CD24 (heat-stable antigen ortholog) is a very small, heavily N- and O-glycosylated sialomucin-like protein whose mature peptide of about 30 residues is attached to the outer leaflet of the plasma membrane by a glycosylphosphatidylinositol (GPI) anchor, concentrating it in lipid rafts. Lacking a cytoplasmic domain, it signals by clustering with raft-associated Src-family kinases such as LYN and FGR. Its glycans make it a ligand for P-selectin, supporting adhesion of carcinoma cells to platelets and endothelium, and its sialylated form is the principal protein ligand of the inhibitory receptor Siglec-10 on macrophages and other innate immune cells. Through Siglec-10 CD24 dampens inflammatory responses to damage-associated molecular patterns such as HMGB1 and HSP70/90, and on tumour cells it acts as an anti-phagocytic "don't eat me" signal. It is expressed on B-cell precursors and mature resting B cells, granulocytes, activated T cells, epithelia and many carcinomas, and modulates B-cell activation and apoptosis, chemokine receptor (CXCR4) function and renal progenitor differentiation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001666 response to hypoxia | IEP PMID:15174142 Modulation of gene expression by hypoxia in human umbilical ... | MARK AS OVER ANNOTATED | Summary: CD24 transcript/protein levels change in hypoxic HUVEC in a transcriptomic/proteomic screen. Reason: Expression-change evidence from a large screen; it says nothing about a CD24 activity in the hypoxia response. Supporting Evidence: PMID:15174142 Modulation of gene expression by hypoxia in human umbilical cord vein endothelial cells |
| GO:0001775 cell activation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Antibody cross-linking of CD24 activates granulocytes and B cells (calcium flux, oxidative burst). Reason: CD24 engagement can trigger leukocyte activation, consistent with the PAINT ancestral assignment, but "cell activation" is a broad, context-dependent outcome of GPI-raft signaling rather than the core ligand function. Supporting Evidence: PMID:8223854 cross-linking of cell-bound anti-CD16, -CD24, -CD59 and -CD67 led to calcium fluxes and activation of the oxidative burst |
| GO:0001775 cell activation | IDA PMID:8223854 Activation of human monocytes and granulocytes by monoclonal... | KEEP AS NON CORE | Summary: Antibody cross-linking of CD24 activates granulocytes and B cells (calcium flux, oxidative burst). Reason: CD24 engagement can trigger leukocyte activation, consistent with the PAINT ancestral assignment, but "cell activation" is a broad, context-dependent outcome of GPI-raft signaling rather than the core ligand function. Supporting Evidence: PMID:8223854 cross-linking of cell-bound anti-CD16, -CD24, -CD59 and -CD67 led to calcium fluxes and activation of the oxidative burst |
| GO:0001959 regulation of cytokine-mediated signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CD24 reduces SDF-1/CXCR4 signaling and migration, apparently by limiting CXCR4 raft association. Reason: Mouse knockout and human breast carcinoma data support modulation of chemokine receptor signaling; this is a modulatory, non-core role. Supporting Evidence: PMID:16390867 CD24 expression reduces SDF-1-mediated cell migration and signalling via CXCR4 |
| GO:0001959 regulation of cytokine-mediated signaling pathway | ISS PMID:16390867 CD24 affects CXCR4 function in pre-B lymphocytes and breast ... | KEEP AS NON CORE | Summary: CD24 reduces SDF-1/CXCR4 signaling and migration, apparently by limiting CXCR4 raft association. Reason: Mouse knockout and human breast carcinoma data support modulation of chemokine receptor signaling; this is a modulatory, non-core role. Supporting Evidence: PMID:16390867 CD24 expression reduces SDF-1-mediated cell migration and signalling via CXCR4 |
| GO:0002237 response to molecule of bacterial origin | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Listeriolysin O causes clustering of CD24 with other GPI proteins in macrophage membranes. Reason: Passive raft clustering of CD24 by a bacterial toxin does not show that CD24 functions in the response to bacterial molecules; CD24/Siglec signaling discriminates against PAMPs rather than mediating responses to them. Supporting Evidence: PMID:15493995 the glycosylphosphatidylinositol-anchored proteins CD14 and CD24, which normally exhibit uniform distribution on J774 cells, undergo clustering upon treatment with LLO PMID:19264983 CD24-deficient mice exhibit increased susceptibility to danger- but not pathogen-associated molecular patterns |
| GO:0002237 response to molecule of bacterial origin | ISS PMID:15493995 Lipid rafts clustering and signalling by listeriolysin O. | MARK AS OVER ANNOTATED | Summary: Listeriolysin O causes clustering of CD24 with other GPI proteins in macrophage membranes. Reason: Passive raft clustering of CD24 by a bacterial toxin does not show that CD24 functions in the response to bacterial molecules; CD24/Siglec signaling discriminates against PAMPs rather than mediating responses to them. Supporting Evidence: PMID:15493995 the glycosylphosphatidylinositol-anchored proteins CD14 and CD24, which normally exhibit uniform distribution on J774 cells, undergo clustering upon treatment with LLO PMID:19264983 CD24-deficient mice exhibit increased susceptibility to danger- but not pathogen-associated molecular patterns |
| GO:0002768 immune response-regulating cell surface receptor signaling pathway | IC PMID:11313396 CD24 induces apoptosis in human B cells via the glycolipid-e... | KEEP AS NON CORE | Summary: CD24 cross-linking on B cells triggers raft-dependent LYN/MAPK signaling. Reason: Supported by the B-cell cross-linking study; a modulatory signaling role of a GPI protein lacking a cytoplasmic tail, non-core relative to its ligand function. Supporting Evidence: PMID:11313396 CD24 mediates intracellular signaling via a GEM-depend |
| GO:0005515 protein binding | IPI PMID:15633604 Inhibition of human CD24 binding to platelet-bound P-selecti... | MODIFY | Summary: CD24 is a glycan-dependent ligand of P-selectin on carcinoma cells and neutrophils. Reason: Generic protein binding is uninformative; the P-selectin interactions support binding to a cell adhesion molecule (P-selectin is a C-type lectin adhesion receptor), i.e. cell adhesion molecule binding. Proposed replacements: cell adhesion molecule binding Supporting Evidence: PMID:9129046 Latex beads coated with purified CD24 from the two carcinoma cell lines but also neutrophils could bind specifically to P-selectin-IgG PMID:15633604 P-selectin ligand CD24 mediates the binding of platelets to prostate cancer line DU145 cells in vitro |
| GO:0005515 protein binding | IPI PMID:22731636 Lyn is involved in CD24-induced ERK1/2 activation in colorec... | MODIFY | Summary: CD24 co-immunoprecipitates with the Src-family kinase LYN in colorectal cancer cells. Reason: The interaction partner is a protein tyrosine kinase; protein kinase binding (already annotated from PMID:8753773) is the informative term. Proposed replacements: protein kinase binding Supporting Evidence: PMID:22731636 The interaction of CD24 and Lyn was identified by co-immunoprecipitation (Co-IP) |
| GO:0005515 protein binding | IPI PMID:8753773 Association of CD24 with the kinase c-fgr in a small cell lu... | MODIFY | Summary: CD24 co-immunoprecipitates with c-fgr in SW2 small cell lung cancer cells. Reason: The paper reports association with the Src-family kinase c-fgr (FGR), so protein kinase binding is the informative term. The WITH/FROM accession UniProtKB:P11362 is FGFR1, which the paper does not study; it appears to be a mis-mapping of "fgr" and should be FGR (UniProtKB:P09769). Proposed replacements: protein kinase binding Supporting Evidence: PMID:8753773 Western analysis of the precipitates showed an association of c-fgr with CD24 in SW2 cells and lyn in K562 cells |
| GO:0005515 protein binding | IPI PMID:9129046 CD24, a mucin-type glycoprotein, is a ligand for P-selectin ... | MODIFY | Summary: CD24 is a glycan-dependent ligand of P-selectin on carcinoma cells and neutrophils. Reason: Generic protein binding is uninformative; the P-selectin interactions support binding to a cell adhesion molecule (P-selectin is a C-type lectin adhesion receptor), i.e. cell adhesion molecule binding. Proposed replacements: cell adhesion molecule binding Supporting Evidence: PMID:9129046 Latex beads coated with purified CD24 from the two carcinoma cell lines but also neutrophils could bind specifically to P-selectin-IgG PMID:15633604 P-selectin ligand CD24 mediates the binding of platelets to prostate cancer line DU145 cells in vitro |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | MODIFY | Summary: CD24 is a GPI-anchored protein of the plasma membrane outer leaflet. Reason: Correct but less specific than supported; the GPI anchor places the whole mature protein on the external side of the plasma membrane (GO:0009897, also carried by the gene via IBA/IEA). Proposed replacements: external side of plasma membrane Supporting Evidence: file:human/CD24/CD24-uniprot.txt SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor, GPI-anchor. PMID:2153173 anchored to the plasma membrane by a phosphoinositol linkage |
| GO:0007155 cell adhesion | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: CD24-family InterPro mapping to cell adhesion. Reason: CD24 mediates P-selectin-dependent adhesion of tumour cells to platelets, so cell adhesion is true, but the more specific heterotypic adhesion role is an accessory outcome of its ligand function. Supporting Evidence: PMID:15633604 P-selectin ligand CD24 mediates the binding of platelets to prostate cancer line DU145 cells in vitro |
| GO:0007204 positive regulation of cytosolic calcium ion concentration | IDA PMID:2153173 Signal transduction in lymphocytic and myeloid cells via CD2... | KEEP AS NON CORE | Summary: CD24 antibody engagement induces cytoplasmic calcium flux in B cells and primed granulocytes. Reason: Experimentally supported downstream readout of CD24 cross-linking; not a core activity. Supporting Evidence: PMID:2153173 We found a clear-cut increase in free cytoplasmic calcium when tonsil B cells or mononuclear cells from B cell chronic lymphatic leukemia patients were preincubated with CD24 mAb PMID:8223854 led to calcium fluxes and activation of the oxidative burst |
| GO:0007204 positive regulation of cytosolic calcium ion concentration | IDA PMID:8223854 Activation of human monocytes and granulocytes by monoclonal... | KEEP AS NON CORE | Summary: CD24 antibody engagement induces cytoplasmic calcium flux in B cells and primed granulocytes. Reason: Experimentally supported downstream readout of CD24 cross-linking; not a core activity. Supporting Evidence: PMID:2153173 We found a clear-cut increase in free cytoplasmic calcium when tonsil B cells or mononuclear cells from B cell chronic lymphatic leukemia patients were preincubated with CD24 mAb PMID:8223854 led to calcium fluxes and activation of the oxidative burst |
| GO:0009897 external side of plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: CD24 is GPI-anchored on the outer leaflet of the plasma membrane, fully exposed to the extracellular space. Reason: The GPI anchor (amidated Gly59) and loss of a cytoplasmic domain place the mature protein on the external side of the plasma membrane, where it is engaged by P-selectin and Siglec-10 on other cells. Supporting Evidence: file:human/CD24/CD24-uniprot.txt SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor, GPI-anchor. PMID:31367043 a heavily glycosylated GPI-anchored surface protein |
| GO:0009897 external side of plasma membrane | IEA GO_REF:0000107 | ACCEPT | Summary: CD24 is GPI-anchored on the outer leaflet of the plasma membrane, fully exposed to the extracellular space. Reason: The GPI anchor (amidated Gly59) and loss of a cytoplasmic domain place the mature protein on the external side of the plasma membrane, where it is engaged by P-selectin and Siglec-10 on other cells. Supporting Evidence: file:human/CD24/CD24-uniprot.txt SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor, GPI-anchor. PMID:31367043 a heavily glycosylated GPI-anchored surface protein |
| GO:0009986 cell surface | IDA PMID:16532032 Repressor roles for TCF-4 and Sfrp1 in Wnt signaling in brea... | MODIFY | Summary: CD24 is detected on the cell surface. Reason: Correct, but the GPI-anchored protein is more precisely on the external side of the plasma membrane (GO:0009897, also carried by the gene), which is part_of cell surface. Proposed replacements: external side of plasma membrane Supporting Evidence: PMID:16390867 CD24 is a small, heavily glycosylated cell-surface protein which is linked to the membrane via a glycosyl-phosphatidylinositol (GPI-) anchor and therefore localizes in lipid rafts |
| GO:0009986 cell surface | IEA GO_REF:0000107 | MODIFY | Summary: CD24 is detected on the cell surface. Reason: Correct, but the GPI-anchored protein is more precisely on the external side of the plasma membrane (GO:0009897, also carried by the gene), which is part_of cell surface. Proposed replacements: external side of plasma membrane Supporting Evidence: PMID:16390867 CD24 is a small, heavily glycosylated cell-surface protein which is linked to the membrane via a glycosyl-phosphatidylinositol (GPI-) anchor and therefore localizes in lipid rafts |
| GO:0016020 membrane | IDA PMID:10037815 Combining SSH and cDNA microarrays for rapid identification ... | MODIFY | Summary: CD24 protein is detected at the membrane of ER-positive breast cancer cells. Reason: Membrane is too general; CD24 is GPI-anchored on the external side of the plasma membrane. Proposed replacements: external side of plasma membrane Supporting Evidence: PMID:10037815 Flow cytometry and immunofluorescence confirmed that CD24 protein was over-expressed |
| GO:0016020 membrane | IEA GO_REF:0000107 | MODIFY | Summary: CD24 protein is detected at the membrane of ER-positive breast cancer cells. Reason: Membrane is too general; CD24 is GPI-anchored on the external side of the plasma membrane. Proposed replacements: external side of plasma membrane Supporting Evidence: PMID:10037815 Flow cytometry and immunofluorescence confirmed that CD24 protein was over-expressed |
| GO:0016055 Wnt signaling pathway | NAS PMID:16532032 Repressor roles for TCF-4 and Sfrp1 in Wnt signaling in brea... | REMOVE | Summary: CD24 is a transcriptional target used as a reporter of Wnt pathway activity. Reason: The paper uses CD24 expression as a readout of TCF-dependent Wnt signaling; being a Wnt target gene is not participation in the signaling pathway. Supporting Evidence: PMID:16532032 We identified CD24 as a Wnt target in MCF10A cells and used its expression a marker of Wnt signaling |
| GO:0016477 cell migration | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CD24 modulates CXCR4-dependent chemotactic migration. Reason: CD24 expression reduces SDF-1-induced migration in pre-B cells and alters it in breast cancer cells; a modulatory role, not migration machinery. Supporting Evidence: PMID:16390867 CD24 expression reduces SDF-1-mediated cell migration and signalling via CXCR4 |
| GO:0016477 cell migration | ISS PMID:16390867 CD24 affects CXCR4 function in pre-B lymphocytes and breast ... | KEEP AS NON CORE | Summary: CD24 modulates CXCR4-dependent chemotactic migration. Reason: CD24 expression reduces SDF-1-induced migration in pre-B cells and alters it in breast cancer cells; a modulatory role, not migration machinery. Supporting Evidence: PMID:16390867 CD24 expression reduces SDF-1-mediated cell migration and signalling via CXCR4 |
| GO:0019901 protein kinase binding | IPI PMID:8753773 Association of CD24 with the kinase c-fgr in a small cell lu... | ACCEPT | Summary: CD24 physically associates with the Src-family kinases LYN and FGR. Reason: Co-immunoprecipitation in SW2 and K562 cells and raft co-fractionation in B cells; this kinase association is how the tail-less GPI protein transduces signals. Supporting Evidence: PMID:8753773 Western analysis of the precipitates showed an association of c-fgr with CD24 in SW2 cells and lyn in K562 cells PMID:11313396 enhanced association of CD24 and Lyn protein tyrosine kinase in GEM as well as increased Lyn kinase activity after CD24 cross-linking |
| GO:0022407 regulation of cell-cell adhesion | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: CD24 family members regulate cell-cell adhesion (PAINT). Reason: Consistent with P-selectin-mediated tumour cell-platelet adhesion; retained as a non-core inherited process. Supporting Evidence: PMID:15633604 P-selectin ligand CD24 mediates the binding of platelets to prostate cancer line DU145 cells in vitro |
| GO:0030246 carbohydrate binding | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ortholog-transferred carbohydrate binding. Reason: CD24 functions as a carrier of glycans recognized by lectins (P-selectin, Siglec-10); it is the ligand, not a carbohydrate-binding protein. No human evidence for CD24 itself binding carbohydrate. Supporting Evidence: PMID:31367043 Siglec-10 has been reported to interact with the highly sialylated form of CD24 |
| GO:0030296 protein tyrosine kinase activator activity | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: CD24 cross-linking increases LYN kinase activity in raft fractions. Reason: Experimental support for CD24 enhancing raft LYN activity; the activation is likely indirect via raft clustering, so it is retained but not treated as the core function. Supporting Evidence: PMID:11313396 enhanced association of CD24 and Lyn protein tyrosine kinase in GEM as well as increased Lyn kinase activity after CD24 cross-linking |
| GO:0030296 protein tyrosine kinase activator activity | IDA PMID:11313396 CD24 induces apoptosis in human B cells via the glycolipid-e... | KEEP AS NON CORE | Summary: CD24 cross-linking increases LYN kinase activity in raft fractions. Reason: Experimental support for CD24 enhancing raft LYN activity; the activation is likely indirect via raft clustering, so it is retained but not treated as the core function. Supporting Evidence: PMID:11313396 enhanced association of CD24 and Lyn protein tyrosine kinase in GEM as well as increased Lyn kinase activity after CD24 cross-linking |
| GO:0030544 Hsp70 protein binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mouse CD24 co-immunoprecipitates with the DAMPs HSP70 and HSP90. Reason: Ortholog-based; CD24 associates with released HSP70/90 and HMGB1 and delivers them to Siglec-G/10 for inhibitory signaling. Retained as non-core binding. Supporting Evidence: PMID:19264983 Coimmunoprecipitations revealed that CD24 associates with both HSP70 and HSP90 |
| GO:0030856 regulation of epithelial cell differentiation | NAS PMID:16930538 Regulation of E-cadherin and TGF-beta3 expression by CD24 in... | KEEP AS NON CORE | Summary: CD24 knockdown alters E-cadherin and TGF-beta3 expression in oral epithelial cells. Reason: Single cell-line RNAi study; regulation of epithelial differentiation is an indirect, non-core effect. Supporting Evidence: PMID:16930538 RNA interference protocols were designed to determine if CD24 could modulate intercellular interactions and regulate the biology of these epithelial cells |
| GO:0031295 T cell costimulation | IDA PMID:11272271 Antibodies recognizing CD24 LAP epitope on human T cells enh... | KEEP AS NON CORE | Summary: Anti-CD24 antibodies enhance CD3/CD28- and IL-2-driven T cell proliferation. Reason: Antibody engagement study supporting a costimulatory-like role on activated T cells; non-core. Supporting Evidence: PMID:11272271 Anti-LAP antibodies strongly enhanced the response of T cells to a combination of anti-CD3/CD28 mAbs and enhanced proliferative response induced by recombinant IL-2 |
| GO:0031514 motile cilium | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-based localization to cilia/microvilli membranes. Reason: Plausible plasma membrane subdomains for an apical GPI-anchored protein in epithelial cells, but human-specific evidence was not reviewed; the core location is the external side of the plasma membrane. Supporting Evidence: file:human/CD24/CD24-uniprot.txt SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor, GPI-anchor. |
| GO:0031528 microvillus membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-based localization to cilia/microvilli membranes. Reason: Plausible plasma membrane subdomains for an apical GPI-anchored protein in epithelial cells, but human-specific evidence was not reviewed; the core location is the external side of the plasma membrane. Supporting Evidence: file:human/CD24/CD24-uniprot.txt SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor, GPI-anchor. |
| GO:0032597 B cell receptor transport into membrane raft | IDA PMID:11313396 CD24 induces apoptosis in human B cells via the glycolipid-e... | KEEP AS NON CORE | Summary: CD24 cross-linking enhances BCR association with raft fractions in B cells. Reason: Supported experimentally as a raft-reorganization effect of CD24 engagement; non-core. Supporting Evidence: PMID:11313396 synergism between the cross-linking of CD24 and that of the B cell receptor for Ag in the effect on apoptosis induction |
| GO:0032600 chemokine receptor transport out of membrane raft | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Loss of CD24 enhances CXCR4 lipid raft association. Reason: CD24 limits CXCR4 raft residence, consistent with transport out of rafts; a modulatory, non-core role. Supporting Evidence: PMID:16390867 the loss of CD24 augmented cellular cholesterol levels and enhanced CXCR4 lipid raft association |
| GO:0032600 chemokine receptor transport out of membrane raft | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Loss of CD24 enhances CXCR4 lipid raft association. Reason: CD24 limits CXCR4 raft residence, consistent with transport out of rafts; a modulatory, non-core role. Supporting Evidence: PMID:16390867 the loss of CD24 augmented cellular cholesterol levels and enhanced CXCR4 lipid raft association |
| GO:0032715 negative regulation of interleukin-6 production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CD24 (via Siglec-G/10) limits DAMP-induced IL-6/TNF/MCP-1 production. Reason: Mouse knockout DCs produce more cytokines in response to HSP70/90; the effect is executed by Siglec signaling triggered by CD24 ligation, so it is retained as a non-core outcome of the core immunoregulatory ligand function. Supporting Evidence: PMID:19264983 CD24-/- and Siglecg-/- DCs produced significantly higher IL-6 and TNF-Ξ± in response to recombinant HSP70 and HSP90 |
| GO:0032720 negative regulation of tumor necrosis factor production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CD24 (via Siglec-G/10) limits DAMP-induced IL-6/TNF/MCP-1 production. Reason: Mouse knockout DCs produce more cytokines in response to HSP70/90; the effect is executed by Siglec signaling triggered by CD24 ligation, so it is retained as a non-core outcome of the core immunoregulatory ligand function. Supporting Evidence: PMID:19264983 CD24-/- and Siglecg-/- DCs produced significantly higher IL-6 and TNF-Ξ± in response to recombinant HSP70 and HSP90 |
| GO:0032913 negative regulation of transforming growth factor beta3 production | IMP PMID:16930538 Regulation of E-cadherin and TGF-beta3 expression by CD24 in... | KEEP AS NON CORE | Summary: CD24 knockdown altered TGF-beta3 expression in an oral epithelial cell line. Reason: Single knockdown study measuring expression; indirect, non-core. Supporting Evidence: PMID:16930538 Regulation of E-cadherin and TGF-beta3 expression by CD24 in cultured oral epithelial cells |
| GO:0042104 positive regulation of activated T cell proliferation | IDA PMID:11272271 Antibodies recognizing CD24 LAP epitope on human T cells enh... | KEEP AS NON CORE | Summary: Anti-CD24 antibodies enhance CD3/CD28- and IL-2-driven T cell proliferation. Reason: Antibody engagement study supporting a costimulatory-like role on activated T cells; non-core. Supporting Evidence: PMID:11272271 Anti-LAP antibodies strongly enhanced the response of T cells to a combination of anti-CD3/CD28 mAbs and enhanced proliferative response induced by recombinant IL-2 |
| GO:0042632 cholesterol homeostasis | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: CD24 loss raises cellular cholesterol in pre-B cells. Reason: A secondary observation in the CXCR4 study; there is no evidence that CD24 participates in cholesterol homeostasis mechanisms. Supporting Evidence: PMID:16390867 the loss of CD24 augmented cellular cholesterol levels |
| GO:0042632 cholesterol homeostasis | ISS PMID:16390867 CD24 affects CXCR4 function in pre-B lymphocytes and breast ... | MARK AS OVER ANNOTATED | Summary: CD24 loss raises cellular cholesterol in pre-B cells. Reason: A secondary observation in the CXCR4 study; there is no evidence that CD24 participates in cholesterol homeostasis mechanisms. Supporting Evidence: PMID:16390867 the loss of CD24 augmented cellular cholesterol levels |
| GO:0043408 regulation of MAPK cascade | IDA PMID:11313396 CD24 induces apoptosis in human B cells via the glycolipid-e... | KEEP AS NON CORE | Summary: CD24 cross-linking activates MAP kinases in Burkitt lymphoma cells. Reason: Experimentally supported downstream signaling effect; non-core. Supporting Evidence: PMID:11313396 We also observed activation of mitogen-activated protein kinases following CD24 cross-linking |
| GO:0043627 response to estrogen | IEP PMID:10037815 Combining SSH and cDNA microarrays for rapid identification ... | MARK AS OVER ANNOTATED | Summary: CD24 is over-expressed in ER-positive breast cancer lines. Reason: Correlation of expression with ER status in cell lines; no estrogen-treatment response or CD24 role in that response was shown. Supporting Evidence: PMID:10037815 Flow cytometry and immunofluorescence confirmed that CD24 protein was over-expressed |
| GO:0045121 membrane raft | IBA GO_REF:0000033 | ACCEPT | Summary: GPI-anchored CD24 resides in glycolipid-enriched membrane rafts. Reason: Biochemical raft (GEM) fractionation in B cells, consistent with its GPI anchor; raft residence is central to how CD24 signals via LYN. Supporting Evidence: PMID:11313396 analysis of biochemically separated glycolipid-enriched membrane (GEM) fractions indicated enhanced association of CD24 and Lyn protein tyrosine kinase in GEM PMID:16390867 linked to the membrane via a glycosyl-phosphatidylinositol (GPI-) anchor and therefore localizes in lipid rafts |
| GO:0045121 membrane raft | IDA PMID:11313396 CD24 induces apoptosis in human B cells via the glycolipid-e... | ACCEPT | Summary: GPI-anchored CD24 resides in glycolipid-enriched membrane rafts. Reason: Biochemical raft (GEM) fractionation in B cells, consistent with its GPI anchor; raft residence is central to how CD24 signals via LYN. Supporting Evidence: PMID:11313396 analysis of biochemically separated glycolipid-enriched membrane (GEM) fractions indicated enhanced association of CD24 and Lyn protein tyrosine kinase in GEM PMID:16390867 linked to the membrane via a glycosyl-phosphatidylinositol (GPI-) anchor and therefore localizes in lipid rafts |
| GO:0045121 membrane raft | IEA GO_REF:0000107 | ACCEPT | Summary: GPI-anchored CD24 resides in glycolipid-enriched membrane rafts. Reason: Biochemical raft (GEM) fractionation in B cells, consistent with its GPI anchor; raft residence is central to how CD24 signals via LYN. Supporting Evidence: PMID:11313396 analysis of biochemically separated glycolipid-enriched membrane (GEM) fractions indicated enhanced association of CD24 and Lyn protein tyrosine kinase in GEM PMID:16390867 linked to the membrane via a glycosyl-phosphatidylinositol (GPI-) anchor and therefore localizes in lipid rafts |
| GO:0045730 respiratory burst | IDA PMID:8223854 Activation of human monocytes and granulocytes by monoclonal... | KEEP AS NON CORE | Summary: CD24 cross-linking triggers the oxidative burst in primed granulocytes. Reason: Antibody cross-linking readout; CD24 does not itself contribute to NADPH oxidase activity. Non-core. Supporting Evidence: PMID:8223854 led to calcium fluxes and activation of the oxidative burst |
| GO:0051879 Hsp90 protein binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mouse CD24 co-immunoprecipitates with the DAMPs HSP70 and HSP90. Reason: Ortholog-based; CD24 associates with released HSP70/90 and HMGB1 and delivers them to Siglec-G/10 for inhibitory signaling. Retained as non-core binding. Supporting Evidence: PMID:19264983 Coimmunoprecipitations revealed that CD24 associates with both HSP70 and HSP90 |
| GO:0060170 ciliary membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-based localization to cilia/microvilli membranes. Reason: Plausible plasma membrane subdomains for an apical GPI-anchored protein in epithelial cells, but human-specific evidence was not reviewed; the core location is the external side of the plasma membrane. Supporting Evidence: file:human/CD24/CD24-uniprot.txt SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor, GPI-anchor. |
| GO:0071638 negative regulation of monocyte chemotactic protein-1 production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CD24 (via Siglec-G/10) limits DAMP-induced IL-6/TNF/MCP-1 production. Reason: Mouse knockout DCs produce more cytokines in response to HSP70/90; the effect is executed by Siglec signaling triggered by CD24 ligation, so it is retained as a non-core outcome of the core immunoregulatory ligand function. Supporting Evidence: PMID:19264983 CD24-/- and Siglecg-/- DCs produced significantly higher IL-6 and TNF-Ξ± in response to recombinant HSP70 and HSP90 |
| GO:0072112 podocyte differentiation | IMP PMID:19092120 Regeneration of glomerular podocytes by human renal progenit... | KEEP AS NON CORE | Summary: CD24+CD133+ renal progenitors differentiate into podocytes and tubular cells. Reason: CD24 is used as a progenitor marker in these studies; a direct role of CD24 in differentiation is not clearly shown in the abstracts. Retained as non-core, deferring to the IMP curation. Supporting Evidence: PMID:19092120 CD133+CD24+ cells consist of a hierarchical population of progenitors PMID:16885410 a subset of parietal epithelial cells (PEC) in the Bowman's capsule exhibit coexpression of the stem cell markers CD24 and CD133 |
| GO:0072139 glomerular parietal epithelial cell differentiation | IMP PMID:19092120 Regeneration of glomerular podocytes by human renal progenit... | KEEP AS NON CORE | Summary: CD24+CD133+ renal progenitors differentiate into podocytes and tubular cells. Reason: CD24 is used as a progenitor marker in these studies; a direct role of CD24 in differentiation is not clearly shown in the abstracts. Retained as non-core, deferring to the IMP curation. Supporting Evidence: PMID:19092120 CD133+CD24+ cells consist of a hierarchical population of progenitors PMID:16885410 a subset of parietal epithelial cells (PEC) in the Bowman's capsule exhibit coexpression of the stem cell markers CD24 and CD133 |
| GO:0097193 intrinsic apoptotic signaling pathway | NAS PMID:11313396 CD24 induces apoptosis in human B cells via the glycolipid-e... | KEEP AS NON CORE | Summary: CD24 cross-linking induces apoptosis in Burkitt lymphoma B cells. Reason: Supported by the cited study (NAS) as an antibody-induced effect; non-core. Supporting Evidence: PMID:11313396 induction of apoptosis in BL cells mediated by cross-linking of CD24 |
| GO:0098609 cell-cell adhesion | NAS PMID:15633604 Inhibition of human CD24 binding to platelet-bound P-selecti... | ACCEPT | Summary: CD24 mediates platelet binding to prostate cancer cells via P-selectin. Reason: Heterotypic cell-cell adhesion is the direct outcome of the P-selectin ligand function of CD24 on carcinoma cells and neutrophils. Supporting Evidence: PMID:15633604 P-selectin ligand CD24 mediates the binding of platelets to prostate cancer line DU145 cells in vitro |
| GO:0106015 negative regulation of inflammatory response to wounding | IEA GO_REF:0000107 | UNDECIDED | Summary: Ortholog-transferred opposite-sign regulation of inflammatory response to wounding. Reason: Both positive and negative regulation were transferred from mouse; the human evidence (Siglec-10-mediated suppression of DAMP responses) supports negative regulation of inflammation, but the specific wounding source studies were not reviewed and the positive-sign row cannot be adjudicated. Supporting Evidence: PMID:19264983 CD24 partners with Siglec-10 in humans or Siglec-G in mice to negatively regulate the immune response to proteins released by damaged cells |
| GO:0106016 positive regulation of inflammatory response to wounding | IEA GO_REF:0000107 | UNDECIDED | Summary: Ortholog-transferred opposite-sign regulation of inflammatory response to wounding. Reason: Both positive and negative regulation were transferred from mouse; the human evidence (Siglec-10-mediated suppression of DAMP responses) supports negative regulation of inflammation, but the specific wounding source studies were not reviewed and the positive-sign row cannot be adjudicated. Supporting Evidence: PMID:19264983 CD24 partners with Siglec-10 in humans or Siglec-G in mice to negatively regulate the immune response to proteins released by damaged cells |
| GO:2000768 positive regulation of nephron tubule epithelial cell differentiation | IMP PMID:16885410 Isolation and characterization of multipotent progenitor cel... | KEEP AS NON CORE | Summary: CD24+CD133+ renal progenitors differentiate into podocytes and tubular cells. Reason: CD24 is used as a progenitor marker in these studies; a direct role of CD24 in differentiation is not clearly shown in the abstracts. Retained as non-core, deferring to the IMP curation. Supporting Evidence: PMID:19092120 CD133+CD24+ cells consist of a hierarchical population of progenitors PMID:16885410 a subset of parietal epithelial cells (PEC) in the Bowman's capsule exhibit coexpression of the stem cell markers CD24 and CD133 |
| GO:0005102 signaling receptor binding | IDA PMID:31367043 CD24 signalling through macrophage Siglec-10 is a target for... | NEW | Summary: CD24 is the primary protein ligand of the inhibitory receptor Siglec-10. Reason: Siglec-10-Fc binding to cells requires CD24, and the CD24-Siglec-10 interaction inhibits macrophage phagocytosis; this ligand activity is the best-characterized CD24 molecular function and is not captured by existing annotations. Supporting Evidence: PMID:31367043 in the absence of surface sialylation, Siglec-10-Fc binding was nearly abolished by CD24 deletion, suggesting that CD24 is the primary protein ligand for Siglec-10 PMID:19264983 Siglec-10, but not Siglecs -5, -7 or -11, bound to CD24 |
| GO:0050777 negative regulation of immune response | IDA PMID:31367043 CD24 signalling through macrophage Siglec-10 is a target for... | NEW | Summary: CD24 on tumour cells inhibits macrophage phagocytosis through Siglec-10. Reason: Genetic deletion or antibody blockade of CD24 augments phagocytosis of human tumour cells, establishing CD24 as an anti-phagocytic inhibitory ligand. Supporting Evidence: PMID:31367043 Genetic ablation of either CD24 or Siglec-10, as well as blockade of the CD24-Siglec-10 interaction using monoclonal antibodies, robustly augment the phagocytosis of all CD24-expressing human tumours that we tested |
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Download this section (compressed HTML)Q: Which CD24 glycoforms (sialylation pattern, specific O-glycans) are required for Siglec-10 versus P-selectin recognition, and do they differ between immune cells and carcinomas?
Q: Does CD24 itself bind HMGB1/HSP70/HSP90 directly in human cells, or does it only scaffold their presentation to Siglec-10?
Experiment: Map glycosylation sites by glycoproteomics on CD24 from tumour lines and test Siglec-10-Fc binding of site-directed glycosylation mutants and glycoengineered cells.
Hypothesis: The CD24 peptide backbone positions specific sialylated O-glycans required for Siglec-10 engagement.
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