CD70

Summary: CD70 supports T-cell immunity through CD27 costimulation.

Reason: Human loss-of-function and CD70-blockade experiments show defective priming of EBV-specific T cells. The primary study distinguishes impaired generation of cytotoxic effectors from an acute requirement during target killing; this is a major physiological output of the ligand.

Summary: CD70 binds the TNF receptor superfamily member CD27.

Reason: The InterPro inference is independently corroborated by expression cloning with a CD27 probe and by WT-versus-mutant CD70 binding to recombinant CD27. This receptor-binding function fits the ligand; it does not imply binding to TNFR1 or TNFR2. Direct human ectodomain SPR and crystallography independently establish the CD27 interface: a CD70 homotrimer engages three CD27 molecules, each contacting two adjacent ligand protomers.

Summary: The annotated CD27 interaction is best described as receptor ligand activity.

Reason: The cached abstract addresses CD27-dependent B-cell survival, but its exact interaction assay was not accessible. The original partner and citation are preserved. Independent CD27-probe cloning and CD70 rescue/CD27-dependence experiments establish the physiological ligand activity, so the refinement rests on those functional studies rather than assuming every screen association is agonistic.

Proposed replacements: receptor ligand activity

Summary: The annotated CD27 interaction is best described as receptor ligand activity.

Reason: The exact P26842–P32970 IntAct record EBI-21555258 maps to HEK293T anti-tag coimmunoprecipitation with spoke expansion; this is association evidence, not an agonism assay. The original partner and citation are preserved. Independent CD27-probe cloning and CD70 rescue/CD27-dependence experiments establish the physiological ligand activity, so the refinement rests on those functional studies rather than assuming every screen association is agonistic.

Proposed replacements: receptor ligand activity

Summary: HuRI reports a CD70–ELOVL4 interaction of uncertain physiological significance.

Reason: The exact P32970–Q9GZR5 pair is present in IntAct records EBI-24806957, EBI-24213529 and EBI-25220414, attributed to PMID32296183 Supplementary Table9 with validated, array and pooled-prey yeast two-hybrid methods. These are related assays from one study, not three independent biological replications. Retain supported generic binding under the project rule; there is no evidence here for a CD70 fatty-acid-elongation activity or a more specific functional replacement.

Summary: The annotated CD27 interaction is best described as receptor ligand activity.

Reason: The primary screen used recombinant cell-surface ectodomains; its exact CD70/CD27 supplemental row was not retrieved. The original partner and citation are preserved. Independent CD27-probe cloning and CD70 rescue/CD27-dependence experiments establish the physiological ligand activity, so the refinement rests on those functional studies rather than assuming every screen association is agonistic. CD27/P26842 identity is taken from the preserved GOA supporting entity, not a newly inspected supplemental target row.

Proposed replacements: receptor ligand activity

Summary: The annotated CD27 interaction is best described as receptor ligand activity.

Reason: The exact P26842–P32970 IntAct record EBI-54533983 maps to HEK293T anti-tag coimmunoprecipitation with spoke expansion; it does not itself establish agonist action. The original partner and citation are preserved. Independent CD27-probe cloning and CD70 rescue/CD27-dependence experiments establish the physiological ligand activity, so the refinement rests on those functional studies rather than assuming every screen association is agonistic.

Proposed replacements: receptor ligand activity

Summary: The annotated CD27 interaction is best described as receptor ligand activity.

Reason: The primary SAVEXIS study used recombinant ectodomain binding; its exact CD70/CD27 supplemental matrix entry was not retrieved. The published correction concerns other figure labels, a concentration unit and missing references, without identifying a CD70 result. The original partner and citation are preserved. Independent CD27-probe cloning and CD70 rescue/CD27-dependence experiments establish the physiological ligand activity, so the refinement rests on those functional studies rather than assuming every screen association is agonistic. CD27/P26842 identity is taken from the preserved GOA supporting entity, not a newly inspected supplemental target row.

Proposed replacements: receptor ligand activity

Summary: The functional CD70 ligand is presented at the plasma membrane.

Reason: WT and mutant cell-surface expression was measured by flow cytometry; recombinant CD27 bound WT CD70-expressing cells.

Summary: The functional CD70 ligand is presented at the plasma membrane.

Reason: Expression cloning identified a cell-surface, type II transmembrane ligand that stimulates costimulated T cells.

Summary: The functional CD70 ligand is presented at the plasma membrane.

Reason: The machine inference agrees with direct human cell-surface expression and ligand-function experiments. PAINT is an ancestral-node inference; the inclusion of human P32970 among descendant evidence is expected and is not circular. No target-specific loss of localization is indicated.

Summary: The functional CD70 ligand is presented at the plasma membrane.

Reason: The abstract reports CD70 protein on human brain tumor cells, including preferential localization on U343 cell processes; this contextual expression supports the location without defining a tumor-specific core activity.

Summary: The functional CD70 ligand is presented at the plasma membrane.

Reason: Surface staining of activated B cells and EBV-infected B cells and the rescue experiments place the active ligand at the plasma membrane.

Summary: The functional CD70 ligand is presented at the plasma membrane.

Reason: Cell-surface expression cloning using a CD27 fusion probe identifies a type II membrane ligand.

Summary: The functional CD70 ligand is presented at the plasma membrane.

Reason: The machine inference agrees with direct human cell-surface expression and ligand-function experiments.

Summary: The functional CD70 ligand is presented at the plasma membrane.

Reason: The cached human reaction places CD70 on activated lymphocyte surfaces in the CD27-binding event.

Summary: The broad immune-response inference can be made mechanistically precise.

Reason: CD70 initiates the CD27 pathway as its extracellular ligand. Direct human cloning, receptor-binding and loss/rescue experiments support the named CD27 signaling pathway more informatively than the broad InterPro-derived immune-response term.

Proposed replacements: CD27 signaling pathway

Summary: Specify the plasma membrane for the active type II membrane ligand.

Reason: The generic membrane inference is valid but less informative than the cell-surface localization established in human expression and functional assays.

Proposed replacements: plasma membrane

Summary: CD70 deficiency affects humoral immunity, with an incompletely resolved cellular mechanism.

Reason: The full study reports hypogammaglobulinemia and reduced switched-memory B-cell proportions. Its Discussion explicitly leaves open intrinsic B-cell differentiation, deficient T-cell help and consequences of viral infection. Retain the existing broad B-cell immunity phenotype without equating it with a demonstrated direct B-cell proliferation activity. This broad immune-response annotation is supported by the measured antibody/memory phenotype; it does not require that the paper directly measured B-cell division.

Summary: Replace the family-level TNF signaling inference with CD27 signaling.

Reason: GO:0033209 describes signaling initiated by tumor necrosis factor itself. CD70 is a distinct TNF-family ligand that directly engages CD27; the official GO:0160162 definition names that ligand–receptor pair. The InterPro family inference should be refined to the directly established pathway. Current QuickGO ancestors of GO:0160162 do not include GO:0033209, corroborating this branch distinction.

Proposed replacements: CD27 signaling pathway

Summary: CD70 positively regulates T-cell proliferation by receptor costimulation.

Reason: The mouse-based electronic transfer describes a real response, independently demonstrated in human cells. Human CD70 on presenting cells supplies the CD27 costimulus, while the responding T cell performs division; positive regulation describes this role more precisely.

Proposed replacements: positive regulation of T cell proliferation

Summary: CD70 can support proliferation in a subset of human malignant B cells through reverse signaling.

Reason: The original human-deficiency paper (PMID:28011864) does not directly resolve a B-cell division assay or the humoral-defect mechanism. Independent PMID:10460611 reports proliferation of a subset of human B-CLLs after CD70, but not CD27, antibody ligation; CD40 ligation enhanced this response and IL-4 inhibited it. Its abstract attributes the response to CD70 agonism rather than blockade of inhibitory CD27 signaling. Retain the biological function as non-core in that malignant-cell context. Detailed assay controls were unavailable, and neither a normal-human-B-cell mechanism nor the original source-specific experimental basis is claimed resolved. PMID:15356138 provides supplementary mouse evidence; CD70 ligation supports proliferation and cell-cycle entry under the tested costimulation conditions. That mouse evidence does not establish a normal-human mechanism.

Summary: CD70 costimulation promotes T-cell proliferation.

Reason: The cloning-study abstract directly describes CD70-transfected cells inducing proliferation of PHA-costimulated T cells. Human CD70 restoration and CD27-dependence experiments provide independent mechanistic support.

Summary: CD70 contributes directly to T-cell activation through CD27.

Reason: CD70 provides a CD27 costimulatory signal in antigen-dependent T-cell activation. Human functional experiments demonstrate activation and expansion, while CD70 blockade reduces activation-marker induction. This is compatible with the PAINT ancestral-node assertion; target self-evidence in the donor set is legitimate, and no divergent loss is inferred.

Summary: CD70 contributes directly to T-cell activation through CD27.

Reason: CD70 provides a CD27 costimulatory signal in antigen-dependent T-cell activation. Human functional experiments demonstrate activation and expansion, while CD70 blockade reduces activation-marker induction.

Summary: CD70 contributes directly to T-cell activation through CD27.

Reason: CD70 provides a CD27 costimulatory signal in antigen-dependent T-cell activation. Human functional experiments demonstrate activation and expansion, while CD70 blockade reduces activation-marker induction.

Summary: CD70 contributes directly to T-cell activation through CD27.

Reason: CD70 provides a CD27 costimulatory signal in antigen-dependent T-cell activation. Human functional experiments demonstrate activation and expansion, while CD70 blockade reduces activation-marker induction.

Summary: Specify positive regulation of T-cell proliferation.

Reason: The broad electronic lymphocyte-proliferation term does not distinguish cell type or the ligand’s signaling role. Human CD70/CD27 experiments directly support a positive T-cell proliferative costimulus. This source-specific refinement concerns forward signaling to T cells; the separate non-core B-cell proliferation assertion is supported by independent CD70 reverse-signaling evidence in its stated experimental contexts.

Proposed replacements: positive regulation of T cell proliferation

Summary: CD70 is a physiological ligand for CD27.

Reason: CD70 binds CD27 and changes receptor-dependent responses: expression cloning, WT/mutant binding, and CD70-deficient B-cell rescue with CD27-dependent T-cell expansion establish the activity. The PAINT node is consistent with direct target evidence; target self-evidence does not constitute circular propagation.

Summary: CD70 is a physiological ligand for CD27.

Reason: CD70 binds CD27 and changes receptor-dependent responses: expression cloning, WT/mutant binding, and CD70-deficient B-cell rescue with CD27-dependent T-cell expansion establish the activity.

Summary: CD70 is a physiological ligand for CD27.

Reason: CD70 binds CD27 and changes receptor-dependent responses: expression cloning, WT/mutant binding, and CD70-deficient B-cell rescue with CD27-dependent T-cell expansion establish the activity.

Summary: CD70 is a physiological ligand for CD27.

Reason: CD70 binds CD27 and changes receptor-dependent responses: expression cloning, WT/mutant binding, and CD70-deficient B-cell rescue with CD27-dependent T-cell expansion establish the activity.

Summary: CD70 is a physiological ligand for CD27.

Reason: CD70 binds CD27 and changes receptor-dependent responses: expression cloning, WT/mutant binding, and CD70-deficient B-cell rescue with CD27-dependent T-cell expansion establish the activity.

Summary: CD70 has been identified in B-cell extracellular-vesicle preparations.

Reason: The cached abstract describes B-cell exosome proteomics. The source-linked Vesiclepedia entry explicitly indexes human CD70 protein to B-cell exosome experiments from PMID20458337, corroborating the target assignment. The original mass-spectrometry supplement was not independently inspected; this index is a representation of the same study, not replication, and study-wide western-blot methods do not establish CD70-specific western validation. Retain this contextual localization without assigning an exosome-biogenesis function.

Summary: CD70/CD27 costimulation contributes to adaptive immune memory.

Reason: Human CD70-deficiency studies reveal altered memory lymphocyte compartments and impaired expansion of EBV-specific T cells. Retain this existing higher-level immune-memory annotation as a physiological consequence; the central molecular activity is CD27 ligation. The IBA provenance, where applicable, is a PAINT ancestral-node assertion supported by target evidence, not a donor-count argument.

Summary: CD70/CD27 costimulation contributes to adaptive immune memory.

Reason: Human CD70-deficiency studies reveal altered memory lymphocyte compartments and impaired expansion of EBV-specific T cells. Retain this existing higher-level immune-memory annotation as a physiological consequence; the central molecular activity is CD27 ligation. The IBA provenance, where applicable, is a PAINT ancestral-node assertion supported by target evidence, not a donor-count argument.

Summary: CD70-mediated CD27 ligation can trigger apoptosis in particular lymphocyte contexts.

Reason: The official PubMed Figure1 caption explicitly describes CD70 versus mock transfectants, including fixed-cell ligand presentation to Ramos, Raji, CD27-transfected pre-B cells and activated human peripheral lymphocytes. Thus CD70 was actually tested despite the title foregrounding CD27 and Siva. Full primary body retrieval failed; the abstract and complete figure legend support contextual retention. CD70 is the extracellular trigger, not the intracellular Siva effector, and this result does not make apoptosis its universal outcome.

Summary: CD70 initiates CD27 signaling as its physiological ligand.

Reason: The official process definition specifically names CD27 binding CD70. Direct expression-cloning and receptor-dependent rescue experiments support this role, which is also represented by the separate CD70 ligand node in production GO-CAM 666b894f00000352. The ligand is not assigned the receptor’s intracellular adaptor or kinase activities.

Summary: CD70 initiates CD27 signaling as its physiological ligand.

Reason: The official process definition specifically names CD27 binding CD70. Direct expression-cloning and receptor-dependent rescue experiments support this role, which is also represented by the separate CD70 ligand node in production GO-CAM 666b894f00000352. The ligand is not assigned the receptor’s intracellular adaptor or kinase activities.

Summary: CD70 initiates CD27 signaling as its physiological ligand.

Reason: The official process definition specifically names CD27 binding CD70. Direct expression-cloning and receptor-dependent rescue experiments support this role, which is also represented by the separate CD70 ligand node in production GO-CAM 666b894f00000352. The ligand is not assigned the receptor’s intracellular adaptor or kinase activities.