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). ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein] ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein] Kinase activity stimulated by CENPE. 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). Cytoplasmic in interphase cells (By similarity). Associates with the kinetochores in early prophase. Kinetochore localization requires BUB1, PLK1 and KNL1 (By similarity). Highly expressed in thymus followed by spleen. 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. 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 (By similarity). 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. Defects in Bub1b are involved in the development of lung and intestinal adenocarcinomas after exposure to a carcinogen. Mice die in utero. Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. BUB1 subfamily.