CD68 (macrosialin in mouse) is a heavily glycosylated type I transmembrane protein of the LAMP family that is strongly and almost selectively expressed by monocytes, tissue macrophages and microglia, where it is the standard histological marker of the lineage. Its 298-residue ectodomain comprises a membrane-distal mucin-like region rich in serine and threonine with tandem repeats, a proline hinge, and a membrane-proximal LAMP-like domain; a short cytoplasmic tail carries lysosomal targeting information. The long isoform is predominantly on late endosomal and lysosomal membranes, consistent with the strongly granular cytoplasmic staining seen in macrophages, while a short isoform and a recirculating pool reach the plasma membrane. Its molecular function is not established; proposed roles include binding of tissue lectins or selectins and participation in the endosomal/lysosomal handling of phagocytosed material, including oxidized LDL in macrophage foam cells.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0002437 inflammatory response to antigenic stimulus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Transferred from mouse macrosialin; CD68 expression rises in inflamed tissue. Reason: An ortholog-transferred inflammatory process term with no direct human evidence; CD68 is a marker of activated macrophages rather than a demonstrated effector of the response. Retained as non-core, deferring to the source annotation. Supporting Evidence: PMID:28601280 HLA-DR and CD68 reflecting immune activation and response to tissue damage |
| GO:0002605 negative regulation of dendritic cell antigen processing and presentation | ISS GO_REF:0000024 | UNDECIDED | Summary: Transferred from mouse: negative regulation of dendritic cell antigen processing and presentation. Reason: The claim rests entirely on the mouse source annotation, whose supporting experiments were not available here; no human evidence was found, and a specific regulatory role for CD68 in dendritic cell antigen presentation cannot be adjudicated from the cached material. Supporting Evidence: file:human/CD68/CD68-uniprot.txt Could play a role in phagocytic activities of tissue |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Ten binary two-hybrid interactions from the HuRI reference interactome. Reason: Generic protein binding is uninformative, and these are systematic two-hybrid pairs (AGR2, MUC1, AQP6, TMEM179B, KTN1, MAL2, TOMM6, PLEKHB2, SGTB, CLEC2D) with no follow-up establishing a CD68 molecular function. Removal does not assert that the interactions are false. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Ten binary two-hybrid interactions from the HuRI reference interactome. Reason: Generic protein binding is uninformative, and these are systematic two-hybrid pairs (AGR2, MUC1, AQP6, TMEM179B, KTN1, MAL2, TOMM6, PLEKHB2, SGTB, CLEC2D) with no follow-up establishing a CD68 molecular function. Removal does not assert that the interactions are false. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Ten binary two-hybrid interactions from the HuRI reference interactome. Reason: Generic protein binding is uninformative, and these are systematic two-hybrid pairs (AGR2, MUC1, AQP6, TMEM179B, KTN1, MAL2, TOMM6, PLEKHB2, SGTB, CLEC2D) with no follow-up establishing a CD68 molecular function. Removal does not assert that the interactions are false. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Ten binary two-hybrid interactions from the HuRI reference interactome. Reason: Generic protein binding is uninformative, and these are systematic two-hybrid pairs (AGR2, MUC1, AQP6, TMEM179B, KTN1, MAL2, TOMM6, PLEKHB2, SGTB, CLEC2D) with no follow-up establishing a CD68 molecular function. Removal does not assert that the interactions are false. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Ten binary two-hybrid interactions from the HuRI reference interactome. Reason: Generic protein binding is uninformative, and these are systematic two-hybrid pairs (AGR2, MUC1, AQP6, TMEM179B, KTN1, MAL2, TOMM6, PLEKHB2, SGTB, CLEC2D) with no follow-up establishing a CD68 molecular function. Removal does not assert that the interactions are false. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Ten binary two-hybrid interactions from the HuRI reference interactome. Reason: Generic protein binding is uninformative, and these are systematic two-hybrid pairs (AGR2, MUC1, AQP6, TMEM179B, KTN1, MAL2, TOMM6, PLEKHB2, SGTB, CLEC2D) with no follow-up establishing a CD68 molecular function. Removal does not assert that the interactions are false. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Ten binary two-hybrid interactions from the HuRI reference interactome. Reason: Generic protein binding is uninformative, and these are systematic two-hybrid pairs (AGR2, MUC1, AQP6, TMEM179B, KTN1, MAL2, TOMM6, PLEKHB2, SGTB, CLEC2D) with no follow-up establishing a CD68 molecular function. Removal does not assert that the interactions are false. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Ten binary two-hybrid interactions from the HuRI reference interactome. Reason: Generic protein binding is uninformative, and these are systematic two-hybrid pairs (AGR2, MUC1, AQP6, TMEM179B, KTN1, MAL2, TOMM6, PLEKHB2, SGTB, CLEC2D) with no follow-up establishing a CD68 molecular function. Removal does not assert that the interactions are false. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Ten binary two-hybrid interactions from the HuRI reference interactome. Reason: Generic protein binding is uninformative, and these are systematic two-hybrid pairs (AGR2, MUC1, AQP6, TMEM179B, KTN1, MAL2, TOMM6, PLEKHB2, SGTB, CLEC2D) with no follow-up establishing a CD68 molecular function. Removal does not assert that the interactions are false. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Ten binary two-hybrid interactions from the HuRI reference interactome. Reason: Generic protein binding is uninformative, and these are systematic two-hybrid pairs (AGR2, MUC1, AQP6, TMEM179B, KTN1, MAL2, TOMM6, PLEKHB2, SGTB, CLEC2D) with no follow-up establishing a CD68 molecular function. Removal does not assert that the interactions are false. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome |
| GO:0005764 lysosome | IEA GO_REF:0000117 | MODIFY | Summary: CD68 is a lysosomal protein. Reason: Correct but less specific than supported; CD68 is an integral membrane protein of the lysosomal membrane (GO:0005765, carried by IBA and UniProt subcellular-location mapping). Proposed replacements: lysosomal membrane Supporting Evidence: file:human/CD68/CD68-uniprot.txt Lysosome membrane; Single-pass type I membrane PMID:7680921 a membrane proximal domain that has significant sequence homology to a family of lysosomal/plasma membrane shuttling proteins known as the lamp 1 group |
| GO:0005764 lysosome | ISS GO_REF:0000024 | MODIFY | Summary: CD68 is a lysosomal protein. Reason: Correct but less specific than supported; CD68 is an integral membrane protein of the lysosomal membrane (GO:0005765, carried by IBA and UniProt subcellular-location mapping). Proposed replacements: lysosomal membrane Supporting Evidence: file:human/CD68/CD68-uniprot.txt Lysosome membrane; Single-pass type I membrane PMID:7680921 a membrane proximal domain that has significant sequence homology to a family of lysosomal/plasma membrane shuttling proteins known as the lamp 1 group |
| GO:0005765 lysosomal membrane | IBA GO_REF:0000033 | ACCEPT | Summary: CD68 is an integral protein of the lysosomal membrane, the predominant location of the long isoform. Reason: The LAMP-like membrane-proximal domain and the UniProt subcellular location support lysosomal membrane residence, and the PAINT assignment places this location across the LAMP family; it explains the granular intracellular staining pattern of CD68 in macrophages. Supporting Evidence: file:human/CD68/CD68-uniprot.txt SUBCELLULAR LOCATION: [Isoform Long]: Endosome membrane; Single-pass PMID:7680921 significant sequence homology to a family of lysosomal/plasma membrane shuttling proteins known as the lamp 1 group |
| GO:0005765 lysosomal membrane | IEA GO_REF:0000044 | ACCEPT | Summary: CD68 is an integral protein of the lysosomal membrane, the predominant location of the long isoform. Reason: The LAMP-like membrane-proximal domain and the UniProt subcellular location support lysosomal membrane residence, and the PAINT assignment places this location across the LAMP family; it explains the granular intracellular staining pattern of CD68 in macrophages. Supporting Evidence: file:human/CD68/CD68-uniprot.txt SUBCELLULAR LOCATION: [Isoform Long]: Endosome membrane; Single-pass PMID:7680921 significant sequence homology to a family of lysosomal/plasma membrane shuttling proteins known as the lamp 1 group |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: A minor pool of CD68, chiefly the short isoform, reaches the plasma membrane. Reason: UniProt assigns the short isoform to the cell membrane and the LAMP family shuttles between lysosomes and the plasma membrane, so a surface pool is real; however, the bulk of CD68 is intracellular in endosomes and lysosomes, so this location is retained as non-core rather than as the principal site. Supporting Evidence: file:human/CD68/CD68-uniprot.txt SUBCELLULAR LOCATION: [Isoform Short]: Cell membrane; Single-pass type file:human/CD68/CD68-uniprot.txt Rapid recirculation of CD68 |
| GO:0005886 plasma membrane | IDA PMID:28601280 Staining of HLA-DR, Iba1 and CD68 in human microglia reveals... | KEEP AS NON CORE | Summary: A minor pool of CD68, chiefly the short isoform, reaches the plasma membrane. Reason: UniProt assigns the short isoform to the cell membrane and the LAMP family shuttles between lysosomes and the plasma membrane, so a surface pool is real; however, the bulk of CD68 is intracellular in endosomes and lysosomes, so this location is retained as non-core rather than as the principal site. Supporting Evidence: file:human/CD68/CD68-uniprot.txt SUBCELLULAR LOCATION: [Isoform Short]: Cell membrane; Single-pass type file:human/CD68/CD68-uniprot.txt Rapid recirculation of CD68 |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: A minor pool of CD68, chiefly the short isoform, reaches the plasma membrane. Reason: UniProt assigns the short isoform to the cell membrane and the LAMP family shuttles between lysosomes and the plasma membrane, so a surface pool is real; however, the bulk of CD68 is intracellular in endosomes and lysosomes, so this location is retained as non-core rather than as the principal site. Supporting Evidence: file:human/CD68/CD68-uniprot.txt SUBCELLULAR LOCATION: [Isoform Short]: Cell membrane; Single-pass type file:human/CD68/CD68-uniprot.txt Rapid recirculation of CD68 |
| GO:0005886 plasma membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: A minor pool of CD68, chiefly the short isoform, reaches the plasma membrane. Reason: UniProt assigns the short isoform to the cell membrane and the LAMP family shuttles between lysosomes and the plasma membrane, so a surface pool is real; however, the bulk of CD68 is intracellular in endosomes and lysosomes, so this location is retained as non-core rather than as the principal site. Supporting Evidence: file:human/CD68/CD68-uniprot.txt SUBCELLULAR LOCATION: [Isoform Short]: Cell membrane; Single-pass type file:human/CD68/CD68-uniprot.txt Rapid recirculation of CD68 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6798739 | KEEP AS NON CORE | Summary: A minor pool of CD68, chiefly the short isoform, reaches the plasma membrane. Reason: UniProt assigns the short isoform to the cell membrane and the LAMP family shuttles between lysosomes and the plasma membrane, so a surface pool is real; however, the bulk of CD68 is intracellular in endosomes and lysosomes, so this location is retained as non-core rather than as the principal site. Supporting Evidence: file:human/CD68/CD68-uniprot.txt SUBCELLULAR LOCATION: [Isoform Short]: Cell membrane; Single-pass type file:human/CD68/CD68-uniprot.txt Rapid recirculation of CD68 |
| GO:0010008 endosome membrane | IEA GO_REF:0000044 | MODIFY | Summary: CD68 is on endosomal membranes. Reason: Correct but less specific than supported; the long isoform is assigned to late endosome membranes (GO:0031902, carried by IBA) and to lysosomal membranes. Proposed replacements: late endosome membrane Supporting Evidence: file:human/CD68/CD68-uniprot.txt SUBCELLULAR LOCATION: [Isoform Long]: Endosome membrane; Single-pass |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: CD68 is a single-pass type I membrane protein. Reason: Membrane is true but uninformative; CD68 is an integral protein of the late endosome and lysosome membranes, with a smaller plasma membrane pool. Proposed replacements: lysosomal membrane late endosome membrane Supporting Evidence: PMID:7680921 The cDNA sequence predicts a type I integral membrane protein of 354 residues with a heavily glycosylated extracellular domain of 298 residues file:human/CD68/CD68-uniprot.txt Lysosome membrane; Single-pass type I membrane |
| GO:0016020 membrane | TAS PMID:7680921 Molecular cloning of CD68, a human macrophage marker related... | MODIFY | Summary: CD68 is a single-pass type I membrane protein. Reason: Membrane is true but uninformative; CD68 is an integral protein of the late endosome and lysosome membranes, with a smaller plasma membrane pool. Proposed replacements: lysosomal membrane late endosome membrane Supporting Evidence: PMID:7680921 The cDNA sequence predicts a type I integral membrane protein of 354 residues with a heavily glycosylated extracellular domain of 298 residues file:human/CD68/CD68-uniprot.txt Lysosome membrane; Single-pass type I membrane |
| GO:0030659 cytoplasmic vesicle membrane | IEA GO_REF:0000117 | MODIFY | Summary: ARBA mapping to cytoplasmic vesicle membrane. Reason: True but uninformative; the specific compartments are the late endosome and lysosome membranes. Proposed replacements: lysosomal membrane late endosome membrane Supporting Evidence: file:human/CD68/CD68-uniprot.txt Lysosome membrane; Single-pass type I membrane |
| GO:0031669 cellular response to nutrient levels | ISS GO_REF:0000024 | UNDECIDED | Summary: Transferred from mouse: cellular response to nutrient levels. Reason: No human evidence was found, and the mouse supporting experiments were not available; this expression-level response cannot be adjudicated here. Supporting Evidence: file:human/CD68/CD68-uniprot.txt Could play a role in phagocytic activities of tissue |
| GO:0031902 late endosome membrane | IBA GO_REF:0000033 | ACCEPT | Summary: CD68 is an integral protein of the late endosome membrane. Reason: UniProt places the long isoform on endosome membranes, and the PAINT node assigns late endosome membrane across the LAMP family, in which CD68's membrane-proximal domain sits. Supporting Evidence: file:human/CD68/CD68-uniprot.txt SUBCELLULAR LOCATION: [Isoform Long]: Endosome membrane; Single-pass PMID:7680921 a family of lysosomal/plasma membrane shuttling proteins known as the lamp 1 group |
| GO:0035425 autocrine signaling | IEA GO_REF:0000107 | UNDECIDED | Summary: Ortholog-transferred autocrine signaling, from rat. Reason: No human or mouse experimental support for CD68 acting in autocrine signaling was found in the reviewed material, and the source study could not be assessed. Supporting Evidence: file:human/CD68/CD68-uniprot.txt Could play a role in phagocytic activities of tissue |
| GO:0035577 azurophil granule membrane | TAS Reactome:R-HSA-6798739 | KEEP AS NON CORE | Summary: CD68 is listed among azurophil granule membrane proteins in the Reactome neutrophil degranulation event. Reason: Consistent with the lysosome-related nature of azurophil granules, though CD68 is characteristically a monocyte/macrophage rather than neutrophil protein; retained as non-core. Supporting Evidence: file:human/CD68/CD68-uniprot.txt Lysosome membrane; Single-pass type I membrane |
| GO:0071222 cellular response to lipopolysaccharide | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Transferred from mouse: CD68 expression responds to lipopolysaccharide. Reason: CD68 transcripts are inducible in myeloid cells, and macrophage activation raises CD68, but this is an expression response rather than a demonstrated participation in LPS signaling; retained as non-core, deferring to the source annotation. Supporting Evidence: PMID:7680921 CD68 transcripts are constitutively present in the promonocyte cell line U937 and are upregulated by phorbol myristic acid (PMA) |
| GO:0072594 establishment of protein localization to organelle | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT assignment of a role in establishment of protein localization to organelle, inherited from the LAMP family. Reason: LAMP-family members contribute to delivery of membrane proteins to lysosomes; CD68-specific evidence is absent, so the inherited process term is retained as non-core rather than removed. Supporting Evidence: PMID:7680921 a family of lysosomal/plasma membrane shuttling proteins known as the lamp 1 group |
| GO:0140052 cellular response to oxidised low-density lipoprotein particle stimulus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Transferred from mouse macrosialin, a reported oxidized-LDL binding protein of macrophages. Reason: The mouse ortholog has been described as binding oxidized LDL in foam cells, which fits CD68's endosomal/lysosomal handling of phagocytosed lipid, but no human experimental support was available; retained as non-core. Supporting Evidence: file:human/CD68/CD68-uniprot.txt Could play a role in phagocytic activities of tissue |
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Download this section (compressed HTML)Q: Does CD68 have any demonstrable ligand-binding activity in human cells, for example for tissue lectins, selectins or oxidized LDL, or is its mucin-like ectodomain purely structural?
Q: What fraction of CD68 is at the plasma membrane in resting versus activated human macrophages, and is that pool isoform-specific (short versus long)?
Experiment: Express tagged long and short isoforms in human macrophages, quantify surface versus total protein by pH-sensitive fluorescent tags and surface biotinylation, and test accessibility of anti-CD68 antibodies on intact versus permeabilized cells.
Hypothesis: The CD68 surface pool is isoform-dependent and sufficient for antibody targeting of macrophages in situ.
Experiment: Knock out CD68 in human monocyte-derived macrophages and compare uptake, lysosomal delivery and degradation of labelled oxidized LDL with wild-type cells, with rescue by each isoform.
Hypothesis: CD68 contributes to lysosomal handling of phagocytosed oxidized LDL.
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