BUB1B

This gene encodes a kinase involved in spindle checkpoint function. The protein has been localized to the kinetochore and plays a role in the inhibition of the anaphase-promoting complex/cyclosome (APC/C), delaying the onset of anaphase and ensuring proper chromosome segregation. Impaired spindle checkpoint function has been found in many forms of cancer. [provided by RefSeq, Jul 2008]

BUB1 Mitotic Checkpoint Serine/Threonine Kinase B

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. 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. May play a role for tumor suppression.

Anaphase-promoting complex-dependent catabolic process Source: Reactome
Apoptotic process Source: UniProtKB-KW
Cell division Source: UniProtKB-KW
Meiotic sister chromatid cohesion, centromeric Source: GO_Central
Metaphase/anaphase transition of mitotic cell cycle Source: Ensembl
Mitotic cell cycle Source: ProtInc
Mitotic cell cycle checkpoint Source: ProtInc
Mitotic spindle assembly checkpoint Source: GO_Central
Mitotic spindle organization Source: Reactome
Protein localization to chromosome, centromeric region Source: Ensembl
Regulation of exit from mitosis Source: Reactome
Regulation of mitotic cell cycle phase transition Source: Reactome
Ubiquitin-dependent protein catabolic process Source: Reactome

Cytoplasm; Nucleus; Centrosome; Kinetochore. Cytoplasmic in interphase cells. Associates with the kinetochores in early prophase. Kinetochore localization requires BUB1, PLK1 and KNL1.

Defects in BUB1B are associated with tumor formation.
Premature chromatid separation trait (PCS): Consists of separate and splayed chromatids with discernible centromeres and involves all or most chromosomes of a metaphase. It is found in up to 2% of metaphases in cultured lymphocytes from approximately 40% of normal individuals. When PCS is present in 5% or more of cells, it is known as the heterozygous PCS trait and has no obvious phenotypic effect, although some have reported decreased fertility. Inheritance is autosomal dominant.
Mosaic variegated aneuploidy syndrome 1 (MVA1): A severe developmental disorder characterized by mosaic aneuploidies, predominantly trisomies and monosomies, involving multiple different chromosomes and tissues. Affected individuals typically present with severe intrauterine growth retardation and microcephaly. Eye anomalies, mild dysmorphism, variable developmental delay, and a broad spectrum of additional congenital abnormalities and medical conditions may also occur. The risk of malignancy is high, with rhabdomyosarcoma, Wilms tumor and leukemia reported in several cases.

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-610.
Acetylation at Lys-250 regulates its degradation and timing in anaphase entry.
Ubiquitinated. Degraded by the proteasome.
Sumoylated with SUMO2 and SUMO3. The sumoylation mediates the association with CENPE at the kinetochore.
Autophosphorylated in vitro. Intramolecular autophosphorylation is stimulated by CENPE. Phosphorylated during mitosis and hyperphosphorylated in mitotically arrested cells. Phosphorylation at Ser-670 and Ser-1043 occurs at kinetochores upon mitotic entry with dephosphorylation at the onset of anaphase.