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Q9Z1S0

- BUB1B_MOUSE

UniProt

Q9Z1S0 - BUB1B_MOUSE

Protein

Mitotic checkpoint serine/threonine-protein kinase BUB1 beta

Gene

Bub1b

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 123 (01 Oct 2014)
      Sequence version 2 (27 Jul 2011)
      Previous versions | rss
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    Functioni

    Essential component of the mitotic checkpoint. Required for normal mitosis progression and tumor suppression. 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. Essential for tumor suppression. May play a role in regulating aging and fertility By similarity.By similarity

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.

    Enzyme regulationi

    Kinase activity stimulated by CENPE.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei572 – 5732Cleavage; by caspase-3By similarity
    Sitei603 – 6042Cleavage; by caspase-3By similarity
    Binding sitei784 – 7841ATPPROSITE-ProRule annotation
    Active sitei871 – 8711Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi762 – 7709ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. protein binding Source: UniProtKB
    3. protein serine/threonine kinase activity Source: UniProtKB-KW

    GO - Biological processi

    1. apoptotic process Source: UniProtKB-KW
    2. metaphase/anaphase transition of mitotic cell cycle Source: MGI
    3. protein localization to chromosome, centromeric region Source: MGI
    4. protein localization to kinetochore Source: Ensembl

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Biological processi

    Apoptosis, Cell cycle, Cell division, Mitosis

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.11.1. 3474.
    ReactomeiREACT_198961. Resolution of Sister Chromatid Cohesion.
    REACT_207679. Separation of Sister Chromatids.
    REACT_222875. APC/C:Cdc20 mediated degradation of mitotic proteins.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (EC:2.7.11.1)
    Alternative name(s):
    MAD3/BUB1-related protein kinase
    Short name:
    BubR1
    Mitotic checkpoint kinase MAD3L
    Gene namesi
    Name:Bub1b
    Synonyms:Mad3l
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 2

    Organism-specific databases

    MGIiMGI:1333889. Bub1b.

    Subcellular locationi

    Cytoplasm By similarity. Nucleus By similarity. Chromosomecentromerekinetochore 2 Publications
    Note: Cytoplasmic in interphase cells By similarity. Associates with the kinetochores in early prophase. Kinetochore localization requires BUB1, PLK1 and CASC5 By similarity.By similarity

    GO - Cellular componenti

    1. condensed chromosome outer kinetochore Source: MGI
    2. condensed nuclear chromosome kinetochore Source: MGI
    3. kinetochore Source: UniProtKB
    4. perinuclear region of cytoplasm Source: Ensembl

    Keywords - Cellular componenti

    Centromere, Chromosome, Cytoplasm, Kinetochore, Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    Defects in Bub1b are involved in the development of lung and intestinal adenocarcinomas after exposure to a carcinogen.

    Disruption phenotypei

    Mice die in utero.1 Publication

    Keywords - Diseasei

    Tumor suppressor

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 10521052Mitotic checkpoint serine/threonine-protein kinase BUB1 betaPRO_0000085674Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei243 – 2431N6-acetyllysine; by PCAFBy similarity
    Modified residuei428 – 4281PhosphoserineBy similarity
    Modified residuei535 – 5351PhosphoserineBy similarity
    Modified residuei659 – 6591PhosphoserineBy similarity
    Modified residuei665 – 6651Phosphoserine; by PLK1By similarity
    Modified residuei781 – 7811Phosphothreonine; by PLK1By similarity
    Modified residuei998 – 9981Phosphothreonine; by PLK1By similarity
    Modified residuei1033 – 10331PhosphoserineBy similarity

    Post-translational modificationi

    Proteolytically cleaved by caspase-3 in a cell cycle specific manner. The cleavage might be involved in the durability of the cell cycle delay.By similarity
    Acetylation at Lys-243 regulates its degradation and timing in anaphase entry.By similarity
    Ubiquitinated. Degraded by the proteasome By similarity.By similarity
    Sumoylated with SUMO2 and SUMO3. The sumoylation mediates the association with CENPE at the kinetochore By similarity.By similarity
    Autophosphorylated in vitro. Intramolecular autophosphorylation stimulated by CENPE. Phosphorylated during mitosis and hyperphosphorylated in mitotically arrested cells. Phosphorylation at Ser-659 and Ser-1033 occurs at kinetochores upon mitotic entry with dephosphorylation at the onset of anaphase.By similarity

    Keywords - PTMi

    Acetylation, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiQ9Z1S0.
    PaxDbiQ9Z1S0.
    PRIDEiQ9Z1S0.

    PTM databases

    PhosphoSiteiQ9Z1S0.

    Expressioni

    Tissue specificityi

    Highly expressed in thymus followed by spleen.

    Gene expression databases

    BgeeiQ9Z1S0.
    GenevestigatoriQ9Z1S0.

    Interactioni

    Subunit structurei

    Interacts with CENPE, CENPF, mitosin, PLK1 and BUB3. Part of a complex containing BUB3, CDC20 and BUB1B. Interacts with anaphase-promoting complex/cyclosome (APC/C). Interacts with CASC5 By similarity.By similarity

    Protein-protein interaction databases

    BioGridi198405. 33 interactions.
    IntActiQ9Z1S0. 29 interactions.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9Z1S0.
    SMRiQ9Z1S0. Positions 16-197, 707-1025.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini56 – 219164BUB1 N-terminalPROSITE-ProRule annotationAdd
    BLAST
    Domaini756 – 1040285Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni146 – 17934Necessary for interaction with CASC5By similarityAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi105 – 1128Nuclear localization signalSequence Analysis
    Motifi217 – 2259D-box

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi205 – 2084Poly-Glu
    Compositional biasi675 – 6806Poly-Ser

    Domaini

    The D-box targets the protein for rapid degradation by ubiquitin-dependent proteolysis during the transition from mitosis to interphase.Curated
    The BUB1 N-terminal domain directs kinetochore localization and binding to BUB3.

    Sequence similaritiesi

    Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. BUB1 subfamily.PROSITE-ProRule annotation
    Contains 1 BUB1 N-terminal domain.PROSITE-ProRule annotation
    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiNOG317001.
    GeneTreeiENSGT00520000055622.
    HOGENOMiHOG000231849.
    HOVERGENiHBG050748.
    InParanoidiA2ARS1.
    KOiK06637.
    OMAiATHSSGF.
    OrthoDBiEOG7DFXCB.
    TreeFamiTF105456.

    Family and domain databases

    InterProiIPR015661. Bub1/Mad3.
    IPR011009. Kinase-like_dom.
    IPR013212. Mad3_BUB1_I.
    IPR000719. Prot_kinase_dom.
    [Graphical view]
    PANTHERiPTHR14030. PTHR14030. 1 hit.
    PfamiPF08311. Mad3_BUB1_I. 1 hit.
    PF00069. Pkinase. 1 hit.
    [Graphical view]
    SMARTiSM00777. Mad3_BUB1_I. 1 hit.
    [Graphical view]
    SUPFAMiSSF56112. SSF56112. 1 hit.
    PROSITEiPS51489. BUB1_N. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q9Z1S0-1 [UniParc]FASTAAdd to Basket

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    MAEASEAMCL EGAEWELSKE NIQPLRHGRV MSTLQGALAK QESAGHTALQ     50
    QQKRAFESEI RFYSGDDPLD VWDRYINWTE QNYPQGGKES NMSALVERAI 100
    EALQGETRYY NDPRFLSLWI KLGHLCNEPL DMYSYLQSQG IGVSLAQFYI 150
    SWAEEYEARE NFKKADIIFQ EGIERKAEPL DRLQSQHRQF QSRVSRQAFL 200
    ALGNEEEEAL EPSEPQRSSL AELKSRGKKM ARAPISRVGG ALKAPGQSRG 250
    FLNAVPQPVH GNRRITVFDE NADTASRTEL SKPVAQPWMA PPVPRAKENE 300
    LQPGPWSTDR PAGRRPHDNP ASVTSIPSVL PSFTPYVEES AQQTVMTPCK 350
    IEPSINHVLS TRKPGREEGD PLQRVQSHQQ GCEEKKEKMM YCKEKIYAGV 400
    GEFSFEEIRA EVFRKKLKER REAELLTSAK KREEMQKQIE EMERRLKAMQ 450
    AVQQEGAGGQ QEEKMPTEDP ARLQIASGPQ EMSGVPLSCS ICPLSSNPRE 500
    ISPAENILQE QPDSKGSSMP FSIFDESLSD KKDKSPATGG PQVLNAQRRP 550
    LSVLKTTEVG TTNEDVSPDI CDELTELEPL SEDAIITGFR NVTLCPNPED 600
    TCDFARAARL ASTPFHEILS SKGIAADPEG LLQEEDLDGK AAEAHHTVHH 650
    QALIIKKLSP IIEESREATH SSGFSRSSSS APSTSSIKGF QLLEKLELTN 700
    DGAEDAIQSP WCSQYRLQLL KSLLELSAFA EFSVEDRPMP VLEIGKEIEL 750
    GPEDYVIKQE HLTCDDYRLF WVAPRSSAEL TMIKASSQPI PWDFYINLKL 800
    KERLNEDYDQ LCSCCQYQDG HVVWYQYINC STLQNLLQHS EFVTHEIIVL 850
    IIYNLLTIVE KLHRAEIVHG DLSPRSLILR NRIHDPYDYV NKDDHAVRIM 900
    DFSYSVDLRV QLDAFAYSGF RTAQILEGQK ILANCSSPYH VDLLGIADLA 950
    HLLLFKEHLH VFWDGLLWKL SQSTSELKDS ELWNKFFVRI LNASDKSTVS 1000
    VLGELAAEMG GAFDATFHSH LNRALWKLGK TISPEALLTQ QDKQPGGSQS 1050
    PA 1052
    Length:1,052
    Mass (Da):118,392
    Last modified:July 27, 2011 - v2
    Checksum:i9EF1ECF3735DD1F4
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti275 – 2751A → T in AAD11940. (PubMed:9889005)Curated
    Sequence conflicti278 – 2781T → P in AAD11940. (PubMed:9889005)Curated
    Sequence conflicti664 – 6641E → D in AAD11940. (PubMed:9889005)Curated
    Sequence conflicti705 – 7051D → N in AAD11940. (PubMed:9889005)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF107296 mRNA. Translation: AAD11940.1.
    AL845470, AL929381 Genomic DNA. Translation: CAM17418.1.
    AL929381, AL845470 Genomic DNA. Translation: CAM19078.1.
    CCDSiCCDS16579.1.
    RefSeqiNP_033903.2. NM_009773.3.
    UniGeneiMm.29133.

    Genome annotation databases

    EnsembliENSMUST00000038341; ENSMUSP00000037126; ENSMUSG00000040084.
    GeneIDi12236.
    KEGGimmu:12236.
    UCSCiuc008lse.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF107296 mRNA. Translation: AAD11940.1 .
    AL845470 , AL929381 Genomic DNA. Translation: CAM17418.1 .
    AL929381 , AL845470 Genomic DNA. Translation: CAM19078.1 .
    CCDSi CCDS16579.1.
    RefSeqi NP_033903.2. NM_009773.3.
    UniGenei Mm.29133.

    3D structure databases

    ProteinModelPortali Q9Z1S0.
    SMRi Q9Z1S0. Positions 16-197, 707-1025.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 198405. 33 interactions.
    IntActi Q9Z1S0. 29 interactions.

    PTM databases

    PhosphoSitei Q9Z1S0.

    Proteomic databases

    MaxQBi Q9Z1S0.
    PaxDbi Q9Z1S0.
    PRIDEi Q9Z1S0.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000038341 ; ENSMUSP00000037126 ; ENSMUSG00000040084 .
    GeneIDi 12236.
    KEGGi mmu:12236.
    UCSCi uc008lse.2. mouse.

    Organism-specific databases

    CTDi 701.
    MGIi MGI:1333889. Bub1b.

    Phylogenomic databases

    eggNOGi NOG317001.
    GeneTreei ENSGT00520000055622.
    HOGENOMi HOG000231849.
    HOVERGENi HBG050748.
    InParanoidi A2ARS1.
    KOi K06637.
    OMAi ATHSSGF.
    OrthoDBi EOG7DFXCB.
    TreeFami TF105456.

    Enzyme and pathway databases

    BRENDAi 2.7.11.1. 3474.
    Reactomei REACT_198961. Resolution of Sister Chromatid Cohesion.
    REACT_207679. Separation of Sister Chromatids.
    REACT_222875. APC/C:Cdc20 mediated degradation of mitotic proteins.

    Miscellaneous databases

    NextBioi 280666.
    PROi Q9Z1S0.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q9Z1S0.
    Genevestigatori Q9Z1S0.

    Family and domain databases

    InterProi IPR015661. Bub1/Mad3.
    IPR011009. Kinase-like_dom.
    IPR013212. Mad3_BUB1_I.
    IPR000719. Prot_kinase_dom.
    [Graphical view ]
    PANTHERi PTHR14030. PTHR14030. 1 hit.
    Pfami PF08311. Mad3_BUB1_I. 1 hit.
    PF00069. Pkinase. 1 hit.
    [Graphical view ]
    SMARTi SM00777. Mad3_BUB1_I. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 1 hit.
    PROSITEi PS51489. BUB1_N. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "The mouse mitotic checkpoint gene bub1b, a novel bub1 family member, is expressed in a cell cycle-dependent manner."
      Davenport J.W., Fernandes E.R., Harris L.D., Neale G.A.M., Goorha R.
      Genomics 55:113-117(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: NIH Swiss.
      Tissue: Embryo.
    2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: C57BL/6J.
    3. "Centromere-associated protein-E is essential for the mammalian mitotic checkpoint to prevent aneuploidy due to single chromosome loss."
      Weaver B.A., Bonday Z.Q., Putkey F.R., Kops G.J., Silk A.D., Cleveland D.W.
      J. Cell Biol. 162:551-563(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: ENZYME REGULATION, INTERACTION WITH CENPE, SUBCELLULAR LOCATION.
    4. "Slippage of mitotic arrest and enhanced tumor development in mice with BubR1 haploinsufficiency."
      Dai W., Wang Q., Liu T., Swamy M., Fang Y., Xie S., Mahmood R., Yang Y.M., Xu M., Rao C.V.
      Cancer Res. 64:440-445(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    5. "BubR1 insufficiency causes early onset of aging-associated phenotypes and infertility in mice."
      Baker D.J., Jeganathan K.B., Cameron J.D., Thompson M., Juneja S., Kopecka A., Kumar R., Jenkins R.B., de Groen P.C., Roche P., van Deursen J.M.
      Nat. Genet. 36:744-749(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, DISRUPTION PHENOTYPE.
    6. "Bub1 maintains centromeric cohesion by activation of the spindle checkpoint."
      Perera D., Tilston V., Hopwood J.A., Barchi M., Boot-Handford R.P., Taylor S.S.
      Dev. Cell 13:566-579(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.

    Entry informationi

    Entry nameiBUB1B_MOUSE
    AccessioniPrimary (citable) accession number: Q9Z1S0
    Secondary accession number(s): A2ARS1
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 30, 2000
    Last sequence update: July 27, 2011
    Last modified: October 1, 2014
    This is version 123 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3