BUB1B

BUB1 mitotic checkpoint serine/threonine kinase B
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2WVI​, 3SI5​, 4GGD​
Identifiers
Symbols	BUB1B ; BUB1beta; BUBR1; Bub1A; MAD3L; MVA1; SSK1; hBUBR1
External IDs	OMIM: 602860 MGI: 1333889 HomoloGene: 933 GeneCards: BUB1B Gene
EC number	2.7.11.1
Gene ontology Molecular function • protein kinase activity • protein serine/threonine kinase activity • protein binding • ATP binding Cellular component • kinetochore • condensed chromosome kinetochore • condensed nuclear chromosome kinetochore • condensed chromosome outer kinetochore • anaphase-promoting complex • cytoplasm • microtubule organizing center • cytosol • perinuclear region of cytoplasm • spindle midzone Biological process • mitotic cell cycle • protein phosphorylation • apoptotic process • mitotic nuclear division • metaphase/anaphase transition of mitotic cell cycle • mitotic cell cycle checkpoint • mitotic spindle assembly checkpoint • small GTPase mediated signal transduction • cell proliferation • anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process • protein localization to kinetochore • cell division • negative regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle • regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	701	12236
Ensembl	ENSG00000156970	ENSMUSG00000040084
UniProt	O60566	Q9Z1S0
RefSeq (mRNA)	NM_001211	NM_009773
RefSeq (protein)	NP_001202	NP_033903
Location (UCSC)	Chr 15: 40.16 – 40.22 Mb	Chr 2: 118.6 – 118.64 Mb
PubMed search

Mitotic checkpoint serine/threonine-protein kinase BUB1 beta is an enzyme that in humans is encoded by the BUB1B gene.^[1]

Function

This gene encodes a kinase involved in spindle checkpoint function and chromosome segregation.^[2] The protein has been localized to the kinetochore and plays a role in the inhibition of the anaphase-promoting complex/cyclosome (APC/C), delaying the onset of anaphase and ensuring proper chromosome segregation. Impaired spindle checkpoint function has been found in many forms of cancer.^[3]

Increased expression of BubR1 in mice extends a healthy lifespan.^[4]

Interactions

BUB1B has been shown to interact with:

• AP2B1,^[5]
• BRCA2^[6]
• BUB3,^[5][7][8]
• CDC20,^{[9][10][11][12][13][14]}
• HDAC1,^[15]
• MAD2L1,^[9] and
• SNCG.^[16]

References

1. Davenport JW, Fernandes ER, Harris LD, Neale GA, Goorha R (March 1999). "The mouse mitotic checkpoint gene bub1b, a novel bub1 family member, is expressed in a cell cycle-dependent manner". Genomics 55 (1): 113–7. doi:10.1006/geno.1998.5629. PMID 9889005.
2. Guo Y, Kim C, Ahmad S, Zhang J, Mao Y (July 2012). "CENP-E--dependent BubR1 autophosphorylation enhances chromosome alignment and the mitotic checkpoint". J Cell Biol. 198 (2): 205–217. doi:10.1083/jcb.201202152. PMID 22801780. Lay summary – Journal of Cell Biology.
3. "Entrez Gene: BUB1B BUB1 budding uninhibited by benzimidazoles 1 homolog beta (yeast)".
4. Baker DJ, Dawlaty MM, Wijshake T, Jeganathan KB, Malureanu L, van Ree JH, Crespo-Diaz R, Reyes S, Seaburg L, Shapiro V, Behfar A, Terzic A, van de Sluis B, van Deursen JM (December 2012). "Increased expression of BubR1 protects against aneuploidy and cancer and extends healthy lifespan". Nat. Cell Biol. 15 (1): 96–102. doi:10.1038/ncb2643. PMID 23242215. Lay summary – Mayo Clinic.
5. Cayrol C, Cougoule C, Wright M (November 2002). "The beta2-adaptin clathrin adaptor interacts with the mitotic checkpoint kinase BubR1". Biochem. Biophys. Res. Commun. 298 (5): 720–30. doi:10.1016/S0006-291X(02)02522-6. PMID 12419313.
6. Futamura M, Arakawa H, Matsuda K, Katagiri T, Saji S, Miki Y, Nakamura Y (March 2000). "Potential role of BRCA2 in a mitotic checkpoint after phosphorylation by hBUBR1". Cancer Res. 60 (6): 1531–5. PMID 10749118.
7. Hoyt MA (September 2001). "A new view of the spindle checkpoint". J. Cell Biol. 154 (5): 909–11. doi:10.1083/jcb.200108010. PMC 2196198. PMID 11535614.
8. Taylor SS, Ha E, McKeon F (July 1998). "The human homologue of Bub3 is required for kinetochore localization of Bub1 and a Mad3/Bub1-related protein kinase". J. Cell Biol. 142 (1): 1–11. doi:10.1083/jcb.142.1.1. PMC 2133037. PMID 9660858.
9. Sudakin V, Chan GK, Yen TJ (September 2001). "Checkpoint inhibition of the APC/C in HeLa cells is mediated by a complex of BUBR1, BUB3, CDC20, and MAD2". J. Cell Biol. 154 (5): 925–36. doi:10.1083/jcb.200102093. PMC 2196190. PMID 11535616.
10. Fang G (March 2002). "Checkpoint protein BubR1 acts synergistically with Mad2 to inhibit anaphase-promoting complex". Mol. Biol. Cell 13 (3): 755–66. doi:10.1091/mbc.01-09-0437. PMC 99596. PMID 11907259.
11. Wu H, Lan Z, Li W, Wu S, Weinstein J, Sakamoto KM, Dai W (September 2000). "p55CDC/hCDC20 is associated with BUBR1 and may be a downstream target of the spindle checkpoint kinase". Oncogene 19 (40): 4557–62. doi:10.1038/sj.onc.1203803. PMID 11030144.
12. Kallio MJ, Beardmore VA, Weinstein J, Gorbsky GJ (September 2002). "Rapid microtubule-independent dynamics of Cdc20 at kinetochores and centrosomes in mammalian cells". J. Cell Biol. 158 (5): 841–7. doi:10.1083/jcb.200201135. PMC 2173153. PMID 12196507.
13. Skoufias DA, Andreassen PR, Lacroix FB, Wilson L, Margolis RL (April 2001). "Mammalian mad2 and bub1/bubR1 recognize distinct spindle-attachment and kinetochore-tension checkpoints". Proc. Natl. Acad. Sci. U.S.A. 98 (8): 4492–7. doi:10.1073/pnas.081076898. PMC 31862. PMID 11274370.
14. Nilsson J, Yekezare M, Minshull J, Pines J (December 2008). "The APC/C maintains the spindle assembly checkpoint by targeting Cdc20 for destruction". Nat. Cell Biol. 10 (12): 1411–20. doi:10.1038/ncb1799. PMC 2635557. PMID 18997788.
15. Yoon YM, Baek KH, Jeong SJ, Shin HJ, Ha GH, Jeon AH, Hwang SG, Chun JS, Lee CW (September 2004). "WD repeat-containing mitotic checkpoint proteins act as transcriptional repressors during interphase". FEBS Lett. (Netherlands) 575 (1–3): 23–9. doi:10.1016/j.febslet.2004.07.089. ISSN 0014-5793. PMID 15388328.
16. Gupta A, Inaba S, Wong OK, Fang G, Liu J (October 2003). "Breast cancer-specific gene 1 interacts with the mitotic checkpoint kinase BubR1". Oncogene 22 (48): 7593–9. doi:10.1038/sj.onc.1206880. PMID 14576821.

Further reading

• Posas F, Saito H (1998). "Activation of the yeast SSK2 MAP kinase kinase kinase by the SSK1 two-component response regulator". EMBO J. 17 (5): 1385–94. doi:10.1093/emboj/17.5.1385. PMC 1170486. PMID 9482735.
• Cahill DP, Lengauer C, Yu J, Riggins GJ, Willson JK, Markowitz SD, Kinzler KW, Vogelstein B (1998). "Mutations of mitotic checkpoint genes in human cancers". Nature 392 (6673): 300–3. doi:10.1038/32688. PMID 9521327.
• Donadelli R, Benatti L, Remuzzi A, Morigi M, Gullans SR, Benigni A, Remuzzi G, Noris M (1998). "Identification of a novel gene--SSK1--in human endothelial cells exposed to shear stress". Biochem. Biophys. Res. Commun. 246 (3): 881–7. doi:10.1006/bbrc.1998.8713. PMID 9618306.
• Chan GK, Schaar BT, Yen TJ (1998). "Characterization of the kinetochore binding domain of CENP-E reveals interactions with the kinetochore proteins CENP-F and hBUBR1". J. Cell Biol. 143 (1): 49–63. doi:10.1083/jcb.143.1.49. PMC 2132809. PMID 9763420.
• Jablonski SA, Chan GK, Cooke CA, Earnshaw WC, Yen TJ (1999). "The hBUB1 and hBUBR1 kinases sequentially assemble onto kinetochores during prophase with hBUBR1 concentrating at the kinetochore plates in mitosis". Chromosoma 107 (6–7): 386–96. doi:10.1007/s004120050322. PMID 9914370.
• Cahill DP, da Costa LT, Carson-Walter EB, Kinzler KW, Vogelstein B, Lengauer C (1999). "Characterization of MAD2B and other mitotic spindle checkpoint genes". Genomics 58 (2): 181–7. doi:10.1006/geno.1999.5831. PMID 10366450.
• Chan GK, Jablonski SA, Sudakin V, Hittle JC, Yen TJ (1999). "Human BUBR1 is a mitotic checkpoint kinase that monitors CENP-E functions at kinetochores and binds the cyclosome/APC". J. Cell Biol. 146 (5): 941–54. doi:10.1083/jcb.146.5.941. PMC 2169490. PMID 10477750.
• Li W, Lan Z, Wu H, Wu S, Meadows J, Chen J, Zhu V, Dai W (2000). "BUBR1 phosphorylation is regulated during mitotic checkpoint activation". Cell Growth Differ. 10 (11): 769–75. PMID 10593653.
• Saffery R, Irvine DV, Griffiths B, Kalitsis P, Choo KH (2001). "Components of the human spindle checkpoint control mechanism localize specifically to the active centromere on dicentric chromosomes". Hum. Genet. 107 (4): 376–84. doi:10.1007/s004390000386. PMID 11129339.
• Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S (2001). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Rep. 1 (3): 287–92. doi:10.1093/embo-reports/kvd058. PMC 1083732. PMID 11256614.
• Kaplan KB, Burds AA, Swedlow JR, Bekir SS, Sorger PK, Näthke IS (2001). "A role for the Adenomatous Polyposis Coli protein in chromosome segregation". Nat. Cell Biol. 3 (4): 429–32. doi:10.1038/35070123. PMID 11283619.
• Tang Z, Bharadwaj R, Li B, Yu H (2001). "Mad2-Independent inhibition of APCCdc20 by the mitotic checkpoint protein BubR1". Dev. Cell 1 (2): 227–37. doi:10.1016/S1534-5807(01)00019-3. PMID 11702782.
• Shichiri M, Yoshinaga K, Hisatomi H, Sugihara K, Hirata Y (2002). "Genetic and epigenetic inactivation of mitotic checkpoint genes hBUB1 and hBUBR1 and their relationship to survival". Cancer Res. 62 (1): 13–7. PMID 11782350.
• Taylor SS, Hussein D, Wang Y, Elderkin S, Morrow CJ (2002). "Kinetochore localisation and phosphorylation of the mitotic checkpoint components Bub1 and BubR1 are differentially regulated by spindle events in human cells". J. Cell. Sci. 114 (Pt 24): 4385–95. PMID 11792804.