BUB1B encodes BubR1, the MAD3-related subunit of the mitotic checkpoint complex (MCC; MAD2-BUBR1-BUB3-CDC20), the diffusible inhibitor generated by the spindle assembly checkpoint. During prometaphase BubR1 is recruited to unattached outer kinetochores through its GLEBS motif-bound partner BUB3, a direct BUB1 interaction and TPR-domain contacts with KNL1; MPS1-phosphorylated KNL1 and the MAD1-C-MAD2 template then drive incorporation of BubR1-BUB3 and MAD2-CDC20 into the MCC. Within the MCC, BubR1 KEN-box, ABBA-motif and D-box degron-like sequences occupy the substrate-recognition sites of CDC20, and its N-terminal TPR domain obstructs binding of the initiating E2 UbcH10, so that APC/C-CDC20 cannot ubiquitinate securin and cyclin B and anaphase is delayed until every kinetochore is attached. The MCC can also inhibit a second, APC/C-bound CDC20, and checkpoint silencing proceeds through p31comet/TRIP13-driven MCC disassembly and CDC20(MCC) autoubiquitination. A second, kinetochore-local function is mediated by the central kinetochore attachment regulatory domain (KARD): CDK1/PLK1 phosphorylation of the KARD LxxIxE motif recruits PP2A-B56, which counteracts Aurora B and MPS1 phosphorylation to stabilise correct kinetochore-microtubule attachments, support chromosome congression and promote checkpoint silencing. The C-terminal kinase-like domain of human BubR1 has degenerate catalytic motifs and is generally regarded as a pseudokinase that acts allosterically to support KARD function; a report that it phosphorylates CENP-E Ser2639 to switch the motor from lateral to end-on microtubule tracking remains contested. BubR1 is cytoplasmic in interphase, accumulates at kinetochores from prophase, and also decorates the spindle midzone in late anaphase. Its abundance is controlled by acetylation (PCAF, CBP, SIRT2) and APC/C-dependent degradation, and it declines with age in mouse tissues. Biallelic loss-of-function variants cause mosaic variegated aneuploidy syndrome 1, with premature chromatid separation, growth restriction, microcephaly and childhood cancer predisposition.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000776 kinetochore | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT node PTN000361607 (the Bub1/BubR1-Mad3 ancestor) places kinetochore localization at the base of the family; human BUBR1 is a canonical outer-kinetochore protein recruited to unattached kinetochores via BUB3 (GLEBS motif), BUB1 and KNL1. Reason: Kinetochore localization is the site of BUBR1's checkpoint and attachment-regulating functions and is directly demonstrated for the human protein (PMID:9660858, PMID:9763420, PMID:22331848). The phylogenetic placement is sound: every extant member used to seed the node (yeast Bub1/Mad3, worm, fly, plant and mammalian Bub1/BubR1) localizes to kinetochores. BUB1B appearing in its own WITH/FROM reflects its experimental annotation being one of the descendant evidences. Supporting Evidence: PMID:9660858 In addition, hBubR1 can localize to kinetochores during prometaphase and the ability to bind Bub3 is required for this localization. PMID:9763420 The combined data show that hBUBR1 assembled onto kinetochores sometime in prophase, after CENP-F but before CENP-E. |
| GO:0000776 kinetochore | IDA PMID:12925705 Centromere-associated protein-E is essential for the mammali... | ACCEPT | Summary: Weaver et al. show that BubR1 is recruited to unattached kinetochores and that CENP-E enhances this recruitment; BubR1 kinetochore signal is diminished in CENP-E-null cells. Reason: Direct immunofluorescence of BubR1 at kinetochores, with a quantitative dependence on its binding partner CENP-E, supports the localization (colocalizes_with qualifier reflects co-staining with kinetochore markers). Supporting Evidence: PMID:12925705 Without CENP-E, diminished levels of BubR1 are recruited to kinetochores and BubR1 kinase activity remains at basal levels. |
| GO:0000776 kinetochore | IDA PMID:17227893 Loss of APC induces polyploidy as a result of a combination ... | ACCEPT | Summary: Dietrich et al. quantified kinetochore-associated BubR1 (against CREST) in U2OS cells and APC-deficient fibroblasts, showing reduced kinetochore BubR1 after loss of the APC tumour suppressor. Reason: BubR1 kinetochore localization is directly imaged and quantified in human cells; the paper's focus on APC/polyploidy does not change the validity of the localization. Supporting Evidence: PMID:17227893 APC-deficient cells accumulate relatively less Bub1 and BubR1 at their kinetochores during mitosis, particularly during prometaphase. |
| GO:0000776 kinetochore | IDA PMID:17363900 The human Nup107-160 nuclear pore subcomplex contributes to ... | ACCEPT | Summary: Zuccolo et al. studied Nup107-160 complex function at kinetochores; BubR1 kinetochore staining was used as a checkpoint/kinetochore readout in Seh1-depleted cells (cached text is abstract-only). Reason: Cached record is abstract-only, so the specific BubR1 image cannot be checked, but kinetochore localization of BubR1 is unambiguous from multiple independent studies (PMID:9763420, PMID:22331848); deferring to the curator who read the full text. Supporting Evidence: PMID:17363900 Further analysis of Seh1-depleted cells revealed impaired chromosome congression, reduced kinetochore tension and kinetochore-microtubule attachment defects. PMID:9763420 The combined data show that hBUBR1 assembled onto kinetochores sometime in prophase, after CENP-F but before CENP-E. |
| GO:0000776 kinetochore | IDA PMID:19465021 A nucleolar protein RRS1 contributes to chromosome congressi... | ACCEPT | Summary: Gambe et al. examined the nucleolar protein RRS1 in chromosome congression; BubR1 kinetochore staining served as a marker in RRS1-depleted cells (abstract-only cache). Reason: Localization is correct and well established; the cached abstract does not show the BubR1 panel, so this row is accepted on the strength of the broader literature and curator judgment. Supporting Evidence: PMID:19465021 RRS1 knockdown also perturbs the centromeric localization of Shugoshin 1 and results in premature separation of sister chromatids. PMID:9660858 In addition, hBubR1 can localize to kinetochores during prometaphase and the ability to bind Bub3 is required for this localization. |
| GO:0000776 kinetochore | IDA PMID:20220147 Defining the molecular basis of BubR1 kinetochore interactio... | ACCEPT | Summary: D'Arcy et al. define the N-terminal TPR domain of human BubR1 and its direct interactions with Blinkin/KNL1 and Bub1 that recruit BubR1 to unattached kinetochores. Reason: The paper directly addresses the molecular basis of BubR1 kinetochore recruitment (TPR-Blinkin and BubR1-Bub1 interactions) in the context of kinetochore-localized BubR1. Supporting Evidence: PMID:20220147 First, BubR1 is recruited to kinetochores incorrectly/not attached to the mitotic spindle through a direct interaction with Bub1. PMID:20220147 BubR1 kinetochore enrichment is dependent on Bub1 and Bub3 (28, 29) and is required to sustain a SAC arrest, as well as for stable kinetochore-microtubule interactions (23). |
| GO:0000776 kinetochore | IDA PMID:22331848 Structural analysis reveals features of the spindle checkpoi... | ACCEPT | Summary: Krenn et al. mapped determinants of Bub1 and BubR1 kinetochore recruitment: TPR-Knl1 KI-motif interactions are dispensable, whereas the Bub3-binding (GLEBS) region is required. Reason: Direct localization of BubR1 deletion mutants in human cells; confirms kinetochore localization and its dependence on Bub3 binding. Supporting Evidence: PMID:22331848 Analogously to the results obtained with Bub1 deletion mutants, deletion of the TPR domain of BubR1 (BubR1(Ξ204) or BubR1(Ξ328)) did not evidently affect kinetochore recruitment (Fig. PMID:22331848 An important conclusion from our analysis is that the integrity of the Bub3-binding region of Bub1 is important for the interaction of Bub1 with BubR1 and with kinetochores (Fig. |
| GO:0000776 kinetochore | IDA PMID:9660858 The human homologue of Bub3 is required for kinetochore loca... | ACCEPT | Summary: Taylor et al. identified hBubR1 as a Mad3/Bub1-related protein that binds hBub3 and localizes to prometaphase kinetochores in a Bub3-dependent manner (a 42-residue GLEBS deletion abolishes both Bub3 binding and kinetochore localization). Reason: Founding demonstration of BubR1 kinetochore localization and its Bub3 dependence. Supporting Evidence: PMID:9660858 In addition, hBubR1 can localize to kinetochores during prometaphase and the ability to bind Bub3 is required for this localization. |
| GO:0000776 kinetochore | IDA PMID:9763420 Characterization of the kinetochore binding domain of CENP-E... | ACCEPT | Summary: Chan et al. showed hBUBR1 assembles onto kinetochores in prophase (after CENP-F, before CENP-E), is enriched on unaligned chromosomes, and co-immunoprecipitates with CENP-E. Reason: Direct immunofluorescence of endogenous hBUBR1 at kinetochores in HeLa cells, including its temporal order of assembly. Supporting Evidence: PMID:9763420 The combined data show that hBUBR1 assembled onto kinetochores sometime in prophase, after CENP-F but before CENP-E. |
| GO:0000776 kinetochore | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara transfer of kinetochore localization from mouse Bub1b, which is itself well supported. Reason: Consistent with abundant direct evidence for human BUBR1 at kinetochores (PMID:9763420, PMID:22331848). Supporting Evidence: PMID:9763420 The combined data show that hBUBR1 assembled onto kinetochores sometime in prophase, after CENP-F but before CENP-E. |
| GO:0000940 outer kinetochore | IDA PMID:19468067 Mitotic control of kinetochore-associated dynein and spindle... | ACCEPT | Summary: Chan et al. (Spindly paper) used BubR1 as the reference outer-kinetochore marker: hSpindly colocalizes with BubR1 adjacent to the CREST (inner centromere) signal. Reason: BubR1 occupies the outer kinetochore, external to CREST antigens, consistent with its recruitment by the KNL1-BUB1-BUB3 outer-kinetochore platform. Supporting Evidence: PMID:19468067 Colocalization with BubR1, adjacent to the CREST signal, indicated that hSpindly is an outer KT protein (Fig. |
| GO:0000940 outer kinetochore | IDA PMID:22331848 Structural analysis reveals features of the spindle checkpoi... | ACCEPT | Summary: Krenn et al. show BubR1 is recruited to kinetochores through the outer-kinetochore protein Knl1 and Bub1/Bub3. Reason: Recruitment through Knl1 (a KMN-network outer-kinetochore subunit) and colocalization with Bub1 place BubR1 in the outer kinetochore. Supporting Evidence: PMID:22331848 An important conclusion from our analysis is that the integrity of the Bub3-binding region of Bub1 is important for the interaction of Bub1 with BubR1 and with kinetochores (Fig. PMID:22331848 (A) Schematic view of the domain structure of Bub1, BubR1, and Knl1; TPR, tetratricopeptide repeats; Bub3-BD, Bub3-binding domain, also known as GLEBS motif; KEN, KEN box; PP1-BD, protein phosphatase 1βbinding domain; KI1, Bub1-binding domain 1; KI2, BubR1-binding domain 2; Mis12-BD, Mis12-binding domain; N, N terminus. |
| GO:0000940 outer kinetochore | IEA GO_REF:0000120 | ACCEPT | Summary: Combined automated (ARBA/Ensembl) assignment of outer kinetochore, mirroring the experimental rows. Reason: Redundant with direct evidence (PMID:19468067, PMID:22331848); consistent. Supporting Evidence: PMID:19468067 Colocalization with BubR1, adjacent to the CREST signal, indicated that hSpindly is an outer KT protein (Fig. |
| GO:0004672 protein kinase activity | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: PAINT node PTN000361607 asserts protein kinase activity for the Bub1/BubR1 ancestor, seeded by genuine kinases (yeast Bub1, human BUB1, worm bub-1) and by the disputed BUB1B/hBubR1 activity. Human BUBR1 retains a C-terminal kinase-like fold but has degenerate glycine-rich and catalytic-loop motifs, and its catalytic competence is disputed: early in vitro autophosphorylation and CENP-E-stimulated activity in immunoprecipitates could not exclude co-purifying kinases, kinase activity is dispensable for APC/C-CDC20 inhibition, and phylogenomic/structural/biochemical work classifies the domain as a pseudokinase whose role is allosteric (promoting KARD phosphorylation and PP2A-B56 recruitment). One 2019 study reports bona fide phosphotransfer by purified human BubR1 onto CENP-E Ser2639, so the activity cannot be called refuted, but it is not the established core function of the protein. Reason: The node placement is reasonable for the ancestral Bub1-like protein, but BUB1B is a paralog whose kinase domain has diverged: it lacks conserved catalytic-loop residues (PMID:9660858), kinase activity is not required for its APC/C-inhibitory function (PMID:11702782), and the field's consensus (see deep research) is that human BubR1 is a pseudokinase, with a single contrary report of phosphotransfer (PMID:31201382). Not refuted, so not REMOVE; but it should not be read as a core function. The propagation issue is target-specific functional divergence (pseudokinase), not a bad source. Propagation Review Root cause: PROPAGATION BAD Failure modes: PSEUDO OR SUBACTIVITY LOSS WRONG ORTHOLOG OR PARALOG Sources checked: PANTHER:PTN000361607 Β· PTN000361607 SUPPORTS SOURCE BUT NOT TARGET Node predates the Bub1/BubR1 duplication; kinase activity is genuine for the Bub1 branch but the BubR1 branch became a pseudokinase in most lineages. UniProtKB:O43683 Β· BUB1 SUPPORTS SOURCE BUT NOT TARGET Human BUB1 is an active Ser/Thr kinase (H2A-T120); the paralog BUB1B is not established to be. UniProtKB:O60566 Β· BUB1B SOURCE WEAK OR INFERRED The target's own experimental kinase annotations rest on immunoprecipitate/autophosphorylation assays and one disputed 2019 report. Supporting Evidence: PMID:9660858 hBubR1 lacks several of the residues that are usually highly conserved among most protein kinases PMID:11702782 Surprisingly, the kinase activity of BubR1 is not required for the inhibition of APCCdc20. PMID:31201382 Despite prior experimental evidence that BubR1 has kinase activity, this has been highly controversial, as a widely held view is that BubR1 is an unusual pseudokinase containing modules to interact with Bub1, Bub3, PP2A-B56 and KNL. file:human/BUB1B/BUB1B-deep-research-falcon.md Phylogenomic, structural and direct biochemical analyses found no convincing intrinsic phosphotransfer activity. |
| GO:0004672 protein kinase activity | IDA PMID:31201382 BubR1 phosphorylates CENP-E as a switch enabling the transit... | MARK AS OVER ANNOTATED | Summary: Huang et al. report crystal structures of the Drosophila BubR1 kinase domain in an active conformation and enzymatic assays showing purified human BubR1 has catalytic activity (reduced by K795A/D911A/D882N) that phosphorylates CENP-E Ser2639, switching CENP-E from lateral to end-on microtubule tracking. Reason: This is a direct experimental claim and must not be dismissed, but it contradicts a substantial body of phylogenomic, structural and biochemical evidence that human BubR1 is a pseudokinase, and the authors themselves note the active-kinase salt-bridge signature is not conserved in human BubR1. Treated as a disputed, non-core activity pending independent reconciliation; the reference is flagged DISPUTED in reference_review. Supporting Evidence: PMID:31201382 Indeed, human BubR1 WT was found to have catalytic activity and our enzymatic assays confirmed that Lys795 and Asp911 are critical for that activity (Fig. 1e ). PMID:31201382 Thus, Ser2639 of CENP-E is a substrate for BubR1 in vitro. PMID:31201382 However, this type of signature of an active kinase is not apparently conserved in human BubR1. |
| GO:0004672 protein kinase activity | NAS PMID:9763420 Characterization of the kinetochore binding domain of CENP-E... | MARK AS OVER ANNOTATED | Summary: Chan et al. 1998 inferred kinase function for hBUBR1 from its C-terminal kinase domain and sequence relationship to BUB1; no activity was measured. Reason: Author-statement based on domain presence only. Human BUBR1 retains a C-terminal kinase-like fold but has degenerate glycine-rich and catalytic-loop motifs, and its catalytic competence is disputed: early in vitro autophosphorylation and CENP-E-stimulated activity in immunoprecipitates could not exclude co-purifying kinases, kinase activity is dispensable for APC/C-CDC20 inhibition, and phylogenomic/structural/biochemical work classifies the domain as a pseudokinase whose role is allosteric (promoting KARD phosphorylation and PP2A-B56 recruitment). One 2019 study reports bona fide phosphotransfer by purified human BubR1 onto CENP-E Ser2639, so the activity cannot be called refuted, but it is not the established core function of the protein. Supporting Evidence: PMID:9763420 The combined data suggest that hBUBR1 may be a protein kinase that has multiple roles in mitosis that include the kinetochore as well as at the spindle midzone during late anaphase and telophase. PMID:9660858 hBubR1 lacks several of the residues that are usually highly conserved among most protein kinases |
| GO:0004672 protein kinase activity | TAS PMID:10477750 Human BUBR1 is a mitotic checkpoint kinase that monitors CEN... | MARK AS OVER ANNOTATED | Summary: Chan et al. 1999 detected kinase activity in hBUBR1 immunoprecipitates that rose after mitotic entry and within 15 min of nocodazole treatment; substrates were hBUBR1 itself (autophosphorylation), MBP and a CENP-E fragment. Reason: Activity was measured in immunoprecipitates from cells, which cannot exclude associated kinases (e.g. PLK1, which phosphorylates BubR1 in mitosis); later work found kinase activity dispensable for APC/C inhibition (PMID:11702782) and classifies the domain as a pseudokinase. Kept as a historical, non-core claim. Supporting Evidence: PMID:10477750 Comparison of hBUBR1 kinase activity between metaphase cells and those that were exposed to nocodazole showed that kinase activity was rapidly stimulated within 15 min of nocodazole treatment PMID:10477750 In the simplest model, unattached kinetochores contain active hBUBR1 kinase that can rapidly activate the soluble pool of hBUBR1 through autophosphorylation. PMID:11702782 Surprisingly, the kinase activity of BubR1 is not required for the inhibition of APCCdc20. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:11702782 Mad2-Independent inhibition of APCCdc20 by the mitotic check... | MARK AS OVER ANNOTATED | Summary: Tang et al. 2001 purified the BubR1-Bub3 complex from mitotic HeLa cells and showed it inhibits APC/C-Cdc20 by blocking Cdc20 binding to APC, and explicitly that BubR1 kinase activity is not required for this inhibition. Reason: The paper's own conclusion is that the kinase activity is dispensable for BubR1's checkpoint function; the Ser/Thr kinase term reflects an in vitro assay whose intrinsic origin is disputed. Non-core and unresolved. Supporting Evidence: PMID:11702782 Surprisingly, the kinase activity of BubR1 is not required for the inhibition of APCCdc20. PMID:11702782 In the absence of Mad2, BubR1 inhibits the activity of APC by blocking the binding of Cdc20 to APC. |
| GO:0004674 protein serine/threonine kinase activity | IEA GO_REF:0000003 | MARK AS OVER ANNOTATED | Summary: EC 2.7.11.1 mapping inherited from UniProt's catalytic-activity annotation, which rests on PMID:10477750 and PMID:31201382. Reason: The EC assignment propagates a disputed activity mechanically. Human BUBR1 retains a C-terminal kinase-like fold but has degenerate glycine-rich and catalytic-loop motifs, and its catalytic competence is disputed: early in vitro autophosphorylation and CENP-E-stimulated activity in immunoprecipitates could not exclude co-purifying kinases, kinase activity is dispensable for APC/C-CDC20 inhibition, and phylogenomic/structural/biochemical work classifies the domain as a pseudokinase whose role is allosteric (promoting KARD phosphorylation and PP2A-B56 recruitment). One 2019 study reports bona fide phosphotransfer by purified human BubR1 onto CENP-E Ser2639, so the activity cannot be called refuted, but it is not the established core function of the protein. Supporting Evidence: file:human/BUB1B/BUB1B-deep-research-falcon.md Phylogenomic, structural and direct biochemical analyses found no convincing intrinsic phosphotransfer activity. PMID:31201382 Despite prior experimental evidence that BubR1 has kinase activity, this has been highly controversial, as a widely held view is that BubR1 is an unusual pseudokinase containing modules to interact with Bub1, Bub3, PP2A-B56 and KNL. |
| GO:0005515 protein binding | IPI PMID:11030144 p55CDC/hCDC20 is associated with BUBR1 and may be a downstre... | MODIFY | Summary: Wu et al. 2000 showed by yeast two-hybrid, GST pull-down, baculovirus co-expression and co-IP from HeLa cells that p55CDC/CDC20 associates with BUBR1, that the association increases on checkpoint activation, and that BUBR1 pulls down APC subunits CDC16/CDC27 from mitotic cells. Reason: Bare protein binding is uninformative. This reference characterises the BUBR1-CDC20 interaction as the means by which BUBR1 (within the MCC) inhibits the APC/C-CDC20 ubiquitin ligase: BUBR1 KEN-box/ABBA degron-like motifs occupy the substrate-recognition sites of CDC20. The informative molecular function is ubiquitin ligase inhibitor activity (GO:1990948). The abstract also reports in vitro phosphorylation of CDC20 by BUBR1 immunoprecipitates; that kinase claim shares the caveats discussed under the kinase rows and is not used as the replacement term. Proposed replacements: ubiquitin ligase inhibitor activity Supporting Evidence: PMID:11030144 Moreover, immunoprecipitation followed by Western blot analyses confirmed that native p55CDC is associated with BUBR1 in HeLa cells. PMID:11030144 Together, our studies strongly suggest that BUBR1 may target APC via p55CDC. |
| GO:0005515 protein binding | IPI PMID:15525512 Phosphorylation of Cdc20 by Bub1 provides a catalytic mechan... | MODIFY | Summary: Tang et al. 2004 is primarily about Bub1 phosphorylating Cdc20; the BUBR1-CDC20 IPI presumably derives from the full text (abstract-only cache), where BubR1-Cdc20 binding is used as a comparator. Reason: Bare protein binding is uninformative. The BubR1-Cdc20 interaction is the established basis of BubR1's APC/C-CDC20 inhibitory activity (PMID:11702782, PMID:27509861); the abstract focuses on Bub1 but the full text (which the curator read) is not available in the cache, so no claim of mis-attribution is made. Proposed replacements: ubiquitin ligase inhibitor activity Supporting Evidence: PMID:15525512 Bub1 directly phosphorylates Cdc20 in vitro and inhibits the ubiquitin ligase activity of APC/C(Cdc20) catalytically. PMID:11702782 In the absence of Mad2, BubR1 inhibits the activity of APC by blocking the binding of Cdc20 to APC. |
| GO:0005515 protein binding | IPI PMID:16760428 Phosphorylation- and polo-box-dependent binding of Plk1 to B... | REMOVE | Summary: Qi et al. 2006 describe Cdk1-primed, polo-box-dependent binding of Plk1 to Bub1; the BubR1-PLK1 pairing presumably comes from the full text (abstract-only cache), consistent with PLK1 binding and phosphorylating BubR1 (S676) in mitosis. Reason: Bare protein binding is uninformative; BUBR1 is a PLK1 substrate/docking partner here, which is not a molecular function of BUBR1. No claim of mis-attribution is made: the abstract foregrounds Bub1 but the curator read the full text. Supporting Evidence: PMID:16760428 We show that Plk1 binds to budding uninhibited by benzimidazole 1 (Bub1) in mitotic human cells. |
| GO:0005515 protein binding | IPI PMID:17981135 Human Blinkin/AF15q14 is required for chromosome alignment a... | REMOVE | Summary: Kiyomitsu et al. 2007 identified Blinkin/KNL1 as the kinetochore docking site whose amino/middle region binds the TPR domains of BubR1 and Bub1, required for chromosome alignment and the mitotic checkpoint. Reason: Bare protein binding is uninformative. The KNL1 (Blinkin) KI2 motif docks the BUBR1 TPR domain; this is a kinetochore-recruitment interaction that supports the kinetochore/outer kinetochore localization rows and the SAC process rows rather than an activity of BUBR1 in its own right. Removal does not dispute the interaction. Supporting Evidence: PMID:17981135 association of the amino and middle domain of blinkin with the TPR domains in the amino termini of BubR1 and Bub1 is essential for BubR1 and Bub1 to execute their distinct mitotic functions |
| GO:0005515 protein binding | IPI PMID:19407811 BubR1 acetylation at prometaphase is required for modulating... | MODIFY | Summary: Choi et al. 2009 study BubR1 acetylation; BubR1-Bub3 co-IP is part of the MCC context. Reason: Bare protein binding is uninformative. BUB3 and BUBR1 are subunits of the same stoichiometric mitotic checkpoint complex (MAD2-BUB1B-BUB3-CDC20), and this reference addresses the interaction in that context; the informative resolution is the complex term GO:0033597 (already annotated by IPI from PMID:27509861). Proposed replacements: mitotic checkpoint complex Supporting Evidence: PMID:19407811 We have found that BubR1 forms a complex with PCAF and is acetylated at lysine 250. PMID:19407811 Importantly, BubR1 binds directly to Cdc20, the WD domain-containing coactivator of the APC/C complex during mitosis (Tang et al, 2001; Yu, 2002; Chan and Yen, 2003). |
| GO:0005515 protein binding | IPI PMID:19407811 BubR1 acetylation at prometaphase is required for modulating... | REMOVE | Summary: Choi et al. 2009 show BubR1 is ubiquitinated and degraded by APC/C-Cdc20 during mitosis (ubiquitin co-IP). Reason: BUBR1 is the substrate of the APC/C-CDC20 ubiquitin ligase here; being modified by an enzyme is not a molecular function of BUBR1, so the bare protein-binding row is uninformative. The interaction itself is not disputed. Supporting Evidence: PMID:19407811 Furthermore, we found that APC/C-Cdc20 was responsible for BubR1 degradation during mitosis. |
| GO:0005515 protein binding | IPI PMID:19407811 BubR1 acetylation at prometaphase is required for modulating... | MODIFY | Summary: Choi et al. 2009 show BubR1 acetylation at K250 controls whether BubR1 acts as an APC/C-Cdc20 inhibitor (pseudosubstrate competing for Cdc20 D-box/KEN-box sites) or becomes an APC/C-Cdc20 substrate. Reason: Bare protein binding is uninformative. This reference characterises the BUBR1-CDC20 interaction as the means by which BUBR1 (within the MCC) inhibits the APC/C-CDC20 ubiquitin ligase: BUBR1 KEN-box/ABBA degron-like motifs occupy the substrate-recognition sites of CDC20. The informative molecular function is ubiquitin ligase inhibitor activity (GO:1990948). Proposed replacements: ubiquitin ligase inhibitor activity Supporting Evidence: PMID:19407811 Importantly, BubR1 binds directly to Cdc20, the WD domain-containing coactivator of the APC/C complex during mitosis (Tang et al, 2001; Yu, 2002; Chan and Yen, 2003). PMID:19407811 Instead, BubR1 functions as a pseudosubstrate of the APC/C complex by competing with genuine substrates of the APC/C complex for the same Cdc20-binding sites (D-box and KEN box) (Burton and Solomon, 2007). |
| GO:0005515 protein binding | IPI PMID:19407811 BubR1 acetylation at prometaphase is required for modulating... | REMOVE | Summary: Choi et al. 2009: BubR1 forms a complex with PCAF at prometaphase kinetochores and is acetylated at K250, which stabilises BubR1 as an APC/C inhibitor. Reason: BUBR1 is the substrate of the acetyltransferase PCAF/KAT2B here; being modified by an enzyme is not a molecular function of BUBR1, so the bare protein-binding row is uninformative. The interaction itself is not disputed. Supporting Evidence: PMID:19407811 We have found that BubR1 forms a complex with PCAF and is acetylated at lysine 250. |
| GO:0005515 protein binding | IPI PMID:20212161 ATP is required for the release of the anaphase-promoting co... | MODIFY | Summary: Miniowitz-Shemtov et al. 2010 examine release of APC/C from MCC (BubR1-Bub3-Mad2-Cdc20) inhibition, showing ATP hydrolysis is required for dissociation of MCC from APC/C and for MCC disassembly. Reason: Bare protein binding is uninformative. This reference characterises the BUBR1-CDC20 interaction as the means by which BUBR1 (within the MCC) inhibits the APC/C-CDC20 ubiquitin ligase: BUBR1 KEN-box/ABBA degron-like motifs occupy the substrate-recognition sites of CDC20. The informative molecular function is ubiquitin ligase inhibitor activity (GO:1990948). Proposed replacements: ubiquitin ligase inhibitor activity Supporting Evidence: PMID:20212161 APC/C is inhibited by a mitotic checkpoint complex (MCC) composed of BubR1, Bub3, Mad2, and Cdc20. |
| GO:0005515 protein binding | IPI PMID:20212161 ATP is required for the release of the anaphase-promoting co... | MODIFY | Summary: Miniowitz-Shemtov et al. 2010: MCC (BubR1, Bub3, Mad2, Cdc20) disassembly requires ATP hydrolysis. Reason: Bare protein binding is uninformative. MAD2L1 and BUBR1 are subunits of the same stoichiometric mitotic checkpoint complex (MAD2-BUB1B-BUB3-CDC20), and this reference addresses the interaction in that context; the informative resolution is the complex term GO:0033597 (already annotated by IPI from PMID:27509861). Proposed replacements: mitotic checkpoint complex Supporting Evidence: PMID:20212161 APC/C is inhibited by a mitotic checkpoint complex (MCC) composed of BubR1, Bub3, Mad2, and Cdc20. |
| GO:0005515 protein binding | IPI PMID:20220147 Defining the molecular basis of BubR1 kinetochore interactio... | REMOVE | Summary: D'Arcy et al. 2010 map the Blinkin-binding groove on the concave face of the BubR1 TPR domain. Reason: Bare protein binding is uninformative. The KNL1 (Blinkin) KI2 motif docks the BUBR1 TPR domain; this is a kinetochore-recruitment interaction that supports the kinetochore/outer kinetochore localization rows and the SAC process rows rather than an activity of BUBR1 in its own right. Removal does not dispute the interaction. Supporting Evidence: PMID:20220147 Both BubR1 and Bub1 undergo direct interactions with Blinkin via their TPR domains, with their respective βBlinkin-bindingβ grooves showing gross structural similarity. |
| GO:0005515 protein binding | IPI PMID:20360068 Systematic analysis of human protein complexes identifies ch... | REMOVE | Summary: High-throughput/systematic interaction dataset in which BUB1B was recovered with BUB1. Reason: Generic protein binding carries no functional information and the cited study does not assign a function to the BUB1 interaction; removal does not imply the interaction is false. Where this partner's interaction has been mechanistically characterised, that is captured by the MODIFY rows citing the primary papers and by the mitotic checkpoint complex annotation. Supporting Evidence: PMID:20360068 Using gene tagging on bacterial artificial chromosomes, protein localization, and tandem-affinity purification-mass spectrometry, the MitoCheck consortium has analyzed about 100 human protein complexes |
| GO:0005515 protein binding | IPI PMID:20360068 Systematic analysis of human protein complexes identifies ch... | REMOVE | Summary: High-throughput/systematic interaction dataset in which BUB1B was recovered with CDC20. MitoCheck BAC-tagging/TAP-MS survey of ~100 mitotic complexes. Reason: Generic protein binding carries no functional information and the cited study does not assign a function to the CDC20 interaction; removal does not imply the interaction is false. Where this partner's interaction has been mechanistically characterised, that is captured by the MODIFY rows citing the primary papers and by the mitotic checkpoint complex annotation. Supporting Evidence: PMID:20360068 Using gene tagging on bacterial artificial chromosomes, protein localization, and tandem-affinity purification-mass spectrometry, the MitoCheck consortium has analyzed about 100 human protein complexes |
| GO:0005515 protein binding | IPI PMID:21300909 p31comet Promotes disassembly of the mitotic checkpoint comp... | MODIFY | Summary: Teichner et al. 2011 show p31comet promotes ATP-dependent disassembly of the MCC, dissociating Cdc20 from BubR1. Reason: Bare protein binding is uninformative. This reference characterises the BUBR1-CDC20 interaction as the means by which BUBR1 (within the MCC) inhibits the APC/C-CDC20 ubiquitin ligase: BUBR1 KEN-box/ABBA degron-like motifs occupy the substrate-recognition sites of CDC20. The informative molecular function is ubiquitin ligase inhibitor activity (GO:1990948). Proposed replacements: ubiquitin ligase inhibitor activity Supporting Evidence: PMID:21300909 Although p31(comet) binds to Mad2, it promotes the dissociation of Cdc20 from BubR1 in MCC. |
| GO:0005515 protein binding | IPI PMID:21300909 p31comet Promotes disassembly of the mitotic checkpoint comp... | MODIFY | Summary: Teichner et al. 2011: p31comet-driven MCC disassembly. Reason: Bare protein binding is uninformative. MAD2L1 and BUBR1 are subunits of the same stoichiometric mitotic checkpoint complex (MAD2-BUB1B-BUB3-CDC20), and this reference addresses the interaction in that context; the informative resolution is the complex term GO:0033597 (already annotated by IPI from PMID:27509861). Proposed replacements: mitotic checkpoint complex Supporting Evidence: PMID:21300909 Although p31(comet) binds to Mad2, it promotes the dissociation of Cdc20 from BubR1 in MCC. |
| GO:0005515 protein binding | IPI PMID:21407176 Evidence that Aurora B is implicated in spindle checkpoint s... | MODIFY | Summary: Santaguida et al. 2011 study Aurora B in SAC signalling; BubR1-Cdc20 co-IP is used as a readout of MCC assembly. Reason: Bare protein binding is uninformative. This reference characterises the BUBR1-CDC20 interaction as the means by which BUBR1 (within the MCC) inhibits the APC/C-CDC20 ubiquitin ligase: BUBR1 KEN-box/ABBA degron-like motifs occupy the substrate-recognition sites of CDC20. The informative molecular function is ubiquitin ligase inhibitor activity (GO:1990948). Proposed replacements: ubiquitin ligase inhibitor activity Supporting Evidence: PMID:21407176 Within the MCC, Mad2, Bub3 and BubR1 form a complex with Cdc20, an APC/C co-activator required for targeting crucial APC/C substrates at the metaphaseβanaphase transition. |
| GO:0005515 protein binding | IPI PMID:21772247 Probing the in vivo function of Mad1:C-Mad2 in the spindle a... | MODIFY | Summary: Fava et al. 2011 use a C-Mad2 conformation-specific antibody; BubR1-Mad2 association reflects C-Mad2 incorporation into the MCC (abstract-only cache). Reason: Bare protein binding is uninformative. MAD2L1 and BUBR1 are subunits of the same stoichiometric mitotic checkpoint complex (MAD2-BUB1B-BUB3-CDC20), and this reference addresses the interaction in that context; the informative resolution is the complex term GO:0033597 (already annotated by IPI from PMID:27509861). Proposed replacements: mitotic checkpoint complex Supporting Evidence: PMID:21772247 Notably, we show that Mad2 requires association with Mad1 to adopt the closed conformation |
| GO:0005515 protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | REMOVE | Summary: High-throughput/systematic interaction dataset in which BUB1B was recovered with BUB3. Human liver Y2H interaction network. Reason: Generic protein binding carries no functional information and the cited study does not assign a function to the BUB3 interaction; removal does not imply the interaction is false. Where this partner's interaction has been mechanistically characterised, that is captured by the MODIFY rows citing the primary papers and by the mitotic checkpoint complex annotation. Supporting Evidence: PMID:21988832 we map the interactions of an unbiased selection of 5026 human liver expression proteins by yeast two-hybrid technology and establish a human liver protein interaction network (HLPN) composed of 3484 interactions among 2582 proteins |
| GO:0005515 protein binding | IPI PMID:22000412 Structure of a Blinkin-BUBR1 complex reveals an interaction ... | MODIFY | Summary: Bolanos-Garcia et al. 2011: Blinkin-BUBR1 structure with MCC context. Reason: Bare protein binding is uninformative. BUB3 and BUBR1 are subunits of the same stoichiometric mitotic checkpoint complex (MAD2-BUB1B-BUB3-CDC20), and this reference addresses the interaction in that context; the informative resolution is the complex term GO:0033597 (already annotated by IPI from PMID:27509861). Proposed replacements: mitotic checkpoint complex Supporting Evidence: PMID:22000412 BUBR1 forms part of the mitotic checkpoint complex (MCC) that inhibits the anaphase-promoting complex or cyclosome (APC/C)E3 ubiquitin ligase activity toward cyclin B1 and securin (Tang et al. |
| GO:0005515 protein binding | IPI PMID:22000412 Structure of a Blinkin-BUBR1 complex reveals an interaction ... | MODIFY | Summary: Bolanos-Garcia et al. 2011 show the BUBR1 KEN26 box is required for Cdc20 and Mad2 binding, and that Blinkin-binding mutants of BUBR1 impair Cdc20 binding and the SAC. Reason: Bare protein binding is uninformative. This reference characterises the BUBR1-CDC20 interaction as the means by which BUBR1 (within the MCC) inhibits the APC/C-CDC20 ubiquitin ligase: BUBR1 KEN-box/ABBA degron-like motifs occupy the substrate-recognition sites of CDC20. The informative molecular function is ubiquitin ligase inhibitor activity (GO:1990948). Proposed replacements: ubiquitin ligase inhibitor activity Supporting Evidence: PMID:22000412 As expected, BUBR1 WT showed binding to Cdc20, Mad2 and Blinkin while BUBR1 KEN26AAA completely lost its interaction with Cdc20 and Mad2 (Figure 4F). PMID:22000412 Finally, using stable isogenic HeLa cell lines we show that specific interference with the interaction between Blinkin and BUBR1 leads to defects in the SAC and the impairment of the interaction of BUBR1 with Cdc20. |
| GO:0005515 protein binding | IPI PMID:22000412 Structure of a Blinkin-BUBR1 complex reveals an interaction ... | MODIFY | Summary: Bolanos-Garcia et al. 2011: BUBR1 KEN26 mutation abolishes Cdc20 and Mad2 binding. Reason: Bare protein binding is uninformative. MAD2L1 and BUBR1 are subunits of the same stoichiometric mitotic checkpoint complex (MAD2-BUB1B-BUB3-CDC20), and this reference addresses the interaction in that context; the informative resolution is the complex term GO:0033597 (already annotated by IPI from PMID:27509861). Proposed replacements: mitotic checkpoint complex Supporting Evidence: PMID:22000412 As expected, BUBR1 WT showed binding to Cdc20, Mad2 and Blinkin while BUBR1 KEN26AAA completely lost its interaction with Cdc20 and Mad2 (Figure 4F). |
| GO:0005515 protein binding | IPI PMID:22000412 Structure of a Blinkin-BUBR1 complex reveals an interaction ... | REMOVE | Summary: Bolanos-Garcia et al. 2011 solved the 2.2 A structure of a Blinkin motif bound to BUBR1 and showed interface mutants cause SAC defects and impaired Cdc20 binding. Reason: Bare protein binding is uninformative. The KNL1 (Blinkin) KI2 motif docks the BUBR1 TPR domain; this is a kinetochore-recruitment interaction that supports the kinetochore/outer kinetochore localization rows and the SAC process rows rather than an activity of BUBR1 in its own right. Removal does not dispute the interaction. Supporting Evidence: PMID:22000412 Finally, using stable isogenic HeLa cell lines we show that specific interference with the interaction between Blinkin and BUBR1 leads to defects in the SAC and the impairment of the interaction of BUBR1 with Cdc20. |
| GO:0005515 protein binding | IPI PMID:22331848 Structural analysis reveals features of the spindle checkpoi... | REMOVE | Summary: Krenn et al. 2012 compared the Bub1-TPR:Knl1-KI1 structure with the BubR1-TPR:KI2 complex; TPR-KI interactions are not essential for kinetochore recruitment. Reason: Bare protein binding is uninformative. The KNL1 (Blinkin) KI2 motif docks the BUBR1 TPR domain; this is a kinetochore-recruitment interaction that supports the kinetochore/outer kinetochore localization rows and the SAC process rows rather than an activity of BUBR1 in its own right. Removal does not dispute the interaction. Supporting Evidence: PMID:22331848 Analogously to the results obtained with Bub1 deletion mutants, deletion of the TPR domain of BubR1 (BubR1(Ξ204) or BubR1(Ξ328)) did not evidently affect kinetochore recruitment (Fig. |
| GO:0005515 protein binding | IPI PMID:24581499 Nuclear pores protect genome integrity by assembling a premi... | MODIFY | Summary: Rodriguez-Bravo et al. 2014 show interphase nuclear-pore-tethered Mad1-Mad2 produces a premitotic Cdc20 inhibitor; BubR1-Cdc20 complexes are part of that inhibitor (abstract-only cache). Reason: Bare protein binding is uninformative. This reference characterises the BUBR1-CDC20 interaction as the means by which BUBR1 (within the MCC) inhibits the APC/C-CDC20 ubiquitin ligase: BUBR1 KEN-box/ABBA degron-like motifs occupy the substrate-recognition sites of CDC20. The informative molecular function is ubiquitin ligase inhibitor activity (GO:1990948). Proposed replacements: ubiquitin ligase inhibitor activity Supporting Evidence: PMID:24581499 This role is mediated by Mad1-Mad2 complexes tethered to the nuclear basket, which activate soluble Mad2 as a binding partner and inhibitor of Cdc20 in the cytoplasm. |
| GO:0005515 protein binding | IPI PMID:24825348 SIRT2 induces the checkpoint kinase BubR1 to increase lifesp... | REMOVE | Summary: North et al. 2014: CBP acetylates BubR1 K668, counteracted by SIRT2. Reason: BUBR1 is the substrate of the acetyltransferase CBP (mouse Crebbp, xeno interaction) here; being modified by an enzyme is not a molecular function of BUBR1, so the bare protein-binding row is uninformative. The interaction itself is not disputed. Supporting Evidence: PMID:24825348 the loss of BubR1 levels with age is due to a decline in NAD(+) and the ability of SIRT2 to maintain lysine-668 of BubR1 in a deacetylated state, which is counteracted by the acetyltransferase CBP |
| GO:0005515 protein binding | IPI PMID:24825348 SIRT2 induces the checkpoint kinase BubR1 to increase lifesp... | REMOVE | Summary: North et al. 2014: SIRT2 deacetylates BubR1 K668, maintaining BubR1 levels with age. Reason: BUBR1 is the substrate of the deacetylase SIRT2 here; being modified by an enzyme is not a molecular function of BUBR1, so the bare protein-binding row is uninformative. The interaction itself is not disputed. Supporting Evidence: PMID:24825348 the loss of BubR1 levels with age is due to a decline in NAD(+) and the ability of SIRT2 to maintain lysine-668 of BubR1 in a deacetylated state, which is counteracted by the acetyltransferase CBP |
| GO:0005515 protein binding | IPI PMID:24825348 SIRT2 induces the checkpoint kinase BubR1 to increase lifesp... | REMOVE | Summary: North et al. 2014: BubR1 K668 acetylation (CBP) and deacetylation (SIRT2) control BubR1 abundance and lifespan in mice. Reason: BUBR1 is the substrate of KAT2B/CBP acetyltransferases and SIRT2 here; being modified by an enzyme is not a molecular function of BUBR1, so the bare protein-binding row is uninformative. The interaction itself is not disputed. Supporting Evidence: PMID:24825348 the loss of BubR1 levels with age is due to a decline in NAD(+) and the ability of SIRT2 to maintain lysine-668 of BubR1 in a deacetylated state, which is counteracted by the acetyltransferase CBP |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | REMOVE | Summary: High-throughput/systematic interaction dataset in which BUB1B was recovered with CDC20. In situ proximity-ligation profiling of 1204 endogenous PPIs in HeLa cells. Reason: Generic protein binding carries no functional information and the cited study does not assign a function to the CDC20 interaction; removal does not imply the interaction is false. Where this partner's interaction has been mechanistically characterised, that is captured by the MODIFY rows citing the primary papers and by the mitotic checkpoint complex annotation. Supporting Evidence: PMID:25241761 we collected βΌ 700 primary antibodies and employed a highly sensitive and specific technique, an in situ proximity ligation assay, to investigate 1204 endogenous PPIs in HeLa cells, and 557 PPIs of them tested positive |
| GO:0005515 protein binding | IPI PMID:25383541 The mitotic checkpoint complex binds a second CDC20 to inhib... | MODIFY | Summary: Izawa & Pines 2015: recombinant MCC with and without BUB3. Reason: Bare protein binding is uninformative. BUB3 and BUBR1 are subunits of the same stoichiometric mitotic checkpoint complex (MAD2-BUB1B-BUB3-CDC20), and this reference addresses the interaction in that context; the informative resolution is the complex term GO:0033597 (already annotated by IPI from PMID:27509861). Proposed replacements: mitotic checkpoint complex Supporting Evidence: PMID:25383541 The MCC is an APC/C inhibitor containing the MAD2, BUBR1 and BUB3 checkpoint proteins in a complex with CDC20 5, where MAD2 and BUBR1 inhibit CDC20 by binding to substrate and APC/C recognition motifs6-8. |
| GO:0005515 protein binding | IPI PMID:25383541 The mitotic checkpoint complex binds a second CDC20 to inhib... | MODIFY | Summary: Izawa & Pines 2015 reconstituted human MCC and show BUBR1 KEN1 is essential for core MCC, while BUBR1 D-box/KEN2 let the MCC bind and inhibit a second, APC/C-bound CDC20. Reason: Bare protein binding is uninformative. This reference characterises the BUBR1-CDC20 interaction as the means by which BUBR1 (within the MCC) inhibits the APC/C-CDC20 ubiquitin ligase: BUBR1 KEN-box/ABBA degron-like motifs occupy the substrate-recognition sites of CDC20. The informative molecular function is ubiquitin ligase inhibitor activity (GO:1990948). Proposed replacements: ubiquitin ligase inhibitor activity Supporting Evidence: PMID:25383541 The MCC is an APC/C inhibitor containing the MAD2, BUBR1 and BUB3 checkpoint proteins in a complex with CDC20 5, where MAD2 and BUBR1 inhibit CDC20 by binding to substrate and APC/C recognition motifs6-8. PMID:25383541 Here, we show that the MCC can inhibit a second CDC20 that has already bound and activated the APC/C. PMID:25383541 the first (K26EN) is essential to form the core MCC |
| GO:0005515 protein binding | IPI PMID:25383541 The mitotic checkpoint complex binds a second CDC20 to inhib... | MODIFY | Summary: Izawa & Pines 2015: recombinant human MCC (MAD2, BUBR1, BUB3, CDC20). Reason: Bare protein binding is uninformative. MAD2L1 and BUBR1 are subunits of the same stoichiometric mitotic checkpoint complex (MAD2-BUB1B-BUB3-CDC20), and this reference addresses the interaction in that context; the informative resolution is the complex term GO:0033597 (already annotated by IPI from PMID:27509861). Proposed replacements: mitotic checkpoint complex Supporting Evidence: PMID:25383541 The MCC is an APC/C inhibitor containing the MAD2, BUBR1 and BUB3 checkpoint proteins in a complex with CDC20 5, where MAD2 and BUBR1 inhibit CDC20 by binding to substrate and APC/C recognition motifs6-8. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: High-throughput/systematic interaction dataset in which BUB1B was recovered with BUB3. HI-II-14 binary Y2H interactome. Reason: Generic protein binding carries no functional information and the cited study does not assign a function to the BUB3 interaction; removal does not imply the interaction is false. Where this partner's interaction has been mechanistically characterised, that is captured by the MODIFY rows citing the primary papers and by the mitotic checkpoint complex annotation. Supporting Evidence: PMID:25416956 Here, we describe a systematic map of ~14,000 high-quality human binary protein-protein interactions. |
| GO:0005515 protein binding | IPI PMID:25502805 A massively parallel pipeline to clone DNA variants and exam... | REMOVE | Summary: High-throughput/systematic interaction dataset in which BUB1B was recovered with CDC20. Variant-interaction pipeline; MVA mutations R727C/L844F destabilise BUB1B and abolish all its interactions. Reason: Generic protein binding carries no functional information and the cited study does not assign a function to the CDC20 interaction; removal does not imply the interaction is false. Where this partner's interaction has been mechanistically characterised, that is captured by the MODIFY rows citing the primary papers and by the mitotic checkpoint complex annotation. Supporting Evidence: PMID:25502805 we find that the mutations R727C and L844F on the spindle checkpoint kinase Bub1b both cause the protein to become unstable and lose all its interactors |
| GO:0005515 protein binding | IPI PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apo... | REMOVE | Summary: High-throughput/systematic interaction dataset in which BUB1B was recovered with BUB1. Reason: Generic protein binding carries no functional information and the cited study does not assign a function to the BUB1 interaction; removal does not imply the interaction is false. Where this partner's interaction has been mechanistically characterised, that is captured by the MODIFY rows citing the primary papers and by the mitotic checkpoint complex annotation. Supporting Evidence: PMID:25852190 We assembled protein interaction maps using mass spectrometry-based protein interaction analysis and quantitative phosphoproteomics. |
| GO:0005515 protein binding | IPI PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apo... | REMOVE | Summary: High-throughput/systematic interaction dataset in which BUB1B was recovered with BUB3. Reason: Generic protein binding carries no functional information and the cited study does not assign a function to the BUB3 interaction; removal does not imply the interaction is false. Where this partner's interaction has been mechanistically characterised, that is captured by the MODIFY rows citing the primary papers and by the mitotic checkpoint complex annotation. Supporting Evidence: PMID:25852190 We assembled protein interaction maps using mass spectrometry-based protein interaction analysis and quantitative phosphoproteomics. |
| GO:0005515 protein binding | IPI PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apo... | REMOVE | Summary: High-throughput/systematic interaction dataset in which BUB1B was recovered with CDC20. Kinase interaction/phosphoproteomic maps in TRAIL-induced apoptosis. Reason: Generic protein binding carries no functional information and the cited study does not assign a function to the CDC20 interaction; removal does not imply the interaction is false. Where this partner's interaction has been mechanistically characterised, that is captured by the MODIFY rows citing the primary papers and by the mitotic checkpoint complex annotation. Supporting Evidence: PMID:25852190 We assembled protein interaction maps using mass spectrometry-based protein interaction analysis and quantitative phosphoproteomics. |
| GO:0005515 protein binding | IPI PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apo... | REMOVE | Summary: High-throughput/systematic interaction dataset in which BUB1B was recovered with MAD2L1. Reason: Generic protein binding carries no functional information and the cited study does not assign a function to the MAD2L1 interaction; removal does not imply the interaction is false. Where this partner's interaction has been mechanistically characterised, that is captured by the MODIFY rows citing the primary papers and by the mitotic checkpoint complex annotation. Supporting Evidence: PMID:25852190 We assembled protein interaction maps using mass spectrometry-based protein interaction analysis and quantitative phosphoproteomics. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | REMOVE | Summary: High-throughput/systematic interaction dataset in which BUB1B was recovered with BUB3. Quantitative BAC-GFP interactome (stoichiometry/abundance). Reason: Generic protein binding carries no functional information and the cited study does not assign a function to the BUB3 interaction; removal does not imply the interaction is false. Where this partner's interaction has been mechanistically characterised, that is captured by the MODIFY rows citing the primary papers and by the mitotic checkpoint complex annotation. Supporting Evidence: PMID:26496610 Using quantitative proteomics, we detect specific interactions, estimate interaction stoichiometries, and measure cellular abundances of interacting proteins. |
| GO:0005515 protein binding | IPI PMID:29883609 PELI1 Selectively Targets Kinase-Active RIP3 for Ubiquitylat... | UNDECIDED | Summary: Choi et al. 2018 identify PELI1 as the E3 ligase for kinase-active RIP3/RIPK3; the RIPK3-BUB1B interaction is not described in the cached abstract (UniProt records it from this paper). Reason: Abstract-only cache; the biological meaning of the RIPK3 interaction cannot be adjudicated, so per the protein-binding policy the row is left UNDECIDED rather than resolved to a function or removed. Supporting Evidence: PMID:29883609 Here, we identify pellino E3 ubiquitin protein ligase 1 (PELI1) as an E3 ligase that targets RIP3 for proteasome-dependent degradation. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | REMOVE | Summary: High-throughput/systematic interaction dataset in which BUB1B was recovered with BUB1. Reason: Generic protein binding carries no functional information and the cited study does not assign a function to the BUB1 interaction; removal does not imply the interaction is false. Where this partner's interaction has been mechanistically characterised, that is captured by the MODIFY rows citing the primary papers and by the mitotic checkpoint complex annotation. Supporting Evidence: PMID:31515488 we leverage the ExAC database of 60,706 human exomes to investigate experimentally the impact of 2009 missense single nucleotide variants (SNVs) across 2185 protein-protein interactions |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | REMOVE | Summary: High-throughput/systematic interaction dataset in which BUB1B was recovered with CDC20. Population-variant interaction-disruption screen. Reason: Generic protein binding carries no functional information and the cited study does not assign a function to the CDC20 interaction; removal does not imply the interaction is false. Where this partner's interaction has been mechanistically characterised, that is captured by the MODIFY rows citing the primary papers and by the mitotic checkpoint complex annotation. Supporting Evidence: PMID:31515488 we leverage the ExAC database of 60,706 human exomes to investigate experimentally the impact of 2009 missense single nucleotide variants (SNVs) across 2185 protein-protein interactions |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | REMOVE | Summary: High-throughput/systematic interaction dataset in which BUB1B was recovered with BUB3. Reason: Generic protein binding carries no functional information and the cited study does not assign a function to the BUB3 interaction; removal does not imply the interaction is false. Where this partner's interaction has been mechanistically characterised, that is captured by the MODIFY rows citing the primary papers and by the mitotic checkpoint complex annotation. Supporting Evidence: PMID:32707033 Here, we present a comprehensive mass-spectrometry-based analysis of a human kinase interaction network covering more than 300 kinases. |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | REMOVE | Summary: High-throughput/systematic interaction dataset in which BUB1B was recovered with CDC20. Kinase interactome (AP-MS, >300 kinases). Reason: Generic protein binding carries no functional information and the cited study does not assign a function to the CDC20 interaction; removal does not imply the interaction is false. Where this partner's interaction has been mechanistically characterised, that is captured by the MODIFY rows citing the primary papers and by the mitotic checkpoint complex annotation. Supporting Evidence: PMID:32707033 Here, we present a comprehensive mass-spectrometry-based analysis of a human kinase interaction network covering more than 300 kinases. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: High-throughput/systematic interaction dataset in which BUB1B was recovered with BUB1. Reason: Generic protein binding carries no functional information and the cited study does not assign a function to the BUB1 interaction; removal does not imply the interaction is false. Where this partner's interaction has been mechanistically characterised, that is captured by the MODIFY rows citing the primary papers and by the mitotic checkpoint complex annotation. Supporting Evidence: PMID:33961781 Through affinity-purification mass spectrometry, we have created two proteome-scale, cell-line-specific interaction networks. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: High-throughput/systematic interaction dataset in which BUB1B was recovered with BUB3. Reason: Generic protein binding carries no functional information and the cited study does not assign a function to the BUB3 interaction; removal does not imply the interaction is false. Where this partner's interaction has been mechanistically characterised, that is captured by the MODIFY rows citing the primary papers and by the mitotic checkpoint complex annotation. Supporting Evidence: PMID:33961781 Through affinity-purification mass spectrometry, we have created two proteome-scale, cell-line-specific interaction networks. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: High-throughput/systematic interaction dataset in which BUB1B was recovered with CDC20. BioPlex 3.0 AP-MS networks. Reason: Generic protein binding carries no functional information and the cited study does not assign a function to the CDC20 interaction; removal does not imply the interaction is false. Where this partner's interaction has been mechanistically characterised, that is captured by the MODIFY rows citing the primary papers and by the mitotic checkpoint complex annotation. Supporting Evidence: PMID:33961781 Through affinity-purification mass spectrometry, we have created two proteome-scale, cell-line-specific interaction networks. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: High-throughput/systematic interaction dataset in which BUB1B was recovered with MAD2L1. Reason: Generic protein binding carries no functional information and the cited study does not assign a function to the MAD2L1 interaction; removal does not imply the interaction is false. Where this partner's interaction has been mechanistically characterised, that is captured by the MODIFY rows citing the primary papers and by the mitotic checkpoint complex annotation. Supporting Evidence: PMID:33961781 Through affinity-purification mass spectrometry, we have created two proteome-scale, cell-line-specific interaction networks. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | REMOVE | Summary: High-throughput/systematic interaction dataset in which BUB1B was recovered with BUB3. Reason: Generic protein binding carries no functional information and the cited study does not assign a function to the BUB3 interaction; removal does not imply the interaction is false. Where this partner's interaction has been mechanistically characterised, that is captured by the MODIFY rows citing the primary papers and by the mitotic checkpoint complex annotation. Supporting Evidence: PMID:35271311 We combined genome engineering, confocal live-cell imaging, mass spectrometry, and data science to systematically map the localization and interactions of human proteins. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | REMOVE | Summary: High-throughput/systematic interaction dataset in which BUB1B was recovered with CDC20. OpenCell endogenous tagging/IP-MS. Reason: Generic protein binding carries no functional information and the cited study does not assign a function to the CDC20 interaction; removal does not imply the interaction is false. Where this partner's interaction has been mechanistically characterised, that is captured by the MODIFY rows citing the primary papers and by the mitotic checkpoint complex annotation. Supporting Evidence: PMID:35271311 We combined genome engineering, confocal live-cell imaging, mass spectrometry, and data science to systematically map the localization and interactions of human proteins. |
| GO:0005515 protein binding | IPI PMID:36931259 A central chaperone-like role for 14-3-3 proteins in human c... | REMOVE | Summary: High-throughput/systematic interaction dataset in which BUB1B was recovered with YWHAE (14-3-3 epsilon). 14-3-3 paralog interactome; BUB1B recovered as a 14-3-3 client. Reason: Generic protein binding carries no functional information and the cited study does not assign a function to the YWHAE (14-3-3 epsilon) interaction; removal does not imply the interaction is false. Where this partner's interaction has been mechanistically characterised, that is captured by the MODIFY rows citing the primary papers and by the mitotic checkpoint complex annotation. Supporting Evidence: PMID:36931259 Here, we map the interactomes of all human 14-3-3 paralogs and systematically characterize the effect of disrupting these interactions on client localization. |
| GO:0005515 protein binding | IPI PMID:37926298 Therapeutic role of 2-stearoxyphenethyl phosphocholine targe... | REMOVE | Summary: Pharmacology paper: the microtubule-targeting compound stPEPC causes mitotic accumulation with increased BUBR1 phosphorylation and MAD2-CDC20 association in colorectal cancer cells; BUBR1-CDC20 co-IP is used as an MCC-activation readout. Reason: Bare protein binding is uninformative; the study does not characterise the BUBR1-CDC20 interaction beyond using it as a checkpoint-activation marker. The functional content (MCC-mediated APC/C inhibition) is captured by the MODIFY rows citing mechanistic papers and by GO:0033597. Supporting Evidence: PMID:37926298 stPEPC showed anti-proliferative properties and mitotic cell accumulation via upregulated phosphorylation of BUBR1 and an association between mitotic arrest deficiency 2 (MAD2) and cell division cycle protein 20 homolog (CDC20). |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: High-throughput/systematic interaction dataset in which BUB1B was recovered with CDC20. U2OS multimodal cell map (AP-MS plus imaging). Reason: Generic protein binding carries no functional information and the cited study does not assign a function to the CDC20 interaction; removal does not imply the interaction is false. Where this partner's interaction has been mechanistically characterised, that is captured by the MODIFY rows citing the primary papers and by the mitotic checkpoint complex annotation. Supporting Evidence: PMID:40205054 Here we construct a global map of human subcellular architecture through joint measurement of biophysical interactions and immunofluorescence images for over 5,100 proteins in U2OS osteosarcoma cells. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: High-throughput/systematic interaction dataset in which BUB1B was recovered with MAD2L1. Reason: Generic protein binding carries no functional information and the cited study does not assign a function to the MAD2L1 interaction; removal does not imply the interaction is false. Where this partner's interaction has been mechanistically characterised, that is captured by the MODIFY rows citing the primary papers and by the mitotic checkpoint complex annotation. Supporting Evidence: PMID:40205054 Here we construct a global map of human subcellular architecture through joint measurement of biophysical interactions and immunofluorescence images for over 5,100 proteins in U2OS osteosarcoma cells. |
| GO:0005515 protein binding | IPI PMID:9660858 The human homologue of Bub3 is required for kinetochore loca... | MODIFY | Summary: Taylor et al. 1998: hBubR1 binds hBub3 through the conserved Bub1/Mad3 homology (GLEBS) segment, and this binding is required for kinetochore localization. Reason: Bare protein binding is uninformative. BUB3 and BUBR1 are subunits of the same stoichiometric mitotic checkpoint complex (MAD2-BUB1B-BUB3-CDC20), and this reference addresses the interaction in that context; the informative resolution is the complex term GO:0033597 (already annotated by IPI from PMID:27509861). Proposed replacements: mitotic checkpoint complex Supporting Evidence: PMID:9660858 In addition, hBubR1 can localize to kinetochores during prometaphase and the ability to bind Bub3 is required for this localization. |
| GO:0005515 protein binding | IPI PMID:9763420 Characterization of the kinetochore binding domain of CENP-E... | REMOVE | Summary: Chan et al. 1998 isolated hBUBR1 in a yeast two-hybrid screen with the CENP-E kinetochore-binding domain and showed CENP-E and hBUBR1 co-immunoprecipitate from HeLa cells. Reason: Bare protein binding is uninformative. The CENP-E interaction is important biology (CENP-E stimulates BubR1 kinase activity in immunoprecipitates and is a proposed BubR1 substrate), but no settled molecular function of BUBR1 can be assigned from it given the disputed kinase activity; the interaction itself is not in doubt. Supporting Evidence: PMID:9763420 This observation, coupled with the fact that CENP-E and hBUBR1 kinase can form a stable complex in vivo, raises the possibility that this complex might participate in the checkpoint pathway. PMID:10477750 Although this interaction was initially identified in a yeast two-hybrid screen for proteins that associate with CENP-E, a stable complex of hBUBR1 and CENP-E was detected in Hela cells. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT node PTN000361608 asserts nuclear localization, seeded largely by yeast Bub1/Mad3 (closed mitosis, so kinetochore proteins are nuclear) plus worm and human members. Human BUBR1 is predominantly cytoplasmic in interphase and acts on kinetochores of condensed chromosomes after nuclear envelope breakdown; UniProt lists a nuclear pool by inference and the protein carries an NLS motif. Reason: Phylogenetically defensible (yeast orthologues are nuclear) and not wrong for human (a nuclear/nucleoplasmic pool and premitotic MCC assembly are plausible), but interphase immunofluorescence shows the bulk of human BUBR1 in the cytoplasm, and its functional sites are kinetochores and the mitotic cytosol. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN000361608 Β· PTN000361608 SUPPORTS TRANSFER Nuclear localization is an open-vs-closed-mitosis compartment convention; for a human protein the corresponding functional site is the kinetochore. Supporting Evidence: PMID:9660858 During interphase, hBubR1 was predominantly cytoplasmic PMID:9763420 Examination of the subcellular distribution of hBUBR1 by immunofluorescence staining showed that it was concentrated in the cytoplasm of all interphase cells |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt subcellular-location keyword 'Nucleus', annotated by inference (ECO:0000305) from mitotic localization papers. Reason: Consistent with the IBA row above; a minor/inferred localization for human BUBR1 whose interphase distribution is mainly cytoplasmic. Supporting Evidence: PMID:9763420 Examination of the subcellular distribution of hBUBR1 by immunofluorescence staining showed that it was concentrated in the cytoplasm of all interphase cells |
| GO:0005680 anaphase-promoting complex | TAS PMID:10477750 Human BUBR1 is a mitotic checkpoint kinase that monitors CEN... | MODIFY | Summary: Chan et al. 1999 found hBUBR1 associated with the cyclosome/APC in mitotically arrested cells. BUBR1 is not a subunit of the APC/C; it binds APC/C-CDC20 as part of the mitotic checkpoint complex, forming the inhibited APC/C-MCC assembly. Reason: Membership of the E3 ligase itself misrepresents the biology: BUBR1 is an inhibitor bound to the APC/C-CDC20 via the MCC. The complex term that BUBR1 is genuinely part of is GO:0033597 mitotic checkpoint complex (cryo-EM of APC/C-MCC, PMID:27509861). Proposed replacements: mitotic checkpoint complex Supporting Evidence: PMID:10477750 As hBUBR1 appears to form a fairly stable complex with the cyclosome/APC in cells arrested in mitosis, its kinase activity may be labile. PMID:27509861 Soluble C-Mad2 engages the N-terminus of Cdc20 (refs 10,11), the mitotic activating subunit of the APC/C, which then binds the BubR1-Bub3 dimer to form the MCC 12. |
| GO:0005737 cytoplasm | IDA GO_REF:0000054 | ACCEPT | Summary: LIFEdb GFP-fusion localization: cytoplasmic in living cells. Reason: Interphase BUBR1 is predominantly cytoplasmic and the MCC acts as a diffusible cytoplasmic APC/C inhibitor in mitosis. Supporting Evidence: PMID:9763420 Examination of the subcellular distribution of hBUBR1 by immunofluorescence staining showed that it was concentrated in the cytoplasm of all interphase cells |
| GO:0005737 cytoplasm | IDA PMID:14706340 Dual roles of human BubR1, a mitotic checkpoint kinase, in t... | ACCEPT | Summary: Shin et al. 2003 followed hBubR1 protein levels and localization during sustained checkpoint activation and polyploidization (abstract-only cache); hBubR1 is cytoplasmic in interphase and its ectopic expression triggers apoptosis of polyploid cells. Reason: Cytoplasmic localization is consistent across the literature; the apoptosis-related findings are a separate, non-core observation not annotated here. Supporting Evidence: PMID:14706340 the introduction of hBubR1 triggers the apoptosis of polyploid cells formed by aberrant exit from mitosis PMID:9763420 Examination of the subcellular distribution of hBUBR1 by immunofluorescence staining showed that it was concentrated in the cytoplasm of all interphase cells |
| GO:0005737 cytoplasm | IDA PMID:20220147 Defining the molecular basis of BubR1 kinetochore interactio... | ACCEPT | Summary: D'Arcy et al. 2010, structural/biochemical study of the BubR1 N-terminus with cellular localization of constructs. Reason: Consistent with the soluble cytoplasmic pool of BubR1/MCC. Supporting Evidence: PMID:20220147 Second, BubR1 inhibits APC/C-Cdc20 ubiquitin ligase activity as part of the MCC (16). PMID:9763420 Examination of the subcellular distribution of hBUBR1 by immunofluorescence staining showed that it was concentrated in the cytoplasm of all interphase cells |
| GO:0005737 cytoplasm | IDA PMID:9763420 Characterization of the kinetochore binding domain of CENP-E... | ACCEPT | Summary: Chan et al. 1998: immunofluorescence shows hBUBR1 concentrated in the cytoplasm of all interphase cells, with kinetochore and spindle-midzone pools in mitosis. Reason: Direct evidence for the cytoplasmic pool of human BUBR1. Supporting Evidence: PMID:9763420 Examination of the subcellular distribution of hBUBR1 by immunofluorescence staining showed that it was concentrated in the cytoplasm of all interphase cells |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location keyword 'Cytoplasm' (PMID:14706340, PMID:9763420). Reason: Consistent with direct evidence. Supporting Evidence: PMID:9763420 Examination of the subcellular distribution of hBUBR1 by immunofluorescence staining showed that it was concentrated in the cytoplasm of all interphase cells |
| GO:0005813 centrosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt subcellular-location keyword 'centrosome', derived from a report that BubR1 negatively regulates PLK1 in interphase and suppresses centrosome amplification (PubMed:19503101, not cached). Reason: A minor, interphase localization with a single supporting report; not part of BUBR1's core kinetochore/MCC function. |
| GO:0005819 spindle | IDA PMID:9763420 Characterization of the kinetochore binding domain of CENP-E... | KEEP AS NON CORE | Summary: Chan et al. 1998 observed hBUBR1 diffusely distributed over the spindle at metaphase and concentrated in two spindle-midzone patches flanking CENP-E in late anaphase/telophase. Reason: A genuine but secondary localization; the midzone pool is consistent with the later proposal that BubR1 regulates CENP-E during central-spindle assembly (PMID:31201382), but this is not the core checkpoint function. Supporting Evidence: PMID:9763420 At this time however, hBUBR1 was diffusely distributed throughout the spindle PMID:9763420 By late anaphase, hBUBR1 was prominently distributed in two patches in the spindle midzone that flanked a narrow stripe of CENP-E |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Human Protein Atlas immunofluorescence: cytosolic. Reason: The MCC is a soluble, diffusible cytosolic inhibitor of APC/C-CDC20, and interphase BUBR1 is cytoplasmic. Supporting Evidence: PMID:11535616 Surprisingly, hBUBR1 complex isolated from interphase HeLa cells (synchronized in the G1/S boundary) inhibited APC/C activity and contained the same subunits found in mitotic MCC (unpublished data). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-141409 | ACCEPT | Summary: Reactome reaction 'Mad1 binds kinetochore' (mitotic spindle checkpoint / APC/C-MCC pathway); BUB1B participates as a subunit of the cytosolic MCC or APC/C-MCC complex. Reason: The MCC assembles and inhibits APC/C-CDC20 in the cytosol; the cytosolic compartment assignment in these SAC/APC/C reactions is correct. Supporting Evidence: PMID:11535616 Purified GSTβhBUBR1:MCC was found to inhibit ubiquitin ligase activity of the APC/C (Fig. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-141422 | ACCEPT | Summary: Reactome reaction 'MAD2 converted to an inhibitory state via interaction with Mad1' (mitotic spindle checkpoint / APC/C-MCC pathway); BUB1B participates as a subunit of the cytosolic MCC or APC/C-MCC complex. Reason: The MCC assembles and inhibits APC/C-CDC20 in the cytosol; the cytosolic compartment assignment in these SAC/APC/C reactions is correct. Supporting Evidence: PMID:11535616 Purified GSTβhBUBR1:MCC was found to inhibit ubiquitin ligase activity of the APC/C (Fig. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-141423 | ACCEPT | Summary: Reactome reaction 'Binding of the MCC complex to the APC/C complex' (mitotic spindle checkpoint / APC/C-MCC pathway); BUB1B participates as a subunit of the cytosolic MCC or APC/C-MCC complex. Reason: The MCC assembles and inhibits APC/C-CDC20 in the cytosol; the cytosolic compartment assignment in these SAC/APC/C reactions is correct. Supporting Evidence: PMID:11535616 Purified GSTβhBUBR1:MCC was found to inhibit ubiquitin ligase activity of the APC/C (Fig. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-141431 | ACCEPT | Summary: Reactome reaction 'MAD2 associates with the Mad1 kinetochore complex' (mitotic spindle checkpoint / APC/C-MCC pathway); BUB1B participates as a subunit of the cytosolic MCC or APC/C-MCC complex. Reason: The MCC assembles and inhibits APC/C-CDC20 in the cytosol; the cytosolic compartment assignment in these SAC/APC/C reactions is correct. Supporting Evidence: PMID:11535616 Purified GSTβhBUBR1:MCC was found to inhibit ubiquitin ligase activity of the APC/C (Fig. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-141437 | ACCEPT | Summary: Reactome reaction 'Formation of the MCC complex' (mitotic spindle checkpoint / APC/C-MCC pathway); BUB1B participates as a subunit of the cytosolic MCC or APC/C-MCC complex. Reason: The MCC assembles and inhibits APC/C-CDC20 in the cytosol; the cytosolic compartment assignment in these SAC/APC/C reactions is correct. Supporting Evidence: PMID:11535616 Purified GSTβhBUBR1:MCC was found to inhibit ubiquitin ligase activity of the APC/C (Fig. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-141439 | ACCEPT | Summary: Reactome reaction 'Release of activated MAD2 from kinetochores' (mitotic spindle checkpoint / APC/C-MCC pathway); BUB1B participates as a subunit of the cytosolic MCC or APC/C-MCC complex. Reason: The MCC assembles and inhibits APC/C-CDC20 in the cytosol; the cytosolic compartment assignment in these SAC/APC/C reactions is correct. Supporting Evidence: PMID:11535616 Purified GSTβhBUBR1:MCC was found to inhibit ubiquitin ligase activity of the APC/C (Fig. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1638803 | ACCEPT | Summary: Reactome reaction 'Phosphorylation of cohesin by PLK1 at centromeres', in which BUB1B is carried as a member of a generic Reactome kinetochore/centromere complex entity; the cytosol assignment is the compartment of that entity. Reason: The location claim itself (cytosol) is correct and identical to the other cytosol rows, so it is accepted for consistency; note, however, that these particular reactions (cohesin regulation, separase cleavage, astral microtubule capture, EML4/NUDC) are peripheral to BUBR1's direct role and the row derives from Reactome complex-entity membership rather than from a BUBR1-specific observation. Supporting Evidence: PMID:9763420 Examination of the subcellular distribution of hBUBR1 by immunofluorescence staining showed that it was concentrated in the cytoplasm of all interphase cells |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1638821 | ACCEPT | Summary: Reactome reaction 'PP2A-B56 dephosphorylates centromeric cohesin', in which BUB1B is carried as a member of a generic Reactome kinetochore/centromere complex entity; the cytosol assignment is the compartment of that entity. Reason: The location claim itself (cytosol) is correct and identical to the other cytosol rows, so it is accepted for consistency; note, however, that these particular reactions (cohesin regulation, separase cleavage, astral microtubule capture, EML4/NUDC) are peripheral to BUBR1's direct role and the row derives from Reactome complex-entity membership rather than from a BUBR1-specific observation. Supporting Evidence: PMID:9763420 Examination of the subcellular distribution of hBUBR1 by immunofluorescence staining showed that it was concentrated in the cytoplasm of all interphase cells |
| GO:0005829 cytosol | TAS Reactome:R-HSA-174104 | ACCEPT | Summary: Reactome reaction 'Ubiquitination of Cyclin A by APC/C:Cdc20 complex' (mitotic spindle checkpoint / APC/C-MCC pathway); BUB1B participates as a subunit of the cytosolic MCC or APC/C-MCC complex. Reason: The MCC assembles and inhibits APC/C-CDC20 in the cytosol; the cytosolic compartment assignment in these SAC/APC/C reactions is correct. Supporting Evidence: PMID:11535616 Purified GSTβhBUBR1:MCC was found to inhibit ubiquitin ligase activity of the APC/C (Fig. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-174171 | ACCEPT | Summary: Reactome reaction 'Association of Cyclin A with the APC/C' (mitotic spindle checkpoint / APC/C-MCC pathway); BUB1B participates as a subunit of the cytosolic MCC or APC/C-MCC complex. Reason: The MCC assembles and inhibits APC/C-CDC20 in the cytosol; the cytosolic compartment assignment in these SAC/APC/C reactions is correct. Supporting Evidence: PMID:11535616 Purified GSTβhBUBR1:MCC was found to inhibit ubiquitin ligase activity of the APC/C (Fig. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-174238 | ACCEPT | Summary: Reactome reaction 'Activation of APC/C:Cdc20 by dissociation of Cdc20:phospho-APC/C from Cdc20:phospho-APC/C:Mad2:Bub3:BubR1' (mitotic spindle checkpoint / APC/C-MCC pathway); BUB1B participates as a subunit of the cytosolic MCC or APC/C-MCC complex. Reason: The MCC assembles and inhibits APC/C-CDC20 in the cytosol; the cytosolic compartment assignment in these SAC/APC/C reactions is correct. Supporting Evidence: PMID:11535616 Purified GSTβhBUBR1:MCC was found to inhibit ubiquitin ligase activity of the APC/C (Fig. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-174255 | ACCEPT | Summary: Reactome reaction 'Degradation multiubiquitinated Cyclin A' (mitotic spindle checkpoint / APC/C-MCC pathway); BUB1B participates as a subunit of the cytosolic MCC or APC/C-MCC complex. Reason: The MCC assembles and inhibits APC/C-CDC20 in the cytosol; the cytosolic compartment assignment in these SAC/APC/C reactions is correct. Supporting Evidence: PMID:11535616 Purified GSTβhBUBR1:MCC was found to inhibit ubiquitin ligase activity of the APC/C (Fig. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-179410 | ACCEPT | Summary: Reactome reaction 'Association of Nek2A with MCC:APC/C' (mitotic spindle checkpoint / APC/C-MCC pathway); BUB1B participates as a subunit of the cytosolic MCC or APC/C-MCC complex. Reason: The MCC assembles and inhibits APC/C-CDC20 in the cytosol; the cytosolic compartment assignment in these SAC/APC/C reactions is correct. Supporting Evidence: PMID:11535616 Purified GSTβhBUBR1:MCC was found to inhibit ubiquitin ligase activity of the APC/C (Fig. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-179417 | ACCEPT | Summary: Reactome reaction 'Multiubiquitination of Nek2A' (mitotic spindle checkpoint / APC/C-MCC pathway); BUB1B participates as a subunit of the cytosolic MCC or APC/C-MCC complex. Reason: The MCC assembles and inhibits APC/C-CDC20 in the cytosol; the cytosolic compartment assignment in these SAC/APC/C reactions is correct. Supporting Evidence: PMID:11535616 Purified GSTβhBUBR1:MCC was found to inhibit ubiquitin ligase activity of the APC/C (Fig. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-179421 | ACCEPT | Summary: Reactome reaction 'Degradation of multiubiquitinated Nek2A' (mitotic spindle checkpoint / APC/C-MCC pathway); BUB1B participates as a subunit of the cytosolic MCC or APC/C-MCC complex. Reason: The MCC assembles and inhibits APC/C-CDC20 in the cytosol; the cytosolic compartment assignment in these SAC/APC/C reactions is correct. Supporting Evidence: PMID:11535616 Purified GSTβhBUBR1:MCC was found to inhibit ubiquitin ligase activity of the APC/C (Fig. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2467809 | ACCEPT | Summary: Reactome reaction 'ESPL1 (Separase) cleaves centromeric cohesin', in which BUB1B is carried as a member of a generic Reactome kinetochore/centromere complex entity; the cytosol assignment is the compartment of that entity. Reason: The location claim itself (cytosol) is correct and identical to the other cytosol rows, so it is accepted for consistency; note, however, that these particular reactions (cohesin regulation, separase cleavage, astral microtubule capture, EML4/NUDC) are peripheral to BUBR1's direct role and the row derives from Reactome complex-entity membership rather than from a BUBR1-specific observation. Supporting Evidence: PMID:9763420 Examination of the subcellular distribution of hBUBR1 by immunofluorescence staining showed that it was concentrated in the cytoplasm of all interphase cells |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2467811 | ACCEPT | Summary: Reactome reaction 'Separation of sister chromatids', in which BUB1B is carried as a member of a generic Reactome kinetochore/centromere complex entity; the cytosol assignment is the compartment of that entity. Reason: The location claim itself (cytosol) is correct and identical to the other cytosol rows, so it is accepted for consistency; note, however, that these particular reactions (cohesin regulation, separase cleavage, astral microtubule capture, EML4/NUDC) are peripheral to BUBR1's direct role and the row derives from Reactome complex-entity membership rather than from a BUBR1-specific observation. Supporting Evidence: PMID:9763420 Examination of the subcellular distribution of hBUBR1 by immunofluorescence staining showed that it was concentrated in the cytoplasm of all interphase cells |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2468287 | ACCEPT | Summary: Reactome reaction 'CDK1 phosphorylates CDCA5 (Sororin) at centromeres', in which BUB1B is carried as a member of a generic Reactome kinetochore/centromere complex entity; the cytosol assignment is the compartment of that entity. Reason: The location claim itself (cytosol) is correct and identical to the other cytosol rows, so it is accepted for consistency; note, however, that these particular reactions (cohesin regulation, separase cleavage, astral microtubule capture, EML4/NUDC) are peripheral to BUBR1's direct role and the row derives from Reactome complex-entity membership rather than from a BUBR1-specific observation. Supporting Evidence: PMID:9763420 Examination of the subcellular distribution of hBUBR1 by immunofluorescence staining showed that it was concentrated in the cytoplasm of all interphase cells |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2484822 | ACCEPT | Summary: Reactome reaction 'Kinetochore assembly', in which BUB1B is carried as a member of a generic Reactome kinetochore/centromere complex entity; the cytosol assignment is the compartment of that entity. Reason: The location claim itself (cytosol) is correct and identical to the other cytosol rows, so it is accepted for consistency; note, however, that these particular reactions (cohesin regulation, separase cleavage, astral microtubule capture, EML4/NUDC) are peripheral to BUBR1's direct role and the row derives from Reactome complex-entity membership rather than from a BUBR1-specific observation. Supporting Evidence: PMID:9763420 Examination of the subcellular distribution of hBUBR1 by immunofluorescence staining showed that it was concentrated in the cytoplasm of all interphase cells |
| GO:0005829 cytosol | TAS Reactome:R-HSA-375302 | ACCEPT | Summary: Reactome reaction 'Kinetochore capture of astral microtubules', in which BUB1B is carried as a member of a generic Reactome kinetochore/centromere complex entity; the cytosol assignment is the compartment of that entity. Reason: The location claim itself (cytosol) is correct and identical to the other cytosol rows, so it is accepted for consistency; note, however, that these particular reactions (cohesin regulation, separase cleavage, astral microtubule capture, EML4/NUDC) are peripheral to BUBR1's direct role and the row derives from Reactome complex-entity membership rather than from a BUBR1-specific observation. Supporting Evidence: PMID:9763420 Examination of the subcellular distribution of hBUBR1 by immunofluorescence staining showed that it was concentrated in the cytoplasm of all interphase cells |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5666129 | ACCEPT | Summary: Reactome reaction 'CDC42:GTP recruits DIAPH2-2 to kinetochores', in which BUB1B is carried as a member of a generic Reactome kinetochore/centromere complex entity; the cytosol assignment is the compartment of that entity. Reason: The location claim itself (cytosol) is correct and identical to the other cytosol rows, so it is accepted for consistency; note, however, that these particular reactions (cohesin regulation, separase cleavage, astral microtubule capture, EML4/NUDC) are peripheral to BUBR1's direct role and the row derives from Reactome complex-entity membership rather than from a BUBR1-specific observation. Supporting Evidence: PMID:9763420 Examination of the subcellular distribution of hBUBR1 by immunofluorescence staining showed that it was concentrated in the cytoplasm of all interphase cells |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5666160 | ACCEPT | Summary: Reactome reaction 'AURKB phosphorylates DIAPH2-2 at kinetochores', in which BUB1B is carried as a member of a generic Reactome kinetochore/centromere complex entity; the cytosol assignment is the compartment of that entity. Reason: The location claim itself (cytosol) is correct and identical to the other cytosol rows, so it is accepted for consistency; note, however, that these particular reactions (cohesin regulation, separase cleavage, astral microtubule capture, EML4/NUDC) are peripheral to BUBR1's direct role and the row derives from Reactome complex-entity membership rather than from a BUBR1-specific observation. Supporting Evidence: PMID:9763420 Examination of the subcellular distribution of hBUBR1 by immunofluorescence staining showed that it was concentrated in the cytoplasm of all interphase cells |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5666169 | ACCEPT | Summary: Reactome reaction 'Kinetochore capture of astral microtubules is positively regulated by CDC42:GTP:p-S196-DIAPH2-2', in which BUB1B is carried as a member of a generic Reactome kinetochore/centromere complex entity; the cytosol assignment is the compartment of that entity. Reason: The location claim itself (cytosol) is correct and identical to the other cytosol rows, so it is accepted for consistency; note, however, that these particular reactions (cohesin regulation, separase cleavage, astral microtubule capture, EML4/NUDC) are peripheral to BUBR1's direct role and the row derives from Reactome complex-entity membership rather than from a BUBR1-specific observation. Supporting Evidence: PMID:9763420 Examination of the subcellular distribution of hBUBR1 by immunofluorescence staining showed that it was concentrated in the cytoplasm of all interphase cells |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9648114 | ACCEPT | Summary: Reactome reaction 'EML4 recruits NUDC to mitotic spindle', in which BUB1B is carried as a member of a generic Reactome kinetochore/centromere complex entity; the cytosol assignment is the compartment of that entity. Reason: The location claim itself (cytosol) is correct and identical to the other cytosol rows, so it is accepted for consistency; note, however, that these particular reactions (cohesin regulation, separase cleavage, astral microtubule capture, EML4/NUDC) are peripheral to BUBR1's direct role and the row derives from Reactome complex-entity membership rather than from a BUBR1-specific observation. Supporting Evidence: PMID:9763420 Examination of the subcellular distribution of hBUBR1 by immunofluorescence staining showed that it was concentrated in the cytoplasm of all interphase cells |
| GO:0007094 mitotic spindle assembly checkpoint signaling | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT node PTN000361607 places mitotic spindle assembly checkpoint signaling at the Bub1/BubR1-Mad3 ancestor, seeded by yeast Bub1 and Mad3, worm, fly, plant and mammalian Bub1/BubR1. Human BUBR1 is the Mad3-like MCC subunit whose KEN/ABBA motifs inhibit APC/C-CDC20. Reason: Core function, directly demonstrated for the human protein (antibody microinjection abrogates mitotic arrest, PMID:10477750; MCC purification, PMID:11535616; APC/C-MCC structure, PMID:27509861) and conserved across the family. Supporting Evidence: PMID:10477750 Furthermore, microinjection of hBUBR1 antibodies abrogated the mitotic arrest and caused cells to exit mitosis. PMID:27509861 Mad2 and BubR1 interact cooperatively with Cdc20 (refs 9,13β18), and synergistically inhibit the APC/C in mitosis 14,19. |
| GO:0007094 mitotic spindle assembly checkpoint signaling | IDA PMID:10477750 Human BUBR1 is a mitotic checkpoint kinase that monitors CEN... | ACCEPT | Summary: Chan et al. 1999: microinjection of hBUBR1 antibodies abrogates nocodazole-induced mitotic arrest and causes premature anaphase with lagging chromosomes; hBUBR1 associates with the APC/C in mitotically arrested cells. Reason: Direct loss-of-function evidence that hBUBR1 is required for the mitotic checkpoint in human cells. Supporting Evidence: PMID:10477750 Furthermore, microinjection of hBUBR1 antibodies abrogated the mitotic arrest and caused cells to exit mitosis. |
| GO:0007094 mitotic spindle assembly checkpoint signaling | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO mapping from the Bub1/Mad3 family signature (IPR015661). Reason: The family signature correctly implies SAC function; redundant with experimental and IBA rows. Supporting Evidence: PMID:10477750 Furthermore, microinjection of hBUBR1 antibodies abrogated the mitotic arrest and caused cells to exit mitosis. |
| GO:0007094 mitotic spindle assembly checkpoint signaling | IMP PMID:20220147 Defining the molecular basis of BubR1 kinetochore interactio... | ACCEPT | Summary: D'Arcy et al. 2010 characterise BubR1 as essential for the mitotic checkpoint and dissect the N-terminal determinants of kinetochore recruitment and APC/C-CDC20 inhibition. Reason: Consistent with the core function; mutational data in this study inform how BubR1 executes SAC signalling. Supporting Evidence: PMID:20220147 BubR1 kinetochore enrichment is dependent on Bub1 and Bub3 (28, 29) and is required to sustain a SAC arrest, as well as for stable kinetochore-microtubule interactions (23). PMID:20220147 Second, BubR1 inhibits APC/C-Cdc20 ubiquitin ligase activity as part of the MCC (16). |
| GO:0007094 mitotic spindle assembly checkpoint signaling | NAS PMID:11535616 Checkpoint inhibition of the APC/C in HeLa cells is mediated... | ACCEPT | Summary: Sudakin et al. 2001 purified the APC/C inhibitor from HeLa cells and defined the MCC as hBUBR1, hBUB3, CDC20 and MAD2 in near-equal stoichiometry, 3,000-fold more potent than recombinant MAD2. Reason: Foundational biochemical definition of the MCC; BUBR1 co-purifies with APC/C inhibitory activity at every step. Supporting Evidence: PMID:11535616 At each of the three successive chromatographic steps, the peaks of APC/C inhibitory activity and hBUBR1 coincided. PMID:11535616 Purified GSTβhBUBR1:MCC was found to inhibit ubiquitin ligase activity of the APC/C (Fig. |
| GO:0033045 regulation of sister chromatid segregation | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA machine-learning assignment of the broad term 'regulation of sister chromatid segregation'. Reason: Broad but correct: SAC signalling delays sister chromatid separation until biorientation, and BUBR1 additionally stabilises kinetochore-microtubule attachments via PP2A-B56. The more specific descendant GO:0007094 is already annotated; an IEA broader than the literature is acceptable. Supporting Evidence: PMID:11702782 In the absence of Mad2, BubR1 inhibits the activity of APC by blocking the binding of Cdc20 to APC. |
| GO:0033597 mitotic checkpoint complex | IPI PMID:27509861 Molecular basis of APC/C regulation by the spindle assembly ... | ACCEPT | Summary: Alfieri et al. 2016 determined the near-atomic cryo-EM structure of human APC/C-MCC: BubR1 degron-like motifs (KEN1/KEN2, ABBA, D-box) occupy the substrate-recognition sites of both the MCC-intrinsic and APC/C-bound CDC20, and the BubR1 TPR blocks UbcH10 binding. Reason: Definitive structural evidence for BUBR1 as a stoichiometric MCC subunit and for its inhibitory mechanism. Supporting Evidence: PMID:27509861 Soluble C-Mad2 engages the N-terminus of Cdc20 (refs 10,11), the mitotic activating subunit of the APC/C, which then binds the BubR1-Bub3 dimer to form the MCC 12. PMID:27509861 Mad2 and BubR1 interact cooperatively with Cdc20 (refs 9,13β18), and synergistically inhibit the APC/C in mitosis 14,19. PMID:27509861 BubR1TPR interacts directly with the UbcH10 interface of Apc2WHB that repositions to contact BubR1TPR (Fig. |
| 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: Lefebvre et al. 2010 (B-cell interactome) confirmed a BUBR1-MCM3 co-IP and confocal imaging showing the proteins co-localized in the nucleus or perinuclearly in germinal-centre B cells. Reason: A single imaging observation in a systems-biology context; consistent with the cytoplasmic interphase pool but not a functionally characterised localization of BUBR1. Supporting Evidence: PMID:20531406 High-resolution confocal imaging showed that these proteins are co-localized either in the nucleus or perinuclearly (Figure 6C). PMID:20531406 BUBR1/MCM3, AURKA/MCM3 interactions were confirmed by endogenous co-immunoprecipitation (co-IP) assays in Ramos (Figure 6A) and ST486 Burkitt's lymphoma lines (data not shown). |
| GO:0051754 meiotic sister chromatid cohesion, centromeric | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT node PTN000361607 asserts a role in meiotic centromeric cohesion, seeded by Drosophila BubR1 and fission yeast Bub1 (both required to protect centromeric cohesin/Shugoshin in meiosis). Human BUBR1 recruits PP2A-B56 through its KARD, and BubR1-PP2A-B56 is part of the cohesin-protection machinery, but there is no direct human meiotic evidence in GOA. Reason: The phylogenetic placement is a considered judgment on a conserved Bub1/BubR1-shugoshin-PP2A module and is not contradicted for human BUBR1 (mouse oocyte studies support a BubR1 requirement in meiotic chromosome segregation), so the IBA is retained; it is graded non-core because the direct human evidence concerns mitosis and the shugoshin-recruiting kinase function of this module resides in the paralog BUB1. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: PANTHER:PTN000361607 Β· PTN000361607 SUPPORTS TRANSFER Node predates the Bub1/BubR1 split; the meiotic cohesion evidence comes from fly BubR1 and pombe Bub1. FB:FBgn0263855 Β· BubR1 SUPPORTS TRANSFER Drosophila BubR1 is required for meiotic centromeric cohesion maintenance. PomBase:SPCC1322.12c Β· bub1 SUPPORTS SOURCE BUT NOT TARGET Pombe Bub1 protects meiotic cohesion via H2A-S121 phosphorylation and Sgo1 recruitment, a kinase function carried in human by BUB1 rather than BUB1B. Supporting Evidence: file:human/BUB1B/BUB1B-deep-research-falcon.md The BUBR1βPP2A-B56 complex opposes Aurora B-driven destabilization of kinetochoreβmicrotubule attachments. file:human/BUB1B/BUB1B-deep-research-falcon.md BUBR1 therefore acts as a targeting platform that positions PP2A-B56 where kinetochore phosphosignalling must be reversed. |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000116 | MARK AS OVER ANNOTATED | Summary: Rhea reaction 17989 (protein serine phosphorylation) mapped from UniProt's catalytic-activity line; the only serine substrate reported for human BubR1 is CENP-E Ser2639 (PMID:31201382). Reason: Same disputed activity as the EC-based row, expressed as a Rhea reaction; graded consistently as non-core/over-annotated rather than removed, because one direct report exists. Supporting Evidence: PMID:31201382 Thus, Ser2639 of CENP-E is a substrate for BubR1 in vitro. PMID:31201382 However, this type of signature of an active kinase is not apparently conserved in human BubR1. |
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Download this section (compressed HTML)Q: Is human BubR1 catalytically active in cells? Independent reproduction of CENP-E Ser2639 phosphorylation by purified, kinase-contaminant-free human BubR1 (or a clean D882N/K795A knock-in) would settle whether the EC 2.7.11.1 and Rhea-derived kinase annotations should be retained or retired.
Q: Should the PP2A-B56 recruitment function be captured in GO for BUB1B (e.g. a PP2A-B56 binding/kinetochore adaptor activity with an attachment-stabilisation process), given that GOA currently carries no annotation for the KARD-dependent role?
Q: Does the IBA-derived meiotic centromeric cohesion term reflect a genuine human BUB1B (rather than BUB1) role, given that shugoshin recruitment by H2A-T120 phosphorylation is a BUB1 kinase function?
Experiment: In vitro phosphotransfer assay with recombinant human BubR1 purified from a kinase-free system (e.g. E. coli) and CENP-E tail as substrate, side by side with the D882N and K795A mutants and with a PLK1-depleted control, to test the disputed intrinsic kinase activity.
Type: biochemical
Experiment: Separation-of-function analysis in human cells combining KEN1/KEN2/ABBA mutants (MCC/APC/C inhibition) with KARD LxxIxE mutants (PP2A-B56 recruitment) to quantify the independent contributions of the two functions to mitotic timing, chromosome alignment and aneuploidy, including MVA patient alleles.
Type: genetic
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