BUB1

2LAH, 4A1G, 4QPM, 4R8Q, 5DMZ69912235ENSG00000169679ENSMUSG00000027379O43683O08901NM_001278616NM_001278617NM_004336NM_001113179NM_009772NP_001265545NP_001265546NP_004327NP_001106650NP_033902Mitotic checkpoint serine/threonine-protein kinase BUB1 also known as BUB1 (budding uninhibited by benzimidazoles 1) is an enzyme that in humans is encoded by the BUB1 gene. Mitotic checkpoint serine/threonine-protein kinase BUB1 also known as BUB1 (budding uninhibited by benzimidazoles 1) is an enzyme that in humans is encoded by the BUB1 gene. Bub1 is a serine/threonine protein kinase first identified in genetic screens of Saccharomyces cerevisiae. The protein is bound to kinetochores and plays a key role in the establishment of the mitotic spindle checkpoint and chromosome congression. The mitotic checkpoint kinase is evolutionarily conserved in organisms as diverse as Saccharomyces cerevisiae and humans. Loss-of-function mutations or absence of Bub1 has been reported to result in aneuploidy, chromosomal instability (CIN) and premature senescence. Bub1p comprises a conserved N-terminal region, a central non-conserved region and a C-terminal serine/threonine kinase domain. The N-terminal region mediates binding of Hs-BUB1 to the mitotic kinetochore protein blinkin (a protein also commonly referred to as AF15q14). The latter interaction is essential for kinetochore localization of Bub1 and its function in cell cycle arrest induced by spindle assembly checkpoint (SAC) activation. The crystal structure of human Bub1 revealed the presence of a N-terminal tetratricopeptide repeat (TPR) domain and a C-terminal kinase domain (residues 784–1085), adopting a canonical kinase fold with two lobes. The ATP binding and the catalytic sites are located at the interface of the two lobes. The N-terminal extension contains three β-strands and an α-helix, wrapping around the N lobe of the kinase domain.:Figure1 In humans Bub1 accumulates gradually during G1 and S phase of the cell cycle, peaks at G2/M, and drops dramatically after mitosis. During prophase it localizes as one of the first proteins to the outer kinetochore, a process generally implicated in correct mitotic timing and checkpoint response to spindle damage.