mitotic checkpoint serine/threonine protein kinase BUB1 beta; EC=2.7.11.1; MAD3/BUB1-related protein kinase; hBUBR1; mitotic checkpoint kinase MAD3L; protein SSK1 (BUB1B BUBR1 MAD3L SSK1)
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Function
- essential component of the mitotic checkpoint
- required for normal mitosis progression
- the mitotic checkpoint delays anaphase until all chromosomes are properly attached to the mitotic spindle
- checkpoint functions
- 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
- to monitor kinetochore activities that depend on the kinetochore motor CENPE
- required for kinetochore localization of CENPE
- negatively regulates PLK1 activity in interphase cells & suppresses centrosome amplification
- implicated in triggering apoptosis in polyploid cells that exit aberrantly from mitotic arrest
- may play a role for tumor suppression
- kinase activity stimulated by CENPE
- proteolytically cleaved by caspase-3 (cell cycle specific); 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-610
- acetylation at Lys-250 regulates its degradation & timing in anaphase entry
- ubiquitinated
- degradated by the proteasome
- sumoylated by SUMO2 & SUMO3
- sumoylation mediates the association with CENPE at the kinetochore
- autophosphorylated in vitro
- intramolecular autophosphorylation is stimulated by CENPE
- phosphorylated during mitosis & hyperphosphorylated in mitotically arrested cells
- phosphorylation at Ser-670 & Ser-1043 occurs at kinetochores upon mitotic entry with dephosphorylation at the onset of anaphase
- interacts with CENPE, CENPF, mitosin, PLK1 & BUB3
- part of a complex containing BUB3, CDC20 & BUB1B
- interacts with anaphase-promoting complex/cyclosome (APC/C)
- interacts with CASC5
Structure
- the CD1 domain directs kinetochore localization & binding to BUB3
- the D-box targets the protein for rapid degradation by ubiquitin-dependent proteolysis during the transition from mitosis to interphase (putative)
- belongs to the protein kinase superfamily, Ser/Thr protein kinase family, BUB1 subfamily
- contains 1 CD1 domain
- contains 1 protein kinase domain
Compartment
- cytoplasm, nucleus, kinetochore, cytoplasm, cytoskeleton, centrosome
- cytoplasmic in interphase cells
- associates with the kinetochores in early prophase
- kinetochore localization requires BUB1, PLK1 & CASC5
Alternative splicing
named isoforms=3
Expression
- highly expressed in thymus followed by spleen
- preferentially expressed in tissues with a high mitotic index
- induced during mitosis
Pathology
- defects in BUB1B are associated with tumor formation
- defects in BUB1B are the cause
More general terms
References
- ↑ UniProt http://www.uniprot.org/uniprot/O60566.html
- ↑ Atlas of Genetics & Cytogenetics in Oncology & Haematology http://atlasgeneticsoncology.org/genes/BUB1BID854ch15q15.html
Database
- Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=701
- Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:701
- OMIM: https://mirror.omim.org/entry/176430
- OMIM: https://mirror.omim.org/entry/257300
- OMIM: https://mirror.omim.org/entry/602860
- UniProt: http://www.uniprot.org/uniprot/O60566.html