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

Written2005-07Sandra Hanks, Nazneen Rahman
Medical Genetics Section of Cancer Genetics, Brookes Lawley Building Institute of Cancer Research, 15 Cotswold Road, Sutton Surrey, SM2 5NG, UK
Updated2012-03Sandra Hanks, Katie Snape, Nazneen Rahman
Institute of Cancer Research, Division of Genetics, Epidemiology, Brookes Lawley Building, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK

(Note : for Links provided by Atlas : click)

Identity

Other aliasBub1A
BUBR1
MAD3L
SSK1
LocusID (NCBI) 701
Atlas_Id 854
Location 15q15.1  [Link to chromosome band 15q15]
Location_base_pair Starts at and ends at bp from pter
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
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 Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ]
  BUB1B/EIF2AK4 (15q15)


Other Cancer prone implicated (Data extracted from papers in the Atlas) [ 1 ]
  Mosaic variegated aneuploidy syndrome


External links

Nomenclature
Cards
AtlasBUB1BID854ch15q15.txt
Aliases
Genomic and cartography
Gene and transcription
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)701
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Protein Interaction databases
Ontologies - Pathways
Clinical trials, drugs, therapy
Miscellaneous
canSAR (ICR) (select the gene name)
Probes
Litterature
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed


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