Q9Z1S0 · BUB1B_MOUSE

  • Protein
    Mitotic checkpoint serine/threonine-protein kinase BUB1 beta
  • Gene
    Bub1b
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

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).

Catalytic activity

Activity regulation

Kinase activity stimulated by CENPE.

Features

Showing features for site, binding site, active site.

TypeIDPosition(s)Description
Site572-573Cleavage; by caspase-3
Site603-604Cleavage; by caspase-3
Binding site762-770ATP (UniProtKB | ChEBI)
Binding site784ATP (UniProtKB | ChEBI)
Active site871Proton acceptor

GO annotations

AspectTerm
Cellular Componentcytoplasm
Cellular Componentcytosol
Cellular Componentkinetochore
Cellular Componentmitotic checkpoint complex
Cellular Componentnucleus
Cellular Componentouter kinetochore
Cellular Componentperinuclear region of cytoplasm
Cellular Componentspindle
Molecular FunctionATP binding
Molecular Functionprotein kinase activity
Molecular Functionprotein serine kinase activity
Molecular Functionprotein serine/threonine kinase activity
Biological Processapoptotic process
Biological Processcell division
Biological Processmeiotic sister chromatid cohesion, centromeric
Biological Processmetaphase/anaphase transition of mitotic cell cycle
Biological Processmitotic spindle assembly checkpoint signaling
Biological Processprotein localization to chromosome, centromeric region

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Mitotic checkpoint serine/threonine-protein kinase BUB1 beta
  • EC number
  • Alternative names
    • MAD3/BUB1-related protein kinase (BubR1)
    • Mitotic checkpoint kinase MAD3L

Gene names

    • Name
      Bub1b
    • Synonyms
      Mad3l

Organism names

  • Taxonomic identifier
  • Strains
    • NIH Swiss
    • C57BL/6J
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    Q9Z1S0
  • Secondary accessions
    • A2ARS1

Proteomes

Organism-specific databases

Subcellular Location

Cytoplasm
Nucleus
Note: Cytoplasmic in interphase cells (By similarity).
Associates with the kinetochores in early prophase. Kinetochore localization requires BUB1, PLK1 and KNL1 (By similarity).

Keywords

Phenotypes & Variants

Involvement in disease

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

Disruption phenotype

Mice die in utero.

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 71 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Keywords

PTM/Processing

Features

Showing features for chain, modified residue.

TypeIDPosition(s)Description
ChainPRO_00000856741-1052Mitotic checkpoint serine/threonine-protein kinase BUB1 beta
Modified residue243N6-acetyllysine; by PCAF
Modified residue360Phosphoserine
Modified residue428Phosphoserine
Modified residue535Phosphoserine
Modified residue659Phosphoserine
Modified residue665Phosphoserine; by PLK1
Modified residue686Phosphoserine
Modified residue781Phosphothreonine; by PLK1
Modified residue998Phosphothreonine; by PLK1
Modified residue1033Phosphoserine
Modified residue1050Phosphoserine

Post-translational modification

Proteolytically cleaved by caspase-3 in a cell cycle specific manner. The cleavage might be involved in the durability of the cell cycle delay.
Acetylation at Lys-243 regulates its degradation and timing in anaphase entry.
Ubiquitinated. Degraded by the proteasome. Ubiquitinated by UBR5, promoting disassembly of the mitotic checkpoint complex from the APC/C complex.
Sumoylated with SUMO2 and SUMO3. The sumoylation mediates the association with CENPE at the kinetochore (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.
Proteolytically cleaved by caspase-3 in a cell cycle specific manner. The cleavage might be involved in the durability of the cell cycle delay. Caspase-3 cleavage is associated with abrogation of the mitotic checkpoint. The major site of cleavage is at Asp-603.

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Highly expressed in thymus followed by spleen.

Gene expression databases

Interaction

Subunit

Interacts with CENPE (PubMed:12925705).
Interacts with PLK1 (By similarity).
Part of a complex containing BUB3, CDC20 and BUB1B (By similarity).
Interacts with anaphase-promoting complex/cyclosome (APC/C) (By similarity).
Interacts with KNL1 (By similarity).
Interacts with KAT2B (By similarity).
Interacts with RIPK3 (By similarity).
Interacts with the closed conformation form of MAD2L1 (By similarity).
Interacts with CDC20 (By similarity).

Protein-protein interaction databases

Miscellaneous

Structure

Family & Domains

Features

Showing features for domain, motif, region, compositional bias.

TypeIDPosition(s)Description
Domain56-219BUB1 N-terminal
Motif105-112Nuclear localization signal
Region146-179Necessary for interaction with KNL1
Region206-256Disordered
Motif217-225D-box
Region272-327Disordered
Region361-381Disordered
Compositional bias496-524Polar residues
Region496-552Disordered
Domain756-1040Protein kinase

Domain

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

Sequence similarities

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. BUB1 subfamily.

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    1,052
  • Mass (Da)
    118,392
  • Last updated
    2011-07-27 v2
  • Checksum
    9EF1ECF3735DD1F4
MAEASEAMCLEGAEWELSKENIQPLRHGRVMSTLQGALAKQESAGHTALQQQKRAFESEIRFYSGDDPLDVWDRYINWTEQNYPQGGKESNMSALVERAIEALQGETRYYNDPRFLSLWIKLGHLCNEPLDMYSYLQSQGIGVSLAQFYISWAEEYEARENFKKADIIFQEGIERKAEPLDRLQSQHRQFQSRVSRQAFLALGNEEEEALEPSEPQRSSLAELKSRGKKMARAPISRVGGALKAPGQSRGFLNAVPQPVHGNRRITVFDENADTASRTELSKPVAQPWMAPPVPRAKENELQPGPWSTDRPAGRRPHDNPASVTSIPSVLPSFTPYVEESAQQTVMTPCKIEPSINHVLSTRKPGREEGDPLQRVQSHQQGCEEKKEKMMYCKEKIYAGVGEFSFEEIRAEVFRKKLKERREAELLTSAKKREEMQKQIEEMERRLKAMQAVQQEGAGGQQEEKMPTEDPARLQIASGPQEMSGVPLSCSICPLSSNPREISPAENILQEQPDSKGSSMPFSIFDESLSDKKDKSPATGGPQVLNAQRRPLSVLKTTEVGTTNEDVSPDICDELTELEPLSEDAIITGFRNVTLCPNPEDTCDFARAARLASTPFHEILSSKGIAADPEGLLQEEDLDGKAAEAHHTVHHQALIIKKLSPIIEESREATHSSGFSRSSSSAPSTSSIKGFQLLEKLELTNDGAEDAIQSPWCSQYRLQLLKSLLELSAFAEFSVEDRPMPVLEIGKEIELGPEDYVIKQEHLTCDDYRLFWVAPRSSAELTMIKASSQPIPWDFYINLKLKERLNEDYDQLCSCCQYQDGHVVWYQYINCSTLQNLLQHSEFVTHEIIVLIIYNLLTIVEKLHRAEIVHGDLSPRSLILRNRIHDPYDYVNKDDHAVRIMDFSYSVDLRVQLDAFAYSGFRTAQILEGQKILANCSSPYHVDLLGIADLAHLLLFKEHLHVFWDGLLWKLSQSTSELKDSELWNKFFVRILNASDKSTVSVLGELAAEMGGAFDATFHSHLNRALWKLGKTISPEALLTQQDKQPGGSQSPA

Features

Showing features for sequence conflict, compositional bias.

TypeIDPosition(s)Description
Sequence conflict275in Ref. 1; AAD11940
Sequence conflict278in Ref. 1; AAD11940
Compositional bias496-524Polar residues
Sequence conflict664in Ref. 1; AAD11940
Sequence conflict705in Ref. 1; AAD11940

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AF107296
EMBL· GenBank· DDBJ
AAD11940.1
EMBL· GenBank· DDBJ
mRNA
AL845470
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
AL929381
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.

Genome annotation databases

Similar Proteins

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