BUB1B (budding uninhibited by benzimidazoles 1 homolog beta (yeast))
2012-03-01 Sandra Hanks , Katie Snape , Nazneen Rahman AffiliationMedical Genetics Section of Cancer Genetics, Brookes Lawley Building Institute of Cancer Research, 15 Cotswold Road, Sutton Surrey, SM2 5NG, UK
Identity
HGNC
LOCATION
15q15.1
LOCUSID
ALIAS
BUB1beta,BUBR1,Bub1A,MAD3L,MVA1,SSK1,hBUBR1
FUSION GENES
DNA/RNA
Figure 1. Schematic representation of BUB1B demonstrating the relative exon sizes.
Description
BUB1B spans 60 kb and is composed of 23 exons.
Proteins
Note
Protein name: BUBR1.
Figure 2. Schematic representation of BUBR1 demonstrating significant functional or structural domains.
Description
1050 amino acids, 120 kDa.
Expression
Ubiquituously expressed. Preferentially expressed in tissues with a high mitotic index.
Localisation
Function
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.
Homology
BUBR1 is the mammalian homologue of yeast Mad3, a significant difference being that BUBR1 possesses a kinase domain which is absent in Mad3.
Mutations
Note
Cells from BUB1B mutation-positive cases demonstrate an abnormal response to nocodazole-induced mitotic checkpoint activation.
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.
Germinal
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
Note
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.
Prognosis
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.
Cytogenetics
The proportion of aneuploid cells varies but is usually >10% and is substantially greater than in normal individuals.
Oncogenesis
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.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 15021889 | 2004 | The spindle checkpoint, aneuploidy, and cancer. | Bharadwaj R et al |
| 9521327 | 1998 | Mutations of mitotic checkpoint genes in human cancers. | Cahill DP et al |
| 14755404 | 2004 | Prenatal diagnosis of premature centromere division-related mosaic variegated aneuploidy. | Chen CP et al |
| 18548531 | 2008 | Clinical and genetic heterogeneity in patients with mosaic variegated aneuploidy: delineation of clinical subtypes. | García-Castillo H et al |
| 16182441 | 2006 | Comparative genomic hybridization and BUB1B mutation analyses in childhood cancers associated with mosaic variegated aneuploidy syndrome. | Hanks S et al |
| 19503101 | 2009 | BubR1 localizes to centrosomes and suppresses centrosome amplification via regulating Plk1 activity in interphase cells. | Izumi H et al |
| 15592459 | 2005 | The human mitotic checkpoint protein BubR1 regulates chromosome-spindle attachments. | Lampson MA et al |
| 12116237 | 2002 | Mosaic variegated aneuploidy with growth hormone deficiency and congenital heart defects. | Lane AH et al |
| 9916837 | 1999 | Child with mosaic variegated aneuploidy and embryonal rhabdomyosarcoma. | Limwongse C et al |
| 16411201 | 2006 | Monoallelic BUB1B mutations and defective mitotic-spindle checkpoint in seven families with premature chromatid separation (PCS) syndrome. | Matsuura S et al |
| 17426725 | 2007 | The spindle-assembly checkpoint in space and time. | Musacchio A et al |
| 11169558 | 2001 | Variegated aneuploidy related to premature centromere division (PCD) is expressed in vivo and is a cancer-prone disease. | Plaja A et al |
| 21552266 | 2011 | Mutations in CEP57 cause mosaic variegated aneuploidy syndrome. | Snape K et al |
| 20516114 | 2010 | Molecular causes for BUBR1 dysfunction in the human cancer predisposition syndrome mosaic variegated aneuploidy. | Suijkerbuijk SJ et al |
| 9660858 | 1998 | The 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
Variants:
dbSNP: 701
ClinVar: 701
TCGA: ENSG00000156970
COSMIC: BUB1B
RNA/Proteins
| Gene ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000156970 | ENST00000287598 | O60566 |
| ENSG00000156970 | ENST00000412359 | O60566 |
| ENSG00000156970 | ENST00000558715 | H0YN44 |
| ENSG00000156970 | ENST00000559733 | H0YMK5 |
Expression (GTEx)
Pathways
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 37782908 | 2024 | Knockdown of BUB1B Inhibits the Proliferation, Migration, and Invasion of Colorectal Cancer by Regulating the JNK/c-Jun Signaling Pathway. | 1 |
| 38043194 | 2024 | BubR1 and cyclin B1 immunoexpression in pleomorphic adenoma and polymorphous adenocarcinoma of minor salivary glands. | 0 |
| 39048649 | 2024 | Correlation of BUB1 and BUB1B with the development and prognosis of endometrial cancer. | 0 |
| 37782908 | 2024 | Knockdown of BUB1B Inhibits the Proliferation, Migration, and Invasion of Colorectal Cancer by Regulating the JNK/c-Jun Signaling Pathway. | 1 |
| 38043194 | 2024 | BubR1 and cyclin B1 immunoexpression in pleomorphic adenoma and polymorphous adenocarcinoma of minor salivary glands. | 0 |
| 39048649 | 2024 | Correlation of BUB1 and BUB1B with the development and prognosis of endometrial cancer. | 0 |
| 38008853 | 2023 | E3-ubiquitin ligase, FBXW7 regulates mitotic progression by targeting BubR1 for ubiquitin-mediated degradation. | 1 |
| 38008853 | 2023 | E3-ubiquitin ligase, FBXW7 regulates mitotic progression by targeting BubR1 for ubiquitin-mediated degradation. | 1 |
| 35068350 | 2022 | BUB1B (BUB1 Mitotic Checkpoint Serine/Threonine Kinase B) promotes lung adenocarcinoma by interacting with Zinc Finger Protein ZNF143 and regulating glycolysis. | 7 |
| 35493295 | 2022 | BUBs Are New Biomarkers of Promoting Tumorigenesis and Affecting Prognosis in Breast Cancer. | 5 |
| 35767360 | 2022 | BubR1 recruitment to the kinetochore via Bub1 enhances spindle assembly checkpoint signaling. | 2 |
| 36577966 | 2022 | Clinical value and potential mechanisms of BUB1B up-regulation in nasopharyngeal carcinoma. | 2 |
| 35068350 | 2022 | BUB1B (BUB1 Mitotic Checkpoint Serine/Threonine Kinase B) promotes lung adenocarcinoma by interacting with Zinc Finger Protein ZNF143 and regulating glycolysis. | 7 |
| 35493295 | 2022 | BUBs Are New Biomarkers of Promoting Tumorigenesis and Affecting Prognosis in Breast Cancer. | 5 |
| 35767360 | 2022 | BubR1 recruitment to the kinetochore via Bub1 enhances spindle assembly checkpoint signaling. | 2 |
Citation
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/bub1b
Historical Card
2005-07-01 BUB1B (budding uninhibited by benzimidazoles 1 homolog beta (yeast)) by Sandra Hanks,Nazneen Rahman Affiliation
Medical Genetics Section of Cancer Genetics, Brookes Lawley Building Institute of Cancer Research, 15 Cotswold Road, Sutton Surrey, SM2 5NG, UK
