Cyclin E1 is a non-catalytic regulatory cyclin that binds CDK2 to form the cyclin E1-CDK2 kinase complex, promoting late G1 progression, G1/S transition, and DNA replication origin licensing. Mouse Ccne1 overlaps with Ccne2 for many mitotic cycles, but E-type cyclins are required for cell-cycle reentry, endoreplication in specialized lineages, and male meiotic chromosome pairing and telomere stability. The protein is primarily nuclear/nucleoplasmic and is controlled by phosphorylation-dependent ubiquitin-mediated degradation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000082 G1/S transition of mitotic cell cycle | IBA GO_REF:0000033 | ACCEPT | Summary: Supported core cyclin E1/CDK2 G1/S function or nuclear localization. Reason: Cyclin E1 is a CDK2 regulatory cyclin that drives the G1/S transition. Supporting Evidence: file:mouse/Ccne1/Ccne1-deep-research-falcon.md Cyclin E1 is a regulatory subunit of CDK2; the cyclin E-CDK2 complex is a central driver of the G1/S transition and S-phase entry. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Supported core cyclin E1/CDK2 G1/S function or nuclear localization. Reason: The term reflects cyclin E1 binding/regulating CDK2 to promote G1/S transition and DNA replication initiation. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Supported but context-specific cyclin E1 biology. Reason: The annotation reflects a meiotic, differentiation, localization, or interaction consequence rather than the primary cyclin E1-CDK2 G1/S regulatory function. |
| GO:0016538 cyclin-dependent protein serine/threonine kinase regulator activity | IBA GO_REF:0000033 | MODIFY | Summary: Supported core cyclin E1/CDK2 G1/S function or nuclear localization. Reason: Cyclin E1 is the non-catalytic cyclin that activates CDK2; the replacement term captures this regulatory activation more specifically than the parent regulator term. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000019791 · ancestral node of PANTHER family PTHR10177 (CYCLINS) SUPPORTS TRANSFER The CDK-partner role is the property this deep cyclin node encodes, seeded across Candida, budding-yeast and fission-yeast cyclins, fly cyclins and the mammalian ones, and it transfers correctly to cyclin E1. The fault is only that a node-level term spanning every cyclin class stops at the generic regulator parent, while cyclin E1's specific role is to activate CDK2. MGI:MGI:88316 · mouse Ccne1 (this gene) SUPPORTS TRANSFER The target's own IBD seed. Mouse Ccne1 carries its own IDA annotation to this very term in GOA, and that experimental evidence is one of the descendant evidences the PAINT curator used when placing the node, so it marks experimental grounding on the target itself. MGI:MGI:88313 · mouse Ccnd1 (cyclin D1) SUPPORTS TRANSFER A second mammalian cyclin seed, also a non-catalytic activating subunit of its CDK; the regulator biology transfers and only the term's generality is at issue. FB:FBgn0000404 SUPPORTS TRANSFER Drosophila seed at the same node, cited by identifier because the local index does not resolve it; part of the invertebrate coverage of this term. Proposed replacements: cyclin-dependent protein serine/threonine kinase activator activity Supporting Evidence: file:mouse/Ccne1/Ccne1-deep-research-falcon.md Cyclin E1 is a regulatory subunit of CDK2; the cyclin E-CDK2 complex is a central driver of the G1/S transition and S-phase entry. |
| GO:0097134 cyclin E1-CDK2 complex | IBA GO_REF:0000033 | ACCEPT | Summary: Supported core cyclin E1/CDK2 G1/S function or nuclear localization. Reason: The term reflects cyclin E1 binding/regulating CDK2 to promote G1/S transition and DNA replication initiation. Supporting Evidence: file:mouse/Ccne1/Ccne1-deep-research-falcon.md Cyclin E1 is a regulatory subunit of CDK2; the cyclin E-CDK2 complex is a central driver of the G1/S transition and S-phase entry. |
| GO:0005815 microtubule organizing center | IBA GO_REF:0000033 | ACCEPT | Summary: Supported core cyclin E1/CDK2 G1/S function or nuclear localization. Reason: The term reflects cyclin E1 binding/regulating CDK2 to promote G1/S transition and DNA replication initiation. |
| GO:1900087 positive regulation of G1/S transition of mitotic cell cycle | IBA GO_REF:0000033 | ACCEPT | Summary: Supported core cyclin E1/CDK2 G1/S function or nuclear localization. Reason: The term reflects cyclin E1 binding/regulating CDK2 to promote G1/S transition and DNA replication initiation. |
| GO:0000723 telomere maintenance | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Supported but context-specific cyclin E1 biology. Reason: The annotation reflects a meiotic, differentiation, localization, or interaction consequence rather than the primary cyclin E1-CDK2 G1/S regulatory function. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Supported core cyclin E1/CDK2 G1/S function or nuclear localization. Reason: The term reflects cyclin E1 binding/regulating CDK2 to promote G1/S transition and DNA replication initiation. |
| GO:0006270 DNA replication initiation | IEA GO_REF:0000117 | ACCEPT | Summary: Supported core cyclin E1/CDK2 G1/S function or nuclear localization. Reason: The term reflects cyclin E1 binding/regulating CDK2 to promote G1/S transition and DNA replication initiation. Supporting Evidence: file:mouse/Ccne1/Ccne1-deep-research-falcon.md Cyclin E1 associates with DNA replication origins and supports pre-replication complex formation by facilitating MCM loading at origins. |
| GO:0007129 homologous chromosome pairing at meiosis | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Supported but context-specific cyclin E1 biology. Reason: The annotation reflects a meiotic, differentiation, localization, or interaction consequence rather than the primary cyclin E1-CDK2 G1/S regulatory function. |
| GO:0016538 cyclin-dependent protein serine/threonine kinase regulator activity | IEA GO_REF:0000117 | MODIFY | Summary: Supported core cyclin E1/CDK2 G1/S function or nuclear localization. Reason: Cyclin E1 is the non-catalytic cyclin that activates CDK2; the replacement term captures this regulatory activation more specifically than the parent regulator term. Proposed replacements: cyclin-dependent protein serine/threonine kinase activator activity Supporting Evidence: file:mouse/Ccne1/Ccne1-deep-research-falcon.md Cyclin E1 is a regulatory subunit of CDK2; the cyclin E-CDK2 complex is a central driver of the G1/S transition and S-phase entry. |
| GO:0019901 protein kinase binding | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Supported but context-specific cyclin E1 biology. Reason: The annotation reflects a meiotic, differentiation, localization, or interaction consequence rather than the primary cyclin E1-CDK2 G1/S regulatory function. |
| GO:0051301 cell division | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: Supported but context-specific cyclin E1 biology. Reason: The annotation reflects a meiotic, differentiation, localization, or interaction consequence rather than the primary cyclin E1-CDK2 G1/S regulatory function. |
| GO:0005515 protein binding | IPI PMID:17700700 Cdk1 is sufficient to drive the mammalian cell cycle. | MARK AS OVER ANNOTATED | Summary: The annotation is too vague to be useful. Reason: Protein binding does not capture the informative cyclin E1-CDK2 regulatory activity and should not be retained as a meaningful function annotation. Supporting Evidence: PMID:17700700 Cdk1 is sufficient to drive the mammalian cell cycle. |
| GO:0005515 protein binding | IPI PMID:19592082 Cyclin A is redundant in fibroblasts but essential in hemato... | MARK AS OVER ANNOTATED | Summary: The annotation is too vague to be useful. Reason: Protein binding does not capture the informative cyclin E1-CDK2 regulatory activity and should not be retained as a meaningful function annotation. Supporting Evidence: PMID:19592082 Cyclin A is redundant in fibroblasts but essential in hematopoietic and embryonic stem cells. |
| GO:0005515 protein binding | IPI PMID:20150892 Genetic analysis of Ras signalling pathways in cell prolifer... | MARK AS OVER ANNOTATED | Summary: The annotation is too vague to be useful. Reason: Protein binding does not capture the informative cyclin E1-CDK2 regulatory activity and should not be retained as a meaningful function annotation. Supporting Evidence: PMID:20150892 Genetic analysis of Ras signalling pathways in cell proliferation, migration and survival. |
| GO:0000082 G1/S transition of mitotic cell cycle | IEA GO_REF:0000107 | ACCEPT | Summary: Supported core cyclin E1/CDK2 G1/S function or nuclear localization. Reason: The term reflects cyclin E1 binding/regulating CDK2 to promote G1/S transition and DNA replication initiation. |
| GO:0005654 nucleoplasm | IEA GO_REF:0000107 | ACCEPT | Summary: Supported core cyclin E1/CDK2 G1/S function or nuclear localization. Reason: The term reflects cyclin E1 binding/regulating CDK2 to promote G1/S transition and DNA replication initiation. |
| GO:1902462 positive regulation of mesenchymal stem cell proliferation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Supported but context-specific cyclin E1 biology. Reason: The annotation reflects a meiotic, differentiation, localization, or interaction consequence rather than the primary cyclin E1-CDK2 G1/S regulatory function. |
| GO:0000082 G1/S transition of mitotic cell cycle | ISO GO_REF:0000119 | ACCEPT | Summary: Supported core cyclin E1/CDK2 G1/S function or nuclear localization. Reason: The term reflects cyclin E1 binding/regulating CDK2 to promote G1/S transition and DNA replication initiation. |
| GO:0005634 nucleus | ISO GO_REF:0000119 | ACCEPT | Summary: Supported core cyclin E1/CDK2 G1/S function or nuclear localization. Reason: The term reflects cyclin E1 binding/regulating CDK2 to promote G1/S transition and DNA replication initiation. |
| GO:0005654 nucleoplasm | ISO GO_REF:0000119 | ACCEPT | Summary: Supported core cyclin E1/CDK2 G1/S function or nuclear localization. Reason: The term reflects cyclin E1 binding/regulating CDK2 to promote G1/S transition and DNA replication initiation. |
| GO:0005813 centrosome | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Supported but context-specific cyclin E1 biology. Reason: The annotation reflects a meiotic, differentiation, localization, or interaction consequence rather than the primary cyclin E1-CDK2 G1/S regulatory function. |
| GO:0019901 protein kinase binding | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Supported but context-specific cyclin E1 biology. Reason: The annotation reflects a meiotic, differentiation, localization, or interaction consequence rather than the primary cyclin E1-CDK2 G1/S regulatory function. |
| GO:0044877 protein-containing complex binding | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Supported but context-specific cyclin E1 biology. Reason: The annotation reflects a meiotic, differentiation, localization, or interaction consequence rather than the primary cyclin E1-CDK2 G1/S regulatory function. |
| GO:0045597 positive regulation of cell differentiation | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Supported but context-specific cyclin E1 biology. Reason: The annotation reflects a meiotic, differentiation, localization, or interaction consequence rather than the primary cyclin E1-CDK2 G1/S regulatory function. |
| GO:0097134 cyclin E1-CDK2 complex | ISO GO_REF:0000119 | ACCEPT | Summary: Supported core cyclin E1/CDK2 G1/S function or nuclear localization. Reason: The term reflects cyclin E1 binding/regulating CDK2 to promote G1/S transition and DNA replication initiation. |
| GO:1902462 positive regulation of mesenchymal stem cell proliferation | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Supported but context-specific cyclin E1 biology. Reason: The annotation reflects a meiotic, differentiation, localization, or interaction consequence rather than the primary cyclin E1-CDK2 G1/S regulatory function. |
| GO:0005634 nucleus | ISS GO_REF:0000024 | ACCEPT | Summary: Supported core cyclin E1/CDK2 G1/S function or nuclear localization. Reason: The term reflects cyclin E1 binding/regulating CDK2 to promote G1/S transition and DNA replication initiation. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IGI PMID:7797074 Regulation of the retinoblastoma protein-related p107 by G1 ... | KEEP AS NON CORE | Summary: Supported but context-specific cyclin E1 biology. Reason: The annotation reflects a meiotic, differentiation, localization, or interaction consequence rather than the primary cyclin E1-CDK2 G1/S regulatory function. Supporting Evidence: PMID:7797074 Regulation of the retinoblastoma protein-related p107 by G1 cyclin complexes. |
| GO:0000723 telomere maintenance | IGI PMID:24586195 Mammalian E-type cyclins control chromosome pairing, telomer... | KEEP AS NON CORE | Summary: Supported but context-specific cyclin E1 biology. Reason: The annotation reflects a meiotic, differentiation, localization, or interaction consequence rather than the primary cyclin E1-CDK2 G1/S regulatory function. Supporting Evidence: PMID:24586195 Mammalian E-type cyclins control chromosome pairing, telomere stability and CDK2 localization in male meiosis. |
| GO:0007129 homologous chromosome pairing at meiosis | IGI PMID:24586195 Mammalian E-type cyclins control chromosome pairing, telomer... | KEEP AS NON CORE | Summary: Supported but context-specific cyclin E1 biology. Reason: The annotation reflects a meiotic, differentiation, localization, or interaction consequence rather than the primary cyclin E1-CDK2 G1/S regulatory function. Supporting Evidence: PMID:24586195 Mammalian E-type cyclins control chromosome pairing, telomere stability and CDK2 localization in male meiosis. |
| GO:0032880 regulation of protein localization | IGI PMID:24586195 Mammalian E-type cyclins control chromosome pairing, telomer... | KEEP AS NON CORE | Summary: Supported but context-specific cyclin E1 biology. Reason: The annotation reflects a meiotic, differentiation, localization, or interaction consequence rather than the primary cyclin E1-CDK2 G1/S regulatory function. Supporting Evidence: PMID:24586195 Mammalian E-type cyclins control chromosome pairing, telomere stability and CDK2 localization in male meiosis. |
| GO:0070192 chromosome organization involved in meiotic cell cycle | IGI PMID:24586195 Mammalian E-type cyclins control chromosome pairing, telomer... | KEEP AS NON CORE | Summary: Supported but context-specific cyclin E1 biology. Reason: The annotation reflects a meiotic, differentiation, localization, or interaction consequence rather than the primary cyclin E1-CDK2 G1/S regulatory function. Supporting Evidence: PMID:24586195 Mammalian E-type cyclins control chromosome pairing, telomere stability and CDK2 localization in male meiosis. |
| GO:0097134 cyclin E1-CDK2 complex | IDA PMID:7739547 Novel INK4 proteins, p19 and p18, are specific inhibitors of... | UNDECIDED | Summary: Cannot be adjudicated here: PMID:7739547 is cached abstract-only. Prior observation, not a verdict: PMID:7739547 is an INK4/CDK4-CDK6 inhibitor paper and only uses cyclin E-CDK2 as a negative-control comparison, not as direct evidence for the cyclin E1-CDK2 complex. Reason: PMID:7739547 is cached abstract-only, so the curator's experimental evidence cannot be inspected here; per CLAUDE.md an experimental annotation is not overruled on that basis. Recorded observation, not a verdict: The cyclin E1-CDK2 complex term is biologically correct for Ccne1 and is retained through other evidence rows, but this specific IDA reference does not demonstrate the complex. Supporting Evidence: PMID:7739547 Novel INK4 proteins, p19 and p18, are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6. |
| GO:0006468 protein phosphorylation | ISS PMID:10500095 Cullin-3 targets cyclin E for ubiquitination and controls S ... | MODIFY | Summary: The annotation attributes catalytic kinase/phosphorylation activity to cyclin E1. Reason: Cyclin E1 is the non-catalytic CDK2 cyclin; the replacement term better captures its regulatory activation of a CDK kinase complex. Proposed replacements: cyclin-dependent protein serine/threonine kinase activator activity Supporting Evidence: PMID:10500095 Cullin-3 targets cyclin E for ubiquitination and controls S phase in mammalian cells. |
| GO:0005515 protein binding | IPI PMID:20215406 Ciz1 cooperates with cyclin-A-CDK2 to activate mammalian DNA... | MARK AS OVER ANNOTATED | Summary: The annotation is too vague to be useful. Reason: Protein binding does not capture the informative cyclin E1-CDK2 regulatory activity and should not be retained as a meaningful function annotation. Supporting Evidence: PMID:20215406 Ciz1 cooperates with cyclin-A-CDK2 to activate mammalian DNA replication in vitro. |
| GO:0019901 protein kinase binding | IPI PMID:11981756 The p21(Cip1) protein, a cyclin inhibitor, regulates the lev... | KEEP AS NON CORE | Summary: Supported but context-specific cyclin E1 biology. Reason: The annotation reflects a meiotic, differentiation, localization, or interaction consequence rather than the primary cyclin E1-CDK2 G1/S regulatory function. Supporting Evidence: PMID:11981756 The p21(Cip1) protein, a cyclin inhibitor, regulates the levels and the intracellular localization of CDC25A in mice regenerating livers. |
| GO:0016055 Wnt signaling pathway | IDA PMID:19056892 A functional link between Wnt signaling and SKP2-independent... | REMOVE | Summary: The cited Wnt/p27 turnover paper does not support direct Ccne1 involvement. Reason: PMID:19056892 describes Wnt-dependent p27 turnover through CUL4A/B in mammary tumors, not a direct Ccne1/cyclin E1 role in Wnt signaling. Supporting Evidence: PMID:19056892 A functional link between Wnt signaling and SKP2-independent p27 turnover in mammary tumors. |
| GO:0005634 nucleus | IDA PMID:10500095 Cullin-3 targets cyclin E for ubiquitination and controls S ... | ACCEPT | Summary: Supported core cyclin E1/CDK2 G1/S function or nuclear localization. Reason: The term reflects cyclin E1 binding/regulating CDK2 to promote G1/S transition and DNA replication initiation. Supporting Evidence: PMID:10500095 Cullin-3 targets cyclin E for ubiquitination and controls S phase in mammalian cells. |
| GO:0005515 protein binding | IPI PMID:10500095 Cullin-3 targets cyclin E for ubiquitination and controls S ... | MARK AS OVER ANNOTATED | Summary: The annotation is too vague to be useful. Reason: Protein binding does not capture the informative cyclin E1-CDK2 regulatory activity and should not be retained as a meaningful function annotation. Supporting Evidence: PMID:10500095 Cullin-3 targets cyclin E for ubiquitination and controls S phase in mammalian cells. |
| GO:0005634 nucleus | ISO PMID:16109376 The bromodomain protein Brd4 is a positive regulatory compon... | REMOVE | Summary: The cited paper does not support Ccne1 nuclear localization. Reason: PMID:16109376 is about Brd4/P-TEFb, cyclin T1, and CDK9 biology, not Ccne1/cyclin E1 localization. Cyclin E1 nuclear localization is supported by other evidence, but this evidence assertion should not be retained. Supporting Evidence: PMID:16109376 The bromodomain protein Brd4 is a positive regulatory component of P-TEFb and stimulates RNA polymerase II-dependent transcription. |
| GO:0016538 cyclin-dependent protein serine/threonine kinase regulator activity | IDA PMID:12970171 Deletion of Mnt leads to disrupted cell cycle control and tu... | MODIFY | Summary: Supported core cyclin E1/CDK2 G1/S function or nuclear localization. Reason: Cyclin E1 is the non-catalytic cyclin that activates CDK2; the replacement term captures this regulatory activation more specifically than the parent regulator term. Proposed replacements: cyclin-dependent protein serine/threonine kinase activator activity Supporting Evidence: PMID:12970171 Deletion of Mnt leads to disrupted cell cycle control and tumorigenesis. file:mouse/Ccne1/Ccne1-deep-research-falcon.md Cyclin E1 is a regulatory subunit of CDK2; the cyclin E-CDK2 complex is a central driver of the G1/S transition and S-phase entry. |
| GO:0051726 regulation of cell cycle | IDA PMID:12970171 Deletion of Mnt leads to disrupted cell cycle control and tu... | ACCEPT | Summary: Supported core cyclin E1/CDK2 G1/S function or nuclear localization. Reason: The term reflects cyclin E1 binding/regulating CDK2 to promote G1/S transition and DNA replication initiation. Supporting Evidence: PMID:12970171 Deletion of Mnt leads to disrupted cell cycle control and tumorigenesis. |
| GO:0000307 cyclin-dependent protein kinase holoenzyme complex | IPI PMID:12970760 Caspase-3 regulates cell cycle in B cells: a consequence of ... | KEEP AS NON CORE | Summary: Supported but context-specific cyclin E1 biology. Reason: The annotation reflects a meiotic, differentiation, localization, or interaction consequence rather than the primary cyclin E1-CDK2 G1/S regulatory function. Supporting Evidence: PMID:12970760 Caspase-3 regulates cell cycle in B cells: a consequence of substrate specificity. |
| GO:0005515 protein binding | IPI PMID:12970760 Caspase-3 regulates cell cycle in B cells: a consequence of ... | MARK AS OVER ANNOTATED | Summary: The annotation is too vague to be useful. Reason: Protein binding does not capture the informative cyclin E1-CDK2 regulatory activity and should not be retained as a meaningful function annotation. Supporting Evidence: PMID:12970760 Caspase-3 regulates cell cycle in B cells: a consequence of substrate specificity. |
| GO:0006468 protein phosphorylation | IDA PMID:12124778 GADD45b and GADD45g are cdc2/cyclinB1 kinase inhibitors with... | UNDECIDED | Summary: Cannot be adjudicated here: PMID:12124778 is cached abstract-only. Prior observation, not a verdict: The cited paper does not support Ccne1 kinase or activator function. Reason: PMID:12124778 is cached abstract-only, so the curator's experimental evidence cannot be inspected here; per CLAUDE.md an experimental annotation is not overruled on that basis. Recorded observation, not a verdict: PMID:12124778 is about Gadd45b/g inhibition of Cdk1/cyclin B1 and explicitly not other Cdk/cyclin complexes, so it cannot support a Ccne1 phosphorylation or CDK activator assertion. Supporting Evidence: PMID:12124778 GADD45b and GADD45g are cdc2/cyclinB1 kinase inhibitors with a role in S and G2/M cell cycle checkpoints induced by genotoxic stress. |
| GO:0016301 kinase activity | IDA PMID:12124778 GADD45b and GADD45g are cdc2/cyclinB1 kinase inhibitors with... | UNDECIDED | Summary: Cannot be adjudicated here: PMID:12124778 is cached abstract-only. Prior observation, not a verdict: The cited paper does not support Ccne1 kinase or activator function. Reason: PMID:12124778 is cached abstract-only, so the curator's experimental evidence cannot be inspected here; per CLAUDE.md an experimental annotation is not overruled on that basis. Recorded observation, not a verdict: PMID:12124778 is about Gadd45b/g inhibition of Cdk1/cyclin B1 and explicitly not other Cdk/cyclin complexes, so it cannot support a Ccne1 kinase activity or CDK activator assertion. Supporting Evidence: PMID:12124778 GADD45b and GADD45g are cdc2/cyclinB1 kinase inhibitors with a role in S and G2/M cell cycle checkpoints induced by genotoxic stress. |
| GO:0006270 DNA replication initiation | IMP PMID:12941272 Cyclin E ablation in the mouse. | ACCEPT | Summary: Supported core cyclin E1/CDK2 G1/S function or nuclear localization. Reason: The term reflects cyclin E1 binding/regulating CDK2 to promote G1/S transition and DNA replication initiation. Supporting Evidence: PMID:12941272 Cyclin E ablation in the mouse. |
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