| Written | 2005-07 | 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 | ||
| Updated | 2012-03 | Sandra Hanks, Katie Snape, Nazneen Rahman |
| Institute of Cancer Research, Division of Genetics, Epidemiology, Brookes Lawley Building, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK |
| Identity |
| Alias_names | budding uninhibited by benzimidazoles 1 (yeast homolog), beta |
| budding uninhibited by benzimidazoles 1 homolog beta (yeast) | |
| Alias_symbol (synonym) | BUBR1 |
| MAD3L | |
| Bub1A | |
| SSK1 | |
| Other alias | |
| HGNC (Hugo) | BUB1B |
| LocusID (NCBI) | 701 |
| Atlas_Id | 854 |
| Location | 15q15.1 [Link to chromosome band 15q15] |
| Location_base_pair | Starts at 40161009 and ends at 40221136 bp from pter ( according to hg19-Feb_2009) [Mapping BUB1B.png] |
| Fusion genes (updated 2016) | BUB1B (15q15.1) / EIF2AK4 (15q15.1) |
| DNA/RNA |
 | |
| Figure 1. Schematic representation of BUB1B demonstrating the relative exon sizes. | |
| Description | BUB1B spans 60 kb and is composed of 23 exons. |
| Protein |
| 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 | Cytoplasmic in interphase cells. Bound to BUB3 or CENPE, it can be localised to nuclear kinetochores. BUBR1 also localises to centrosomes during interphase. |
| 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 |
| Note | |
| Entity | Mosaic variegated aneuploidy (MVA) |
| 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. |
| To be noted |
| Biallelic mutations in CEP57 have also been identified in individuals with MVA syndrome. |
| Bibliography |
| The spindle checkpoint, aneuploidy, and cancer. |
| Bharadwaj R, Yu H. |
| Oncogene. 2004 Mar 15;23(11):2016-27. (REVIEW) |
| PMID 15021889 |
| Mutations of mitotic checkpoint genes in human cancers. |
| Cahill DP, Lengauer C, Yu J, Riggins GJ, Willson JK, Markowitz SD, Kinzler KW, Vogelstein B. |
| Nature. 1998 Mar 19;392(6673):300-3. |
| PMID 9521327 |
| Prenatal diagnosis of premature centromere division-related mosaic variegated aneuploidy. |
| Chen CP, Lee CC, Chen WL, Wang W, Tzen CY. |
| Prenat Diagn. 2004 Jan;24(1):19-25. (REVIEW) |
| PMID 14755404 |
| Clinical and genetic heterogeneity in patients with mosaic variegated aneuploidy: delineation of clinical subtypes. |
| Garcia-Castillo H, Vasquez-Velasquez AI, Rivera H, Barros-Nunez P. |
| Am J Med Genet A. 2008 Jul 1;146A(13):1687-95. (REVIEW) |
| PMID 18548531 |
| Comparative genomic hybridization and BUB1B mutation analyses in childhood cancers associated with mosaic variegated aneuploidy syndrome. |
| Hanks S, Coleman K, Summersgill B, Messahel B, Williamson D, Pritchard-Jones K, Strefford J, Swansbury J, Plaja A, Shipley J, Rahman N. |
| Cancer Lett. 2006 Aug 8;239(2):234-8. Epub 2005 Sep 22. |
| PMID 16182441 |
| BubR1 localizes to centrosomes and suppresses centrosome amplification via regulating Plk1 activity in interphase cells. |
| Izumi H, Matsumoto Y, Ikeuchi T, Saya H, Kajii T, Matsuura S. |
| Oncogene. 2009 Aug 6;28(31):2806-20. Epub 2009 Jun 8. |
| PMID 19503101 |
| The human mitotic checkpoint protein BubR1 regulates chromosome-spindle attachments. |
| Lampson MA, Kapoor TM. |
| Nat Cell Biol. 2005 Jan;7(1):93-8. Epub 2004 Dec 12. |
| PMID 15592459 |
| Mosaic variegated aneuploidy with growth hormone deficiency and congenital heart defects. |
| Lane AH, Aijaz N, Galvin-Parton P, Lanman J, Mangano R, Wilson TA. |
| Am J Med Genet. 2002 Jul 1;110(3):273-7. |
| PMID 12116237 |
| Child with mosaic variegated aneuploidy and embryonal rhabdomyosarcoma. |
| Limwongse C, Schwartz S, Bocian M, Robin NH. |
| Am J Med Genet. 1999 Jan 1;82(1):20-4. (REVIEW) |
| PMID 9916837 |
| Monoallelic BUB1B mutations and defective mitotic-spindle checkpoint in seven families with premature chromatid separation (PCS) syndrome. |
| Matsuura S, Matsumoto Y, Morishima K, Izumi H, Matsumoto H, Ito E, Tsutsui K, Kobayashi J, Tauchi H, Kajiwara Y, Hama S, Kurisu K, Tahara H, Oshimura M, Komatsu K, Ikeuchi T, Kajii T. |
| Am J Med Genet A. 2006 Feb 15;140(4):358-67. |
| PMID 16411201 |
| The spindle-assembly checkpoint in space and time. |
| Musacchio A, Salmon ED. |
| Nat Rev Mol Cell Biol. 2007 May;8(5):379-93. Epub 2007 Apr 11. (REVIEW) |
| PMID 17426725 |
| Variegated aneuploidy related to premature centromere division (PCD) is expressed in vivo and is a cancer-prone disease. |
| Plaja A, Vendrell T, Smeets D, Sarret E, Gili T, Catala V, Mediano C, Scheres JM. |
| Am J Med Genet. 2001 Jan 22;98(3):216-23. (REVIEW) |
| PMID 11169558 |
| Mutations in CEP57 cause mosaic variegated aneuploidy syndrome. |
| Snape K, Hanks S, Ruark E, Barros-Nunez P, Elliott A, Murray A, Lane AH, Shannon N, Callier P, Chitayat D, Clayton-Smith J, Fitzpatrick DR, Gisselsson D, Jacquemont S, Asakura-Hay K, Micale MA, Tolmie J, Turnpenny PD, Wright M, Douglas J, Rahman N. |
| Nat Genet. 2011 Jun;43(6):527-9. Epub 2011 May 8. |
| PMID 21552266 |
| Molecular causes for BUBR1 dysfunction in the human cancer predisposition syndrome mosaic variegated aneuploidy. |
| Suijkerbuijk SJ, van Osch MH, Bos FL, Hanks S, Rahman N, Kops GJ. |
| Cancer Res. 2010 Jun 15;70(12):4891-900. Epub 2010 Jun 1. |
| PMID 20516114 |
| The human homologue of Bub3 is required for kinetochore localization of Bub1 and a Mad3/Bub1-related protein kinase. |
| Taylor SS, Ha E, McKeon F. |
| J Cell Biol. 1998 Jul 13;142(1):1-11. |
| PMID 9660858 |
| Citation |
| This paper should be referenced as such : |
| Hanks, S ; Snape, K ; Rahman, N |
| BUB1B (budding uninhibited by benzimidazoles 1 homolog beta (yeast)) |
| Atlas Genet Cytogenet Oncol Haematol. 2012;16(8):518-520. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Genes/BUB1BID854ch15q15.html |
| History of this paper: |
| Hanks, S ; Rahman, N. BUB1B (BUB1 budding uninhibited by benzimidazoles 1 homolog beta (yeast)). Atlas Genet Cytogenet Oncol Haematol. 2005;9(4):284-285. |
| http://documents.irevues.inist.fr/bitstream/handle/2042/38238/07-2005-BUB1BID854ch15q15.pdf |
| Other Cancer prone implicated (Data extracted from papers in the Atlas) [ 2 ] |
| Mosaic variegated aneuploidy syndrome Variegated aneuploidy related to premature centromere division (PCD) |
| External links |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Fri Jun 30 11:02:13 CEST 2017 |
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