CD40 is a type I membrane receptor for CD40 ligand (CD154/TNFSF5). Its extracellular region recognizes ligand, while cytoplasmic motifs recruit TRAF proteins and organize signaling that activates NF-kappaB and MAP kinase pathways. This receptor activity helps antigen-presenting cells coordinate immune responses and enables B-cell activation, proliferation and differentiation together with other inputs such as IL4. CD40 also mediates context-dependent inflammatory, endothelial and tumor-cell responses. It has no intrinsic protein kinase or ubiquitin ligase activity. The membrane isoform supplies transmembrane signaling, whereas an alternatively spliced product is secreted. Biallelic loss of functional CD40 causes immunodeficiency with hyper-IgM type 3.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0002768 immune response-regulating cell surface receptor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: Inherited immune receptor signaling is a central CD40 role. Reason: Retain the PAINT judgment at PTN005324942: CD40 itself recognizes an extracellular ligand and recruits intracellular signal-transducing proteins. Human ligand-response studies independently establish this role. The original IBD/tree/MSA was not reconstructed, and the short donor list is not an evidential defect. |
| GO:0005515 protein binding | IPI PMID:10518213 The structural basis for the recognition of diverse receptor... | MODIFY | Summary: CD40 binds the ubiquitin ligase TRAF2. Reason: The original human TRAF2/CD40 peptide co-crystal establishes a physical docking interface. Official PDB entries 1CZZ/1D00 identify the same source; isolated peptide/domain constructs are distinguished from intact ligand-stimulated receptors. GO:0031625 records the verified enzyme class of the exact binding partner. It neither assigns ubiquitin-transfer chemistry to CD40 nor asserts that the original interaction assay measured catalysis. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:10518213 TRAF2 in complex with peptides from the TNFR family members CD40 |
| GO:0005515 protein binding | IPI PMID:12140561 Distinct molecular mechanism for initiating TRAF6 signalling... | MODIFY | Summary: CD40 binds the ubiquitin ligase TRAF6. Reason: The original TRAF6/CD40 peptide structure establishes a docking mode different from TRAF2. Official PDB 1LB6 identifies human TRAF6 and a nine-residue CD40 peptide; this is a peptide/domain assay. GO:0031625 records the verified enzyme class of the exact binding partner. It neither assigns ubiquitin-transfer chemistry to CD40 nor asserts that the original interaction assay measured catalysis. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:12140561 in complex with TRAF6-binding peptides from CD40 |
| GO:0005515 protein binding | IPI PMID:20676093 The transmembrane activator TACI triggers immunoglobulin cla... | MODIFY | Summary: CD40 binds the ubiquitin ligase TRAF2. Reason: Selected complete Methods in the TACI-focused source specify human GST-CD40 cytoplasmic residues 216β277 and human B-cell lysate pull-downs blotted for TRAF proteins. Exact figure-lane outcomes were not reanalyzed. Separate CD40/TRAF2 co-crystal evidence corroborates the same partner, without transferring TACIβMyD88 biology or calling a lysate pull-down purified binary binding. GO:0031625 records the verified enzyme class of the exact binding partner. It neither assigns ubiquitin-transfer chemistry to CD40 nor asserts that the original interaction assay measured catalysis. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:10518213 TRAF2 in complex with peptides from the TNFR family members CD40 |
| GO:0005515 protein binding | IPI PMID:20676093 The transmembrane activator TACI triggers immunoglobulin cla... | MODIFY | Summary: CD40 binds the ubiquitin ligase TRAF6. Reason: Selected complete Methods specify human GST-CD40 residues 216β277 with human B-cell lysates and TRAF immunoblots. Exact figure pixels were not inspected. Separate CD40/TRAF6 peptide structures support the same edge; TACI-specific MyD88 recruitment is not assigned to CD40. GO:0031625 records the verified enzyme class of the exact binding partner. It neither assigns ubiquitin-transfer chemistry to CD40 nor asserts that the original interaction assay measured catalysis. Proposed replacements: ubiquitin protein ligase binding |
| GO:0005515 protein binding | IPI PMID:23334419 OTUD7B controls non-canonical NF-ΞΊB activation through deubi... | KEEP AS NON CORE | Summary: Qualified CD40 association with mouse OTUD7B is retained. Reason: Selected original receptor-complex assays use mouse M12 B cells stably expressing human CD40, distinct from mouse Otud7b-knockout B-cell phenotypes. Anti-human CD40 stimulation and precipitation, TRAF3 knockdown and Otud7b UBA-domain controls support recruitment to the signaling complex. The exact B2RUR8 mouse partner and Xeno designation are preserved. This is not demonstrated purified binary CD40βOTUD7B recognition, and the deubiquitinase partner is not assigned the ligase class of neighboring TRAF proteins. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MODIFY | Summary: CD40 binds the ubiquitin ligase TRAF2. Reason: This original source is a proteome-scale human interaction map. Its canonical HTML is partial and the exact supplementary CD40 target row was not inspected. The exact CD40/TRAF2 pair is also recorded in the IntAct-derived UniProt block, sharing curation provenance; independent peptide-structure evidence establishes that this receptor can bind the same E3 partner. GO:0031625 records the verified enzyme class of the exact binding partner. It neither assigns ubiquitin-transfer chemistry to CD40 nor asserts that the original interaction assay measured catalysis. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: file:human/CD40/CD40-uniprot.txt P25942; Q12933: TRAF2; |
| GO:0005515 protein binding | IPI PMID:25502805 A massively parallel pipeline to clone DNA variants and exam... | MODIFY | Summary: CD40 binds the ubiquitin ligase TRAF2. Reason: Clone-seq combines variant cloning with interaction assays; the exact CD40 target table and construct controls were not inspected. The IntAct-derived UniProt pair is the same underlying interaction provenance, while independent CD40/TRAF2 structural evidence supports the partner-class inference. No claim is made that this original screen resolved the structural interface. GO:0031625 records the verified enzyme class of the exact binding partner. It neither assigns ubiquitin-transfer chemistry to CD40 nor asserts that the original interaction assay measured catalysis. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: file:human/CD40/CD40-uniprot.txt P25942; Q12933: TRAF2; |
| GO:0005515 protein binding | IPI PMID:25910212 Widespread macromolecular interaction perturbations in human... | MODIFY | Summary: CD40 binds the ubiquitin ligase TRAF2. Reason: The disease-variant interaction source has a partial canonical HTML body, and its exact CD40 target panel was not inspected. The IntAct-derived UniProt pair is not an independent replicate. Separate CD40/TRAF2 structural evidence supports the exact partner-class refinement, without attributing every variant or interface result to CD40. GO:0031625 records the verified enzyme class of the exact binding partner. It neither assigns ubiquitin-transfer chemistry to CD40 nor asserts that the original interaction assay measured catalysis. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: file:human/CD40/CD40-uniprot.txt P25942; Q12933: TRAF2; |
| GO:0005515 protein binding | IPI PMID:26210919 Phosphorylation of serine 523 on 5-lipoxygenase in human B l... | UNDECIDED | Summary: The source-specific CD40-PIK3R1 assay is unresolved. Reason: The complete cached abstract and official PubMed record for PMID:26210919 describe 5-lipoxygenase phosphorylation in human B-cell models. Original full-text interaction controls and the exact CD40-PIK3R1 provenance were not recovered. This does not establish wrong-gene attribution or justify removing a curated experimental edge; the exact P27986 partner is preserved. |
| GO:0005515 protein binding | IPI PMID:31331973 Integrin Binding to the Trimeric Interface of CD40L Plays a ... | KEEP AS NON CORE | Summary: Qualified CD40 association with CD40L is retained. Reason: The human ligand study explicitly distinguishes CD40 binding from integrin binding and downstream activation. Retain ligand binding; the CD40L-integrin interface is not a CD40-integrin-binding activity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | MODIFY | Summary: CD40 binds the ubiquitin ligase TRAF2. Reason: The population-variant interaction screen was read at the complete-abstract level; the exact CD40 target table was not inspected. Its IntAct-derived pair is not a new independent experiment. Independent CD40/TRAF2 peptide structures support this qualitative partner-class inference without recertifying the screen constructs. GO:0031625 records the verified enzyme class of the exact binding partner. It neither assigns ubiquitin-transfer chemistry to CD40 nor asserts that the original interaction assay measured catalysis. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: file:human/CD40/CD40-uniprot.txt P25942; Q12933: TRAF2; |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: The curated CD40-MAL interaction is retained with assay limits. Reason: The exact CD40 partner accession, P21145, matches source-linked IntAct records for HuRI, including validated two-hybrid, array and prey-pooling assays. These records describe the same screen provenance, not independent replication. Retain this experimentally supported generic interaction as non-core; a native physiological role, transport activity or more specific receptor function is not established by the heterologous yeast assay. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: The curated CD40-MIP interaction is retained with assay limits. Reason: The exact CD40 partner accession, P30301, matches source-linked IntAct records for HuRI, including validated two-hybrid, array and prey-pooling assays. These records describe the same screen provenance, not independent replication. Retain this experimentally supported generic interaction as non-core; a native physiological role, transport activity or more specific receptor function is not established by the heterologous yeast assay. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: The curated CD40-SLC7A1 interaction is retained with assay limits. Reason: The exact CD40 partner accession, P30825, matches source-linked IntAct records for HuRI, including validated two-hybrid, array and prey-pooling assays. These records describe the same screen provenance, not independent replication. Retain this experimentally supported generic interaction as non-core; a native physiological role, transport activity or more specific receptor function is not established by the heterologous yeast assay. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: The curated CD40-PLP1 isoform 2 interaction is retained with assay limits. Reason: The exact CD40 partner accession, P60201-2, matches source-linked IntAct records for HuRI, including validated two-hybrid, array and prey-pooling assays. These records describe the same screen provenance, not independent replication. Retain this experimentally supported generic interaction as non-core; a native physiological role, transport activity or more specific receptor function is not established by the heterologous yeast assay. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: CD40 binds the ubiquitin ligase TRAF2. Reason: Exact CD40/TRAF2 target records include validated two-hybrid assays in HuRI. The records share the original screen provenance. Separate CD40/TRAF2 structures supply independent same-edge evidence. GO:0031625 captures the independently verified E3 enzyme class of TRAF2, without assigning ubiquitin-transfer chemistry to CD40 or claiming that the interaction screen measured catalysis or native signaling. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: file:human/CD40/CD40-uniprot.txt P25942; Q12933: TRAF2; |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: The curated CD40-EBP interaction is retained with assay limits. Reason: The exact CD40 partner accession, Q15125, matches source-linked IntAct records for HuRI, including validated two-hybrid, array and prey-pooling assays. These records describe the same screen provenance, not independent replication. Retain this experimentally supported generic interaction as non-core; a native physiological role, transport activity or more specific receptor function is not established by the heterologous yeast assay. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: The curated CD40-TMEM128 isoform 2 interaction is retained with assay limits. Reason: The exact CD40 partner accession, Q5BJH2-2, matches source-linked IntAct records for HuRI, including validated two-hybrid, array and prey-pooling assays. These records describe the same screen provenance, not independent replication. Retain this experimentally supported generic interaction as non-core; a native physiological role, transport activity or more specific receptor function is not established by the heterologous yeast assay. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: The curated CD40-DEFB121 interaction is retained with assay limits. Reason: The exact CD40 partner accession, Q5J5C9, matches source-linked IntAct records for HuRI, including validated two-hybrid, array and prey-pooling assays. These records describe the same screen provenance, not independent replication. Retain this experimentally supported generic interaction as non-core; a native physiological role, transport activity or more specific receptor function is not established by the heterologous yeast assay. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: The curated CD40-MFSD5 interaction is retained with assay limits. Reason: The exact CD40 partner accession, Q6N075, matches source-linked IntAct records for HuRI, including validated two-hybrid, array and prey-pooling assays. These records describe the same screen provenance, not independent replication. Retain this experimentally supported generic interaction as non-core; a native physiological role, transport activity or more specific receptor function is not established by the heterologous yeast assay. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: The curated CD40-TMEM107 interaction is retained with assay limits. Reason: The exact CD40 partner accession, Q6UX40, matches source-linked IntAct records for HuRI, including validated two-hybrid, array and prey-pooling assays. These records describe the same screen provenance, not independent replication. Retain this experimentally supported generic interaction as non-core; a native physiological role, transport activity or more specific receptor function is not established by the heterologous yeast assay. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: The curated CD40-CYB561A3 interaction is retained with assay limits. Reason: The exact CD40 partner accession, Q8NBI2, matches source-linked IntAct records for HuRI, including validated two-hybrid, array and prey-pooling assays. These records describe the same screen provenance, not independent replication. Retain this experimentally supported generic interaction as non-core; a native physiological role, transport activity or more specific receptor function is not established by the heterologous yeast assay. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: The curated CD40-TLCD1 interaction is retained with assay limits. Reason: The exact CD40 partner accession, Q96CP7, matches source-linked IntAct records for HuRI, including validated two-hybrid, array and prey-pooling assays. These records describe the same screen provenance, not independent replication. Retain this experimentally supported generic interaction as non-core; a native physiological role, transport activity or more specific receptor function is not established by the heterologous yeast assay. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: The curated CD40-CMTM5 isoform 2 interaction is retained with assay limits. Reason: The exact CD40 partner accession, Q96DZ9-2, matches source-linked IntAct records for HuRI, including validated two-hybrid, array and prey-pooling assays. These records describe the same screen provenance, not independent replication. Retain this experimentally supported generic interaction as non-core; a native physiological role, transport activity or more specific receptor function is not established by the heterologous yeast assay. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: The curated CD40-SLC39A13 interaction is retained with assay limits. Reason: The exact CD40 partner accession, Q96H72, matches source-linked IntAct records for HuRI, including validated two-hybrid, array and prey-pooling assays. These records describe the same screen provenance, not independent replication. Retain this experimentally supported generic interaction as non-core; a native physiological role, transport activity or more specific receptor function is not established by the heterologous yeast assay. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: The curated CD40-SLC30A3 interaction is retained with assay limits. Reason: The exact CD40 partner accession, Q99726, matches source-linked IntAct records for HuRI, including validated two-hybrid, array and prey-pooling assays. These records describe the same screen provenance, not independent replication. Retain this experimentally supported generic interaction as non-core; a native physiological role, transport activity or more specific receptor function is not established by the heterologous yeast assay. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: The curated CD40-SLC30A2 interaction is retained with assay limits. Reason: The exact CD40 partner accession, Q9BRI3, matches source-linked IntAct records for HuRI, including validated two-hybrid, array and prey-pooling assays. These records describe the same screen provenance, not independent replication. Retain this experimentally supported generic interaction as non-core; a native physiological role, transport activity or more specific receptor function is not established by the heterologous yeast assay. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: The curated CD40-TMEM147 interaction is retained with assay limits. Reason: The exact CD40 partner accession, Q9BVK8, matches source-linked IntAct records for HuRI, including validated two-hybrid, array and prey-pooling assays. These records describe the same screen provenance, not independent replication. Retain this experimentally supported generic interaction as non-core; a native physiological role, transport activity or more specific receptor function is not established by the heterologous yeast assay. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: The curated CD40-CMTM6 interaction is retained with assay limits. Reason: The exact CD40 partner accession, Q9NX76, matches source-linked IntAct records for HuRI, including validated two-hybrid, array and prey-pooling assays. These records describe the same screen provenance, not independent replication. Retain this experimentally supported generic interaction as non-core; a native physiological role, transport activity or more specific receptor function is not established by the heterologous yeast assay. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: The curated CD40-INSIG2 interaction is retained with assay limits. Reason: The exact CD40 partner accession, Q9Y5U4, matches source-linked IntAct records for HuRI, including validated two-hybrid, array and prey-pooling assays. These records describe the same screen provenance, not independent replication. Retain this experimentally supported generic interaction as non-core; a native physiological role, transport activity or more specific receptor function is not established by the heterologous yeast assay. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: CD40 binds the ubiquitin ligase TRAF2. Reason: Exact source-linked BioPlex records identify CD40/TRAF2 association in both HEK293T and HCT116 anti-tag coimmunoprecipitation experiments. Spoke-expanded AP-MS evidence supports complex association; independent CD40/TRAF2 peptide structures establish direct binding separately. GO:0031625 captures the verified E3 class of TRAF2, without turning the AP-MS association into a resolved interface or attributing ubiquitin-transfer chemistry to CD40. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: file:human/CD40/CD40-uniprot.txt P25942; Q12933: TRAF2; |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: Qualified CD40 association with CMTM6 is retained. Reason: The exact CD40 bait/CMTM6 prey pair is present in the HCT116 anti-tag coimmunoprecipitation record IM-29278-19647 from BioPlex. Its spoke-expanded AP-MS association supports retention as a non-core generic interaction. It does not demonstrate a direct binary interface, a physiological signaling role, or CMTM6 activity performed by CD40. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | KEEP AS NON CORE | Summary: Qualified CD40 association with SLC7A1 is retained. Reason: The author-released U2OS AP-MS network contains the CD40/SLC7A1 edge (NDEx edge 619332). Selected Methods describe HA-tagged human ORFeome baits. This verifies the qualitative association assertion; the network does not resolve a direct binary interface or establish amino-acid transport, transporter regulation or a native signaling role for CD40. Retain the supported generic interaction as non-core. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: CD40 binds the ubiquitin ligase TRAF2. Reason: The author-released U2OS AP-MS network contains the CD40/TRAF2 edge (NDEx edge 619354), supporting the source-specific association. Independent CD40/TRAF2 peptide structures and reviewed partner enzyme identity support GO:0031625. The refinement describes binding to an E3, not receptor catalysis, and does not claim that every AP-MS association is a direct interface or a native signaling event. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: file:human/CD40/CD40-uniprot.txt P25942; Q12933: TRAF2; |
| GO:0005515 protein binding | IPI PMID:7527023 A novel RING finger protein interacts with the cytoplasmic d... | MODIFY | Summary: CD40 binds the ubiquitin ligase TRAF3. Reason: The complete original abstract identifies a protein that binds the CD40 cytoplasmic domain; the preserved Q13114 partner is TRAF3/CD40BP. Its E3 class is independently established by the reviewed TRAF3 record, not inferred solely from the RING-finger description in the old paper. Full original construct Methods were not recovered. GO:0031625 records the verified enzyme class of the exact binding partner. It neither assigns ubiquitin-transfer chemistry to CD40 nor asserts that the original interaction assay measured catalysis. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:7527023 proteins that bind the CD40 cytoplasmic domain |
| GO:0005515 protein binding | IPI PMID:9468137 CD40 ligand on activated platelets triggers an inflammatory ... | KEEP AS NON CORE | Summary: Qualified CD40 association with CD40L is retained. Reason: Activated platelets display CD40L and can stimulate endothelial responses through CD40. This supports the ligand-receptor association. It does not by itself settle the separate assertion that CD40 participates in platelet activation. Supporting Evidence: |
| GO:0005576 extracellular region | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Extracellular localization applies to a secreted CD40 alternative product. Reason: The immutable reviewed UniProt entry distinguishes membrane isoform I from secreted isoform II. The unqualified broad extracellular mapping is therefore retained with product scope; it does not mean the canonical membrane receptor is constitutively released or that every secreted molecule has identical signaling capacity. Human Raji-cell transcript cloning in PMID:11172023 independently identifies the type II splice product; mouse functional and secretion experiments in that paper are not treated as direct human isoform assays. |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | ACCEPT | Summary: The membrane CD40 receptor is localized at the plasma membrane. Reason: The original HPA immunofluorescence image was not inspected, but human cell-surface flow cytometry and receptor topology independently support the compartment. |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: The membrane CD40 receptor is localized at the plasma membrane. Reason: The combined automated annotation retains both the mouse orthology input and the location mapping; independent human surface assays support plasma-membrane placement. |
| GO:0005886 plasma membrane | ISS GO_REF:0000024 | ACCEPT | Summary: The membrane CD40 receptor is localized at the plasma membrane. Reason: Retain curator-mediated transfer from mouse CD40 with independent human surface-receptor evidence. |
| GO:0005886 plasma membrane | TAS PMID:10748139 Recruitment of CD40 and tumor necrosis factor receptor-assoc... | ACCEPT | Summary: The membrane CD40 receptor is localized at the plasma membrane. Reason: The cited receptor recruitment study places CD40 at plasma-membrane microdomains; complete original species/construct Methods were not read. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-199404 | ACCEPT | Summary: The membrane CD40 receptor is localized at the plasma membrane. Reason: The complete Reactome ligand-binding summary supports the surface receptor context. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5668414 | ACCEPT | Summary: The membrane CD40 receptor is localized at the plasma membrane. Reason: The Reactome event places CD40 in a receptor-associated signaling context; TRAF2/cIAP chemistry belongs to those enzymes. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5668454 | ACCEPT | Summary: The membrane CD40 receptor is localized at the plasma membrane. Reason: The Reactome summary describes cIAP-dependent TRAF3 ubiquitination, not intrinsic CD40 catalysis. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5668481 | ACCEPT | Summary: The membrane CD40 receptor is localized at the plasma membrane. Reason: The Reactome event describes downstream TRAF3 proteasomal degradation; the receptor remains membrane-associated. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5676597 | ACCEPT | Summary: The membrane CD40 receptor is localized at the plasma membrane. Reason: The Reactome recruitment summary explicitly describes the signaling complex binding CD40. |
| GO:0006874 intracellular calcium ion homeostasis | IEA GO_REF:0000120 | MODIFY | Summary: Human target evidence supports a CD40-dependent cytosolic calcium increase. Reason: In human U87/HMC-1 cocultures, CD40 blockade and depletion reduce the measured calcium rise. This independent target evidence supports positive regulation of cytosolic calcium concentration rather than demonstrating steady-state homeostasis. The refinement does not reconstruct the original ARBA rule or mouse donor chain, or exclude a homeostatic role in other contexts. The electronic evidence code and all original source inputs remain intact. Proposed replacements: positive regulation of cytosolic calcium ion concentration Supporting Evidence: |
| GO:0006874 intracellular calcium ion homeostasis | IMP PMID:21410936 Signal pathways in astrocytes activated by cross-talk betwee... | MODIFY | Summary: CD40 promotes a calcium rise in the measured coculture context. Reason: In human U87/HMC-1 cocultures, anti-CD40 treatment and CD40 siRNA reduce the Fluo-3 calcium rise. Separate primary mouse astrocyte/BMMC experiments are not relabeled human. The assay measures increased calcium rather than steady-state homeostasis; positive regulation of cytosolic calcium concentration better captures this conditional signal. Proposed replacements: positive regulation of cytosolic calcium ion concentration Supporting Evidence: PMID:21410936 also decreased [Ca2+]i levels in co-cultured-U87 cells |
| GO:0006952 defense response | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Defense response is a broad consequence of CD40 immune signaling. Reason: The electronic parent-level process is biologically compatible with CD40-mediated immune activation, but is less informative than its receptor pathway. Exact ARBA conditions were not inspected; no specific antimicrobial mechanism is inferred. Supporting Evidence: |
| GO:0006954 inflammatory response | TAS PMID:2475341 A B-lymphocyte activation molecule related to the nerve grow... | KEEP AS NON CORE | Summary: Inflammatory responses are a context-dependent CD40 role. Reason: The original cloning abstract chiefly establishes the Bp50/CD40 antigen and regulated expression. Independent ligand-triggered endothelial and dendritic-cell responses support inflammatory participation; retain the broad TAS process without making the cloning source an uninspected direct inflammation assay. |
| GO:0007259 cell surface receptor signaling pathway via JAK-STAT | IMP PMID:21410936 Signal pathways in astrocytes activated by cross-talk betwee... | KEEP AS NON CORE | Summary: CD40 influences JAK-STAT signaling in astrocyte/mast-cell coculture. Reason: The selected human U87/HMC-1 experiments show signaling changes after CD40 blockade and a later TNF/TNFR1-dependent reactivation loop. Retain this conditional pathway involvement, while distinguishing it from direct JAK recruitment by CD40 or intrinsic receptor kinase activity. Mouse primary-cell experiments are separate. Supporting Evidence: |
| GO:0009897 external side of plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: The CD40 ectodomain is exposed at the cell surface. Reason: The type I receptor topology and independent human surface-antibody measurements support this placement. The PAINT node/tree was not reconstructed; neither donor count nor target inclusion is treated as a defect. |
| GO:0009897 external side of plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: The CD40 ectodomain is exposed at the cell surface. Reason: The type I receptor topology and independent human surface-antibody measurements support this placement. Combined orthology/InterPro inputs are retained without pretending to reconstruct the exact rule. |
| GO:0009986 cell surface | HDA PMID:23981064 Mycobacterium tuberculosis infection of human dendritic cell... | ACCEPT | Summary: The CD40 ectodomain is exposed at the cell surface. Reason: The type I receptor topology and independent human surface-antibody measurements support this placement. Selected complete Methods and Results in the restored canonical HTML describe human monocyte-derived dendritic cells, CD40 flow cytometry, Fc-receptor blocking and isotype controls. No figure-pixel analysis is claimed. |
| GO:0009986 cell surface | IEA GO_REF:0000107 | ACCEPT | Summary: The CD40 ectodomain is exposed at the cell surface. Reason: The type I receptor topology and independent human surface-antibody measurements support this placement. The mouse orthology transfer is corroborated by direct human surface measurements. |
| GO:0010468 regulation of gene expression | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: CD40 signaling regulates expression of downstream genes. Reason: This ARBA term is an upstream signaling consequence, supported by ligand/knockdown effects on cytokine and activation-induced cytidine deaminase transcripts. CD40 is not a DNA-binding transcription factor, and individual rule logic was not inspected. |
| GO:0019724 B cell mediated immunity | IEA GO_REF:0000107 | ACCEPT | Summary: CD40 receptor signaling contributes directly to B-cell-mediated immunity. Reason: Retain the mouse-derived automated assertion with independent human B-cell CD40L responses. CD40 performs the receptor step rather than merely being an inert necessity marker; its cooperation with IL4 is retained. Human biallelic CD40 deficiency further supports the receptor role in productive B-cell immune responses, with patient surface-expression and in vitro immunoglobulin assays. |
| GO:0019899 enzyme binding | IPI PMID:12223522 Disruption of CD40/CD40 ligand interaction with cleavage of ... | UNDECIDED | Summary: Elastase-dependent CD40 cleavage is verified, but the binding assertion needs original controls. Reason: The complete abstract describes human fibroblast CD40 cleavage by neutrophil elastase, including fixed cells, lysates and membrane preparations. This is substrate processing; the specific physical-binding experiment underlying the IPI enzyme-binding annotation was not recovered. Do not infer a stable binding function solely from cleavage, or reject the curator from an abstract. Supporting Evidence: |
| GO:0023035 CD40 signaling pathway | IDA PMID:15708970 TNF receptor (TNFR)-associated factor (TRAF) 3 serves as an ... | ACCEPT | Summary: CD40 itself performs the receptor step in its signaling pathway. Reason: CD40-tail mutations separate TRAF-dependent canonical and noncanonical signaling; complete original construct Methods were not reconstructed. Cached GO-CAM models 663d668500001599 and 663d668500001704 independently retain this receptor role, rather than assigning TRAF catalytic activity to CD40. Supporting Evidence: |
| GO:0023035 CD40 signaling pathway | IDA PMID:31331973 Integrin Binding to the Trimeric Interface of CD40L Plays a ... | ACCEPT | Summary: CD40 itself performs the receptor step in its signaling pathway. Reason: Human CD40L mutations distinguish retained CD40 binding from impaired integrin binding and downstream receptor activation. Cached GO-CAM models 663d668500001599 and 663d668500001704 independently retain this receptor role, rather than assigning TRAF catalytic activity to CD40. Supporting Evidence: |
| GO:0023035 CD40 signaling pathway | IDA PMID:8910514 Identification of TRAF6, a novel tumor necrosis factor recep... | ACCEPT | Summary: CD40 itself performs the receptor step in its signaling pathway. Reason: CD40-tail deletion mapping and TRAF6-mediated NF-kappaB assays establish the receptor-proximal step. Cached GO-CAM models 663d668500001599 and 663d668500001704 independently retain this receptor role, rather than assigning TRAF catalytic activity to CD40. Supporting Evidence: PMID:8910514 NFkappaB activation triggered by CD40 lacking residues 246-277 |
| GO:0023035 CD40 signaling pathway | IEA GO_REF:0000120 | ACCEPT | Summary: CD40 itself performs the receptor step in its signaling pathway. Reason: Combined ARBA and mouse orthology inputs agree with independent human ligand-response evidence; the individual rule was not reconstructed. Cached GO-CAM models 663d668500001599 and 663d668500001704 independently retain this receptor role, rather than assigning TRAF catalytic activity to CD40. Supporting Evidence: |
| GO:0023035 CD40 signaling pathway | IMP PMID:21410936 Signal pathways in astrocytes activated by cross-talk betwee... | ACCEPT | Summary: CD40 itself performs the receptor step in its signaling pathway. Reason: Human U87 CD40 blockade and siRNA reduce coculture-induced signaling; primary mouse astrocytes were assessed separately. Cached GO-CAM models 663d668500001599 and 663d668500001704 independently retain this receptor role, rather than assigning TRAF catalytic activity to CD40. Supporting Evidence: PMID:21410936 These effects were inhibited by anti-CD40 antibody or CD40 siRNA |
| GO:0030168 platelet activation | NAS PMID:9468137 CD40 ligand on activated platelets triggers an inflammatory ... | KEEP AS NON CORE | Summary: CD40 can mediate platelet activation in the tested ligand context. Reason: Independent PMID:12676820 reports soluble CD40L-trimer-induced granule release and morphology changes blocked by CD40 antibodies, without aggregation. This supports contextual receptor participation. The original PMID:9468137 abstract concerns platelet CD40L acting on endothelium; its exact NAS provenance remains unverified and is not declared erroneous. Supporting Evidence: PMID:12676820 showing that activation was mediated by CD40L binding to platelet CD40. |
| GO:0031625 ubiquitin protein ligase binding | IPI PMID:11279055 A diverse family of proteins containing tumor necrosis facto... | KEEP AS NON CORE | Summary: CD40 associates with the TRIM37/MUL ubiquitin ligase. Reason: O94972 is TRIM37/MUL, not TRAF7. Selected original Methods/Results and the Fig.3 caption in the external author reproduction (https://www.researchgate.net/publication/12054562_A_Diverse_Family_of_Proteins_Containing_Tumor_Necrosis_Factor_Receptor-associated_Factor_Domains) test MUL and TRAF2 domains against GST receptor tails, using reticulocyte translation or Myc-tagged 293T lysates and specificity controls. The canonical cache remains abstract-only. This supports a domain-level association, not a demonstrated physiological full-length TRIM37βCD40 complex. The reviewed partner is an E3 enzyme; the old binding assay did not measure its catalysis. Supporting Evidence: |
| GO:0031625 ubiquitin protein ligase binding | IPI PMID:11279055 A diverse family of proteins containing tumor necrosis facto... | ACCEPT | Summary: CD40 recruits the TRAF2 ubiquitin ligase through its tail. Reason: The external author reproduction (https://www.researchgate.net/publication/12054562_A_Diverse_Family_of_Proteins_Containing_Tumor_Necrosis_Factor_Receptor-associated_Factor_Domains) tests the TRAF2 domain against receptor cytoplasmic tails with construct controls. The canonical cache is abstract-only. Independent CD40/TRAF2 co-crystal evidence supports the same docking interaction; CD40 is not assigned ubiquitin transfer. This structurally supported docking activity is an explicit core facet of receptor signaling. The separate TRIM37 domain association does not establish an equivalent physiological role for that partner. |
| GO:0035631 CD40 receptor complex | IBA GO_REF:0000033 | ACCEPT | Summary: CD40 is a component of its ligand-triggered receptor signaling complex. Reason: Receptor-tail recruitment of TRAF proteins supports complex membership. Retain the curated PAINT inheritance without reconstructing the full IBD tree or treating the number of donors as a defect. |
| GO:0035631 CD40 receptor complex | IEA GO_REF:0000107 | ACCEPT | Summary: CD40 is a component of its ligand-triggered receptor signaling complex. Reason: Receptor-tail recruitment of TRAF proteins supports complex membership. The mouse orthology transfer is supported by independent human ligand-receptor and tail-interface evidence. |
| GO:0035631 CD40 receptor complex | ISS GO_REF:0000024 | ACCEPT | Summary: CD40 is a component of its ligand-triggered receptor signaling complex. Reason: Receptor-tail recruitment of TRAF proteins supports complex membership. The manual mouse-to-human transfer is retained with independent target receptor-complex evidence. |
| GO:0038023 signaling receptor activity | IDA PMID:38494863 CD40 stimulation via CD40 ligand enhances adenovirus-mediate... | MODIFY | Summary: CD40 acts as a transmembrane signaling receptor. Reason: Human CD40-positive tumor cell lines respond differently to CD40L-bearing and control viruses. CD46 mediates viral entry, and CD40-dependent signaling is separated from general oncolysis; not every death-marker change is CD40 specific. GO:0004888 states the membrane-spanning signal-transduction role more precisely than the broad source term. The TNF-specific GO:0005031 is not assigned merely from superfamily membership. Proposed replacements: transmembrane signaling receptor activity Supporting Evidence: PMID:38494863 CD40, the receptor for TMZβCD40L |
| GO:0038023 signaling receptor activity | IEA GO_REF:0000002 | MODIFY | Summary: CD40 acts as a transmembrane signaling receptor. Reason: The InterPro receptor-family assertion is refined using the target ligand-recognition and signaling mechanism, without transferring intrinsic kinase or TNF-binding activity. GO:0004888 states the membrane-spanning signal-transduction role more precisely than the broad source term. The TNF-specific GO:0005031 is not assigned merely from superfamily membership. Proposed replacements: transmembrane signaling receptor activity Supporting Evidence: PMID:31331973 CD40 simultaneously bind to CD40L |
| GO:0038023 signaling receptor activity | TAS PMID:10092834 Differential effects of CD40 ligand/trimer stimulation on th... | MODIFY | Summary: CD40 acts as a transmembrane signaling receptor. Reason: Soluble trimeric CD40L agonist changes dendritic-cell chemokine production. The original full Methods were not recovered, so detailed construct/species claims beyond the abstract are avoided. GO:0004888 states the membrane-spanning signal-transduction role more precisely than the broad source term. The TNF-specific GO:0005031 is not assigned merely from superfamily membership. Proposed replacements: transmembrane signaling receptor activity Supporting Evidence: PMID:10092834 Stimulation of monocyte-derived DCs with CD40LT enhanced the production |
| GO:0042100 B cell proliferation | NAS PMID:8605945 Cleavage of membrane-bound CD40 ligand is not required for i... | ACCEPT | Summary: CD40 signaling supports human B-cell proliferation. Reason: The original study compares human B cells stimulated with wild-type versus uncleavable human CD40L and shows proliferation together with IL4. CD40 supplies the receptor signal; this is not intrinsic cell-cycle enzyme activity. Supporting Evidence: PMID:8605945 induce, in conjunction with interleukin-4, B cell proliferation |
| GO:0042113 B cell activation | IBA GO_REF:0000033 | ACCEPT | Summary: B-cell activation is a central output of CD40 receptor signaling. Reason: The PAINT assertion at PTN001133995 is retained; the tree/MSA was not independently reconstructed and its donor list is not treated as weak support. Independent human B-cell ligand-response experiments corroborate the biology. |
| GO:0042113 B cell activation | IEA GO_REF:0000002 | ACCEPT | Summary: B-cell activation is a central output of CD40 receptor signaling. Reason: The InterPro-derived assertion agrees with the experimentally supported receptor role. Independent human B-cell ligand-response experiments corroborate the biology. |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IEP PMID:12761501 Large-scale identification and characterization of human gen... | KEEP AS NON CORE | Summary: CD40 can promote canonical NF-kappaB signaling. Reason: The original human HEK293 expression-screen abstract establishes a reporter-based assay class, but its exact target table was not inspected. Independent receptor-tail and ligand-response evidence supports canonical signaling. Retain the machine IEP code and avoid claiming native B-cell kinetics from overexpression. |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IMP PMID:21410936 Signal pathways in astrocytes activated by cross-talk betwee... | KEEP AS NON CORE | Summary: CD40 promotes canonical NF-kappaB signaling in the tested coculture. Reason: Human U87 CD40 blockade/siRNA reduces NF-kappaB DNA-binding readouts in astrocyte/mast-cell coculture. This is a context-specific regulatory output of the receptor; it is not DNA binding or NF-kappaB enzymatic activity by CD40. Supporting Evidence: |
| GO:0043410 positive regulation of MAPK cascade | IMP PMID:21410936 Signal pathways in astrocytes activated by cross-talk betwee... | KEEP AS NON CORE | Summary: CD40 positively regulates MAP kinase activation in the tested cells. Reason: Anti-CD40 antibody and CD40 siRNA reduce ERK/JNK/p38 phosphorylation in human U87 coculture. The result supports upstream receptor regulation, not catalytic MAP kinase activity or a universal response in all tissues. Supporting Evidence: |
| GO:0043536 positive regulation of blood vessel endothelial cell migration | IMP PMID:28566713 A PPARΞ³-dependent miR-424/503-CD40 axis regulates inflammati... | KEEP AS NON CORE | Summary: CD40 promotes endothelial migration under inflammatory stimulation. Reason: Selected human HUVEC experiments show reduced LPS-induced migration after CD40 knockdown and rescue of miRNA-dependent inhibition by CD40 overexpression. Retain this endothelial context, without extending the mouse miRNA-knockout experiments to a human CD40 knockout. Supporting Evidence: |
| GO:0045766 positive regulation of angiogenesis | IMP PMID:28566713 A PPARΞ³-dependent miR-424/503-CD40 axis regulates inflammati... | KEEP AS NON CORE | Summary: CD40 contributes to inflammatory endothelial angiogenic responses. Reason: The HUVEC CD40 knockdown and overexpression-rescue experiments include tube-formation endpoints. Sprouting, miRNA and mouse Matrigel experiments are supporting context with different manipulated entities. These assays support a conditional positive regulatory role rather than a universal structural angiogenesis function. Supporting Evidence: |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IGI PMID:12574355 Human activation-induced cytidine deaminase is induced by IL... | KEEP AS NON CORE | Summary: CD40 cooperates with IL4 to increase transcriptional output. Reason: The human B-cell study measures activation-induced cytidine deaminase expression and signaling synergy. Preserve the IL4 genetic-interaction partner, while recognizing CD40 as an upstream receptor rather than a nuclear transcription factor. Supporting Evidence: |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:21410936 Signal pathways in astrocytes activated by cross-talk betwee... | KEEP AS NON CORE | Summary: CD40-dependent signaling can increase cytokine transcription. Reason: CD40 blockade and siRNA reduce cytokine mRNA and transcription-factor readouts in human U87/HMC-1 coculture. The evidence establishes receptor-mediated regulation and includes secondary cytokine feedback, not direct binding of CD40 to RNA polymerase II. Supporting Evidence: |
| GO:0050776 regulation of immune response | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Immune-process regulation is a broad parent-level CD40 role. Reason: The InterPro-derived term is biologically sound but less specific than CD40 signaling and B-cell activation. It is retained as non-core parent coverage without inventing an unmeasured immune mechanism. |
| GO:0051094 positive regulation of developmental process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Positive developmental regulation is broad contextual coverage. Reason: CD40 signaling can promote immune-cell activation and differentiation; this broad electronic parent term is retained outside the core. The individual ARBA rule and every developmental tissue context were not inspected, and no organ-specific developmental claim is inferred. |
| GO:0051240 positive regulation of multicellular organismal process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Positive multicellular-process regulation is broad contextual coverage. Reason: Retain this electronic ancestor-level process as non-core in light of receptor-mediated immune and endothelial responses. Individual ARBA conditions were not inspected; this is not evidence that CD40 directly performs every downstream multicellular event. |
| GO:0065003 protein-containing complex assembly | TAS PMID:10748139 Recruitment of CD40 and tumor necrosis factor receptor-assoc... | KEEP AS NON CORE | Summary: CD40 participates in assembling its receptor-associated signaling machinery. Reason: The receptor is itself a docking component: engagement recruits TRAF2/TRAF3 to membrane microdomains. Retain the broad assembly annotation as non-core because the core receptor description already captures this step; no NEW redundant assembly ancestor is proposed. |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | KEEP AS NON CORE | Summary: Exosomal detection is a context-dependent localization. Reason: The original B-cell exosome proteomic abstract supports the assay context, but the exact CD40 peptide table and vesicle-specific controls were not inspected. Retain curator-supported exosomal detection as non-core, without treating all CD40 molecules or the secreted isoform as exosomal. Supporting Evidence: |
| GO:0071260 cellular response to mechanical stimulus | IEP PMID:19593445 Expression of the Bcl-2 protein BAD promotes prostate cancer... | UNDECIDED | Summary: The mechanical-stimulus expression assertion needs source provenance resolution. Reason: Selected complete Methods from the available XML describe BAD manipulation in prostate cancer cells; the target-specific CD40 mechanical-stimulus experiment was not recovered. Absence from the inspected passages or an automated text search is not proof that the full supplementary/provenance record excludes CD40. Preserve the IEP assertion while asking for the original assay mapping. |
| GO:0090037 positive regulation of protein kinase C signaling | IMP PMID:21410936 Signal pathways in astrocytes activated by cross-talk betwee... | KEEP AS NON CORE | Summary: CD40 promotes PKC signaling in the tested coculture. Reason: CD40 blockade and siRNA reduce phosphorylation of selected PKC isoforms downstream of Rho/calcium signaling in human U87 cells. Some PKC isoforms were unaffected. Retain a bounded positive regulatory process, not intrinsic receptor protein kinase activity. Supporting Evidence: |
| GO:1902216 positive regulation of interleukin-4-mediated signaling pathway | IGI PMID:12574355 Human activation-induced cytidine deaminase is induced by IL... | KEEP AS NON CORE | Summary: CD40 cooperates with IL4 signaling in human B cells. Reason: The original genetic-interaction context concerns IL4/CD40 synergy and activation-induced cytidine deaminase induction. Preserve IL4 as the supporting entity; CD40 neither replaces the IL4 receptor nor acquires intrinsic JAK/STAT activity. Supporting Evidence: |
| GO:2000353 positive regulation of endothelial cell apoptotic process | IDA PMID:12885753 A20 protects from CD40-CD40 ligand-mediated endothelial cell... | KEEP AS NON CORE | Summary: CD40 can promote endothelial apoptosis in a proinflammatory context. Reason: The source explicitly studies human coronary artery endothelial cells and reports CD40-associated apoptosis under proinflammatory conditions, with A20 protection. Retain the context-dependent regulatory outcome rather than defining apoptosis as the constitutive receptor function. Supporting Evidence: |
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Download this section (compressed HTML)Q: What exact original experiments and identifier mapping support the CD40-PIK3R1 IPI assertion from PMID:26210919 and the mechanical-stimulus IEP assertion from PMID:19593445?
Q: Which ligand presentation states and cell types select CD40-TRAF2/3 versus TRAF6 complexes, and how does secreted isoform II alter native membrane-receptor signaling?
Q: What original NAS provenance maps PMID:9468137 to platelet activation, separately from the independent CD40 receptor evidence in PMID:12676820?
Q: Which original donor experiments and ARBA conditions support steady-state calcium homeostasis, as distinct from the observed transient calcium rise after CD40 engagement?
Experiment: Compare expression-matched human CD40 tail mutants and membrane versus soluble CD40L using ligand-binding controls, timed TRAF recruitment, calcium imaging and canonical/noncanonical NF-kappaB measurements; test secreted isoform II separately.
Hypothesis: Ligand presentation and receptor-tail contacts determine CD40 signaling branch selection independently of receptor abundance.
Type: genetic and biochemical
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