CD46 (membrane cofactor protein) is a type I membrane glycoprotein with four extracellular complement-control domains and alternatively spliced extracellular and cytoplasmic regions. It binds C3b and C4b and acts as a cofactor for their proteolytic inactivation by complement factor I, protecting host cell surfaces from complement injury. In human T cells, CD46 also provides a costimulatory signal with the T-cell receptor and helps regulate the transition from inflammatory responses to IL-10-producing regulatory responses. Its extracellular interaction with Jagged1 regulates the availability of this ligand for Notch receptors. Cytoplasmic tail variants differ in signaling and interaction capacity. CD46 is also present on the inner acrosomal membrane of human sperm and can be exploited as an entry receptor by certain pathogens, including the Edmonston strain of measles virus. Impaired complement regulation by some CD46 variants predisposes to atypical hemolytic uremic syndrome. Vesicle-associated and shed soluble forms can retain factor I cofactor activity outside the cell.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0002079 inner acrosomal membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: CD46 occurs on the inner acrosomal membrane of human sperm. Reason: The source is an electronic transfer of a reviewed subcellular-location statement. The independently cached human sperm study supports this specialized location. It does not establish a general sperm-fusion activity, and no fertilization process is inferred from localization alone. |
| GO:0002250 adaptive immune response | IC PMID:12540904 Activation of human CD4+ cells with CD3 and CD46 induces a T... | KEEP AS NON CORE | Summary: CD46 contributes to human adaptive immune regulation. Reason: This curator inference from regulatory T-cell differentiation is consistent with CD3/CD46 costimulation and the IL-10-producing phenotype. The broad immune-system term is correct but less informative than the receptor activity and specific T-cell responses. Supporting Evidence: |
| GO:0002456 T cell mediated immunity | IBA GO_REF:0000033 | ACCEPT | Summary: CD46 contributes to human T-cell-mediated immunity. Reason: The PAINT assertion is consistent with independent human receptor stimulation and CD46-deficiency evidence. The target occurring among the descendant evidence sources does not make this phylogenetic annotation circular. The original PAINT node placement was not independently reconstructed. |
| GO:0002456 T cell mediated immunity | IMP PMID:23086448 The CD46-Jagged1 interaction is critical for human TH1 immun... | ACCEPT | Summary: CD46 supports human T-cell cytokine responses. Reason: The full article studies human CD46-deficient patient T cells as well as receptor stimulation, Jagged1 binding and Notch-dependent cytokine responses. Defects vary with residual receptor expression and stimulation conditions; the annotation does not imply that every T-cell response is absent in every carrier. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18796626 Mutations in complement C3 predispose to development of atyp... | MODIFY | Summary: CD46 binds the complement fragment C3b. Reason: The exact CD46/C3 pair has an IntAct ELISA record linked to Figure 2A-1 of the original study; the cached original publication itself is abstract-only. Independent complement-function studies support the same ligand-specific activity. GO:0001851 is more informative than generic protein binding. CD46 supplies cofactor activity for factor I; it is not the protease that cleaves C3b. Proposed replacements: complement component C3b binding |
| GO:0005515 protein binding | IPI PMID:23086448 The CD46-Jagged1 interaction is critical for human TH1 immun... | MODIFY | Summary: CD46 binds the complement fragment C3b. Reason: The full article uses C3b as a positive binding control in recombinant CD46 binding assays. Independent complement-function studies support the same ligand-specific activity. GO:0001851 is more informative than generic protein binding. CD46 supplies cofactor activity for factor I; it is not the protease that cleaves C3b. Proposed replacements: complement component C3b binding |
| GO:0005515 protein binding | IPI PMID:23086448 The CD46-Jagged1 interaction is critical for human TH1 immun... | MODIFY | Summary: CD46 binds and sequesters Jagged1, regulating its availability to Notch receptors. Reason: The original full article establishes extracellular CD46-Jagged1 binding by recombinant assays, surface plasmon resonance and NMR, then relates the interaction to ligand availability in human T cells. The more informative molecular activity is protein sequestering. This replacement is supported by the mechanistic source and does not imply that the high-throughput atlas itself demonstrated sequestration or that CD46 directly binds Notch1. Proposed replacements: protein sequestering activity Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:35922511 A physical wiring diagram for the human immune system. | MODIFY | Summary: CD46 binds and sequesters Jagged1, regulating its availability to Notch receptors. Reason: The original extracellular interaction atlas is accessible, but its exact CD46-Jagged1 supplementary assay row was not independently recovered. The same specific pair and its sequestration mechanism are established independently in PMID:23086448. The more informative molecular activity is protein sequestering. This replacement is supported by the mechanistic source and does not imply that the high-throughput atlas itself demonstrated sequestration or that CD46 directly binds Notch1. Proposed replacements: protein sequestering activity |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The C-terminal CD46 peptide binds an isolated PDZ domain from UniProtKB:A4D2P6. Reason: The exact publication-linked IntAct records contain quantified micromolar affinities from the holdup assay for a CD46 fragment spanning canonical residues 383-392 and a PDZ domain of this partner. This supports PDZ domain binding as a more precise molecular description. The evidence concerns a short CYT1-tail peptide and isolated domains in vitro, not an endogenous full-length complex or all CD46 splice products. This screening interaction is not used as a core physiological function. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | UNDECIDED | Summary: The CD46 fragmentomics assertion requires clarification of the recorded affinity values for UniProtKB:O75970. Reason: The exact publication-linked IntAct records were inspected, but this partner has only entries encoded as kd:1.0x10(molar), unlike the quantifiable micromolar values for other CD46 partners. The primary paper reports many pairs below the assay quantification threshold. These records alone cannot establish a positive interaction; the original supplementary target values and the meaning of this encoding were not verified. They also do not justify declaring binding impossible in every context. The original experimental annotation and partner are preserved pending clarification. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The C-terminal CD46 peptide binds an isolated PDZ domain from UniProtKB:P78352. Reason: The exact publication-linked IntAct records contain quantified micromolar affinities from the holdup assay for a CD46 fragment spanning canonical residues 383-392 and a PDZ domain of this partner. This supports PDZ domain binding as a more precise molecular description. The evidence concerns a short CYT1-tail peptide and isolated domains in vitro, not an endogenous full-length complex or all CD46 splice products. This screening interaction is not used as a core physiological function. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | UNDECIDED | Summary: The CD46 fragmentomics assertion requires clarification of the recorded affinity values for UniProtKB:Q07157. Reason: The exact publication-linked IntAct records were inspected, but this partner has only entries encoded as kd:1.0x10(molar), unlike the quantifiable micromolar values for other CD46 partners. The primary paper reports many pairs below the assay quantification threshold. These records alone cannot establish a positive interaction; the original supplementary target values and the meaning of this encoding were not verified. They also do not justify declaring binding impossible in every context. The original experimental annotation and partner are preserved pending clarification. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | UNDECIDED | Summary: The CD46 fragmentomics assertion requires clarification of the recorded affinity values for UniProtKB:Q14005. Reason: The exact publication-linked IntAct records were inspected, but this partner has only entries encoded as kd:1.0x10(molar), unlike the quantifiable micromolar values for other CD46 partners. The primary paper reports many pairs below the assay quantification threshold. These records alone cannot establish a positive interaction; the original supplementary target values and the meaning of this encoding were not verified. They also do not justify declaring binding impossible in every context. The original experimental annotation and partner are preserved pending clarification. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The C-terminal CD46 peptide binds an isolated PDZ domain from UniProtKB:Q14160. Reason: The exact publication-linked IntAct records contain quantified micromolar affinities from the holdup assay for a CD46 fragment spanning canonical residues 383-392 and a PDZ domain of this partner. This supports PDZ domain binding as a more precise molecular description. The evidence concerns a short CYT1-tail peptide and isolated domains in vitro, not an endogenous full-length complex or all CD46 splice products. This screening interaction is not used as a core physiological function. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The C-terminal CD46 peptide binds an isolated PDZ domain from UniProtKB:Q5T2W1. Reason: The exact publication-linked IntAct records contain quantified micromolar affinities from the holdup assay for a CD46 fragment spanning canonical residues 383-392 and a PDZ domain of this partner. This supports PDZ domain binding as a more precise molecular description. The evidence concerns a short CYT1-tail peptide and isolated domains in vitro, not an endogenous full-length complex or all CD46 splice products. This screening interaction is not used as a core physiological function. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | UNDECIDED | Summary: The CD46 fragmentomics assertion requires clarification of the recorded affinity values for UniProtKB:Q68DX3. Reason: The exact publication-linked IntAct records were inspected, but this partner has only entries encoded as kd:1.0x10(molar), unlike the quantifiable micromolar values for other CD46 partners. The primary paper reports many pairs below the assay quantification threshold. These records alone cannot establish a positive interaction; the original supplementary target values and the meaning of this encoding were not verified. They also do not justify declaring binding impossible in every context. The original experimental annotation and partner are preserved pending clarification. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The C-terminal CD46 peptide binds an isolated PDZ domain from UniProtKB:Q86UL8. Reason: The exact publication-linked IntAct records contain quantified micromolar affinities from the holdup assay for a CD46 fragment spanning canonical residues 383-392 and a PDZ domain of this partner. This supports PDZ domain binding as a more precise molecular description. The evidence concerns a short CYT1-tail peptide and isolated domains in vitro, not an endogenous full-length complex or all CD46 splice products. This screening interaction is not used as a core physiological function. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | UNDECIDED | Summary: The CD46 fragmentomics assertion requires clarification of the recorded affinity values for UniProtKB:Q86UT5. Reason: The exact publication-linked IntAct records were inspected, but this partner has only entries encoded as kd:1.0x10(molar), unlike the quantifiable micromolar values for other CD46 partners. The primary paper reports many pairs below the assay quantification threshold. These records alone cannot establish a positive interaction; the original supplementary target values and the meaning of this encoding were not verified. They also do not justify declaring binding impossible in every context. The original experimental annotation and partner are preserved pending clarification. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | UNDECIDED | Summary: The CD46 fragmentomics assertion requires clarification of the recorded affinity values for UniProtKB:Q8N448. Reason: The exact publication-linked IntAct records were inspected, but this partner has only entries encoded as kd:1.0x10(molar), unlike the quantifiable micromolar values for other CD46 partners. The primary paper reports many pairs below the assay quantification threshold. These records alone cannot establish a positive interaction; the original supplementary target values and the meaning of this encoding were not verified. They also do not justify declaring binding impossible in every context. The original experimental annotation and partner are preserved pending clarification. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | UNDECIDED | Summary: The CD46 fragmentomics assertion requires clarification of the recorded affinity values for UniProtKB:Q8NI35. Reason: The exact publication-linked IntAct records were inspected, but this partner has only entries encoded as kd:1.0x10(molar), unlike the quantifiable micromolar values for other CD46 partners. The primary paper reports many pairs below the assay quantification threshold. These records alone cannot establish a positive interaction; the original supplementary target values and the meaning of this encoding were not verified. They also do not justify declaring binding impossible in every context. The original experimental annotation and partner are preserved pending clarification. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | UNDECIDED | Summary: The CD46 fragmentomics assertion requires clarification of the recorded affinity values for UniProtKB:Q8TBB1. Reason: The exact publication-linked IntAct records were inspected, but this partner has only entries encoded as kd:1.0x10(molar), unlike the quantifiable micromolar values for other CD46 partners. The primary paper reports many pairs below the assay quantification threshold. These records alone cannot establish a positive interaction; the original supplementary target values and the meaning of this encoding were not verified. They also do not justify declaring binding impossible in every context. The original experimental annotation and partner are preserved pending clarification. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The C-terminal CD46 peptide binds an isolated PDZ domain from UniProtKB:Q92796. Reason: The exact publication-linked IntAct records contain quantified micromolar affinities from the holdup assay for a CD46 fragment spanning canonical residues 383-392 and a PDZ domain of this partner. This supports PDZ domain binding as a more precise molecular description. The evidence concerns a short CYT1-tail peptide and isolated domains in vitro, not an endogenous full-length complex or all CD46 splice products. This screening interaction is not used as a core physiological function. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | UNDECIDED | Summary: The CD46 fragmentomics assertion requires clarification of the recorded affinity values for UniProtKB:Q99767. Reason: The exact publication-linked IntAct records were inspected, but this partner has only entries encoded as kd:1.0x10(molar), unlike the quantifiable micromolar values for other CD46 partners. The primary paper reports many pairs below the assay quantification threshold. These records alone cannot establish a positive interaction; the original supplementary target values and the meaning of this encoding were not verified. They also do not justify declaring binding impossible in every context. The original experimental annotation and partner are preserved pending clarification. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The C-terminal CD46 peptide binds an isolated PDZ domain from UniProtKB:Q9C0E4. Reason: The exact publication-linked IntAct records contain quantified micromolar affinities from the holdup assay for a CD46 fragment spanning canonical residues 383-392 and a PDZ domain of this partner. This supports PDZ domain binding as a more precise molecular description. The evidence concerns a short CYT1-tail peptide and isolated domains in vitro, not an endogenous full-length complex or all CD46 splice products. This screening interaction is not used as a core physiological function. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | UNDECIDED | Summary: The CD46 fragmentomics assertion requires clarification of the recorded affinity values for UniProtKB:Q9Y3R0. Reason: The exact publication-linked IntAct records were inspected, but this partner has only entries encoded as kd:1.0x10(molar), unlike the quantifiable micromolar values for other CD46 partners. The primary paper reports many pairs below the assay quantification threshold. These records alone cannot establish a positive interaction; the original supplementary target values and the meaning of this encoding were not verified. They also do not justify declaring binding impossible in every context. The original experimental annotation and partner are preserved pending clarification. Supporting Evidence: |
| GO:0005576 extracellular region | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Released vesicular and soluble CD46 can remain complement-active outside the cell. Reason: The original qualifier is is_active_in, so an extracellular ectodomain alone is not the full justification. The primary abstract reports tumor-cell release of vesicle-associated CD46 and soluble CD46 lacking the transmembrane and cytoplasmic regions; both forms promoted factor I-mediated C3b cleavage. This directly supports extracellular functional activity. The context-dependent released forms are retained as non-core alongside the principal membrane role. Full methods were not accessible, and neither constitutive secretion by all tissues nor exosome identity is inferred; the PAINT node placement was not reconstructed. Supporting Evidence: PMID:15307194 Both vesicular and soluble forms of CD46 remained functional and promoted C3b cleavage by factor I. file:human/CD46/CD46-uniprot.txt |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: CD46 is a plasma-membrane receptor and complement regulator. Reason: The phylogenetic annotation agrees with the experimentally supported membrane topology and human cell-surface assays. The target appearing among source descendants is legitimate PAINT evidence, not circularity. |
| GO:0005886 plasma membrane | IDA PMID:20534589 Characterization of the membrane-targeting C1 domain in Past... | ACCEPT | Summary: Human CD46 is present at the plasma membrane in the assayed cells. Reason: Although this article primarily investigates a bacterial toxin, the full methods and results explicitly use anti-human CD46 surface staining as a plasma-membrane marker in the imaging experiments. The annotation is target-specific and is not rejected because the paper title foregrounds another protein. Supporting Evidence: |
| GO:0005886 plasma membrane | NAS PMID:1711570 Membrane cofactor protein of the complement system: alternat... | ACCEPT | Summary: CD46 is an integral plasma-membrane glycoprotein. Reason: The cached abstract describes cloned MCP/CD46 isoforms with transmembrane and cytoplasmic regions. Independent surface-labeling and receptor-function experiments corroborate this location. The original NAS or TAS code is retained unchanged. |
| GO:0005886 plasma membrane | TAS PMID:1711570 Membrane cofactor protein of the complement system: alternat... | ACCEPT | Summary: CD46 is an integral plasma-membrane glycoprotein. Reason: The cached abstract describes cloned MCP/CD46 isoforms with transmembrane and cytoplasmic regions. Independent surface-labeling and receptor-function experiments corroborate this location. The original NAS or TAS code is retained unchanged. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-1006143 | ACCEPT | Summary: CD46 acts at the plasma membrane during factor I-dependent complement inactivation. Reason: The cached Reactome event places membrane cofactor protein in C3b/C4b recognition and factor I recruitment or cleavage reactions. CD46 is the membrane-associated cofactor; the cleavage is catalyzed by factor I. Independent topology and surface assays support the compartment. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8951486 | ACCEPT | Summary: CD46 acts at the plasma membrane during factor I-dependent complement inactivation. Reason: The cached Reactome event places membrane cofactor protein in C3b/C4b recognition and factor I recruitment or cleavage reactions. CD46 is the membrane-associated cofactor; the cleavage is catalyzed by factor I. Independent topology and surface assays support the compartment. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-977602 | ACCEPT | Summary: CD46 acts at the plasma membrane during factor I-dependent complement inactivation. Reason: The cached Reactome event places membrane cofactor protein in C3b/C4b recognition and factor I recruitment or cleavage reactions. CD46 is the membrane-associated cofactor; the cleavage is catalyzed by factor I. Independent topology and surface assays support the compartment. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-977615 | ACCEPT | Summary: CD46 acts at the plasma membrane during factor I-dependent complement inactivation. Reason: The cached Reactome event places membrane cofactor protein in C3b/C4b recognition and factor I recruitment or cleavage reactions. CD46 is the membrane-associated cofactor; the cleavage is catalyzed by factor I. Independent topology and surface assays support the compartment. |
| GO:0005925 focal adhesion | HDA PMID:21423176 Analysis of the myosin-II-responsive focal adhesion proteome... | UNDECIDED | Summary: The focal-adhesion proteomics assignment remains unverified at the CD46 target-row level. Reason: The original full article describes a large myosin-dependent focal-adhesion proteome, but the CD46-specific supplementary identification and its localization context were not accessible in the material inspected. The lack of CD46 in the main text is not evidence of misattribution. Without the target-level evidence, this specific HDA location remains undecided rather than being removed. Supporting Evidence: |
| GO:0008593 regulation of Notch signaling pathway | IDA PMID:23086448 The CD46-Jagged1 interaction is critical for human TH1 immun... | ACCEPT | Summary: CD46 regulates Notch signaling through its interaction with Jagged1. Reason: Recombinant binding, resting-cell colocalization, receptor downregulation, ligand competition and signaling measurements support regulation of the Jagged1-Notch interaction. CD46 is not assigned Notch-receptor or protease activity; the source supports ligand sequestration and regulated availability. Supporting Evidence: |
| GO:0009986 cell surface | IDA PMID:23086448 The CD46-Jagged1 interaction is critical for human TH1 immun... | ACCEPT | Summary: CD46 is exposed on the cell surface. Reason: Direct cell-surface staining, ligand-binding experiments and receptor downregulation in the human T-cell study independently support the location. The electronic InterPro assertion, where applicable, is corroborated by these experiments without claiming that the mapping rule was independently reconstructed. |
| GO:0009986 cell surface | IEA GO_REF:0000002 | ACCEPT | Summary: CD46 is exposed on the cell surface. Reason: Direct cell-surface staining, ligand-binding experiments and receptor downregulation in the human T-cell study independently support the location. The electronic InterPro assertion, where applicable, is corroborated by these experiments without claiming that the mapping rule was independently reconstructed. |
| GO:0016020 membrane | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: CD46 is a membrane protein. Reason: The broad electronic membrane location is correct for the transmembrane receptor and is corroborated by cloned isoforms and surface imaging. More precise plasma-membrane and cell-surface annotations describe its major site of action; specialized sperm localization is retained separately. |
| GO:0032733 positive regulation of interleukin-10 production | IDA PMID:12540904 Activation of human CD4+ cells with CD3 and CD46 induces a T... | ACCEPT | Summary: CD46 costimulation promotes IL-10 production by human CD4 T cells. Reason: The original abstract directly reports an IL-10-producing phenotype after CD3/CD46 co-engagement in the presence of IL-2. The later full mechanistic study supports an IL-2- and stimulation-dependent cytokine switch. This is a receptor-mediated regulatory activity, not IL-10 synthesis by CD46 itself. Supporting Evidence: PMID:12540904 induces a Tr1-specific cytokine phenotype in human CD4+ T cells |
| GO:0038023 signaling receptor activity | TAS PMID:8402913 The human CD46 molecule is a receptor for measles virus (Edm... | MODIFY | Summary: CD46 mediates entry of the Edmonston strain of measles virus. Reason: The original abstract demonstrates human CD46-dependent measles-virus binding and infection in transfected hamster cells, with inhibition by anti-CD46 antibodies. This supports virus receptor activity, rather than endogenous signal transduction. The distinct human T-cell costimulatory activity is represented separately with its own source; virus usage is a non-core exploitation of the host membrane protein. Proposed replacements: virus receptor activity Supporting Evidence: |
| GO:0042102 positive regulation of T cell proliferation | IDA PMID:12540904 Activation of human CD4+ cells with CD3 and CD46 induces a T... | ACCEPT | Summary: CD46 costimulation promotes proliferation of human T cells. Reason: The original abstract explicitly reports strong proliferation following CD3/CD46 co-engagement with IL-2. Independent human receptor costimulation experiments corroborate this response. The annotation describes a contextual regulatory contribution, not a cell-autonomous mitogenic enzyme activity or a universal proliferation defect in CD46 deficiency. |
| GO:0043382 positive regulation of memory T cell differentiation | IDA PMID:12540904 Activation of human CD4+ cells with CD3 and CD46 induces a T... | KEEP AS NON CORE | Summary: CD3/CD46-costimulated human T cells acquire a memory phenotype. Reason: This outcome is explicitly reported in the original abstract and is compatible with the curator assignment. It is a downstream, context-dependent differentiation phenotype rather than a distinct defining molecular activity of CD46. Supporting Evidence: |
| GO:0045296 cadherin binding | IPI PMID:23086448 The CD46-Jagged1 interaction is critical for human TH1 immun... | UNDECIDED | Summary: The specific cadherin-binding assertion requires target-level confirmation. Reason: The full source describes CD46 association with alpha-E-catenin and cites Supplementary Figure 4a for human T-cell experiments. The GOA supporting entity is E-cadherin/CDH1 (P12830), and the relevant supplementary evidence was not recovered. Association with a catenin or cadherin-containing complex cannot by itself resolve the precise cadherin-binding claim. This is an evidence-access limitation, not a conclusion that the curator used the wrong gene or that the interaction is false. Supporting Evidence: |
| GO:0045591 positive regulation of regulatory T cell differentiation | IDA PMID:12540904 Activation of human CD4+ cells with CD3 and CD46 induces a T... | ACCEPT | Summary: CD46 costimulation supports an IL-10-producing regulatory T-cell phenotype. Reason: The original abstract directly links CD3/CD46 co-engagement with IL-2 to Tr1 differentiation and suppression of bystander T-cell activation. The annotation is appropriate at the stated regulatory T-cell level; it is not narrowed to an untested FOXP3-positive lineage. Supporting Evidence: |
| GO:0045959 negative regulation of complement activation, classical pathway | IBA GO_REF:0000033 | ACCEPT | Summary: CD46 limits classical complement activation by supporting factor I-mediated C4b inactivation. Reason: The inherited cofactor function is biologically consistent with human MCP/CD46 studies and the cached C4b reactions. CD46 binds the complement substrate and supplies the cofactor contribution; factor I performs the proteolysis. The original PAINT node placement was not independently reconstructed, and donor count is not treated as a measure of annotation quality. A human-MCP-transfected-cell study directly supports the C4b-cofactor arm under classical-pathway activation; its measured C3b cofactor effects depend on the activation context. |
| GO:0050776 regulation of immune response | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: CD46 regulates immune responses. Reason: The broad electronic process is consistent with complement control and human T-cell costimulation. These specific activities provide the useful mechanistic description; a separate broad immune-response core is unnecessary. |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | UNDECIDED | Summary: The exosome proteomics assignment awaits inspection of the CD46-specific identification. Reason: The cached abstract describes a B-cell exosome proteome, but it does not report the CD46 target row and full target-level data were not recovered. The original experimental annotation is preserved without assuming that every membrane protein is an exosome constituent or rejecting it because the abstract focuses on the proteome as a whole. Supporting Evidence: |
| GO:0071636 positive regulation of transforming growth factor beta production | IDA PMID:12540904 Activation of human CD4+ cells with CD3 and CD46 induces a T... | UNDECIDED | Summary: The specific TGF-beta-production result remains unverified. Reason: The accessible original abstract establishes IL-10 production, proliferation and a regulatory phenotype after CD3/CD46 costimulation, but does not report the TGF-beta measurement. Full-text access attempts did not recover the relevant experiment. A generic Tr1 phenotype is not substituted for that cytokine-specific evidence; the original experimental assertion is retained undecided. Supporting Evidence: |
| GO:0140311 protein sequestering activity | IDA PMID:23086448 The CD46-Jagged1 interaction is critical for human TH1 immun... | ACCEPT | Summary: CD46 sequesters Jagged1 and regulates its availability to Notch receptors. Reason: The full paper establishes direct CD46-Jagged1 ectodomain binding and a cell-surface model in which abundant CD46 associates with Jagged1 in resting human T cells. CD46 downregulation permits greater Jagged1-Notch association. This supports protein sequestering activity without assigning Notch-receptor activity to CD46. Supporting Evidence: PMID:23086448 We propose a model in which CD46 sequesters Jagged1 on resting T cells |
| GO:0004888 transmembrane signaling receptor activity | IDA PMID:10843656 Cutting edge: CD46, a new costimulatory molecule for T cells... | NEW | Summary: CD46 functions as a costimulatory transmembrane signaling receptor in human T cells. Reason: The authentic cached primary abstract explicitly reports CD46 aggregation-induced phosphorylation of p120CBL and LAT in human T cells, and proliferation following CD46/CD3 costimulation. CD46 itself acts as the receptor that transmits the initiating signal; it is not assigned the kinase activity of recruited proteins. This independently sourced molecular-function assertion is separate from the original measles-entry annotation. Full methods and the exact stimulation constructs were not accessible; no physiological ligand identity or universal isoform activity is inferred. This adds no process annotation. Supporting Evidence: PMID:10843656 CD46 aggregation on human T cells induces p120CBL and linker for activation of T cells (LAT) phosphorylation. |
| GO:0001855 complement component C4b binding | IDA PMID:1717583 Contribution of the repeating domains of membrane cofactor p... | NEW | Summary: CD46 binds C4b as part of its complement factor I cofactor activity. Reason: The primary study directly assessed MCP ligand binding by ELISA and tested SCR deletion mutants, demonstrating C4b binding and altered binding after domain deletion. This adds the experimentally established C4b recognition activity already described biologically, rather than inferring it solely from a disease phenotype or another complement regulator. GO:0001855 is a molecular-function term; no new process is added. The retained classical-complement process is supported independently by C4b cleavage experiments, while the original C3b-binding refinements remain unchanged. Only the primary abstracts were accessible. |
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Download this section (compressed HTML)Q: How should the 10 M values in publication-linked fragmentomics records be interpreted, and which corresponding original Supplementary Data 1 measurements support positive CD46 binding?
Suggested experts: IntAct curators, authors of PMID:36115835
Q: Which experiment in PMID:23086448 directly supports the CD46-CDH1 cadherin-binding annotation, as distinct from alpha-E-catenin association?
Q: Can the TGF-beta measurement in PMID:12540904 and the exact CD46 entries in the exosome and focal-adhesion proteomic supplements be recovered for adjudication?
Q: Would a dedicated molecular-function term describe CD46 complement factor I cofactor activity more precisely than complement binding without assigning protease activity?
Experiment: Compare the CYT1 tail and CYT2 or other tail variants in endogenous-cell interaction assays for the PDZ partners with quantified fragment affinities, using tail-motif mutations and matched surface expression to distinguish peptide recognition from full-length physiological complexes.
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