BUB1B encodes BUBR1, a mitotic checkpoint protein that restrains chromosome segregation and helps establish stable kinetochore–microtubule attachments. In the mitotic checkpoint complex with BUB3, MAD2 and CDC20, BUBR1 uses degron-like motifs and its N-terminal TPR domain to inhibit APC/C substrate recognition and ubiquitination, delaying anaphase. A separate kinetochore function uses its central KARD region and LxxIxE motif to recruit PP2A-B56; this positions phosphatase activity to balance mitotic kinase signaling, promote chromosome alignment and facilitate checkpoint silencing. Human BUBR1 has a C-terminal kinase-like domain with important noncatalytic functions, while intrinsic kinase activity remains disputed because positive and negative biochemical studies use different constructs and assay conditions. BUBR1 is predominantly cytoplasmic in interphase, accumulates at mitotic kinetochores and can redistribute along the anaphase spindle. Biallelic pathogenic variants cause mosaic variegated aneuploidy syndrome 1, characterized by chromosome-segregation errors and developmental abnormalities.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000776 kinetochore | IBA GO_REF:0000033 | ACCEPT | Summary: Human BUBR1 localizes to and functions at kinetochores. Reason: The exact non-negated kinetochore IBD at PTN000361607 and its complete donor set match the GOA source. Independent human localization is described in PMID:9763420, and PMID:9660858 reports ectopic human BUBR1 recruitment under Bub3 coexpression. Target self-inclusion is legitimate experimental grounding. No full ancestral tree/MSA was inspected, so the previous claim that every listed extant member was independently verified or that a particular duplication topology was reconstructed is not retained. |
| GO:0000776 kinetochore | IDA PMID:12925705 Centromere-associated protein-E is essential for the mammali... | ACCEPT | Summary: BUBR1 acts at mitotic kinetochores. Reason: PMID:12925705 directly quantifies BUBR1 kinetochore staining in CENP-E-depleted and control HeLa cells, alongside distinct mouse experiments. The human localization supports this assertion. |
| GO:0000776 kinetochore | IDA PMID:17227893 Loss of APC induces polyploidy as a result of a combination ... | ACCEPT | Summary: BUBR1 acts at mitotic kinetochores. Reason: The inspected U2OS Results and Figure 2 caption quantify kinetochore-associated BUBR1 with CREST costaining. The linked erratum corrects author order, not this result. |
| GO:0000776 kinetochore | IDA PMID:17363900 The human Nup107-160 nuclear pore subcomplex contributes to ... | ACCEPT | Summary: BUBR1 acts at mitotic kinetochores. Reason: The cached NUP107-160 study abstract does not expose its exact BUBR1 localization panel. The location is independently established in human HeLa cells; retain the experimental assertion without claiming the uninspected panel was verified. |
| GO:0000776 kinetochore | IDA PMID:19465021 A nucleolar protein RRS1 contributes to chromosome congressi... | ACCEPT | Summary: BUBR1 acts at mitotic kinetochores. Reason: The cached RRS1 study abstract does not expose its exact BUBR1 panel. Independent human BUBR1 imaging establishes kinetochore localization, so the assertion is retained with the original experiment limitation explicit. |
| GO:0000776 kinetochore | IDA PMID:20220147 Defining the molecular basis of BubR1 kinetochore interactio... | ACCEPT | Summary: BUBR1 acts at mitotic kinetochores. Reason: The human BUBR1 TPR/KNL1 study demonstrates the interaction underlying kinetochore recruitment. Human imaging in PMID:9763420 independently establishes the location; no new localization image is inferred from the structural assay. |
| GO:0000776 kinetochore | IDA PMID:22331848 Structural analysis reveals features of the spindle checkpoi... | ACCEPT | Summary: BUBR1 acts at mitotic kinetochores. Reason: Human BUBR1 deletion constructs are assessed at HeLa kinetochores in the inspected Results. Deleting the TPR region does not abolish recruitment, which depends on additional interactions. |
| GO:0000776 kinetochore | IDA PMID:9660858 The human homologue of Bub3 is required for kinetochore loca... | ACCEPT | Summary: BUBR1 acts at mitotic kinetochores. Reason: Human BUBR1 expressed in BHK cells is recruited to kinetochores when human BUB3 is coexpressed. This is a human protein assay in a heterologous mammalian cell background, corroborated by endogenous HeLa localization. |
| GO:0000776 kinetochore | IDA PMID:9763420 Characterization of the kinetochore binding domain of CENP-E... | ACCEPT | Summary: BUBR1 acts at mitotic kinetochores. Reason: Endogenous human BUBR1 staining begins at kinetochores in prophase and is stronger on unaligned prometaphase chromosomes in the inspected HeLa Results. Supporting Evidence: |
| GO:0000776 kinetochore | IEA GO_REF:0000107 | ACCEPT | Summary: BUBR1 acts at mitotic kinetochores. Reason: The mouse orthology transfer is concordant with independently established human kinetochore localization. The exact donor assay was not traced; the human evidence supports the location directly. |
| GO:0000940 outer kinetochore | IDA PMID:19468067 Mitotic control of kinetochore-associated dynein and spindle... | ACCEPT | Summary: BUBR1 acts at mitotic kinetochores. Reason: The inspected HeLa S3 Results and Figure 1C caption use BUBR1 as the outer-kinetochore marker adjacent to CREST, with hSpindly colocalization. This supports outer-kinetochore placement without assigning hSpindly activities to BUBR1. |
| GO:0000940 outer kinetochore | IDA PMID:22331848 Structural analysis reveals features of the spindle checkpoi... | ACCEPT | Summary: BUBR1 acts at mitotic kinetochores. Reason: The human recruitment study and its kinetochore domain framework support outer-kinetochore placement, corroborated by the BUBR1/CREST localization in PMID:19468067. No inference of constitutive structural membership throughout the cell cycle is made. |
| GO:0000940 outer kinetochore | IEA GO_REF:0000120 | ACCEPT | Summary: BUBR1 acts at mitotic kinetochores. Reason: The automated outer-kinetochore assertion agrees with direct human BUBR1 imaging relative to CREST. The source rule and mouse identifiers remain unchanged; their full derivation was not reconstructed. |
| GO:0004672 protein kinase activity | IBA GO_REF:0000033 | UNDECIDED | Summary: Intrinsic human BUBR1 kinase activity remains disputed. Reason: The source kinase IBD at PTN000361607 represents a phylogenetic assertion with legitimate human target evidence, not a pairwise similarity transfer. The complete ancestral tree/MSA and placement rationale were not inspected, so an erroneous pre-duplication placement or target-specific loss is not established. Positive human full-length assays in PMID:31201382 conflict with negative biochemical evidence in PMID:22698286. Preserve the inherited assertion as unresolved rather than declaring the self-source circular or the node wrong. The positive human Sf9-derived assays include active-site mutants and inhibitor-resistant rescue controls; these are substantive target evidence, not just transfer from the Drosophila structure. The human bacterial-domain and cellular immunoprecipitate controls in the negative study remain a genuine counterpoint with different preparation boundaries. |
| GO:0004672 protein kinase activity | IDA PMID:31201382 BubR1 phosphorylates CENP-E as a switch enabling the transit... | UNDECIDED | Summary: Strong positive human kinase assays conflict with negative primary biochemical tests. Reason: The inspected human Sf9-derived preparations in PMID:31201382 show reduced activity with K795A/D911A, loss of CENP-E Ser2639 phosphorylation with D911A or D882N, and BRT-1-sensitive phosphorylation. BRT-1-binding-site variants retained activity and rescued drug-treated mitotic phenotypes, while the D882N analysis addressed the stability objection. These controls support taking intrinsic activity seriously; they are not dismissed as an untested contamination hypothesis. Nevertheless, PMID:22698286 reports no human bacterial kinase-domain activity with active BUB1 controls and persistence of cellular immunoprecipitate-associated activity after kinase-domain removal or mutation. The divergent constructs, expression systems and activity-attribution results have not been reconciled. Retain UNDECIDED for the biological catalytic assertion, rather than equating kinase dispensability with absence or converting an unresolved conflict into overannotation. The crystal structure is Drosophila; the human assays are distinct. Supporting Evidence: PMID:31201382 human BubR1 WT was found to have catalytic activity |
| GO:0004672 protein kinase activity | NAS PMID:9763420 Characterization of the kinetochore binding domain of CENP-E... | UNDECIDED | Summary: Intrinsic human BUBR1 kinase activity remains disputed. Reason: This NAS record preserves an early author-level kinase assignment. The inspected source abstract, introduction and selected interaction/localization Results do not independently resolve intrinsic catalysis; no claim is made that every original assay or supplement was inspected or that the whole paper lacks an assay. The later positive human Sf9, catalytic-mutant and inhibitor-rescue evidence in PMID:31201382 must be considered alongside the negative human-domain and immunoprecipitate controls in PMID:22698286. Accordingly the catalytic claim remains UNDECIDED, not demonstrably false or merely excessive because it originated as NAS. |
| GO:0004672 protein kinase activity | TAS PMID:10477750 Human BUBR1 is a mitotic checkpoint kinase that monitors CEN... | UNDECIDED | Summary: Intrinsic human BUBR1 kinase activity remains disputed. Reason: The inspected original human HeLa immunoprecipitate assays report phosphorylation associated with BUBR1, including mitotic/nocodazole dependence. Those observations are preserved. They do not on their own distinguish intrinsic BUBR1 catalysis from associated activity, which the negative primary study tested explicitly. The later Sf9/catalytic-mutant/BRT-1 rescue evidence is a substantive positive counterpoint. Retain UNDECIDED because the attribution conflict remains unresolved; MARK_AS_OVER_ANNOTATED would overstate a conclusion that intrinsic activity has been excluded. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:11702782 Mad2-Independent inhibition of APCCdc20 by the mitotic check... | UNDECIDED | Summary: Intrinsic human BUBR1 kinase activity remains disputed. Reason: The complete cached abstract of PMID:11702782 states that kinase activity is dispensable for APC/C inhibition; it does not show that catalytic activity is absent under all conditions. The source-specific kinase assay details were not inspected. Positive human Sf9/catalytic-mutant evidence and negative human kinase-domain/immunoprecipitate controls are considered independently. Their unresolved conflict warrants UNDECIDED rather than treating the noncatalytic checkpoint mechanism as proof of no activity. |
| GO:0004674 protein serine/threonine kinase activity | IEA GO_REF:0000003 | UNDECIDED | Summary: Intrinsic human BUBR1 kinase activity remains disputed. Reason: The EC mapping faithfully records a curated serine/threonine-kinase claim. Its biological premise remains disputed by positive human Sf9/catalytic-mutant assays versus negative human-domain and immunoprecipitate controls, rather than being settled by the electronic provenance. Retain UNDECIDED; no target loss or absence of catalysis is inferred merely from kinase dispensability for checkpoint signaling. |
| GO:0005515 protein binding | IPI PMID:11030144 p55CDC/hCDC20 is associated with BUBR1 and may be a downstre... | MODIFY | Summary: BUBR1 binding to CDC20 inhibits APC/C activation. Reason: The complete cached abstract reports human BUBR1–CDC20 binding by two-hybrid, pull-down and endogenous coimmunoprecipitation, and suggests targeting of APC/C through CDC20. Independently inspected human MCC biochemical and structural studies establish the inhibitory mechanism, supporting a functional MF refinement rather than generic binding. Proposed replacements: ubiquitin ligase inhibitor activity |
| GO:0005515 protein binding | IPI PMID:15525512 Phosphorylation of Cdc20 by Bub1 provides a catalytic mechan... | MODIFY | Summary: BUBR1–CDC20 association is independently established; the original source record is retained with its access limit. Reason: Human recombinant MCC inhibition and APC/C–MCC structural experiments independently establish BUBR1 contacts that occupy CDC20 substrate-recognition sites and inhibit the ligase. The complete abstract foregrounds BUB1-mediated CDC20 phosphorylation. It does not expose the BUBR1 assay, and the full text/supplementary interaction record was not inspected. This is not proof of a wrong paralog; the individual experiment remains uninspected. The broad interaction claim is adjudicated using this independent target evidence and deference to the original experimental curator; the unread source-specific table or assay is not represented as independently verified. Refine to ubiquitin ligase inhibitor activity on the independently established BUBR1–CDC20 mechanism, consistently with the other CDC20 rows; the original interaction assay alone is not claimed to demonstrate inhibition. Proposed replacements: ubiquitin ligase inhibitor activity |
| GO:0005515 protein binding | IPI PMID:16760428 Phosphorylation- and polo-box-dependent binding of Plk1 to B... | KEEP AS NON CORE | Summary: BUBR1 association with PLK1 is supported. Reason: Indexed primary Results explicitly report endogenous BUBR1 coimmunoprecipitation with PLK1 during mitosis, referring to Supplementary Figure 1. The supplement image was not viewed. Retain the physical association; the paper does not establish a specific PLK1 regulator activity for BUBR1. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17981135 Human Blinkin/AF15q14 is required for chromosome alignment a... | KEEP AS NON CORE | Summary: BUBR1 binds the kinetochore scaffold KNL1/Blinkin. Reason: The complete source abstract explicitly identifies BUBR1 binding to Blinkin. Independently inspected recombinant human Results in PMID:22331848 resolve the BUBR1 TPR–KNL1 KI2 interaction. Retain binding without transferring the entire scaffold activity to this one contact. |
| GO:0005515 protein binding | IPI PMID:19407811 BubR1 acetylation at prometaphase is required for modulating... | KEEP AS NON CORE | Summary: BUBR1 associates with BUB3. Reason: The inspected acetylation study reports that BUB3 binding was unchanged by BUBR1 K250 substitutions, with supplementary Figure 9 cited but its image not viewed. Independent GST–BUB3 recovery of human BUBR1 confirms this interaction. Complex membership is recorded separately; it is not a replacement MF. |
| GO:0005515 protein binding | IPI PMID:19407811 BubR1 acetylation at prometaphase is required for modulating... | UNDECIDED | Summary: The ubiquitin record needs distinction between conjugation and noncovalent binding. Reason: The inspected Results demonstrate polyubiquitinated BUBR1 and its degradation. GO binding inherits selective noncovalent interaction from GO:0005488, so covalent ubiquitin conjugation alone does not establish this MF. The exact curated UBC interaction record and any distinct noncovalent assay were not inspected. Preserve uncertainty rather than reject a potentially additional experiment. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19407811 BubR1 acetylation at prometaphase is required for modulating... | MODIFY | Summary: BUBR1–CDC20 association participates in APC/C inhibition. Reason: The inspected Results report CDC20 binding by the BUBR1 K250 variants while examining APC/C-dependent regulation. Direct human MCC reconstitution and structural data establish the inhibitor activity of BUBR1, providing the appropriate functional refinement. Proposed replacements: ubiquitin ligase inhibitor activity |
| GO:0005515 protein binding | IPI PMID:19407811 BubR1 acetylation at prometaphase is required for modulating... | KEEP AS NON CORE | Summary: BUBR1 associates with PCAF/KAT2B. Reason: The inspected human-cell Results report PCAF coimmunoprecipitation with BUBR1 and acetylation of BUBR1. BUBR1 is the acetyltransferase substrate here; retain physical association without assigning acetyltransferase activity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:20212161 ATP is required for the release of the anaphase-promoting co... | MODIFY | Summary: CDC20 binding places BUBR1 in the inhibitory MCC. Reason: The complete abstract identifies BUBR1, BUB3, MAD2 and CDC20 in inhibitory MCC and reports ATP-dependent disassembly without identifying the responsible energy-consuming mechanism. Independently inspected human MCC studies establish BUBR1 ubiquitin-ligase inhibition. The disassembly requirement does not assign ATPase activity to BUBR1. Proposed replacements: ubiquitin ligase inhibitor activity |
| GO:0005515 protein binding | IPI PMID:20212161 ATP is required for the release of the anaphase-promoting co... | KEEP AS NON CORE | Summary: BUBR1 and MAD2 associate in the checkpoint complex. Reason: The complete abstract describes the MAD2-containing inhibitory MCC and its ATP-dependent disassembly. Retain the supported complex association; a binary interface or an ATPase activity for BUBR1 is not inferred. |
| GO:0005515 protein binding | IPI PMID:20220147 Defining the molecular basis of BubR1 kinetochore interactio... | KEEP AS NON CORE | Summary: Human BUBR1 binds KNL1/Blinkin. Reason: The inspected source Results directly test human BUBR1 and Blinkin constructs by stringent three-reporter yeast two-hybrid analysis and structure-guided mutagenesis. The TPR binding groove contributes to this contact. Supporting Evidence: PMID:20220147 We confirmed the interaction between BubR1(1–237) and Blinkin(1–728) using a yeast two-hybrid assay |
| GO:0005515 protein binding | IPI PMID:20360068 Systematic analysis of human protein complexes identifies ch... | KEEP AS NON CORE | Summary: BUBR1–BUB1 association is independently established; the original source record is retained with its access limit. Reason: Human BUBR1/BUB1 constructs were tested in a stringent three-reporter yeast two-hybrid system; the inspected Results explicitly establish heterodimerization through regions downstream of their N-terminal TPR domains. The complete abstract describes a general coimmunoprecipitation interaction-mapping method; the target-specific supplementary record was not inspected. The broad interaction claim is adjudicated using this independent target evidence and deference to the original experimental curator; the unread source-specific table or assay is not represented as independently verified. Retain the supported generic interaction as non-core under the standing project instruction; no additional molecular activity is inferred from association alone. |
| GO:0005515 protein binding | IPI PMID:20360068 Systematic analysis of human protein complexes identifies ch... | MODIFY | Summary: BUBR1–CDC20 association is independently established; the original source record is retained with its access limit. Reason: Human recombinant MCC inhibition and APC/C–MCC structural experiments independently establish BUBR1 contacts that occupy CDC20 substrate-recognition sites and inhibit the ligase. The complete abstract describes a general coimmunoprecipitation interaction-mapping method; the target-specific supplementary record was not inspected. The broad interaction claim is adjudicated using this independent target evidence and deference to the original experimental curator; the unread source-specific table or assay is not represented as independently verified. Refine to ubiquitin ligase inhibitor activity on the independently established BUBR1–CDC20 mechanism, consistently with the other CDC20 rows; the original interaction assay alone is not claimed to demonstrate inhibition. Proposed replacements: ubiquitin ligase inhibitor activity |
| GO:0005515 protein binding | IPI PMID:21300909 p31comet Promotes disassembly of the mitotic checkpoint comp... | MODIFY | Summary: BUBR1–CDC20 interaction is part of APC/C inhibition. Reason: The complete source abstract describes release of CDC20 from BUBR1 during MCC disassembly. Independent human reconstitution resolves the inhibitory BUBR1–CDC20 mechanism, supporting ubiquitin-ligase inhibitor activity. Proposed replacements: ubiquitin ligase inhibitor activity |
| GO:0005515 protein binding | IPI PMID:21300909 p31comet Promotes disassembly of the mitotic checkpoint comp... | KEEP AS NON CORE | Summary: BUBR1 and MAD2 occur in the MCC. Reason: The source abstract explicitly studies p31comet-dependent dissociation of the MAD2-containing MCC. This supports complex association, corroborated by human MCC purification; no direct binary binding geometry is assigned. |
| GO:0005515 protein binding | IPI PMID:21407176 Evidence that Aurora B is implicated in spindle checkpoint s... | KEEP AS NON CORE | Summary: The source supports BUBR1-containing MCC association with CDC20. Reason: The inspected Results report inhibitor-dependent MCC dissociation and the Methods specify anti-CDC20 immunoprecipitation from HeLa lysates. The original Figure 3C image was not separately inspected. Retain the complex association with independent human MCC corroboration, without claiming a source-specific binary affinity measurement. |
| GO:0005515 protein binding | IPI PMID:21772247 Probing the in vivo function of Mad1:C-Mad2 in the spindle a... | KEEP AS NON CORE | Summary: BUBR1–MAD2 association is independently established; the original source record is retained with its access limit. Reason: Human HeLa MCC purification and reciprocal immunoprecipitation independently establish BUBR1–MAD2 coassociation. This supports complex-associated binding without asserting an isolated binary interface from that experiment. The complete abstract concerns MAD1-bound MAD2 conversion; the BUBR1–MAD2 experiment behind this source assertion was not available in the inspected text. The broad interaction claim is adjudicated using this independent target evidence and deference to the original experimental curator; the unread source-specific table or assay is not represented as independently verified. Retain the supported generic interaction as non-core under the standing project instruction; no additional molecular activity is inferred from association alone. Supporting Evidence: PMID:11535616 The MAD2 immunoprecipitates contained all four MCC subunits |
| GO:0005515 protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | KEEP AS NON CORE | Summary: BUBR1–BUB3 association is independently established; the original source record is retained with its access limit. Reason: Human BUBR1 and BUB3 constructs show GST-dependent copurification in BHK cells, loss of association after deleting the BUB3-binding region, and corroborating human-construct two-hybrid interaction. The complete abstract and available liver-interactome body describe the screen, but the exact BUBR1–BUB3 supplementary pair was not inspected. The official erratum corrects an author name. The broad interaction claim is adjudicated using this independent target evidence and deference to the original experimental curator; the unread source-specific table or assay is not represented as independently verified. Retain the supported generic interaction as non-core under the standing project instruction; no additional molecular activity is inferred from association alone. |
| GO:0005515 protein binding | IPI PMID:22000412 Structure of a Blinkin-BUBR1 complex reveals an interaction ... | KEEP AS NON CORE | Summary: BUBR1–BUB3 association is independently established; the original source record is retained with its access limit. Reason: Human BUBR1 and BUB3 constructs show GST-dependent copurification in BHK cells, loss of association after deleting the BUB3-binding region, and corroborating human-construct two-hybrid interaction. The actual Results resolve BUBR1–Blinkin and discuss CDC20/MAD2 binding, but the BUB3-specific interaction assay underlying this row was not inspected. The broad interaction claim is adjudicated using this independent target evidence and deference to the original experimental curator; the unread source-specific table or assay is not represented as independently verified. Retain the supported generic interaction as non-core under the standing project instruction; no additional molecular activity is inferred from association alone. |
| GO:0005515 protein binding | IPI PMID:22000412 Structure of a Blinkin-BUBR1 complex reveals an interaction ... | MODIFY | Summary: BUBR1 KEN-box binding to CDC20 supports checkpoint inhibition. Reason: The inspected source Results report CDC20 recovery with wild-type BUBR1 and loss with KEN26AAA, alongside checkpoint rescue assays. Direct human MCC structures establish the inhibitory mechanism, supporting a specific inhibitor MF. Proposed replacements: ubiquitin ligase inhibitor activity |
| GO:0005515 protein binding | IPI PMID:22000412 Structure of a Blinkin-BUBR1 complex reveals an interaction ... | KEEP AS NON CORE | Summary: BUBR1 and MAD2 associate in the checkpoint complex. Reason: The inspected Results report wild-type BUBR1 association with MAD2 and loss with the KEN26AAA mutant. Retain association without equating KEN dependence with an independently measured binary interface. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22000412 Structure of a Blinkin-BUBR1 complex reveals an interaction ... | KEEP AS NON CORE | Summary: BUBR1 binds the KNL1/Blinkin KI2 region. Reason: The inspected human-fragment binding, ITC and structural Results establish the BUBR1–Blinkin contact. The GOA partner accession retains its isoform suffix; the assay does not establish that binding is unique to that isoform. The erratum corrects an affiliation and Figure 3B comparison legend. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22331848 Structural analysis reveals features of the spindle checkpoi... | KEEP AS NON CORE | Summary: BUBR1 binds KNL1 through its TPR domain. Reason: Recombinant human BUBR1(1–204) forms a complex with KNL1(201–250), containing KI2, in the inspected size-exclusion Results. This contact is distinct from the other recruitment mechanisms that allow TPR-deleted BUBR1 to reach kinetochores. Supporting Evidence: PMID:22331848 The latter bound Knl1(201–250), which contains the KI2 motif |
| GO:0005515 protein binding | IPI PMID:24581499 Nuclear pores protect genome integrity by assembling a premi... | MODIFY | Summary: BUBR1–CDC20 association is independently established; the original source record is retained with its access limit. Reason: Human recombinant MCC inhibition and APC/C–MCC structural experiments independently establish BUBR1 contacts that occupy CDC20 substrate-recognition sites and inhibit the ligase. The complete abstract concerns nuclear-pore-tethered MAD1–MAD2 generation of a premitotic CDC20 inhibitor. The exact BUBR1–CDC20 interaction experiment underlying this row was not inspected; no BUBR1 activity is inferred from the MAD1–MAD2 mechanism. The broad interaction claim is adjudicated using this independent target evidence and deference to the original experimental curator; the unread source-specific table or assay is not represented as independently verified. Refine to ubiquitin ligase inhibitor activity on the independently established BUBR1–CDC20 mechanism, consistently with the other CDC20 rows; the original interaction assay alone is not claimed to demonstrate inhibition. Proposed replacements: ubiquitin ligase inhibitor activity |
| GO:0005515 protein binding | IPI PMID:24825348 SIRT2 induces the checkpoint kinase BubR1 to increase lifesp... | KEEP AS NON CORE | Summary: BUBR1 association with CBP is supported. Reason: Indexed primary Results report CBP binding to BUBR1 during analysis of BUBR1 acetylation and stability. GOA and UniProt identify the partner as the mouse Crebbp accession P45481, a xenogeneic interaction. Preserve that source identity; exact construct provenance was not independently resolved from the accessed Methods excerpt. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:24825348 SIRT2 induces the checkpoint kinase BubR1 to increase lifesp... | KEEP AS NON CORE | Summary: BUBR1 associates with SIRT2. Reason: Indexed primary Results report SIRT2–BUBR1 binding and endogenous coimmunoprecipitation while studying deacetylation of BUBR1. Retain the interaction without assigning SIRT2 deacetylase catalysis to its BUBR1 substrate. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:24825348 SIRT2 induces the checkpoint kinase BubR1 to increase lifesp... | KEEP AS NON CORE | Summary: BUBR1–PCAF/KAT2B association is independently established; the original source record is retained with its access limit. Reason: Independent human HeLa IP/immunoblot Results directly demonstrate BUBR1–PCAF complex formation in nocodazole-arrested cells, with much less association in asynchronous cells. The accessed source Results establish CBP and SIRT2 contacts and compare effects of PCAF on BUBR1 abundance, but the exact PCAF binding assay underlying this row was not inspected. Absence of an abundance effect is not evidence against binding. The broad interaction claim is adjudicated using this independent target evidence and deference to the original experimental curator; the unread source-specific table or assay is not represented as independently verified. Retain the supported generic interaction as non-core under the standing project instruction; no additional molecular activity is inferred from association alone. |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | MODIFY | Summary: BUBR1–CDC20 association is independently established; the original source record is retained with its access limit. Reason: Human recombinant MCC inhibition and APC/C–MCC structural experiments independently establish BUBR1 contacts that occupy CDC20 substrate-recognition sites and inhibit the ligase. The complete abstract describes an in situ proximity ligation assay of 1,204 endogenous protein pairs in HeLa cells, with 557 positive pairs. The specific BUBR1–CDC20 target record was not inspected. The broad interaction claim is adjudicated using this independent target evidence and deference to the original experimental curator; the unread source-specific table or assay is not represented as independently verified. Refine to ubiquitin ligase inhibitor activity on the independently established BUBR1–CDC20 mechanism, consistently with the other CDC20 rows; the original interaction assay alone is not claimed to demonstrate inhibition. Proposed replacements: ubiquitin ligase inhibitor activity |
| GO:0005515 protein binding | IPI PMID:25383541 The mitotic checkpoint complex binds a second CDC20 to inhib... | KEEP AS NON CORE | Summary: BUBR1 associates with BUB3 in reconstituted MCC. Reason: The inspected main Results and Extended Data Figure 2 caption describe recombinant human MCC preparations with and without BUB3, including copurification. This supports the complex association; it does not require a separate catalytic activity for BUBR1. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25383541 The mitotic checkpoint complex binds a second CDC20 to inhib... | MODIFY | Summary: BUBR1 binding to CDC20 directly inhibits APC/C. Reason: Human recombinant MCC, BUBR1 D-box/KEN2 mutants and reconstituted ubiquitination assays directly show how BUBR1 contacts a second APC/C-bound CDC20 and inhibits the ligase. This source supports the more informative inhibitor MF. Proposed replacements: ubiquitin ligase inhibitor activity |
| GO:0005515 protein binding | IPI PMID:25383541 The mitotic checkpoint complex binds a second CDC20 to inhib... | KEEP AS NON CORE | Summary: BUBR1 associates with MAD2 in human MCC. Reason: The inspected source coexpresses and copurifies human BUBR1, MAD2 and CDC20 and tests MCC stabilization in HeLa cells. Retain physical complex association without replacing this MF by a cellular-component term. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: BUBR1–BUB3 association is independently established; the original source record is retained with its access limit. Reason: Human BUBR1 and BUB3 constructs show GST-dependent copurification in BHK cells, loss of association after deleting the BUB3-binding region, and corroborating human-construct two-hybrid interaction. The abstract and available interactome text describe the systematic screen; the BUBR1–BUB3 supplementary entry was not inspected. The broad interaction claim is adjudicated using this independent target evidence and deference to the original experimental curator; the unread source-specific table or assay is not represented as independently verified. Retain the supported generic interaction as non-core under the standing project instruction; no additional molecular activity is inferred from association alone. |
| GO:0005515 protein binding | IPI PMID:25502805 A massively parallel pipeline to clone DNA variants and exam... | MODIFY | Summary: BUBR1–CDC20 association is independently established; the original source record is retained with its access limit. Reason: Human recombinant MCC inhibition and APC/C–MCC structural experiments independently establish BUBR1 contacts that occupy CDC20 substrate-recognition sites and inhibit the ligase. Actual Results discuss BUB1B R727C/L844F instability and loss of interactions, but the exact wild-type CDC20 pair record was not exposed in the inspected paragraphs. The broad interaction claim is adjudicated using this independent target evidence and deference to the original experimental curator; the unread source-specific table or assay is not represented as independently verified. Refine to ubiquitin ligase inhibitor activity on the independently established BUBR1–CDC20 mechanism, consistently with the other CDC20 rows; the original interaction assay alone is not claimed to demonstrate inhibition. Proposed replacements: ubiquitin ligase inhibitor activity |
| GO:0005515 protein binding | IPI PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apo... | KEEP AS NON CORE | Summary: BUBR1–BUB1 association is independently established; the original source record is retained with its access limit. Reason: Human BUBR1/BUB1 constructs were tested in a stringent three-reporter yeast two-hybrid system; the inspected Results explicitly establish heterodimerization through regions downstream of their N-terminal TPR domains. The complete abstract describes kinase RNAi and overexpression screens for TRAIL-induced apoptosis in DLD-1 cells, with mass-spectrometry interaction maps and quantitative phosphoproteomics. The individual BUBR1 partner assay or supplementary record was not inspected. The broad interaction claim is adjudicated using this independent target evidence and deference to the original experimental curator; the unread source-specific table or assay is not represented as independently verified. Retain the supported generic interaction as non-core under the standing project instruction; no additional molecular activity is inferred from association alone. |
| GO:0005515 protein binding | IPI PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apo... | KEEP AS NON CORE | Summary: BUBR1–BUB3 association is independently established; the original source record is retained with its access limit. Reason: Human BUBR1 and BUB3 constructs show GST-dependent copurification in BHK cells, loss of association after deleting the BUB3-binding region, and corroborating human-construct two-hybrid interaction. The complete abstract describes kinase RNAi and overexpression screens for TRAIL-induced apoptosis in DLD-1 cells, with mass-spectrometry interaction maps and quantitative phosphoproteomics. The individual BUBR1 partner assay or supplementary record was not inspected. The broad interaction claim is adjudicated using this independent target evidence and deference to the original experimental curator; the unread source-specific table or assay is not represented as independently verified. Retain the supported generic interaction as non-core under the standing project instruction; no additional molecular activity is inferred from association alone. |
| GO:0005515 protein binding | IPI PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apo... | MODIFY | Summary: BUBR1–CDC20 association is independently established; the original source record is retained with its access limit. Reason: Human recombinant MCC inhibition and APC/C–MCC structural experiments independently establish BUBR1 contacts that occupy CDC20 substrate-recognition sites and inhibit the ligase. The complete abstract describes kinase RNAi and overexpression screens for TRAIL-induced apoptosis in DLD-1 cells, with mass-spectrometry interaction maps and quantitative phosphoproteomics. The individual BUBR1 partner assay or supplementary record was not inspected. The broad interaction claim is adjudicated using this independent target evidence and deference to the original experimental curator; the unread source-specific table or assay is not represented as independently verified. Refine to ubiquitin ligase inhibitor activity on the independently established BUBR1–CDC20 mechanism, consistently with the other CDC20 rows; the original interaction assay alone is not claimed to demonstrate inhibition. Proposed replacements: ubiquitin ligase inhibitor activity |
| GO:0005515 protein binding | IPI PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apo... | KEEP AS NON CORE | Summary: BUBR1–MAD2 association is independently established; the original source record is retained with its access limit. Reason: Human HeLa MCC purification and reciprocal immunoprecipitation independently establish BUBR1–MAD2 coassociation. This supports complex-associated binding without asserting an isolated binary interface from that experiment. The complete abstract describes kinase RNAi and overexpression screens for TRAIL-induced apoptosis in DLD-1 cells, with mass-spectrometry interaction maps and quantitative phosphoproteomics. The individual BUBR1 partner assay or supplementary record was not inspected. The broad interaction claim is adjudicated using this independent target evidence and deference to the original experimental curator; the unread source-specific table or assay is not represented as independently verified. Retain the supported generic interaction as non-core under the standing project instruction; no additional molecular activity is inferred from association alone. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | KEEP AS NON CORE | Summary: BUBR1–BUB3 association is independently established; the original source record is retained with its access limit. Reason: Human BUBR1 and BUB3 constructs show GST-dependent copurification in BHK cells, loss of association after deleting the BUB3-binding region, and corroborating human-construct two-hybrid interaction. The complete abstract describes a protein-interaction screen; the BUBR1–BUB3 target record was not inspected. The broad interaction claim is adjudicated using this independent target evidence and deference to the original experimental curator; the unread source-specific table or assay is not represented as independently verified. Retain the supported generic interaction as non-core under the standing project instruction; no additional molecular activity is inferred from association alone. |
| GO:0005515 protein binding | IPI PMID:29883609 PELI1 Selectively Targets Kinase-Active RIP3 for Ubiquitylat... | UNDECIDED | Summary: The source-specific interaction remains unresolved. Reason: The complete abstract concerns PELI1-mediated RIPK3 regulation and does not expose the BUBR1–RIPK3 assay. Full source evidence remains uninspected; the title is not a basis for declaring misattribution. The curated partner is UniProtKB:Q9Y572. Under the standing project policy, supported generic binding is retained as non-core when no finer MF is justified; this unread record remains UNDECIDED rather than being removed for lack of specificity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | KEEP AS NON CORE | Summary: BUBR1–BUB1 association is independently established; the original source record is retained with its access limit. Reason: Human BUBR1/BUB1 constructs were tested in a stringent three-reporter yeast two-hybrid system; the inspected Results explicitly establish heterodimerization through regions downstream of their N-terminal TPR domains. The full-text cache contains general interactome methods and results, but the individual BUBR1 partner entry in the underlying interaction data was not inspected. The broad interaction claim is adjudicated using this independent target evidence and deference to the original experimental curator; the unread source-specific table or assay is not represented as independently verified. Retain the supported generic interaction as non-core under the standing project instruction; no additional molecular activity is inferred from association alone. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | MODIFY | Summary: BUBR1–CDC20 association is independently established; the original source record is retained with its access limit. Reason: Human recombinant MCC inhibition and APC/C–MCC structural experiments independently establish BUBR1 contacts that occupy CDC20 substrate-recognition sites and inhibit the ligase. The full-text cache contains general interactome methods and results, but the individual BUBR1 partner entry in the underlying interaction data was not inspected. The broad interaction claim is adjudicated using this independent target evidence and deference to the original experimental curator; the unread source-specific table or assay is not represented as independently verified. Refine to ubiquitin ligase inhibitor activity on the independently established BUBR1–CDC20 mechanism, consistently with the other CDC20 rows; the original interaction assay alone is not claimed to demonstrate inhibition. Proposed replacements: ubiquitin ligase inhibitor activity |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | KEEP AS NON CORE | Summary: BUBR1–BUB3 association is independently established; the original source record is retained with its access limit. Reason: Human BUBR1 and BUB3 constructs show GST-dependent copurification in BHK cells, loss of association after deleting the BUB3-binding region, and corroborating human-construct two-hybrid interaction. The complete abstract and available interactome body do not expose the specific BUBR1 pair; its underlying data row was not inspected. The broad interaction claim is adjudicated using this independent target evidence and deference to the original experimental curator; the unread source-specific table or assay is not represented as independently verified. Retain the supported generic interaction as non-core under the standing project instruction; no additional molecular activity is inferred from association alone. |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | MODIFY | Summary: BUBR1–CDC20 association is independently established; the original source record is retained with its access limit. Reason: Human recombinant MCC inhibition and APC/C–MCC structural experiments independently establish BUBR1 contacts that occupy CDC20 substrate-recognition sites and inhibit the ligase. The complete abstract and available interactome body do not expose the specific BUBR1 pair; its underlying data row was not inspected. The broad interaction claim is adjudicated using this independent target evidence and deference to the original experimental curator; the unread source-specific table or assay is not represented as independently verified. Refine to ubiquitin ligase inhibitor activity on the independently established BUBR1–CDC20 mechanism, consistently with the other CDC20 rows; the original interaction assay alone is not claimed to demonstrate inhibition. Proposed replacements: ubiquitin ligase inhibitor activity |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: BUBR1–BUB1 association is independently established; the original source record is retained with its access limit. Reason: Human BUBR1/BUB1 constructs were tested in a stringent three-reporter yeast two-hybrid system; the inspected Results explicitly establish heterodimerization through regions downstream of their N-terminal TPR domains. The available abstract and partial BioPlex body provide screen context, but the individual BUBR1 partner entry and validation were not inspected. The broad interaction claim is adjudicated using this independent target evidence and deference to the original experimental curator; the unread source-specific table or assay is not represented as independently verified. Retain the supported generic interaction as non-core under the standing project instruction; no additional molecular activity is inferred from association alone. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: BUBR1–BUB3 association is independently established; the original source record is retained with its access limit. Reason: Human BUBR1 and BUB3 constructs show GST-dependent copurification in BHK cells, loss of association after deleting the BUB3-binding region, and corroborating human-construct two-hybrid interaction. The available abstract and partial BioPlex body provide screen context, but the individual BUBR1 partner entry and validation were not inspected. The broad interaction claim is adjudicated using this independent target evidence and deference to the original experimental curator; the unread source-specific table or assay is not represented as independently verified. Retain the supported generic interaction as non-core under the standing project instruction; no additional molecular activity is inferred from association alone. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: BUBR1–CDC20 association is independently established; the original source record is retained with its access limit. Reason: Human recombinant MCC inhibition and APC/C–MCC structural experiments independently establish BUBR1 contacts that occupy CDC20 substrate-recognition sites and inhibit the ligase. The available abstract and partial BioPlex body provide screen context, but the individual BUBR1 partner entry and validation were not inspected. The broad interaction claim is adjudicated using this independent target evidence and deference to the original experimental curator; the unread source-specific table or assay is not represented as independently verified. Refine to ubiquitin ligase inhibitor activity on the independently established BUBR1–CDC20 mechanism, consistently with the other CDC20 rows; the original interaction assay alone is not claimed to demonstrate inhibition. Proposed replacements: ubiquitin ligase inhibitor activity |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: BUBR1–MAD2 association is independently established; the original source record is retained with its access limit. Reason: Human HeLa MCC purification and reciprocal immunoprecipitation independently establish BUBR1–MAD2 coassociation. This supports complex-associated binding without asserting an isolated binary interface from that experiment. The available abstract and partial BioPlex body provide screen context, but the individual BUBR1 partner entry and validation were not inspected. The broad interaction claim is adjudicated using this independent target evidence and deference to the original experimental curator; the unread source-specific table or assay is not represented as independently verified. Retain the supported generic interaction as non-core under the standing project instruction; no additional molecular activity is inferred from association alone. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | KEEP AS NON CORE | Summary: BUBR1–BUB3 association is independently established; the original source record is retained with its access limit. Reason: Human BUBR1 and BUB3 constructs show GST-dependent copurification in BHK cells, loss of association after deleting the BUB3-binding region, and corroborating human-construct two-hybrid interaction. The available abstract and partial interaction-map text do not expose the individual BUBR1 partner assay; the target data record was not inspected. The broad interaction claim is adjudicated using this independent target evidence and deference to the original experimental curator; the unread source-specific table or assay is not represented as independently verified. Retain the supported generic interaction as non-core under the standing project instruction; no additional molecular activity is inferred from association alone. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MODIFY | Summary: BUBR1–CDC20 association is independently established; the original source record is retained with its access limit. Reason: Human recombinant MCC inhibition and APC/C–MCC structural experiments independently establish BUBR1 contacts that occupy CDC20 substrate-recognition sites and inhibit the ligase. The available abstract and partial interaction-map text do not expose the individual BUBR1 partner assay; the target data record was not inspected. The broad interaction claim is adjudicated using this independent target evidence and deference to the original experimental curator; the unread source-specific table or assay is not represented as independently verified. Refine to ubiquitin ligase inhibitor activity on the independently established BUBR1–CDC20 mechanism, consistently with the other CDC20 rows; the original interaction assay alone is not claimed to demonstrate inhibition. Proposed replacements: ubiquitin ligase inhibitor activity |
| GO:0005515 protein binding | IPI PMID:36931259 A central chaperone-like role for 14-3-3 proteins in human c... | UNDECIDED | Summary: The source-specific interaction remains unresolved. Reason: The complete cached abstract does not expose the BUBR1–YWHAE target assay. No claim that the paper lacks such an assay is made. The curated partner is UniProtKB:P62258. Under the standing project policy, supported generic binding is retained as non-core when no finer MF is justified; this unread record remains UNDECIDED rather than being removed for lack of specificity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:37926298 Therapeutic role of 2-stearoxyphenethyl phosphocholine targe... | MODIFY | Summary: BUBR1–CDC20 association is independently established; the original source record is retained with its access limit. Reason: Human recombinant MCC inhibition and APC/C–MCC structural experiments independently establish BUBR1 contacts that occupy CDC20 substrate-recognition sites and inhibit the ligase. The complete pharmacology abstract reports BUBR1 phosphorylation and MAD2–CDC20 association; it does not show the specific BUBR1–CDC20 interaction assay. The full experiment remains uninspected. The broad interaction claim is adjudicated using this independent target evidence and deference to the original experimental curator; the unread source-specific table or assay is not represented as independently verified. Refine to ubiquitin ligase inhibitor activity on the independently established BUBR1–CDC20 mechanism, consistently with the other CDC20 rows; the original interaction assay alone is not claimed to demonstrate inhibition. Proposed replacements: ubiquitin ligase inhibitor activity |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: BUBR1–CDC20 association is independently established; the original source record is retained with its access limit. Reason: Human recombinant MCC inhibition and APC/C–MCC structural experiments independently establish BUBR1 contacts that occupy CDC20 substrate-recognition sites and inhibit the ligase. The available abstract and partial systematic interaction-map text do not expose the BUBR1 pair-specific assay; the underlying data entry was not inspected. The broad interaction claim is adjudicated using this independent target evidence and deference to the original experimental curator; the unread source-specific table or assay is not represented as independently verified. Refine to ubiquitin ligase inhibitor activity on the independently established BUBR1–CDC20 mechanism, consistently with the other CDC20 rows; the original interaction assay alone is not claimed to demonstrate inhibition. Proposed replacements: ubiquitin ligase inhibitor activity |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | KEEP AS NON CORE | Summary: BUBR1–MAD2 association is independently established; the original source record is retained with its access limit. Reason: Human HeLa MCC purification and reciprocal immunoprecipitation independently establish BUBR1–MAD2 coassociation. This supports complex-associated binding without asserting an isolated binary interface from that experiment. The available abstract and partial systematic interaction-map text do not expose the BUBR1 pair-specific assay; the underlying data entry was not inspected. The broad interaction claim is adjudicated using this independent target evidence and deference to the original experimental curator; the unread source-specific table or assay is not represented as independently verified. Retain the supported generic interaction as non-core under the standing project instruction; no additional molecular activity is inferred from association alone. |
| GO:0005515 protein binding | IPI PMID:9660858 The human homologue of Bub3 is required for kinetochore loca... | KEEP AS NON CORE | Summary: Human BUBR1 binds BUB3. Reason: The inspected source expresses human constructs in BHK cells and recovers BUBR1 with GST–BUB3, with loss after deletion of the conserved binding region. BUB3 coexpression also promotes BUBR1 kinetochore localization. This is supported binding, separate from MCC membership. Supporting Evidence: PMID:9660858 hBubR1 can physically interact with hBub3 in mammalian cells |
| GO:0005515 protein binding | IPI PMID:9763420 Characterization of the kinetochore binding domain of CENP-E... | KEEP AS NON CORE | Summary: Human BUBR1 associates with CENP-E. Reason: The inspected HeLa-library two-hybrid, endogenous reciprocal coimmunoprecipitation and fragment-cotransfection Results establish CENP-E–BUBR1 association. The Discussion explicitly leaves direct binary binding unresolved in that study, so no stronger interface claim is made. Supporting Evidence: |
| GO:0005634 nucleus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: The inherited nuclear location is retained as a secondary, cell-cycle-dependent compartment. Reason: The exact nuclear IBD at PTN000361608 includes the human target as descendant evidence. The inspected human PMID:9763420 Results distinguish predominantly cytoplasmic interphase staining from kinetochore recruitment beginning in early prophase; these data do not require constitutive interphase nuclear enrichment. Retain the broad inherited compartment as non-core without inventing a human NLS, an unmeasured nucleoplasmic pool, or a yeast open-versus-closed-mitosis explanation for the node. The full tree and every donor nuclear experiment were not inspected. Human Ramos-cell confocal results in PMID:20531406 independently describe nuclear or perinuclear colocalization; this context does not establish constitutive nuclear enrichment. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Nuclear localization is a secondary context. Reason: The UniProt location transfer is retained with human Ramos-cell confocal evidence for nuclear or perinuclear colocalization. Predominant interphase cytoplasmic staining in HeLa cells is not a contradiction of every nuclear pool; no constitutive nuclear enrichment is inferred. |
| GO:0005680 anaphase-promoting complex | TAS PMID:10477750 Human BUBR1 is a mitotic checkpoint kinase that monitors CEN... | MODIFY | Summary: BUBR1 belongs to the inhibitory MCC associated with APC/C. Reason: The original human study shows mitotic coassociation with APC/C subunits. Later biochemical separation and structures distinguish the BUBR1-containing MCC from the catalytic APC/C complex. GO:0005680 denotes the ubiquitin-ligase complex; MCC membership is the more precise cellular-component assertion and does not deny the observed supercomplex association. Proposed replacements: mitotic checkpoint complex |
| GO:0005737 cytoplasm | IDA GO_REF:0000054 | ACCEPT | Summary: BUBR1 has a functional cytoplasmic pool. Reason: Human HeLa imaging in PMID:9763420 directly shows a cytoplasmic interphase pool, and human biochemical MCC purification supports the soluble cytosolic checkpoint pool. The exact original localization panel or database image was not independently inspected; the retained broad compartment is independently well established. |
| GO:0005737 cytoplasm | IDA PMID:14706340 Dual roles of human BubR1, a mitotic checkpoint kinase, in t... | ACCEPT | Summary: BUBR1 has a functional cytoplasmic pool. Reason: Human HeLa imaging in PMID:9763420 directly shows a cytoplasmic interphase pool, and human biochemical MCC purification supports the soluble cytosolic checkpoint pool. The exact original localization panel or database image was not independently inspected; the retained broad compartment is independently well established. |
| GO:0005737 cytoplasm | IDA PMID:20220147 Defining the molecular basis of BubR1 kinetochore interactio... | ACCEPT | Summary: BUBR1 has a functional cytoplasmic pool. Reason: Human HeLa imaging in PMID:9763420 directly shows a cytoplasmic interphase pool, and human biochemical MCC purification supports the soluble cytosolic checkpoint pool. The exact original localization panel or database image was not independently inspected; the retained broad compartment is independently well established. |
| GO:0005737 cytoplasm | IDA PMID:9763420 Characterization of the kinetochore binding domain of CENP-E... | ACCEPT | Summary: BUBR1 has a functional cytoplasmic pool. Reason: Human HeLa imaging in PMID:9763420 directly shows a cytoplasmic interphase pool, and human biochemical MCC purification supports the soluble cytosolic checkpoint pool. Supporting Evidence: PMID:9763420 it was concentrated in the cytoplasm of all interphase cells |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: BUBR1 has a functional cytoplasmic pool. Reason: Human HeLa imaging in PMID:9763420 directly shows a cytoplasmic interphase pool, and human biochemical MCC purification supports the soluble cytosolic checkpoint pool. |
| GO:0005813 centrosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Retain the curated centrosomal pool of BUBR1 as non-core. Reason: The immutable UniProt record explicitly records centrosomal localization and identifies the original centrosome study. The independently read official primary abstract also explicitly reports localization, separately from centrosome-amplification phenotypes; its URL and access limit are recorded in the notes. Retain the claim by curator deference with UniProt as the in-repository support. The original localization images and full experimental section were not inspected, and centrosome-number phenotypes alone are not used as localization evidence. Supporting Evidence: GO_REF:0000044 file:human/BUB1B/BUB1B-uniprot.txt |
| GO:0005819 spindle | IDA PMID:9763420 Characterization of the kinetochore binding domain of CENP-E... | KEEP AS NON CORE | Summary: BUBR1 transiently decorates the anaphase spindle. Reason: The inspected human HeLa Results describe diffuse spindle distribution in mid-anaphase and two patches in the late-anaphase spindle midzone, distinct from CENP-E. Retain this stage-specific location as non-core; no microtubule motor or constitutive spindle structural role is inferred. Supporting Evidence: |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: BUBR1 has a functional cytoplasmic pool. Reason: Human HeLa imaging in PMID:9763420 directly shows a cytoplasmic interphase pool, and human biochemical MCC purification supports the soluble cytosolic checkpoint pool. The exact original localization panel or database image was not independently inspected; the retained broad compartment is independently well established. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-141409 | ACCEPT | Summary: BUBR1 functions in the soluble cytosolic checkpoint pool. Reason: The cached Reactome entry describes Mad1 binds kinetochore. This source row asserts cytosol, not that BUBR1 catalyzes every reaction named by the pathway entry. Retain the compartment on independent human cytoplasmic imaging and soluble MCC purification; the short Reactome summary does not expose the complete participant graph. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-141422 | ACCEPT | Summary: BUBR1 functions in the soluble cytosolic checkpoint pool. Reason: The cached Reactome entry describes MAD2 converted to an inhibitory state via interaction with Mad1. This source row asserts cytosol, not that BUBR1 catalyzes every reaction named by the pathway entry. Retain the compartment on independent human cytoplasmic imaging and soluble MCC purification; the short Reactome summary does not expose the complete participant graph. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-141423 | ACCEPT | Summary: BUBR1 functions in the soluble cytosolic checkpoint pool. Reason: The cached Reactome entry describes Binding of the MCC complex to the APC/C complex. This source row asserts cytosol, not that BUBR1 catalyzes every reaction named by the pathway entry. Retain the compartment on independent human cytoplasmic imaging and soluble MCC purification; the short Reactome summary does not expose the complete participant graph. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-141431 | ACCEPT | Summary: BUBR1 functions in the soluble cytosolic checkpoint pool. Reason: The cached Reactome entry describes MAD2 associates with the Mad1 kinetochore complex. This source row asserts cytosol, not that BUBR1 catalyzes every reaction named by the pathway entry. Retain the compartment on independent human cytoplasmic imaging and soluble MCC purification; the short Reactome summary does not expose the complete participant graph. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-141437 | ACCEPT | Summary: BUBR1 functions in the soluble cytosolic checkpoint pool. Reason: The cached Reactome entry describes Formation of the MCC complex. This source row asserts cytosol, not that BUBR1 catalyzes every reaction named by the pathway entry. Retain the compartment on independent human cytoplasmic imaging and soluble MCC purification; the short Reactome summary does not expose the complete participant graph. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-141439 | ACCEPT | Summary: BUBR1 functions in the soluble cytosolic checkpoint pool. Reason: The cached Reactome entry describes Release of activated MAD2 from kinetochores. This source row asserts cytosol, not that BUBR1 catalyzes every reaction named by the pathway entry. Retain the compartment on independent human cytoplasmic imaging and soluble MCC purification; the short Reactome summary does not expose the complete participant graph. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1638803 | ACCEPT | Summary: BUBR1 functions in the soluble cytosolic checkpoint pool. Reason: The cached Reactome entry describes Phosphorylation of cohesin by PLK1 at centromeres. This source row asserts cytosol, not that BUBR1 catalyzes every reaction named by the pathway entry. Retain the compartment on independent human cytoplasmic imaging and soluble MCC purification; the short Reactome summary does not expose the complete participant graph. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1638821 | ACCEPT | Summary: BUBR1 functions in the soluble cytosolic checkpoint pool. Reason: The cached Reactome entry describes PP2A-B56 dephosphorylates centromeric cohesin. This source row asserts cytosol, not that BUBR1 catalyzes every reaction named by the pathway entry. Retain the compartment on independent human cytoplasmic imaging and soluble MCC purification; the short Reactome summary does not expose the complete participant graph. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-174104 | ACCEPT | Summary: BUBR1 functions in the soluble cytosolic checkpoint pool. Reason: The cached Reactome entry describes Ubiquitination of Cyclin A by APC/C:Cdc20 complex. This source row asserts cytosol, not that BUBR1 catalyzes every reaction named by the pathway entry. Retain the compartment on independent human cytoplasmic imaging and soluble MCC purification; the short Reactome summary does not expose the complete participant graph. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-174171 | ACCEPT | Summary: BUBR1 functions in the soluble cytosolic checkpoint pool. Reason: The cached Reactome entry describes Association of Cyclin A with the APC/C. This source row asserts cytosol, not that BUBR1 catalyzes every reaction named by the pathway entry. Retain the compartment on independent human cytoplasmic imaging and soluble MCC purification; the short Reactome summary does not expose the complete participant graph. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-174238 | ACCEPT | Summary: BUBR1 functions in the soluble cytosolic checkpoint pool. Reason: The cached Reactome entry describes Activation of APC/C:Cdc20 by dissociation of Cdc20:phospho-APC/C from Cdc20:phospho-APC/C:Mad2:Bub3:BubR1. This source row asserts cytosol, not that BUBR1 catalyzes every reaction named by the pathway entry. Retain the compartment on independent human cytoplasmic imaging and soluble MCC purification; the short Reactome summary does not expose the complete participant graph. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-174255 | ACCEPT | Summary: BUBR1 functions in the soluble cytosolic checkpoint pool. Reason: The cached Reactome entry describes Degradation multiubiquitinated Cyclin A. This source row asserts cytosol, not that BUBR1 catalyzes every reaction named by the pathway entry. Retain the compartment on independent human cytoplasmic imaging and soluble MCC purification; the short Reactome summary does not expose the complete participant graph. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-179410 | ACCEPT | Summary: BUBR1 functions in the soluble cytosolic checkpoint pool. Reason: The cached Reactome entry describes Association of Nek2A with MCC:APC/C. This source row asserts cytosol, not that BUBR1 catalyzes every reaction named by the pathway entry. Retain the compartment on independent human cytoplasmic imaging and soluble MCC purification; the short Reactome summary does not expose the complete participant graph. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-179417 | ACCEPT | Summary: BUBR1 functions in the soluble cytosolic checkpoint pool. Reason: The cached Reactome entry describes Multiubiquitination of Nek2A. This source row asserts cytosol, not that BUBR1 catalyzes every reaction named by the pathway entry. Retain the compartment on independent human cytoplasmic imaging and soluble MCC purification; the short Reactome summary does not expose the complete participant graph. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-179421 | ACCEPT | Summary: BUBR1 functions in the soluble cytosolic checkpoint pool. Reason: The cached Reactome entry describes Degradation of multiubiquitinated Nek2A. This source row asserts cytosol, not that BUBR1 catalyzes every reaction named by the pathway entry. Retain the compartment on independent human cytoplasmic imaging and soluble MCC purification; the short Reactome summary does not expose the complete participant graph. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2467809 | ACCEPT | Summary: BUBR1 functions in the soluble cytosolic checkpoint pool. Reason: The cached Reactome entry describes ESPL1 (Separase) cleaves centromeric cohesin. This source row asserts cytosol, not that BUBR1 catalyzes every reaction named by the pathway entry. Retain the compartment on independent human cytoplasmic imaging and soluble MCC purification; the short Reactome summary does not expose the complete participant graph. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2467811 | ACCEPT | Summary: BUBR1 functions in the soluble cytosolic checkpoint pool. Reason: The cached Reactome entry describes Separation of sister chromatids. This source row asserts cytosol, not that BUBR1 catalyzes every reaction named by the pathway entry. Retain the compartment on independent human cytoplasmic imaging and soluble MCC purification; the short Reactome summary does not expose the complete participant graph. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2468287 | ACCEPT | Summary: BUBR1 functions in the soluble cytosolic checkpoint pool. Reason: The cached Reactome entry describes CDK1 phosphorylates CDCA5 (Sororin) at centromeres. This source row asserts cytosol, not that BUBR1 catalyzes every reaction named by the pathway entry. Retain the compartment on independent human cytoplasmic imaging and soluble MCC purification; the short Reactome summary does not expose the complete participant graph. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2484822 | ACCEPT | Summary: BUBR1 functions in the soluble cytosolic checkpoint pool. Reason: The cached Reactome entry describes Kinetochore assembly. This source row asserts cytosol, not that BUBR1 catalyzes every reaction named by the pathway entry. Retain the compartment on independent human cytoplasmic imaging and soluble MCC purification; the short Reactome summary does not expose the complete participant graph. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-375302 | ACCEPT | Summary: BUBR1 functions in the soluble cytosolic checkpoint pool. Reason: The cached Reactome entry describes Kinetochore capture of astral microtubules. This source row asserts cytosol, not that BUBR1 catalyzes every reaction named by the pathway entry. Retain the compartment on independent human cytoplasmic imaging and soluble MCC purification; the short Reactome summary does not expose the complete participant graph. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5666129 | ACCEPT | Summary: BUBR1 functions in the soluble cytosolic checkpoint pool. Reason: The cached Reactome entry describes CDC42:GTP recruits DIAPH2-2 to kinetochores. This source row asserts cytosol, not that BUBR1 catalyzes every reaction named by the pathway entry. Retain the compartment on independent human cytoplasmic imaging and soluble MCC purification; the short Reactome summary does not expose the complete participant graph. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5666160 | ACCEPT | Summary: BUBR1 functions in the soluble cytosolic checkpoint pool. Reason: The cached Reactome entry describes AURKB phosphorylates DIAPH2-2 at kinetochores. This source row asserts cytosol, not that BUBR1 catalyzes every reaction named by the pathway entry. Retain the compartment on independent human cytoplasmic imaging and soluble MCC purification; the short Reactome summary does not expose the complete participant graph. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5666169 | ACCEPT | Summary: BUBR1 functions in the soluble cytosolic checkpoint pool. Reason: The cached Reactome entry describes Kinetochore capture of astral microtubules is positively regulated by CDC42:GTP:p-S196-DIAPH2-2. This source row asserts cytosol, not that BUBR1 catalyzes every reaction named by the pathway entry. Retain the compartment on independent human cytoplasmic imaging and soluble MCC purification; the short Reactome summary does not expose the complete participant graph. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9648114 | ACCEPT | Summary: BUBR1 functions in the soluble cytosolic checkpoint pool. Reason: The cached Reactome entry describes EML4 recruits NUDC to mitotic spindle. This source row asserts cytosol, not that BUBR1 catalyzes every reaction named by the pathway entry. Retain the compartment on independent human cytoplasmic imaging and soluble MCC purification; the short Reactome summary does not expose the complete participant graph. |
| GO:0007094 mitotic spindle assembly checkpoint signaling | IBA GO_REF:0000033 | ACCEPT | Summary: BUBR1 directly participates in mitotic spindle-checkpoint signaling. Reason: The exact non-negated checkpoint IBD at PTN000361607 and its seed set match this source. Independent human experiments demonstrate checkpoint dependence on BUBR1 (PMID:10477750), and purification of an APC/C-inhibitory BUBR1/BUB3/CDC20/MAD2 complex from HeLa cells supplies a direct mechanism (PMID:11535616). These findings support the inherited pathway without depending on BUBR1 kinase catalysis or a newly reconstructed family duplication history. Human self-source is not circular evidence. |
| GO:0007094 mitotic spindle assembly checkpoint signaling | IDA PMID:10477750 Human BUBR1 is a mitotic checkpoint kinase that monitors CEN... | ACCEPT | Summary: BUBR1 directly enforces the mitotic checkpoint. Reason: In the original human HeLa study, antibody interference with BUBR1 and a BUBR1 deletion construct prevented sustained nocodazole arrest and allowed abnormal mitotic exit. Those cell experiments support checkpoint participation without establishing which BUBR1 activity is catalytic. Independent human MCC purification and recombinant APC/C inhibition identify the inhibitory mechanism. Retain the source IDA process annotation. Supporting Evidence: PMID:10477750 disruption of hBUBR1 function prevented cells from arresting in mitosis |
| GO:0007094 mitotic spindle assembly checkpoint signaling | IEA GO_REF:0000002 | ACCEPT | Summary: BUBR1 directly enforces the mitotic checkpoint. Reason: The source IEA maps InterPro:IPR015661 to spindle-checkpoint signaling. Independently inspected human checkpoint-interference experiments, MCC purification and recombinant APC/C inhibition substantiate this target-level process. Family membership is consistent with, rather than a substitute for, the direct human mechanism. |
| GO:0007094 mitotic spindle assembly checkpoint signaling | IMP PMID:20220147 Defining the molecular basis of BubR1 kinetochore interactio... | ACCEPT | Summary: BUBR1 directly enforces the mitotic checkpoint. Reason: The original structural study directly tests human BUBR1–Blinkin/BUB1/BUB3 interaction determinants, but its proposed linkage to sustained checkpoint arrest is partly a model and the exact source IMP assay was not independently resolved. Retain the process by curator deference because independent human BUBR1-interference experiments and MCC inhibitory biochemistry establish direct checkpoint participation. The original paper is not represented as a newly inspected checkpoint-rescue assay. |
| GO:0007094 mitotic spindle assembly checkpoint signaling | NAS PMID:11535616 Checkpoint inhibition of the APC/C in HeLa cells is mediated... | ACCEPT | Summary: BUBR1 directly enforces the mitotic checkpoint. Reason: The source paper purifies an inhibitory human HeLa complex containing BUBR1, BUB3, CDC20 and MAD2 and directly assays APC/C inhibition. This supplies a physical inhibitory mechanism for checkpoint signaling. Retain the NAS source code unchanged; the experimental content corroborates the process without assigning BUBR1 intrinsic kinase activity. Supporting Evidence: PMID:11535616 Purified GST–hBUBR1:MCC was found to inhibit ubiquitin ligase activity of the APC/C |
| GO:0033045 regulation of sister chromatid segregation | IEA GO_REF:0000117 | ACCEPT | Summary: BUBR1 directly enforces the mitotic checkpoint. Reason: Human checkpoint perturbation, MCC purification and reconstituted APC/C inhibition establish that BUBR1 itself supplies inhibitory contacts that restrain anaphase and sister-chromatid separation. This is direct participation, independent of the disputed intrinsic kinase activity. |
| GO:0033597 mitotic checkpoint complex | IPI PMID:27509861 Molecular basis of APC/C regulation by the spindle assembly ... | ACCEPT | Summary: BUBR1 is an inhibitory MCC subunit. Reason: The inspected recombinant human APC/C–MCC structural and biochemical experiments explicitly include BUBR1 with BUB3, CDC20 and MAD2. BUBR1 inhibitory contacts are distinct from APC/C ubiquitin-ligase catalysis. |
| GO:0048471 perinuclear region of cytoplasm | IDA PMID:20531406 A human B-cell interactome identifies MYB and FOXM1 as maste... | KEEP AS NON CORE | Summary: Perinuclear BUBR1 staining occurs in a human lymphoma-cell context. Reason: The inspected Results and confocal Methods report nuclear or perinuclear colocalization of BUBR1 with MCM3 in Ramos cells. This is not direct imaging of normal germinal-centre tissue. Retain the reported context-dependent compartment without elevating it to a core location. Supporting Evidence: |
| GO:0051754 meiotic sister chromatid cohesion, centromeric | IBA GO_REF:0000033 | UNDECIDED | Summary: The meiotic cohesion transfer is plausible but its target-level evolutionary and mechanistic scope remains unresolved. Reason: The exact PTN000361607 IBD is seeded by FBgn0263855 and SPCC1322.12c. Official FlyBase identifies the former as BubR1 and links the exact centromeric meiotic-cohesion term to Malmanche et al. (2007) mutant evidence; PomBase identifies the latter as Bub1 with meiotic cohesion and H2A-kinase-related annotations. These are real donor assertions, not weak evidence merely because there are two donors. However, the relevant full donor experiments and complete ancestral tree/MSA were not inspected. Human mitotic PP2A recruitment or attachment control alone does not establish the specific meiotic process. Retain uncertainty without asserting target loss, a wrong node, or an unverified pre-duplication topology. This is uncertainty about the exact meiotic participation and inheritance scope, not a requirement for a separate human experiment or a rejection of phylogenetic inference. No contrary target experiment is asserted and the IBA is not removed. Supporting Evidence: GO_REF:0000033 |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000116 | UNDECIDED | Summary: Intrinsic human BUBR1 kinase activity remains disputed. Reason: PMID:31201382 directly reports recombinant CENP-E-tail phosphorylation at Ser2639, loss with substrate S2639A and BUBR1 D911A/D882N, BRT-1 sensitivity, and corroborating mitotic-cell phosphorylation observations. This is positive serine-specific evidence, not a generic kinase-domain prediction. The attribution of intrinsic human BUBR1 catalysis nevertheless remains in conflict with negative human-domain and cellular immunoprecipitate tests under different conditions. Preserve the RHEA-derived source and leave the catalytic judgment UNDECIDED pending reconciliation; noncatalytic checkpoint activity is not evidence against every catalytic condition. |
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Download this section (compressed HTML)Q: Which differences in human BUBR1 construct, purification, associated kinases and substrate account for the conflicting positive and negative intrinsic kinase assays?
Q: Does the ancestral meiotic centromeric-cohesion assertion reflect a conserved human BUBR1 mechanism? Full donor assays and PAINT node placement remain to be examined.
Q: Which source-specific screen interactions and the distinct centrosomal localization can be confirmed from original target-level records?
Experiment: Compare full-length human BUBR1 and kinase-domain constructs purified from matched expression systems, with quantitative contaminant controls, catalytic-site and stability controls, and CENP-E and histone substrates. Separate phosphotransfer from protein-stability and PP2A-recruitment effects.
Type: biochemical
Experiment: Use separable CDC20-contact and KARD/B56-binding mutants in human cells to quantify checkpoint inhibition, phosphatase recruitment and attachment stabilization, with expression and kinetochore-localization controls.
Type: genetic
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