalised TLR4:MD-2:LPS on the endosome membrane (Reactome:R-HSA-937075). Reason: CD14 drives LPS-induced endocytosis of TLR4 and delivers it to endosomes for TRIF signalling, so CD14 plausibly accompanies the complex into endosomes. Its primary site of action is the plasma membrane. Supporting Evidence: PMID:22078883 the plasma membrane localized Pattern Recognition Receptor (PRR) CD14 is required for the microbe-induced endocytosis of TLR4 PMID:22078883 This cascade begins with CD14 transporting LPS to TLR4, and culminates with CD14 delivering TLR4 to the endosomal signaling machinery that is needed to induce IFN expression file:human/CD14/CD14-deep-research-falcon.md Following ligand engagement, CD14 facilitates internalization of the TLR4/MD-2 complex from the plasma membrane into early endosomes |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-9823904 | KEEP AS NON CORE | Summary: Reactome places CD14 with internalised TLR4:MD-2:LPS on the endosome membrane (Reactome:R-HSA-9823904). Reason: CD14 drives LPS-induced endocytosis of TLR4 and delivers it to endosomes for TRIF signalling, so CD14 plausibly accompanies the complex into endosomes. Its primary site of action is the plasma membrane. Supporting Evidence: PMID:22078883 the plasma membrane localized Pattern Recognition Receptor (PRR) CD14 is required for the microbe-induced endocytosis of TLR4 PMID:22078883 This cascade begins with CD14 transporting LPS to TLR4, and culminates with CD14 delivering TLR4 to the endosomal signaling machinery that is needed to induce IFN expression file:human/CD14/CD14-deep-research-falcon.md Following ligand engagement, CD14 facilitates internalization of the TLR4/MD-2 complex from the plasma membrane into early endosomes |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-9823906 | KEEP AS NON CORE | Summary: Reactome places CD14 with internalised TLR4:MD-2:LPS on the endosome membrane (Reactome:R-HSA-9823906). Reason: CD14 drives LPS-induced endocytosis of TLR4 and delivers it to endosomes for TRIF signalling, so CD14 plausibly accompanies the complex into endosomes. Its primary site of action is the plasma membrane. Supporting Evidence: PMID:22078883 the plasma membrane localized Pattern Recognition Receptor (PRR) CD14 is required for the microbe-induced endocytosis of TLR4 PMID:22078883 This cascade begins with CD14 transporting LPS to TLR4, and culminates with CD14 delivering TLR4 to the endosomal signaling machinery that is needed to induce IFN expression file:human/CD14/CD14-deep-research-falcon.md Following ligand engagement, CD14 facilitates internalization of the TLR4/MD-2 complex from the plasma membrane into early endosomes |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-9823910 | KEEP AS NON CORE | Summary: Reactome places CD14 with internalised TLR4:MD-2:LPS on the endosome membrane (Reactome:R-HSA-9823910). Reason: CD14 drives LPS-induced endocytosis of TLR4 and delivers it to endosomes for TRIF signalling, so CD14 plausibly accompanies the complex into endosomes. Its primary site of action is the plasma membrane. Supporting Evidence: PMID:22078883 the plasma membrane localized Pattern Recognition Receptor (PRR) CD14 is required for the microbe-induced endocytosis of TLR4 PMID:22078883 This cascade begins with CD14 transporting LPS to TLR4, and culminates with CD14 delivering TLR4 to the endosomal signaling machinery that is needed to induce IFN expression file:human/CD14/CD14-deep-research-falcon.md Following ligand engagement, CD14 facilitates internalization of the TLR4/MD-2 complex from the plasma membrane into early endosomes |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-9823932 | KEEP AS NON CORE | Summary: Reactome places CD14 with internalised TLR4:MD-2:LPS on the endosome membrane (Reactome:R-HSA-9823932). Reason: CD14 drives LPS-induced endocytosis of TLR4 and delivers it to endosomes for TRIF signalling, so CD14 plausibly accompanies the complex into endosomes. Its primary site of action is the plasma membrane. Supporting Evidence: PMID:22078883 the plasma membrane localized Pattern Recognition Receptor (PRR) CD14 is required for the microbe-induced endocytosis of TLR4 PMID:22078883 This cascade begins with CD14 transporting LPS to TLR4, and culminates with CD14 delivering TLR4 to the endosomal signaling machinery that is needed to induce IFN expression file:human/CD14/CD14-deep-research-falcon.md Following ligand engagement, CD14 facilitates internalization of the TLR4/MD-2 complex from the plasma membrane into early endosomes |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-9823934 | KEEP AS NON CORE | Summary: Reactome places CD14 with internalised TLR4:MD-2:LPS on the endosome membrane (Reactome:R-HSA-9823934). Reason: CD14 drives LPS-induced endocytosis of TLR4 and delivers it to endosomes for TRIF signalling, so CD14 plausibly accompanies the complex into endosomes. Its primary site of action is the plasma membrane. Supporting Evidence: PMID:22078883 the plasma membrane localized Pattern Recognition Receptor (PRR) CD14 is required for the microbe-induced endocytosis of TLR4 PMID:22078883 This cascade begins with CD14 transporting LPS to TLR4, and culminates with CD14 delivering TLR4 to the endosomal signaling machinery that is needed to induce IFN expression file:human/CD14/CD14-deep-research-falcon.md Following ligand engagement, CD14 facilitates internalization of the TLR4/MD-2 complex from the plasma membrane into early endosomes |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-9823939 | KEEP AS NON CORE | Summary: Reactome places CD14 with internalised TLR4:MD-2:LPS on the endosome membrane (Reactome:R-HSA-9823939). Reason: CD14 drives LPS-induced endocytosis of TLR4 and delivers it to endosomes for TRIF signalling, so CD14 plausibly accompanies the complex into endosomes. Its primary site of action is the plasma membrane. Supporting Evidence: PMID:22078883 the plasma membrane localized Pattern Recognition Receptor (PRR) CD14 is required for the microbe-induced endocytosis of TLR4 PMID:22078883 This cascade begins with CD14 transporting LPS to TLR4, and culminates with CD14 delivering TLR4 to the endosomal signaling machinery that is needed to induce IFN expression file:human/CD14/CD14-deep-research-falcon.md Following ligand engagement, CD14 facilitates internalization of the TLR4/MD-2 complex from the plasma membrane into early endosomes |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-9824882 | KEEP AS NON CORE | Summary: Reactome places CD14 with internalised TLR4:MD-2:LPS on the endosome membrane (Reactome:R-HSA-9824882). Reason: CD14 drives LPS-induced endocytosis of TLR4 and delivers it to endosomes for TRIF signalling, so CD14 plausibly accompanies the complex into endosomes. Its primary site of action is the plasma membrane. Supporting Evidence: PMID:22078883 the plasma membrane localized Pattern Recognition Receptor (PRR) CD14 is required for the microbe-induced endocytosis of TLR4 PMID:22078883 This cascade begins with CD14 transporting LPS to TLR4, and culminates with CD14 delivering TLR4 to the endosomal signaling machinery that is needed to induce IFN expression file:human/CD14/CD14-deep-research-falcon.md Following ligand engagement, CD14 facilitates internalization of the TLR4/MD-2 complex from the plasma membrane into early endosomes |
| GO:0016019 peptidoglycan immune receptor activity | TAS PMID:8798531 CD14 is a cell-activating receptor for bacterial peptidoglyc... | MODIFY | Summary: Human CD14 expressed in 70Z/3 cells conferred responsiveness to peptidoglycan, and anti-CD14 blocked the response. Reason: The term note restricts GO:0016019 to proteins with receptor activity and recommends peptidoglycan binding otherwise. CD14 is GPI-anchored and acts by presenting ligands to transmembrane signalling receptors; the paper shows CD14-dependent responsiveness, consistent with CD14 binding peptidoglycan, not with CD14 transducing the signal itself. Proposed replacements: peptidoglycan binding Supporting Evidence: PMID:8798531 Both peptidoglycan- and endotoxin-induced activation of NF-kappaB were inhibited by anti-CD14 mAb PMID:8798531 70Z/3-CD14 cells were responsive to both insoluble and soluble peptidoglycan |
| GO:0030667 secretory granule membrane | TAS Reactome:R-HSA-6798743 | KEEP AS NON CORE | Summary: Reactome neutrophil degranulation reaction lists CD14 as a secretory granule membrane protein delivered to the cell surface. Reason: Plausible for granulocyte CD14 (UniProt notes weak granulocyte expression); a storage compartment rather than a site of function. |
| GO:0031663 lipopolysaccharide-mediated signaling pathway | IEA GO_REF:0000108 | ACCEPT | Summary: Inferred from LPS-related MF; CD14 participates in LPS-initiated signalling by delivering LPS to TLR4-MD-2. Reason: Participation is supported by direct evidence. Supporting Evidence: PMID:27986454 LPS transfer to TLR4-MD2 is catalyzed by both LPS binding protein (LBP) and CD14 PMID:1698311 CD14, a differentiation antigen of monocytes, was found to bind complexes of LPS and LBP, and blockade of CD14 with monoclonal antibodies prevented synthesis of TNF-alpha by whole blood incubated with LPS |
| GO:0031666 positive regulation of lipopolysaccharide-mediated signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred positive regulation of LPS-mediated signalling. Reason: CD14 sensitises cells to low LPS doses, so a positive-regulation reading is defensible, but CD14 is better described as a participant in the pathway (GO:0034142, GO:0031663). Supporting Evidence: PMID:1698311 CD14, a differentiation antigen of monocytes, was found to bind complexes of LPS and LBP, and blockade of CD14 with monoclonal antibodies prevented synthesis of TNF-alpha by whole blood incubated with LPS |
| GO:0032481 positive regulation of type I interferon production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred positive regulation of type I interferon production. Reason: Supported by the requirement of CD14 for TLR4 endocytosis and TRIF-dependent IFN expression; an output of the pathway rather than a core activity. Supporting Evidence: PMID:22078883 Notably, while CD14 is marginally important for MyD88-dependent TNFΞ± expression, it is essential for TRIF-mediated IFN expression |
| GO:0032729 positive regulation of type II interferon production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of IFN-gamma production transferred from mouse Cd14. Reason: An indirect downstream consequence of CD14-dependent innate signalling in mouse; no human-specific evidence was reviewed, but it is not implausible. |
| GO:0032729 positive regulation of type II interferon production | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Positive regulation of IFN-gamma production transferred from mouse Cd14. Reason: An indirect downstream consequence of CD14-dependent innate signalling in mouse; no human-specific evidence was reviewed, but it is not implausible. |
| GO:0032757 positive regulation of interleukin-8 production | IMP PMID:15039339 Cell surface-associated elongation factor Tu mediates the at... | KEEP AS NON CORE | Summary: Soluble CD14 (from human milk) was required for EF-Tu-induced IL-8 release by HT29 epithelial cells. Reason: Downstream cytokine output of sCD14-dependent signalling; correct but indirect. Supporting Evidence: PMID:15039339 The involvement of sCD14 was confirmed by the fact that this increase was greatly diminished when EF-Tu was incubated in the presence of MY4 anti-CD14 antibodies |
| GO:0032760 positive regulation of tumor necrosis factor production | IDA PMID:12594207 Lipoteichoic acid (LTA) of Streptococcus pneumoniae and Stap... | KEEP AS NON CORE | Summary: CD14 is required for LPS- and LTA-induced TNF production by monocytes/macrophages. Reason: Downstream cytokine output of TLR signalling in which CD14 acts as ligand carrier; correct but indirect. Supporting Evidence: PMID:12594207 Activation was LBP- and CD14-dependent |
| GO:0032760 positive regulation of tumor necrosis factor production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CD14 is required for LPS- and LTA-induced TNF production by monocytes/macrophages. Reason: Downstream cytokine output of TLR signalling in which CD14 acts as ligand carrier; correct but indirect. Supporting Evidence: PMID:1698311 CD14, a differentiation antigen of monocytes, was found to bind complexes of LPS and LBP, and blockade of CD14 with monoclonal antibodies prevented synthesis of TNF-alpha by whole blood incubated with LPS |
| GO:0032760 positive regulation of tumor necrosis factor production | IMP PMID:8612135 Resistance to endotoxin shock and reduced dissemination of g... | KEEP AS NON CORE | Summary: CD14 is required for LPS- and LTA-induced TNF production by monocytes/macrophages. Reason: Downstream cytokine output of TLR signalling in which CD14 acts as ligand carrier; correct but indirect. Supporting Evidence: PMID:8612135 CD14-deficient mice were found to be highly resistant to shock induced by either live Gram-negative bacteria or LPS |
| GO:0034142 toll-like receptor 4 signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: CD14 extracts LPS from LBP and delivers it to TLR4-MD-2, and membrane CD14 is required for TLR4 dimerization and endocytosis; it is a component of the TLR4 signalling pathway. Reason: CD14 performs a step of the pathway (ligand transfer to the receptor), passing the participation test, and appears as the carrier node in the TLR4 GO-CAM. The IBA and IDA rows agree. Supporting Evidence: PMID:27986454 LPS transfer to TLR4-MD2 is catalyzed by both LPS binding protein (LBP) and CD14 PMID:27986454 Subsequently, the single LPS molecule bound to CD14 was transferred to TLR4-MD2 in a TLR4-dependent manner PMID:20133493 We found that LPS-induced TLR4/MD-2 dimerization occurred only in membrane-associated CD14 (mCD14)-expressing cells PMID:22078883 the plasma membrane localized Pattern Recognition Receptor (PRR) CD14 is required for the microbe-induced endocytosis of TLR4 |
| GO:0034142 toll-like receptor 4 signaling pathway | IDA PMID:27986454 Reconstruction of LPS Transfer Cascade Reveals Structural De... | ACCEPT | Summary: CD14 extracts LPS from LBP and delivers it to TLR4-MD-2, and membrane CD14 is required for TLR4 dimerization and endocytosis; it is a component of the TLR4 signalling pathway. Reason: CD14 performs a step of the pathway (ligand transfer to the receptor), passing the participation test, and appears as the carrier node in the TLR4 GO-CAM. The IBA and IDA rows agree. Supporting Evidence: PMID:27986454 LPS transfer to TLR4-MD2 is catalyzed by both LPS binding protein (LBP) and CD14 PMID:27986454 Subsequently, the single LPS molecule bound to CD14 was transferred to TLR4-MD2 in a TLR4-dependent manner PMID:20133493 We found that LPS-induced TLR4/MD-2 dimerization occurred only in membrane-associated CD14 (mCD14)-expressing cells PMID:22078883 the plasma membrane localized Pattern Recognition Receptor (PRR) CD14 is required for the microbe-induced endocytosis of TLR4 |
| GO:0034145 positive regulation of toll-like receptor 4 signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of TLR4 signalling, transferred from mouse Cd14. Reason: CD14 increases TLR4 responses (dimerization, endocytosis, low-dose sensitivity), but it performs the ligand-transfer step and is therefore primarily a participant (GO:0034142); the regulation term is redundant rather than wrong. Supporting Evidence: PMID:20133493 We found that LPS-induced TLR4/MD-2 dimerization occurred only in membrane-associated CD14 (mCD14)-expressing cells PMID:22078883 the plasma membrane localized Pattern Recognition Receptor (PRR) CD14 is required for the microbe-induced endocytosis of TLR4 |
| GO:0034145 positive regulation of toll-like receptor 4 signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Positive regulation of TLR4 signalling, transferred from mouse Cd14. Reason: CD14 increases TLR4 responses (dimerization, endocytosis, low-dose sensitivity), but it performs the ligand-transfer step and is therefore primarily a participant (GO:0034142); the regulation term is redundant rather than wrong. Supporting Evidence: PMID:20133493 We found that LPS-induced TLR4/MD-2 dimerization occurred only in membrane-associated CD14 (mCD14)-expressing cells PMID:22078883 the plasma membrane localized Pattern Recognition Receptor (PRR) CD14 is required for the microbe-induced endocytosis of TLR4 |
| GO:0045121 membrane raft | IBA GO_REF:0000033 | ACCEPT | Summary: CD14 associates with lipid rafts, where ligand-engaged TLR2 heterodimers are recruited. Reason: GPI-anchored proteins partition to rafts, and TLR2 receptor clusters with CD14 accumulate in rafts on stimulation. Supporting Evidence: PMID:16880211 Upon stimulation by the specific ligand, these heterodimers are recruited within lipid rafts PMID:16880211 All TLR2 receptor clusters accumulate in lipid rafts and are targeted to the Golgi apparatus |
| GO:0045121 membrane raft | IDA PMID:16880211 Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 ... | ACCEPT | Summary: CD14 associates with lipid rafts, where ligand-engaged TLR2 heterodimers are recruited. Reason: GPI-anchored proteins partition to rafts, and TLR2 receptor clusters with CD14 accumulate in rafts on stimulation. Supporting Evidence: PMID:16880211 Upon stimulation by the specific ligand, these heterodimers are recruited within lipid rafts PMID:16880211 All TLR2 receptor clusters accumulate in lipid rafts and are targeted to the Golgi apparatus |
| GO:0045121 membrane raft | IEA GO_REF:0000120 | ACCEPT | Summary: CD14 associates with lipid rafts, where ligand-engaged TLR2 heterodimers are recruited. Reason: GPI-anchored proteins partition to rafts, and TLR2 receptor clusters with CD14 accumulate in rafts on stimulation. Supporting Evidence: PMID:16880211 Upon stimulation by the specific ligand, these heterodimers are recruited within lipid rafts PMID:16880211 All TLR2 receptor clusters accumulate in lipid rafts and are targeted to the Golgi apparatus |
| GO:0045807 positive regulation of endocytosis | IEA GO_REF:0000107 | ACCEPT | Summary: Ortholog-transferred positive regulation of endocytosis. Reason: CD14 is required for microbe-induced endocytosis of TLR4 and controls TLR4 trafficking to endosomes. Supporting Evidence: PMID:22078883 the plasma membrane localized Pattern Recognition Receptor (PRR) CD14 is required for the microbe-induced endocytosis of TLR4 PMID:22078883 This cascade begins with CD14 transporting LPS to TLR4, and culminates with CD14 delivering TLR4 to the endosomal signaling machinery that is needed to induce IFN expression |
| GO:0046696 lipopolysaccharide receptor complex | IBA GO_REF:0000033 | ACCEPT | Summary: CD14 is one of the three proteins of the LPS receptor complex with TLR4 and MD-2. Reason: The GO term definition names CD14; LPS cross-links to TLR4 and MD-2 only when CD14 is present, and the complex is the unit that recognises LPS at the cell surface. CD14 membership may be transient (it hands LPS to TLR4-MD-2), which the complex term accommodates. Supporting Evidence: PMID:11274165 LPS is cross-linked specifically to TLR4 and MD-2 only when co-expressed with CD14 PMID:11274165 Thus, LPS binds directly to each of the members of the tripartite LPS receptor complex |
| GO:0046696 lipopolysaccharide receptor complex | IDA PMID:11274165 Lipopolysaccharide is in close proximity to each of the prot... | ACCEPT | Summary: CD14 is one of the three proteins of the LPS receptor complex with TLR4 and MD-2. Reason: The GO term definition names CD14; LPS cross-links to TLR4 and MD-2 only when CD14 is present, and the complex is the unit that recognises LPS at the cell surface. CD14 membership may be transient (it hands LPS to TLR4-MD-2), which the complex term accommodates. Supporting Evidence: PMID:11274165 LPS is cross-linked specifically to TLR4 and MD-2 only when co-expressed with CD14 PMID:11274165 Thus, LPS binds directly to each of the members of the tripartite LPS receptor complex |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: CD14 identified in exosome proteomics datasets. Reason: High-throughput detection in exosomes is consistent with GPI-anchored/soluble CD14 in body fluids but is not functionally informative. |
| GO:0070062 extracellular exosome | HDA PMID:19199708 Proteomic analysis of human parotid gland exosomes by multid... | KEEP AS NON CORE | Summary: CD14 identified in exosome proteomics datasets. Reason: High-throughput detection in exosomes is consistent with GPI-anchored/soluble CD14 in body fluids but is not functionally informative. |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | KEEP AS NON CORE | Summary: CD14 identified in exosome proteomics datasets. Reason: High-throughput detection in exosomes is consistent with GPI-anchored/soluble CD14 in body fluids but is not functionally informative. |
| GO:0070891 lipoteichoic acid binding | IDA PMID:12594207 Lipoteichoic acid (LTA) of Streptococcus pneumoniae and Stap... | ACCEPT | Summary: CD14 forms complexes with lipoteichoic acid, which LBP transfers onto soluble CD14. Reason: The cited study shows LTA-sCD14 complex formation and LBP-catalysed transfer of LTA to CD14 by native gel electrophoresis, and CD14-dependent cell activation by LTA. Consistent with CD14 binding a range of acylated microbial ligands. Supporting Evidence: PMID:12594207 formation of complexes of LTA with LBP and soluble CD14 as well as catalytic transfer of LTA to CD14 by LBP was verified by PhastGel(TM) native gel electrophoresis PMID:12594207 Activation was LBP- and CD14-dependent |
| GO:0071219 cellular response to molecule of bacterial origin | IDA PMID:15039339 Cell surface-associated elongation factor Tu mediates the at... | ACCEPT | Summary: sCD14-dependent IL-8 response of intestinal epithelial cells to bacterial EF-Tu. Reason: Consistent with CD14 as a broad acceptor of bacterial molecules. Supporting Evidence: PMID:15039339 The involvement of sCD14 was confirmed by the fact that this increase was greatly diminished when EF-Tu was incubated in the presence of MY4 anti-CD14 antibodies |
| GO:0071222 cellular response to lipopolysaccharide | IBA GO_REF:0000033 | ACCEPT | Summary: CD14 is required for sensitive cellular responses to LPS. Reason: Anti-CD14 blocks LPS-induced TNF, Cd14-null mice resist LPS shock, and CD14 delivers LPS to TLR4-MD-2. IBA, IDA, IEA and IMP rows agree. Supporting Evidence: PMID:1698311 CD14, a differentiation antigen of monocytes, was found to bind complexes of LPS and LBP, and blockade of CD14 with monoclonal antibodies prevented synthesis of TNF-alpha by whole blood incubated with LPS PMID:27986454 LPS transfer to TLR4-MD2 is catalyzed by both LPS binding protein (LBP) and CD14 |
| GO:0071222 cellular response to lipopolysaccharide | IDA PMID:12594207 Lipoteichoic acid (LTA) of Streptococcus pneumoniae and Stap... | ACCEPT | Summary: CD14 is required for sensitive cellular responses to LPS. Reason: Anti-CD14 blocks LPS-induced TNF, Cd14-null mice resist LPS shock, and CD14 delivers LPS to TLR4-MD-2. IBA, IDA, IEA and IMP rows agree. Supporting Evidence: PMID:12594207 Activation was LBP- and CD14-dependent |
| GO:0071222 cellular response to lipopolysaccharide | IEA GO_REF:0000107 | ACCEPT | Summary: CD14 is required for sensitive cellular responses to LPS. Reason: Anti-CD14 blocks LPS-induced TNF, Cd14-null mice resist LPS shock, and CD14 delivers LPS to TLR4-MD-2. IBA, IDA, IEA and IMP rows agree. Supporting Evidence: PMID:1698311 CD14, a differentiation antigen of monocytes, was found to bind complexes of LPS and LBP, and blockade of CD14 with monoclonal antibodies prevented synthesis of TNF-alpha by whole blood incubated with LPS PMID:27986454 LPS transfer to TLR4-MD2 is catalyzed by both LPS binding protein (LBP) and CD14 |
| GO:0071222 cellular response to lipopolysaccharide | IMP PMID:8612135 Resistance to endotoxin shock and reduced dissemination of g... | ACCEPT | Summary: CD14 is required for sensitive cellular responses to LPS. Reason: Anti-CD14 blocks LPS-induced TNF, Cd14-null mice resist LPS shock, and CD14 delivers LPS to TLR4-MD-2. IBA, IDA, IEA and IMP rows agree. Supporting Evidence: PMID:8612135 CD14-deficient mice were found to be highly resistant to shock induced by either live Gram-negative bacteria or LPS |
| GO:0071223 cellular response to lipoteichoic acid | IDA PMID:12594207 Lipoteichoic acid (LTA) of Streptococcus pneumoniae and Stap... | ACCEPT | Summary: LTA activation of human mononuclear phagocytes is LBP- and CD14-dependent. Reason: Directly supported. Supporting Evidence: PMID:12594207 formation of complexes of LTA with LBP and soluble CD14 as well as catalytic transfer of LTA to CD14 by LBP was verified by PhastGel(TM) native gel electrophoresis PMID:12594207 Activation was LBP- and CD14-dependent |
| 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: CD14 participates in cellular response to diacyl bacterial lipopeptide as a ligand-delivering co-receptor for TLR2 heterodimers. Reason: CD14 enhances TLR2 responses to di- and triacylated lipopeptides and acts as their carrier to TLR2 heterodimers; the curator-cited study places CD14 with ligand-engaged TLR2 clusters. Supporting Evidence: PMID:15294986 Activation of Chinese hamster ovary cells transfected with TLR-2 by both lipopeptides was enhanced by cotransfection of CD14 PMID:23430250 either LBP or sCD14 can drive ternary complex formation and TLR activation by acting as mobile carriers of triacylated lipopeptides or lipoproteins |
| 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: CD14 participates in cellular response to triacyl bacterial lipopeptide as a ligand-delivering co-receptor for TLR2 heterodimers. Reason: CD14 enhances TLR2 responses to di- and triacylated lipopeptides and acts as their carrier to TLR2 heterodimers; the curator-cited study places CD14 with ligand-engaged TLR2 clusters. Supporting Evidence: PMID:15294986 Activation of Chinese hamster ovary cells transfected with TLR-2 by both lipopeptides was enhanced by cotransfection of CD14 PMID:23430250 either LBP or sCD14 can drive ternary complex formation and TLR activation by acting as mobile carriers of triacylated lipopeptides or lipoproteins |
| GO:0140104 molecular carrier activity | IDA PMID:15294986 Lipopolysaccharide binding protein binds to triacylated and ... | ACCEPT | Summary: CD14 accepts lipidated microbial ligands (LPS, lipopeptides) from LBP and delivers them to TLR4-MD-2 or TLR1/TLR2 signalling receptors, dissociating after transfer. Reason: This is the most accurate description of the molecular activity of CD14 and matches the production GO-CAMs for TLR4 and TLR1-TLR2 signalling, which model CD14 as molecular carrier activity. Reconstitution shows LPS moving LBP -> CD14 -> TLR4-MD2, and sCD14 drives TLR1-TLR2-lipopeptide complex formation without remaining in the complex. Supporting Evidence: PMID:27986454 LPS transfer to TLR4-MD2 is catalyzed by both LPS binding protein (LBP) and CD14 PMID:27986454 Subsequently, the single LPS molecule bound to CD14 was transferred to TLR4-MD2 in a TLR4-dependent manner PMID:23430250 either LBP or sCD14 can drive ternary complex formation and TLR activation by acting as mobile carriers of triacylated lipopeptides or lipoproteins PMID:23430250 However, neither LBP nor sCD14 was physically associated with the final ternary complex PMID:1698311 CD14, a differentiation antigen of monocytes, was found to bind complexes of LPS and LBP, and blockade of CD14 with monoclonal antibodies prevented synthesis of TNF-alpha by whole blood incubated with LPS |
| GO:0140104 molecular carrier activity | IDA PMID:1698311 CD14, a receptor for complexes of lipopolysaccharide (LPS) a... | ACCEPT | Summary: CD14 accepts lipidated microbial ligands (LPS, lipopeptides) from LBP and delivers them to TLR4-MD-2 or TLR1/TLR2 signalling receptors, dissociating after transfer. Reason: This is the most accurate description of the molecular activity of CD14 and matches the production GO-CAMs for TLR4 and TLR1-TLR2 signalling, which model CD14 as molecular carrier activity. Reconstitution shows LPS moving LBP -> CD14 -> TLR4-MD2, and sCD14 drives TLR1-TLR2-lipopeptide complex formation without remaining in the complex. Supporting Evidence: PMID:27986454 LPS transfer to TLR4-MD2 is catalyzed by both LPS binding protein (LBP) and CD14 PMID:27986454 Subsequently, the single LPS molecule bound to CD14 was transferred to TLR4-MD2 in a TLR4-dependent manner PMID:23430250 either LBP or sCD14 can drive ternary complex formation and TLR activation by acting as mobile carriers of triacylated lipopeptides or lipoproteins PMID:23430250 However, neither LBP nor sCD14 was physically associated with the final ternary complex PMID:1698311 CD14, a differentiation antigen of monocytes, was found to bind complexes of LPS and LBP, and blockade of CD14 with monoclonal antibodies prevented synthesis of TNF-alpha by whole blood incubated with LPS |
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Download this section (compressed HTML)Q: Membrane CD14 drives Syk/PLCgamma2-dependent TLR4 endocytosis independently of its ligand-transfer role. Should this be captured as coreceptor activity (GO:0015026) in addition to molecular carrier activity, and is the endocytosis role conserved in human monocytes as it is in mouse dendritic cells and macrophages?
Q: GO:0001875 lipopolysaccharide immune receptor activity is propagated from human CD14 to mouse Cd14 by ISO/IEA. If the human annotation is replaced by molecular carrier activity, should the propagated rows follow, and should GO:0001875 be reserved for the TLR4-MD-2 signalling unit?
Q: How much of the CD14 dependence of TLR2 lipopeptide and peptidoglycan responses reflects ligand carriage versus contaminating lipoproteins in peptidoglycan preparations?
Experiment: Compare TLR4 endocytosis and TRIF-dependent IFN-beta output in CD14-knockout human monocyte-derived macrophages reconstituted with wild-type CD14, a pocket mutant unable to bind LPS, or a transmembrane-anchored CD14 lacking the GPI signal.
Hypothesis: CD14 drives TLR4 endocytosis through its GPI anchor and raft partitioning, separable from its LPS-carrier activity.
Type: genetic complementation with functional readouts
Experiment: Single-molecule reconstitution of lipopeptide transfer from LBP to CD14 to TLR2-TLR1 and TLR2-TLR6, measuring whether CD14 dissociates after transfer as it does for LPS and TLR4-MD-2.
Hypothesis: CD14 acts as a transient carrier for all acylated ligands rather than a stable receptor subunit.
Type: in vitro reconstitution / single-molecule biophysics
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