Hmdb loader
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Identification
HMDB Protein ID HMDBP01451
Secondary Accession Numbers
  • 6747
Name Mitotic checkpoint serine/threonine-protein kinase BUB1 beta
Synonyms
  1. MAD3/BUB1-related protein kinase
  2. Mitotic checkpoint kinase MAD3L
  3. Protein SSK1
  4. hBUBR1
Gene Name BUB1B
Protein Type Enzyme
Biological Properties
General Function Involved in protein kinase activity
Specific Function Essential component of the mitotic checkpoint. Required for normal mitosis progression. The mitotic checkpoint delays anaphase until all chromosomes are properly attached to the mitotic spindle. One of its checkpoint functions is to inhibit the activity of the anaphase-promoting complex/cyclosome (APC/C) by blocking the binding of CDC20 to APC/C, independently of its kinase activity. The other is to monitor kinetochore activities that depend on the kinetochore motor CENPE. Required for kinetochore localization of CENPE. Negatively regulates PLK1 activity in interphase cells and suppresses centrosome amplification. Also implicated in triggering apoptosis in polyploid cells that exit aberrantly from mitotic arrest. May play a role for tumor suppression
Pathways Not Available
Reactions Not Available
GO Classification
Function
binding
catalytic activity
transferase activity
transferase activity, transferring phosphorus-containing groups
kinase activity
nucleoside binding
purine nucleoside binding
adenyl nucleotide binding
adenyl ribonucleotide binding
atp binding
protein kinase activity
Process
phosphorus metabolic process
phosphate metabolic process
metabolic process
cellular metabolic process
protein amino acid phosphorylation
phosphorylation
Cellular Location
  1. Nucleus
  2. Cytoplasm
  3. Cytoplasm
  4. cytoskeleton
  5. Chromosome
  6. centromere
  7. centrosome
  8. kinetochore
Gene Properties
Chromosome Location Chromosome:1
Locus 15q15
SNPs BUB1B
Gene Sequence
>3153 bp
ATGGCGGCGGTGAAGAAGGAAGGGGGTGCTCTGAGTGAAGCCATGTCCCTGGAGGGAGAT
GAATGGGAACTGAGTAAAGAAAATGTACAACCTTTAAGGCAAGGGCGGATCATGTCCACG
CTTCAGGGAGCACTGGCACAAGAATCTGCCTGTAACAATACTCTTCAGCAGCAGAAACGG
GCATTTGAATATGAAATTCGATTTTACACTGGAAATGACCCTCTGGATGTTTGGGATAGG
TATATCAGCTGGACAGAGCAGAACTATCCTCAAGGTGGGAAGGAGAGTAATATGTCAACG
TTATTAGAAAGAGCTGTAGAAGCACTACAAGGAGAAAAACGATATTATAGTGATCCTCGA
TTTCTCAATCTCTGGCTTAAATTAGGGCGTTTATGCAATGAGCCTTTGGATATGTACAGT
TACTTGCACAACCAAGGGATTGGTGTTTCACTTGCTCAGTTCTATATCTCATGGGCAGAA
GAATATGAAGCTAGAGAAAACTTTAGGAAAGCAGATGCGATATTTCAGGAAGGGATTCAA
CAGAAGGCTGAACCACTAGAAAGACTACAGTCCCAGCACCGACAATTCCAAGCTCGAGTG
TCTCGGCAAACTCTGTTGGCACTTGAGAAAGAAGAAGAGGAGGAAGTTTTTGAGTCTTCT
GTACCACAACGAAGCACACTAGCTGAACTAAAGAGCAAAGGGAAAAAGACAGCAAGAGCT
CCAATCATCCGTGTAGGAGGTGCTCTCAAGGCTCCAAGCCAGAACAGAGGACTCCAAAAT
CCATTTCCTCAACAGATGCAAAATAATAGTAGAATTACTGTTTTTGATGAAAATGCTGAT
GAGGCTTCTACAGCAGAGTTGTCTAAGCCTACAGTCCAGCCATGGATAGCACCCCCCATG
CCCAGGGCCAAAGAGAATGAGCTGCAAGCAGGCCCTTGGAACACAGGCAGGTCCTTGGAA
CACAGGCCTCGTGGCAATACAGCTTCACTGATAGCTGTACCCGCTGTGCTTCCCAGTTTC
ACTCCATATGTGGAAGAGACTGCACAACAGCCAGTTATGACACCATGTAAAATTGAACCT
AGTATAAACCACATCCTAAGCACCAGAAAGCCTGGAAAGGAAGAAGGAGATCCTCTACAA
AGGGTTCAGAGCCATCAGCAAGCGTCTGAGGAGAAGAAAGAGAAGATGATGTATTGTAAG
GAGAAGATTTATGCAGGAGTAGGGGAATTCTCCTTTGAAGAAATTCGGGCTGAAGTTTTC
CGGAAGAAATTAAAAGAGCAAAGGGAAGCCGAGCTATTGACCAGTGCAGAGAAGAGAGCA
GAAATGCAGAAACAGATTGAAGAGATGGAGAAGAAGCTAAAAGAAATCCAAACTACTCAG
CAAGAAAGAACAGGTGATCAGCAAGAAGAGACGATGCCTACAAAGGAGACAACTAAACTG
CAAATTGCTTCCGAGTCTCAGAAAATACCAGGAATGACTCTATCCAGTTCTGTTTGTCAA
GTAAACTGTTGTGCCAGAGAAACTTCACTTGCGGAGAACATTTGGCAGGAACAACCTCAT
TCTAAAGGTCCCAGTGTACCTTTCTCCATTTTTGATGAGTTTCTTCTTTCAGAAAAGAAG
AATAAAAGTCCTCCTGCAGATCCCCCACGAGTTTTAGCTCAACGAAGACCCCTTGCAGTT
CTCAAAACCTCAGAAAGCATCACCTCAAATGAAGATGTGTCTCCAGATGTTTGTGATGAA
TTTACAGGAATTGAACCCTTGAGCGAGGATGCCATTATCACAGGCTTCAGAAATGTAACA
ATTTGTCCTAACCCAGAAGACACTTGTGACTTTGCCAGAGCAGCTCGTTTTGTATCCACT
CCTTTTCATGAGATAATGTCCTTGAAGGATCTCCCTTCTGATCCTGAGAGACTGTTACCG
GAAGAAGATCTAGATGTAAAGACCTCTGAGGACCAGCAGACAGCTTGTGGCACTATCTAC
AGTCAGACTCTCAGCATCAAGAAGCTGAGCCCAATTATTGAAGACAGTCGTGAAGCCACA
CACTCCTCTGGCTTCTCTGGTTCTTCTGCCTCGGTTGCAAGCACCTCCTCCATCAAATGT
CTTCAAATTCCTGAGAAACTAGAACTTACTAATGAGACTTCAGAAAACCCTACTCAGTCA
CCATGGTGTTCACAGTATCGCAGACAGCTACTGAAGTCCCTACCAGAGTTAAGTGCCTCT
GCAGAGTTGTGTATAGAAGACAGACCAATGCCTAAGTTGGAAATTGAGAAGGAAATTGAA
TTAGGTAATGAGGATTACTGCATTAAACGAGAATACCTAATATGTGAAGATTACAAGTTA
TTCTGGGTGGCGCCAAGAAACTCTGCAGAATTAACAGTAATAAAGGTATCTTCTCAACCT
GTCCCATGGGACTTTTATATCAACCTCAAGTTAAAGGAACGTTTAAATGAAGATTTTGAT
CATTTTTGCAGCTGTTATCAATATCAAGATGGCTGTATTGTTTGGCACCAATATATAAAC
TGCTTCACCCTTCAGGATCTTCTCCAACACAGTGAATATATTACCCATGAAATAACAGTG
TTGATTATTTATAACCTTTTGACAATAGTGGAGATGCTACACAAAGCAGAAATAGTCCAT
GGTGACTTGAGTCCAAGGTGTCTGATTCTCAGAAACAGAATCCACGATCCCTATGATTGT
AACAAGAACAATCAAGCTTTGAAGATAGTGGACTTTTCCTACAGTGTTGACCTTAGGGTG
CAGCTGGATGTTTTTACCCTCAGCGGCTTTCGGACTGTACAGATCCTGGAAGGACAAAAG
ATCCTGGCTAACTGTTCTTCTCCCTACCAGGTAGACCTGTTTGGTATAGCAGATTTAGCA
CATTTACTATTGTTCAAGGAACACCTACAGGTCTTCTGGGATGGGTCCTTCTGGAAACTT
AGCCAAAATATTTCTGAGCTAAAAGATGGTGAATTGTGGAATAAATTCTTTGTGCGGATT
CTGAATGCCAATGATGAGGCCACAGTGTCTGTTCTTGGGGAGCTTGCAGCAGAAATGAAT
GGGGTTTTTGACACTACATTCCAAAGTCACCTGAACAAAGCCTTATGGAAGGTAGGGAAG
TTAACTAGTCCTGGGGCTTTGCTCTTTCAGTGA
Protein Properties
Number of Residues 1050
Molecular Weight 119544.2
Theoretical pI 4.94
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>Mitotic checkpoint serine/threonine-protein kinase BUB1 beta
MAAVKKEGGALSEAMSLEGDEWELSKENVQPLRQGRIMSTLQGALAQESACNNTLQQQKR
AFEYEIRFYTGNDPLDVWDRYISWTEQNYPQGGKESNMSTLLERAVEALQGEKRYYSDPR
FLNLWLKLGRLCNEPLDMYSYLHNQGIGVSLAQFYISWAEEYEARENFRKADAIFQEGIQ
QKAEPLERLQSQHRQFQARVSRQTLLALEKEEEEEVFESSVPQRSTLAELKSKGKKTARA
PIIRVGGALKAPSQNRGLQNPFPQQMQNNSRITVFDENADEASTAELSKPTVQPWIAPPM
PRAKENELQAGPWNTGRSLEHRPRGNTASLIAVPAVLPSFTPYVEETARQPVMTPCKIEP
SINHILSTRKPGKEEGDPLQRVQSHQQASEEKKEKMMYCKEKIYAGVGEFSFEEIRAEVF
RKKLKEQREAELLTSAEKRAEMQKQIEEMEKKLKEIQTTQQERTGDQQEETMPTKETTKL
QIASESQKIPGMTLSSSVCQVNCCARETSLAENIWQEQPHSKGPSVPFSIFDEFLLSEKK
NKSPPADPPRVLAQRRPLAVLKTSESITSNEDVSPDVCDEFTGIEPLSEDAIITGFRNVT
ICPNPEDTCDFARAARFVSTPFHEIMSLKDLPSDPERLLPEEDLDVKTSEDQQTACGTIY
SQTLSIKKLSPIIEDSREATHSSGFSGSSASVASTSSIKCLQIPEKLELTNETSENPTQS
PWCSQYRRQLLKSLPELSASAELCIEDRPMPKLEIEKEIELGNEDYCIKREYLICEDYKL
FWVAPRNSAELTVIKVSSQPVPWDFYINLKLKERLNEDFDHFCSCYQYQDGCIVWHQYIN
CFTLQDLLQHSEYITHEITVLIIYNLLTIVEMLHKAEIVHGDLSPRCLILRNRIHDPYDC
NKNNQALKIVDFSYSVDLRVQLDVFTLSGFRTVQILEGQKILANCSSPYQVDLFGIADLA
HLLLFKEHLQVFWDGSFWKLSQNISELKDGELWNKFFVRILNANDEATVSVLGELAAEMN
GVFDTTFQSHLNKALWKVGKLTSPGALLFQ
GenBank ID Protein 59814247
UniProtKB/Swiss-Prot ID O60566
UniProtKB/Swiss-Prot Entry Name BUB1B_HUMAN
PDB IDs Not Available
GenBank Gene ID NM_001211.5
GeneCard ID BUB1B
GenAtlas ID BUB1B
HGNC ID HGNC:1149
References
General References
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  3. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648 ]
  4. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [PubMed:18691976 ]
  5. Imami K, Sugiyama N, Kyono Y, Tomita M, Ishihama Y: Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column. Anal Sci. 2008 Jan;24(1):161-6. [PubMed:18187866 ]
  6. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [PubMed:19413330 ]
  7. Wang B, Malik R, Nigg EA, Korner R: Evaluation of the low-specificity protease elastase for large-scale phosphoproteome analysis. Anal Chem. 2008 Dec 15;80(24):9526-33. doi: 10.1021/ac801708p. [PubMed:19007248 ]
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  9. Cahill DP, Lengauer C, Yu J, Riggins GJ, Willson JK, Markowitz SD, Kinzler KW, Vogelstein B: Mutations of mitotic checkpoint genes in human cancers. Nature. 1998 Mar 19;392(6673):300-3. [PubMed:9521327 ]
  10. Taylor SS, Ha E, McKeon F: The human homologue of Bub3 is required for kinetochore localization of Bub1 and a Mad3/Bub1-related protein kinase. J Cell Biol. 1998 Jul 13;142(1):1-11. [PubMed:9660858 ]
  11. Cahill DP, da Costa LT, Carson-Walter EB, Kinzler KW, Vogelstein B, Lengauer C: Characterization of MAD2B and other mitotic spindle checkpoint genes. Genomics. 1999 Jun 1;58(2):181-7. [PubMed:10366450 ]
  12. Johnson VL, Scott MI, Holt SV, Hussein D, Taylor SS: Bub1 is required for kinetochore localization of BubR1, Cenp-E, Cenp-F and Mad2, and chromosome congression. J Cell Sci. 2004 Mar 15;117(Pt 8):1577-89. [PubMed:15020684 ]
  13. Qi W, Tang Z, Yu H: Phosphorylation- and polo-box-dependent binding of Plk1 to Bub1 is required for the kinetochore localization of Plk1. Mol Biol Cell. 2006 Aug;17(8):3705-16. Epub 2006 Jun 7. [PubMed:16760428 ]
  14. Kiyomitsu T, Obuse C, Yanagida M: Human Blinkin/AF15q14 is required for chromosome alignment and the mitotic checkpoint through direct interaction with Bub1 and BubR1. Dev Cell. 2007 Nov;13(5):663-76. [PubMed:17981135 ]
  15. Donadelli R, Benatti L, Remuzzi A, Morigi M, Gullans SR, Benigni A, Remuzzi G, Noris M: Identification of a novel gene--SSK1--in human endothelial cells exposed to shear stress. Biochem Biophys Res Commun. 1998 May 29;246(3):881-7. [PubMed:9618306 ]
  16. Chan GK, Schaar BT, Yen TJ: Characterization of the kinetochore binding domain of CENP-E reveals interactions with the kinetochore proteins CENP-F and hBUBR1. J Cell Biol. 1998 Oct 5;143(1):49-63. [PubMed:9763420 ]
  17. Davenport JW, Fernandes ER, Harris LD, Neale GA, Goorha R: The mouse mitotic checkpoint gene bub1b, a novel bub1 family member, is expressed in a cell cycle-dependent manner. Genomics. 1999 Jan 1;55(1):113-7. [PubMed:9889005 ]
  18. Li W, Lan Z, Wu H, Wu S, Meadows J, Chen J, Zhu V, Dai W: BUBR1 phosphorylation is regulated during mitotic checkpoint activation. Cell Growth Differ. 1999 Nov;10(11):769-75. [PubMed:10593653 ]
  19. Chan GK, Jablonski SA, Sudakin V, Hittle JC, Yen TJ: Human BUBR1 is a mitotic checkpoint kinase that monitors CENP-E functions at kinetochores and binds the cyclosome/APC. J Cell Biol. 1999 Sep 6;146(5):941-54. [PubMed:10477750 ]
  20. Tang Z, Bharadwaj R, Li B, Yu H: Mad2-Independent inhibition of APCCdc20 by the mitotic checkpoint protein BubR1. Dev Cell. 2001 Aug;1(2):227-37. [PubMed:11702782 ]
  21. Shin HJ, Baek KH, Jeon AH, Park MT, Lee SJ, Kang CM, Lee HS, Yoo SH, Chung DH, Sung YC, McKeon F, Lee CW: Dual roles of human BubR1, a mitotic checkpoint kinase, in the monitoring of chromosomal instability. Cancer Cell. 2003 Dec;4(6):483-97. [PubMed:14706340 ]
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  28. Park SY, Kim S, Cho H, Kwon SH, Chae S, Kang D, Seong YS, Cho H: Depletion of BubR1 promotes premature centrosomal localization of cyclin B1 and accelerates mitotic entry. Cell Cycle. 2009 Jun 1;8(11):1754-64. Epub 2009 Jun 4. [PubMed:19411850 ]
  29. Huang Y, Yao Y, Xu HZ, Wang ZG, Lu L, Dai W: Defects in chromosome congression and mitotic progression in KIF18A-deficient cells are partly mediated through impaired functions of CENP-E. Cell Cycle. 2009 Aug 15;8(16):2643-9. Epub 2009 Aug 29. [PubMed:19625775 ]
  30. Choi E, Choe H, Min J, Choi JY, Kim J, Lee H: BubR1 acetylation at prometaphase is required for modulating APC/C activity and timing of mitosis. EMBO J. 2009 Jul 22;28(14):2077-89. doi: 10.1038/emboj.2009.123. Epub 2009 Apr 30. [PubMed:19407811 ]
  31. Izumi H, Matsumoto Y, Ikeuchi T, Saya H, Kajii T, Matsuura S: BubR1 localizes to centrosomes and suppresses centrosome amplification via regulating Plk1 activity in interphase cells. Oncogene. 2009 Aug 6;28(31):2806-20. doi: 10.1038/onc.2009.141. Epub 2009 Jun 8. [PubMed:19503101 ]
  32. Hanks S, Coleman K, Reid S, Plaja A, Firth H, Fitzpatrick D, Kidd A, Mehes K, Nash R, Robin N, Shannon N, Tolmie J, Swansbury J, Irrthum A, Douglas J, Rahman N: Constitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B. Nat Genet. 2004 Nov;36(11):1159-61. Epub 2004 Oct 10. [PubMed:15475955 ]
  33. 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: Monoallelic BUB1B mutations and defective mitotic-spindle checkpoint in seven families with premature chromatid separation (PCS) syndrome. Am J Med Genet A. 2006 Feb 15;140(4):358-67. [PubMed:16411201 ]