Bub1 was initially identified as the mammalian homolog to the yeast protein through a cDNA screen. Bub1 encodes a kinase involved in the formation of the spindle checkpoint, an important mechanism that ensures high fidelity mitotic chromosome segregation. It is thought to be required for assembly of a functional inner centromere, sister chromatid cohesion via targeting of the Shugoshim protein and metaphase congression. Bub1 functions by phosphorylating cdc20, a member of the mitotic checkpoint complex and activating the spindle checkpoint. A related protein kinase Bub3 interacts with Bub1 and targets it to kinetochores prior to chromosome alignment. Mutations in bub1 have been associated with aneuploidy and several forms of cancer.

Serine/threonine-protein kinase that performs 2 crucial functions during mitosis: it is essential for spindle-assembly checkpoint signaling and for correct chromosome alignment. Has a key role in the assembly of checkpoint proteins at the kinetochore, being required for the subsequent localization of CENPF, BUB1B, CENPE and MAD2L1. Required for the kinetochore localization of PLK1. Plays an important role in defining SGOL1 localization and thereby affects sister chromatid cohesion. Acts as a substrate for anaphase-promoting complex or cyclosome (APC/C) in complex with its activator CDH1 (APC/C-Cdh1). Necessary for ensuring proper chromosome segregation and binding to BUB3 is essential for this function. Can regulate chromosome segregation in a kinetochore-independent manner. Can phosphorylate BUB3. The BUB1-BUB3 complex plays a role in the inhibition of APC/C when spindle-assembly checkpoint is activated and inhibits the ubiquitin ligase activity of APC/C by phosphorylating its activator CDC20. This complex can also phosphorylate MAD1L1. Kinase activity is essential for inhibition of APC/CCDC20 and for chromosome alignment but does not play a major role in the spindle-assembly checkpoint activity. Mediates cell death in response to chromosome missegregation and acts to suppress spontaneous tumorigenesis.