Cyclin D2 is a noncatalytic regulatory subunit of cyclin-dependent kinases that couples growth signals to G1 progression and entry into S phase. Its association with CDK4 or CDK6 promotes retinoblastoma-family protein phosphorylation by the kinase subunit, relieving restraint on cell-cycle progression. Cyclin D2-containing complexes redistribute between the cytoplasm and nucleus, with nuclear-envelope and chromatin-associated populations observed during cell-cycle entry. Cyclin D2 abundance is controlled by ubiquitin-dependent proteolysis. Pathogenic CCND2 variants cause megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000082 G1/S transition of mitotic cell cycle | IBA GO_REF:0000033 | ACCEPT | Summary: Retain the conserved G1/S cyclin function. Reason: PAINT places the G1/S assertion at PTN000019791 in the cyclin family. Human CCND2-containing complexes promote cell-cycle entry, independently supporting the inherited role. The target appearing among experimental descendants is expected evidence for the ancestral assertion, not circularity. Supporting Evidence: |
| GO:0000082 G1/S transition of mitotic cell cycle | IDA PMID:18827403 Migratory localization of cyclin D2-Cdk4 complex suggests a ... | ACCEPT | Summary: Cyclin D2-CDK4 promotes entry into S phase. Reason: The official full paper reports human CCND2 and CDK4 constructs, coexpression in HeLa and NIH-3T3 cells, and accelerated DNA synthesis in synchronized NIH-3T3 cells compared with empty-vector and truncated-CCND2 controls. Human HeLa proliferation and localization are also measured. This is a regulatory cyclin contribution to G1/S transition, not intrinsic catalysis by CCND2. Supporting Evidence: PMID:18827403 acceleration with overexpression of cyclin D2 and Cdk4 |
| GO:0000082 G1/S transition of mitotic cell cycle | IEA GO_REF:0000117 | ACCEPT | Summary: The electronic G1/S assignment agrees with direct cyclin biology. Reason: ARBA00028571 is retained because the regulatory D2-CDK4 mechanism and actual cell-cycle experiments independently support G1/S progression; the electronic source is not treated as another experiment. Supporting Evidence: |
| GO:0000082 G1/S transition of mitotic cell cycle | NAS PMID:7603984 Growth suppression by p16ink4 requires functional retinoblas... | ACCEPT | Summary: Retain the historical G1/S statement with independent target support. Reason: The available PMID:7603984 abstract focuses on p16-dependent arrest and the requirement for functional RB in human cells and mouse fibroblasts. It does not independently resolve a CCND2-specific perturbation. The NAS assertion nevertheless describes an established CCND2 function supported by the directly examined D2-CDK4 study; no citation error is inferred from the abstract focus. |
| GO:0000082 G1/S transition of mitotic cell cycle | TAS PMID:33854239 The AMBRA1 E3 ligase adaptor regulates the stability of cycl... | ACCEPT | Summary: Cyclin D2 is part of the D-cyclin machinery driving G1/S entry. Reason: The actual AMBRA1 paper measures increased D1/D2/D3 levels and half-lives, and tests joint overexpression of all three D cyclins in human U2OS cells. It supports the stated D-cyclin role but does not isolate every response to D2 alone. Independent D2-CDK4 evidence and the GO-CAM assignment support this existing TAS row. |
| GO:0000307 cyclin-dependent protein kinase holoenzyme complex | IBA GO_REF:0000033 | ACCEPT | Summary: CCND2 is a cyclin-dependent kinase holoenzyme subunit. Reason: The PTN000019791 inheritance agrees with direct assembly of CCND2 with CDK4 and CDK6. The holoenzyme contains a regulatory cyclin and a catalytic kinase; complex membership does not assign kinase activity to the cyclin. |
| GO:0000307 cyclin-dependent protein kinase holoenzyme complex | IDA PMID:18827403 Migratory localization of cyclin D2-Cdk4 complex suggests a ... | ACCEPT | Summary: Human cyclin D2 forms a complex with CDK4. Reason: Human full-length CCND2 interacts with CDK4 in yeast two-hybrid and tagged HEK293T coimmunoprecipitation experiments. The N-terminal deletion weakens the association. The source supports holoenzyme membership, with functional consequences assessed separately in cell-cycle assays. Supporting Evidence: |
| GO:0000307 cyclin-dependent protein kinase holoenzyme complex | IDA PMID:8114739 Identification of G1 kinase activity for cdk6, a novel cycli... | ACCEPT | Summary: Cyclin D2 associates with the CDK6 holoenzyme. Reason: The accessible original abstract explicitly reports D1, D2 and D3 association with human CDK6 in human-cell lysates and activation after coexpression in Sf9 cells. The cache remains abstract-only despite its Full Text heading. This supports complex membership without assigning the catalytic reaction to CCND2. Supporting Evidence: |
| GO:0000785 chromatin | IDA PMID:18827403 Migratory localization of cyclin D2-Cdk4 complex suggests a ... | KEEP AS NON CORE | Summary: Retain the experimentally observed chromatin-associated population. Reason: The complete publisher paper reports tagged human CCND2-CDK4 localization at chromatin in HeLa cells (Table II and Figure 4 narrative) and colocalization with chromatin and RB in NIH-3T3 assays using human constructs. This is spatial association under coexpression conditions, not sequence-specific DNA binding or a separate chromatin-modifying activity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:11896535 Cell cycle progression of chronic lymphocytic leukemia cells... | MODIFY | Summary: Refine the functional CCND2-CDK4 interaction to kinase activation. Reason: PMID:11896535 explicitly reports CCND2-CDK4 immune complexes from stimulated human B-CLL cells that phosphorylate RB in vitro. Together with human D2-CDK4 construct experiments, this supports the cyclin regulatory activity rather than an undifferentiated interaction. CDK4 performs the phosphotransfer; CCND2 is its activating regulatory subunit. The lack of CDK6 association in these B-CLL conditions is not generalized to other cells. Proposed replacements: cyclin-dependent protein serine/threonine kinase activator activity |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | KEEP AS NON CORE | Summary: Retain the CDKN1A/p21 association with source-specific limits. Reason: The original human interactome screen provides a curated p21 interaction; the complete abstract was read but its exact target table was not reanalysed. The exact source partner is preserved. Generic binding is retained as non-core under the project override; the interaction alone does not demonstrate a new regulatory activity of CCND2. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | KEEP AS NON CORE | Summary: Retain the CDKN1B/p27 association with source-specific limits. Reason: This separately preserved edge concerns p27 in the same human interaction resource; it is not merged with the p21 edge. The exact source partner is preserved. Generic binding is retained as non-core under the project override; the interaction alone does not demonstrate a new regulatory activity of CCND2. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:16765349 Increased p21 expression and complex formation with cyclin E... | KEEP AS NON CORE | Summary: Retain the CDKN1A/p21 association with source-specific limits. Reason: The abstract explicitly studies human Nalm-6 cells and foregrounds cyclin E-CDK2. The CCND2-p21 experiment is not visible in the abstract; that foreground is not evidence of a wrong-gene annotation. The exact source partner is preserved. Generic binding is retained as non-core under the project override; the interaction alone does not demonstrate a new regulatory activity of CCND2. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:23455922 Interlaboratory reproducibility of large-scale human protein... | MODIFY | Summary: Refine the CDK5 interaction to serine/threonine kinase binding. Reason: The standardized AP-MS study assayed 32 human kinases. The exact CCND2-CDK5 table entry and direct interface were not independently inspected; the retained curator interaction is also recorded in reviewed UniProt. The source already asserts protein binding to this exact kinase, and the corroborated partner class permits GO:0120283 without assigning kinase catalysis, activation, or an atomic interface to CCND2. The uninspected target-assay details remain explicit. Proposed replacements: protein serine/threonine kinase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:23602568 The protein interaction landscape of the human CMGC kinase g... | MODIFY | Summary: Refine the CDK5 interaction to serine/threonine kinase binding. Reason: This CMGC kinase-complex study reports a human proteomic interaction resource. The curated CDK5 edge is corroborated by reviewed UniProt, while the original target-specific pull-down controls remain uninspected. The source already asserts protein binding to this exact kinase, and the corroborated partner class permits GO:0120283 without assigning kinase catalysis, activation, or an atomic interface to CCND2. The uninspected target-assay details remain explicit. Proposed replacements: protein serine/threonine kinase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | KEEP AS NON CORE | Summary: Retain the CDKN1A/p21 association with source-specific limits. Reason: The study uses endogenous in situ proximity ligation in HeLa cells. Proximity evidence supports an association, not a solved direct interface; the specific p21 edge is retained with curated corroboration. The exact source partner is preserved. Generic binding is retained as non-core under the project override; the interaction alone does not demonstrate a new regulatory activity of CCND2. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Retain the CDKN1A/p21 association with source-specific limits. Reason: The human binary interactome resource supports a curator-recorded p21 edge. Its specific clone/construct table was not reread; reviewed UniProt independently lists the same pair. The exact source partner is preserved. Generic binding is retained as non-core under the project override; the interaction alone does not demonstrate a new regulatory activity of CCND2. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MODIFY | Summary: Refine the CDK5 interaction to serine/threonine kinase binding. Reason: The binary human interactome source and reviewed UniProt agree on the exact CDK5 partner. The original target clone and assay trace were not independently reconstructed. The source already asserts protein binding to this exact kinase, and the corroborated partner class permits GO:0120283 without assigning kinase catalysis, activation, or an atomic interface to CCND2. The uninspected target-assay details remain explicit. Proposed replacements: protein serine/threonine kinase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25910212 Widespread macromolecular interaction perturbations in human... | MODIFY | Summary: Refine the CDK4 interaction to serine/threonine kinase binding. Reason: The disease-variant interaction resource supplies this CDK4 edge. Independent full primary D2-CDK4 binding experiments corroborate the wild-type pair, without attributing an uninspected variant effect to this row. The source already asserts protein binding to this exact kinase, and the corroborated partner class permits GO:0120283 without assigning kinase catalysis, activation, or an atomic interface to CCND2. The uninspected target-assay details remain explicit. Proposed replacements: protein serine/threonine kinase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25910212 Widespread macromolecular interaction perturbations in human... | KEEP AS NON CORE | Summary: Retain the CDKN1B/p27 association with source-specific limits. Reason: This disease-variant screen records the p27 interaction. No specific mutation-dependent gain or loss is asserted without the target table; reviewed UniProt corroborates the pair. The exact source partner is preserved. Generic binding is retained as non-core under the project override; the interaction alone does not demonstrate a new regulatory activity of CCND2. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:26871637 Widespread Expansion of Protein Interaction Capabilities by ... | MODIFY | Summary: Refine the CDK5 interaction to serine/threonine kinase binding. Reason: The alternative-splicing study compares human protein isoform interactions. The exact tested construct is not inferred to be the naturally truncated CCND2 isoform merely from the paper theme; the preserved row has no such isoform assignment. The source already asserts protein binding to this exact kinase, and the corroborated partner class permits GO:0120283 without assigning kinase catalysis, activation, or an atomic interface to CCND2. The uninspected target-assay details remain explicit. Proposed replacements: protein serine/threonine kinase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:27107012 Pooled-matrix protein interaction screens using Barcode Fusi... | MODIFY | Summary: Refine the CDK4 interaction to serine/threonine kinase binding. Reason: The Barcode Fusion Genetics study is a multiplexed yeast two-hybrid resource. Its CDK4 edge is consistent with independently read human CCND2-CDK4 primary experiments; no target-specific reporter score is invented. The source already asserts protein binding to this exact kinase, and the corroborated partner class permits GO:0120283 without assigning kinase catalysis, activation, or an atomic interface to CCND2. The uninspected target-assay details remain explicit. Proposed replacements: protein serine/threonine kinase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:27107012 Pooled-matrix protein interaction screens using Barcode Fusi... | KEEP AS NON CORE | Summary: Retain the CDKN1A/p21 association with source-specific limits. Reason: This BFG-Y2H p21 edge is retained independently of the two kinase edges from the same paper. The exact pair-level barcode result was not reanalysed. The exact source partner is preserved. Generic binding is retained as non-core under the project override; the interaction alone does not demonstrate a new regulatory activity of CCND2. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:27107012 Pooled-matrix protein interaction screens using Barcode Fusi... | MODIFY | Summary: Refine the CDK5 interaction to serine/threonine kinase binding. Reason: The BFG-Y2H interaction records CDK5 rather than CDK4. Reviewed UniProt corroborates the pair, but a binary interaction does not establish activation of CDK5. The source already asserts protein binding to this exact kinase, and the corroborated partner class permits GO:0120283 without assigning kinase catalysis, activation, or an atomic interface to CCND2. The uninspected target-assay details remain explicit. Proposed replacements: protein serine/threonine kinase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: Refine the CDK4 interaction to serine/threonine kinase binding. Reason: BioPlex 2.0 records the exact CDK4 association. AP-MS detects coassociation and its individual complex topology was not reconstructed; independent human D2-CDK4 binding supports the pair. The source already asserts protein binding to this exact kinase, and the corroborated partner class permits GO:0120283 without assigning kinase catalysis, activation, or an atomic interface to CCND2. The uninspected target-assay details remain explicit. Proposed replacements: protein serine/threonine kinase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: Refine the CDK2 interaction to serine/threonine kinase binding. Reason: This separate BioPlex 2.0 edge is to CDK2. The reviewed UniProt entry corroborates the pair; the association is not used to claim that CCND2 activates CDK2 in every physiological setting. The source already asserts protein binding to this exact kinase, and the corroborated partner class permits GO:0120283 without assigning kinase catalysis, activation, or an atomic interface to CCND2. The uninspected target-assay details remain explicit. Proposed replacements: protein serine/threonine kinase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | KEEP AS NON CORE | Summary: Retain the CDKN1A/p21 association with source-specific limits. Reason: The BioPlex 2.0 p21 coassociation is retained as context-dependent complex evidence; no additional scaffold or inhibitor activity is assigned to CCND2 from this edge. The exact source partner is preserved. Generic binding is retained as non-core under the project override; the interaction alone does not demonstrate a new regulatory activity of CCND2. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | KEEP AS NON CORE | Summary: Retain the CDKN1B/p27 association with source-specific limits. Reason: The separate BioPlex 2.0 p27 coassociation is retained with the same AP-MS access limit. p27 activity is not transferred to the cyclin. The exact source partner is preserved. Generic binding is retained as non-core under the project override; the interaction alone does not demonstrate a new regulatory activity of CCND2. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: Refine the CDK5 interaction to serine/threonine kinase binding. Reason: BioPlex 2.0 and reviewed UniProt support the CDK5 association. Coassociation does not by itself establish kinase activation, direct substrate recognition, or a neuronal process. The source already asserts protein binding to this exact kinase, and the corroborated partner class permits GO:0120283 without assigning kinase catalysis, activation, or an atomic interface to CCND2. The uninspected target-assay details remain explicit. Proposed replacements: protein serine/threonine kinase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | MODIFY | Summary: Refine the CDK4 interaction to serine/threonine kinase binding. Reason: The population-variant interaction screen records the CDK4 edge. Independent wild-type human CCND2-CDK4 assays corroborate it; the exact screened allele remains outside the independently examined evidence. The source already asserts protein binding to this exact kinase, and the corroborated partner class permits GO:0120283 without assigning kinase catalysis, activation, or an atomic interface to CCND2. The uninspected target-assay details remain explicit. Proposed replacements: protein serine/threonine kinase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | KEEP AS NON CORE | Summary: Retain the CDKN1A/p21 association with source-specific limits. Reason: This population-variant screen also records p21 binding. The exact allele-specific result was not reanalysed, so the existing association is retained without a new effect-of-variant claim. The exact source partner is preserved. Generic binding is retained as non-core under the project override; the interaction alone does not demonstrate a new regulatory activity of CCND2. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: Refine the CDK4 interaction to serine/threonine kinase binding. Reason: HuRI records a human binary CCND2-CDK4 edge. Independent primary binding and functional evidence support the pair, but no HuRI target reporter value is claimed here. The source already asserts protein binding to this exact kinase, and the corroborated partner class permits GO:0120283 without assigning kinase catalysis, activation, or an atomic interface to CCND2. The uninspected target-assay details remain explicit. Proposed replacements: protein serine/threonine kinase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Retain the CDKN1A/p21 association with source-specific limits. Reason: The HuRI p21 edge agrees with reviewed UniProt. The target clone and orthogonal validation data were not independently inspected; the supported association is retained under the project policy. The exact source partner is preserved. Generic binding is retained as non-core under the project override; the interaction alone does not demonstrate a new regulatory activity of CCND2. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: Refine the CDK5 interaction to serine/threonine kinase binding. Reason: The HuRI CDK5 edge is a binary-interaction assertion supported qualitatively by reviewed UniProt. It is not evidence of CDK5 activation or a specific neuronal phenotype. The source already asserts protein binding to this exact kinase, and the corroborated partner class permits GO:0120283 without assigning kinase catalysis, activation, or an atomic interface to CCND2. The uninspected target-assay details remain explicit. Proposed replacements: protein serine/threonine kinase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | MODIFY | Summary: Refine the CDK5 interaction to serine/threonine kinase binding. Reason: The kinase interaction network is an AP-MS/co-complex resource. Retain the exact curated CDK5 interaction with UniProt corroboration; its specific pull-down controls and complex topology were not reanalysed. The source already asserts protein binding to this exact kinase, and the corroborated partner class permits GO:0120283 without assigning kinase catalysis, activation, or an atomic interface to CCND2. The uninspected target-assay details remain explicit. Proposed replacements: protein serine/threonine kinase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Refine the CDK4 interaction to serine/threonine kinase binding. Reason: BioPlex 3.0 compares 293T and HCT116 interaction networks. The preserved cache is partial HTML; no particular cell-line-specific CCND2 edge is claimed beyond the source annotation. Direct human primary evidence supports the CDK4 pair. The source already asserts protein binding to this exact kinase, and the corroborated partner class permits GO:0120283 without assigning kinase catalysis, activation, or an atomic interface to CCND2. The uninspected target-assay details remain explicit. Proposed replacements: protein serine/threonine kinase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Refine the CDK2 interaction to serine/threonine kinase binding. Reason: This is the separate CDK2 edge from BioPlex 3.0. The reviewed UniProt interaction supports the pair, while the target-specific cell-line comparison is not independently resolved from the partial cache. The source already asserts protein binding to this exact kinase, and the corroborated partner class permits GO:0120283 without assigning kinase catalysis, activation, or an atomic interface to CCND2. The uninspected target-assay details remain explicit. Proposed replacements: protein serine/threonine kinase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: Retain the CDKN1A/p21 association with source-specific limits. Reason: The BioPlex 3.0 p21 association is retained without claiming a direct interface or a particular cell-line restriction from the partial HTML cache. The exact source partner is preserved. Generic binding is retained as non-core under the project override; the interaction alone does not demonstrate a new regulatory activity of CCND2. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: Retain the CDKN1B/p27 association with source-specific limits. Reason: The BioPlex 3.0 p27 association is retained separately from p21. Reviewed UniProt lists both pairs, and the uninspected target table is not used to manufacture a mechanistic distinction. The exact source partner is preserved. Generic binding is retained as non-core under the project override; the interaction alone does not demonstrate a new regulatory activity of CCND2. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Refine the CDK5 interaction to serine/threonine kinase binding. Reason: The BioPlex 3.0 CDK5 association is qualitatively corroborated by reviewed UniProt. Its partial HTML cache does not establish a particular isoform, cellular restriction, or activation mechanism. The source already asserts protein binding to this exact kinase, and the corroborated partner class permits GO:0120283 without assigning kinase catalysis, activation, or an atomic interface to CCND2. The uninspected target-assay details remain explicit. Proposed replacements: protein serine/threonine kinase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:39526800 A comprehensive two-hybrid analysis to explore the Legionell... | MODIFY | Summary: Refine the CDK4 interaction to serine/threonine kinase binding. Reason: The actual Legionella paper includes a human positive-reference interaction set, with 20 of 21 expected pairs detected. The exact CCND2-CDK4 supplemental row was not inspected, so it is not asserted to be one of those 20; independent human D2-CDK4 experiments and reviewed UniProt support this curated pair. The bacterial title is not evidence of misattribution. The source already asserts protein binding to this exact kinase, and the corroborated partner class permits GO:0120283 without assigning kinase catalysis, activation, or an atomic interface to CCND2. The uninspected target-assay details remain explicit. Proposed replacements: protein serine/threonine kinase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: Refine the CDK2 interaction to serine/threonine kinase binding. Reason: The multimodal human U2OS map includes physical-interaction measurements. The exact CCND2-CDK2 target assay was not independently reconstructed; reviewed UniProt provides qualitative pair corroboration. Neither the map nor the partner identity is used to assign catalysis to CCND2. The source already asserts protein binding to this exact kinase, and the corroborated partner class permits GO:0120283 without assigning kinase catalysis, activation, or an atomic interface to CCND2. The uninspected target-assay details remain explicit. Proposed replacements: protein serine/threonine kinase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:9840943 Cyclin E2, a novel human G1 cyclin and activating partner of... | MODIFY | Summary: Refine the CDK2 interaction to serine/threonine kinase binding. Reason: The abstract foregrounds human cyclin E2, but this does not refute a curator-extracted CCND2-CDK2 interaction elsewhere in the paper. The actual CCND2 target experiment remains uninspected; reviewed UniProt independently lists the pair, supporting retention and partner-class refinement rather than a wrong-gene claim. The source already asserts protein binding to this exact kinase, and the corroborated partner class permits GO:0120283 without assigning kinase catalysis, activation, or an atomic interface to CCND2. The uninspected target-assay details remain explicit. Proposed replacements: protein serine/threonine kinase binding Supporting Evidence: |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Nuclear localization is conserved and directly observed. Reason: The PTN000019791 localization inference agrees with human CCND2 construct localization during cell-cycle entry. It does not imply constitutive nuclear residence in all phases. Supporting Evidence: |
| GO:0005634 nucleus | IDA PMID:18827403 Migratory localization of cyclin D2-Cdk4 complex suggests a ... | ACCEPT | Summary: Human CCND2-containing complexes enter the nucleus. Reason: The full source reports tagged human CCND2-CDK4 localization in HeLa cells and human-construct experiments in NIH-3T3 cells, with controls for tags and an N-terminal CCND2 deletion. Nuclear entry is dynamic and cell-cycle-associated. Supporting Evidence: |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Retain the combined electronic nuclear localization. Reason: The combined orthology and curated-location mapping agrees with directly observed nuclear CCND2-containing complexes; it is retained as an inference rather than new experimental evidence. Supporting Evidence: |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Retain the curated nucleoplasmic staining assignment. Reason: This is an immunofluorescence-curated IDA annotation under GO_REF:0000052. The exact HPA images and antibody controls were not independently reanalysed, but nuclear localization is independently supported. Retain the existing regional localization without equating it to a new activity or a universal compartment. Supporting Evidence: |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-1226094 | KEEP AS NON CORE | Summary: Retain the pathway-associated nucleoplasmic localization. Reason: The cached event emphasizes cyclin D1-dependent RBL2 phosphorylation and is not itself a CCND2 localization experiment. The exact Reactome-derived GOA localization is preserved and is biologically consistent with independent nuclear CCND2 evidence. The cached event summary alone is not treated as direct observation of CCND2 in this compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-1226095 | KEEP AS NON CORE | Summary: Retain the pathway-associated nucleoplasmic localization. Reason: The event describes D-cyclin/CDK4/6 action on RBL1, rather than an independent imaging assay. The exact Reactome-derived GOA localization is preserved and is biologically consistent with independent nuclear CCND2 evidence. The cached event summary alone is not treated as direct observation of CCND2 in this compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-69227 | KEEP AS NON CORE | Summary: Retain the pathway-associated nucleoplasmic localization. Reason: The event explicitly includes CCND2 among D cyclins paired with CDK4/6 for RB1 phosphorylation. The exact Reactome-derived GOA localization is preserved and is biologically consistent with independent nuclear CCND2 evidence. The cached event summary alone is not treated as direct observation of CCND2 in this compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8942803 | KEEP AS NON CORE | Summary: Retain the pathway-associated nucleoplasmic localization. Reason: The event describes cytoplasm-to-nucleus translocation of D-cyclin/CDK4/6 complexes and discusses Cip/Kip-dependent import. The exact Reactome-derived GOA localization is preserved and is biologically consistent with independent nuclear CCND2 evidence. The cached event summary alone is not treated as direct observation of CCND2 in this compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8942836 | KEEP AS NON CORE | Summary: Retain the pathway-associated nucleoplasmic localization. Reason: The event describes activating T-loop phosphorylation of CDK4/6, not catalytic activity of the cyclin. The exact Reactome-derived GOA localization is preserved and is biologically consistent with independent nuclear CCND2 evidence. The cached event summary alone is not treated as direct observation of CCND2 in this compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9754129 | KEEP AS NON CORE | Summary: Retain the pathway-associated nucleoplasmic localization. Reason: The inhibitor event distinguishes D1-, D2- and D3-containing CDK6 complexes; it is not an independent CCND2 localization assay. The exact Reactome-derived GOA localization is preserved and is biologically consistent with independent nuclear CCND2 evidence. The cached event summary alone is not treated as direct observation of CCND2 in this compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9754130 | KEEP AS NON CORE | Summary: Retain the pathway-associated nucleoplasmic localization. Reason: The inhibitor event includes candidate inhibition of D2-containing CDK4 complexes, with explicit limits on several compounds. The exact Reactome-derived GOA localization is preserved and is biologically consistent with independent nuclear CCND2 evidence. The cached event summary alone is not treated as direct observation of CCND2 in this compartment. |
| GO:0005730 nucleolus | IDA PMID:18827403 Migratory localization of cyclin D2-Cdk4 complex suggests a ... | KEEP AS NON CORE | Summary: Retain nucleolar localization observed under coexpression conditions. Reason: The complete publisher paper explicitly records nucleolar localization in 88 of 384 HeLa cells coexpressing tagged full-length human CCND2 and CDK4 (Table II). This supports the original location with an overexpression/context limit; it does not establish a separate ribosome-biogenesis activity. Supporting Evidence: |
| GO:0005737 cytoplasm | EXP PMID:18827403 Migratory localization of cyclin D2-Cdk4 complex suggests a ... | ACCEPT | Summary: CCND2 has a cytoplasmic phase before nuclear import. Reason: Human CCND2/CDK4 coexpression experiments in HeLa cells show a cytoplasmic population before nuclear-envelope accumulation. Endogenous murine proteins in NIH-3T3 provide separate corroboration, not interchangeable human measurements. Supporting Evidence: |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Retain the inherited cytoplasmic localization. Reason: PTN000019791 supports an ancestral localization consistent with the target experiment. No target-specific loss or divergence contradicts this conserved feature. Supporting Evidence: |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: The curated-location electronic cytoplasmic mapping is appropriate. Reason: SL-0086 maps the reviewed UniProt cytoplasmic location to GO and agrees with the actual CCND2 cellular localization study. It does not add a distinct biological activity. Supporting Evidence: |
| GO:0005815 microtubule organizing center | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain the PAINT MTOC inference as a non-core localization. Reason: The actual cached PAINT record identifies the non-negated IBD at PTN007424001 in PTHR10177, dated 2025-12-18, with fungal and vertebrate experimental descendants. This is a phylogenetic ancestral assertion, not a donor-count vote. The complete tree/MSA node placement and target-specific MTOC images were not independently reconstructed, and no CCND2-specific loss has been established. Retain curator deference with that limit; the main cyclin mechanism does not establish a microtubule-nucleation activity, and this location is not placed in the core. |
| GO:0005829 cytosol | IDA PMID:18827403 Migratory localization of cyclin D2-Cdk4 complex suggests a ... | ACCEPT | Summary: The soluble cytoplasmic CCND2 population is supported. Reason: The full localization study describes cytoplasmic complex assembly and the cytosolic surface of the nuclear pores before nuclear entry. This is compatible with the source cytosol assignment and does not imply an integral membrane protein. Supporting Evidence: |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8942803 | ACCEPT | Summary: Retain cytosol as the starting compartment for complex translocation. Reason: The complete Reactome summary explicitly describes CDK4/6:CCND complexes moving from cytoplasm to nucleus; the preserved GOA assignment is corroborated by direct CCND2 localization. No independent event-specific microscopy is inferred from the pathway summary. |
| GO:0008284 positive regulation of cell population proliferation | IMP PMID:24130168 Characterization of microRNA-29 family expression and invest... | UNDECIDED | Summary: Keep the source-specific positive regulation of cell population proliferation assertion unresolved. Reason: PMID:24130168 reports miR-29 targeting of CCND2 and MMP2 in gastric cancer, but the canonical cache is abstract-only and the exact CCND2 perturbation, rescue and endpoint controls were not accessible. Official reciprocal links establish a 2024 erratum (DOI:10.1093/carcin/bgae070), whose corrected material could not be read. This is not evidence of retraction or of an incorrect phenotype, but neither the correction scope nor this particular source assertion is resolved. General cyclin biology is assessed independently and does not silently repair this source-specific uncertainty. Supporting Evidence: |
| GO:0016538 cyclin-dependent protein serine/threonine kinase regulator activity | IBA GO_REF:0000033 | ACCEPT | Summary: CCND2 is a conserved regulator of CDK serine/threonine kinase activity. Reason: The PTN000019791 inherited regulator assignment agrees with direct cyclin-dependent activation. Retain the supported broader source assertion; the core synthesis selects the existing, more precise activator term instead of redundantly listing both molecular functions. |
| GO:0019901 protein kinase binding | IPI PMID:8114739 Identification of G1 kinase activity for cdk6, a novel cycli... | MODIFY | Summary: Refine CDK6 binding to the demonstrated cyclin activator activity. Reason: The original abstract explicitly reports cyclin-D association with human CDK6 in human-cell lysates and activation by cyclin coexpression in Sf9 cells. The regulatory subunit is CCND2; CDK6 catalyses phosphorylation. The replacement captures the activating role supported by this same source, without importing a CDK6 catalytic annotation into CCND2. Proposed replacements: cyclin-dependent protein serine/threonine kinase activator activity Supporting Evidence: PMID:8114739 activated by coexpression with D-type cyclins |
| GO:0031965 nuclear membrane | IDA PMID:18827403 Migratory localization of cyclin D2-Cdk4 complex suggests a ... | KEEP AS NON CORE | Summary: Retain transient nuclear-envelope association. Reason: The full human-construct paper shows tagged CCND2-CDK4 colocalization with lamin B at the HeLa nuclear envelope and accumulation near nuclear pores. This is a transient localization during import, not a claim of membrane insertion or a constitutive membrane structural role. Supporting Evidence: |
| GO:0031965 nuclear membrane | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: The electronic nuclear-membrane mapping has experimental support. Reason: ARBA/SL-0182 reproduces the location supported by the human-construct localization paper. Preserve the source and its transient, peripheral-association interpretation; no separate membrane activity is inferred. Supporting Evidence: |
| GO:0043066 negative regulation of apoptotic process | IMP PMID:24130168 Characterization of microRNA-29 family expression and invest... | UNDECIDED | Summary: Keep the source-specific negative regulation of apoptotic process assertion unresolved. Reason: PMID:24130168 reports miR-29 targeting of CCND2 and MMP2 in gastric cancer, but the canonical cache is abstract-only and the exact CCND2 perturbation, rescue and endpoint controls were not accessible. Official reciprocal links establish a 2024 erratum (DOI:10.1093/carcin/bgae070), whose corrected material could not be read. This is not evidence of retraction or of an incorrect phenotype, but neither the correction scope nor this particular source assertion is resolved. General cyclin biology is assessed independently and does not silently repair this source-specific uncertainty. Supporting Evidence: |
| GO:0043539 protein serine/threonine kinase activator activity | IDA PMID:8114739 Identification of G1 kinase activity for cdk6, a novel cycli... | MODIFY | Summary: Use the existing CDK-specific activator term. Reason: The source names CDK6 and D-type cyclins, so cyclin-dependent protein serine/threonine kinase activator activity is more precise than the broad serine/threonine kinase activator term. This refines the existing row rather than manufacturing a new molecular function. Proposed replacements: cyclin-dependent protein serine/threonine kinase activator activity Supporting Evidence: PMID:8114739 activated by coexpression with D-type cyclins |
| GO:0061575 cyclin-dependent protein serine/threonine kinase activator activity | IDA PMID:18827403 Migratory localization of cyclin D2-Cdk4 complex suggests a ... | ACCEPT | Summary: CCND2 activates a CDK-containing regulatory complex. Reason: The full primary evidence connects intact human CCND2-CDK4 assembly with altered S-phase entry, nuclear access and RB phosphorylation, with a weakened-association N-terminal deletion control. These results support the cyclin activator function; the kinase subunit performs phosphotransfer. Supporting Evidence: PMID:18827403 pRb phosphorylation and DNA synthesis |
| GO:0061575 cyclin-dependent protein serine/threonine kinase activator activity | IEA GO_REF:0000117 | ACCEPT | Summary: Retain the electronic CDK activator assignment. Reason: The ARBA00091227 inference agrees with direct CCND2-CDK4/CDK6 activation evidence and the existing experimental activator annotation. |
| GO:0061575 cyclin-dependent protein serine/threonine kinase activator activity | TAS PMID:33854239 The AMBRA1 E3 ligase adaptor regulates the stability of cycl... | ACCEPT | Summary: Retain the D-cyclin activator statement. Reason: The AMBRA1 paper frames D cyclins as CDK4/6 activators and experimentally alters D-cyclin abundance and combined expression. Its D1-centred detailed kinase and ubiquitination assays are not relabelled as D2-specific experiments. Independent CCND2 studies support the existing TAS function. |
| GO:0097129 cyclin D2-CDK4 complex | IEA GO_REF:0000107 | ACCEPT | Summary: Cyclin D2-CDK4 complex membership is conserved and directly corroborated. Reason: The orthology transfer from mouse agrees with actual human CCND2-CDK4 interaction assays and human B-CLL immune complexes. GO:0097129 specifically names this regulatory-catalytic pair; it does not claim that CCND2 is a kinase. |
| GO:0097129 cyclin D2-CDK4 complex | IPI PMID:11896535 Cell cycle progression of chronic lymphocytic leukemia cells... | ACCEPT | Summary: Retain the functional D2-CDK4 complex in stimulated B-CLL cells. Reason: The original abstract explicitly identifies CCND2-CDK4 immune complexes from stimulated B-CLL cells and their RB phosphorylation in vitro. This supports the named complex with a defined cellular context, rather than every D-cyclin/CDK combination. Supporting Evidence: |
| GO:1900087 positive regulation of G1/S transition of mitotic cell cycle | IBA GO_REF:0000033 | ACCEPT | Summary: Retain the positive G1/S phylogenetic assertion. Reason: The actual PAINT record places GO:1900087 at PTN000808639 and includes target P30279 as descendant experimental evidence. That self occurrence is expected, not circularity. Human-construct experiments support acceleration of S-phase entry, with the actual DNA-synthesis kinetics measured in NIH-3T3 cells. Supporting Evidence: |
| GO:1900087 positive regulation of G1/S transition of mitotic cell cycle | IMP PMID:24130168 Characterization of microRNA-29 family expression and invest... | UNDECIDED | Summary: Keep the source-specific positive regulation of G1/S transition of mitotic cell cycle assertion unresolved. Reason: PMID:24130168 reports miR-29 targeting of CCND2 and MMP2 in gastric cancer, but the canonical cache is abstract-only and the exact CCND2 perturbation, rescue and endpoint controls were not accessible. Official reciprocal links establish a 2024 erratum (DOI:10.1093/carcin/bgae070), whose corrected material could not be read. This is not evidence of retraction or of an incorrect phenotype, but neither the correction scope nor this particular source assertion is resolved. General cyclin biology is assessed independently and does not silently repair this source-specific uncertainty. Supporting Evidence: |
| GO:1901992 positive regulation of mitotic cell cycle phase transition | IEA GO_REF:0000117 | ACCEPT | Summary: Positive regulation of mitotic phase transition is supported at G1/S. Reason: The broad ARBA assertion is consistent with the demonstrated G1/S regulatory role. It is not expanded into an untested G2/M function; the core uses the existing G1/S process for specificity. Supporting Evidence: |
| GO:2000045 regulation of G1/S transition of mitotic cell cycle | IEA GO_REF:0000117 | ACCEPT | Summary: Regulation of G1/S transition matches CCND2 function. Reason: The electronic assignment captures the established regulatory cyclin role. Retain the source term while selecting the existing G1/S transition term in the nonredundant core synthesis. Supporting Evidence: |
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Q: Does a CCND2 population associate with a microtubule-organizing center in a defined phase of the human cell cycle, and which partner anchors it there?
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