CD27 (TNFRSF7) is a type I transmembrane costimulatory receptor of the tumor necrosis factor receptor superfamily. Its extracellular region recognizes CD70, while its short cytoplasmic tail couples ligand engagement to intracellular signaling partners including TRAF2. Cell-surface CD27 supports T-cell activation and expansion together with antigen-receptor signals, and contributes to context-dependent B-cell differentiation, antibody responses, survival and T-cell memory programs. Soluble CD27 also occurs extracellularly. Recessive loss of human CD27 impairs immune control of Epstein–Barr virus and causes lymphoproliferative syndrome 2.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004888 transmembrane signaling receptor activity | IDA PMID:28011863 Inherited CD70 deficiency in humans reveals a critical role ... | ACCEPT | Summary: CD27 transduces CD70-dependent costimulatory signals. Reason: The human study tests CD27 directly despite its CD70-focused title: CD27-Fc binding, anti-CD27 blockade, and T cells from a CD27 p.W110X patient establish the receptor-dependent response. CD27-deficient cells respond to anti-CD3/CD28 yet poorly to CD70-expressing B cells plus anti-CD3. Selected complete Results, Methods and captions were read. Supporting Evidence: |
| GO:0004888 transmembrane signaling receptor activity | IEA GO_REF:0000120 | ACCEPT | Summary: Automated receptor assignment agrees with direct human CD27 evidence. Reason: The preserved ARBA, ortholog and domain assertions are consistent with experimentally established human CD70-responsive transmembrane receptor activity. This corroborates the biological assignment without claiming a reconstruction of every automated rule. Supporting Evidence: |
| GO:0004888 transmembrane signaling receptor activity | NAS PMID:14556986 CD27 synergizes with CD40 to induce IgM, IgG, and IgA antibo... | ACCEPT | Summary: CD27 is a signaling receptor in the B-cell costimulation assay. Reason: The cited study uses anti-CD27 stimulation of peripheral-blood B-cell compartments and detects cooperation with CD40 and IL-2/IL-10. The abstract supports receptor signaling; direct human CD70/CD27 controls independently establish the molecular role. |
| GO:0005515 protein binding | IPI PMID:12324477 CD27 and CD40 inhibit p53-independent mitochondrial pathways... | KEEP AS NON CORE | Summary: Retain the CD70 ligand interaction as non-core generic binding. Reason: Human CD27-positive Ramos cells were cocultured with human CD70-expressing murine 300-19 feeder cells in the inspected original Methods and Results (DOI:10.1074/jbc.M209050200, author-uploaded original). CD70-dependent protection was reversed by anti-CD70. Direct CD27-Fc ligand binding independently corroborates the pair. The informative own activity is the separately represented receptor activity; generic binding is retained under the project override. |
| GO:0005515 protein binding | IPI PMID:16683188 The zinc containing pro-apoptotic protein siva interacts wit... | KEEP AS NON CORE | Summary: Retain CD27 association with SIVA1. Reason: The complete cached abstract explicitly reports directed two-hybrid mapping of the Siva N-terminal region that binds CD27, so the PMP22-focused title does not make this a wrong-gene citation. The original CD27/Siva coimmunoprecipitation study and the exact UniProt edge independently corroborate the pair. A finer own molecular activity is not established by this interaction alone. |
| GO:0005515 protein binding | IPI PMID:16683188 The zinc containing pro-apoptotic protein siva interacts wit... | KEEP AS NON CORE | Summary: Retain the curated SIVA1-1 interaction without claiming isoform-exclusive function. Reason: The original source partner O15304-1 is preserved. The paper explicitly reports CD27/Siva directed two-hybrid mapping, and independent CD27/SIVA1 interaction evidence supports the same gene pair. The cached abstract does not resolve all construct boundaries; the source isoform-specific edge is retained as curated rather than interpreted as exclusivity. |
| GO:0005515 protein binding | IPI PMID:25910212 Widespread macromolecular interaction perturbations in human... | KEEP AS NON CORE | Summary: Retain the ACTN2 interaction as non-core. Reason: The original interaction-screen assertion is preserved, and the reviewed CD27 UniProt record independently lists the exact ACTN2 P35609 edge. The complete abstract provides screen context but the original target-level table was not inspected. This supports retention of the generic pair without assigning actin binding or a structural activity to CD27. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | KEEP AS NON CORE | Summary: Retain screen-derived CD70 binding, independently corroborated by receptor studies. Reason: The original interactome target row is not claimed to have been inspected. CD70 P32970 is independently established as the CD27 ligand by direct expression cloning/CD27-Fc binding and human receptor-dependent activation. Generic binding is less informative than the receptor activity already represented. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Retain the CIB1 interaction as non-core. Reason: The HuRI source edge and its Q99828 partner are preserved; the reviewed UniProt record independently lists the exact CIB1 interaction. The complete abstract was read but the target-specific original screen table was not. No calcium-binding activity or physiological mechanism is transferred from CIB1 to CD27. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | KEEP AS NON CORE | Summary: Retain the SPRED1 interaction as non-core. Reason: The preserved Q7Z699 screen edge is independently present in the reviewed CD27 UniProt interaction record. The original paper is a neurodegeneration-centered interactome study, which does not exclude its assaying CD27. Exact target-table and construct details remain unverified; no pathway-specific own activity is inferred. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32822567 A Human IgSF Cell-Surface Interactome Reveals a Complex Netw... | KEEP AS NON CORE | Summary: Retain CD70 binding from the cell-surface interaction screen. Reason: The curated source edge is consistent with direct, independent CD27/CD70 receptor-ligand experiments. The paper-wide cell-surface assay context is accessible, but an original target-table reconstruction is not claimed. Generic binding remains non-core beside the informative receptor activity. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: Retain CD70 binding from the proteome-scale network. Reason: Independent direct CD27/CD70 experiments establish this exact pair. The original network edge and partner are preserved without implying that the screen measured receptor activation or that its target-level table was inspected. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: Retain the TRAF2 interaction as non-core generic binding. Reason: The exact Q12933 edge is corroborated by the reviewed UniProt record and independent receptor-tail/TRAF2 studies. The proteome-scale screen does not itself establish a specific signaling output. CD27 remains the receptor and TRAF2 the recruited adaptor; no adaptor activity is transferred to CD27. |
| GO:0005515 protein binding | IPI PMID:35922511 A physical wiring diagram for the human immune system. | KEEP AS NON CORE | Summary: Retain the independently established CD70 interaction. Reason: Direct receptor-ligand evidence corroborates the CD70 pair independently of the immune-wiring screen. The official 2024 correction concerns a CLC4M figure label, a concentration label and missing single-cell-method references; it is not a retraction or an identified CD27-edge correction. The original target-level screen table remains uninspected. |
| GO:0005515 protein binding | IPI PMID:36217029 A proteome-scale map of the SARS-CoV-2-human contactome. | KEEP AS NON CORE | Summary: Retain the viral replication-protein interaction as non-core. Reason: The exact P0DTD1-PRO_0000449624 interaction is corroborated in the reviewed UniProt CD27 record as a xenolog interaction. The contactome abstract establishes assay context but does not resolve all target-specific constructs or infection relevance. Retain the curated pair without assigning a viral replication process to CD27. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:9177220 CD27, a member of the tumor necrosis factor receptor family,... | KEEP AS NON CORE | Summary: Retain the CD27–SIVA1 interaction. Reason: The original study reports CD27 cytoplasmic-tail two-hybrid screening and coimmunoprecipitation of human CD27 with GFP-Siva in transfected 293 cells, with GFP and expression controls in the inspected original figure captions. Association is established; generic binding does not summarize the receptor’s core activity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:9692890 The TNF receptor family member CD27 signals to Jun N-termina... | KEEP AS NON CORE | Summary: Retain TRAF2 binding with the original species limit. Reason: The complete abstract reports receptor-tail two-hybrid association and dominant-negative TRAF2 experiments, while the physiological JNK assay explicitly uses primary murine lymph-node T cells. Human CD27’s exact TRAF2 edge is independently in reviewed UniProt and the later internalization study; full construct Methods for this 1998 source were not inspected. |
| GO:0005576 extracellular region | NAS PMID:12624711 High levels of serum soluble CD27 correlated with renal dysf... | KEEP AS NON CORE | Summary: Soluble CD27 occurs extracellularly. Reason: The cited human study measures serum soluble CD27 by ELISA. This supports extracellular localization of the soluble form, distinct from the membrane receptor’s active signaling location. The abstract’s proposed renal-apoptosis interpretation is not needed to retain this localization and is not adopted as a core role. Supporting Evidence: |
| GO:0005886 plasma membrane | IDA PMID:28011863 Inherited CD70 deficiency in humans reveals a critical role ... | ACCEPT | Summary: The signaling receptor acts at the plasma membrane. Reason: Human cell-surface flow cytometry, CD27-Fc ligand binding and receptor-dependent costimulation directly support this active location. CD27 p.W110X abolishes surface expression in the patient cells, whereas control T cells express the receptor. Supporting Evidence: |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Automated plasma-membrane localization agrees with direct human evidence. Reason: The preserved ARBA, mouse ortholog and subcellular-location sources agree with CD27’s transmembrane topology and actual human surface measurements. No reconstruction of the complete rule execution is claimed. Supporting Evidence: |
| GO:0005886 plasma membrane | NAS PMID:12324477 CD27 and CD40 inhibit p53-independent mitochondrial pathways... | ACCEPT | Summary: CD27 is present at the cell surface in the B-cell assay. Reason: The selected original Methods identify CD27-positive human Ramos cells stimulated through human CD70-bearing feeder cells. This agrees with the established membrane topology and direct human flow-cytometric evidence. The canonical 2002 cache remains abstract-only; original Methods were accessed externally at DOI:10.1074/jbc.M209050200. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5669024 | ACCEPT | Summary: Retain the curated Reactome-derived plasma-membrane assignment. Reason: The complete cached human event explicitly describes CD27 as a dimeric membrane glycoprotein on the surface of most T lymphocytes and its CD70 interaction. Human receptor experiments independently support the membrane location. |
| GO:0007166 cell surface receptor signaling pathway | NAS PMID:14556986 CD27 synergizes with CD40 to induce IgM, IgG, and IgA antibo... | KEEP AS NON CORE | Summary: Broad cell-surface signaling is correct but subsumed by CD27 signaling. Reason: CD27 ligation is an active receptor step in the cited B-cell costimulation system. The existing specific CD27 signaling pathway annotations describe the same core role more precisely, so the broad process is retained without duplicating it in the core synthesis. Supporting Evidence: |
| GO:0009897 external side of plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Retain inherited extracellular-facing membrane activity. Reason: The PAINT assertion is compatible with the receptor’s extracellular CD70-binding domain and direct human surface-ligand experiments. Its MGI descendant evidence and ancestral node are preserved. The original IBD node placement was not independently reconstructed; no donor-count or similarity-only argument is used. Supporting Evidence: |
| GO:0009897 external side of plasma membrane | IEA GO_REF:0000107 | ACCEPT | Summary: Retain ortholog-supported external plasma-membrane localization. Reason: Mouse-to-human electronic transfer is biologically corroborated by human CD27 surface expression and extracellular-domain ligand binding. The exact donor identifiers remain unchanged. Supporting Evidence: |
| GO:0009986 cell surface | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cell-surface localization is correct but broad. Reason: Direct human flow cytometry and receptor-ligand experiments corroborate the transferred location. Plasma-membrane receptor activity and its external-facing domain provide the more informative core location; the broader source assertion remains intact. Supporting Evidence: |
| GO:0016064 immunoglobulin mediated immune response | NAS PMID:14556986 CD27 synergizes with CD40 to induce IgM, IgG, and IgA antibo... | KEEP AS NON CORE | Summary: Retain the context-dependent antibody-response role. Reason: The complete abstract reports increased IgM, IgG and IgA production when CD27 stimulation is combined with CD40 stimulation and both IL-2 and IL-10. This is a B-cell costimulatory output rather than a separate molecular activity or a claim that CD27 itself binds immunoglobulin. Supporting Evidence: |
| GO:0042110 T cell activation | IDA PMID:28011863 Inherited CD70 deficiency in humans reveals a critical role ... | ACCEPT | Summary: CD27 directly costimulates T-cell activation. Reason: The inspected human experiments combine CD70-positive or CRISPR-disrupted B-cell stimulators, anti-CD3, anti-CD27 blockade and CD27-deficient T cells with an anti-CD3/CD28 response control. These establish CD27-mediated costimulation, not independent antigen recognition. Supporting Evidence: |
| GO:0043027 cysteine-type endopeptidase inhibitor activity involved in apoptotic process | IDA PMID:12324477 CD27 and CD40 inhibit p53-independent mitochondrial pathways... | MARK AS OVER ANNOTATED | Summary: Reduced caspase activation does not establish direct caspase-inhibitor activity. Reason: GO:0043027 requires binding to and reducing cysteine-type endopeptidase activity. The inspected original Methods and Results instead show human Ramos CD27 signaling from CD70-bearing feeder cells, Bcl-2/Bcl-XL and mitochondrial changes, and reduced caspase/PARP cleavage. Peptide caspase inhibitors are separate experimental reagents. These establish upstream suppression of apoptosis, already represented by GO:0043066, without demonstrating CD27 as the enzyme inhibitor. Original selected Methods/Results were accessed in the author-uploaded JBC paper, DOI:10.1074/jbc.M209050200; the immutable cache remains abstract-only. Supporting Evidence: PMID:12324477 CD27 and CD40 co-stimulatory signals regulated |
| GO:0043066 negative regulation of apoptotic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain inherited antiapoptotic signaling as a context-dependent role. Reason: The PAINT assertion agrees with direct human B-cell protection after CD27 stimulation. P26842 in WITH/FROM is legitimate target descendant evidence, not circularity. The original IBD placement was not reconstructed. Proapoptotic responses in different cell/stimulation contexts do not negate this experimentally supported antiapoptotic role. |
| GO:0043066 negative regulation of apoptotic process | IDA PMID:12324477 CD27 and CD40 inhibit p53-independent mitochondrial pathways... | KEEP AS NON CORE | Summary: CD27 suppresses BCR-induced apoptosis in human Ramos cells. Reason: The original CD70-feeder, vector-feeder, BCR-ligation and p53-mutant controls support a genuine context-dependent survival response involving mitochondrial pathways. This is upstream signaling and is distinct from a direct enzyme-inhibitor activity. The canonical abstract and externally accessed selected original Methods/Results agree. Supporting Evidence: |
| GO:0043066 negative regulation of apoptotic process | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Retain automated antiapoptotic regulation with context limits. Reason: Direct human B-cell evidence corroborates the biological assignment, while the exact ARBA/domain/ortholog sources remain preserved. This does not imply an invariably prosurvival response in every CD27-expressing cell or reconstruction of the complete automated rule. Supporting Evidence: |
| GO:0045579 positive regulation of B cell differentiation | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Retain positive regulation of B-cell differentiation as non-core. Reason: The domain-derived assertion is compatible with human CD27-dependent B-cell differentiation summarized in the cited review and with cytokine-dependent antibody production. CD27 supplies a receptor signal rather than being merely a marker, but the downstream cell-fate outcome is kept separate from the molecular core. |
| GO:0045579 positive regulation of B cell differentiation | NAS PMID:10809378 Memory B cells and CD27. | KEEP AS NON CORE | Summary: CD27 signaling can promote B-cell differentiation toward plasma cells. Reason: The complete review abstract explicitly distinguishes CD27 as a memory marker from ligation-derived signals promoting entry into the plasma-cell pathway. This NAS assertion is retained as a reviewed functional role; no new primary experiment is attributed to the review. Supporting Evidence: |
| GO:0045582 positive regulation of T cell differentiation | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Retain regulation of T-cell differentiation as a downstream receptor role. Reason: The family-derived assertion is compatible with CD27 costimulation of activated human T cells and the later CD27-internalization study’s memory-programming findings. This is a context-dependent outcome of receptor signaling, not a second molecular activity. Exact InterPro source objects remain unchanged. |
| GO:0046330 positive regulation of JNK cascade | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain transferred positive regulation of JNK signaling. Reason: The donor-linked murine study directly measures CD27 augmentation of TCR-induced JNK activity and implicates TRAF2. This supports the preserved ortholog transfer at the biological level. It does not establish that CD27 is a kinase, and full donor construct Methods have not been inspected. Supporting Evidence: |
| GO:0046330 positive regulation of JNK cascade | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain curator-mediated ortholog transfer of JNK regulation. Reason: The direct murine T-cell JNK activation evidence supports this conserved receptor-signaling output. The original ISS source and donor are retained; the inference is not reclassified as a direct human assay. Supporting Evidence: |
| GO:0090717 adaptive immune memory response involving T cells and B cells | IMP PMID:28011863 Inherited CD70 deficiency in humans reveals a critical role ... | UNDECIDED | Summary: The exact combined T- and B-cell memory assertion remains unresolved. Reason: The paper contains direct human CD27-deficient T-cell costimulation experiments, so it is not a wrong-gene citation. However, the reduced memory-B-cell counts are from the CD70-deficient index patient, and the authors distinguish impaired T-cell expansion from intrinsic memory differentiation, noting that memory T-cell immunity may be preserved. The inspected Methods/Results do not resolve the original CD27-specific IMP mapping to this combined memory term. Later CD27 memory-programming evidence supports a broader role but does not reconstruct this exact source assertion. |
| GO:0097191 extrinsic apoptotic signaling pathway | IDA PMID:9177220 CD27, a member of the tumor necrosis factor receptor family,... | KEEP AS NON CORE | Summary: Retain a context-dependent extrinsic apoptotic response. Reason: The original report tests CD70-triggered apoptosis in Ramos/Raji cells, human CD27-transfected murine pre-B cells and activated human lymphocytes, with ligand/vector and cell-stimulation controls described in the inspected original captions. Receptor-tail association with Siva is independently demonstrated. This bounded signaling response is retained alongside, not confused with, the antiapoptotic BCR-context experiments; a death-domain or universal death-receptor function is not asserted. |
| GO:0160162 CD27 signaling pathway | IDA PMID:28011863 Inherited CD70 deficiency in humans reveals a critical role ... | ACCEPT | Summary: Human CD27 performs the receptor step of CD27 signaling. Reason: Direct receptor blockade and CD27 p.W110X patient-cell controls demonstrate the CD70-dependent signaling response. The cached GO-CAM model 666b894f00000352 independently places CD27 receptor activity in this pathway; the term is not inferred solely from a disease phenotype. Supporting Evidence: |
| GO:0160162 CD27 signaling pathway | IDA PMID:8387892 Molecular and biological characterization of a ligand for CD... | ACCEPT | Summary: CD70 engagement initiates CD27-dependent signaling. Reason: The original cloning paper uses a CD27 extracellular-domain–IgG fusion probe to identify its ligand and reports stimulation of costimulated T-cell proliferation and cytolytic-cell generation. Later human receptor-deficiency controls corroborate the pathway assignment; complete original Methods for the 1993 paper remain inaccessible. |
| GO:0160162 CD27 signaling pathway | IEA GO_REF:0000120 | ACCEPT | Summary: Retain automated assignment to the CD27 signaling pathway. Reason: The exact automated and mouse-ortholog sources agree with the directly established human receptor-ligand signaling mechanism and the existing GO-CAM context. No new process annotation is needed to express this core role. |
| GO:1901224 positive regulation of non-canonical NF-kappaB signal transduction | NAS PMID:12324477 CD27 and CD40 inhibit p53-independent mitochondrial pathways... | UNDECIDED | Summary: Noncanonical signaling has independent support; the original source mapping remains unresolved. Reason: The inspected original 2002 B-cell paper measures mitochondrial apoptosis and caspase activation, not an identified p100/RelB-processing assay; introductory NF-kappaB citations are not original branch-specific experiments. The separately retrieved PMID:15485626 abstract explicitly reports CD70-induced p100 processing and receptor-associated CD27/NIK/IKK signaling, supporting this biological branch. Its full Methods, construct species and assay boundaries remain inaccessible. This corroboration does not reconstruct the original 2002 NAS mapping, which remains UNDECIDED without claiming that CD27 lacks noncanonical signaling. |
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Download this section (compressed HTML)Q: Which ligand-presentation and intracellular-signaling contexts determine the balance between CD27-mediated survival, proliferative costimulation and apoptosis?
Q: Which distinct features of CD27 signaling regulate establishment of B-cell memory versus T-cell memory independently of acute expansion?
Experiment: Compare matched human CD27 wild-type and signaling-tail mutants under controlled membrane-bound CD70 presentation, separating early signaling, proliferation, mitochondrial apoptosis and later memory-state readouts.
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