Geminin restricts DNA replication licensing by binding CDT1 and preventing productive MCM engagement. It also regulates transcription through AP4-associated repression and selected Hox proteins. APC/C-dependent degradation during mitosis limits its abundance. Stabilizing GMNN variants can cause autosomal-dominant Meier-Gorlin syndrome, linking replication control to human growth.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003682 chromatin binding | IDA PMID:11125146 Inhibition of eukaryotic DNA replication by geminin binding ... | KEEP AS NON CORE | Reason: Retain chromatin association as noncore: positive Flag-GemL26A origin ChIP does not establish direct DNA contact; Science Fig. 3B measures CDT1. |
| GO:0003712 transcription coregulator activity | IBA GO_REF:0000033 | TOO GENERAL | Reason: PAINT places coregulation at Bilateria AN0/PTN000332476. The target inherits this function; existing transcription corepressor activity (GO:0003714) captures its more specific role. Original PAINT evidence: paint_ancestry.assertions[0].literal_ibd (source GAF line 39130). Supporting Evidence: GO_REF:0000033 file:human/GMNN/GMNN-evidence.json |
| GO:0003714 transcription corepressor activity | IEA GO_REF:0000107 | ACCEPT | Reason: Retain AP4-associated corepression: mouse transfection constructs coexist with endogenous human perturbation evidence. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:11125146 Inhibition of eukaryotic DNA replication by geminin binding ... | MODIFY | Reason: Human reconstitution, mutagenesis and docking support steric exclusion of MCM2. Proposed replacements: protein sequestering activity Supporting Evidence: PMID:11125146 geminin interacts tightly with Cdt1 PMID:41365879 sterically clashes with the MCM2 C-terminus PMID:15260975 Both interactions are essential for replication inhibition. |
| GO:0005515 protein binding | IPI PMID:11125146 Inhibition of eukaryotic DNA replication by geminin binding ... | MODIFY | Reason: Retain Xenopus CDT1 binding. Proposed replacements: protein sequestering activity |
| GO:0005515 protein binding | IPI PMID:14993212 Cdt1 phosphorylation by cyclin A-dependent kinases negativel... | MODIFY | Reason: Retain CDT1 pull-down. Proposed replacements: protein sequestering activity |
| GO:0005515 protein binding | IPI PMID:15232106 Self-assembling protein microarrays. | REMOVE | Reason: Retain the human protein-array contact with CDKN2A. Remove the uninformative binding label; no specific regulatory role follows from this assay. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:15232106 Self-assembling protein microarrays. | MODIFY | Reason: Retain array-detected CDT1 binding. Proposed replacements: protein sequestering activity |
| GO:0005515 protein binding | IPI PMID:16482215 Two E3 ubiquitin ligases, SCF-Skp2 and DDB1-Cul4, target hum... | MODIFY | Reason: Retain HeLa CDT1 binding. Proposed replacements: protein sequestering activity |
| GO:0005515 protein binding | IPI PMID:17318181 Cdt1 associates dynamically with chromatin throughout G1 and... | MODIFY | Reason: Retain CDT1-dependent chromatin recruitment. Proposed replacements: protein sequestering activity |
| GO:0005515 protein binding | IPI PMID:19906994 Quaternary structure of the human Cdt1-Geminin complex regul... | MODIFY | Reason: Retain human binding and Xenopus inhibition. Proposed replacements: protein sequestering activity |
| GO:0005515 protein binding | IPI PMID:20932478 A WD-repeat protein stabilizes ORC binding to chromatin. | REMOVE | Reason: Endogenous ORCA/LRWD1 coimmunoprecipitates with Geminin. Preserve this association; it does not identify a distinct molecular role for the generic binding annotation. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21543332 Idas, a novel phylogenetically conserved geminin-related pro... | REMOVE | Reason: Preserve Geminin–Idas binding. Idas modulates Geminin; that direction does not establish an inhibitory activity of Geminin toward Idas. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21543332 Idas, a novel phylogenetically conserved geminin-related pro... | MODIFY | Reason: Retain Idas-study CDT1 contact. Proposed replacements: protein sequestering activity |
| GO:0005515 protein binding | IPI PMID:21856198 JNK1 phosphorylation of Cdt1 inhibits recruitment of HBO1 hi... | MODIFY | Reason: Retain CDT1/HBO1 association; no direct HBO1-binding inference. Proposed replacements: protein sequestering activity |
| GO:0005515 protein binding | IPI PMID:22581055 Recruitment of the human Cdt1 replication licensing protein ... | MODIFY | Reason: Retain CDT1 contact; Hec1 assays do not establish sequestration. Proposed replacements: protein sequestering activity |
| GO:0005515 protein binding | IPI PMID:22615398 Structural basis for homeodomain recognition by the cell-cyc... | MODIFY | Reason: Human geminin’s 171–190 region blocks HOXC9–DNA binding; interface mutants lose inhibition. Refine to transcription regulator inhibitor activity: this mechanism prevents DNA engagement, rather than recruiting repression machinery at a promoter. Proposed replacements: transcription regulator inhibitor activity Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:23708001 Emi1 preferentially inhibits ubiquitin chain elongation by t... | REMOVE | Reason: Remove the uninformative binding label while preserving the curated FBXO5 association. The inspected primary text does not resolve that particular contact or an inhibitory role. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Uninformative binding. Reason: Retain CCDC146-2 interaction evidence and recorded fragment boundaries; generic protein binding supplies no functional mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Uninformative binding. Reason: Retain ZNF439 interaction evidence; its transcription-factor identity alone does not establish GMNN coregulation. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MODIFY | Reason: Retain HeLa AP-MS contact. Proposed replacements: protein sequestering activity |
| GO:0005515 protein binding | IPI PMID:27107012 Pooled-matrix protein interaction screens using Barcode Fusi... | MODIFY | Reason: Retain yeast interaction; Geminin-bait autoactivation remains a limitation. Proposed replacements: protein sequestering activity |
| GO:0005515 protein binding | IPI PMID:27229929 Systematic interactome mapping of acute lymphoblastic leukem... | REMOVE | Reason: Preserve the curated CDKN2A contact from the human-protein yeast screen. Remove generic binding without inferring a regulatory mechanism or pair-specific orthogonal validation. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Reason: Preserve the HEK293T Geminin–MCIDAS association. AP-MS does not establish a specific functional binding mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Reason: Preserve the literal CCDC146-2 partner and HEK293T co-complex evidence. Remove generic binding without inferring isoform equivalence or a mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Reason: Retain HEK293T CDT1 association. Proposed replacements: protein sequestering activity |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | REMOVE | Summary: Uninformative binding. Reason: Retain CCDC146 binding; variant-screen features do not establish a specific GMNN molecular role. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | REMOVE | Summary: Uninformative binding. Reason: Retain ZNF439 binding; the measured contact does not by itself establish transcriptional regulation. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative binding. Reason: Retain ZNF250-3 contact; the generic label adds no specific GMNN molecular role. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative binding. Reason: Retain PTPN11-2 contact; binding alone does not establish phosphatase regulation by GMNN. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative binding. Reason: Retain KANK2 contact; generic protein binding supplies no defined GMNN molecular role. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative binding. Reason: Retain SAPCD2 contact; association alone does not define a specific GMNN regulatory function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative binding. Reason: Retain CCDC146 contact and fragment metadata; generic binding lacks functional specificity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative binding. Reason: Retain ZNF439 contact; this interaction alone does not establish GMNN transcriptional coregulation. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative binding. Reason: Retain LNX1 contact; binding alone does not demonstrate ubiquitin-ligase regulation by GMNN. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative binding. Reason: Retain GLIS2 contact; the screen does not establish GMNN as its transcriptional coregulator. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Uninformative binding. Reason: Retain MCIDAS co-purification with tagged GMNN in HEK293T cells; the generic label adds no mechanistic specificity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Uninformative binding. Reason: Retain CCDC146 co-purification. Original BioPlex labels its bait Q8IYE0-2; current IntAct uses Q8IYE0. This distinction does not establish clone equivalence or a specific molecular role. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Reason: Preserve the HEK293T contact and extension; AP-MS alone does not establish sequestration. Proposed replacements: protein sequestering activity |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Reason: PAINT places nuclear activity at Bilateria AN0/PTN000332476, ancestral to the target and grounded by experimental descendants. Preserve the distinct is_active_in assertion alongside more specific localization records. Original PAINT evidence: paint_ancestry.assertions[4].literal_ibd (source GAF line 34579). Supporting Evidence: GO_REF:0000033 file:human/GMNN/GMNN-evidence.json |
| GO:0005634 nucleus | IDA PMID:21543332 Idas, a novel phylogenetically conserved geminin-related pro... | TOO GENERAL | Reason: Accepted located_in nucleoplasm entails this broader located_in nucleus assertion; positive localization evidence is retained. Supporting Evidence: |
| GO:0005634 nucleus | IDA PMID:24217620 The histone demethylase LSD1/KDM1A promotes the DNA damage r... | TOO GENERAL | Reason: Accepted located_in nucleoplasm entails this broader located_in nucleus assertion; positive localization evidence is retained. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | TOO GENERAL | Reason: Accepted located_in nucleoplasm entails this broader located_in nucleus assertion; positive localization evidence is retained. |
| GO:0005634 nucleus | NAS PMID:19906994 Quaternary structure of the human Cdt1-Geminin complex regul... | TOO GENERAL | Reason: Accepted located_in nucleoplasm entails this broader located_in nucleus assertion; positive localization evidence is retained. Supporting Evidence: |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Reason: The current HPA record reports supported main nucleoplasm localization by ICC/IF. This agrees with Geminin’s nuclear functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-68712 | ACCEPT | Reason: The exact event contains nucleoplasmic CDT1:GMNN and polyubiquitinated GMNN participants. Preserve participant localization despite the event-level cytosol label. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-68825 | ACCEPT | Reason: Polyubiquitinated GMNN is an explicit nucleoplasmic substrate of this event. Retain location without assigning Geminin the proteasome’s catalytic process. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-69299 | ACCEPT | Reason: The event directly joins nucleoplasmic GMNN to CDT1. Retain the product-specific participant location. |
| GO:0005737 cytoplasm | IDA PMID:21543332 Idas, a novel phylogenetically conserved geminin-related pro... | KEEP AS NON CORE | Reason: The study observes cytoplasmic Geminin-GFP before Idas-driven nuclear accumulation. Retain this positive conditional localization as non-core. Supporting Evidence: |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Reason: Cytoplasmic localization is supported and context dependent; retain as secondary to the nuclear licensing and transcriptional functions. |
| GO:0006275 regulation of DNA replication | IEA GO_REF:0000002 | TOO GENERAL | Reason: The family mapping is biologically sound but broad; existing GO:1903467 specifies the licensing restriction and is its descendant. |
| GO:0006275 regulation of DNA replication | IMP PMID:17234884 The APC/C inhibitor, Emi1, is essential for prevention of re... | TOO GENERAL | Reason: The Emi1 study links Geminin loss to rereplication. Existing GO:1903467 states the supported licensing mechanism more precisely. Supporting Evidence: |
| GO:0007346 regulation of mitotic cell cycle | IDA PMID:21543332 Idas, a novel phylogenetically conserved geminin-related pro... | TOO GENERAL | Reason: Accepted GO:1903467 entails this broader regulation term; the positive source assertion is retained. Supporting Evidence: |
| GO:0008156 negative regulation of DNA replication | IDA PMID:9635433 Geminin, an inhibitor of DNA replication, is degraded during... | TOO GENERAL | Reason: Accepted GO:1903467 entails this broader regulation term; the positive source assertion is retained. Supporting Evidence: |
| GO:0008156 negative regulation of DNA replication | IEA GO_REF:0000107 | TOO GENERAL | Reason: The mouse donor has experimental grounding; existing GO:1903467 captures the negative licensing process more specifically. |
| GO:0017053 transcription repressor complex | IBA GO_REF:0000033 | ACCEPT | Reason: PAINT places the repressor complex at AN81/PTN002667131. Human Hox–geminin interaction and inhibition ground the sole human donor; self-evidence is legitimate. Preserve the distinct structural and reporter assay contexts. Original PAINT evidence: paint_ancestry.assertions[5].literal_ibd (source GAF line 3209). |
| GO:0017053 transcription repressor complex | IPI PMID:22615398 Structural basis for homeodomain recognition by the cell-cyc... | ACCEPT | Reason: Binding, interface mutants, EMSA and HeLa reporters support a functional Hox–geminin repressor complex. The human HOXC9 structural complex and full-length HOXD9 reporter experiments provide distinct evidence. Supporting Evidence: |
| GO:0030174 regulation of DNA-templated DNA replication initiation | IBA GO_REF:0000033 | TOO GENERAL | Reason: PAINT places this supported role at Bilateria AN0/PTN000332476, with legitimate human self-evidence. Retained GO:1903467 is an is_a descendant specifying licensing restriction. Original PAINT evidence: paint_ancestry.assertions[1].literal_ibd (source GAF line 43790). |
| GO:0030174 regulation of DNA-templated DNA replication initiation | IDA PMID:24064211 The Geminin and Idas coiled coils preferentially form a hete... | TOO GENERAL | Reason: Accepted GO:1903467 entails this broader regulation term; the positive source assertion is retained. Supporting Evidence: |
| GO:0030174 regulation of DNA-templated DNA replication initiation | IEA GO_REF:0000117 | TOO GENERAL | Reason: The regulatory assignment is supported; retained GO:1903467 is an is_a descendant specifying licensing restriction. Supporting Evidence: |
| GO:0042826 histone deacetylase binding | IPI PMID:16924111 A repressor complex, AP4 transcription factor and geminin, n... | KEEP AS NON CORE | Reason: Retain positive AP4–SMRT–HDAC3 coassociation as contextual binding evidence. Corepression remains core; purified binary HDAC3 binding was not established. Supporting Evidence: PMID:16924111 SMRT and histone deacetylase 3 are recruited. |
| GO:0045786 negative regulation of cell cycle | IBA GO_REF:0000033 | TOO GENERAL | Reason: PAINT places this function at Euteleostomi AN81/PTN002667131, ancestral to the target. Existing negative regulation of DNA replication initiation (GO:1903467) entails this broader cell-cycle term; the inherited assertion is biologically coherent. Original PAINT evidence: paint_ancestry.assertions[2].literal_ibd (source GAF line 8701). Supporting Evidence: GO_REF:0000033 file:human/GMNN/GMNN-evidence.json |
| GO:0045786 negative regulation of cell cycle | IDA PMID:19906994 Quaternary structure of the human Cdt1-Geminin complex regul... | TOO GENERAL | Reason: Accepted GO:1903467 entails this broader regulation term; the positive source assertion is retained. Supporting Evidence: |
| GO:0045786 negative regulation of cell cycle | IDA PMID:9635433 Geminin, an inhibitor of DNA replication, is degraded during... | TOO GENERAL | Reason: Accepted GO:1903467 entails this broader regulation term; the positive source assertion is retained. Supporting Evidence: |
| GO:0045786 negative regulation of cell cycle | IEA GO_REF:0000107 | TOO GENERAL | Reason: The orthology inference is sound but broad; existing GO:1903467 is a descendant describing the direct licensing restriction. |
| GO:0045786 negative regulation of cell cycle | NAS PMID:22615398 Structural basis for homeodomain recognition by the cell-cyc... | TOO GENERAL | Reason: The paper discusses Hox-associated proliferative control. Independently accepted licensing term GO:1903467 entails this broad cell-cycle term. Supporting Evidence: |
| GO:0045892 negative regulation of DNA-templated transcription | IBA GO_REF:0000033 | ACCEPT | Reason: PAINT places repression at AN81/PTN002667131. Endogenous perturbation and promoter-associated complexes support human corepression; transfected mouse constructs are not human-protein assays. Geminin collaborates with DNA-binding AP4. Original PAINT evidence: paint_ancestry.assertions[3].literal_ibd (source GAF line 345). |
| GO:0045892 negative regulation of DNA-templated transcription | IDA PMID:16924111 A repressor complex, AP4 transcription factor and geminin, n... | ACCEPT | Reason: Endogenous depletion and reporter rescue support corepression in HEK293T cells. Transfected Gem/AP4 cDNAs were mouse-derived; native human complexes and mixed-species assays support the role. AP4 binds promoter DNA; geminin does not. Supporting Evidence: |
| GO:0045892 negative regulation of DNA-templated transcription | IEA GO_REF:0000107 | ACCEPT | Reason: Mouse and human assays support conserved transcriptional repression. Supporting Evidence: |
| GO:0065003 protein-containing complex assembly | IEA GO_REF:0000107 | KEEP AS NON CORE | Reason: Retain SMRT recruitment as contextual complex assembly; the specific core activity is transcriptional repression. Supporting Evidence: |
| GO:0140297 DNA-binding transcription factor binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Reason: Retain AP4 binding as mechanistic support for corepression, with mouse experimental grounding. Supporting Evidence: |
| GO:1903467 negative regulation of mitotic DNA replication initiation | IDA PMID:11125146 Inhibition of eukaryotic DNA replication by geminin binding ... | ACCEPT | Reason: Full-length human Geminin blocks MCM loading and DNA synthesis in Xenopus extracts; added CDT1 rescues. Retain the specific negative licensing process. Supporting Evidence: |
| GO:2000104 negative regulation of DNA-templated DNA replication | IDA PMID:19906994 Quaternary structure of the human Cdt1-Geminin complex regul... | TOO GENERAL | Reason: Accepted GO:1903467 entails this broader regulation term; the positive source assertion is retained. Supporting Evidence: PMID:19906994 In higher eukaryotes, timely inhibition of Cdt1 by Geminin is essential to prevent DNA rereplication. |
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Download this section (compressed HTML)Q: Which assay supports the GMNN–FBXO5 contact assigned to PMID:23708001?
Experiment: Measure endogenous CDT1–Geminin stoichiometry by calibrated crosslinking/native quantification with tagged-protein and cell-cycle controls.
Hypothesis: Endogenous CDT1–Geminin complexes remain 1:2 throughout S/G2.
Type: Endogenous complex stoichiometry
What is not known — curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: Endogenous human-cell CDT1–Geminin stoichiometries remain unresolved.
OPEN BIOLOGY RESIDUAL_SUBGAP
What is known: Purified inhibitory 1:2 trimers occur at equimolar CDT1 monomer:Geminin dimer, including full-length CDT1.
Provenance (the field's own admissions):
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