Cd48

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005515 protein binding	IPI PMID:1383383 CD48 is a counter-receptor for mouse CD2 and is involved in ...	MODIFY	Summary: IPI with mouse CD2 (P08920): CD48 identified as the counter-receptor recognized by a mouse CD2-Ig fusion; soluble CD48 and anti-CD48 mAbs block CD2-Ig binding. Reason: Generic protein binding is uninformative. The interaction shown is the heterophilic binding of CD48 to the T-cell adhesion molecule CD2, for which CD48 is the principal ligand in rodents (PMID:1383383; direct adhesion measurements with murine proteins, PMID:12356317). The informative MF is cell adhesion molecule binding. Proposed replacements: cell adhesion molecule binding Supporting Evidence: PMID:1383383 These results indicate that CD48 is a ligand for mouse CD2 and is involved in regulating T cell activation. PMID:1383383 Moreover, sCD48 also inhibited the mCD2Rg binding to the cellular ligand. PMID:12356317 heterophilic adhesion between the murine T-cell adhesion glycoprotein CD2 and its ligand CD48 file:mouse/Cd48/Cd48-uniprot.txt Interacts with CD2 (PubMed:1383383). Interacts with CD244;
GO:0005576 extracellular region	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: IEA extracellular region, reflecting the soluble form of CD48 documented for human CD48 (UniProt "Secreted", by similarity to P09326). Reason: A soluble form of CD48 circulates in human plasma and the location is transferred to mouse by similarity; plausible (GPI-anchored proteins can be shed) but not directly shown for mouse CD48, and secondary to the GPI-anchored cell-surface form where CD48 performs its ligand functions. Supporting Evidence: file:mouse/Cd48/Cd48-uniprot.txt {ECO:0000250\|UniProtKB:P09326}. Secreted
GO:0005576 extracellular region	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: ISO extracellular region, reflecting the soluble form of CD48 documented for human CD48 (UniProt "Secreted", by similarity to P09326). Reason: A soluble form of CD48 circulates in human plasma and the location is transferred to mouse by similarity; plausible (GPI-anchored proteins can be shed) but not directly shown for mouse CD48, and secondary to the GPI-anchored cell-surface form where CD48 performs its ligand functions. Supporting Evidence: file:mouse/Cd48/Cd48-uniprot.txt {ECO:0000250\|UniProtKB:P09326}. Secreted
GO:0005576 extracellular region	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: ISS extracellular region, reflecting the soluble form of CD48 documented for human CD48 (UniProt "Secreted", by similarity to P09326). Reason: A soluble form of CD48 circulates in human plasma and the location is transferred to mouse by similarity; plausible (GPI-anchored proteins can be shed) but not directly shown for mouse CD48, and secondary to the GPI-anchored cell-surface form where CD48 performs its ligand functions. Supporting Evidence: file:mouse/Cd48/Cd48-uniprot.txt {ECO:0000250\|UniProtKB:P09326}. Secreted
GO:0005886 plasma membrane	EXP PMID:1383383 CD48 is a counter-receptor for mouse CD2 and is involved in ...	ACCEPT	Summary: CD48 identified as a GPI-anchored cell-surface glycoprotein on mouse hematopoietic cells. Reason: Plasma membrane localization of mouse CD48 is well established: it is a GPI-anchored glycoprotein on the surface of hematopoietic cells (PMID:1383383), where it acts as a ligand for CD2 and 2B4. Supporting Evidence: PMID:1383383 The putative mouse CD2 ligand recognized by this mAb was a glycosyl phosphatidylinositol-anchored glycoprotein file:mouse/Cd48/Cd48-uniprot.txt Cell membrane {ECO:0000269\|PubMed:1383383};
GO:0005886 plasma membrane	IEA GO_REF:0000120	ACCEPT	Summary: IEA plasma membrane, consistent with experimental data for mouse CD48. Reason: Plasma membrane localization of mouse CD48 is well established: it is a GPI-anchored glycoprotein on the surface of hematopoietic cells (PMID:1383383), where it acts as a ligand for CD2 and 2B4. Supporting Evidence: file:mouse/Cd48/Cd48-uniprot.txt Cell membrane {ECO:0000269\|PubMed:1383383}; PMID:1383383 The putative mouse CD2 ligand recognized by this mAb was a glycosyl phosphatidylinositol-anchored glycoprotein
GO:0005886 plasma membrane	ISO GO_REF:0000096	ACCEPT	Summary: ISO plasma membrane, consistent with experimental data for mouse CD48. Reason: Plasma membrane localization of mouse CD48 is well established: it is a GPI-anchored glycoprotein on the surface of hematopoietic cells (PMID:1383383), where it acts as a ligand for CD2 and 2B4. Supporting Evidence: file:mouse/Cd48/Cd48-uniprot.txt Cell membrane {ECO:0000269\|PubMed:1383383}; PMID:1383383 The putative mouse CD2 ligand recognized by this mAb was a glycosyl phosphatidylinositol-anchored glycoprotein
GO:0005886 plasma membrane	ISO GO_REF:0000119	ACCEPT	Summary: ISO plasma membrane, consistent with experimental data for mouse CD48. Reason: Plasma membrane localization of mouse CD48 is well established: it is a GPI-anchored glycoprotein on the surface of hematopoietic cells (PMID:1383383), where it acts as a ligand for CD2 and 2B4. Supporting Evidence: file:mouse/Cd48/Cd48-uniprot.txt Cell membrane {ECO:0000269\|PubMed:1383383}; PMID:1383383 The putative mouse CD2 ligand recognized by this mAb was a glycosyl phosphatidylinositol-anchored glycoprotein
GO:0006955 immune response	IBA GO_REF:0000033	ACCEPT	Summary: IBA immune response for the CD2/SLAM family node (PTN000249437). Reason: CD48 is a pan-hematopoietic ligand for CD2 and 2B4 that regulates T cell and NK cell activity (PMID:1383383, PMID:9841922); immune response is correct, if general, for the family and for CD48. Supporting Evidence: PMID:1383383 These results indicate that CD48 is a ligand for mouse CD2 and is involved in regulating T cell activation. PMID:9841922 The interaction between 2B4 and CD48 identified in this study represents a new ligand pair that is conserved between rodents and humans within the CD2 subset of IgSF molecules.
GO:0007165 signal transduction	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: IBA signal transduction (PTN000249437). Reason: CD48 has no cytoplasmic domain, but participates in signaling as a ligand that engages 2B4 and CD2 and as a raft-resident component whose co-engagement with the TCR enhances raft-dependent zeta phosphorylation (PMID:9881969). The general term is acceptable; T cell activation and NK cell activation describe its role better. Supporting Evidence: PMID:9881969 CD48/TCR coengagement qualitatively and quantitatively enhances lipid raft-dependent zeta association with the actin cytoskeleton and zeta tyrosine phosphorylation. PMID:1383383 These results indicate that CD48 is a ligand for mouse CD2 and is involved in regulating T cell activation.
GO:0007165 signal transduction	IDA PMID:1383383 CD48 is a counter-receptor for mouse CD2 and is involved in ...	KEEP AS NON CORE	Summary: Anti-CD48 mAb crosslinking augmented anti-CD3 responses of splenic T cells. Reason: Antibody crosslinking of CD48 modulates TCR-driven responses, consistent with later work showing CD2:CD48 interactions enhance TCR signaling via lipid rafts (PMID:9881969). Signal transduction is very general; accepted as non-core with the more specific T cell activation annotation capturing the biology. Supporting Evidence: PMID:1383383 HM48-1 inhibited the phytohemagglutinin response and, when crosslinked, augmented the anti-CD3 response of splenic T cells PMID:9881969 We demonstrate that CD2:CD48 interactions enhance TCR-mediated functions.
GO:0009897 external side of plasma membrane	IBA GO_REF:0000033	ACCEPT	Summary: IBA external side of plasma membrane (PTN008989435). Reason: CD48 is GPI-anchored to the outer leaflet of the plasma membrane, making external side of plasma membrane the most precise location for the mature protein. Supporting Evidence: PMID:1383383 The putative mouse CD2 ligand recognized by this mAb was a glycosyl phosphatidylinositol-anchored glycoprotein file:mouse/Cd48/Cd48-uniprot.txt Lipid-anchor, GPI-anchor {ECO:0000269\|PubMed:1693656}. Membrane raft
GO:0009897 external side of plasma membrane	IDA PMID:1383383 CD48 is a counter-receptor for mouse CD2 and is involved in ...	ACCEPT	Summary: Surface staining of mouse hematopoietic cells with anti-CD48 mAb HM48-1; GPI-anchored glycoprotein. Reason: CD48 is GPI-anchored to the outer leaflet of the plasma membrane, making external side of plasma membrane the most precise location for the mature protein. Supporting Evidence: PMID:1383383 The putative mouse CD2 ligand recognized by this mAb was a glycosyl phosphatidylinositol-anchored glycoprotein file:mouse/Cd48/Cd48-uniprot.txt Cell membrane {ECO:0000269\|PubMed:1383383};
GO:0009897 external side of plasma membrane	IDA PMID:18971422 Aldehyde dehydrogenase 1a1 is dispensable for stem cell func...	ACCEPT	Summary: IDA from a hematopoietic stem cell study in which CD48 surface staining is presumably used as a SLAM-family marker for flow cytometric HSC purification (abstract-only cache does not mention CD48). Reason: The location is correct and well established for GPI-anchored CD48; the curator read the full text, where CD48 surface detection on hematopoietic cells is the likely basis. The paper is not about CD48 function, so it contributes little beyond confirming cell-surface expression. Supporting Evidence: file:mouse/Cd48/Cd48-uniprot.txt Cell membrane {ECO:0000269\|PubMed:1383383}; file:mouse/Cd48/Cd48-uniprot.txt Lipid-anchor, GPI-anchor {ECO:0000269\|PubMed:1693656}. Membrane raft
GO:0009897 external side of plasma membrane	IDA PMID:20660734 MicroRNAs enriched in hematopoietic stem cells differentiall...	ACCEPT	Summary: IDA from a hematopoietic stem cell study in which CD48 surface staining is presumably used as a SLAM-family marker for flow cytometric HSC purification (abstract-only cache does not mention CD48). Reason: The location is correct and well established for GPI-anchored CD48; the curator read the full text, where CD48 surface detection on hematopoietic cells is the likely basis. The paper is not about CD48 function, so it contributes little beyond confirming cell-surface expression. Supporting Evidence: file:mouse/Cd48/Cd48-uniprot.txt Cell membrane {ECO:0000269\|PubMed:1383383}; file:mouse/Cd48/Cd48-uniprot.txt Lipid-anchor, GPI-anchor {ECO:0000269\|PubMed:1693656}. Membrane raft
GO:0016020 membrane	IEA GO_REF:0000002	ACCEPT	Summary: IEA membrane from InterPro IPR015631 (CD2/SLAM receptor). Reason: Correct though general; CD48 is a GPI-anchored plasma membrane protein. Supporting Evidence: file:mouse/Cd48/Cd48-uniprot.txt Lipid-anchor, GPI-anchor {ECO:0000269\|PubMed:1693656}. Membrane raft
GO:0030101 natural killer cell activation	IBA GO_REF:0000033	MODIFY	Summary: Mouse CD48 regulates NK cell activation in both directions through 2B4; the dominant in vivo effect is inhibitory, so the positive 'natural killer cell activation' term, transferred from human, misstates its role. Reason: Re-assessed with an OpenScientist hypothesis run and the primary mouse literature. In mouse the direction of the CD48-2B4 signal is opposite to human: 2B4 ligation by CD48 on target cells inhibits NK lysis and IFN-gamma (PMID:15123744), 2B4-CD48 forms an MHC-independent inhibitory self-tolerance system (PMID:15870174), and deleting the whole Slam locus, including Cd48, enhances NK activation, with the inhibition mapping solely to 2B4 (PMID:27573813). The main contrary genetic result (PMID:15905190) was reinterpreted by the same group as prevention of fratricide (PMID:17537992). An activating contribution does exist in trans: CD48 on MHC-I-deficient targets contributes to missing-self NK activation (PMID:27054584). CD48 is therefore a bidirectional regulator of mouse NK activation through 2B4, not a participant in a positive activation process; the human-derived positive term should be replaced by the direction-neutral regulation term, with the well-supported inhibitory role captured separately (negative regulation of NK cell mediated cytotoxicity, NEW). This follows the convention for HLA-E, a ligand of both inhibitory and activating NK receptors, which carries regulation terms rather than NK cell activation. Not REMOVE, because trans activation by CD48 is directly documented in mouse. For the IBA: the node PTN008532944 is seeded by human CD2 and CD48, where the axis is activating; mouse Cd48 lies inside the clade but has target-specific experimental evidence that the 2B4 output diverges in rodents. Propagation Review Root cause: PROPAGATION BAD Failure modes: REGULATORY SIGN INVERSION LINEAGE OR TAXON MISMATCH Sources checked: PANTHER:PTN008532944 SUPPORTS SOURCE BUT NOT TARGET PAINT node seeded by human CD2 and human CD48 (UniProtKB:P09326), where CD48-2B4 signalling activates NK cells. Rodent Cd48 is inside the clade; the divergence is in the direction of the 2B4 output in rodents, not in CD48 binding. Mouse has experimental evidence of the reversed direction (PMID:15123744, PMID:27573813). Proposed replacements: regulation of natural killer cell activation Supporting Evidence: PMID:15123744 Surprisingly, we have found, using antibody-blocking and 2B4-deficient NK cells, that NK lysis of CD48(+) tumor and allogeneic targets is inhibited by 2B4 ligation. PMID:27573813 Analyses of mice lacking individual SFRs showed that the inhibitory function of the Slam locus was due solely to 2B4 and was not influenced positively or negatively by other SFRs. PMID:27054584 Here we show that the expression of the Signaling Lymphocyte Activation Molecule (SLAM) family members CD48 and Ly9 (CD229) by MHC-I-deficient tumor cells significantly contributes to NK cell activation. PMID:17537992 We show that in the absence of 2B4 signaling, activated NK cells have defective cytotoxicity and proliferation because of fratricide and not due to the absence of a 2B4-dependent activation signal. PMID:16002700 In human NK cells, 2B4/CD48 interaction induces activation signals, whereas in murine NK cells it sends inhibitory signals.
GO:0030101 natural killer cell activation	ISO GO_REF:0000119	MODIFY	Summary: Mouse CD48 regulates NK cell activation in both directions through 2B4; the dominant in vivo effect is inhibitory, so the positive 'natural killer cell activation' term, transferred from human, misstates its role. Reason: Re-assessed with an OpenScientist hypothesis run and the primary mouse literature. In mouse the direction of the CD48-2B4 signal is opposite to human: 2B4 ligation by CD48 on target cells inhibits NK lysis and IFN-gamma (PMID:15123744), 2B4-CD48 forms an MHC-independent inhibitory self-tolerance system (PMID:15870174), and deleting the whole Slam locus, including Cd48, enhances NK activation, with the inhibition mapping solely to 2B4 (PMID:27573813). The main contrary genetic result (PMID:15905190) was reinterpreted by the same group as prevention of fratricide (PMID:17537992). An activating contribution does exist in trans: CD48 on MHC-I-deficient targets contributes to missing-self NK activation (PMID:27054584). CD48 is therefore a bidirectional regulator of mouse NK activation through 2B4, not a participant in a positive activation process; the human-derived positive term should be replaced by the direction-neutral regulation term, with the well-supported inhibitory role captured separately (negative regulation of NK cell mediated cytotoxicity, NEW). This follows the convention for HLA-E, a ligand of both inhibitory and activating NK receptors, which carries regulation terms rather than NK cell activation. Not REMOVE, because trans activation by CD48 is directly documented in mouse. The ISO source is human CD48 (PMID:27249817 and related), where 2B4 signalling is activating; that direction does not transfer to mouse. Propagation Review Root cause: PROPAGATION BAD Failure modes: REGULATORY SIGN INVERSION LINEAGE OR TAXON MISMATCH Sources checked: UniProtKB:P09326 · CD48 SUPPORTS SOURCE BUT NOT TARGET Human CD48, whose IDA (PMID:27249817) shows CD48-2B4 activating human NK cells. Correct for human; the activating direction does not hold in mouse. Proposed replacements: regulation of natural killer cell activation Supporting Evidence: PMID:15123744 Surprisingly, we have found, using antibody-blocking and 2B4-deficient NK cells, that NK lysis of CD48(+) tumor and allogeneic targets is inhibited by 2B4 ligation. PMID:27573813 Analyses of mice lacking individual SFRs showed that the inhibitory function of the Slam locus was due solely to 2B4 and was not influenced positively or negatively by other SFRs. PMID:27054584 Here we show that the expression of the Signaling Lymphocyte Activation Molecule (SLAM) family members CD48 and Ly9 (CD229) by MHC-I-deficient tumor cells significantly contributes to NK cell activation. PMID:17537992 We show that in the absence of 2B4 signaling, activated NK cells have defective cytotoxicity and proliferation because of fratricide and not due to the absence of a 2B4-dependent activation signal. PMID:16002700 In human NK cells, 2B4/CD48 interaction induces activation signals, whereas in murine NK cells it sends inhibitory signals.
GO:0030101 natural killer cell activation	ISO GO_REF:0000119	MODIFY	Summary: Mouse CD48 regulates NK cell activation in both directions through 2B4; the dominant in vivo effect is inhibitory, so the positive 'natural killer cell activation' term, transferred from human, misstates its role. Reason: Re-assessed with an OpenScientist hypothesis run and the primary mouse literature. In mouse the direction of the CD48-2B4 signal is opposite to human: 2B4 ligation by CD48 on target cells inhibits NK lysis and IFN-gamma (PMID:15123744), 2B4-CD48 forms an MHC-independent inhibitory self-tolerance system (PMID:15870174), and deleting the whole Slam locus, including Cd48, enhances NK activation, with the inhibition mapping solely to 2B4 (PMID:27573813). The main contrary genetic result (PMID:15905190) was reinterpreted by the same group as prevention of fratricide (PMID:17537992). An activating contribution does exist in trans: CD48 on MHC-I-deficient targets contributes to missing-self NK activation (PMID:27054584). CD48 is therefore a bidirectional regulator of mouse NK activation through 2B4, not a participant in a positive activation process; the human-derived positive term should be replaced by the direction-neutral regulation term, with the well-supported inhibitory role captured separately (negative regulation of NK cell mediated cytotoxicity, NEW). This follows the convention for HLA-E, a ligand of both inhibitory and activating NK receptors, which carries regulation terms rather than NK cell activation. Not REMOVE, because trans activation by CD48 is directly documented in mouse. The ISO source is human CD48 (PMID:27249817 and related), where 2B4 signalling is activating; that direction does not transfer to mouse. Propagation Review Root cause: PROPAGATION BAD Failure modes: REGULATORY SIGN INVERSION LINEAGE OR TAXON MISMATCH Sources checked: UniProtKB:P09326 · CD48 SUPPORTS SOURCE BUT NOT TARGET Human CD48, whose IDA (PMID:27249817) shows CD48-2B4 activating human NK cells. Correct for human; the activating direction does not hold in mouse. Proposed replacements: regulation of natural killer cell activation Supporting Evidence: PMID:15123744 Surprisingly, we have found, using antibody-blocking and 2B4-deficient NK cells, that NK lysis of CD48(+) tumor and allogeneic targets is inhibited by 2B4 ligation. PMID:27573813 Analyses of mice lacking individual SFRs showed that the inhibitory function of the Slam locus was due solely to 2B4 and was not influenced positively or negatively by other SFRs. PMID:27054584 Here we show that the expression of the Signaling Lymphocyte Activation Molecule (SLAM) family members CD48 and Ly9 (CD229) by MHC-I-deficient tumor cells significantly contributes to NK cell activation. PMID:17537992 We show that in the absence of 2B4 signaling, activated NK cells have defective cytotoxicity and proliferation because of fratricide and not due to the absence of a 2B4-dependent activation signal. PMID:16002700 In human NK cells, 2B4/CD48 interaction induces activation signals, whereas in murine NK cells it sends inhibitory signals.
GO:0032991 protein-containing complex	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: ISO protein-containing complex from rat Cd48 (RGD:620620). Reason: Protein-containing complex is an uninformative cellular component. CD48 forms transient receptor-ligand complexes with CD2 and 2B4 across cell junctions and associates with raft-resident kinases, but it is not a stable subunit of a defined complex; the binding interactions are better captured by MF terms (receptor ligand activity, cell adhesion molecule binding). Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: RGD:620620 UNRESOLVED Rat Cd48 donor; the underlying rat annotation was not traced here. The transfer between rodent orthologs is phylogenetically sound, but the complex term itself is too uninformative to add value for mouse. Supporting Evidence: file:mouse/Cd48/Cd48-uniprot.txt Interacts with CD2 (PubMed:1383383). Interacts with CD244; PMID:17950006 We determined the structure of the complex between the N-terminal domains of mouse 2B4 and CD48
GO:0034113 heterotypic cell-cell adhesion	IBA GO_REF:0000033	ACCEPT	Summary: IBA heterotypic cell-cell adhesion (PTN008532944). Reason: In rodents CD48 is the principal CD2 counter-receptor and mediates weak heterophilic CD2-CD48 adhesion, measured directly between extended membrane surfaces carrying the murine proteins (PMID:12356317; PMID:1383383). Although low-affinity, this transient adhesion at the T cell:APC contact is the context in which CD48 co-stimulates TCR signaling, so it is part of the core rodent CD2-ligand function. Harmonized with the rat Cd48 review, which accepts the same IBA as core for the same reason; the human CD48 review keeps it non-core because human CD2 binds mainly CD58, a species difference rather than an inconsistency. Supporting Evidence: PMID:12356317 heterophilic adhesion between the murine T-cell adhesion glycoprotein CD2 and its ligand CD48 PMID:12356317 these measurements between extended membrane surfaces directly confirm that the low-affinity CD2-CD48 bond generates weak adhesion PMID:1383383 These results indicate that CD48 is a ligand for mouse CD2 and is involved in regulating T cell activation.
GO:0042110 T cell activation	IDA PMID:1383383 CD48 is a counter-receptor for mouse CD2 and is involved in ...	ACCEPT	Summary: Anti-CD48 mAb inhibited PHA responses and, when crosslinked, augmented anti-CD3 responses of splenic T cells. Reason: Supported by the mAb data in PMID:1383383 and by later work showing that CD2:CD48 engagement at the T cell:APC contact enhances TCR-mediated functions and raft-dependent zeta phosphorylation in mouse T cells (PMID:9881969). CD48 acts here as the CD2 ligand and a raft component co-engaged with the TCR. Supporting Evidence: PMID:1383383 HM48-1 inhibited the phytohemagglutinin response and, when crosslinked, augmented the anti-CD3 response of splenic T cells PMID:1383383 These results indicate that CD48 is a ligand for mouse CD2 and is involved in regulating T cell activation. PMID:9881969 We demonstrate that CD2:CD48 interactions enhance TCR-mediated functions. PMID:9881969 CD48/TCR coengagement qualitatively and quantitatively enhances lipid raft-dependent zeta association with the actin cytoskeleton and zeta tyrosine phosphorylation.
GO:0045121 membrane raft	IEA GO_REF:0000044	ACCEPT	Summary: IEA membrane raft from UniProt subcellular location (by similarity to human). Reason: GPI-anchored CD48 partitions into lipid rafts; in mouse T cells CD48 engagement recruits rafts to the site of T cell:APC contact and enhances raft-dependent TCR zeta signaling (PMID:9881969). Raft residence is also documented for the human ortholog. Supporting Evidence: file:mouse/Cd48/Cd48-uniprot.txt Lipid-anchor, GPI-anchor {ECO:0000269\|PubMed:1693656}. Membrane raft PMID:9881969 CD48/TCR coengagement qualitatively and quantitatively enhances lipid raft-dependent zeta association with the actin cytoskeleton and zeta tyrosine phosphorylation.
GO:0045121 membrane raft	ISO GO_REF:0000119	ACCEPT	Summary: ISO membrane raft from human CD48. Reason: GPI-anchored CD48 partitions into lipid rafts; in mouse T cells CD48 engagement recruits rafts to the site of T cell:APC contact and enhances raft-dependent TCR zeta signaling (PMID:9881969). Raft residence is also documented for the human ortholog. Supporting Evidence: PMID:9881969 CD48/TCR coengagement qualitatively and quantitatively enhances lipid raft-dependent zeta association with the actin cytoskeleton and zeta tyrosine phosphorylation. file:mouse/Cd48/Cd48-uniprot.txt Lipid-anchor, GPI-anchor {ECO:0000269\|PubMed:1693656}. Membrane raft
GO:0045121 membrane raft	ISO GO_REF:0000119	ACCEPT	Summary: ISO membrane raft from human CD48. Reason: GPI-anchored CD48 partitions into lipid rafts; in mouse T cells CD48 engagement recruits rafts to the site of T cell:APC contact and enhances raft-dependent TCR zeta signaling (PMID:9881969). Raft residence is also documented for the human ortholog. Supporting Evidence: PMID:9881969 CD48/TCR coengagement qualitatively and quantitatively enhances lipid raft-dependent zeta association with the actin cytoskeleton and zeta tyrosine phosphorylation. file:mouse/Cd48/Cd48-uniprot.txt Lipid-anchor, GPI-anchor {ECO:0000269\|PubMed:1693656}. Membrane raft
GO:0045121 membrane raft	ISS GO_REF:0000024	ACCEPT	Summary: ISS membrane raft from human CD48 (UniProt). Reason: GPI-anchored CD48 partitions into lipid rafts; in mouse T cells CD48 engagement recruits rafts to the site of T cell:APC contact and enhances raft-dependent TCR zeta signaling (PMID:9881969). Raft residence is also documented for the human ortholog. Supporting Evidence: file:mouse/Cd48/Cd48-uniprot.txt Lipid-anchor, GPI-anchor {ECO:0000269\|PubMed:1693656}. Membrane raft PMID:9881969 CD48/TCR coengagement qualitatively and quantitatively enhances lipid raft-dependent zeta association with the actin cytoskeleton and zeta tyrosine phosphorylation.
GO:0045321 leukocyte activation	IEA GO_REF:0000117	ACCEPT	Summary: IEA (ARBA) leukocyte activation. Reason: Correct general process; CD48 contributes to T cell activation as the CD2 ligand (PMID:1383383, PMID:9881969) and to regulation of NK cells via 2B4 (PMID:9841922). Supporting Evidence: PMID:1383383 These results indicate that CD48 is a ligand for mouse CD2 and is involved in regulating T cell activation. PMID:9881969 We demonstrate that CD2:CD48 interactions enhance TCR-mediated functions.
GO:0045576 mast cell activation	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: ISO mast cell activation from rat Cd48 (RGD:620620). Reason: CD48 is expressed on mast cells and has been implicated in mast cell responses (e.g. to FimH-expressing bacteria and via 2B4 interactions in allergic inflammation), but no evidence is cached here for mouse; the transfer from rat is plausible for a conserved pan-hematopoietic ligand. Kept as a non-core, cell-type-specific process. Supporting Evidence: file:mouse/Cd48/Cd48-uniprot.txt Interacts with CD2 (PubMed:1383383). Interacts with CD244;
GO:0048018 receptor ligand activity	IBA GO_REF:0000033	ACCEPT	Summary: IBA receptor ligand activity, from human CD48 experimental evidence. Reason: Core molecular function, directly supported for mouse: soluble mouse CD48 binds mouse 2B4 (Kd ~16 uM), 6-9-fold more strongly than CD2 (PMID:9841922), and the mouse 2B4-CD48 complex structure defines the binding interface (PMID:17950006). CD48 engagement regulates 2B4 signaling in NK cells. Supporting Evidence: PMID:9841922 purified soluble mCD48 bound m2B4 with a six- to ninefold higher affinity (Kd approximately 16 microM at 37 degreesC) than its other ligand, CD2. PMID:17950006 We determined the structure of the complex between the N-terminal domains of mouse 2B4 and CD48 PMID:9841922 The interaction between 2B4 and CD48 identified in this study represents a new ligand pair that is conserved between rodents and humans within the CD2 subset of IgSF molecules.
GO:0048018 receptor ligand activity	ISO GO_REF:0000119	ACCEPT	Summary: ISO receptor ligand activity, from human CD48 experimental evidence. Reason: Core molecular function, directly supported for mouse: soluble mouse CD48 binds mouse 2B4 (Kd ~16 uM), 6-9-fold more strongly than CD2 (PMID:9841922), and the mouse 2B4-CD48 complex structure defines the binding interface (PMID:17950006). CD48 engagement regulates 2B4 signaling in NK cells. Supporting Evidence: PMID:9841922 purified soluble mCD48 bound m2B4 with a six- to ninefold higher affinity (Kd approximately 16 microM at 37 degreesC) than its other ligand, CD2. PMID:17950006 We determined the structure of the complex between the N-terminal domains of mouse 2B4 and CD48 PMID:9841922 The interaction between 2B4 and CD48 identified in this study represents a new ligand pair that is conserved between rodents and humans within the CD2 subset of IgSF molecules.
GO:0045953 negative regulation of natural killer cell mediated cytotoxicity	IDA PMID:15123744 2B4 acts as a non-major histocompatibility complex binding i...	NEW	Summary: CD48 on target cells engages 2B4 on mouse NK cells and inhibits NK cytotoxicity; this is an MHC-independent self-tolerance mechanism. Reason: Participation: CD48 supplies the ligand that engages the inhibitory receptor; NK lysis is inhibited specifically for CD48-positive targets and relieved by 2B4 deficiency (PMID:15123744), the same axis protects syngeneic cells in vivo (PMID:15870174), and whole-locus deletion including Cd48 enhances NK responses (PMID:27573813). Comparator: HLA-E, the ligand of the inhibitory receptor NKG2A, carries GO:0045953 by IDA. Proposed in addition to the direction-neutral regulation term because inhibition is the dominant, multi-laboratory, in vivo-supported outcome in mouse. Supporting Evidence: PMID:15123744 Surprisingly, we have found, using antibody-blocking and 2B4-deficient NK cells, that NK lysis of CD48(+) tumor and allogeneic targets is inhibited by 2B4 ligation. PMID:15123744 Using a peritoneal tumor clearance assay, it was found that 2B4(-/-) mice have increased clearance of CD48(+) tumor cells in vivo. PMID:15870174 Here, we show that 2B4 (CD244) and CD48 represent a second system for murine NK-cell self-recognition. PMID:27573813 Analyses of mice lacking individual SFRs showed that the inhibitory function of the Slam locus was due solely to 2B4 and was not influenced positively or negatively by other SFRs.

Gene Description

Existing Annotations Review

Core Functions

Ligand of the SLAM-family receptor 2B4 (CD244). Cell-surface CD48 binds the 2B4 V domain (Kd ~16 uM in mouse). In mouse NK cells this engagement is predominantly inhibitory, restraining NK cytotoxicity toward CD48-positive cells, with an activating contribution in missing-self recognition.

Principal CD2 counter-receptor in rodents. Heterophilic CD2-CD48 binding mediates weak adhesion and, at the T cell:APC contact, recruits CD48-containing lipid rafts to enhance TCR zeta phosphorylation and T cell activation.

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

OpenScientist

📚 Additional Documentation

Notes

📄 View Raw YAML