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Protein

Mitotic checkpoint serine/threonine-protein kinase BUB1

Gene

Bub1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. Essential during early and later stages of embryonic development. Necessary for postimplantation embryogenesis and proliferation of primary embryonic fibroblasts and plays an important role in spermatogenesis and fertility.3 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

Autophosphorylated when the cells enters mitosis.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei795 – 7951ATPPROSITE-ProRule annotation
Active sitei891 – 8911Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi767 – 7759ATPPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

  • apoptotic process Source: UniProtKB-KW
  • cell division Source: UniProtKB-KW
  • chromosome segregation Source: MGI
  • embryo development Source: UniProtKB
  • mitotic nuclear division Source: UniProtKB-KW
  • mitotic spindle assembly checkpoint Source: InterPro
  • positive regulation of intrinsic apoptotic signaling pathway Source: MGI
  • regulation of chromosome segregation Source: MGI
  • regulation of sister chromatid cohesion Source: UniProtKB
  • spindle assembly checkpoint Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Apoptosis, Cell cycle, Cell division, Chromosome partition, Mitosis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.1. 3474.

Names & Taxonomyi

Protein namesi
Recommended name:
Mitotic checkpoint serine/threonine-protein kinase BUB1 (EC:2.7.11.1)
Short name:
mBUB1
Alternative name(s):
BUB1A
Gene namesi
Name:Bub1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1100510. Bub1.

Subcellular locationi

  • Nucleus
  • Chromosomecentromerekinetochore

  • Note: Nuclear in interphase cells. Accumulates gradually during G1 and S phase of the cell cycle, peaks at G2/M, and drops dramatically after mitosis. Localizes to the outer kinetochore. Kinetochore localization is required for normal mitotic timing and checkpoint response to spindle damage and occurs very early in prophase. AURKB, CASC5 and INCENP are required for kinetochore localization (By similarity).By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Centromere, Chromosome, Kinetochore, Nucleus

Pathology & Biotechi

Disruption phenotypei

Early embryonic lethality.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 10581058Mitotic checkpoint serine/threonine-protein kinase BUB1PRO_0000085672Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei313 – 3131PhosphoserineBy similarity
Modified residuei550 – 5501PhosphoserineBy similarity
Modified residuei579 – 5791PhosphoserineBy similarity
Modified residuei582 – 5821PhosphoserineBy similarity
Modified residuei595 – 5951Phosphothreonine; by CDK1By similarity

Post-translational modificationi

Upon spindle-assembly checkpoint activation it is hyperphosphorylated and its kinase activity toward CDC20 is stimulated. Phosphorylation at Thr-595 is required for interaction with PLK1, phosphorylation at this site probably creates a binding site for the POLO-box domain of PLK1, thus enhancing the PLK1-BUB1 interaction (By similarity).By similarity
Ubiquitinated and degraded during mitotic exit by APC/C-Cdh1.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO08901.
MaxQBiO08901.
PaxDbiO08901.
PRIDEiO08901.

PTM databases

iPTMnetiO08901.
PhosphoSiteiO08901.

Expressioni

Tissue specificityi

Highly expressed in testis. Weakly expressed in spleen and lung.1 Publication

Interactioni

Subunit structurei

Interacts with BUB3 and CASC5. Interacts (when phosphorylated) with PLK1. The BUB1-BUB3 complex interacts with MAD1L1 (By similarity).By similarity

Protein-protein interaction databases

BioGridi198404. 54 interactions.
IntActiO08901. 15 interactions.
STRINGi10090.ENSMUSP00000028858.

Structurei

3D structure databases

ProteinModelPortaliO08901.
SMRiO08901. Positions 1-148, 714-1054.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini11 – 182172BUB1 N-terminalPROSITE-ProRule annotationAdd
BLAST
Domaini761 – 1058298Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 146146Necessary for kinetochore localizationBy similarityAdd
BLAST
Regioni99 – 13234Necessary for interaction with CASC5By similarityAdd
BLAST
Regioni229 – 25527Necessary for interaction with BUB3By similarityAdd
BLAST
Regioni446 – 46419Essential for loading of BUBR1, MAD1L1 and MAD2L1 to kinetochoresBy similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi58 – 658Nuclear localization signalSequence analysis
Motifi522 – 5243KEN box 1By similarity
Motifi611 – 6133KEN box 2By similarity

Domaini

The KEN box is required for its ubiquitination and degradation.By similarity
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

eggNOGiKOG1166. Eukaryota.
ENOG410XQ67. LUCA.
HOVERGENiHBG003709.
InParanoidiO08901.
KOiK02178.

Family and domain databases

InterProiIPR015661. Bub1/Mad3.
IPR011009. Kinase-like_dom.
IPR013212. Mad3/Bub1_I.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR14030. PTHR14030. 2 hits.
PfamiPF08311. Mad3_BUB1_I. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00777. Mad3_BUB1_I. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS51489. BUB1_N. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O08901-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDNLENVFRM FEAHMQSYTG NDPLGEWESF IKWVEENFPD NKEYLMTLLE
60 70 80 90 100
HLMKEFLHKK NYHNDSRFIN YCLKFAEYNS DRHQFFEFLY NQGIGTKSSY
110 120 130 140 150
IYMSWAGHLE AQGELQHASA IFQTGIHNEA EPKELLQQQY RLFQARLTGI
160 170 180 190 200
HLPAQATTSE PLHSAQILNQ VMMTNSSPEK NSACVPKSQG SECSGVASST
210 220 230 240 250
CDEKSNMEQR VIMISKSECS VSSSVAPKPE AQQVMYCKEK LIRGDSEFSF
260 270 280 290 300
EELRAQKYNQ RKKHEQWVSE DRNYMKRKEA NAFEEQLLKQ KMDELHKKLH
310 320 330 340 350
QVVELSHKDL PASENRPDVS LVCVGQNTCS QQELRGPSLS SISHQTSESS
360 370 380 390 400
GEKPQEEPSV PLMVNAVNST LLFPAANLPA LPVPVSGQSL TDSRCVNQSV
410 420 430 440 450
HEFMPQCGPE TKEVCETNKV ASINDFHTTP NTSLGMVQGT PCKVQPSPTV
460 470 480 490 500
HTKEALGFIM DMFQAPTLPD ISDDKDEWPS LDQNEDAFEA QFQKNAVSSG
510 520 530 540 550
DWGVKKIMTL SSAFPIFEDG NKENYGLPQP KNKPLGARTF GERSLSKYSS
560 570 580 590 600
RSNEMPHTDE FMDDSTVCGI RCNKTLAPSP KSIGDFTSAA QLSSTPFHKF
610 620 630 640 650
PADLVQIPED KENVVATQYT HMALDSCKEN IVDLSKGRKL GPIQEKISAS
660 670 680 690 700
LPCPSQPATG GLFTQEAVFG LEAFKCTGID HATVEDLSDA NAGLQVECVQ
710 720 730 740 750
TLGNVNAPSF TVENPWDDEL ILKLLSGLSK PVTSYSNTFE WQSKLPAIKT
760 770 780 790 800
KTEYQLGSLL VYVNHLLGEG AFAQVFEAIH GDVRNAKSEQ KCILKVQRPA
810 820 830 840 850
NSWEFYIGMQ LMERLKPEVH HMFIKFYSAH LFKNGSILVG ELYSYGTLLN
860 870 880 890 900
VINLYKNTSE KVMPQALVLT FAIRMLYMVE QVHSCEIIHG DIKPDNFILG
910 920 930 940 950
HRFLEQADED LATGLALIDL GQSIDMKLFP KGTVFTGKCE TSGFQCPEML
960 970 980 990 1000
SNKPWNYQID YFGVAATIYC MLFGSYMKVK NEGGVWKPEG LFRRLPHLDM
1010 1020 1030 1040 1050
WEEFFHIMLN IPDCHNLPSL DFLRQNMKKL LEQQYSNKIK TLRNRLIVML

SEYKRSRK
Length:1,058
Mass (Da):119,563
Last modified:July 1, 1997 - v1
Checksum:iD179DAD4583A2C2F
GO

Sequence cautioni

The sequence AAC53533.1 differs from that shown. Reason: Erroneous initiation. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti187 – 1871K → R in AAC53533 (PubMed:9441741).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF002823 mRNA. Translation: AAC53226.1.
U89795 mRNA. Translation: AAC53533.1. Different initiation.
PIRiT30178.
T31004.
RefSeqiNP_001106650.1. NM_001113179.1.
NP_033902.2. NM_009772.2.
UniGeneiMm.2185.

Genome annotation databases

GeneIDi12235.
KEGGimmu:12235.
UCSCiuc008mgd.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF002823 mRNA. Translation: AAC53226.1.
U89795 mRNA. Translation: AAC53533.1. Different initiation.
PIRiT30178.
T31004.
RefSeqiNP_001106650.1. NM_001113179.1.
NP_033902.2. NM_009772.2.
UniGeneiMm.2185.

3D structure databases

ProteinModelPortaliO08901.
SMRiO08901. Positions 1-148, 714-1054.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi198404. 54 interactions.
IntActiO08901. 15 interactions.
STRINGi10090.ENSMUSP00000028858.

PTM databases

iPTMnetiO08901.
PhosphoSiteiO08901.

Proteomic databases

EPDiO08901.
MaxQBiO08901.
PaxDbiO08901.
PRIDEiO08901.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi12235.
KEGGimmu:12235.
UCSCiuc008mgd.2. mouse.

Organism-specific databases

CTDi699.
MGIiMGI:1100510. Bub1.

Phylogenomic databases

eggNOGiKOG1166. Eukaryota.
ENOG410XQ67. LUCA.
HOVERGENiHBG003709.
InParanoidiO08901.
KOiK02178.

Enzyme and pathway databases

BRENDAi2.7.11.1. 3474.

Miscellaneous databases

NextBioi280662.
PROiO08901.
SOURCEiSearch...

Family and domain databases

InterProiIPR015661. Bub1/Mad3.
IPR011009. Kinase-like_dom.
IPR013212. Mad3/Bub1_I.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR14030. PTHR14030. 2 hits.
PfamiPF08311. Mad3_BUB1_I. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00777. Mad3_BUB1_I. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS51489. BUB1_N. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Kinetochore localization of murine Bub1 is required for normal mitotic timing and checkpoint response to spindle damage."
    Taylor S.S., McKeon F.
    Cell 89:727-735(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Mammalian BUB1 protein kinases: map positions and in vivo expression."
    Pangilinan F., Li Q., Weaver T., Lewis B.C., Dang C.V., Spencer F.
    Genomics 46:379-388(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: C57BL/6J.
  3. "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: FUNCTION, TISSUE SPECIFICITY.
  4. "Bub1 mediates cell death in response to chromosome missegregation and acts to suppress spontaneous tumorigenesis."
    Jeganathan K., Malureanu L., Baker D.J., Abraham S.C., van Deursen J.M.
    J. Cell Biol. 179:255-267(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  5. "Inactivating the spindle checkpoint kinase Bub1 during embryonic development results in a global shutdown of proliferation."
    Tilston V., Taylor S.S., Perera D.
    BMC Res. Notes 2:190-190(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  6. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Testis.

Entry informationi

Entry nameiBUB1_MOUSE
AccessioniPrimary (citable) accession number: O08901
Secondary accession number(s): O09007
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: July 1, 1997
Last modified: May 11, 2016
This is version 123 of the entry and version 1 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.