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Q9Z1S0

- BUB1B_MOUSE

UniProt

Q9Z1S0 - BUB1B_MOUSE

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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

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 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
Complete GO annotation...

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
Complete GO annotation...

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 51-197, 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.
InParanoidiQ9Z1S0.
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

« Hide

        10         20         30         40         50
MAEASEAMCL EGAEWELSKE NIQPLRHGRV MSTLQGALAK QESAGHTALQ
60 70 80 90 100
QQKRAFESEI RFYSGDDPLD VWDRYINWTE QNYPQGGKES NMSALVERAI
110 120 130 140 150
EALQGETRYY NDPRFLSLWI KLGHLCNEPL DMYSYLQSQG IGVSLAQFYI
160 170 180 190 200
SWAEEYEARE NFKKADIIFQ EGIERKAEPL DRLQSQHRQF QSRVSRQAFL
210 220 230 240 250
ALGNEEEEAL EPSEPQRSSL AELKSRGKKM ARAPISRVGG ALKAPGQSRG
260 270 280 290 300
FLNAVPQPVH GNRRITVFDE NADTASRTEL SKPVAQPWMA PPVPRAKENE
310 320 330 340 350
LQPGPWSTDR PAGRRPHDNP ASVTSIPSVL PSFTPYVEES AQQTVMTPCK
360 370 380 390 400
IEPSINHVLS TRKPGREEGD PLQRVQSHQQ GCEEKKEKMM YCKEKIYAGV
410 420 430 440 450
GEFSFEEIRA EVFRKKLKER REAELLTSAK KREEMQKQIE EMERRLKAMQ
460 470 480 490 500
AVQQEGAGGQ QEEKMPTEDP ARLQIASGPQ EMSGVPLSCS ICPLSSNPRE
510 520 530 540 550
ISPAENILQE QPDSKGSSMP FSIFDESLSD KKDKSPATGG PQVLNAQRRP
560 570 580 590 600
LSVLKTTEVG TTNEDVSPDI CDELTELEPL SEDAIITGFR NVTLCPNPED
610 620 630 640 650
TCDFARAARL ASTPFHEILS SKGIAADPEG LLQEEDLDGK AAEAHHTVHH
660 670 680 690 700
QALIIKKLSP IIEESREATH SSGFSRSSSS APSTSSIKGF QLLEKLELTN
710 720 730 740 750
DGAEDAIQSP WCSQYRLQLL KSLLELSAFA EFSVEDRPMP VLEIGKEIEL
760 770 780 790 800
GPEDYVIKQE HLTCDDYRLF WVAPRSSAEL TMIKASSQPI PWDFYINLKL
810 820 830 840 850
KERLNEDYDQ LCSCCQYQDG HVVWYQYINC STLQNLLQHS EFVTHEIIVL
860 870 880 890 900
IIYNLLTIVE KLHRAEIVHG DLSPRSLILR NRIHDPYDYV NKDDHAVRIM
910 920 930 940 950
DFSYSVDLRV QLDAFAYSGF RTAQILEGQK ILANCSSPYH VDLLGIADLA
960 970 980 990 1000
HLLLFKEHLH VFWDGLLWKL SQSTSELKDS ELWNKFFVRI LNASDKSTVS
1010 1020 1030 1040 1050
VLGELAAEMG GAFDATFHSH LNRALWKLGK TISPEALLTQ QDKQPGGSQS

PA
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 51-197, 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 Q9Z1S0.
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

« Hide 'large scale' publications
  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 29, 2014
This is version 124 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