BUB1B (budding uninhibited by benzimidazoles 1 homolog beta (yeast))

2012-03-01   Sandra Hanks , Katie Snape , Nazneen Rahman 

Medical Genetics Section of Cancer Genetics, Brookes Lawley Building Institute of Cancer Research, 15 Cotswold Road, Sutton Surrey, SM2 5NG, UK




Atlas Image
Figure 1. Schematic representation of BUB1B demonstrating the relative exon sizes.


BUB1B spans 60 kb and is composed of 23 exons.



Protein name: BUBR1.
Atlas Image
Figure 2. Schematic representation of BUBR1 demonstrating significant functional or structural domains.


1050 amino acids, 120 kDa.


Ubiquituously expressed. Preferentially expressed in tissues with a high mitotic index.


Cytoplasmic in interphase cells. Bound to BUB3 or CENPE, it can be localised to nuclear kinetochores. BUBR1 also localises to centrosomes during interphase.


A central component of the mitotic spindle checkpoint that directly inhibits the anaphase-promoting complex/cyclosome until sister chromatids are correctly attached to the spindle, thus ensuring proper chromosome segregation during cell division. Also binds the motor protein CENPE, an interaction required for regulation of kinetochore-microtubule interactions and checkpoint signalling.


BUBR1 is the mammalian homologue of yeast Mad3, a significant difference being that BUBR1 possesses a kinase domain which is absent in Mad3.



Cells from BUB1B mutation-positive cases demonstrate an abnormal response to nocodazole-induced mitotic checkpoint activation.
Atlas Image
Figure 3. Schematic representation of BUB1B demonstrating the relative exon sizes and positions of known mutations. Truncating mutations are depicted above the figure, with missense mutations below. Biallelic mutations are represented by coloured lines, with mutations in the same individual in matching colours. Monoallelic mutations are represented by black lines and font.


Biallelic germline mutations have been found in eight MVA pedigrees (figure 3). Each family carries one missense mutation and one mutation that results in premature protein truncation or an absent transcript. Monoallelic truncating mutations have also been reported in several cases.

Implicated in

Entity name
Mosaic variegated aneuploidy (MVA)
MVA is a rare recessive condition characterised by mosaic aneuploidies, predominantly trisomies and monosomies, involving multiple different chromosomes and tissues. Affected individuals typically present with severe intrauterine growth retardation and microcephaly. Eye anomalies, mild dysmorphism, variable developmental delay and a broad spectrum of additional congenital abnormalities and medical conditions may also occur.
There is early mortality in a significant proportion of cases due to failure to thrive and/or complications of congenital abnormalities, epilepsy, infections or malignancy.
The proportion of aneuploid cells varies but is usually >10% and is substantially greater than in normal individuals.
The risk of malignancy in MVA is high, with Wilms tumour, rhabdomyosarcoma, leukaemia and granulosa cell tumour of the ovary reported in several cases. Myelodysplastic syndrome has also been observed. Three of the eight cases with biallelic BUB1B mutations developed a rhabdomyosarcoma and one individual developed a granulosa cell tumour of the ovary. Wilms tumour and rhabdomyosarcoma have been reported in monoallelic BUB1B cases.


Pubmed IDLast YearTitleAuthors
150218892004The spindle checkpoint, aneuploidy, and cancer.Bharadwaj R et al
95213271998Mutations of mitotic checkpoint genes in human cancers.Cahill DP et al
147554042004Prenatal diagnosis of premature centromere division-related mosaic variegated aneuploidy.Chen CP et al
185485312008Clinical and genetic heterogeneity in patients with mosaic variegated aneuploidy: delineation of clinical subtypes.García-Castillo H et al
161824412006Comparative genomic hybridization and BUB1B mutation analyses in childhood cancers associated with mosaic variegated aneuploidy syndrome.Hanks S et al
195031012009BubR1 localizes to centrosomes and suppresses centrosome amplification via regulating Plk1 activity in interphase cells.Izumi H et al
155924592005The human mitotic checkpoint protein BubR1 regulates chromosome-spindle attachments.Lampson MA et al
121162372002Mosaic variegated aneuploidy with growth hormone deficiency and congenital heart defects.Lane AH et al
99168371999Child with mosaic variegated aneuploidy and embryonal rhabdomyosarcoma.Limwongse C et al
164112012006Monoallelic BUB1B mutations and defective mitotic-spindle checkpoint in seven families with premature chromatid separation (PCS) syndrome.Matsuura S et al
174267252007The spindle-assembly checkpoint in space and time.Musacchio A et al
111695582001Variegated aneuploidy related to premature centromere division (PCD) is expressed in vivo and is a cancer-prone disease.Plaja A et al
215522662011Mutations in CEP57 cause mosaic variegated aneuploidy syndrome.Snape K et al
205161142010Molecular causes for BUBR1 dysfunction in the human cancer predisposition syndrome mosaic variegated aneuploidy.Suijkerbuijk SJ et al
96608581998The human homologue of Bub3 is required for kinetochore localization of Bub1 and a Mad3/Bub1-related protein kinase.Taylor SS et al

Other Information

Locus ID:

NCBI: 701
MIM: 602860
HGNC: 1149
Ensembl: ENSG00000156970


dbSNP: 701
ClinVar: 701
TCGA: ENSG00000156970


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Cell cycleKEGGko04110
Cell cycleKEGGhsa04110
HTLV-I infectionKEGGko05166
HTLV-I infectionKEGGhsa05166
Signal TransductionREACTOMER-HSA-162582
Signaling by Rho GTPasesREACTOMER-HSA-194315
RHO GTPase EffectorsREACTOMER-HSA-195258
RHO GTPases Activate ForminsREACTOMER-HSA-5663220
Cell CycleREACTOMER-HSA-1640170
Cell Cycle CheckpointsREACTOMER-HSA-69620
Mitotic Spindle CheckpointREACTOMER-HSA-69618
Inhibition of the proteolytic activity of APC/C required for the onset of anaphase by mitotic spindle checkpoint componentsREACTOMER-HSA-141405
Inactivation of APC/C via direct inhibition of the APC/C complexREACTOMER-HSA-141430
Cell Cycle, MitoticREACTOMER-HSA-69278
Mitotic PrometaphaseREACTOMER-HSA-68877
Resolution of Sister Chromatid CohesionREACTOMER-HSA-2500257
Mitotic Metaphase and AnaphaseREACTOMER-HSA-2555396
Mitotic AnaphaseREACTOMER-HSA-68882
Separation of Sister ChromatidsREACTOMER-HSA-2467813
Regulation of mitotic cell cycleREACTOMER-HSA-453276
APC/C-mediated degradation of cell cycle proteinsREACTOMER-HSA-174143
Regulation of APC/C activators between G1/S and early anaphaseREACTOMER-HSA-176408
Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteinsREACTOMER-HSA-176814
APC/C:Cdc20 mediated degradation of mitotic proteinsREACTOMER-HSA-176409
APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpointREACTOMER-HSA-179419
Cdc20:Phospho-APC/C mediated degradation of Cyclin AREACTOMER-HSA-174184
APC-Cdc20 mediated degradation of Nek2AREACTOMER-HSA-179409


Pubmed IDYearTitleCitations
154759552004Constitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B.178
191547222009Unattached kinetochores catalyze production of an anaphase inhibitor that requires a Mad2 template to prime Cdc20 for BubR1 binding.128
155924592005The human mitotic checkpoint protein BubR1 regulates chromosome-spindle attachments.127
119072592002Checkpoint protein BubR1 acts synergistically with Mad2 to inhibit anaphase-promoting complex.122
230795972012Integration of kinase and phosphatase activities by BUBR1 ensures formation of stable kinetochore-microtubule attachments.100
117928042001Kinetochore localisation and phosphorylation of the mitotic checkpoint components Bub1 and BubR1 are differentially regulated by spindle events in human cells.88
191394322009Gene expression profiling reveals a new classification of adrenocortical tumors and identifies molecular predictors of malignancy and survival.82
233453992013Direct binding between BubR1 and B56-PP2A phosphatase complexes regulate mitotic progression.73
221009202011p31comet-mediated extraction of Mad2 from the MCC promotes efficient mitotic exit.70
161449042005Microtubule capture by CENP-E silences BubR1-dependent mitotic checkpoint signaling.62


Sandra Hanks ; Katie Snape ; Nazneen Rahman

BUB1B (budding uninhibited by benzimidazoles 1 homolog beta (yeast))

Atlas Genet Cytogenet Oncol Haematol. 2012-03-01

Online version: http://atlasgeneticsoncology.org/gene/854/bub1bid854ch15q15

Historical Card

2005-07-01 BUB1B (budding uninhibited by benzimidazoles 1 homolog beta (yeast)) by  Sandra Hanks,Nazneen Rahman 

Medical Genetics Section of Cancer Genetics, Brookes Lawley Building Institute of Cancer Research, 15 Cotswold Road, Sutton Surrey, SM2 5NG, UK