Human cells contain two related protein kinases, BUB1 and BUBR1, that appear to have evolved from a single ancestral BUB1 gene. Both kinases are concentrated near the surface of the kinetochore where they monitor kinetochore-microtubule interactions. BUB1 and BUBR1 bind to kinetochores and are postulated to be components of the mitotic checkpoint, which monitors kinetochore activities to determine if chromosomes have achieved alignment at the spindle equator. BUBR1 is essential for normal mitotic progression as it prevents cells from prematurely entering anaphase. BUB3 is a conserved component of the mitotic spindle assembly complex and is also involved with the essential spindle checkpoint pathway that operates during early embryogenesis.