RB1 encodes the retinoblastoma-associated protein (pRb / p105-Rb / p110-RB1), the founding member of the pocket protein family and a nuclear, chromatin-bound tumor suppressor. Its core evolved activity is to enforce the G1 restriction point by binding activator E2F transcription factors (E2F1/2/3) through the RB_A/RB_B pocket domains, masking their transactivation domains and recruiting chromatin-modifying corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases, polycomb factors) to E2F-target promoters required for S-phase entry. Activity is switched off by sequential cyclin-CDK phosphorylation: Cyclin D-CDK4/6 and Cyclin E-CDK2 progressively phosphorylate ~16 Ser/Thr sites, with an early reversible intermediate phosphorylation at T373/S608 followed by cooperative C-terminal hyperphosphorylation (S780, S807/S811, T826) that fully releases E2F. Genome-wide ChIP studies show RB1 occupies thousands of loci across promoters, enhancers, and CTCF-bound sites, and the same scaffolding activity supports several non-canonical functions that are well documented but mechanistically downstream of the E2F-repression core: repression of RNA polymerase III transcription (via TFIIIB binding), genome maintenance (interactions with Ku70/Ku80/XRCC5/XRCC6 in cNHEJ and with BRG1 in HR-coupled programs), heterochromatin/SAHF formation in cellular senescence, and lineage-specific transcriptional cooperation with non-E2F partners (RUNX2, AR, CEBPD, PU.1). RB1 is the mutated locus in hereditary retinoblastoma and is recurrently lost in many adult tumors; its functional state is a clinically actionable biomarker for CDK4/6 inhibitor response.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0031175 neuron projection development | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA annotation projected from the PANTHER PTHR13742 (RB/pocket-protein) family tree via GO_REF:0000033. RB1 has documented roles in neuronal differentiation in vivo (e.g. murine Rb1 loss causes defects in retinal, cortical and CNS neuron development; the Rb/E2F axis regulates terminal differentiation in many neuronal lineages — deep research synthesis). However, neuron projection development is a tissue/cell-type-specific outcome of the broader Rb-E2F transcriptional repression program rather than a constitutive core RB1 function. The core RB1 function (Rb-E2F complex, G1/S transition repression, transcription coregulator activity, nucleoplasmic localization) is captured by other rows in this annotation set. Reason: Tissue/cell-type-specific neuronal differentiation context rather than a core RB1 function. Canonical RB1 activity (Rb-E2F complex assembly, negative regulation of G1/S transition, chromatin-bound transcription corepression with HDAC1/SUV39H1/BRG1) is already captured by direct experimental and IPI evidence elsewhere in this file (PMID:7923370; PMID:16360038 IPI on GO:0035189). Mechanical IBA-PANTHER batch (batch 6 of #347). |
| GO:0048667 cell morphogenesis involved in neuron differentiation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA annotation projected from the PANTHER PTHR13742 (RB/pocket-protein) family tree via GO_REF:0000033. As with GO:0031175 above, RB1 contributes to terminal neuronal differentiation in specific developmental contexts via the Rb-E2F transcriptional program, but cell morphogenesis involved in neuron differentiation is a downstream tissue-specific consequence rather than a core RB1 molecular/cellular function. Reason: Tissue/cell-type-specific neuronal differentiation context rather than a core RB1 function. Canonical RB1 activity (Rb-E2F complex assembly, negative regulation of G1/S transition, chromatin-bound transcription corepression with HDAC1/SUV39H1/BRG1) is already captured by direct experimental and IPI evidence elsewhere in this file (PMID:7923370; PMID:16360038 IPI on GO:0035189). Mechanical IBA-PANTHER batch (batch 6 of #347). |
| GO:0000785 chromatin | IBA GO_REF:0000033 | ACCEPT | Summary: IBA annotation projected from the PANTHER PTHR13742 (RB/pocket-protein) family tree via GO_REF:0000033 for chromatin localization. Hypophosphorylated active RB1 is chromatin-bound at E2F target gene promoters and recruits chromatin-modifying corepressors (HDAC1, SUV39H1, BRG1/SMARCA4) — this is a canonical, well-supported RB1 cellular localization (PMID:7923370; deep research synthesis). Chromatin binding is independently supported by direct experimental evidence elsewhere in this file. Reason: Canonical RB1 localization, well supported by experimental evidence already present in this file (PMID:7923370 RB-BRG1 cooperation; PMID:17540172 IDA rows on heterochromatin/chromatin lock complex) and by independent Reactome TAS rows previously ACCEPTed in PRs #440/#444. Mechanical IBA-PANTHER batch (batch 6 of #347). |
| GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | MODIFY | Summary: IBA annotation projected from the PANTHER PTHR13742 (RB/pocket-protein) family tree via GO_REF:0000033 for sequence-specific DNA binding at Pol II regulatory regions. RB1 itself does not contain a sequence-specific DNA-binding domain; its occupancy of E2F target gene promoters (E2F sites in regulatory regions) is mediated indirectly by binding the activator E2F1/2/3 transcription factors (which contain the sequence-specific winged-helix DNA-binding domain) via the RB_A/RB_B pocket. The sequence specificity is therefore contributed by E2F1/2/3, not by RB1. GO no longer has a non-sequence-specific Pol II regulatory-region DNA-binding term (GO:0001012 was merged into GO:0000977), so RB1's indirect, complex-mediated occupancy of regulatory chromatin is best captured by chromatin binding (GO:0003682). Reason: Essence of the annotation (RB1 occupies Pol II regulatory regions via the Rb-E2F complex) is correct, but the "sequence-specific" qualifier of GO:0000977 does not apply to RB1: sequence specificity is contributed by E2F1/2/3 (winged-helix DNA-binding domain), while RB1 binds the E2F protein via the RB_A/RB_B pocket rather than DNA directly. Replace with GO:0001012 (RNA polymerase II transcription regulatory region DNA binding), which captures the regulatory-region occupancy without the sequence-specific binding claim. Mechanical IBA-PANTHER batch (batch 6 of #347); action adjusted in response to PR #490 review. GO has since merged GO:0001012 into GO:0000977 (it is now an alt_id of the sequence-specific term), so the non-sequence-specific DNA-binding option no longer exists; the replacement is now chromatin binding (GO:0003682), which captures RB1's E2F-mediated occupancy of regulatory chromatin without asserting direct DNA binding. It is consistent with the ACCEPTed chromatin (GO:0000785) localization row in this file and with the co-purification of RB1 with core histones and HP1gamma in the L3MBTL1 chromatin-lock complex (PMID:17540172). Proposed replacements: chromatin binding Supporting Evidence: PMID:17540172 L3MBTL1 is in a complex with core histones, histone H1b, HP1gamma, and Rb. |
| GO:0035189 Rb-E2F complex | IBA GO_REF:0000033 | ACCEPT | Summary: IBA annotation projected from the PANTHER PTHR13742 (RB/pocket-protein) family tree via GO_REF:0000033 for the Rb-E2F complex. RB1 is the defining pocket-protein component of the Rb-E2F transcriptional repressor complex; the RB_A/RB_B pocket directly engages activator E2F1/2/3 transactivation domains and DP1/DP2 heterodimer partners to occupy E2F target gene promoters (PMID:7923370; deep research synthesis). Independently supported by IPI evidence (PMID:16360038) on this same GO:0035189 term elsewhere in this annotation set and by the parallel IEA Ensembl-Compara row ACCEPTed in PR #461. Reason: Canonical RB1 function — Rb-E2F complex is the namesake of the RB1 mechanism. Well supported by direct IPI evidence (PMID:16360038) on this exact term elsewhere in this file and by the parallel IEA row ACCEPTed in PR #461. Mechanical IBA-PANTHER batch (batch 6 of #347). |
| GO:2000134 negative regulation of G1/S transition of mitotic cell cycle | IBA GO_REF:0000033 | ACCEPT | Summary: IBA annotation projected from the PANTHER PTHR13742 (RB/pocket-protein) family tree via GO_REF:0000033 for negative regulation of the G1/S transition. Hypophosphorylated RB1 sequesters activator E2F1/2/3 and prevents transcription of S-phase entry genes (CCNE1, CDC6, MCM2-7, etc.); CDK4/6-Cyclin D phosphorylation of RB1 inactivates this repression and licenses G1/S progression (PMID:7923370; deep research synthesis). This is one of the most canonical RB1 functions, central to its tumor-suppressor role. Reason: Canonical RB1 tumor-suppressor function — restraint of the G1/S transition via E2F sequestration is one of the best-characterized RB1 activities. Well supported by direct experimental and Reactome TAS evidence elsewhere in this file (PMID:19149898 TAS rows on G1/S regulation; ACCEPTed in earlier batches). Mechanical IBA-PANTHER batch (batch 6 of #347). |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation propagated via UniProt-keyword/InterPro2GO (GO_REF:0000120) for nuclear localization. RB1 is a canonical nuclear protein; hypophosphorylated active RB1 occupies E2F-target gene promoters in the nucleoplasm and recruits chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4) (PMID:7923370; deep research synthesis). Nuclear localization is also independently supported by IDA (PMID:1531329, PMID:20940255) and by 17 Reactome TAS rows on GO:0005654 nucleoplasm already ACCEPTed in PR #444. Reason: Canonical RB1 function/localization, well supported by experimental evidence already present in this file (PMID:7923370 RB-BRG1 cooperation; IDA/EXP rows in this annotation set) and by independent Reactome TAS rows previously ACCEPTed in PRs #440/#444. Mechanical IEA-canonical batch (batch 5 of #347). |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: IEA annotation propagated via UniProt-keyword/InterPro2GO (GO_REF:0000120) for cytoplasmic localization. RB1 is canonically a nuclear protein (active hypophosphorylated RB1 occupies E2F-target promoters in the nucleoplasm), but cytoplasmic localization is a real conditional secondary state. UniProt P06400 CC SUBCELLULAR LOCATION records cytoplasmic localization "when hyperphosphorylated (By similarity)" (projected from mouse Rb1 P13405) and additionally notes that interaction with PKP3 (Plakophilin 3) may sequester RB1 to the cytoplasm (By similarity, from P13405). PMID:20940255 (Pickard et al. 2010) independently shows RB1 mislocalizes to the cytoplasm when not PCAF-acetylated during keratinocyte differentiation. None of these cytoplasmic contexts represent the canonical Rb-E2F transcriptional corepressor function captured by core_functions[0]. Reason: Cytoplasmic localization is a real but non-core secondary state — represents inactive/sequestered or apoptotic-context RB1, downstream of the defining nuclear Rb-E2F transcriptional corepressor activity already ACCEPTed (GO:0005634 nucleus IEA in batch 5; 17 Reactome TAS GO:0005654 nucleoplasm rows ACCEPTed in PR #444; PMID:20940255 EXP nuclear localization). Same precedent as the GO:0005819 spindle KEEP_AS_NON_CORE row in batch 15 (#551) — IEA localization counterpart to a non-core RB1 functional context. |
| GO:0006357 regulation of transcription by RNA polymerase II | IEA GO_REF:0000002 | ACCEPT | Summary: IEA annotation propagated via InterPro2GO (GO_REF:0000002) for regulation of transcription by RNA polymerase II. RB1 is a chromatin-bound corepressor of Pol II transcription, primarily through binding and inhibition of activator E2F1/2/3 transcription factors at the RB_A/RB_B pocket and recruitment of chromatin-modifying complexes (HDAC1, SUV39H1, BRG1/SMARCA4) (PMID:7923370; deep research synthesis). Pol II transcriptional regulation is also captured by GO:0000122 TAS (PMID:19149898) elsewhere in this file. Reason: Canonical RB1 function/localization, well supported by experimental evidence already present in this file (PMID:7923370 RB-BRG1 cooperation; IDA/EXP rows in this annotation set) and by independent Reactome TAS rows previously ACCEPTed in PRs #440/#444. Mechanical IEA-canonical batch (batch 5 of #347). |
| GO:0032502 developmental process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: IEA annotation propagated via GO_REF:0000117 (electronic, ARBA/InterPro2GO-type) for the high-level grouping term developmental process. RB1 is a pleiotropic tumor suppressor whose non-canonical biology genuinely extends to promotion of differentiation across multiple lineages (myocytes, adipocytes, erythroid and neuronal precursors) and to senescence and lineage-fidelity maintenance (deep research synthesis: sanidas2024patternsinthe; huang2024therapeuticstrategiesfor; corroborated by PMID:9448006 discussion noting nonphosphorylated pRB promotes differentiation of myocytes, adipocytes, erythroid and neuronal cells). However, developmental process is an extremely broad grouping term and these developmental roles are downstream contexts of, not equivalent to, the defining Rb-E2F G1/S transcriptional corepressor activity captured by core_functions[0]. Reason: RB1's developmental roles are real and literature-supported but represent pleiotropic non-core contexts downstream of the defining Rb-E2F cell-cycle corepressor function (already ACCEPTed: GO:0051726 regulation of cell cycle, GO:0006357 regulation of transcription by Pol II, the GO:0045892 IDA rows, and the 17 Reactome nucleoplasm TAS rows). Same KEEP_AS_NON_CORE precedent as the GO:0005737 cytoplasm and GO:0005819 spindle (batch 15, #551) rows — a real but non-core IEA aspect retained on record rather than removed. The term is too high-level to be core; it is not wrong. |
| GO:0051726 regulation of cell cycle | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation propagated via UniProt-keyword/InterPro2GO (GO_REF:0000120) for regulation of cell cycle. RB1 is the prototypical pocket-protein G1/S-checkpoint regulator; hypophosphorylated RB1 represses E2F-driven S-phase entry and is two-step inactivated by Cyclin D-CDK4/6 then Cyclin E-CDK2 phosphorylation (PMID:7923370; deep research synthesis). Cell-cycle regulation is also captured by GO:2000134 TAS (PMID:19149898) and multiple IDA/IMP rows elsewhere in this file. Reason: Canonical RB1 function/localization, well supported by experimental evidence already present in this file (PMID:7923370 RB-BRG1 cooperation; IDA/EXP rows in this annotation set) and by independent Reactome TAS rows previously ACCEPTed in PRs #440/#444. Mechanical IEA-canonical batch (batch 5 of #347). |
| GO:0005515 protein binding | IPI PMID:10779361 Mutagenesis of the pRB pocket reveals that cell cycle arrest... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:10944455 RBP95, a novel leucine zipper protein, binds to the retinobl... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:11268000 Ebp1, an ErbB-3 binding protein, interacts with Rb and affec... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:12434308 Protein Phosphatase 1 binds strongly to the retinoblastoma p... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:12502741 Structural basis for the recognition of the E2F transactivat... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:12598654 Crystal structure of the retinoblastoma tumor suppressor pro... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:12743606 The adenovirus E1A oncoprotein recruits the cellular TRRAP/G... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:12813456 Interaction of the HPV E7 proteins with the pCAF acetyltrans... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:1331501 Homologous sequences in adenovirus E1A and human papillomavi... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:14555653 LEK1 is a potential inhibitor of pocket protein-mediated cel... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:14645241 Interactions between activating signal cointegrator-2 and th... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:15084261 Cyclin C/cdk3 promotes Rb-dependent G0 exit. | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:16061792 Association of the human papillomavirus type 16 E7 oncoprote... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:16249186 Structure of the human Papillomavirus E7 oncoprotein and its... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:16286473 The retinoblastoma family proteins bind to and activate diac... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:16360038 Structure of the Rb C-terminal domain bound to E2F1-DP1: a m... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:16374512 DNA-damage-responsive acetylation of pRb regulates binding t... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:16510145 Effects of MdmX on Mdm2-mediated downregulation of pRB. | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:16616919 The arginine methyltransferase PRMT2 binds RB and regulates ... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:16763564 Roles for APIS and the 20S proteasome in adenovirus E1A-depe... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:16766265 HMGA2 induces pituitary tumorigenesis by enhancing E2F1 acti... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:17045206 p53 family members in myogenic differentiation and rhabdomyo... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:17274640 A limited screen for protein interactions reveals new roles ... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:17292836 Structure of the oncoprotein gankyrin in complex with S6 ATP... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:17349581 Kras(G12D) and Smad4/Dpc4 haploinsufficiency cooperate to in... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:17380128 Phosphorylation of pRB at Ser612 by Chk1/2 leads to a comple... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:17620057 Deacetylation of the retinoblastoma tumour suppressor protei... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:18391203 EBV-encoded EBNA-6 binds and targets MRS18-2 to the nucleus,... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:1870208 Purification and characterization of human papillomavirus ty... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:19017275 Shigella flexneri type III secretion system effectors OspB a... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:19249677 Proapoptotic function of the retinoblastoma tumor suppressor... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:19513100 Direct binding of pRb/E2F-2 to GATA-1 regulates maturation a... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:19651603 Structural basis for subversion of cellular control mechanis... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:20088881 Targeting mechanism of the retinoblastoma tumor suppressor b... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:20195357 A comprehensive resource of interacting protein regions for ... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:20871633 p38 phosphorylates Rb on Ser567 by a novel, cell cycle-indep... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:21119616 Interplay between lysine methylation and Cdk phosphorylation... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:21139044 Rb-Raf-1 interaction disruptor RRD-251 induces apoptosis in ... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:2138977 The regions of the retinoblastoma protein needed for binding... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:2153075 The region of the HPV E7 oncoprotein homologous to adenoviru... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:2162480 Definition of the minimal simian virus 40 large T antigen- a... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:2189724 Two distinct and frequently mutated regions of retinoblastom... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:21903422 Mapping a dynamic innate immunity protein interaction networ... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:21952639 NIRF constitutes a nodal point in the cell cycle network and... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:22157815 The SNF2-like helicase HELLS mediates E2F3-dependent transcr... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:22301153 The coronavirus endoribonuclease Nsp15 interacts with retino... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:22366686 Senescence is an endogenous trigger for microRNA-directed tr... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:22615382 H3K4 demethylation by Jarid1a and Jarid1b contributes to ret... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:22773103 LEDGF (p75) promotes DNA-end resection and homologous recomb... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:22810586 Interpreting cancer genomes using systematic host network pe... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:22898364 Comparative analysis of virus-host interactomes with a mamma... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:23472054 The ING1a tumor suppressor regulates endocytosis to induce c... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:23602568 The protein interaction landscape of the human CMGC kinase g... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:23752268 The functional interactome landscape of the human histone de... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:23783631 Modulation of allostery by protein intrinsic disorder. | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:23859194 Mitogen-activated protein kinase p38 and retinoblastoma prot... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:24823443 HAUSP, a novel deubiquitinase for Rb - MDM2 the critical reg... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:25609649 Proteomic analyses reveal distinct chromatin-associated and ... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:25814554 Phospho-tyrosine dependent protein-protein interaction netwo... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:29521627 A compartmentalized signaling network mediates crossover con... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:29997244 LuTHy: a double-readout bioluminescence-based two-hybrid tec... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:34591612 A protein interaction landscape of breast cancer. | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:34591642 A protein network map of head and neck cancer reveals PIK3CA... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:35140242 Human transcription factor protein interaction networks. | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:39938803 Structural and functional analysis of cancer-associated miss... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:7592647 Association of human Pur alpha with the retinoblastoma prote... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:7664264 The nuclear tyrosine kinase Rak associates with the retinobl... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:7791904 Interaction between the retinoblastoma protein and the oncop... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:7890747 Binding of an interferon-inducible protein (p202) to the ret... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:7923370 The retinoblastoma protein and BRG1 form a complex and coope... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:8756624 Cyclin-binding motifs are essential for the function of p21C... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:9067421 A DNA polymerase alpha accessory protein exhibits structural... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:9468139 Retinoblastoma protein recruits histone deacetylase to repre... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:9468140 Retinoblastoma protein represses transcription by recruiting... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:9608663 The rubella virus putative replicase interacts with the reti... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:9697699 A retinoblastoma-binding protein that affects cell-cycle con... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:9881977 Direct suppression of Stat1 function during adenoviral infec... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0042802 identical protein binding | IPI PMID:16360038 Structure of the Rb C-terminal domain bound to E2F1-DP1: a m... | MARK AS OVER ANNOTATED | Summary: Rubin et al. 2005 (PMID:16360038, Cell) is the crystal structure of the Rb C-terminal domain (RbC) bound to the E2F1-DP1 heterodimer. It characterizes a high-affinity heterotypic interaction in which RbC contacts the marked-box domains of E2F1 and DP1, plus a phosphorylation-induced intramolecular RbC-pocket contact within a single RB1 molecule. It does not demonstrate RB1 homodimerization or RB1-RB1 self-association, and RB1 is not characterized as a homodimer in its core E2F-repression / chromatin-scaffolding biology. GO:0042802 identical protein binding implies an RB1-RB1 interaction that this paper does not support. The informative interactions from this structure are already captured by the batch-17 ACCEPT rows GO:0035189 (Rb-E2F complex) and GO:0060090 (molecular adaptor activity). Reason: The cited Rubin 2005 structure characterizes heterotypic RbC-E2F1-DP1 binding, not RB1 self-association; identical protein binding is an unsupported, uninformative generic binding term for this evidence. Conservative demotion consistent with the GO:0005515 precedent in this same review and the batch-17 handling of PMID:16360038. A second independent GO:0042802 row (PMID:8288605) remains PENDING and is deferred to a later batch. |
| GO:0042802 identical protein binding | IPI PMID:8288605 Identification of discrete structural domains in the retinob... | KEEP AS NON CORE | Summary: IPI annotation for identical protein binding sourced from Hensey et al. 1994 (PMID:8288605). This study expressed and purified recombinant full-length human p110RB and an N-terminally truncated p56RB, and used non-denaturing PAGE, electron microscopy and yeast two-hybrid analysis to show that full-length RB1 self-associates into oligomeric/higher-order structures via interactions between its amino- and carboxy-terminal domains, a property absent from the N-terminally truncated form. This is genuine, specific evidence for RB1 homo-oligomerization (identical protein binding), distinct from the heterotypic RbC-E2F1-DP1 contacts cited for the other GO:0042802 row (PMID:16360038) that was demoted because that source did not characterize self-association. Reason: RB1 self-oligomerization is a real, specifically-evidenced biochemical property (yeast two-hybrid + native PAGE + EM in PMID:8288605), so the term is correctly supported here and is informative rather than generic protein binding. However it is a secondary structural property, not the defining E2F-pocket corepressor / chromatin-scaffold activity captured by core_functions[0] (GO:0003714); kept on record at non-core priority. This resolves the GO:0042802 (PMID:8288605) row explicitly deferred by the batch-17 handling of the PMID:16360038 counterpart. Mechanical binding-partner-MF batch (batch 22 of #347). |
| GO:0002062 chondrocyte differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Tissue-specific differentiation phenotype projected from mouse Rb1 ortholog via Ensembl Compara (IEA GO_REF:0000107): Rb1 is required for chondrocyte differentiation and endochondral ossification in conditional-knockout mouse skeletal models, but this is a downstream lineage-specific consequence of RB1's core E2F-repression / chromatin-scaffolding activity (e.g. partnering with RUNX2 in cartilage/bone progenitors) rather than a primary RB1 molecular function. Reason: Real biology but a downstream / tissue-specific consequence of RB1's core role in E2F-mediated G1/S repression and chromatin scaffolding (RB_A/RB_B pocket binding, HDAC1/SUV39H1/BRG1 recruitment) rather than a primary RB1 function. Kept on record at non-core priority. These rows are mouse Rb1 phenotypes projected to human via Ensembl/PANTHER (IEA GO_REF:0000107) and InterPro/UniProt ISS templates (GO_REF:0000024, plus PMIDs 19417128 and 24027266) - same non-core treatment as analogous tissue-specific ortholog projections in prior reviews. |
| GO:0003180 aortic valve morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Tissue-specific developmental phenotype projected from mouse Rb1 ortholog: Rb1-null mouse hearts exhibit cardiac valve defects, but this is a downstream developmental consequence of Rb1's core role in E2F-mediated proliferation/differentiation control in cardiac neural crest and valvular interstitial cells, not a primary RB1 molecular function. Reason: Real biology but a downstream / tissue-specific consequence of RB1's core role in E2F-mediated G1/S repression and chromatin scaffolding (RB_A/RB_B pocket binding, HDAC1/SUV39H1/BRG1 recruitment) rather than a primary RB1 function. Kept on record at non-core priority. These rows are mouse Rb1 phenotypes projected to human via Ensembl/PANTHER (IEA GO_REF:0000107) and InterPro/UniProt ISS templates (GO_REF:0000024, plus PMIDs 19417128 and 24027266) - same non-core treatment as analogous tissue-specific ortholog projections in prior reviews. |
| GO:0005667 transcription regulator complex | IEA GO_REF:0000107 | ACCEPT | Summary: IEA annotation projected from mouse Rb1 via Ensembl Compara (GO_REF:0000107) for transcription regulator complex. RB1 is the defining component of the Rb-E2F transcriptional repressor complex and broadly participates in chromatin-bound transcription regulator assemblies with HDAC1, SUV39H1, BRG1/SMARCA4, and lineage-specific TFs (PMID:7923370; deep research synthesis). Independently supported by the more specific GO:0035189 Rb-E2F complex IPI rows in this file. Reason: Canonical RB1 function/localization, well supported by experimental evidence already present in this file (PMID:7923370 RB-BRG1 cooperation; IDA/EXP rows in this annotation set) and by independent Reactome TAS rows previously ACCEPTed in PRs #440/#444. Mechanical IEA-canonical batch (batch 5 of #347). |
| GO:0005819 spindle | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA annotation projected from mouse Rb1 via Ensembl Compara (GO_REF:0000107) for spindle localization. RB1 has a documented but non-core mitotic-fidelity role at the centromere/condensin II axis (CAP-D3 mislocalization, merotelic attachment, lagging chromosomes) shown by Manning et al. 2010 PMID:20551165 — this is the same mitotic-fidelity biology that motivates spindle-adjacent localization, but it is downstream of, and tangential to, RB1's defining function as the Rb-E2F transcriptional corepressor that enforces the G1/S restriction point. Reason: RB1's contribution to mitotic centromere/cohesion fidelity (Manning 2010 PMID:20551165) is a real but non-core mitotic role that explains a downstream cancer consequence (CIN/aneuploidy in RB1-null tumors) rather than defining RB1's primary molecular activity. The canonical RB1 core function (Rb-E2F complex assembly, negative regulation of G1/S transition, chromatin-bound transcription corepression with HDAC1/SUV39H1/BRG1) is already captured by direct experimental evidence elsewhere in this file (PMID:7923370 IDA, PMID:16360038 IPI on GO:0035189). Spindle IEA projected from mouse Rb1 ortholog (GO_REF:0000107) is the localization counterpart to the PMID:20551165 mitotic-fidelity IMP cluster already KEEP_AS_NON_CORE in batch 11 of #347. |
| GO:0006915 apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Downstream phenotype projected from mouse Rb1 ortholog via Ensembl Compara (IEA GO_REF:0000107): Rb1 loss sensitises cells to apoptosis through deregulated E2F1-driven proapoptotic gene programs (e.g. p73, BIM, APAF1) and altered Bcl-2-family balance, but apoptotic engagement is a context-dependent consequence of RB1's core E2F-repression / chromatin-scaffolding activity rather than a primary RB1 molecular function. Consistent with the existing KEEP_AS_NON_CORE treatment of GO:2001234 negative regulation of apoptotic signaling pathway (ISS PMID:24027266) elsewhere in this file. Reason: Real biology but a downstream / tissue-specific consequence of RB1's core role in E2F-mediated G1/S repression and chromatin scaffolding (RB_A/RB_B pocket binding, HDAC1/SUV39H1/BRG1 recruitment) rather than a primary RB1 function. Kept on record at non-core priority. These rows are mouse Rb1 phenotypes projected to human via Ensembl/PANTHER (IEA GO_REF:0000107) and InterPro/UniProt ISS templates (GO_REF:0000024, plus PMIDs 19417128 and 24027266) - same non-core treatment as analogous tissue-specific ortholog projections in prior reviews. |
| GO:0007283 spermatogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Tissue-specific developmental phenotype projected from mouse Rb1 ortholog via Ensembl Compara (IEA GO_REF:0000107): germ-cell-conditional Rb1 deletion in the mouse compromises spermatogonial / Sertoli-cell programs and male fertility, but spermatogenesis is a downstream lineage-specific consequence of RB1's core E2F-repression / chromatin-scaffolding role in proliferating progenitors rather than a primary RB1 molecular function. Reason: Real biology but a downstream / tissue-specific consequence of RB1's core role in E2F-mediated G1/S repression and chromatin scaffolding (RB_A/RB_B pocket binding, HDAC1/SUV39H1/BRG1 recruitment) rather than a primary RB1 function. Kept on record at non-core priority. These rows are mouse Rb1 phenotypes projected to human via Ensembl/PANTHER (IEA GO_REF:0000107) and InterPro/UniProt ISS templates (GO_REF:0000024, plus PMIDs 19417128 and 24027266) - same non-core treatment as analogous tissue-specific ortholog projections in prior reviews. |
| GO:0019899 enzyme binding | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: IEA annotation projected from mouse Rb1 via Ensembl Compara (GO_REF:0000107) for enzyme binding. GO:0019899 is an uninformative generic MF parent term that captures the broad class of RB1's enzymatic-partner interactions without naming what RB1 actually does mechanistically. RB1's informative enzyme-binding biology is already captured at higher specificity by the chromatin-modifying enzyme interactions ACCEPTed in this file (HDAC1, SUV39H1, BRG1/SMARCA4 corepressor recruitment via the RB_A/RB_B pocket; PMID:7923370 RB-BRG1 cooperation; deep research synthesis) and by the GO:0001047 / GO:0003682 chromatin-binding rows. Per CLAUDE.md curation guidelines, generic adapter/binding parent terms should be demoted in favor of more specific MF annotations. Reason: Generic enzyme binding is uninformative for RB1's well-characterized adapter/scaffolding biology with chromatin-modifying enzymes (HDAC1, SUV39H1, BRG1/SMARCA4) and cell-cycle kinases (CDK4/CDK6 phosphorylation of RB1). Same precedent as the uniform demotion of generic GO:0005515 protein binding IPI rows in this file (50+ rows ACCEPTed as MARK_AS_OVER_ANNOTATED per BAG3 #313 / KRAS #349 / BCAP31 PR #317 / RB1 PR #430 precedent). |
| GO:0030308 negative regulation of cell growth | IEA GO_REF:0000107 | ACCEPT | Summary: IEA annotation projected from mouse Rb1 via Ensembl Compara (GO_REF:0000107) for negative regulation of cell growth. RB1 is the prototypical pocket-protein antiproliferative tumor suppressor: hypophosphorylated RB1 binds activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, masks their transactivation domains, recruits chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4) and durably represses S-phase gene transcription, thereby restricting net cellular growth and proliferation (PMID:7923370; deep research synthesis). Already captured at higher specificity in this file via the GO:2000134 negative regulation of G1/S transition TAS row (PMID:19149898) ACCEPTed in batch 9 and the GO:0051726 regulation of cell cycle IEA row ACCEPTed in batch 5. Reason: Canonical RB1 antiproliferative function, well supported by experimental evidence already present in this file (PMID:7923370 RB-BRG1 cooperation; IDA/EXP rows in this annotation set) and by independent Reactome TAS rows previously ACCEPTed in PRs #440/#444. Mechanical IEA-canonical batch (batch 14 of #347). |
| GO:0032869 cellular response to insulin stimulus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Tissue-specific metabolic phenotype projected from mouse Rb1 ortholog via Ensembl Compara (IEA GO_REF:0000107): Rb1 modulates insulin sensitivity in adipocytes and beta cells through E2F-mediated control of metabolic / differentiation gene programs (paralleling the existing GO:0120163 cold-induced thermogenesis ISS row at line 1296), but insulin-stimulus response is a context-dependent metabolic consequence of RB1's core E2F-repression / chromatin-scaffolding activity rather than a primary RB1 molecular function. Reason: Real biology but a downstream / tissue-specific consequence of RB1's core role in E2F-mediated G1/S repression and chromatin scaffolding (RB_A/RB_B pocket binding, HDAC1/SUV39H1/BRG1 recruitment) rather than a primary RB1 function. Kept on record at non-core priority. These rows are mouse Rb1 phenotypes projected to human via Ensembl/PANTHER (IEA GO_REF:0000107) and InterPro/UniProt ISS templates (GO_REF:0000024, plus PMIDs 19417128 and 24027266) - same non-core treatment as analogous tissue-specific ortholog projections in prior reviews. |
| GO:0035189 Rb-E2F complex | IEA GO_REF:0000107 | ACCEPT | Summary: IEA annotation projected from mouse Rb1 via Ensembl Compara (GO_REF:0000107) for Rb-E2F complex. RB1 is the defining pocket-protein component of the Rb-E2F transcriptional repressor complex; the RB_A/RB_B pocket directly engages activator E2F1/2/3 transactivation domains and DP heterodimer partners to occupy E2F target gene promoters (PMID:7923370; deep research synthesis). Independently supported by IPI evidence (PMID:16360038) on this exact term elsewhere in this file. Reason: Canonical RB1 function/localization, well supported by experimental evidence already present in this file (PMID:7923370 RB-BRG1 cooperation; IDA/EXP rows in this annotation set) and by independent Reactome TAS rows previously ACCEPTed in PRs #440/#444. Mechanical IEA-canonical batch (batch 5 of #347). |
| GO:0045786 negative regulation of cell cycle | IEA GO_REF:0000107 | ACCEPT | Summary: IEA annotation projected from mouse Rb1 via Ensembl Compara (GO_REF:0000107) for negative regulation of cell cycle. Negative regulation of cell-cycle progression is the defining RB1 tumor-suppressor activity: hypophosphorylated RB1 sequesters activator E2Fs and represses S-phase genes at the G1 restriction point until it is sequentially inactivated by Cyclin D-CDK4/6 and Cyclin E-CDK2 phosphorylation (PMID:7923370; deep research synthesis). Already captured at higher specificity in this file via the GO:2000134 negative regulation of G1/S transition TAS row (PMID:19149898) ACCEPTed in batch 9 and the GO:0051726 regulation of cell cycle IEA row ACCEPTed in batch 5. Reason: Canonical RB1 cell-cycle-restriction function, well supported by experimental evidence already present in this file (PMID:7923370 RB-BRG1 cooperation; IDA/EXP rows in this annotation set) and by independent Reactome TAS rows previously ACCEPTed in PRs #440/#444. Mechanical IEA-canonical batch (batch 14 of #347). |
| GO:0050728 negative regulation of inflammatory response | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Downstream tissue-level phenotype projected from mouse Rb1 ortholog: Rb1 loss can increase tissue inflammation as part of the senescence-associated secretory phenotype (SASP) and altered chromatin programs, but inflammatory regulation is a contextual consequence of RB1's core E2F-repression / chromatin-scaffolding activity rather than a primary RB1 function. Reason: Real biology but a downstream / tissue-specific consequence of RB1's core role in E2F-mediated G1/S repression and chromatin scaffolding (RB_A/RB_B pocket binding, HDAC1/SUV39H1/BRG1 recruitment) rather than a primary RB1 function. Kept on record at non-core priority. These rows are mouse Rb1 phenotypes projected to human via Ensembl/PANTHER (IEA GO_REF:0000107) and InterPro/UniProt ISS templates (GO_REF:0000024, plus PMIDs 19417128 and 24027266) - same non-core treatment as analogous tissue-specific ortholog projections in prior reviews. |
| GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding | IEA GO_REF:0000107 | ACCEPT | Summary: IEA annotation projected from mouse Rb1 via Ensembl Compara (GO_REF:0000107) for RNA polymerase II-specific DNA-binding transcription factor binding. RB1 directly binds the E2F1/2/3 activator transcription factors (sequence-specific Pol II TFs) via its RB_A/RB_B pocket; this is the canonical RB1 molecular function (PMID:7923370; deep research synthesis). Independently supported by IPI evidence on the related Rb-E2F complex (GO:0035189) and by core_functions[0] in this file. Reason: Canonical RB1 function/localization, well supported by experimental evidence already present in this file (PMID:7923370 RB-BRG1 cooperation; IDA/EXP rows in this annotation set) and by independent Reactome TAS rows previously ACCEPTed in PRs #440/#444. Mechanical IEA-canonical batch (batch 5 of #347). |
| GO:0120163 negative regulation of cold-induced thermogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Tissue-specific phenotype projected from mouse Rb1: Rb1 represses brown-adipocyte / thermogenic gene programs (Ucp1) in white adipose tissue (PMID:19417128), but cold-induced thermogenesis is a downstream metabolic consequence of RB1's role in adipocyte differentiation/transcription control rather than a core RB1 function. Reason: Real biology but a downstream / tissue-specific consequence of RB1's core role in E2F-mediated G1/S repression and chromatin scaffolding (RB_A/RB_B pocket binding, HDAC1/SUV39H1/BRG1 recruitment) rather than a primary RB1 function. Kept on record at non-core priority. These rows are mouse Rb1 phenotypes projected to human via Ensembl/PANTHER (IEA GO_REF:0000107) and InterPro/UniProt ISS templates (GO_REF:0000024, plus PMIDs 19417128 and 24027266) - same non-core treatment as analogous tissue-specific ortholog projections in prior reviews. |
| GO:0140297 DNA-binding transcription factor binding | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: IEA annotation projected from mouse Rb1 via Ensembl Compara (GO_REF:0000107) for DNA-binding transcription factor binding. RB1 binds multiple sequence-specific DNA-binding transcription factors — most prominently activator E2F1/2/3 via the RB_A/RB_B pocket, and lineage-specific TFs (RUNX2, AR, CEBPD, PU.1) in differentiation contexts (PMID:7923370; deep research synthesis). Same canonical function captured more specifically by GO:0061629 (RNA polymerase II-specific DNA-binding transcription factor binding) which is also ACCEPTed in this file, and all of RB1's characterised TF-binding partners (E2F1/2/3, RUNX2, AR, CEBPD, PU.1) are Pol II-specific TFs, so the parent adds no additional biological information beyond what the child captures. Reason: Parent term of GO:0061629 (RNA polymerase II-specific DNA-binding transcription factor binding), which is ACCEPTed in this same batch and captures the full scope of RB1's TF-binding biology — every characterised RB1 partner (E2F1/2/3, RUNX2, AR, CEBPD, PU.1) is a Pol II-specific TF, so the more general GO:0140297 is not entirely wrong but represents an over-annotation per the schema definition. |
| GO:1903055 positive regulation of extracellular matrix organization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Downstream tissue-level phenotype projected from mouse Rb1 ortholog: Rb1 modulates ECM organization through transcriptional control of stromal/fibroblast programs, but ECM organization is a contextual consequence of RB1's core E2F-repression / chromatin-scaffolding role rather than a primary molecular function. Reason: Real biology but a downstream / tissue-specific consequence of RB1's core role in E2F-mediated G1/S repression and chromatin scaffolding (RB_A/RB_B pocket binding, HDAC1/SUV39H1/BRG1 recruitment) rather than a primary RB1 function. Kept on record at non-core priority. These rows are mouse Rb1 phenotypes projected to human via Ensembl/PANTHER (IEA GO_REF:0000107) and InterPro/UniProt ISS templates (GO_REF:0000024, plus PMIDs 19417128 and 24027266) - same non-core treatment as analogous tissue-specific ortholog projections in prior reviews. |
| GO:1903944 negative regulation of hepatocyte apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Tissue-specific phenotype projected from mouse Rb1 ortholog: Rb1 modulates hepatocyte apoptosis sensitivity in liver-specific contexts, but this is a downstream tissue-level consequence of RB1's core E2F / cell-cycle / chromatin role rather than a primary molecular function. Reason: Real biology but a downstream / tissue-specific consequence of RB1's core role in E2F-mediated G1/S repression and chromatin scaffolding (RB_A/RB_B pocket binding, HDAC1/SUV39H1/BRG1 recruitment) rather than a primary RB1 function. Kept on record at non-core priority. These rows are mouse Rb1 phenotypes projected to human via Ensembl/PANTHER (IEA GO_REF:0000107) and InterPro/UniProt ISS templates (GO_REF:0000024, plus PMIDs 19417128 and 24027266) - same non-core treatment as analogous tissue-specific ortholog projections in prior reviews. |
| GO:1904028 positive regulation of collagen fibril organization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Downstream tissue-level phenotype projected from mouse Rb1 ortholog: Rb1 affects collagen-fibril organization via transcriptional regulation of stromal programs, but collagen-fibril organization is a contextual consequence of RB1's core role in cell-cycle / differentiation control rather than a primary molecular function. Reason: Real biology but a downstream / tissue-specific consequence of RB1's core role in E2F-mediated G1/S repression and chromatin scaffolding (RB_A/RB_B pocket binding, HDAC1/SUV39H1/BRG1 recruitment) rather than a primary RB1 function. Kept on record at non-core priority. These rows are mouse Rb1 phenotypes projected to human via Ensembl/PANTHER (IEA GO_REF:0000107) and InterPro/UniProt ISS templates (GO_REF:0000024, plus PMIDs 19417128 and 24027266) - same non-core treatment as analogous tissue-specific ortholog projections in prior reviews. |
| GO:1904761 negative regulation of myofibroblast differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Tissue-specific phenotype projected from mouse Rb1 ortholog: Rb1 restricts myofibroblast differentiation programs in fibrotic contexts, but this is a downstream cell-fate consequence of RB1's core E2F-repression / chromatin-scaffolding role rather than a primary molecular function. Reason: Real biology but a downstream / tissue-specific consequence of RB1's core role in E2F-mediated G1/S repression and chromatin scaffolding (RB_A/RB_B pocket binding, HDAC1/SUV39H1/BRG1 recruitment) rather than a primary RB1 function. Kept on record at non-core priority. These rows are mouse Rb1 phenotypes projected to human via Ensembl/PANTHER (IEA GO_REF:0000107) and InterPro/UniProt ISS templates (GO_REF:0000024, plus PMIDs 19417128 and 24027266) - same non-core treatment as analogous tissue-specific ortholog projections in prior reviews. |
| GO:2001234 negative regulation of apoptotic signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Downstream phenotype projected from mouse Rb1 ortholog: Rb1 affects apoptotic signaling sensitivity through E2F-target regulation (e.g. via BCL-2 family genes and cell-cycle/apoptosis crosstalk), but apoptotic-pathway regulation is a context-dependent consequence of RB1's core E2F-repression / chromatin-scaffolding role rather than a primary RB1 function. Reason: Real biology but a downstream / tissue-specific consequence of RB1's core role in E2F-mediated G1/S repression and chromatin scaffolding (RB_A/RB_B pocket binding, HDAC1/SUV39H1/BRG1 recruitment) rather than a primary RB1 function. Kept on record at non-core priority. These rows are mouse Rb1 phenotypes projected to human via Ensembl/PANTHER (IEA GO_REF:0000107) and InterPro/UniProt ISS templates (GO_REF:0000024, plus PMIDs 19417128 and 24027266) - same non-core treatment as analogous tissue-specific ortholog projections in prior reviews. |
| GO:0005634 nucleus | IDA PMID:17540172 L3MBTL1, a histone-methylation-dependent chromatin lock. | ACCEPT | Summary: IDA annotation for nuclear localization sourced from the chromatin lock complex paper (Trojer et al. 2007 Cell, PMID:17540172). RB1 was co-purified with L3MBTL1, core histones, histone H1b, and HP1gamma as a chromatin-bound nuclear complex that compacts facultative heterochromatin. Nuclear localization is the canonical compartment for active hypophosphorylated RB1 and is independently supported by 17 Reactome TAS rows on GO:0005654 nucleoplasm previously ACCEPTed (PR #444) and by IEA propagations ACCEPTed in PR #461. Reason: Canonical RB1 localization, well supported by experimental evidence already present in this file (PMID:7923370 RB-BRG1 cooperation; 17 Reactome TAS nucleoplasm rows ACCEPTed in PR #444) and by the L3MBTL1 chromatin-lock complex co-purification reported in PMID:17540172. Mechanical PMID:17540172-cluster batch (batch 7 of #347). |
| GO:0031507 heterochromatin formation | IDA PMID:17540172 L3MBTL1, a histone-methylation-dependent chromatin lock. | ACCEPT | Summary: IDA annotation from the L3MBTL1 chromatin lock complex paper (Trojer et al. 2007 Cell, PMID:17540172). The L3MBTL1 MBT domains, in a complex with RB1, core histones, histone H1b, and HP1gamma, compact nucleosomal arrays dependent on mono- and dimethylation of histone H4 lysine 20 and histone H1b lysine 26 — the defining biochemistry of facultative heterochromatin formation. RB1 participates in this chromatin-compaction activity as a stoichiometric complex member. Reason: Canonical RB1 function, directly supported by IDA evidence in PMID:17540172 showing RB1 in the L3MBTL1 chromatin lock complex that compacts nucleosomal arrays into facultative heterochromatin. Consistent with RB1's broader role in chromatin scaffolding (RB_A/RB_B pocket binding, HDAC1/SUV39H1/BRG1 recruitment) captured in core_functions[0]. Mechanical PMID:17540172-cluster batch (batch 7 of #347). |
| GO:0045892 negative regulation of DNA-templated transcription | IMP PMID:17540172 L3MBTL1, a histone-methylation-dependent chromatin lock. | ACCEPT | Summary: IMP annotation from the L3MBTL1 chromatin lock complex paper (Trojer et al. 2007 Cell, PMID:17540172). L3MBTL1, in a complex with RB1, was shown to negatively regulate the expression of a subset of genes regulated by E2F — directly linking the chromatin-lock biochemistry to repression of RB-E2F target genes. This is a canonical RB1 transcriptional repressor function delivered via chromatin compaction rather than only via E2F transactivation-domain masking. Reason: Canonical RB1 function, well supported by IMP evidence in PMID:17540172 (L3MBTL1+RB1 chromatin lock represses a subset of E2F target genes) and consistent with the broader RB-E2F repressor mechanism captured in core_functions[0]. Mechanical PMID:17540172-cluster batch (batch 7 of #347). |
| GO:0061793 chromatin lock complex | IPI PMID:17540172 L3MBTL1, a histone-methylation-dependent chromatin lock. | ACCEPT | Summary: IPI annotation from the namesake paper (Trojer et al. 2007 Cell, PMID:17540172) — RB1 co-purifies with L3MBTL1, core histones, histone H1b, and HP1gamma as the chromatin lock complex. GO:0061793 chromatin lock complex was defined for this exact biochemistry. RB1 is a stoichiometric component of this complex and contributes the E2F-target-gene specificity that links the L3MBTL1 H4K20me1/2-reading chromatin-compaction activity to RB1-controlled promoter sets. Reason: RB1 is a defining stoichiometric component of the chromatin lock complex per the namesake paper (PMID:17540172, IPI partner = L3MBTL1; cross-supports the same paper's IDA/IMP entries for GO:0031507 heterochromatin formation and GO:0045892 negative regulation of DNA-templated transcription already in this batch). Mechanical PMID:17540172-cluster batch (batch 7 of #347). |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: IDA annotation for nucleoplasmic localization sourced from the Human Protein Atlas immunofluorescence curation (GO_REF:0000052). RB1 is a canonical nuclear/nucleoplasmic protein; hypophosphorylated active RB1 occupies E2F-target gene promoters in the nucleoplasm and recruits chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4) (PMID:7923370; deep research synthesis). Nucleoplasmic localization is also independently supported by 17 Reactome TAS rows on GO:0005654 already ACCEPTed in PR #444 and by IEA propagations ACCEPTed in PR #461. Reason: Canonical RB1 localization, well supported by experimental evidence already present in this file (PMID:7923370 RB-BRG1 cooperation; 17 Reactome TAS nucleoplasm rows ACCEPTed in PR #444) and by HPA immunofluorescence curation (GO_REF:0000052). Mechanical canonical-nuclear-localization batch (batch 10 of #347). |
| GO:0005634 nucleus | IDA PMID:1531329 The interaction of RB with E2F coincides with an inhibition ... | ACCEPT | Summary: IDA annotation for nuclear localization sourced from the RB-E2F interaction paper (Hiebert et al. 1992 Genes Dev, PMID:1531329). The paper demonstrates that RB1 interacts with E2F in a complex that inhibits E2F transcriptional activity, with the in vivo biochemistry performed on nuclear extracts. Nuclear localization is the canonical compartment for active hypophosphorylated RB1 and is independently supported by 17 Reactome TAS rows on GO:0005654 nucleoplasm previously ACCEPTed (PR #444), by IEA propagations ACCEPTed in PR #461, and by the IDA nucleoplasm row from PMID:17540172 ACCEPTed in PR #499. Reason: Canonical RB1 localization, well supported by experimental evidence already present in this file (PMID:7923370 RB-BRG1 cooperation; 17 Reactome TAS nucleoplasm rows ACCEPTed in PR #444). The Hiebert et al. 1992 paper is the canonical RB-E2F interaction paper and directly supports nuclear localization of RB1. Mechanical canonical-nuclear-localization batch (batch 10 of #347). |
| GO:0006355 regulation of DNA-templated transcription | IDA PMID:1531329 The interaction of RB with E2F coincides with an inhibition ... | MODIFY | Summary: IDA annotation from Hiebert et al. 1992 (PMID:1531329, "The interaction of RB with E2F coincides with an inhibition of the transcriptional activity of E2F"), a canonical RB-E2F repression paper. Transfection assays of the adenovirus E2 promoter show that "formation of the complex containing pRB and E2F coincides with an inhibition of E2F-dependent transcriptional activity" and that "a mutant pRB protein that does not associate with E2F does not inhibit transcription." This directly demonstrates that RB1 *negatively* (not merely "regulates") regulates DNA-templated transcription. The generic parent GO:0006355 is too broad for this directional finding; the specific child GO:0045892 (negative regulation of DNA-templated transcription) is exactly what is shown, is already captured in core_functions[0].directly_involved_in, and is concordantly supported by IDA/TAS rows elsewhere in this file (PMID:12065415, PMID:10783144, PMID:19223331, PMID:19149898). Reason: Essence of the annotation (RB1 represses transcription via the Rb-E2F complex) is correct and canonical, but GO:0006355 is too general for the directional repressor activity that PMID:1531329 directly demonstrates. Replace with GO:0045892 (negative regulation of DNA-templated transcription), the specific term already present in core_functions[0]. Mechanical transcription-regulation batch (batch 20 of #347). Proposed replacements: negative regulation of DNA-templated transcription |
| GO:0035189 Rb-E2F complex | IPI PMID:16360038 Structure of the Rb C-terminal domain bound to E2F1-DP1: a m... | ACCEPT | Summary: IPI annotation for the Rb-E2F complex sourced from Rubin et al. 2005 (PMID:16360038, Cell), the landmark crystal structure of the Rb C-terminal domain (RbC) bound to the E2F1-DP1 heterodimer. The paper demonstrates a high-affinity RbC-E2F-DP interaction shared by all Rb and E2F family members and resolves an intertwined heterodimer in which the marked box domains of both E2F1 and DP1 contact RbC. This is direct structural evidence for the namesake Rb-E2F complex — the defining RB1 assembly already captured by core_functions[0] (in_complex: GO:0035189) and independently supported by the IBA GO:0035189 row ACCEPTed in batch 6 (which cites this same PMID:16360038 as its IPI anchor) and the parallel IEA Ensembl-Compara row ACCEPTed in PR #461. Reason: Canonical RB1 function — the Rb-E2F complex is the namesake of the RB1 mechanism and is directly demonstrated at atomic resolution by PMID:16360038 (Rubin et al. 2005 RbC-E2F1-DP1 crystal structure). Reinforces core_functions[0] (in_complex: GO:0035189) and is consistent with the IBA GO:0035189 row already ACCEPTed in batch 6 and the IEA row ACCEPTed in PR #461. PMID:16360038 (Rubin et al. 2005) canonical RB-E2F structural batch (batch 17 of #347). |
| GO:0005634 nucleus | EXP PMID:20940255 Acetylation of Rb by PCAF is required for nuclear localizati... | ACCEPT | Summary: EXP annotation for nuclear localization sourced from Pickard et al. 2010 (PMID:20940255), "Acetylation of Rb by PCAF is required for nuclear localization and keratinocyte differentiation." The paper directly characterizes RB1 nuclear localization and shows that PCAF-mediated acetylation of Rb is required for its retention in the nucleus during keratinocyte differentiation. Nuclear localization is the canonical compartment for active hypophosphorylated RB1 and is independently supported by 17 Reactome TAS rows on GO:0005654 nucleoplasm previously ACCEPTed (PR #444) and by IEA propagations ACCEPTed in PR #461. Reason: Canonical RB1 localization, directly characterized by the cited paper (PMID:20940255) — RB1 nuclear localization is the explicit subject of the Pickard et al. 2010 study. Also independently supported by 17 Reactome TAS nucleoplasm rows ACCEPTed in PR #444 and by canonical IEA propagations. Mechanical canonical-nuclear-localization batch (batch 10 of #347). |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation projected from mouse Rb1 (UniProtKB:P13405) via GO_REF:0000024 for cytoplasmic localization. Same biology as the parallel IEA GO_REF:0000120 cytoplasm row in this file: cytoplasmic localization is a real but conditional secondary state. UniProt P06400 CC SUBCELLULAR LOCATION records cytoplasmic localization "when hyperphosphorylated (By similarity)" plus PKP3 (Plakophilin 3) interaction-mediated sequestration (both By similarity from P13405); PMID:20940255 independently shows RB1 mislocalizes to the cytoplasm when not PCAF-acetylated during keratinocyte differentiation. Not the canonical Rb-E2F nuclear corepressor function captured by core_functions[0]. Reason: Cytoplasmic localization is a real but non-core secondary state — represents inactive/sequestered or apoptotic-context RB1, downstream of the defining nuclear Rb-E2F transcriptional corepressor activity already ACCEPTed (GO:0005634 nucleus IEA in batch 5; 17 Reactome TAS GO:0005654 nucleoplasm rows ACCEPTed in PR #444; PMID:20940255 EXP nuclear localization). Same precedent as the GO:0005819 spindle KEEP_AS_NON_CORE row in batch 15 (#551). Resolves both PENDING cytoplasm rows (IEA + ISS) in a single batch since they describe identical biology from parallel propagation routes. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | TAS PMID:19149898 The chromatin remodelling factor BRG1 is a novel binding par... | ACCEPT | Summary: TAS annotation citing Becker et al. 2009 (PMID:19149898), which reviews hypophosphorylated pRb as a Pol II transcriptional corepressor that silences E2F-target S-phase genes via the RB-E2F repressor complex (and recruits chromatin-modifying partners HDAC1, BRM, BRG1/SMARCA4). Negative regulation of Pol II transcription is a canonical core RB1 activity; already ACCEPTed elsewhere in this file via IEA (GO_REF:0000107) and supported by IDA evidence on PMID:7923370 and PMID:1531329. Reason: Negative regulation of Pol II transcription is one of the best-characterized RB1 activities and is consistent with the existing core_functions[0] block (E2F repression at S-phase promoters). PMID:19149898 explicitly describes pRb as forming "active pRb-E2F transcriptional repressor complexes that silence genes required for S-phase entry." Mechanical TAS batch (batch 9 of #347) — all 8 PMID:19149898 TAS rows describe canonical RB1 repressor/cell-cycle functions and are uniformly ACCEPTed in this batch. |
| GO:2000134 negative regulation of G1/S transition of mitotic cell cycle | TAS PMID:19149898 The chromatin remodelling factor BRG1 is a novel binding par... | ACCEPT | Summary: TAS annotation citing Becker et al. 2009 (PMID:19149898), which reviews the prototypical RB1 function at the G1/S restriction point — hypophosphorylated pRb sequesters E2F1/2/3 and prevents S-phase entry until inactivated by Cyclin D-CDK4/6 and Cyclin E-CDK2 phosphorylation. Negative regulation of G1/S is a canonical core RB1 activity, already captured elsewhere in this file via IBA (PR #490, GO_REF:0000033) and IEA propagation. Reason: Negative regulation of the G1/S transition is the defining RB1 tumor-suppressor activity, central to the existing core_functions[0] block. PMID:19149898 directly describes the CDK4/6/Cyclin D - pRb - E2F switch at the G1/S restriction point. Mechanical TAS batch (batch 9 of #347). |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-188386 | ACCEPT | Summary: TAS annotation for nucleoplasmic localization sourced from a Reactome pathway event. RB1 is a chromatin-bound nuclear corepressor that occupies E2F-target gene promoters in the nucleoplasm; nucleoplasmic localization of hypophosphorylated active RB1 is well established and is the compartment in which RB1 binds E2F1/2/3 and recruits chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4) (PMID:7923370; deep research synthesis). Reason: Nucleoplasmic localization is the canonical compartment for active hypophosphorylated RB1 and is well supported across the literature. Each of the 17 Reactome TAS events is a separate nucleoplasm annotation describing the same localization context, so they are mechanically consolidated to ACCEPT with a uniform template (BRAF PR #440 / KRAS PR #349 precedent for analogous Reactome TAS localization sweeps). |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-188390 | ACCEPT | Summary: TAS annotation for nucleoplasmic localization sourced from a Reactome pathway event. RB1 is a chromatin-bound nuclear corepressor that occupies E2F-target gene promoters in the nucleoplasm; nucleoplasmic localization of hypophosphorylated active RB1 is well established and is the compartment in which RB1 binds E2F1/2/3 and recruits chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4) (PMID:7923370; deep research synthesis). Reason: Nucleoplasmic localization is the canonical compartment for active hypophosphorylated RB1 and is well supported across the literature. Each of the 17 Reactome TAS events is a separate nucleoplasm annotation describing the same localization context, so they are mechanically consolidated to ACCEPT with a uniform template (BRAF PR #440 / KRAS PR #349 precedent for analogous Reactome TAS localization sweeps). |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-69227 | ACCEPT | Summary: TAS annotation for nucleoplasmic localization sourced from a Reactome pathway event. RB1 is a chromatin-bound nuclear corepressor that occupies E2F-target gene promoters in the nucleoplasm; nucleoplasmic localization of hypophosphorylated active RB1 is well established and is the compartment in which RB1 binds E2F1/2/3 and recruits chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4) (PMID:7923370; deep research synthesis). Reason: Nucleoplasmic localization is the canonical compartment for active hypophosphorylated RB1 and is well supported across the literature. Each of the 17 Reactome TAS events is a separate nucleoplasm annotation describing the same localization context, so they are mechanically consolidated to ACCEPT with a uniform template (BRAF PR #440 / KRAS PR #349 precedent for analogous Reactome TAS localization sweeps). |
| GO:0051276 chromosome organization | IMP PMID:20551165 Loss of pRB causes centromere dysfunction and chromosomal in... | KEEP AS NON CORE | Summary: IMP annotation from Manning et al. 2010 (PMID:20551165), which showed that pRB depletion compromises centromeric localization of CAP-D3/condensin II and chromosome cohesion, leading to merotelic attachment and chromosome missegregation. Real RB1 biology — RB1 loss undermines mitotic fidelity via condensin II / centromere effects — but this is a non-cell-cycle-arrest mitotic phenotype that is downstream of, and tangential to, RB1's defining function as the Rb-E2F transcriptional corepressor that enforces the G1/S restriction point. The Manning study explicitly frames this as separate from RB1's "best-known regulation of the G1/S-phase transition." Reason: RB1's contribution to mitotic centromere/cohesion fidelity (Manning 2010 PMID:20551165) is a real but non-core mitotic role that explains a downstream cancer consequence (CIN/aneuploidy in RB1-null tumors) rather than defining RB1's primary molecular activity. The canonical RB1 core function (Rb-E2F complex assembly, negative regulation of G1/S transition, chromatin-bound transcription corepression with HDAC1/SUV39H1/BRG1) is already captured by direct experimental evidence elsewhere in this file (PMID:7923370 IDA, PMID:16360038 IPI on GO:0035189). Mechanical PMID:20551165 single-paper batch (batch 11 of #347) — all 6 IMP rows from this paper consolidated to KEEP_AS_NON_CORE with a uniform template. |
| GO:0060090 molecular adaptor activity | EXP PMID:16360038 Structure of the Rb C-terminal domain bound to E2F1-DP1: a m... | ACCEPT | Summary: EXP annotation for molecular adaptor activity sourced from Rubin et al. 2005 (PMID:16360038, Cell). The crystal structure of RbC bound to E2F1-DP1 shows RbC forming an intertwined heterodimer that simultaneously contacts the marked box domains of both E2F1 and DP1, while the Rb pocket independently engages the E2F transactivation domain. RB1 thereby acts as a molecular adaptor/scaffold that bridges the activator E2F-DP heterodimer to the pocket and, in the cellular context, to recruited chromatin-modifying corepressors (HDAC1, SUV39H1, BRG1/SMARCA4) — the bridging architecture underpinning core_functions[0] (masking E2F transactivation domains and recruiting chromatin corepressors). Per CLAUDE.md curation guidelines, this informative adaptor MF term is preferred over the generic GO:0005515 protein binding rows uniformly demoted elsewhere in this file. Reason: Canonical RB1 scaffolding/adaptor molecular function, demonstrated by direct experimental (EXP) structural evidence in PMID:16360038 (Rubin et al. 2005): RbC simultaneously bridges the E2F1 and DP1 marked box domains, the structural basis for RB1 tethering activator E2F-DP heterodimers to the pocket and to recruited chromatin corepressors. Informative MF term preferred over generic protein binding per CLAUDE.md, and consistent with the bridging mechanism described in core_functions[0]. PMID:16360038 (Rubin et al. 2005) canonical RB-E2F structural batch (batch 17 of #347). |
| GO:0140297 DNA-binding transcription factor binding | IPI PMID:19223331 HMGB1 and HMGB2 proteins up-regulate cellular expression of ... | MARK AS OVER ANNOTATED | Summary: IPI annotation for DNA-binding transcription factor binding citing Stros et al. 2009 (PMID:19223331). In this study, GST pull-down and co-immunoprecipitation demonstrate a direct physical pRb-HMGB1 interaction, and ectopic pRb suppresses HMGB1/HMGB2-driven transactivation of the topo IIalpha (TOP2A) promoter by modulating NF-Y occupancy. RB1 binding DNA-binding transcription factors is a genuine RB1 molecular activity (canonically activator E2F1/2/3 via the RB_A/RB_B pocket, plus lineage-specific TFs), but the same biology is captured more specifically by GO:0061629 (RNA polymerase II-specific DNA-binding transcription factor binding), already ACCEPTed in this file, since every characterised RB1 TF partner (E2F1/2/3, RUNX2, AR, CEBPD, PU.1; and the Pol II-context HMGB1/NF-Y axis here) is Pol II-specific. Reason: Consistent with the established in-file decision on the GO:0140297 IEA row (GO_REF:0000107): GO:0140297 is the over-general parent of GO:0061629 (RNA polymerase II-specific DNA-binding transcription factor binding), which is ACCEPTed and captures the full scope of RB1's TF-binding biology. The parent adds no biological information beyond the ACCEPTed child, so the term is not wrong but represents an over-annotation. The PMID:19223331 pRb-HMGB1 interaction is a Pol II transcription-context interaction already covered by the child term. Mechanical binding-partner-MF batch (batch 22 of #347). |
| GO:0003714 transcription corepressor activity | TAS PMID:19149898 The chromatin remodelling factor BRG1 is a novel binding par... | ACCEPT | Summary: TAS annotation citing Becker et al. 2009 (PMID:19149898), which describes hypophosphorylated pRb as a transcriptional corepressor that represses E2F-target promoters via chromatin remodeling — including direct interactions with HDAC1, BRM, and the SWI/SNF catalytic subunit BRG1/SMARCA4. Transcription corepressor activity is a canonical RB1 MF activity already supported by IDA evidence elsewhere in this file. Reason: Transcription corepressor activity is one of the defining biochemical activities of RB1 at E2F-target promoters and is consistent with the existing core_functions[0] block. PMID:19149898 explicitly frames pRb as forming "transcriptional repressor complexes that silence genes required for S-phase entry." Mechanical TAS batch (batch 9 of #347). |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9659782 | ACCEPT | Summary: TAS annotation for nucleoplasmic localization sourced from a Reactome pathway event. RB1 is a chromatin-bound nuclear corepressor that occupies E2F-target gene promoters in the nucleoplasm; nucleoplasmic localization of hypophosphorylated active RB1 is well established and is the compartment in which RB1 binds E2F1/2/3 and recruits chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4) (PMID:7923370; deep research synthesis). Reason: Nucleoplasmic localization is the canonical compartment for active hypophosphorylated RB1 and is well supported across the literature. Each of the 17 Reactome TAS events is a separate nucleoplasm annotation describing the same localization context, so they are mechanically consolidated to ACCEPT with a uniform template (BRAF PR #440 / KRAS PR #349 precedent for analogous Reactome TAS localization sweeps). |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-113503 | ACCEPT | Summary: TAS annotation for nucleoplasmic localization sourced from a Reactome pathway event. RB1 is a chromatin-bound nuclear corepressor that occupies E2F-target gene promoters in the nucleoplasm; nucleoplasmic localization of hypophosphorylated active RB1 is well established and is the compartment in which RB1 binds E2F1/2/3 and recruits chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4) (PMID:7923370; deep research synthesis). Reason: Nucleoplasmic localization is the canonical compartment for active hypophosphorylated RB1 and is well supported across the literature. Each of the 17 Reactome TAS events is a separate nucleoplasm annotation describing the same localization context, so they are mechanically consolidated to ACCEPT with a uniform template (BRAF PR #440 / KRAS PR #349 precedent for analogous Reactome TAS localization sweeps). |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-187948 | ACCEPT | Summary: TAS annotation for nucleoplasmic localization sourced from a Reactome pathway event. RB1 is a chromatin-bound nuclear corepressor that occupies E2F-target gene promoters in the nucleoplasm; nucleoplasmic localization of hypophosphorylated active RB1 is well established and is the compartment in which RB1 binds E2F1/2/3 and recruits chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4) (PMID:7923370; deep research synthesis). Reason: Nucleoplasmic localization is the canonical compartment for active hypophosphorylated RB1 and is well supported across the literature. Each of the 17 Reactome TAS events is a separate nucleoplasm annotation describing the same localization context, so they are mechanically consolidated to ACCEPT with a uniform template (BRAF PR #440 / KRAS PR #349 precedent for analogous Reactome TAS localization sweeps). |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9687377 | ACCEPT | Summary: TAS annotation for nucleoplasmic localization sourced from a Reactome pathway event. RB1 is a chromatin-bound nuclear corepressor that occupies E2F-target gene promoters in the nucleoplasm; nucleoplasmic localization of hypophosphorylated active RB1 is well established and is the compartment in which RB1 binds E2F1/2/3 and recruits chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4) (PMID:7923370; deep research synthesis). Reason: Nucleoplasmic localization is the canonical compartment for active hypophosphorylated RB1 and is well supported across the literature. Each of the 17 Reactome TAS events is a separate nucleoplasm annotation describing the same localization context, so they are mechanically consolidated to ACCEPT with a uniform template (BRAF PR #440 / KRAS PR #349 precedent for analogous Reactome TAS localization sweeps). |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9851127 | ACCEPT | Summary: TAS annotation for nucleoplasmic localization sourced from a Reactome pathway event. RB1 is a chromatin-bound nuclear corepressor that occupies E2F-target gene promoters in the nucleoplasm; nucleoplasmic localization of hypophosphorylated active RB1 is well established and is the compartment in which RB1 binds E2F1/2/3 and recruits chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4) (PMID:7923370; deep research synthesis). Reason: Nucleoplasmic localization is the canonical compartment for active hypophosphorylated RB1 and is well supported across the literature. Each of the 17 Reactome TAS events is a separate nucleoplasm annotation describing the same localization context, so they are mechanically consolidated to ACCEPT with a uniform template (BRAF PR #440 / KRAS PR #349 precedent for analogous Reactome TAS localization sweeps). |
| GO:0005634 nucleus | TAS PMID:3657987 The retinoblastoma susceptibility gene encodes a nuclear pho... | ACCEPT | Summary: TAS annotation for nuclear localization sourced from Lee et al. 1987 Nature (PMID:3657987), the foundational paper that identified the retinoblastoma gene product as a nuclear phosphoprotein. The paper explicitly states that "biochemical fractionation and immunofluorescence studies demonstrate that the majority of the protein is located within the nucleus." This is the original characterization of RB1 as a nuclear protein and is independently corroborated by 17 Reactome TAS rows on GO:0005654 nucleoplasm previously ACCEPTed (PR #444), IDA evidence (PMID:17540172 in PR #499, PMID:1531329, PMID:20940255 in this batch), and canonical IEA propagations ACCEPTed in PR #461. Reason: Canonical RB1 localization established in the foundational Lee et al. 1987 Nature paper (PMID:3657987), which directly demonstrates nuclear localization by both biochemical fractionation and immunofluorescence. Nuclear localization is one of the defining features of RB1 from the moment the gene was cloned. Mechanical canonical-nuclear-localization batch (batch 10 of #347). |
| GO:0030308 negative regulation of cell growth | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation projected via UniProt/InterPro template (GO_REF:0000024) for negative regulation of cell growth, based on conservation of the RB pocket domain. RB1 is the prototypical pocket-protein antiproliferative tumor suppressor: hypophosphorylated RB1 binds activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket and represses S-phase gene transcription, restricting net cellular growth and proliferation (PMID:7923370; deep research synthesis). Already captured at higher specificity in this file via the GO:2000134 negative regulation of G1/S transition TAS row (PMID:19149898) ACCEPTed in batch 9. Reason: Canonical RB1 antiproliferative function, well supported by experimental evidence already present in this file (PMID:7923370 RB-BRG1 cooperation; IDA/EXP rows in this annotation set) and by independent Reactome TAS rows previously ACCEPTed in PRs #440/#444. Mechanical ISS-canonical batch (batch 14 of #347). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9660615 | KEEP AS NON CORE | Summary: TAS annotation for cytosolic localization sourced from a Reactome disease event ('Defective RB1 does not translocate to the nucleus') describing loss-of-function RB1 nonsense/frameshift/NLS-deletion mutants (e.g. RB1 R830_G887 / delEx24-25) that lack the bipartite C-terminal NLS (residues 860-876) and are retained in the cytosol (PMID:8413247 Zacksenhaus et al. 1993; PMID:9326330 Bremner et al. 1997). Wild-type RB1 is a nuclear chromatin-bound corepressor; cytosolic retention is restricted to NLS-loss tumor mutants and is therefore a pathological mislocalization rather than a constitutive cellular compartment for the wild-type protein. Reason: Real biology in a disease/mutant context (NLS-loss RB1 cancer mutants retained in the cytosol) but not a core wild-type RB1 localization. RB1's core compartment is the nucleus / nucleoplasm, where it carries out E2F repression and chromatin scaffolding (already ACCEPTed via the 17 R-HSA nucleoplasm TAS rows). Keeping on record at non-core priority is consistent with the analogous treatment of disease/ortholog-projected rows already in this file (e.g. PMID:24027266 GO:2001234 apoptosis row at line 1287 and PMID:19417128 GO:0120163 thermogenesis row at line 1296). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9659820 | KEEP AS NON CORE | Summary: TAS annotation for cytosolic localization sourced from the Reactome event 'RB1 translocates to the nucleus', which describes the bipartite C-terminal NLS-dependent (residues 860-876) translocation of RB1 from the cytosol to the nucleus (PMID:8413247 Zacksenhaus et al. 1993). In the absence of the NLS only a small portion of RB1 reaches the nucleus while a large portion is retained in the cytosol. Cytosolic localization is therefore a transient pre-import state and an NLS-loss-mutant pathological state, not the steady-state compartment for the active wild-type protein. Reason: Real biology in a disease/mutant context (NLS-loss RB1 cancer mutants retained in the cytosol) but not a core wild-type RB1 localization. RB1's core compartment is the nucleus / nucleoplasm, where it carries out E2F repression and chromatin scaffolding (already ACCEPTed via the 17 R-HSA nucleoplasm TAS rows). Keeping on record at non-core priority is consistent with the analogous treatment of disease/ortholog-projected rows already in this file (e.g. PMID:24027266 GO:2001234 apoptosis row at line 1287 and PMID:19417128 GO:0120163 thermogenesis row at line 1296). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9682712 | KEEP AS NON CORE | Summary: TAS annotation for cytosolic localization sourced from the Reactome event 'nsp15 binds RB1', which describes SARS-CoV-1 non-structural protein 15 (nsp15) binding RB1 via its LXCXE/D motif and retaining RB1 in the cytosol (PMID:22301140 Bhardwaj et al. 2012). This is a viral-hijack mislocalization context — wild-type RB1 in uninfected cells is a chromatin-bound nuclear corepressor; cytosolic retention here is driven by viral nsp15 sequestration rather than reflecting a constitutive RB1 compartment. Reason: Real biology in a disease/infection context (SARS-CoV-1 nsp15 sequesters wild-type RB1 in the cytosol via LXCXE/D-motif binding) but not a core wild-type RB1 localization in uninfected cells. RB1's core compartment is the nucleus / nucleoplasm, where it carries out E2F repression and chromatin scaffolding (already ACCEPTed via the 17 R-HSA nucleoplasm TAS rows). Keeping on record at non-core priority is consistent with the analogous treatment of disease/ortholog-projected rows already in this file (e.g. PMID:24027266 GO:2001234 apoptosis row at line 1287 and PMID:19417128 GO:0120163 thermogenesis row at line 1296). |
| GO:0045786 negative regulation of cell cycle | ISS PMID:24027266 MiR-26b, upregulated in Alzheimer's disease, activates cell ... | ACCEPT | Summary: ISS annotation citing PMID:24027266 (MiR-26b in Alzheimer's disease — miR-26b directly represses RB1 to drive cell-cycle re-entry in postmitotic neurons). The source paper's mechanism establishes RB1 as the canonical brake on cell-cycle progression: loss of RB1 via miR-26b targeting is sufficient to license aberrant cell-cycle re-entry. Negative regulation of cell cycle is the defining RB1 tumor-suppressor activity (PMID:7923370; deep research synthesis), already captured at higher specificity in this file via the GO:2000134 negative regulation of G1/S transition TAS row (PMID:19149898) ACCEPTed in batch 9 and the GO:0051726 regulation of cell cycle IEA row ACCEPTed in batch 5. Reason: Canonical RB1 cell-cycle-restriction function, well supported by experimental evidence already present in this file (PMID:7923370 RB-BRG1 cooperation; IDA/EXP rows in this annotation set) and by independent Reactome TAS rows previously ACCEPTed in PRs #440/#444. Mechanical ISS-canonical batch (batch 14 of #347). |
| GO:2001234 negative regulation of apoptotic signaling pathway | ISS PMID:24027266 MiR-26b, upregulated in Alzheimer's disease, activates cell ... | KEEP AS NON CORE | Summary: Downstream phenotype projected from mouse Rb1 ortholog: Rb1 affects apoptotic signaling sensitivity through E2F-target regulation (e.g. via BCL-2 family genes and cell-cycle/apoptosis crosstalk), but apoptotic-pathway regulation is a context-dependent consequence of RB1's core E2F-repression / chromatin-scaffolding role rather than a primary RB1 function. Reason: Real biology but a downstream / tissue-specific consequence of RB1's core role in E2F-mediated G1/S repression and chromatin scaffolding (RB_A/RB_B pocket binding, HDAC1/SUV39H1/BRG1 recruitment) rather than a primary RB1 function. Kept on record at non-core priority. These rows are mouse Rb1 phenotypes projected to human via Ensembl/PANTHER (IEA GO_REF:0000107) and InterPro/UniProt ISS templates (GO_REF:0000024, plus PMIDs 19417128 and 24027266) - same non-core treatment as analogous tissue-specific ortholog projections in prior reviews. |
| GO:0120163 negative regulation of cold-induced thermogenesis | ISS PMID:19417128 Haploinsufficiency of the retinoblastoma protein gene reduce... | KEEP AS NON CORE | Summary: Tissue-specific phenotype projected from mouse Rb1: Rb1 represses brown-adipocyte / thermogenic gene programs (Ucp1) in white adipose tissue (PMID:19417128), but cold-induced thermogenesis is a downstream metabolic consequence of RB1's role in adipocyte differentiation/transcription control rather than a core RB1 function. Reason: Real biology but a downstream / tissue-specific consequence of RB1's core role in E2F-mediated G1/S repression and chromatin scaffolding (RB_A/RB_B pocket binding, HDAC1/SUV39H1/BRG1 recruitment) rather than a primary RB1 function. Kept on record at non-core priority. These rows are mouse Rb1 phenotypes projected to human via Ensembl/PANTHER (IEA GO_REF:0000107) and InterPro/UniProt ISS templates (GO_REF:0000024, plus PMIDs 19417128 and 24027266) - same non-core treatment as analogous tissue-specific ortholog projections in prior reviews. |
| GO:0003180 aortic valve morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Tissue-specific developmental phenotype projected from mouse Rb1 ortholog: Rb1-null mouse hearts exhibit cardiac valve defects, but this is a downstream developmental consequence of Rb1's core role in E2F-mediated proliferation/differentiation control in cardiac neural crest and valvular interstitial cells, not a primary RB1 molecular function. Reason: Real biology but a downstream / tissue-specific consequence of RB1's core role in E2F-mediated G1/S repression and chromatin scaffolding (RB_A/RB_B pocket binding, HDAC1/SUV39H1/BRG1 recruitment) rather than a primary RB1 function. Kept on record at non-core priority. These rows are mouse Rb1 phenotypes projected to human via Ensembl/PANTHER (IEA GO_REF:0000107) and InterPro/UniProt ISS templates (GO_REF:0000024, plus PMIDs 19417128 and 24027266) - same non-core treatment as analogous tissue-specific ortholog projections in prior reviews. |
| GO:0050728 negative regulation of inflammatory response | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Downstream tissue-level phenotype projected from mouse Rb1 ortholog: Rb1 loss can increase tissue inflammation as part of the senescence-associated secretory phenotype (SASP) and altered chromatin programs, but inflammatory regulation is a contextual consequence of RB1's core E2F-repression / chromatin-scaffolding activity rather than a primary RB1 function. Reason: Real biology but a downstream / tissue-specific consequence of RB1's core role in E2F-mediated G1/S repression and chromatin scaffolding (RB_A/RB_B pocket binding, HDAC1/SUV39H1/BRG1 recruitment) rather than a primary RB1 function. Kept on record at non-core priority. These rows are mouse Rb1 phenotypes projected to human via Ensembl/PANTHER (IEA GO_REF:0000107) and InterPro/UniProt ISS templates (GO_REF:0000024, plus PMIDs 19417128 and 24027266) - same non-core treatment as analogous tissue-specific ortholog projections in prior reviews. |
| GO:1903055 positive regulation of extracellular matrix organization | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Downstream tissue-level phenotype projected from mouse Rb1 ortholog: Rb1 modulates ECM organization through transcriptional control of stromal/fibroblast programs, but ECM organization is a contextual consequence of RB1's core E2F-repression / chromatin-scaffolding role rather than a primary molecular function. Reason: Real biology but a downstream / tissue-specific consequence of RB1's core role in E2F-mediated G1/S repression and chromatin scaffolding (RB_A/RB_B pocket binding, HDAC1/SUV39H1/BRG1 recruitment) rather than a primary RB1 function. Kept on record at non-core priority. These rows are mouse Rb1 phenotypes projected to human via Ensembl/PANTHER (IEA GO_REF:0000107) and InterPro/UniProt ISS templates (GO_REF:0000024, plus PMIDs 19417128 and 24027266) - same non-core treatment as analogous tissue-specific ortholog projections in prior reviews. |
| GO:1904028 positive regulation of collagen fibril organization | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Downstream tissue-level phenotype projected from mouse Rb1 ortholog: Rb1 affects collagen-fibril organization via transcriptional regulation of stromal programs, but collagen-fibril organization is a contextual consequence of RB1's core role in cell-cycle / differentiation control rather than a primary molecular function. Reason: Real biology but a downstream / tissue-specific consequence of RB1's core role in E2F-mediated G1/S repression and chromatin scaffolding (RB_A/RB_B pocket binding, HDAC1/SUV39H1/BRG1 recruitment) rather than a primary RB1 function. Kept on record at non-core priority. These rows are mouse Rb1 phenotypes projected to human via Ensembl/PANTHER (IEA GO_REF:0000107) and InterPro/UniProt ISS templates (GO_REF:0000024, plus PMIDs 19417128 and 24027266) - same non-core treatment as analogous tissue-specific ortholog projections in prior reviews. |
| GO:1904761 negative regulation of myofibroblast differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Tissue-specific phenotype projected from mouse Rb1 ortholog: Rb1 restricts myofibroblast differentiation programs in fibrotic contexts, but this is a downstream cell-fate consequence of RB1's core E2F-repression / chromatin-scaffolding role rather than a primary molecular function. Reason: Real biology but a downstream / tissue-specific consequence of RB1's core role in E2F-mediated G1/S repression and chromatin scaffolding (RB_A/RB_B pocket binding, HDAC1/SUV39H1/BRG1 recruitment) rather than a primary RB1 function. Kept on record at non-core priority. These rows are mouse Rb1 phenotypes projected to human via Ensembl/PANTHER (IEA GO_REF:0000107) and InterPro/UniProt ISS templates (GO_REF:0000024, plus PMIDs 19417128 and 24027266) - same non-core treatment as analogous tissue-specific ortholog projections in prior reviews. |
| GO:0005634 nucleus | NAS PMID:2730637 Homology between a region of the human retinoblastoma gene a... | ACCEPT | Summary: NAS annotation for nuclear localization derived from Taya et al. 1989 (PMID:2730637), a paper primarily about homology between the RB1 gene and L1 family repetitive sequences. The paper discusses DNA-binding properties of RB1 (which implicitly involves nuclear localization) but does not directly characterize subcellular localization. The NAS evidence is weak as a primary source, but the annotated function (nuclear localization) is independently and robustly supported by IDA evidence (PMID:1531329, PMID:20940255, PMID:17540172), TAS evidence (PMID:3657987 — the original Lee et al. 1987 nuclear-phosphoprotein paper), and 17 Reactome TAS rows on GO:0005654 nucleoplasm previously ACCEPTed (PR #444). Reason: The underlying annotation (nuclear localization) is one of the most robustly established RB1 facts, independently supported by multiple IDA/EXP/TAS rows from the foundational literature. The specific NAS source (PMID:2730637) is weak provenance individually, but consistent with the broader literature and not biologically wrong. Mechanical canonical-nuclear-localization batch (batch 10 of #347). |
| GO:0006355 regulation of DNA-templated transcription | NAS PMID:2730637 Homology between a region of the human retinoblastoma gene a... | MODIFY | Summary: NAS annotation derived from Taya et al. 1989 (PMID:2730637), a paper about homology between a region of the RB1 gene and L1-family repetitive sequences that only speculatively "discusses" possible DNA-binding properties of RB1; it does not characterize RB1 transcriptional regulation. The NAS source is therefore weak provenance for this term individually (the same weak-NAS PMID:2730637 situation was handled for the adjacent nuclear-localization row in batch 10). However, the underlying function — RB1 repression of E2F-dependent, DNA-templated transcription — is one of the most robustly established RB1 facts (core_functions[0]) and is directionally negative. The generic GO:0006355 is too broad; the specific child GO:0045892 (negative regulation of DNA-templated transcription) is the curation-preferred term and is independently supported by IDA/TAS evidence elsewhere in this file (PMID:1531329, PMID:12065415, PMID:10783144, PMID:19223331, PMID:19149898). Reason: Essence (RB1 regulates DNA-templated transcription) is sound and canonical, but the NAS source is a sequence-homology paper and the generic GO:0006355 is too broad for RB1's well-established negative/repressor activity. Replace with the specific GO:0045892 (negative regulation of DNA-templated transcription) already present in core_functions[0]; conservative MODIFY rather than REMOVE, consistent with the batch-10 handling of the weak-NAS PMID:2730637 localization row. Mechanical transcription-regulation batch (batch 20 of #347). Proposed replacements: negative regulation of DNA-templated transcription |
| GO:0061676 importin-alpha family protein binding | IPI PMID:12695505 Structural basis for the specificity of bipartite nuclear lo... | KEEP AS NON CORE | Summary: IPI annotation for importin-alpha family protein binding sourced from Fontes et al. 2003 (PMID:12695505). This study co-crystallized mammalian importin-alpha with a peptide corresponding to the bipartite nuclear localization sequence of human retinoblastoma protein, defining the structural basis by which importin-alpha specifically recognizes the RB1 NLS. This is genuine, specific (informative) evidence that RB1 binds the importin-alpha nuclear-import receptor. Reason: RB1-importin-alpha binding is correctly and specifically supported by the PMID:12695505 co-crystal structure and is informative rather than generic protein binding, but it represents the nuclear-import transport mechanism that delivers RB1 to its compartment rather than the defining nuclear E2F-corepressor / chromatin-scaffold activity in core_functions[0]. Kept on record at non-core priority, consistent with the file's treatment of localization/transport mechanisms (e.g., GO:0005737 cytoplasm KEEP_AS_NON_CORE) relative to the core corepressor function. Mechanical binding-partner-MF batch (batch 22 of #347). |
| GO:0005654 nucleoplasm | IDA PMID:8245034 Structural and functional characterization of the HPV16 E7 p... | ACCEPT | Summary: IDA annotation for nucleoplasmic localization sourced from Pahel et al. 1993 (PMID:8245034), an HPV16 E7 biochemistry paper. E7 is a "nuclear phosphoprotein" that binds RB1 "avidly and specifically" and can dissociate the E2F transcription factor from RB1 in vitro. The biochemistry of the E7–RB1 interaction is performed on nuclear RB1, supporting RB1 nucleoplasmic localization. Nucleoplasmic localization is the canonical compartment for active hypophosphorylated RB1 and is independently supported by 17 Reactome TAS rows on GO:0005654 already ACCEPTed (PR #444), by IDA evidence (PMID:17540172 in PR #499, GO_REF:0000052 HPA in this batch), and by canonical IEA propagations ACCEPTed in PR #461. Reason: Canonical RB1 nucleoplasmic localization, well supported by experimental evidence already present in this file (17 Reactome TAS rows ACCEPTed in PR #444; IDA from PMID:17540172 ACCEPTed in PR #499). The E7-RB1 interaction characterized in PMID:8245034 is well established to occur in the nucleus where RB1 binds chromatin. Mechanical canonical-nuclear-localization batch (batch 10 of #347). |
| GO:0035189 Rb-E2F complex | IDA PMID:8245034 Structural and functional characterization of the HPV16 E7 p... | ACCEPT | Summary: Pahel et al. 1993 (PMID:8245034) characterizes purified HPV16 E7 and shows it "binds the retinoblastoma protein avidly and specifically, and it can dissociate the E2F transcription factor when assayed in vitro." Demonstrating that E7 dissociates E2F from RB1 directly evidences the pre-existing RB1-E2F complex. The Rb-E2F complex is the namesake, canonical RB1 mechanism: the RB_A/RB_B pocket engages activator E2F1/2/3 to occupy E2F target promoters (PMID:7923370; deep research synthesis). This exact GO:0035189 term is already independently ACCEPTed on IBA (GO_REF:0000033, batch 6), IPI (PMID:16360038, batch 17), and IEA (PR #461) evidence elsewhere in this file. Reason: Canonical core RB1 function — the Rb-E2F complex is the defining RB1 mechanism, independently and robustly supported across IBA/IPI/IEA evidence already ACCEPTed on this exact term in this file. Same canonical-Rb-E2F ACCEPT precedent as the batch-17 PMID:16360038 structural rows. Mechanical canonical-Rb-E2F batch (batch 19 of #347). |
| GO:0097718 disordered domain specific binding | IPI PMID:8245034 Structural and functional characterization of the HPV16 E7 p... | MARK AS OVER ANNOTATED | Summary: Pahel et al. 1993 (PMID:8245034) is an HPV16 E7 biochemistry paper showing E7 (an intrinsically disordered viral oncoprotein) binds RB1 and dissociates E2F. GO:0097718 disordered domain specific binding is a generic, uninformative binding term that does not capture RB1's specific LxCxE-cleft / RB_A-RB_B pocket adapter biology, and the paper does not set out to characterize RB1's binding specificity for disordered domains as such. The informative interaction from this paper is already captured by the ACCEPTed GO:0035189 (Rb-E2F complex) row from the same reference. Reason: Generic, uninformative binding term for RB1's well-characterized adapter/scaffolding biology, derived from an HPV E7 biochemistry paper rather than a study of RB1 disordered-domain binding specificity. Conservative demotion consistent with the uniform GO:0005515 protein-binding precedent in this same review and the batch-18 PMID:16360038 generic-binding handling (GO:0042802 / GO:0051219). Mechanical generic-binding batch (batch 19 of #347). |
| GO:0010629 negative regulation of gene expression | IMP PMID:25100735 Post-transcriptional gene expression control by NANOS is up-... | ACCEPT | Summary: IMP annotation from Miles et al. 2014 (PMID:25100735), which shows that NANOS (NANOS1/NANOS3) "is directly repressed by pRb/E2F in flies and humans." siRNA depletion of the pocket proteins (including pRb) from human BJ fibroblasts produced "a strong up-regulation in the expression of the NANOS1 and NANOS3 genes," and ChIP showed that dREAM (E2F4/p107/p130) occupancy at the NANOS1 promoter is pRb-dependent. This is direct functional (IMP) evidence that RB1 negatively regulates target-gene expression — a canonical instance of RB1's defining transcriptional corepressor activity (core_functions[0]), concordant with the GO:0045892 IDA/TAS rows ACCEPTed elsewhere in this file (PMID:12065415, PMID:10783144, PMID:19223331, PMID:19149898). Reason: Canonical RB1 transcriptional repressor activity — pRb directly represses NANOS1/3 expression (IMP via pocket-protein depletion plus dREAM-promoter ChIP). Maps to core_functions[0] (Rb-E2F transcriptional corepressor) and is independently supported by the GO:0045892 negative-regulation rows already ACCEPTed in this file. Mechanical transcription-regulation batch (batch 20 of #347). |
| GO:2000679 positive regulation of transcription regulatory region DNA binding | IDA PMID:25100735 Post-transcriptional gene expression control by NANOS is up-... | KEEP AS NON CORE | Summary: IDA annotation from Miles et al. 2014 (PMID:25100735). ChIP experiments show that pRb stabilizes binding of the dREAM repressor components (E2F4, p107, p130) at the NANOS1 promoter: "these observations suggest that pRb stabilizes dREAM-binding to the NANOS1 promoter," and "the binding of these dREAM components to the NANOS1 promoter was dramatically reduced by knockdown of pRb." This biologically supports GO:2000679 (RB1 positively regulating occupancy of a transcription regulatory region by the repressor complex); the finding is correct and not an over-annotation. However, it describes a fine-grained downstream mechanistic consequence of RB1's repressor scaffold rather than RB1's core function; the core activity (transcriptional corepression / negative regulation of DNA-templated transcription) is already captured in core_functions[0]. Reason: Biologically correct and IDA-supported (pRb stabilizes dREAM/E2F4 occupancy at the NANOS1 promoter), but a specific mechanistic detail of the repressor-scaffold mechanism rather than a core RB1 function. Retain as non-core; the core repressor activity is represented by core_functions[0] and the GO:0045892 rows. Mechanical transcription-regulation batch (batch 20 of #347). |
| GO:0005515 protein binding | IPI PMID:12037672 Physical interaction between pRb and cdk9/cyclinT2 complex. | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0008024 cyclin/CDK positive transcription elongation factor complex | IDA PMID:12037672 Physical interaction between pRb and cdk9/cyclinT2 complex. | MARK AS OVER ANNOTATED | Summary: IDA cellular-component annotation citing Simone et al. 2002 (PMID:12037672), "Physical interaction between pRb and cdk9/cyclinT2 complex." That paper demonstrates an in vitro and in vivo physical interaction between pRb (C-terminal domain, residues 835-928) and the cdk9/cyclinT2 complex, and maps cdk9-mediated phosphorylation of the pRb C-terminus (S795/S807/S811). pRb is thus an interactor and phosphorylation substrate of cdk9/cyclinT2 (P-TEFb), not a constitutive structural subunit of the cyclin/CDK positive transcription elongation factor complex (GO:0008024). The authors themselves describe pRb and cdk9/cyclinT2 as "located in a nuclear multiprotein complex," i.e. a transient/regulatory association, which does not establish stable membership of the P-TEFb elongation factor complex itself. Reason: The cited evidence supports a physical interaction with and phosphorylation by cdk9/cyclinT2, but a CC complex-membership term (GO:0008024) implies pRb is a stable subunit of P-TEFb, which the source does not establish — pRb is a substrate/interactor, not a core subunit. Conservative demotion (the association is real, so not REMOVE) consistent with the in-file handling of interaction-derived over-specific terms (e.g. the GO:0042802/PMID:16360038 batch-17 demotion). The genuine pRb-cdk9 interaction is better represented as a binding/phospho-substrate relationship than as P-TEFb complex membership. |
| GO:0005515 protein binding | IPI PMID:15107404 Liver tumors escape negative control of proliferation via PI... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-188191 | ACCEPT | Summary: TAS annotation for nucleoplasmic localization sourced from a Reactome pathway event. RB1 is a chromatin-bound nuclear corepressor that occupies E2F-target gene promoters in the nucleoplasm; nucleoplasmic localization of hypophosphorylated active RB1 is well established and is the compartment in which RB1 binds E2F1/2/3 and recruits chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4) (PMID:7923370; deep research synthesis). Reason: Nucleoplasmic localization is the canonical compartment for active hypophosphorylated RB1 and is well supported across the literature. Each of the 17 Reactome TAS events is a separate nucleoplasm annotation describing the same localization context, so they are mechanically consolidated to ACCEPT with a uniform template (BRAF PR #440 / KRAS PR #349 precedent for analogous Reactome TAS localization sweeps). |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-2172666 | ACCEPT | Summary: TAS annotation for nucleoplasmic localization sourced from a Reactome pathway event. RB1 is a chromatin-bound nuclear corepressor that occupies E2F-target gene promoters in the nucleoplasm; nucleoplasmic localization of hypophosphorylated active RB1 is well established and is the compartment in which RB1 binds E2F1/2/3 and recruits chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4) (PMID:7923370; deep research synthesis). Reason: Nucleoplasmic localization is the canonical compartment for active hypophosphorylated RB1 and is well supported across the literature. Each of the 17 Reactome TAS events is a separate nucleoplasm annotation describing the same localization context, so they are mechanically consolidated to ACCEPT with a uniform template (BRAF PR #440 / KRAS PR #349 precedent for analogous Reactome TAS localization sweeps). |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9018017 | ACCEPT | Summary: TAS annotation for nucleoplasmic localization sourced from a Reactome pathway event. RB1 is a chromatin-bound nuclear corepressor that occupies E2F-target gene promoters in the nucleoplasm; nucleoplasmic localization of hypophosphorylated active RB1 is well established and is the compartment in which RB1 binds E2F1/2/3 and recruits chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4) (PMID:7923370; deep research synthesis). Reason: Nucleoplasmic localization is the canonical compartment for active hypophosphorylated RB1 and is well supported across the literature. Each of the 17 Reactome TAS events is a separate nucleoplasm annotation describing the same localization context, so they are mechanically consolidated to ACCEPT with a uniform template (BRAF PR #440 / KRAS PR #349 precedent for analogous Reactome TAS localization sweeps). |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9659820 | ACCEPT | Summary: TAS annotation for nucleoplasmic localization sourced from a Reactome pathway event. RB1 is a chromatin-bound nuclear corepressor that occupies E2F-target gene promoters in the nucleoplasm; nucleoplasmic localization of hypophosphorylated active RB1 is well established and is the compartment in which RB1 binds E2F1/2/3 and recruits chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4) (PMID:7923370; deep research synthesis). Reason: Nucleoplasmic localization is the canonical compartment for active hypophosphorylated RB1 and is well supported across the literature. Each of the 17 Reactome TAS events is a separate nucleoplasm annotation describing the same localization context, so they are mechanically consolidated to ACCEPT with a uniform template (BRAF PR #440 / KRAS PR #349 precedent for analogous Reactome TAS localization sweeps). |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9686969 | ACCEPT | Summary: TAS annotation for nucleoplasmic localization sourced from a Reactome pathway event. RB1 is a chromatin-bound nuclear corepressor that occupies E2F-target gene promoters in the nucleoplasm; nucleoplasmic localization of hypophosphorylated active RB1 is well established and is the compartment in which RB1 binds E2F1/2/3 and recruits chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4) (PMID:7923370; deep research synthesis). Reason: Nucleoplasmic localization is the canonical compartment for active hypophosphorylated RB1 and is well supported across the literature. Each of the 17 Reactome TAS events is a separate nucleoplasm annotation describing the same localization context, so they are mechanically consolidated to ACCEPT with a uniform template (BRAF PR #440 / KRAS PR #349 precedent for analogous Reactome TAS localization sweeps). |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9686980 | ACCEPT | Summary: TAS annotation for nucleoplasmic localization sourced from a Reactome pathway event. RB1 is a chromatin-bound nuclear corepressor that occupies E2F-target gene promoters in the nucleoplasm; nucleoplasmic localization of hypophosphorylated active RB1 is well established and is the compartment in which RB1 binds E2F1/2/3 and recruits chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4) (PMID:7923370; deep research synthesis). Reason: Nucleoplasmic localization is the canonical compartment for active hypophosphorylated RB1 and is well supported across the literature. Each of the 17 Reactome TAS events is a separate nucleoplasm annotation describing the same localization context, so they are mechanically consolidated to ACCEPT with a uniform template (BRAF PR #440 / KRAS PR #349 precedent for analogous Reactome TAS localization sweeps). |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9768288 | ACCEPT | Summary: TAS annotation for nucleoplasmic localization sourced from a Reactome pathway event. RB1 is a chromatin-bound nuclear corepressor that occupies E2F-target gene promoters in the nucleoplasm; nucleoplasmic localization of hypophosphorylated active RB1 is well established and is the compartment in which RB1 binds E2F1/2/3 and recruits chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4) (PMID:7923370; deep research synthesis). Reason: Nucleoplasmic localization is the canonical compartment for active hypophosphorylated RB1 and is well supported across the literature. Each of the 17 Reactome TAS events is a separate nucleoplasm annotation describing the same localization context, so they are mechanically consolidated to ACCEPT with a uniform template (BRAF PR #440 / KRAS PR #349 precedent for analogous Reactome TAS localization sweeps). |
| GO:0005654 nucleoplasm | TAS Reactome:R-NUL-8985474 | ACCEPT | Summary: TAS annotation for nucleoplasmic localization sourced from a Reactome pathway event. RB1 is a chromatin-bound nuclear corepressor that occupies E2F-target gene promoters in the nucleoplasm; nucleoplasmic localization of hypophosphorylated active RB1 is well established and is the compartment in which RB1 binds E2F1/2/3 and recruits chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4) (PMID:7923370; deep research synthesis). Reason: Nucleoplasmic localization is the canonical compartment for active hypophosphorylated RB1 and is well supported across the literature. Each of the 17 Reactome TAS events is a separate nucleoplasm annotation describing the same localization context, so they are mechanically consolidated to ACCEPT with a uniform template (BRAF PR #440 / KRAS PR #349 precedent for analogous Reactome TAS localization sweeps). |
| GO:0005654 nucleoplasm | TAS Reactome:R-NUL-8985490 | ACCEPT | Summary: TAS annotation for nucleoplasmic localization sourced from a Reactome pathway event. RB1 is a chromatin-bound nuclear corepressor that occupies E2F-target gene promoters in the nucleoplasm; nucleoplasmic localization of hypophosphorylated active RB1 is well established and is the compartment in which RB1 binds E2F1/2/3 and recruits chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4) (PMID:7923370; deep research synthesis). Reason: Nucleoplasmic localization is the canonical compartment for active hypophosphorylated RB1 and is well supported across the literature. Each of the 17 Reactome TAS events is a separate nucleoplasm annotation describing the same localization context, so they are mechanically consolidated to ACCEPT with a uniform template (BRAF PR #440 / KRAS PR #349 precedent for analogous Reactome TAS localization sweeps). |
| GO:0005515 protein binding | IPI PMID:7651420 Characterization of a novel 350-kilodalton nuclear phosphopr... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0045892 negative regulation of DNA-templated transcription | IDA PMID:12065415 Prohibitin requires Brg-1 and Brm for the repression of E2F ... | ACCEPT | Summary: IDA annotation supporting RB1's canonical role as a negative regulator of DNA-templated transcription, sourced from the Prohibitin/Brg-1/Brm paper (PMID:12065415) which directly shows that pRb-mediated repression of E2F-target gene promoters and the resulting cell-growth suppression require the SWI/SNF chromatin remodelers BRG1/SMARCA4 and BRM. Negative regulation of DNA-templated transcription is RB1's defining transcriptional activity at E2F-target promoters (PMID:7923370; deep research synthesis), already captured in core_functions[0] (Rb-E2F transcriptional corepressor) and independently supported by TAS PMID:19149898 (ACCEPTed in batch 9 of #347). Reason: Canonical RB1 corepressor activity, well anchored to the pRb-E2F repressor model and to RB1's SWI/SNF (BRG1/BRM) chromatin-remodeler partnership already supported elsewhere in this file (GO:0006338 chromatin remodeling TAS PMID:19149898 ACCEPTed, GO:0016514 SWI/SNF complex TAS ACCEPTed). The PMID:12065415 paper provides direct experimental evidence (IDA) for pRb-mediated repression at E2F-target promoters via prohibitin/SWI/SNF cooperation. Mechanical canonical-corepressor IDA batch (batch 13 of #347) — 3 IDA rows on GO:0045892 from primary literature uniformly consolidated to ACCEPT. |
| GO:0007346 regulation of mitotic cell cycle | IMP PMID:20551165 Loss of pRB causes centromere dysfunction and chromosomal in... | KEEP AS NON CORE | Summary: IMP annotation from Manning et al. 2010 (PMID:20551165), which showed that pRB depletion slows mitotic progression and promotes aneuploidy through compromised centromere function and chromosome cohesion (CAP-D3/condensin II mislocalization, merotelic attachment, lagging chromosomes). Real RB1 biology — RB1 loss alters mitotic timing/fidelity — but this is a non-cell-cycle-arrest mitotic phenotype downstream of RB1's primary G1/S corepressor activity, and "regulation of mitotic cell cycle" is a very broad parent term that does not capture the specific Manning et al. mitotic-fidelity mechanism. Reason: RB1's contribution to mitotic centromere/cohesion fidelity (Manning 2010 PMID:20551165) is a real but non-core mitotic role that explains a downstream cancer consequence (CIN/aneuploidy in RB1-null tumors) rather than defining RB1's primary molecular activity. The canonical RB1 core function (Rb-E2F complex assembly, negative regulation of G1/S transition, chromatin-bound transcription corepression with HDAC1/SUV39H1/BRG1) is already captured by direct experimental evidence elsewhere in this file (PMID:7923370 IDA, PMID:16360038 IPI on GO:0035189). Mechanical PMID:20551165 single-paper batch (batch 11 of #347) — all 6 IMP rows from this paper consolidated to KEEP_AS_NON_CORE with a uniform template. |
| GO:0031134 sister chromatid biorientation | IMP PMID:20551165 Loss of pRB causes centromere dysfunction and chromosomal in... | KEEP AS NON CORE | Summary: IMP annotation from Manning et al. 2010 (PMID:20551165), which showed that pRB depletion causes merotelic kinetochore-microtubule attachments and failure of chromosome congression — the cellular consequence of compromised centromere/cohesion architecture (CAP-D3/condensin II mislocalization, increased intercentromeric distance). Sister chromatid biorientation defects directly explain the lagging chromosomes and missegregation phenotype reported in the paper. Real RB1 biology but a non-core mitotic-fidelity role rather than RB1's defining transcriptional corepressor activity. Reason: RB1's contribution to mitotic centromere/cohesion fidelity (Manning 2010 PMID:20551165) is a real but non-core mitotic role that explains a downstream cancer consequence (CIN/aneuploidy in RB1-null tumors) rather than defining RB1's primary molecular activity. The canonical RB1 core function (Rb-E2F complex assembly, negative regulation of G1/S transition, chromatin-bound transcription corepression with HDAC1/SUV39H1/BRG1) is already captured by direct experimental evidence elsewhere in this file (PMID:7923370 IDA, PMID:16360038 IPI on GO:0035189). Mechanical PMID:20551165 single-paper batch (batch 11 of #347) — all 6 IMP rows from this paper consolidated to KEEP_AS_NON_CORE with a uniform template. |
| GO:0034088 maintenance of mitotic sister chromatid cohesion | IMP PMID:20551165 Loss of pRB causes centromere dysfunction and chromosomal in... | KEEP AS NON CORE | Summary: IMP annotation from Manning et al. 2010 (PMID:20551165), which directly showed that pRB depletion compromises centromeric chromosome cohesion (increased intercentromeric distance, deformed centromeric structure) via mislocalization of CAP-D3/condensin II. The paper explicitly identifies cohesion maintenance at centromeres as a function disrupted by pRB loss. Real RB1 biology — RB1 is required for maintenance of mitotic centromere cohesion via the condensin II pathway — but this is a non-core mitotic-fidelity role rather than RB1's defining transcriptional corepressor activity. Reason: RB1's contribution to mitotic centromere/cohesion fidelity (Manning 2010 PMID:20551165) is a real but non-core mitotic role that explains a downstream cancer consequence (CIN/aneuploidy in RB1-null tumors) rather than defining RB1's primary molecular activity. The canonical RB1 core function (Rb-E2F complex assembly, negative regulation of G1/S transition, chromatin-bound transcription corepression with HDAC1/SUV39H1/BRG1) is already captured by direct experimental evidence elsewhere in this file (PMID:7923370 IDA, PMID:16360038 IPI on GO:0035189). Mechanical PMID:20551165 single-paper batch (batch 11 of #347) — all 6 IMP rows from this paper consolidated to KEEP_AS_NON_CORE with a uniform template. |
| GO:0045842 positive regulation of mitotic metaphase/anaphase transition | IMP PMID:20551165 Loss of pRB causes centromere dysfunction and chromosomal in... | KEEP AS NON CORE | Summary: IMP annotation from Manning et al. 2010 (PMID:20551165), which showed that pRB-depleted cells experience mitotic delay with lagging chromosomes following compromised centromere cohesion and merotelic attachment. The "positive regulation of metaphase/anaphase transition" framing reflects the paper's observation that loss of pRB impairs timely progression through metaphase/anaphase due to faulty kinetochore-microtubule attachments and the resulting spindle checkpoint engagement. Real RB1 biology — RB1 supports timely metaphase-to-anaphase progression by maintaining the centromere/cohesion architecture required for proper kinetochore attachment — but this is a non-core mitotic-fidelity role rather than RB1's defining transcriptional corepressor activity. Reason: RB1's contribution to mitotic centromere/cohesion fidelity (Manning 2010 PMID:20551165) is a real but non-core mitotic role that explains a downstream cancer consequence (CIN/aneuploidy in RB1-null tumors) rather than defining RB1's primary molecular activity. The canonical RB1 core function (Rb-E2F complex assembly, negative regulation of G1/S transition, chromatin-bound transcription corepression with HDAC1/SUV39H1/BRG1) is already captured by direct experimental evidence elsewhere in this file (PMID:7923370 IDA, PMID:16360038 IPI on GO:0035189). Mechanical PMID:20551165 single-paper batch (batch 11 of #347) — all 6 IMP rows from this paper consolidated to KEEP_AS_NON_CORE with a uniform template. |
| GO:0071459 protein localization to chromosome, centromeric region | IMP PMID:20551165 Loss of pRB causes centromere dysfunction and chromosomal in... | KEEP AS NON CORE | Summary: IMP annotation from Manning et al. 2010 (PMID:20551165), which directly showed that pRB depletion compromises centromeric localization of CAP-D3/condensin II — the most specific molecular finding of the paper and the mechanistic basis for the downstream cohesion/segregation defects. RB1 is required for proper recruitment of the condensin II complex to centromeric chromatin. Real RB1 biology — RB1 supports centromeric protein localization via condensin II recruitment — but this is a non-core mitotic-fidelity role rather than RB1's defining transcriptional corepressor activity. Reason: RB1's contribution to mitotic centromere/cohesion fidelity (Manning 2010 PMID:20551165) is a real but non-core mitotic role that explains a downstream cancer consequence (CIN/aneuploidy in RB1-null tumors) rather than defining RB1's primary molecular activity. The canonical RB1 core function (Rb-E2F complex assembly, negative regulation of G1/S transition, chromatin-bound transcription corepression with HDAC1/SUV39H1/BRG1) is already captured by direct experimental evidence elsewhere in this file (PMID:7923370 IDA, PMID:16360038 IPI on GO:0035189). Mechanical PMID:20551165 single-paper batch (batch 11 of #347) — all 6 IMP rows from this paper consolidated to KEEP_AS_NON_CORE with a uniform template. |
| GO:0005515 protein binding | IPI PMID:20870719 Methylation of the retinoblastoma tumor suppressor by SMYD2. | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:16964284 Prohibitin, a protein downregulated by androgens, represses ... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:11571652 The de-ubiquitinating enzyme Unp interacts with the retinobl... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:10613832 Reduced stability of retinoblastoma protein by gankyrin, an ... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0045892 negative regulation of DNA-templated transcription | IDA PMID:19223331 HMGB1 and HMGB2 proteins up-regulate cellular expression of ... | ACCEPT | Summary: IDA annotation supporting RB1's canonical role as a negative regulator of DNA-templated transcription, sourced from the HMGB1/HMGB2 topoisomerase IIalpha paper (PMID:19223331) which characterizes pRb-mediated repression of the human topoisomerase IIalpha promoter and the antagonistic activity of HMGB1/HMGB2 on this repression. The paper provides direct experimental evidence (IDA) for pRb-mediated repression of an endogenous promoter. Negative regulation of DNA-templated transcription is RB1's defining transcriptional activity (PMID:7923370; deep research synthesis), already captured in core_functions[0] (Rb-E2F transcriptional corepressor) and independently supported by TAS PMID:19149898 (ACCEPTed in batch 9 of #347). Reason: Canonical RB1 corepressor activity demonstrated by direct experimental evidence (IDA) on an endogenous target promoter (TOP2A). PMID:19223331 frames pRb as a repressor of the human topoisomerase IIalpha promoter that HMGB1/HMGB2 counteract. Consistent with RB1's defining corepressor activity already captured by core_functions[0] and supported by TAS PMID:19149898 (ACCEPTed in batch 9 of #347) and analogous IDA/IMP rows elsewhere in this file. Mechanical canonical-corepressor IDA batch (batch 13 of #347) — 3 IDA rows on GO:0045892 from primary literature uniformly consolidated to ACCEPT. |
| GO:0005515 protein binding | IPI PMID:7503932 Dual retinoblastoma-binding proteins with properties related... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0007265 Ras protein signal transduction | IEP PMID:9054499 Oncogenic ras provokes premature cell senescence associated ... | REMOVE | Summary: IEP annotation citing Serrano et al. 1997 (PMID:9054499), "Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a." That paper establishes that oncogenic RAS induces a permanent G1 arrest (oncogene-induced senescence) accompanied by accumulation of p53 and p16INK4a, with p16/p53 inactivation preventing the arrest. RB1 is not characterized in this study as a Ras-pathway transducer; its only relationship to this work is as a downstream effector of the p16INK4a-CDK4/6 arm engaged during RAS-induced senescence. GO:0007265 Ras protein signal transduction denotes the small-GTPase Ras signaling relay itself (GEF/GAP/effector cascade), of which RB1 is categorically not a member. Reason: Categorical functional-class mismatch: RB1 is a chromatin-bound transcriptional corepressor / G1-S effector, not a component or regulator of the Ras GTPase signal-transduction cascade (GO:0007265). The IEP source (PMID:9054499) is a p16/p53 oncogene-induced-senescence paper that does not interrogate RB1's role in Ras signaling at all. Per the schema, a wrong functional class (REMOVE, "unlikely to be correct based on combined evidence") is distinct from over-granularity (MARK_AS_OVER_ANNOTATED); this is the former, following the in-file batch-22 GO:0031625/PMID:10944455 REMOVE precedent for an evidence-class mismatch. RB1's genuine downstream role in RAS/oncogene-induced senescence would belong as a senescence/cell-cycle annotation with its own source, not as Ras signal transduction. |
| GO:0005515 protein binding | IPI PMID:15542589 LIM domains-containing protein 1 (LIMD1), a tumor suppressor... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:10783144 Identification of a novel partner of RNA polymerase II subun... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0045892 negative regulation of DNA-templated transcription | IDA PMID:10783144 Identification of a novel partner of RNA polymerase II subun... | ACCEPT | Summary: IDA annotation supporting RB1's canonical role as a negative regulator of DNA-templated transcription, sourced from the Che-1/AATF paper (PMID:10783144) — "Identification of a novel partner of RNA polymerase II subunit 11, Che-1, which interacts with and affects the growth suppression function of Rb." The paper demonstrates pRb's growth-suppression activity at Pol II-driven gene programs and shows that Che-1 (AATF, the human Bfr2 homolog) modulates this activity through its interaction with Rb. Negative regulation of DNA-templated transcription is RB1's defining transcriptional activity (PMID:7923370; deep research synthesis), already captured in core_functions[0] (Rb-E2F transcriptional corepressor) and independently supported by TAS PMID:19149898 (ACCEPTed in batch 9 of #347). Reason: Canonical RB1 corepressor activity demonstrated by direct experimental evidence (IDA) on Pol II-driven growth-suppression promoter activity, in the context of the Che-1/AATF interaction with Rb. Consistent with RB1's defining corepressor activity already captured by core_functions[0] and supported by TAS PMID:19149898 (ACCEPTed in batch 9 of #347) and analogous IDA rows on this term elsewhere in this file. Mechanical canonical-corepressor IDA batch (batch 13 of #347) — 3 IDA rows on GO:0045892 from primary literature uniformly consolidated to ACCEPT. |
| GO:0051219 phosphoprotein binding | IPI PMID:16360038 Structure of the Rb C-terminal domain bound to E2F1-DP1: a m... | MARK AS OVER ANNOTATED | Summary: Rubin et al. 2005 (PMID:16360038, Cell) demonstrates that CDK phosphorylation of RB1 itself drives E2F release: phosphorylation at S788/S795 directly destabilizes one set of RbC-E2F-DP contacts, while phosphorylation at T821/T826 induces an intramolecular RbC-pocket interaction that destabilizes the remaining contacts. RB1 is the phosphoprotein in this mechanism and phosphorylation promotes dissociation; the paper does not show RB1 binding to a phosphorylated partner protein. GO:0051219 phosphoprotein binding (binding a phosphorylated protein) is therefore not supported by this evidence and mischaracterizes the phospho-regulation-of-RB1 / E2F-release mechanism the paper actually establishes. Reason: The cited paper characterizes phosphorylation OF RB1 driving E2F release, the opposite of RB1 binding a phosphoprotein partner; the term is unsupported by this source. Conservative demotion consistent with the GO:0005515 precedent in this review and the batch-17 handling of PMID:16360038. |
| GO:0045445 myoblast differentiation | IMP PMID:15541338 Regulation of Rb gene expression by an MBD2-interacting zinc... | KEEP AS NON CORE | Summary: IMP annotation citing Sekimata & Homma 2004 (PMID:15541338), "Regulation of Rb gene expression by an MBD2-interacting zinc finger protein MIZF during myogenic differentiation." The study shows MIZF represses Rb transcription; forced MIZF expression in C2C12 myoblasts lowers Rb (and myogenin/Troponin-T) and blocks differentiation into multinucleated myotubes, indicating that induction of Rb expression is required for myogenic differentiation. RB1's pro-differentiation role in the myogenic lineage is well established (deep research synthesis; corroborated by PMID:9448006 discussion noting nonphosphorylated pRB promotes myocyte differentiation). The evidence here is somewhat indirect (it manipulates MIZF rather than RB1 directly), but the conclusion that Rb is needed for myoblast differentiation is consistent with the broader literature. Reason: RB1's role in myoblast/myogenic differentiation is real and literature-supported but is a lineage-specific developmental context downstream of the defining Rb-E2F cell-cycle-exit/transcriptional-corepressor activity (core_functions[0]; ACCEPTed GO:0051726, GO:0045892 rows), not a core molecular function. Retained on record as non-core, consistent with the GO:0032502 developmental process KEEP_AS_NON_CORE decision in this batch and the broader non-core differentiation/senescence framing in the deep research synthesis. |
| GO:0005515 protein binding | IPI PMID:17540172 L3MBTL1, a histone-methylation-dependent chromatin lock. | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0031625 ubiquitin protein ligase binding | IPI PMID:10944455 RBP95, a novel leucine zipper protein, binds to the retinobl... | REMOVE | Summary: IPI annotation for ubiquitin protein ligase binding citing Wen & Ao 2000 (PMID:10944455). That paper characterizes RBP95, a novel 838-residue basic-region leucine-zipper protein that binds pRb through a conserved LXCXE motif engaging the entire pocket region, and proposes RBP95 functions in RNA polymerase II-mediated transcription/processing. RBP95 is not a ubiquitin protein ligase and the study describes no ubiquitin-ligase activity, ubiquitination, or E3-ligase interaction; the cited evidence therefore does not support the term GO:0031625 ubiquitin protein ligase binding. Reason: The cited source does not support GO:0031625: PMID:10944455 (Wen & Ao 2000) characterizes RBP95, an LXCXE-motif basic-region leucine-zipper transcription-associated partner with no ubiquitin-ligase activity, RING/HECT domain, or ubiquitination assay. The evidence gap is categorical (a bZIP transcription partner vs. a ubiquitin protein ligase are unrelated functional classes), not a matter of over-granularity, so per the schema this is REMOVE ("unlikely to be correct based on combined evidence") rather than MARK_AS_OVER_ANNOTATED ("not entirely wrong... over-annotation"). This differs from the in-file GO:0042802/PMID:16360038 precedent, where the evidence was within the correct functional class but heterotypic rather than homotypic (a scope issue). If separate evidence exists that RB1 binds a ubiquitin ligase, it belongs as a new annotation with its own source. Mechanical binding-partner-MF batch (batch 22 of #347). |
| GO:0006338 chromatin remodeling | TAS PMID:19149898 The chromatin remodelling factor BRG1 is a novel binding par... | ACCEPT | Summary: TAS annotation citing Becker et al. 2009 (PMID:19149898), which describes pRb-mediated chromatin remodeling at E2F-target promoters via recruitment of BRM, BRG1/SMARCA4 (SWI/SNF catalytic subunit), and HDAC1. Chromatin remodeling is a canonical RB1 BP activity supported by extensive primary literature (PMID:7923370; deep research synthesis). Reason: Chromatin remodeling via SWI/SNF and histone-deacetylase recruitment is a canonical mechanism for RB1-mediated E2F repression. PMID:19149898 directly states pRb "can repress gene transcription at least partly by remodelling chromatin structure through its interactions with proteins such as HDAC1, BRM and BRG1." Mechanical TAS batch (batch 9 of #347). |
| GO:0016514 SWI/SNF complex | TAS PMID:19149898 The chromatin remodelling factor BRG1 is a novel binding par... | ACCEPT | Summary: TAS annotation citing Becker et al. 2009 (PMID:19149898), which describes RB1 association with the SWI/SNF chromatin-remodeling complex via the catalytic subunits BRM and BRG1/SMARCA4. The RB1-BRG1 interaction recruits SWI/SNF to E2F-responsive promoters to enhance pRb transcriptional repressor activity (cited refs 4 and 5 in Becker et al.). Reason: RB1's recruitment of SWI/SNF to E2F-target chromatin is one of the canonical chromatin-coregulator interactions for RB1, with direct biochemical support across multiple primary papers. PMID:19149898 explicitly describes "BRG1, as the catalytic core of the SWI/SNF chromatin remodelling complex, the interaction between BRG1 and pRb was proposed to recruit the complex to E2F responsive promoters." Mechanical TAS batch (batch 9 of #347). |
| GO:0035189 Rb-E2F complex | TAS PMID:19149898 The chromatin remodelling factor BRG1 is a novel binding par... | ACCEPT | Summary: TAS annotation citing Becker et al. 2009 (PMID:19149898), which describes "active pRb-E2F transcriptional repressor complexes that silence genes required for S-phase entry." Rb-E2F complex membership is the defining biochemical complex for RB1's tumor-suppressor function and is already independently captured in this file by IBA (PR #490) and IPI (PMID:8245034) evidence. Reason: Rb-E2F complex membership is the defining biochemical complex for RB1's tumor-suppressor activity at the G1/S restriction point. PMID:19149898 directly anchors this annotation to the active pRb-E2F repressor complex framework. Mechanical TAS batch (batch 9 of #347). |
| GO:0045892 negative regulation of DNA-templated transcription | TAS PMID:19149898 The chromatin remodelling factor BRG1 is a novel binding par... | ACCEPT | Summary: TAS annotation citing Becker et al. 2009 (PMID:19149898), which reviews pRb as a transcriptional corepressor that silences E2F-target genes via chromatin remodeling. Negative regulation of DNA-templated transcription is the general BP parent of the canonical pRb-E2F repression activity (GO:0000122 is the Pol II-specific child) and is already supported by IDA evidence on PMID:12065415 and PMID:10783144 elsewhere in this file. Reason: Negative regulation of DNA-templated transcription is a canonical RB1 activity, well anchored to the pRb-E2F repressor model that PMID:19149898 reviews. Mechanical TAS batch (batch 9 of #347). |
| GO:0051726 regulation of cell cycle | TAS PMID:19149898 The chromatin remodelling factor BRG1 is a novel binding par... | ACCEPT | Summary: TAS annotation citing Becker et al. 2009 (PMID:19149898), which reviews the canonical p16INK4a–Cyclin D-CDK4/6–pRb–E2F G1/S switch. Regulation of cell cycle is a canonical RB1 BP, already captured in this file via IEA propagation (GO_REF:0000120) and by multiple direct experimental rows on G1/S regulators. Reason: Regulation of the cell cycle is one of the defining RB1 tumor-suppressor functions, central to the existing core_functions[0] block (G1/S restriction). PMID:19149898 directly anchors RB1 to the canonical CDK4/6-cyclin D-pRb-E2F G1/S switch. Mechanical TAS batch (batch 9 of #347). |
| GO:0005515 protein binding | IPI PMID:11073990 A novel Rb- and p300-binding protein inhibits transactivatio... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0005515 protein binding | IPI PMID:9448006 The promyelocytic leukemia gene product (PML) forms stable c... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0016605 PML body | IDA PMID:9448006 The promyelocytic leukemia gene product (PML) forms stable c... | KEEP AS NON CORE | Summary: IDA annotation citing Alcalay et al. 1998 (PMID:9448006), "The promyelocytic leukemia gene product (PML) forms stable complexes with the retinoblastoma protein." By immunofluorescence the authors directly demonstrate that endogenous nonphosphorylated (hypophosphorylated) pRB colocalizes with PML within PML nuclear bodies (NBs), and that PML and pRB form stable complexes in vivo via the pRB pocket region; PML-RARalpha expression delocalizes pRB from the NBs. This is direct experimental evidence (IDA) for localization of a fraction of hypophosphorylated pRB to PML bodies. PML-NB localization is a specific subnuclear context linked to growth suppression / differentiation / senescence, distinct from the canonical nucleoplasmic E2F-target-promoter localization that constitutes RB1's core compartment. Reason: Directly demonstrated (IDA) localization of hypophosphorylated pRB to PML nuclear bodies is real but represents a specialized, low-stoichiometry (~0.5-1%) subnuclear pool in a growth-suppressive/differentiation context, not the canonical nucleoplasmic compartment where active RB1 occupies E2F-target promoters (captured by the ACCEPTed GO:0005654 nucleoplasm Reactome TAS rows). Retained as a real non-core localization, same precedent as the GO:0005819 spindle (batch 15, #551) and GO:0005737 cytoplasm KEEP_AS_NON_CORE rows. |
| GO:0005515 protein binding | IPI PMID:9395244 Phosphorylated retinoblastoma protein stimulates DNA polymer... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0019900 kinase binding | IDA PMID:16286473 The retinoblastoma family proteins bind to and activate diac... | KEEP AS NON CORE | Summary: IDA annotation for kinase binding sourced from Los et al. 2006 (PMID:16286473, J Biol Chem). The paper demonstrates that hypophosphorylated pRB binds directly to the lipid kinase diacylglycerol kinase zeta (DGKzeta) in vitro and in vivo (pRB had previously been shown to bind phosphatidylinositol-4-phosphate 5-kinases), with binding dependent on pRB phosphorylation status [PMID:16286473 "DGKzeta ... interacts with pRB in vitro and in vivo. Binding of DGKzeta to pRB is dependent on the phosphorylation status of pRB, since only hypophosphorylated pRB interacts with DGKzeta"]. GO:0019900 is appropriately informative and preferred over the generic GO:0005515 protein binding rows uniformly demoted elsewhere in this file, and the direct binding is well supported. This lipid-kinase effector interaction is a peripheral, non-core relationship — RB1's core molecular function is E2F-DP pocket binding and chromatin-corepressor recruitment (core_functions[0]), not lipid-signaling enzyme binding. Reason: Direct, phosphorylation-dependent pRB–DGKzeta binding is well supported by IDA evidence in PMID:16286473, and GO:0019900 (kinase binding) is appropriately informative (preferred over generic protein binding per CLAUDE.md). Retained as non-core because the DGKzeta/lipid-kinase interaction is a downstream effector relationship peripheral to RB1's canonical E2F-pocket/chromatin tumor-suppressor function. Kinase-interaction cluster (batch 21 of #347). |
| GO:0043550 regulation of lipid kinase activity | IDA PMID:16286473 The retinoblastoma family proteins bind to and activate diac... | MODIFY | Summary: IDA annotation for regulation of lipid kinase activity sourced from Los et al. 2006 (PMID:16286473, J Biol Chem). The paper shows that pRB (and the related pocket proteins p107 and p130) specifically and potently STIMULATE the activity of the lipid kinase DGKzeta in vitro [PMID:16286473 "we found that pRB, p107, and p130 potently stimulate DGKzeta activity in vitro"], proposing DGKzeta as a downstream effector of pRB that regulates nuclear diacylglycerol/phosphatidic acid levels. The recorded term GO:0043550 (regulation of lipid kinase activity) is directionally unspecified and therefore too general for this evidence, which demonstrates positive regulation/stimulation specifically. This is a peripheral, non-core lipid-signaling effector role rather than RB1's canonical E2F/cell-cycle function. Reason: Essence (RB1 regulates a lipid kinase) is sound and supported by IDA in PMID:16286473, but the data specifically show stimulation/activation of DGKzeta, so the directionally-neutral GO:0043550 is too general. Replace with the specific child GO:0090218 (positive regulation of lipid kinase activity); conservative MODIFY rather than ACCEPT-as-is, consistent with the batch-20 handling of the over-general GO:0006355 transcription row. Non-core lipid-signaling effector role. Kinase-interaction cluster (batch 21 of #347). Proposed replacements: positive regulation of lipid kinase activity |
| GO:0005515 protein binding | IPI PMID:9858607 Rb inhibits the intrinsic kinase activity of TATA-binding pr... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation records a physical interaction (IPI) but uses the uninformative generic term GO:0005515. RB1 has dozens of well-characterized binding partners — activator E2Fs (E2F1/2/3) via the RB_A/RB_B pocket, chromatin corepressors (HDAC1, SUV39H1, BRG1/SMARCA4, DNA methyltransferases), DNA repair factors (Ku70/Ku80), and lineage-specific transcription cofactors (RUNX2, AR, CEBPD, PU.1) — and specific MF terms should be preferred per CLAUDE.md curation guidelines. Reason: Generic 'protein binding' is uninformative for RB1's well-characterized adapter/scaffolding biology. Same precedent as BAG3 (#313) and KRAS (#349) where all GO:0005515 IPI rows were uniformly demoted. |
| GO:0006469 negative regulation of protein kinase activity | IPI PMID:9858607 Rb inhibits the intrinsic kinase activity of TATA-binding pr... | KEEP AS NON CORE | Summary: IPI annotation for negative regulation of protein kinase activity sourced from Siegert & Robbins 1999 (PMID:9858607, Mol Cell Biol). The large pocket of Rb binds directly to the TFIID subunit TAFII250 (TAF1) and dose-responsively inhibits its intrinsic, bipartite kinase activity — both TAFII250 autophosphorylation and transphosphorylation of the RAP74 subunit of TFIIF [PMID:9858607 "Rb is able to inhibit the kinase activity of immunopurified and gel-purified recombinant TAFII250. Rb inhibits the autophosphorylation of TAFII250 as well as its phosphorylation of the RAP74 subunit of TFIIF in a dose-responsive manner"]. Tumor-derived Rb pocket mutants are functionally defective for this kinase inhibition despite retaining binding [PMID:9858607 "two different tumor-derived Rb pocket mutants, C706F and Deltaex22, are functionally defective for kinase inhibition, even though they are able to bind the amino terminus of TAFII250"], linking the activity to the tumor-suppressor pocket. GO:0006469 is well supported and specific. The authors frame this as a novel, promoter-context-specific transcriptional-regulation mechanism — a peripheral facet rather than RB1's canonical E2F-masking/chromatin-corepressor core function. Reason: Direct, dose-responsive Rb inhibition of TAFII250 (TAF1) kinase activity is well supported in PMID:9858607, and GO:0006469 (negative regulation of protein kinase activity) is specific and accurate. Retained as non-core because the authors frame it as a novel, promoter-specific accessory mechanism of transcriptional repression, distinct from RB1's canonical E2F-pocket/chromatin-corepressor core function (core_functions[0]). Kinase-interaction cluster (batch 21 of #347). |
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