Bub1b
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.
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).
Involvement in disease
Defects in Bub1b are involved in the development of lung and intestinal adenocarcinomas after exposure to a carcinogen.
Post-translational modifications
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.
Sequence Similarities
Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. BUB1 subfamily.
Tissue Specificity
Highly expressed in thymus followed by spleen.
Cellular localization
- Cytoplasm
- Nucleus
- Chromosome
- Centromere
- Kinetochore
- Cytoplasmic in interphase cells (By similarity). Associates with the kinetochores in early prophase. Kinetochore localization requires BUB1, PLK1 and KNL1 (By similarity).
Alternative names
Mad3l, Bub1b, Mitotic checkpoint serine/threonine-protein kinase BUB1 beta, MAD3/BUB1-related protein kinase, Mitotic checkpoint kinase MAD3L, BubR1