CBFB

Summary: Mouse-ortholog evidence supports context-specific transcriptional repression by RUNX–CBFB complexes.

Reason: The Q08024 transfer is compatible with the actual Cbfb conditional deletion and re-expression experiments in PMID:18258917. Those experiments connect Cbfb-containing complexes with repression of the Th-POK program. This is a lineage-specific output of the cofactor, rather than evidence that CBFB is an autonomous DNA-binding repressor.

Summary: Retain the curated mouse-derived negative transcriptional regulation assertion.

Reason: The source-specific ISS assertion is supported by Cbfb loss and rescue in the mouse T-cell study, with anti-Cbfβ chromatin association at the relevant locus. Human transfer is retained with the developmental context explicit; the direct DNA-contacting component remains RUNX.

Summary: CBFB contributes to Vif-dependent APOBEC polyubiquitination through ubiquitin-ligase-complex assembly.

Reason: PMID:22190036 directly reports that CBFB is required for Vif association with CUL5, APOBEC3G polyubiquitination and degradation in the tested viral system, while Vif–APOBEC association is preserved. The complementary structural study supports a stabilizing assembly role. This is participation as a cofactor in a hijacked complex, not intrinsic ubiquitin-ligase catalysis or a general requirement for all CUL5 substrates.

Summary: Unqualified intrinsic DNA binding exceeds the established CBFB mechanism.

Reason: The official DNA-binding definition concerns selective noncovalent interaction with DNA. Human structural and biochemical evidence identifies CBFB as the non-DNA-contacting subunit that stabilizes RUNX DNA binding. The rat-derived electronic assertion lacks the contributes_to flag present in the separate sequence-specific DNA-binding assertions. Those weaker complex contributions are retained; this unqualified activity is excessive.

Summary: The PAINT coactivator assertion captures the conserved RUNX cofactor mechanism.

Reason: CBFB binding stabilizes the RUNX DNA-binding conformation and supports transcription of selected RUNX targets. Human structural, enhancer and knockdown studies substantiate this activity. The IBA represents a curated ancestral placement, not a donor-count test; the Drosophila descendant evidence does not make it a speculative one-to-one transfer.

Summary: Retain the domain-based transcription coactivator activity assignment.

Reason: The InterPro mapping agrees with the demonstrated CBFB–RUNX complex and target-gene activation. The official coactivator definition accommodates a cofactor that binds a DNA-binding transcription factor. It does not require CBFB to contact DNA itself or imply that every RUNX-associated promoter is activated.

Summary: The human RUNX1–CBFB structure supports DNA-binding transcription factor binding.

Reason: PMID:10856244 resolves the interface between human RUNX1 Runt-domain and CBFB fragments. This directly supports CBFB binding to a DNA-binding transcription factor. Crystal contacts and a fragment complex do not establish every full-length cellular assembly state, but the partner's functional identity is unambiguous.

Proposed replacements: DNA-binding transcription factor binding

Summary: RUNX1 allosteric regulation provides a more informative binding activity.

Reason: The cited structural and biochemical work demonstrates CBFB interaction with the RUNX1 Runt domain and its effect on the DNA-binding conformation. DNA-binding transcription factor binding describes the activity of CBFB; DNA contact and the reported ionic effects on the Runt-domain system are not reassigned as intrinsic CBFB activities.

Proposed replacements: DNA-binding transcription factor binding

Summary: The co-immunoprecipitation experiment substantiates CBFB binding to RUNX1.

Reason: The actual PMID:17431401 Results explicitly assay Flag-Runx1 and CBFβ in 293T cells and retain their association in the presence of Cdk6. The Methods identify a mouse Runx1 cDNA; the assay is not described as an exclusively human recombinant pair. The conserved association and independent human structure support the more informative transcription-factor-binding term without attributing CDK6 kinase activity to CBFB.

Proposed replacements: DNA-binding transcription factor binding

Summary: Retain the reported CBFB–MAP2 interaction as a qualified non-core association.

Reason: The preserved IPI partner is P11137/MAP2 from the mRNA-display interaction-region screen. The exact pair is independently corroborated in the archived UniProt interaction section. Its original fragment coordinates and validation subset were not authenticated here; the global verification rate is not a pair-specific control. No microtubule activity or direct cellular mechanism is inferred from this association.

Summary: Retain the reported CBFB–INTS13 interaction with screen-specific limits.

Reason: The source partner Q9NVM9/INTS13 is corroborated by the archived UniProt interaction record. The original source describes mRNA-display interaction regions, but exact target coordinates and individual validation were not independently established. This supports a bounded association under the project policy, not assignment of Integrator enzymatic activity or membership in every Integrator complex.

Summary: Endogenous CBFB–RUNX2 association supports DNA-binding transcription factor binding.

Reason: PMID:20591170 reports RUNX2 immunoprecipitation with CBFB detection in human MDA-MB-231 extracts, including IgG and input controls. CBFB depletion affects selected RUNX2 targets, while chromatin association does not guarantee activation of every bound promoter. Refine the generic interaction to the demonstrated transcription-factor partner class.

Proposed replacements: DNA-binding transcription factor binding

Summary: CBFB associates with HIV-1 Vif in a virus-recruited ubiquitin-ligase assembly.

Reason: The Vif interaction is supported by the cited functional work and the later pentameric structure. This is a non-core viral co-option of the host protein. A virus-specific association does not establish a general CBFB enzymatic function, and no narrower binding term is invented solely from the viral partner.

Summary: The Vif–CBFB structural interface supports a non-core viral-protein association.

Reason: PMID:24402281 directly resolves the Vif-containing CUL5–ELOB–ELOC–CBFB assembly. Vif binds CBFB through a surface that overlaps RUNX recognition. This explains competitive viral recruitment without making CBFB a ubiquitin ligase or a constitutive component of all CUL5 complexes.

Summary: Wild-type CBFB–RUNX1 controls support transcription-factor binding independently of the oncogenic fusion.

Reason: The full primary Results compare endogenous RUNX1 association with CBFβ-SMMHC and wild-type CBFβ in human ME-1 cells. The selective inhibitor preferentially dissociates the fusion complex while leaving the wild-type association largely intact. Thus the source assays wild-type CBFB as well as the fusion; refine its binding term without transferring the fusion's leukemia phenotype to normal CBFB.

Proposed replacements: DNA-binding transcription factor binding

Summary: The RUNX1 partner is plausible, but the exact PMID:2845103 citation provenance remains unresolved.

Reason: The cached abstract foregrounds bacterial adenylate kinase and cannot establish what the original curator or database record linked to this interaction. The exact IntAct publication record was inaccessible. Independent human RUNX1–CBFB structural evidence corroborates the pair, but it does not justify silently replacing this machine citation with PMID:10856244 or declaring a wrong-gene error from the abstract alone.

Summary: Retain the HuRI association with the exact RUNX1-8 partner.

Reason: The source-specific isoform accession is preserved. The curated interaction and archived UniProt record corroborate the pair, which is also consistent with established RUNX binding. Exact screen orientation, construct coverage and target-specific orthogonal validation were not authenticated; no isoform-exclusive mechanism is claimed.

Summary: Retain the HuRI association with RUNX3-2 as a qualified interaction.

Reason: The exact Q13761-2 partner is preserved and agrees with the archived UniProt interaction record. Independent RUNX3 binding assays support the general pair. Neither those assays nor the high-throughput provenance establishes that the interaction is unique to this isoform, and its original HuRI target controls remain uninspected.

Summary: Retain the BioPlex CBFB–RUNX1 coassociation without treating it as an isolated direct-binding assay.

Reason: The AP-MS source assertion agrees with archived UniProt and independent structural evidence for the pair. The selected canonical cache is partial; exact target bait orientation and quantitative controls were not independently recovered. The narrower core binding activity is supported elsewhere, while this individual screen annotation remains qualified non-core.

Summary: Retain the BioPlex CBFB–RUNX3 association with target-table limits.

Reason: The exact RUNX3 partner is independently corroborated by UniProt and direct cellular interface experiments. AP-MS can recover a co-complex association and the original screen's target controls were not read from the partial canonical source. No additional catalytic or DNA-contacting role follows from this row.

Summary: Retain the BioPlex CBFB–RUNX2 association as contextual interaction evidence.

Reason: The archived interaction record and independent endogenous RUNX2 co-immunoprecipitation substantiate the biological pair. The original BioPlex quantitative target entry was not independently authenticated. Preserve the non-core screen assertion without claiming a direct interface was resolved by that screen.

Summary: Retain the breast-cell AP-MS association between CBFB and RUNX1.

Reason: The source reports affinity-purification interaction networks in three human breast cell lines. This exact pair is corroborated by UniProt and separate structural work; the original bait-specific quantitative table was not independently inspected. The screen does not by itself establish a new breast-cancer process performed by CBFB.

Summary: Retain the breast-cell AP-MS association with RUNX2.

Reason: The machine partner and archived interaction record agree, and independent endogenous human breast-cell co-immunoprecipitation supports the pair. The exact original screen's target scores remain uninspected, so retain bounded coassociation without inferring a new disease-specific mechanism.

Summary: Retain the chromosome-21 screen's RUNX1 interaction with explicit access limits.

Reason: The canonical source is abstract-only and describes a human-brain-library yeast-two-hybrid screen. Although this exact source's target construct and confirmation are unavailable, archived UniProt and direct structural studies independently substantiate the RUNX1–CBFB pair. Retain a qualified generic association; the paper's neurological context is not a CBFB neuronal function assertion.

Summary: Nuclear localization supports the principal transcriptional-cofactor role.

Reason: The electronic cellular-component assignment agrees with archived UniProt and directly assayed nuclear CBFB in human cells, including controlled nuclear-extract immunoblots and promoter-associated complexes. Nuclear localization does not exclude cytoplasmic or viral-recruited pools.

Summary: Retain the ortholog-derived nucleus annotation with independent human support.

Reason: The conserved nuclear cofactor mechanism is directly consistent with human nuclear extracts and chromatin-associated RUNX–CBFB complexes. This source row is retained independently of the electronic duplicate; duplication of location across evidence types is legitimate.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The event explicitly assembles the RUNX1–CBFB heterodimer and distinguishes RUNX1 DNA contact from the CBFB cofactor. Its projected nucleoplasmic location agrees with independent human nuclear and promoter-associated CBFB evidence. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The event describes CBFB binding the RUNX3 Runt domain. The curated nucleoplasm assertion agrees with human nuclear RUNX–CBFB complexes; its developmental and cancer context does not establish additional CBFB process terms. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: KMT2A is modeled binding RUNX1 with or without CBFB. Retain the nucleoplasmic component location with independent nuclear CBFB support, without requiring CBFB for every KMT2A association or transferring methyltransferase activity. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The FOXP3-promoter event explicitly includes the RUNX1–CBFB complex. This is consistent with nucleoplasmic cofactor localization; RUNX1 supplies the DNA-binding interface. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The summary describes RUNX1–FOXP3 binding and does not independently assay CBFB. The source annotation is a curated event-component location, supported by separate human nuclear CBFB evidence; no direct CBFB–FOXP3 interface is inferred. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The IL2-promoter model contains RUNX1–CBFB and NFATC2. Retain the nucleoplasmic cofactor location, without attributing NFAT DNA recognition or every immune response to CBFB. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The IL2 event explicitly retains CBFB in the FOXP3/RUNX1/NFAT assembly. This supports the modeled nuclear context, while the individual promoter contacts belong to the DNA-binding factors. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The IFNG promoter event includes the RUNX1–CBFB heterodimer. Its nucleoplasm projection agrees with the established nuclear cofactor role and does not assert autonomous CBFB promoter recognition. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: FOXP3 associates with the RUNX1–CBFB complex at the IFNG promoter in the model. Retain the existing nucleoplasmic location without converting this event context into an additional CBFB immune-process annotation. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The modeled RUNX1–CBFB complex occupies the first IL2RA intron. This is a nuclear chromatin context compatible with independent CBFB localization, not a direct CBFB DNA-contact claim. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The IL2RA intronic event contains FOXP3-bound RUNX1–CBFB. The summary's possible NFATC2 participation remains provisional; the accepted annotation concerns nucleoplasm only. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The CTLA4-promoter event explicitly contains the RUNX1–CBFB complex. The curated nucleoplasm assertion agrees with nuclear cofactor evidence; promoter specificity is supplied by the associated DNA-binding proteins. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The FOXP3/RUNX1–CBFB CTLA4-promoter assembly provides the modeled nuclear context. Probable NFAT association is not treated as an established direct CBFB interaction. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The TNFRSF18 promoter/intron event includes RUNX1–CBFB. Retain nucleoplasmic localization without attributing the receptor's signaling activity to its transcriptional cofactor. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The TNFRSF18 intronic assembly contains FOXP3 and RUNX1–CBFB; its nuclear location is compatible with independent CBFB evidence. The stated possible NFAT involvement is not upgraded. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The RSPO3 promoter event explicitly includes RUNX1–CBFB and FOXP3. Retain the location, without treating CBFB as the encoded WNT ligand or adding WNT pathway activity from a target gene's role. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The RUNX2–SMAD1 event places the assembly in the nucleus but calls CBFB association presumptive. Independent human nuclear CBFB evidence supports the location; SMAD/EP300 phosphorylation and acetylation are not CBFB activities. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The summary describes RUNX2–SMAD1 at the SMAD6 promoter, rather than a target-specific CBFB assay. Retain the curated nucleoplasm projection with independent localization support, without asserting direct CBFB–SMAD binding. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: HIPK2 acts on RUNX1 and EP300 in a RUNX1–CBFB complex. The accepted annotation is the cofactor's nucleoplasmic location; kinase and acetyltransferase chemistry belong to the named enzymes. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The HIPK2 event follows RUNX1–CBFB formation. Nuclear localization is appropriate, while the phosphorylation sites and kinase activity are RUNX1/HIPK2 properties rather than CBFB catalysis. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: EP300 associates with the RUNX1–CBFB complex in the transcriptional model. Retain the nucleoplasmic location; the summary does not make CBFB an acetyltransferase. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The model contains RUNX1–CBFB associated with ESR1. Its nuclear complex context agrees with CBFB's cofactor role, without assigning estrogen sensing or receptor activity to CBFB. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The GPAM enhancer summary specifies RUNX1/ESR1 DNA occupancy rather than an independent CBFB assay. The existing component-localization projection is consistent with separate nuclear CBFB evidence; GPAM metabolic activity is not transferred. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The KCTD6 enhancer event supplies a RUNX1/ESR1 regulatory context. Retain the projected nucleoplasmic CBFB location while separating curated complex inclusion from directly assayed CBFB occupancy. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: RUNX1 and ESR1 are modeled at the AXIN1 intron. The source's nucleoplasm projection is compatible with independent CBFB localization; the summary does not itself demonstrate direct CBFB DNA contact. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: Both general and placental LIFR promoters are modeled with RUNX1–CBFB. Retain the nuclear cofactor location without inferring a placental-specific CBFB mechanism or receptor activity. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The event describes PRMT1 methylation of RUNX1, with mouse functional context. Retain the curated nucleoplasmic component location based on independent CBFB evidence; methyltransferase chemistry remains PRMT1's function. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: Reactome explicitly models RUNX1–CBFB in this PRMT1 complex because of promoter colocalization. That assumption is adequate context for the supported nuclear location, not proof of a direct CBFB–PRMT1 interface. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The ITGA2B repressor assembly explicitly includes RUNX1–CBFB with SIN3A, PRMT6 and HDAC1. Retain the nucleoplasmic cofactor location while preserving the possible SIN3B involvement and partner-specific histone chemistry. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The RUNX1–CBFB corepressor model supports a nuclear complex context. The more extensively studied SIN3A interaction is distinguished from SIN3B; no CBFB deacetylase or methyltransferase activity follows. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The ITGA2B promoter model contains RUNX1–CBFB plus GATA-associated chromatin regulators. Nuclear localization is supported; inferred recruitment details and chromatin-enzyme activities are not independent CBFB functions. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: RUNX1–CBFB is modeled at the TJP1 promoter. This supports the nuclear cofactor context rather than localizing CBFB itself to the tight junction encoded by its target gene. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The OCLN-promoter event explicitly contains RUNX1–CBFB. Retain the nucleoplasmic location; occludin's membrane-junction role is not a CBFB localization or activity claim. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The CLDN5-promoter event supports a nuclear RUNX1–CBFB context. The downstream claudin protein's junctional location is not transferred to CBFB. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: MLL methylates promoter-associated histones in the ITGA2B assembly. The location-only CBFB projection is compatible with its nuclear cofactor role; CBFB is not assigned the MLL enzyme activity. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The PRMT6 ITGA2B event concerns histone methylation in a transcriptional assembly. Retain the independently supported nucleoplasmic CBFB location without treating the event summary as a CBFB catalytic assay. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The GP1BA repressor model explicitly includes RUNX1–CBFB. Its nucleus-associated context is appropriate, while possible SIN3B membership and the histone modifications retain their stated evidence limits. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The GP1BA histone-methylation event supplies a nuclear regulatory context. The curated CBFB location is retained with independent support; PRMT6 performs the methylation. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The GP1BA promoter assembly contains RUNX1–CBFB and GATA1-associated factors. Nuclear localization is consistent, but the summary's analogy-based PRMT1 effects are not upgraded to new CBFB activities. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The MLL GP1BA event represents promoter chromatin modification. Retain the nuclear cofactor's projected compartment while leaving methyltransferase activity on the MLL complex. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The THBS1 promoter assembly includes RUNX1–CBFB, with some chromatin details explicitly inferred by analogy. Those limits do not contradict the independently supported nucleoplasmic location, but prevent new mechanistic assertions from this event alone. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The THBS1 repressor event explicitly includes RUNX1–CBFB. Its assumed histone-state details remain assumptions; the accepted assertion is only the established nuclear compartment. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: MLL-mediated THBS1 chromatin modification is explicitly modeled with assumptions. Retain CBFB's curated component location with independent nuclear evidence, without claiming direct CBFB enzyme assays or proving those modeled reactions. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The THBS1 PRMT6 event concerns the enzyme's histone modification. The projected CBFB nucleoplasm annotation agrees with its nuclear role; methyltransferase activity is not assigned to the cofactor. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The MIR27A promoter model contains RUNX1–CBFB with GATA factors. Retain the nuclear location while distinguishing directly stated complex context from analogy-based PRMT1/chromatin details. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The MLL MIR27A event describes promoter-associated histone methylation. Its CBFB compartment projection is compatible with independent localization, without making CBFB the methyltransferase. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The PRMT6 MIR27A event supports the nuclear regulatory assembly context. CBFB's accepted location does not imply histone-arginine methylation activity. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The MIR27A repression model explicitly includes RUNX1–CBFB. Preserve the nuclear cofactor location and the source's distinctions among SIN3, PRMT6 and HDAC1 roles. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The RUNX1–CBFB/PRC1 association is modeled at target promoters, with exact composition unresolved. The nucleoplasmic location is supported independently and does not require claiming a fixed PRC1 subtype or uniform transcriptional direction. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The NR4A3 promoter event explicitly includes RUNX1–CBFB. Retain the nucleoplasmic cofactor location while leaving sequence recognition to RUNX1. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The SERPINB13 promoter event contains RUNX1–CBFB. Its location projection agrees with independent nuclear evidence and does not transfer the target protein's activity to CBFB. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The PRKCQ promoter event models RUNX1–CBFB. Retain the cofactor's nuclear location without assigning the encoded kinase's activity. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The PF4 promoter assembly contains RUNX1–CBFB at RUNX response elements. This supports the nuclear complex context; CBFB itself is not given sequence-recognition or chemokine activity. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The MYL9 promoter event supports nucleoplasmic RUNX1–CBFB localization. The encoded myosin regulatory subunit's contractile role is not transferred to CBFB. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The SWI/SNF recruitment model includes RUNX1–CBFB in a nuclear assembly, while the precise downstream chromatin effects remain unresolved. CBFB is not assigned ATP-dependent remodeling or every direct contact attributed to RUNX1. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The CSF2 promoter assembly explicitly contains RUNX1–CBFB and CREBBP. Retain the nuclear location, consistent with independent enhancer studies, while distinguishing cofactor participation from acetyltransferase activity. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: CREBBP associates with the RUNX1–CBFB complex through the RUNX1 C-terminal region. The event supports the nuclear complex context, not a direct CBFB–CREBBP interface or intrinsic acetyltransferase activity. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: RUNX1–CBFB is modeled at the NFE2 promoter. Retain its nucleoplasmic location without transferring the encoded transcription factor's DNA recognition to CBFB. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The LGALS3 promoter event includes RUNX2–CBFB. Nuclear occupancy is consistent with independent human evidence, while occupancy need not mean CBFB-dependent activation of this target in every cell type. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The separate RUNX1–CBFB LGALS3 promoter event also supports the nuclear context. Its location can be retained without imposing the transcriptional dependencies of the RUNX2 system. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The CDK6 event explicitly preserves RUNX1–CBFB association and distinguishes binding from CDK6 catalysis. Retain the nuclear complex location; neither kinase nor cyclin-binding activity is reassigned to CBFB. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The event includes a RUNX1–CBFB/ELF1 assembly but explicitly states that ELF1 does not directly bind CBFB. This supports nucleoplasmic complex localization while ruling out an inferred direct CBFB–ELF1 interface from the event title. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: ELF2 associates with the RUNX1–CBFB assembly through a RUNX1 interaction region. Retain the nuclear location without assigning CBFB the partner-specific interface or ETS DNA-binding activity. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The IL3 promoter summary focuses on RUNX1 and ELF1, rather than an independent CBFB assay. The curated CBFB compartment projection agrees with separate nuclear cofactor evidence; synergistic transcription is not automatically assigned to CBFB from that summary. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: PAX5 associates with the RUNX1–CBFB assembly through its interaction with RUNX1. Retain the nuclear cofactor location, without giving CBFB PAX5's DNA-binding activity or assuming a direct CBFB interface. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The BLK promoter event contains RUNX1–CBFB with alternative ETS/PAX5 partners. The larger simultaneous complex remains explicitly unresolved; that uncertainty does not undermine the independently supported nucleoplasmic location. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The PRKCB promoter event contains RUNX1–CBFB. Retain the nuclear complex location; the encoded kinase activity is not a property of CBFB. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The CR1 promoter model explicitly contains RUNX1–CBFB. Nuclear localization is appropriate, without inferring that CBFB is itself a complement receptor or membrane protein from the target gene. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The ITGA5 event calls CBFB association with RUNX2 presumptive. Retain the curated nucleoplasm projection with independent human localization support, without upgrading this particular promoter's CBFB occupancy to a direct assay. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The ITGBL1 promoter event likewise uses presumed RUNX2–CBFB association. The nuclear location is independently supported; the exact event's cofactor occupancy and extracellular target-protein role are not overinterpreted. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The MMP13 event models phosphorylated RUNX2–CBFB promoter association. Retain the nuclear location without attributing AKT kinase or MMP13 protease activity to CBFB. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The ITGAL/ITGA4 event makes RUNX3–CBFB association presumptive and leaves direct ITGA4 promoter binding unproven. Independent CBFB localization supports the compartment annotation without resolving those event-specific gaps. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: RUNX3 is modeled at the RUNX1 promoter with presumed CBFB association. Retain the nuclear cofactor location, while separating conserved complex biology from a directly verified CBFB promoter assay. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: EP300 associates with RUNX3, presumed to retain CBFB. The accepted annotation is the independently supported nuclear compartment, not a CBFB acetyltransferase or an experimentally resolved direct EP300–CBFB interface. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The event describes EP300 acetylation of RUNX3. Retain the nuclear component location with independent CBFB evidence; acetylation and the consequent RUNX3 stability effects are not autonomous CBFB activities. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: Acetylated RUNX3 binds BRD2 in this nuclear regulatory context. The CBFB nucleoplasm projection is consistent with its cofactor role, without asserting that CBFB reads acetyl-lysine or directly contacts BRD2. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: CCND1 displaces EP300 from RUNX3 in the modeled assembly. Retain CBFB's nuclear compartment with independent support, without claiming a CBFB-specific displacement assay. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: CCND1-mediated HDAC4 recruitment concerns RUNX3 regulation. The location-only CBFB assertion remains compatible with independent nuclear evidence; recruitment is not recast as a demonstrated CBFB adaptor mechanism. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: HDAC4 performs RUNX3 deacetylation in this event. Retain the nuclear cofactor compartment while leaving the enzyme activity and substrate modification on the actual participants. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The p14-ARF promoter event distinguishes known RUNX1–CBFB recognition from possible RUNX3 recognition. Retain the nuclear location without turning the similarity-based alternative into a verified CBFB-specific assay. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The TAL1 assembly explicitly contains RUNX1 with CBFB and several alternative components. Nuclear localization is appropriate; the variable assembly and CDK7 regulatory activity are not collapsed into a fixed CBFB mechanism. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The MYB enhancer model explicitly includes CBFB with RUNX1/GATA3/TAL1. Retain the nucleoplasmic cofactor location without assigning CBFB the DNA-binding activities of those factors. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: RUNX1 is modeled binding YAP1 with CBFB presumptively present. The nucleus annotation is supported independently, without assuming direct CBFB–YAP1 contact or attributing ABL1 phosphorylation to CBFB. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The ITCH promoter event includes presumed RUNX1–CBFB with YAP1. Retain nuclear location; the encoded ITCH ubiquitin-ligase activity is not transferred to the transcriptional cofactor. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The CDK4 event explicitly assumes phosphorylation within a RUNX2–CBFB complex and distinguishes isoform/site mappings. Retain the supported nuclear location without turning the modeled context into CBFB kinase activity or an independent validation of every phosphorylation consequence. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The PPM1D event acknowledges that the RUNX2 phosphorylation site's effect on CBFB binding was not tested. The curated component location is consistent with nuclear CBFB evidence; phosphatase activity and the BAX response are not assigned to CBFB from that assumption. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The BAX promoter event presumes RUNX2–CBFB association. Nuclear localization can be retained with independent support without manufacturing an additional CBFB apoptosis function or a direct promoter-specific assay. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The BGLAP promoter event describes RUNX2–CBFB binding and several partner-dependent regulatory effects. Retain the nuclear cofactor location while preserving species/isoform site distinctions and leaving RUNX2 DNA contact separate. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The CDK1 event distinguishes endogenous human RUNX2 phosphorylation from presumed CBFB association. The accepted assertion is nucleoplasmic CBFB, not kinase activity or a fully demonstrated cofactor requirement for mitotic regulation. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The SMURF1 promoter event uses presumed RUNX2–CBFB association. Retain the independently supported nuclear location without attributing the encoded ubiquitin ligase's catalytic function to CBFB. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: Retain the nucleoplasmic location of the RUNX cofactor.

Reason: The exact R-NUL identifier is preserved. The summary explicitly combines recombinant human AKT1, mouse Runx2-5 and endogenous human CBFB; its human species header does not make all constructs human. Retain the curated nucleoplasmic CBFB location with independent human nuclear evidence, without assigning AKT1 phosphorylation chemistry to CBFB or silently humanizing the mouse substrate. The compartment is the curated GOA projection, not an independent localization experiment in the cached summary.

Summary: CBFB regulates transcription as the non-DNA-contacting RUNX cofactor.

Reason: The ARBA process assignment agrees with human structural, enhancer and target-expression experiments. CBFB stabilizes RUNX DNA binding and contributes to selected transcriptional complexes; the direction of regulation depends on the promoter and cellular context.

Summary: The inherited RNA-polymerase-II regulatory role is a core CBFB function.

Reason: The PAINT assertion represents an ancestral functional placement supported by descendant evidence, including the target's own experimental annotations. The human accession in WITH/FROM is legitimate evidence for that node, not circularity. Direct target experiments support the conserved RUNX cofactor role without claiming that CBFB itself contacts promoter DNA.

Summary: The human GM-CSF enhancer study supports CBFB-dependent transcriptional regulation.

Reason: The paper combines recombinant Runt-domain/CBFB biochemistry with regulatory-site and reporter assays. Human-locus transgenic-mouse T/mast-cell experiments are distinguished from reporter assays in human CEM/Jurkat lines. These results support the cofactor's role in the RUNX-dependent enhancer system, not autonomous CBFB sequence recognition.

Summary: Endogenous human RUNX2–CBFB complexes regulate selected target genes.

Reason: In MDA-MB-231 cells, two independent CBFB hairpins reduce CBFB while RUNX2 protein remains unchanged; selected target transcripts and invasion decline. Endogenous co-immunoprecipitation and chromatin assays support the complex. Galectin-3 remains CBFB-independent despite promoter occupancy, so the result is not generalized to every RUNX2 target.

Summary: The exact scope of this legacy broad-transcription assertion remains unresolved beyond the established RUNX cofactor role.

Reason: GO:0006366 describes RNA synthesis from a DNA template by RNA polymerase II. Independent human binding, enhancer and target-gene experiments support CBFB-dependent transcriptional regulation, but do not by themselves settle whether this legacy TAS assertion denotes participation in the RNA-synthesis process rather than its regulation. The PMID:8351518 abstract identifies the leukemia fusion and describes normal core-binding-factor transcriptional regulation; its full original text remains inaccessible after a publisher access attempt. A cofactor need not catalyze RNA synthesis or contact DNA to participate in a process, so absence of those activities is not sufficient grounds for REMOVE or a confident over-annotation claim. Retain uncertainty for this exact source assertion without negating the separately accepted regulatory function or manufacturing a redundant replacement to GO:0006357.

Summary: Recovered in a membrane-fraction proteome without protein-specific evidence that it associates with membranes.

Reason: UniProt: nucleus; transcription-factor subunit with no membrane association. (Manual re-review for OMICS_EVIDENCE, 2026-10-10; previous action: UNDECIDED.)

Summary: CBFB is the beta subunit of core-binding factor complexes.

Reason: The PAINT complex annotation agrees with direct human RUNX1 structure and RUNX2/RUNX3 cellular evidence. Target self-inclusion among the descendant evidence is expected for a grounded ancestral placement, not circular support. The complex contains a RUNX DNA-binding subunit and CBFB cofactor.

Summary: The human RUNX1–CBFB structure directly supports core-binding-factor complex membership.

Reason: The Runt-domain/CBFB fragment structure resolves the heterodimeric interface. It establishes the relevant complex while leaving full-length regulatory partners and cellular assembly dynamics outside the crystallographic claim.

Summary: Endogenous RUNX2 coassociation supports CBFB complex membership in human cells.

Reason: The actual human breast-cell experiments include endogenous RUNX2 immunoprecipitation, IgG/input controls and nuclear CBFB measurements. The transcriptional perturbations further support a functional complex without requiring every occupied promoter to respond identically.

Summary: RUNX3 association and interface perturbation support CBFB complex membership.

Reason: Human HEK293T/U2OS experiments map RUNX3–CBFB association to the Runt region and test interface mutations, with co-immunoprecipitation and proximity-assay controls. CBFB depletion and rescue also affect RUNX3 stability. Proximity ligation alone is not taken as a solved direct interface, nor is RUNX3's repair activity reassigned as a CBFB enzyme function.

Summary: Retain the conserved RUNX–CBFB complex assertion from the T-cell study.

Reason: Selected original mouse conditional-deletion, re-expression and chromatin-association text supports Cbfb-containing RUNX regulatory complexes. Independent human structural and cellular evidence confirms the conserved complex membership. The cache remains abstract-only despite the separately recorded selected external body access.

Summary: The mouse donor supports repression of the CD4-lineage program in a T-cell context.

Reason: Conditional Cbfb deletion derepresses Th-POK, and Cbfb re-expression suppresses it in the tested CD8-intermediate population. Retain the human transfer as a lineage-specific output of the cofactor, rather than its universal transcriptional effect.

Summary: Retain the curated mouse-derived negative CD4 differentiation role.

Reason: The source-specific transfer agrees with Cbfb-dependent Th-POK repression in the mouse lineage-decision study. The original cellular context is retained; this is not presented as a direct human differentiation assay.

Summary: Mouse-ortholog evidence supports the cytotoxic CD8-lineage regulatory outcome.

Reason: The conditional mouse study links RUNX–Cbfb complexes and Th-POK repression to cytotoxic-lineage differentiation. That developmental output is compatible with the conserved cofactor mechanism and retained non-core, without equating CBFB with a CD8 receptor or a lineage-specific DNA-binding factor.

Summary: Retain the manual positive CD8 differentiation transfer with mouse-model scope.

Reason: The Cbfb perturbation and lineage experiments support the curated developmental inference. The human assertion is an ortholog transfer, not a new human experimental claim, and the lineage effect is secondary to the general transcriptional-cofactor activity.

Summary: CBFB contributes to sequence-specific DNA binding by the RUNX complex.

Reason: The contributes_to flag is essential here: human structural and biochemical evidence shows allosteric stabilization of RUNX DNA binding without CBFB contacting DNA. The PAINT assertion concerns this complex contribution, so it is compatible with the rejection of unqualified intrinsic DNA binding.

Summary: Retain the ortholog-derived contribution to RUNX sequence-specific DNA binding.

Reason: This electronic source explicitly uses contributes_to, matching CBFB's experimentally established non-DNA-contacting cofactor role. Independent human evidence supports the mouse-derived transfer; the molecular interface with DNA remains on the RUNX subunit.

Summary: The manual mouse transfer correctly records a contribution to DNA binding.

Reason: The qualified assertion describes stabilization of RUNX–DNA association, not a separate CBFB DNA-binding surface. Human structural and allosteric experiments substantiate that conserved contribution without altering the original source object.

Summary: Coactivator activity supports positive transcriptional regulation.

Reason: The GO activity-to-process mapping is consistent with CBFB-dependent expression of selected RUNX targets in human cells. The same cofactor can participate in repressive complexes elsewhere; that contextual difference does not negate this supported positive regulatory function.