CD63 (LAMP-3, tetraspanin-30) is a four-transmembrane-domain glycoprotein with a large, heavily N-glycosylated second extracellular loop and a C-terminal GYEVM lysosomal sorting motif. At steady state most of the protein resides on intracellular membranes: late endosomes, multivesicular bodies and their intraluminal vesicles, lysosomes, melanosomes and secretory granules such as platelet dense granules, neutrophil azurophil granules and endothelial Weibel-Palade bodies. It cycles to the plasma membrane, where it is exposed on the cell surface and is strongly up-regulated at the surface after degranulation, which makes it a classical activation marker of platelets, basophils and mast cells; intraluminal vesicles carrying CD63 are released as exosomes, for which it is a standard marker. As a tetraspanin it organizes membrane microdomains: it is a cell-surface binding partner for TIMP1, associates with beta1 integrin, CD9 and integrin alphaIIbbeta3, bridges VEGFR2 to beta1 integrin and controls VEGFR2 internalization, and drives ESCRT-independent sorting of the PMEL luminal domain into intraluminal vesicles during melanosome biogenesis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0002092 positive regulation of receptor internalization | IMP PMID:23632027 Tetraspanin CD63 promotes vascular endothelial growth factor... | ACCEPT | Summary: CD63 silencing impairs VEGF-induced internalization of VEGFR2 in endothelial cells. Reason: Direct loss-of-function evidence in primary human endothelial cells that CD63 promotes receptor internalization. Supporting Evidence: PMID:23632027 CD63 was furthermore required for efficient internalization of VEGFR2 in response to VEGF |
| GO:0005515 protein binding | IPI PMID:16917503 Identification of CD63 as a tissue inhibitor of metalloprote... | MODIFY | Summary: CD63 is the cell-surface binding partner of TIMP1. Reason: Generic protein binding is uninformative; the evidence shows CD63 acting as a cell-surface receptor that binds the extracellular ligand TIMP1 and transduces integrin/survival signaling. Proposed replacements: signaling receptor activity Supporting Evidence: PMID:16917503 the present study identified CD63 as a cell surface binding partner for TIMP-1, regulating cell survival and polarization via TIMP-1 modulation of tetraspanin/integrin signaling complex PMID:24635319 TIMP-1 modulates chemotaxis of human neural stem cells through CD63 and integrin signalling |
| GO:0005515 protein binding | IPI PMID:20374249 The pathogenic E. coli type III effector EspZ interacts with... | REMOVE | Summary: Reported interaction with the enteropathogenic E. coli effector EspZ. Reason: Generic protein binding is uninformative, and an interaction with a bacterial type III effector does not define a CD63 molecular function. Removal does not mean the interaction is false. Supporting Evidence: PMID:20374249 The pathogenic E. coli type III effector EspZ interacts with host CD98 and facilitates host cell prosurvival signalling |
| GO:0005515 protein binding | IPI PMID:25312088 Investigation of membrane protein-protein interactions using... | REMOVE | Summary: FRET/PLA detection of proximity between CD63 and a retroviral envelope protein. Reason: Generic protein binding is uninformative; the cited work is a methods paper demonstrating a FRET-PLA assay, and no specific CD63 function follows from it. Supporting Evidence: PMID:25312088 We have developed correlative FRET-PLA to monitor i |
| GO:0005515 protein binding | IPI PMID:28030805 TIMP-1 and CD82, a promising combined evaluation marker for ... | MODIFY | Summary: CD63 is the cell-surface binding partner of TIMP1. Reason: Generic protein binding is uninformative; the evidence shows CD63 acting as a cell-surface receptor that binds the extracellular ligand TIMP1 and transduces integrin/survival signaling. Proposed replacements: signaling receptor activity Supporting Evidence: PMID:16917503 the present study identified CD63 as a cell surface binding partner for TIMP-1, regulating cell survival and polarization via TIMP-1 modulation of tetraspanin/integrin signaling complex PMID:24635319 TIMP-1 modulates chemotaxis of human neural stem cells through CD63 and integrin signalling |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary interactome (HuRI) interaction with TMEM80. Reason: Generic protein binding from a systematic two-hybrid map; uninformative about CD63 function. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome |
| GO:0005576 extracellular region | IDA PMID:25645918 Human neutrophils secrete bioactive paucimannosidic proteins... | MODIFY | Summary: CD63 is detected outside the cell, in secreted vesicles. Reason: Extracellular region is correct but less specific than the evidence supports; CD63 reaches the extracellular space on secreted exosomes/granule-derived vesicles, and extracellular exosome is already annotated with multiple IDA/HDA rows. Proposed replacements: extracellular exosome Supporting Evidence: PMID:25645918 Human neutrophils secrete bioactive paucimannosidic proteins from azurophilic granules into pathogen-infected sputum file:human/CD63/CD63-uniprot.txt Secreted, extracellular exosome |
| GO:0005576 extracellular region | IEA GO_REF:0000044 | MODIFY | Summary: CD63 is detected outside the cell, in secreted vesicles. Reason: Extracellular region is correct but less specific than the evidence supports; CD63 reaches the extracellular space on secreted exosomes/granule-derived vesicles, and extracellular exosome is already annotated with multiple IDA/HDA rows. Proposed replacements: extracellular exosome Supporting Evidence: PMID:25645918 Human neutrophils secrete bioactive paucimannosidic proteins from azurophilic granules into pathogen-infected sputum file:human/CD63/CD63-uniprot.txt Secreted, extracellular exosome |
| GO:0005764 lysosome | IEA GO_REF:0000107 | MODIFY | Summary: CD63 is a lysosomal protein. Reason: Correct but less specific than supported; CD63 is an integral lysosomal membrane protein (GO:0005765, carried by several experimental rows). Proposed replacements: lysosomal membrane Supporting Evidence: file:human/CD63/CD63-uniprot.txt Lysosome membrane |
| GO:0005765 lysosomal membrane | EXP PMID:19640571 Palmitoylation supports the association of tetraspanin CD63 ... | ACCEPT | Summary: CD63 is an integral membrane protein of the lysosomal membrane. Reason: Established by the original cloning work and confirmed by lysosomal membrane proteomics and imaging; the C-terminal GYEVM motif targets it to the endosomal/lysosomal system. Supporting Evidence: PMID:1993697 CD63 antigen. A novel lysosomal membrane glycoprotein PMID:17897319 Integral and associated lysosomal membrane proteins file:human/CD63/CD63-uniprot.txt Lysosome membrane |
| GO:0005765 lysosomal membrane | HDA PMID:17897319 Integral and associated lysosomal membrane proteins. | ACCEPT | Summary: CD63 is an integral membrane protein of the lysosomal membrane. Reason: Established by the original cloning work and confirmed by lysosomal membrane proteomics and imaging; the C-terminal GYEVM motif targets it to the endosomal/lysosomal system. Supporting Evidence: PMID:1993697 CD63 antigen. A novel lysosomal membrane glycoprotein PMID:17897319 Integral and associated lysosomal membrane proteins file:human/CD63/CD63-uniprot.txt Lysosome membrane |
| GO:0005765 lysosomal membrane | IDA PMID:22431521 The role of ceroid lipofuscinosis neuronal protein 5 (CLN5) ... | ACCEPT | Summary: CD63 is an integral membrane protein of the lysosomal membrane. Reason: Established by the original cloning work and confirmed by lysosomal membrane proteomics and imaging; the C-terminal GYEVM motif targets it to the endosomal/lysosomal system. Supporting Evidence: PMID:1993697 CD63 antigen. A novel lysosomal membrane glycoprotein PMID:17897319 Integral and associated lysosomal membrane proteins file:human/CD63/CD63-uniprot.txt Lysosome membrane |
| GO:0005765 lysosomal membrane | IDA PMID:23632027 Tetraspanin CD63 promotes vascular endothelial growth factor... | ACCEPT | Summary: CD63 is an integral membrane protein of the lysosomal membrane. Reason: Established by the original cloning work and confirmed by lysosomal membrane proteomics and imaging; the C-terminal GYEVM motif targets it to the endosomal/lysosomal system. Supporting Evidence: PMID:1993697 CD63 antigen. A novel lysosomal membrane glycoprotein PMID:17897319 Integral and associated lysosomal membrane proteins file:human/CD63/CD63-uniprot.txt Lysosome membrane |
| GO:0005765 lysosomal membrane | IEA GO_REF:0000120 | ACCEPT | Summary: CD63 is an integral membrane protein of the lysosomal membrane. Reason: Established by the original cloning work and confirmed by lysosomal membrane proteomics and imaging; the C-terminal GYEVM motif targets it to the endosomal/lysosomal system. Supporting Evidence: PMID:1993697 CD63 antigen. A novel lysosomal membrane glycoprotein PMID:17897319 Integral and associated lysosomal membrane proteins file:human/CD63/CD63-uniprot.txt Lysosome membrane |
| GO:0005765 lysosomal membrane | TAS PMID:1993697 CD63 antigen. A novel lysosomal membrane glycoprotein, clone... | ACCEPT | Summary: CD63 is an integral membrane protein of the lysosomal membrane. Reason: Established by the original cloning work and confirmed by lysosomal membrane proteomics and imaging; the C-terminal GYEVM motif targets it to the endosomal/lysosomal system. Supporting Evidence: PMID:1993697 CD63 antigen. A novel lysosomal membrane glycoprotein PMID:17897319 Integral and associated lysosomal membrane proteins file:human/CD63/CD63-uniprot.txt Lysosome membrane |
| GO:0005770 late endosome | IEA GO_REF:0000107 | MODIFY | Summary: CD63 localizes to late endosomes. Reason: Correct but less specific than supported; CD63 is an integral protein of the late endosome membrane and of intraluminal vesicles (both annotated experimentally). Proposed replacements: late endosome membrane Supporting Evidence: PMID:10793155 the tetraspanin CD63/lamp3 distributes predominantly to the internal membranes of multivesicular-multilamellar late endosomes |
| GO:0005771 multivesicular body | IEA GO_REF:0000044 | MODIFY | Summary: CD63 localizes to multivesicular bodies. Reason: Correct but less specific than supported; experimental rows place CD63 on the MVB limiting membrane and on intraluminal vesicles. Proposed replacements: multivesicular body membrane multivesicular body, internal vesicle Supporting Evidence: PMID:10793155 distributes predominantly to the internal membranes of multivesicular-multilamellar late endosomes |
| GO:0005886 plasma membrane | EXP PMID:15351990 LAMP-1 and LAMP-2, but not LAMP-3, are reliable markers for ... | ACCEPT | Summary: CD63 cycles to the plasma membrane, where it associates with integrins and VEGFR2 and is exposed on the cell surface. Reason: Surface biotinylation, flow cytometry of activated platelets and mast cells, co-immunoprecipitation with surface integrins and the TIMP1 binding studies all place a pool of CD63 in the plasma membrane; the large second extracellular loop is exposed outside the cell. Most of the protein is intracellular at steady state, but the surface pool is functionally important and increases after degranulation. Supporting Evidence: PMID:19640571 Palmitoylation supports the association of tetraspanin CD63 with CD9 and integrin alphaIIbbeta3 in activated platelets PMID:16917503 confirmed CD63 interactions with TIMP-1, integrin beta1, and their co-localizations on the cell surface of human breast epithelial MCF10A cells file:human/CD63/CD63-uniprot.txt SUBCELLULAR LOCATION: Cell membrane |
| GO:0005886 plasma membrane | EXP PMID:19640571 Palmitoylation supports the association of tetraspanin CD63 ... | ACCEPT | Summary: CD63 cycles to the plasma membrane, where it associates with integrins and VEGFR2 and is exposed on the cell surface. Reason: Surface biotinylation, flow cytometry of activated platelets and mast cells, co-immunoprecipitation with surface integrins and the TIMP1 binding studies all place a pool of CD63 in the plasma membrane; the large second extracellular loop is exposed outside the cell. Most of the protein is intracellular at steady state, but the surface pool is functionally important and increases after degranulation. Supporting Evidence: PMID:19640571 Palmitoylation supports the association of tetraspanin CD63 with CD9 and integrin alphaIIbbeta3 in activated platelets PMID:16917503 confirmed CD63 interactions with TIMP-1, integrin beta1, and their co-localizations on the cell surface of human breast epithelial MCF10A cells file:human/CD63/CD63-uniprot.txt SUBCELLULAR LOCATION: Cell membrane |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: CD63 cycles to the plasma membrane, where it associates with integrins and VEGFR2 and is exposed on the cell surface. Reason: Surface biotinylation, flow cytometry of activated platelets and mast cells, co-immunoprecipitation with surface integrins and the TIMP1 binding studies all place a pool of CD63 in the plasma membrane; the large second extracellular loop is exposed outside the cell. Most of the protein is intracellular at steady state, but the surface pool is functionally important and increases after degranulation. Supporting Evidence: PMID:19640571 Palmitoylation supports the association of tetraspanin CD63 with CD9 and integrin alphaIIbbeta3 in activated platelets PMID:16917503 confirmed CD63 interactions with TIMP-1, integrin beta1, and their co-localizations on the cell surface of human breast epithelial MCF10A cells file:human/CD63/CD63-uniprot.txt SUBCELLULAR LOCATION: Cell membrane |
| GO:0005886 plasma membrane | IDA PMID:16917503 Identification of CD63 as a tissue inhibitor of metalloprote... | ACCEPT | Summary: CD63 cycles to the plasma membrane, where it associates with integrins and VEGFR2 and is exposed on the cell surface. Reason: Surface biotinylation, flow cytometry of activated platelets and mast cells, co-immunoprecipitation with surface integrins and the TIMP1 binding studies all place a pool of CD63 in the plasma membrane; the large second extracellular loop is exposed outside the cell. Most of the protein is intracellular at steady state, but the surface pool is functionally important and increases after degranulation. Supporting Evidence: PMID:19640571 Palmitoylation supports the association of tetraspanin CD63 with CD9 and integrin alphaIIbbeta3 in activated platelets PMID:16917503 confirmed CD63 interactions with TIMP-1, integrin beta1, and their co-localizations on the cell surface of human breast epithelial MCF10A cells file:human/CD63/CD63-uniprot.txt SUBCELLULAR LOCATION: Cell membrane |
| GO:0005886 plasma membrane | IDA PMID:23632027 Tetraspanin CD63 promotes vascular endothelial growth factor... | ACCEPT | Summary: CD63 cycles to the plasma membrane, where it associates with integrins and VEGFR2 and is exposed on the cell surface. Reason: Surface biotinylation, flow cytometry of activated platelets and mast cells, co-immunoprecipitation with surface integrins and the TIMP1 binding studies all place a pool of CD63 in the plasma membrane; the large second extracellular loop is exposed outside the cell. Most of the protein is intracellular at steady state, but the surface pool is functionally important and increases after degranulation. Supporting Evidence: PMID:19640571 Palmitoylation supports the association of tetraspanin CD63 with CD9 and integrin alphaIIbbeta3 in activated platelets PMID:16917503 confirmed CD63 interactions with TIMP-1, integrin beta1, and their co-localizations on the cell surface of human breast epithelial MCF10A cells file:human/CD63/CD63-uniprot.txt SUBCELLULAR LOCATION: Cell membrane |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: CD63 cycles to the plasma membrane, where it associates with integrins and VEGFR2 and is exposed on the cell surface. Reason: Surface biotinylation, flow cytometry of activated platelets and mast cells, co-immunoprecipitation with surface integrins and the TIMP1 binding studies all place a pool of CD63 in the plasma membrane; the large second extracellular loop is exposed outside the cell. Most of the protein is intracellular at steady state, but the surface pool is functionally important and increases after degranulation. Supporting Evidence: PMID:19640571 Palmitoylation supports the association of tetraspanin CD63 with CD9 and integrin alphaIIbbeta3 in activated platelets PMID:16917503 confirmed CD63 interactions with TIMP-1, integrin beta1, and their co-localizations on the cell surface of human breast epithelial MCF10A cells file:human/CD63/CD63-uniprot.txt SUBCELLULAR LOCATION: Cell membrane |
| GO:0005886 plasma membrane | TAS PMID:1993697 CD63 antigen. A novel lysosomal membrane glycoprotein, clone... | ACCEPT | Summary: CD63 cycles to the plasma membrane, where it associates with integrins and VEGFR2 and is exposed on the cell surface. Reason: Surface biotinylation, flow cytometry of activated platelets and mast cells, co-immunoprecipitation with surface integrins and the TIMP1 binding studies all place a pool of CD63 in the plasma membrane; the large second extracellular loop is exposed outside the cell. Most of the protein is intracellular at steady state, but the surface pool is functionally important and increases after degranulation. Supporting Evidence: PMID:19640571 Palmitoylation supports the association of tetraspanin CD63 with CD9 and integrin alphaIIbbeta3 in activated platelets PMID:16917503 confirmed CD63 interactions with TIMP-1, integrin beta1, and their co-localizations on the cell surface of human breast epithelial MCF10A cells file:human/CD63/CD63-uniprot.txt SUBCELLULAR LOCATION: Cell membrane |
| GO:0005886 plasma membrane | TAS PMID:8661157 Genetic localization of Cd63, a member of the transmembrane ... | ACCEPT | Summary: CD63 cycles to the plasma membrane, where it associates with integrins and VEGFR2 and is exposed on the cell surface. Reason: Surface biotinylation, flow cytometry of activated platelets and mast cells, co-immunoprecipitation with surface integrins and the TIMP1 binding studies all place a pool of CD63 in the plasma membrane; the large second extracellular loop is exposed outside the cell. Most of the protein is intracellular at steady state, but the surface pool is functionally important and increases after degranulation. Supporting Evidence: PMID:19640571 Palmitoylation supports the association of tetraspanin CD63 with CD9 and integrin alphaIIbbeta3 in activated platelets PMID:16917503 confirmed CD63 interactions with TIMP-1, integrin beta1, and their co-localizations on the cell surface of human breast epithelial MCF10A cells file:human/CD63/CD63-uniprot.txt SUBCELLULAR LOCATION: Cell membrane |
| GO:0005886 plasma membrane | TAS PMID:9602068 Characterisation of the mouse homologue of CD151 (PETA-3/SFA... | ACCEPT | Summary: CD63 cycles to the plasma membrane, where it associates with integrins and VEGFR2 and is exposed on the cell surface. Reason: Surface biotinylation, flow cytometry of activated platelets and mast cells, co-immunoprecipitation with surface integrins and the TIMP1 binding studies all place a pool of CD63 in the plasma membrane; the large second extracellular loop is exposed outside the cell. Most of the protein is intracellular at steady state, but the surface pool is functionally important and increases after degranulation. Supporting Evidence: PMID:19640571 Palmitoylation supports the association of tetraspanin CD63 with CD9 and integrin alphaIIbbeta3 in activated platelets PMID:16917503 confirmed CD63 interactions with TIMP-1, integrin beta1, and their co-localizations on the cell surface of human breast epithelial MCF10A cells file:human/CD63/CD63-uniprot.txt SUBCELLULAR LOCATION: Cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-481010 | ACCEPT | Summary: CD63 cycles to the plasma membrane, where it associates with integrins and VEGFR2 and is exposed on the cell surface. Reason: Surface biotinylation, flow cytometry of activated platelets and mast cells, co-immunoprecipitation with surface integrins and the TIMP1 binding studies all place a pool of CD63 in the plasma membrane; the large second extracellular loop is exposed outside the cell. Most of the protein is intracellular at steady state, but the surface pool is functionally important and increases after degranulation. Supporting Evidence: PMID:19640571 Palmitoylation supports the association of tetraspanin CD63 with CD9 and integrin alphaIIbbeta3 in activated platelets PMID:16917503 confirmed CD63 interactions with TIMP-1, integrin beta1, and their co-localizations on the cell surface of human breast epithelial MCF10A cells file:human/CD63/CD63-uniprot.txt SUBCELLULAR LOCATION: Cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6798739 | ACCEPT | Summary: CD63 cycles to the plasma membrane, where it associates with integrins and VEGFR2 and is exposed on the cell surface. Reason: Surface biotinylation, flow cytometry of activated platelets and mast cells, co-immunoprecipitation with surface integrins and the TIMP1 binding studies all place a pool of CD63 in the plasma membrane; the large second extracellular loop is exposed outside the cell. Most of the protein is intracellular at steady state, but the surface pool is functionally important and increases after degranulation. Supporting Evidence: PMID:19640571 Palmitoylation supports the association of tetraspanin CD63 with CD9 and integrin alphaIIbbeta3 in activated platelets PMID:16917503 confirmed CD63 interactions with TIMP-1, integrin beta1, and their co-localizations on the cell surface of human breast epithelial MCF10A cells file:human/CD63/CD63-uniprot.txt SUBCELLULAR LOCATION: Cell membrane |
| GO:0007160 cell-matrix adhesion | IMP PMID:23632027 Tetraspanin CD63 promotes vascular endothelial growth factor... | ACCEPT | Summary: CD63 silencing impairs endothelial cell adhesion and spreading on matrix through beta1 integrin. Reason: Loss-of-function evidence in primary human endothelial cells linking CD63 to beta1-integrin-dependent adhesion. Supporting Evidence: PMID:23632027 silencing of CD63 in primary ECs arrested capillary sprouting and tube formation in vitro because of impaired adhesion and migration of ECs |
| GO:0009986 cell surface | EXP PMID:16917503 Identification of CD63 as a tissue inhibitor of metalloprote... | ACCEPT | Summary: A pool of CD63 is present on the cell surface with its large extracellular loop exposed. Reason: Antibody labelling of intact cells, TIMP1 surface-binding assays and surface co-localization with beta1 integrin establish surface exposure; this is the basis for CD63 as a degranulation marker and an antibody target. Supporting Evidence: PMID:16917503 Small hairpin RNA (shRNA)-mediated CD63 downregulation effectively reduced TIMP-1 binding to the cell surface PMID:24635319 TIMP-1 modulates chemotaxis of human neural stem cells through CD63 and integrin signalling file:human/CD63/CD63-uniprot.txt Cell surface |
| GO:0009986 cell surface | EXP PMID:23632027 Tetraspanin CD63 promotes vascular endothelial growth factor... | ACCEPT | Summary: A pool of CD63 is present on the cell surface with its large extracellular loop exposed. Reason: Antibody labelling of intact cells, TIMP1 surface-binding assays and surface co-localization with beta1 integrin establish surface exposure; this is the basis for CD63 as a degranulation marker and an antibody target. Supporting Evidence: PMID:16917503 Small hairpin RNA (shRNA)-mediated CD63 downregulation effectively reduced TIMP-1 binding to the cell surface PMID:24635319 TIMP-1 modulates chemotaxis of human neural stem cells through CD63 and integrin signalling file:human/CD63/CD63-uniprot.txt Cell surface |
| GO:0009986 cell surface | EXP PMID:24635319 TIMP-1 modulates chemotaxis of human neural stem cells throu... | ACCEPT | Summary: A pool of CD63 is present on the cell surface with its large extracellular loop exposed. Reason: Antibody labelling of intact cells, TIMP1 surface-binding assays and surface co-localization with beta1 integrin establish surface exposure; this is the basis for CD63 as a degranulation marker and an antibody target. Supporting Evidence: PMID:16917503 Small hairpin RNA (shRNA)-mediated CD63 downregulation effectively reduced TIMP-1 binding to the cell surface PMID:24635319 TIMP-1 modulates chemotaxis of human neural stem cells through CD63 and integrin signalling file:human/CD63/CD63-uniprot.txt Cell surface |
| GO:0009986 cell surface | IDA PMID:15647390 CD63 interacts with the carboxy terminus of the colonic H+-K... | ACCEPT | Summary: A pool of CD63 is present on the cell surface with its large extracellular loop exposed. Reason: Antibody labelling of intact cells, TIMP1 surface-binding assays and surface co-localization with beta1 integrin establish surface exposure; this is the basis for CD63 as a degranulation marker and an antibody target. Supporting Evidence: PMID:16917503 Small hairpin RNA (shRNA)-mediated CD63 downregulation effectively reduced TIMP-1 binding to the cell surface PMID:24635319 TIMP-1 modulates chemotaxis of human neural stem cells through CD63 and integrin signalling file:human/CD63/CD63-uniprot.txt Cell surface |
| GO:0009986 cell surface | IEA GO_REF:0000044 | ACCEPT | Summary: A pool of CD63 is present on the cell surface with its large extracellular loop exposed. Reason: Antibody labelling of intact cells, TIMP1 surface-binding assays and surface co-localization with beta1 integrin establish surface exposure; this is the basis for CD63 as a degranulation marker and an antibody target. Supporting Evidence: PMID:16917503 Small hairpin RNA (shRNA)-mediated CD63 downregulation effectively reduced TIMP-1 binding to the cell surface PMID:24635319 TIMP-1 modulates chemotaxis of human neural stem cells through CD63 and integrin signalling file:human/CD63/CD63-uniprot.txt Cell surface |
| GO:0010008 endosome membrane | IDA PMID:15229288 Over-expression of Rififylin, a new RING finger and FYVE-lik... | ACCEPT | Summary: CD63 is an integral protein of endosomal membranes. Reason: Imaging and exosome-biogenesis studies place CD63 throughout the endosomal system; this is its principal steady-state location. Supporting Evidence: PMID:10793155 the tetraspanin CD63/lamp3 distributes predominantly to the internal membranes of multivesicular-multilamellar late endosomes PMID:22660413 Syndecan-syntenin-ALIX regulates the biogenesis of exosomes |
| GO:0010008 endosome membrane | IDA PMID:22660413 Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. | ACCEPT | Summary: CD63 is an integral protein of endosomal membranes. Reason: Imaging and exosome-biogenesis studies place CD63 throughout the endosomal system; this is its principal steady-state location. Supporting Evidence: PMID:10793155 the tetraspanin CD63/lamp3 distributes predominantly to the internal membranes of multivesicular-multilamellar late endosomes PMID:22660413 Syndecan-syntenin-ALIX regulates the biogenesis of exosomes |
| GO:0010633 negative regulation of epithelial cell migration | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred negative regulation of epithelial cell migration. Reason: CD63 modulates migration in several systems (endothelial cells, neural stem cells), though human data show reduced migration on CD63 loss in endothelium; the signed epithelial term is retained as a non-core, cell-type-specific role. Supporting Evidence: PMID:23632027 impaired adhesion and migration of ECs |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: Tetraspanin-family InterPro mapping to membrane. Reason: Membrane is true but uninformative here; CD63 is an integral protein of the late endosome/lysosome membranes and of the plasma membrane, both annotated. Proposed replacements: lysosomal membrane plasma membrane Supporting Evidence: file:human/CD63/CD63-uniprot.txt Lysosome membrane file:human/CD63/CD63-uniprot.txt SUBCELLULAR LOCATION: Cell membrane |
| GO:0016477 cell migration | IMP PMID:23632027 Tetraspanin CD63 promotes vascular endothelial growth factor... | KEEP AS NON CORE | Summary: CD63 silencing impairs endothelial cell migration and sprouting. Reason: Supported by the endothelial loss-of-function study; migration is a downstream cellular outcome of the adhesion/receptor-organizing function. Supporting Evidence: PMID:23632027 impaired adhesion and migration of ECs |
| GO:0030154 cell differentiation | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: ARBA rule mapping to the generic term cell differentiation. Reason: An automatic association-rule term with no CD63-specific evidence; the specific differentiation-related role documented for CD63 is melanosome maturation, which is annotated separately. Supporting Evidence: PMID:21962903 Inactivating CD63 in cell culture or in mice impairs amyloidogenesis and downstream melanosome morphogenesis |
| GO:0030855 epithelial cell differentiation | IEA GO_REF:0000107 | UNDECIDED | Summary: Ortholog-transferred epithelial cell differentiation. Reason: Transferred from rat; no human or mouse experimental support for a CD63 role in epithelial differentiation was found in the reviewed literature, and the source study was not available for assessment. Supporting Evidence: file:human/CD63/CD63-uniprot.txt SUBCELLULAR LOCATION: Cell membrane |
| GO:0031088 platelet dense granule membrane | TAS Reactome:R-HSA-481010 | ACCEPT | Summary: CD63 is a membrane component of platelet dense granules and is exposed on the surface after platelet activation. Reason: CD63 was originally described as a platelet activation marker, consistent with granule-membrane residence and activation-induced surface delivery. Supporting Evidence: PMID:1993697 originally described as a blood platelet activation marker PMID:19640571 Palmitoylation supports the association of tetraspanin CD63 with CD9 and integrin alphaIIbbeta3 in activated platelets |
| GO:0031902 late endosome membrane | EXP PMID:10793155 The tetraspanin CD63/lamp3 cycles between endocytic and secr... | ACCEPT | Summary: CD63 is an integral protein of the late endosome membrane. Reason: Immuno-electron microscopy in human endothelial cells and imaging in endothelial and other cells place CD63 on late endosomal membranes; this is a principal steady-state location. Supporting Evidence: PMID:10793155 the tetraspanin CD63/lamp3 distributes predominantly to the internal membranes of multivesicular-multilamellar late endosomes |
| GO:0031902 late endosome membrane | IDA PMID:23632027 Tetraspanin CD63 promotes vascular endothelial growth factor... | ACCEPT | Summary: CD63 is an integral protein of the late endosome membrane. Reason: Immuno-electron microscopy in human endothelial cells and imaging in endothelial and other cells place CD63 on late endosomal membranes; this is a principal steady-state location. Supporting Evidence: PMID:10793155 the tetraspanin CD63/lamp3 distributes predominantly to the internal membranes of multivesicular-multilamellar late endosomes |
| GO:0031902 late endosome membrane | IEA GO_REF:0000044 | ACCEPT | Summary: CD63 is an integral protein of the late endosome membrane. Reason: Immuno-electron microscopy in human endothelial cells and imaging in endothelial and other cells place CD63 on late endosomal membranes; this is a principal steady-state location. Supporting Evidence: PMID:10793155 the tetraspanin CD63/lamp3 distributes predominantly to the internal membranes of multivesicular-multilamellar late endosomes |
| GO:0031904 endosome lumen | IDA PMID:22660413 Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. | KEEP AS NON CORE | Summary: CD63 is detected in the endosome lumen, on intraluminal vesicles. Reason: CD63 is a membrane protein of intraluminal vesicles rather than a soluble luminal protein; the term is retained as a lower-precision description of that compartment. Supporting Evidence: PMID:22660413 Syndecan-syntenin-ALIX regulates the biogenesis of exosomes |
| GO:0031982 vesicle | IEA GO_REF:0000117 | MODIFY | Summary: ARBA mapping to vesicle. Reason: Vesicle is true but uninformative; the specific vesicular compartments (MVB internal vesicles, extracellular exosomes) are annotated experimentally. Proposed replacements: multivesicular body, internal vesicle extracellular exosome Supporting Evidence: PMID:10793155 distributes predominantly to the internal membranes of multivesicular-multilamellar late endosomes |
| GO:0032585 multivesicular body membrane | HDA PMID:12519789 Proteomic and biochemical analyses of human B cell-derived e... | ACCEPT | Summary: CD63 is on multivesicular body membranes, including intraluminal vesicles. Reason: Immuno-EM and exosome proteomics; this compartment is where CD63 performs ESCRT-independent cargo sorting. Supporting Evidence: PMID:12519789 Proteomic and biochemical analyses of human B cell-derived exosomes PMID:26280656 LAPTM4B facilitates late endosomal ceramide export to control cell death pathways |
| GO:0032585 multivesicular body membrane | IDA PMID:26280656 LAPTM4B facilitates late endosomal ceramide export to contro... | ACCEPT | Summary: CD63 is on multivesicular body membranes, including intraluminal vesicles. Reason: Immuno-EM and exosome proteomics; this compartment is where CD63 performs ESCRT-independent cargo sorting. Supporting Evidence: PMID:12519789 Proteomic and biochemical analyses of human B cell-derived exosomes PMID:26280656 LAPTM4B facilitates late endosomal ceramide export to control cell death pathways |
| GO:0032991 protein-containing complex | IEA GO_REF:0000107 | MODIFY | Summary: CD63 is part of protein complexes. Reason: Correct but uninformative; the documented complexes are tetraspanin-enriched microdomains containing CD9 and integrins, and the VEGFR2-beta1 integrin assembly. Complex binding is the more informative claim and is annotated separately. Proposed replacements: tetraspanin-enriched microdomain Supporting Evidence: PMID:19640571 Palmitoylation supports the association of tetraspanin CD63 with CD9 and integrin alphaIIbbeta3 in activated platelets PMID:23632027 CD63 associated with both Ξ²1 integrin and the main VEGF receptor on ECs, VEGFR2 |
| GO:0035577 azurophil granule membrane | TAS Reactome:R-HSA-6798739 | ACCEPT | Summary: CD63 is a membrane protein of neutrophil azurophil granules. Reason: Consistent with its lysosome-related granule residence and with its appearance at the neutrophil surface and in secretions after degranulation. Supporting Evidence: PMID:25645918 Human neutrophils secrete bioactive paucimannosidic proteins from azurophilic granules into pathogen-infected sputum |
| GO:0035646 endosome to melanosome transport | IMP PMID:21962903 The tetraspanin CD63 regulates ESCRT-independent and -depend... | ACCEPT | Summary: CD63 is required for sorting of the PMEL luminal domain into intraluminal vesicles en route to melanosomes. Reason: Loss-of-function in cells and mice directly implicates CD63 in this ESCRT-independent sorting step of melanosome biogenesis. Supporting Evidence: PMID:21962903 the tetraspanin CD63 directly participates in ESCRT-independent sorting of the PMEL luminal domain, but not of traditional ESCRT-dependent cargoes, to ILVs |
| GO:0042470 melanosome | EXP PMID:21962903 The tetraspanin CD63 regulates ESCRT-independent and -depend... | ACCEPT | Summary: CD63 localizes to melanosomes, the lysosome-related organelles of pigment cells. Reason: Direct imaging in melanocytic cells; consistent with its role in PMEL sorting and melanosome maturation. Supporting Evidence: PMID:21962903 PMEL-a component of melanocyte LROs (melanosomes)-is sorte file:human/CD63/CD63-uniprot.txt Melanosome |
| GO:0042470 melanosome | IEA GO_REF:0000044 | ACCEPT | Summary: CD63 localizes to melanosomes, the lysosome-related organelles of pigment cells. Reason: Direct imaging in melanocytic cells; consistent with its role in PMEL sorting and melanosome maturation. Supporting Evidence: PMID:21962903 PMEL-a component of melanocyte LROs (melanosomes)-is sorte file:human/CD63/CD63-uniprot.txt Melanosome |
| GO:0043473 pigmentation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CD63 loss impairs melanosome morphogenesis and hence pigmentation. Reason: Pigmentation is an organism-level outcome of the melanosome sorting function; retained as non-core. Supporting Evidence: PMID:21962903 Inactivating CD63 in cell culture or in mice impairs amyloidogenesis and downstream melanosome morphogenesis |
| GO:0044877 protein-containing complex binding | IEA GO_REF:0000107 | ACCEPT | Summary: CD63 binds multiprotein assemblies, including integrin and receptor complexes. Reason: CD63 associates with the CD9/integrin alphaIIbbeta3 complex in platelets and bridges VEGFR2 with beta1 integrin, which is the mechanistic core of its tetraspanin function. Supporting Evidence: PMID:19640571 Tetraspanin comple PMID:23632027 CD63 serves to bridge between Ξ²1 integrin and VEGFR2 because CD63 silencing disrupted VEGFR2-Ξ²1 integrin complex formation |
| GO:0045785 positive regulation of cell adhesion | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CD63 promotes integrin-dependent adhesion. Reason: Consistent with the human TIMP1/beta1-integrin and endothelial studies; a downstream cellular outcome of the receptor-organizing function. Supporting Evidence: PMID:16917503 TIMP-1 expression correlated with the level of active integrin beta1 on the cell surface independent of cell adhesion PMID:23632027 impaired adhesion and migration of ECs |
| GO:0045807 positive regulation of endocytosis | IEA GO_REF:0000107 | ACCEPT | Summary: CD63 promotes endocytosis of surface receptors, including VEGFR2. Reason: Directly supported in human endothelial cells; the same claim underlies the IMP positive regulation of receptor internalization row. Supporting Evidence: PMID:23632027 CD63 was furthermore required for efficient internalization of VEGFR2 in response to VEGF |
| GO:0048757 pigment granule maturation | IMP PMID:21962903 The tetraspanin CD63 regulates ESCRT-independent and -depend... | ACCEPT | Summary: CD63 is required for melanosome (pigment granule) maturation. Reason: CD63 inactivation impairs PMEL amyloid formation and downstream melanosome morphogenesis in cells and mice. Supporting Evidence: PMID:21962903 Inactivating CD63 in cell culture or in mice impairs amyloidogenesis and downstream melanosome morphogenesis |
| GO:0050931 pigment cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred pigment cell differentiation. Reason: Downstream of the melanosome biogenesis role and transferred from mouse; retained as non-core. Supporting Evidence: PMID:21962903 downstream melanosome morphogenesis |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | ACCEPT | Summary: CD63 is a canonical marker of secreted exosomes, derived from MVB intraluminal vesicles. Reason: Detected by proteomics and immunoisolation in exosomes from plasma, urine, B cells, T cells and cultured cells; this reflects release of the intraluminal vesicles in which CD63 resides. Supporting Evidence: PMID:15908444 We provide here the first evidence for the presence of exosomes in vivo, in the blood PMID:19056867 Normal human urine contains large numbers of exosomes file:human/CD63/CD63-uniprot.txt Secreted, extracellular exosome |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | ACCEPT | Summary: CD63 is a canonical marker of secreted exosomes, derived from MVB intraluminal vesicles. Reason: Detected by proteomics and immunoisolation in exosomes from plasma, urine, B cells, T cells and cultured cells; this reflects release of the intraluminal vesicles in which CD63 resides. Supporting Evidence: PMID:15908444 We provide here the first evidence for the presence of exosomes in vivo, in the blood PMID:19056867 Normal human urine contains large numbers of exosomes file:human/CD63/CD63-uniprot.txt Secreted, extracellular exosome |
| GO:0070062 extracellular exosome | IDA PMID:15908444 Exosomal-like vesicles are present in human blood plasma. | ACCEPT | Summary: CD63 is a canonical marker of secreted exosomes, derived from MVB intraluminal vesicles. Reason: Detected by proteomics and immunoisolation in exosomes from plasma, urine, B cells, T cells and cultured cells; this reflects release of the intraluminal vesicles in which CD63 resides. Supporting Evidence: PMID:15908444 We provide here the first evidence for the presence of exosomes in vivo, in the blood PMID:19056867 Normal human urine contains large numbers of exosomes file:human/CD63/CD63-uniprot.txt Secreted, extracellular exosome |
| GO:0070062 extracellular exosome | IDA PMID:21505438 Unidirectional transfer of microRNA-loaded exosomes from T c... | ACCEPT | Summary: CD63 is a canonical marker of secreted exosomes, derived from MVB intraluminal vesicles. Reason: Detected by proteomics and immunoisolation in exosomes from plasma, urine, B cells, T cells and cultured cells; this reflects release of the intraluminal vesicles in which CD63 resides. Supporting Evidence: PMID:15908444 We provide here the first evidence for the presence of exosomes in vivo, in the blood PMID:19056867 Normal human urine contains large numbers of exosomes file:human/CD63/CD63-uniprot.txt Secreted, extracellular exosome |
| GO:0070062 extracellular exosome | IDA PMID:23092844 Monitoring the Rab27 associated exosome pathway using nanopa... | ACCEPT | Summary: CD63 is a canonical marker of secreted exosomes, derived from MVB intraluminal vesicles. Reason: Detected by proteomics and immunoisolation in exosomes from plasma, urine, B cells, T cells and cultured cells; this reflects release of the intraluminal vesicles in which CD63 resides. Supporting Evidence: PMID:15908444 We provide here the first evidence for the presence of exosomes in vivo, in the blood PMID:19056867 Normal human urine contains large numbers of exosomes file:human/CD63/CD63-uniprot.txt Secreted, extracellular exosome |
| GO:0070062 extracellular exosome | IDA PMID:26387950 Apolipoprotein E Regulates Amyloid Formation within Endosome... | ACCEPT | Summary: CD63 is a canonical marker of secreted exosomes, derived from MVB intraluminal vesicles. Reason: Detected by proteomics and immunoisolation in exosomes from plasma, urine, B cells, T cells and cultured cells; this reflects release of the intraluminal vesicles in which CD63 resides. Supporting Evidence: PMID:15908444 We provide here the first evidence for the presence of exosomes in vivo, in the blood PMID:19056867 Normal human urine contains large numbers of exosomes file:human/CD63/CD63-uniprot.txt Secreted, extracellular exosome |
| GO:0070062 extracellular exosome | IDA PMID:30871575 Exosome microRNA signatures in patients with complex regiona... | ACCEPT | Summary: CD63 is a canonical marker of secreted exosomes, derived from MVB intraluminal vesicles. Reason: Detected by proteomics and immunoisolation in exosomes from plasma, urine, B cells, T cells and cultured cells; this reflects release of the intraluminal vesicles in which CD63 resides. Supporting Evidence: PMID:15908444 We provide here the first evidence for the presence of exosomes in vivo, in the blood PMID:19056867 Normal human urine contains large numbers of exosomes file:human/CD63/CD63-uniprot.txt Secreted, extracellular exosome |
| GO:0070062 extracellular exosome | IEA GO_REF:0000107 | ACCEPT | Summary: CD63 is a canonical marker of secreted exosomes, derived from MVB intraluminal vesicles. Reason: Detected by proteomics and immunoisolation in exosomes from plasma, urine, B cells, T cells and cultured cells; this reflects release of the intraluminal vesicles in which CD63 resides. Supporting Evidence: PMID:15908444 We provide here the first evidence for the presence of exosomes in vivo, in the blood PMID:19056867 Normal human urine contains large numbers of exosomes file:human/CD63/CD63-uniprot.txt Secreted, extracellular exosome |
| GO:0097487 multivesicular body, internal vesicle | IDA PMID:21962903 The tetraspanin CD63 regulates ESCRT-independent and -depend... | ACCEPT | Summary: CD63 resides on the intraluminal vesicles of multivesicular bodies. Reason: Immuno-EM in melanocytic and other cells; this is the location at which CD63 sorts PMEL and from which exosomal CD63 derives. Supporting Evidence: PMID:21962903 Cargo sorting to intraluminal vesicles (ILVs) of multivesicular endosomes is required for lysosome-related organelle (LRO) biogenesis PMID:26387950 Apolipoprotein E Regulates Amyloid Formation within Endosomes of Pigment Cells |
| GO:0097487 multivesicular body, internal vesicle | IDA PMID:26280656 LAPTM4B facilitates late endosomal ceramide export to contro... | ACCEPT | Summary: CD63 resides on the intraluminal vesicles of multivesicular bodies. Reason: Immuno-EM in melanocytic and other cells; this is the location at which CD63 sorts PMEL and from which exosomal CD63 derives. Supporting Evidence: PMID:21962903 Cargo sorting to intraluminal vesicles (ILVs) of multivesicular endosomes is required for lysosome-related organelle (LRO) biogenesis PMID:26387950 Apolipoprotein E Regulates Amyloid Formation within Endosomes of Pigment Cells |
| GO:0097487 multivesicular body, internal vesicle | IDA PMID:26387950 Apolipoprotein E Regulates Amyloid Formation within Endosome... | ACCEPT | Summary: CD63 resides on the intraluminal vesicles of multivesicular bodies. Reason: Immuno-EM in melanocytic and other cells; this is the location at which CD63 sorts PMEL and from which exosomal CD63 derives. Supporting Evidence: PMID:21962903 Cargo sorting to intraluminal vesicles (ILVs) of multivesicular endosomes is required for lysosome-related organelle (LRO) biogenesis PMID:26387950 Apolipoprotein E Regulates Amyloid Formation within Endosomes of Pigment Cells |
| GO:1900746 regulation of vascular endothelial growth factor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: CD63 bridges VEGFR2 to beta1 integrin and is required for VEGFR2 activation and downstream signaling. Reason: Silencing in primary human endothelial cells disrupts the VEGFR2-beta1 integrin complex and attenuates signaling, and VEGF fails to induce VEGFR2 phosphorylation in CD63-deficient mouse lungs; the IBA assigns the same role at the ancestral node. Supporting Evidence: PMID:23632027 CD63 silencing disrupted VEGFR2-Ξ²1 integrin complex formation identified using proximity ligation assays PMID:23632027 systemic delivery of VEGF failed to potently induce VEGFR2 phosphorylation and downstream signaling in CD63-deficient mouse lungs |
| GO:1900746 regulation of vascular endothelial growth factor signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: CD63 bridges VEGFR2 to beta1 integrin and is required for VEGFR2 activation and downstream signaling. Reason: Silencing in primary human endothelial cells disrupts the VEGFR2-beta1 integrin complex and attenuates signaling, and VEGF fails to induce VEGFR2 phosphorylation in CD63-deficient mouse lungs; the IBA assigns the same role at the ancestral node. Supporting Evidence: PMID:23632027 CD63 silencing disrupted VEGFR2-Ξ²1 integrin complex formation identified using proximity ligation assays PMID:23632027 systemic delivery of VEGF failed to potently induce VEGFR2 phosphorylation and downstream signaling in CD63-deficient mouse lungs |
| GO:1900746 regulation of vascular endothelial growth factor signaling pathway | IMP PMID:23632027 Tetraspanin CD63 promotes vascular endothelial growth factor... | ACCEPT | Summary: CD63 bridges VEGFR2 to beta1 integrin and is required for VEGFR2 activation and downstream signaling. Reason: Silencing in primary human endothelial cells disrupts the VEGFR2-beta1 integrin complex and attenuates signaling, and VEGF fails to induce VEGFR2 phosphorylation in CD63-deficient mouse lungs; the IBA assigns the same role at the ancestral node. Supporting Evidence: PMID:23632027 CD63 silencing disrupted VEGFR2-Ξ²1 integrin complex formation identified using proximity ligation assays PMID:23632027 systemic delivery of VEGF failed to potently induce VEGFR2 phosphorylation and downstream signaling in CD63-deficient mouse lungs |
| GO:1901379 regulation of potassium ion transmembrane transport | IDA PMID:15647390 CD63 interacts with the carboxy terminus of the colonic H+-K... | KEEP AS NON CORE | Summary: CD63 binds the colonic H+-K+-ATPase C-terminus and limits its surface abundance and Rb+ uptake. Reason: A specific instance of the general CD63 role in controlling surface abundance of membrane proteins; retained as a non-core, tissue-specific effect. Supporting Evidence: PMID:15647390 suppression of CD63 by RNA interference increased cell surface expression of HKalpha(2)/NKbeta(1) and (86)Rb(+) uptake |
| GO:2001046 positive regulation of integrin-mediated signaling pathway | IMP PMID:16917503 Identification of CD63 as a tissue inhibitor of metalloprote... | ACCEPT | Summary: CD63 promotes beta1 integrin activation and signaling. Reason: CD63 knockdown reverses TIMP1-mediated beta1 integrin activation and survival signaling in human breast epithelial cells, and attenuates beta1 signaling in endothelial cells. Supporting Evidence: PMID:16917503 consequently reversed TIMP-1-mediated integrin beta1 activation, cell survival signaling and apoptosis inhibition PMID:23632027 Signaling downstream of Ξ²1 integrin and VEGFR2 was attenuated in CD63-silenced cells |
| GO:2001046 positive regulation of integrin-mediated signaling pathway | IMP PMID:23632027 Tetraspanin CD63 promotes vascular endothelial growth factor... | ACCEPT | Summary: CD63 promotes beta1 integrin activation and signaling. Reason: CD63 knockdown reverses TIMP1-mediated beta1 integrin activation and survival signaling in human breast epithelial cells, and attenuates beta1 signaling in endothelial cells. Supporting Evidence: PMID:16917503 consequently reversed TIMP-1-mediated integrin beta1 activation, cell survival signaling and apoptosis inhibition PMID:23632027 Signaling downstream of Ξ²1 integrin and VEGFR2 was attenuated in CD63-silenced cells |
Loading supporting contentβ¦
Download this section (compressed HTML)Q: What fraction of total cellular CD63 is exposed at the plasma membrane in resting versus activated cells of each lineage, and how quickly does the surface pool turn over?
Q: How does CD63 select the PMEL luminal domain for ESCRT-independent intraluminal vesicle sorting - through direct binding, through local lipid ordering, or both?
Experiment: Compare surface labelling and TIMP1 binding of cells expressing CD63 with loop-swap or loop-deletion mutants, quantifying surface versus total protein by ratiometric flow cytometry with pH-sensitive tags.
Hypothesis: The large second extracellular loop of CD63 is the surface-exposed element that binds TIMP1 and determines antibody accessibility.
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)