Canmetcon
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Identification
HMDB Protein ID HMDBP01182
Secondary Accession Numbers
  • 6478
Name Mitotic checkpoint serine/threonine-protein kinase BUB1
Synonyms
  1. BUB1A
  2. hBUB1
Gene Name BUB1
Protein Type Enzyme
Biological Properties
General Function Involved in protein kinase activity
Specific Function Serine/threonine-protein kinase that performs 2 crucial functions during mitosis:it is essential for spindle-assembly checkpoint signaling and for correct chromosome alignment. Has a key role in the assembly of checkpoint proteins at the kinetochore, being required for the subsequent localization of CENPF, BUB1B, CENPE and MAD2L1. Required for the kinetochore localization of PLK1. Plays an important role in defining SGOL1 localization and thereby affects sister chromatid cohesion. Acts as a substrate for anaphase-promoting complex or cyclosome (APC/C) in complex with its activator CDH1 (APC/C-Cdh1). Necessary for ensuring proper chromosome segregation and binding to BUB3 is essential for this function. Can regulate chromosome segregation in a kinetochore-independent manner. Can phosphorylate BUB3. The BUB1-BUB3 complex plays a role in the inhibition of APC/C when spindle-assembly checkpoint is activated and inhibits the ubiquitin ligase activity of APC/C by phosphorylating its activator CDC20. This complex can also phosphorylate MAD1L1. Kinase activity is essential for inhibition of APC/CCDC20 and for chromosome alignment but does not play a major role in the spindle-assembly checkpoint activity. Mediates cell death in response to chromosome missegregation and acts to suppress spontaneous tumorigenesis
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
protein serine/threonine kinase activity
Process
phosphorus metabolic process
phosphate metabolic process
metabolic process
cellular metabolic process
protein amino acid phosphorylation
phosphorylation
Cellular Location
  1. Nucleus
  2. Chromosome
  3. centromere
  4. kinetochore
Gene Properties
Chromosome Location Chromosome:2
Locus 2q14
SNPs BUB1
Gene Sequence
>3258 bp
ATGGACACCCCGGAAAATGTCCTTCAGATGCTTGAAGCCCACATGCAGAGCTACAAGGGC
AATGACCCTCTTGGTGAATGGGAAAGATACATACAGTGGGTAGAAGAGAATTTTCCTGAG
AATAAAGAATACTTGATAACTTTACTAGAACATTTAATGAAGGAATTTTTAGATAAGAAG
AAATACCACAATGACCCAAGATTCATCAGTTATTGTTTAAAATTTGCTGAGTACAACAGT
GACCTCCATCAATTTTTTGAGTTTCTGTACAACCATGGGATTGGAACCCTGTCATCCCCT
CTGTACATTGCCTGGGCGGGGCATCTGGAAGCCCAAGGAGAGCTGCAGCATGCCAGTGCT
GTCCTTCAGAGAGGAATTCAAAACCAGGCTGAACCCAGAGAGTTCCTGCAACAACAATAC
AGGTTATTTCAGACACGCCTCACTGAAACCCATTTGCCAGCTCAAGCTAGAACCTCAGAA
CCTCTGCATAATGTTCAGGTTTTAAATCAAATGATAACATCAAAATCAAATCCAGGAAAT
AACATGGCCTGCATTTCTAAGAATCAGGGTTCAGAGCTTTCTGGAGTGATATCTTCAGCT
TGTGATAAAGAGTCAAATATGGAACGAAGAGTGATCACGATTTCTAAATCAGAATATTCT
GTGCACTCATCTTTGGCATCCAAAGTTGATGTTGAGCAGGTTGTTATGTATTGCAAGGAG
AAGCTTATTCGTGGGGAATCAGAATTTTCCTTTGAAGAATTGAGAGCCCAGAAATACAAT
CAACGGAGAAAGCATGAGCAATGGGTAAATGAAGACAGACATTATATGAAAAGGAAAGAA
GCAAATGCTTTTGAAGAACAGCTATTAAAACAGAAAATGGATGAACTTCATAAGAAGTTG
CATCAGGTGGTGGAGACATCCCATGAGGATCTGCCCGCTTCCCAGGAAAGGTCCGAGGTT
AATCCAGCACGTATGGGGCCAAGTGTAGGCTCCCAGCAGGAACTGAGAGCGCCATGTCTT
CCAGTAACCTATCAGCAGACACCAGTGAACATGGAAAAGAACCCAAGAGAGGCACCTCCT
GTTGTTCCTCCTTTGGCAAATGCTATTTCTGCAGCTTTGGTGTCCCCAGCCACCAGCCAG
AGCATTGCTCCTCCTGTTCCTTTGAAAGCCCAGACAGTAACAGACTCCATGTTTGCAGTG
GCCAGCAAAGATGCTGGATGTGTGAATAAGAGTACTCATGAATTCAAGCCACAGAGTGGA
GCAGAGATCAAAGAAGGGTGTGAAACACATAAGGTTGCCAACACAAGTTCTTTTCACACA
ACTCCAAACACATCACTGGGAATGGTTCAGGCAACGCCATCCAAAGTGCAGCCATCACCC
ACCGTGCACACAAAAGAAGCATTAGGTTTCATCATGAATATGTTTCAGGCTCCTACACTT
CCTGATATTTCTGATGACAAAGATGAATGGCAATCTCTAGATCAAAATGAAGATGCATTT
GAAGCCCAGTTTCAAAAAAATGTAAGGTCATCTGGGGCTTGGGGAGTCAATAAGATCATC
TCTTCTTTGTCATCTGCTTTTCATGTGTTTGAAGATGGAAACAAAGAAAATTATGGATTA
CCACAGCCTAAAAATAAACCCACAGGAGCCAGGACCTTTGGAGAACGCTCTGTCAGCAGA
CTTCCTTCAAAACCAAAGGAGGAAGTGCCTCATGCTGAAGAGTTTTTGGATGACTCAACT
GTATGGGGTATTCGCTGCAACAAAACCCTGGCACCCAGTCCTAAGAGCCCAGGAGACTTC
ACATCTGCTGCACAACTTGCGTCTACACCATTCCACAAGCTTCCAGTGGAGTCAGTGCAC
ATTTTAGAAGATAAAGAAAATGTGGTAGCAAAACAGTGTACCCAGGCGACTTTGGATTCT
TGTGAGGAAAACATGGTGGTGCCTTCAAGGGATGGAAAATTCAGTCCAATTCAAGAGAAA
AGCCCAAAACAGGCCTTGTCGTCTCACATGTATTCAGCATCCTTACTTCGTCTGAGCCAG
CCTGCTGCAGGTGGGGTACTTACCTGTGAGGCAGAGTTGGGCGTTGAGGCTTGCAGACTC
ACAGACACTGACGCTGCCATTGCAGAAGATCCACCAGATGCTATTGCTGGGCTCCAAGCA
GAATGGATGCAGATGAGTTCACTTGGGACTGTTGATGCTCCAAACTTCATTGTTGGGAAC
CCATGGGATGATAAGCTGATTTTCAAACTTTTATCTGGGCTTTCTAAACCAGTGAGTTCC
TATCCAAATACTTTTGAATGGCAATGTAAACTTCCAGCCATCAAGCCCAAGACTGAATTT
CAATTGGGTTCTAAGCTGGTCTATGTCCATCACCTTCTTGGAGAAGGAGCCTTTGCCCAG
GTGTACGAAGCTACCCAGGGAGATCTGAATGATGCTAAAAATAAACAGAAATTTGTTTTA
AAGGTCCAAAAGCCTGCCAACCCCTGGGAATTCTACATTGGGACCCAGTTGATGGAAAGA
CTAAAGCCATCTATGCAGCACATGTTTATGAAGTTCTATTCTGCCCACTTATTCCAGAAT
GGCAGTGTATTAGTAGGAGAGCTCTACAGCTATGGAACATTATTAAATGCCATTAACCTC
TATAAAAATACCCCTGAAAAAGTGATGCCTCAAGGTCTTGTCATCTCTTTTGCTATGAGA
ATGCTTTACATGATTGAGCAAGTGCATGACTGTGAAATCATTCATGGAGACATTAAACCA
GACAATTTCATACTTGGAAACGGATTTTTGGAACAGGATGATGAAGATGATTTATCTGCT
GGCTTGGCACTGATTGACCTGGGTCAGAGTATAGATATGAAACTTTTTCCAAAAGGAACT
ATATTCACAGCAAAGTGTGAAACATCTGGTTTTCAGTGTGTTGAGATGCTCAGCAACAAA
CCATGGAACTACCAGATCGATTACTTTGGGGTTGCTGCAACAGTATATTGCATGCTCTTT
GGCACTTACATGAAAGTGAAAAATGAAGGAGGAGAGTGTAAGCCTGAAGGTCTTTTTAGA
AGGCTTCCTCATTTGGATATGTGGAATGAATTTTTTCATGTTATGTTGAATATTCCAGAT
TGTCATCATCTTCCATCTTTGGATTTGTTAAGGCAAAAGCTGAAGAAAGTATTTCAACAA
CACTATACTAACAAGATTAGGGCCCTACGTAATAGGCTAATTGTACTGCTCTTAGAATGT
AAGCGTTCACGAAAATAA
Protein Properties
Number of Residues 1085
Molecular Weight 122374.4
Theoretical pI 6.44
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>Mitotic checkpoint serine/threonine-protein kinase BUB1
MDTPENVLQMLEAHMQSYKGNDPLGEWERYIQWVEENFPENKEYLITLLEHLMKEFLDKK
KYHNDPRFISYCLKFAEYNSDLHQFFEFLYNHGIGTLSSPLYIAWAGHLEAQGELQHASA
VLQRGIQNQAEPREFLQQQYRLFQTRLTETHLPAQARTSEPLHNVQVLNQMITSKSNPGN
NMACISKNQGSELSGVISSACDKESNMERRVITISKSEYSVHSSLASKVDVEQVVMYCKE
KLIRGESEFSFEELRAQKYNQRRKHEQWVNEDRHYMKRKEANAFEEQLLKQKMDELHKKL
HQVVETSHEDLPASQERSEVNPARMGPSVGSQQELRAPCLPVTYQQTPVNMEKNPREAPP
VVPPLANAISAALVSPATSQSIAPPVPLKAQTVTDSMFAVASKDAGCVNKSTHEFKPQSG
AEIKEGCETHKVANTSSFHTTPNTSLGMVQATPSKVQPSPTVHTKEALGFIMNMFQAPTL
PDISDDKDEWQSLDQNEDAFEAQFQKNVRSSGAWGVNKIISSLSSAFHVFEDGNKENYGL
PQPKNKPTGARTFGERSVSRLPSKPKEEVPHAEEFLDDSTVWGIRCNKTLAPSPKSPGDF
TSAAQLASTPFHKLPVESVHILEDKENVVAKQCTQATLDSCEENMVVPSRDGKFSPIQEK
SPKQALSSHMYSASLLRLSQPAAGGVLTCEAELGVEACRLTDTDAAIAEDPPDAIAGLQA
EWMQMSSLGTVDAPNFIVGNPWDDKLIFKLLSGLSKPVSSYPNTFEWQCKLPAIKPKTEF
QLGSKLVYVHHLLGEGAFAQVYEATQGDLNDAKNKQKFVLKVQKPANPWEFYIGTQLMER
LKPSMQHMFMKFYSAHLFQNGSVLVGELYSYGTLLNAINLYKNTPEKVMPQGLVISFAMR
MLYMIEQVHDCEIIHGDIKPDNFILGNGFLEQDDEDDLSAGLALIDLGQSIDMKLFPKGT
IFTAKCETSGFQCVEMLSNKPWNYQIDYFGVAATVYCMLFGTYMKVKNEGGECKPEGLFR
RLPHLDMWNEFFHVMLNIPDCHHLPSLDLLRQKLKKVFQQHYTNKIRALRNRLIVLLLEC
KRSRK
GenBank ID Protein 4757878
UniProtKB/Swiss-Prot ID O43683
UniProtKB/Swiss-Prot Entry Name BUB1_HUMAN
PDB IDs Not Available
GenBank Gene ID NM_004336.3
GeneCard ID BUB1
GenAtlas ID BUB1
HGNC ID HGNC:1148
References
General References
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  2. 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 ]
  3. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [PubMed:19690332 ]
  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 ]
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  10. Ouyang B, Lan Z, Meadows J, Pan H, Fukasawa K, Li W, Dai W: Human Bub1: a putative spindle checkpoint kinase closely linked to cell proliferation. Cell Growth Differ. 1998 Oct;9(10):877-85. [PubMed:9790499 ]
  11. 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 ]
  12. Seeley TW, Wang L, Zhen JY: Phosphorylation of human MAD1 by the BUB1 kinase in vitro. Biochem Biophys Res Commun. 1999 Apr 13;257(2):589-95. [PubMed:10198256 ]
  13. 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 ]
  14. Pangilinan F, Li Q, Weaver T, Lewis BC, Dang CV, Spencer F: Mammalian BUB1 protein kinases: map positions and in vivo expression. Genomics. 1997 Dec 15;46(3):379-88. [PubMed:9441741 ]
  15. 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 ]
  16. Tang Z, Shu H, Oncel D, Chen S, Yu H: Phosphorylation of Cdc20 by Bub1 provides a catalytic mechanism for APC/C inhibition by the spindle checkpoint. Mol Cell. 2004 Nov 5;16(3):387-97. [PubMed:15525512 ]
  17. Kitajima TS, Hauf S, Ohsugi M, Yamamoto T, Watanabe Y: Human Bub1 defines the persistent cohesion site along the mitotic chromosome by affecting Shugoshin localization. Curr Biol. 2005 Feb 22;15(4):353-9. [PubMed:15723797 ]
  18. 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 ]
  19. 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 ]
  20. Qi W, Yu H: KEN-box-dependent degradation of the Bub1 spindle checkpoint kinase by the anaphase-promoting complex/cyclosome. J Biol Chem. 2007 Feb 9;282(6):3672-9. Epub 2006 Dec 11. [PubMed:17158872 ]
  21. Hein J, Boichuk S, Wu J, Cheng Y, Freire R, Jat PS, Roberts TM, Gjoerup OV: Simian virus 40 large T antigen disrupts genome integrity and activates a DNA damage response via Bub1 binding. J Virol. 2009 Jan;83(1):117-27. doi: 10.1128/JVI.01515-08. Epub 2008 Oct 15. [PubMed:18922873 ]
  22. Klebig C, Korinth D, Meraldi P: Bub1 regulates chromosome segregation in a kinetochore-independent manner. J Cell Biol. 2009 Jun 1;185(5):841-58. doi: 10.1083/jcb.200902128. [PubMed:19487456 ]
  23. Hempen PM, Kurpad H, Calhoun ES, Abraham S, Kern SE: A double missense variation of the BUB1 gene and a defective mitotic spindle checkpoint in the pancreatic cancer cell line Hs766T. Hum Mutat. 2003 Apr;21(4):445. [PubMed:12655561 ]