The gene spans 40.2 kb and is composed of 25 exons.

NM_004336.3, see pdf above.

Uniprot accession number: NP_004327.1.
ENZYME entry (serine/threonine protein kinase): EC 2.7.11.1.
Amino acid sequence (FASTA format): see pdf above.

1085 amino acids, 122.37 kDa.

Ubiquituously expressed.

Cytoplasmic in interphase cells. It is localized in nuclear kinetochores in cells with an unsatisfied mitotic checkpoint in a process that requires BUB1 binding to Blinkin and BUB3.

BUB1 is required for chromosome congression, kinetochore localization of BUBR1, CENP-E, CENP-F and Mad2 in cells with mitotic checkpoint unsatisfied and for the establishment and/or maintenance of efficient bipolar attachment to spindle microtubules (Johnson et al., 2004; Lampson and Kapoor, 2005; McGuinness et al., 2009). Deletion of Bub1 from S. pombe increases the rate of chromosome missegregation (Bernard et al., 1998) while deletion of Bub1 from S. cerevisiae results in slow growth and elevated chromosome loss (Warren et al., 2002).
BUB1 is recruited very early in prophase (Wong and Fang, 2006) and is essential for assembly of the functional inner centromere (Taylor et al., 1998; Boyarchuk et al., 2007). It accumulates at the kinetochore in SAC-activated cells and assures the correct kinetochore formation.
The N-terminal region mediates the binding of BUB1 to the mitotic kinetochore protein Blinkin (a protein also commonly referred to as KNL1/Spc105/AF15q14); the interaction is essential for the kinetochore localization of BUB1 induced in cells with an unsatisfied mitotic checkpoint (Kiyomitsu et al., 2007). N-terminal BUB1 is organised as a triple tandem of the TPR motif (Bolanos-Garcia et al., 2009). In fission yeast, the Bub1 N-terminal residues 1-179 are required for targeting the protein Shugoshin 1 (SGO1) to centromeres (Vaur et al., 2005) while deletion of residues 28-160 results in a truncated protein unable to recruit Bub3 and Mad3/BUB1B to kinetochores (Vanoosthuyse et al., 2004). The C-terminal region contains a catalytic, serine threonine kinase domain that resembles the mechanism of activation of CDKs by cyclins (Kang et al., 2008).

The bub1 gene is conserved in chimpanzee, cow, mouse, rat, chicken, and zebrafish. Homology exists with the gene encoding for the mitotic checkpoint kinase BUBR1 (a BUB1 paralogue) (Bolanos-Garcia and Blundell, 2011).

Bub1 region	Mutation	Residue	Domain	Clinical condition	Reference
N-terminal	GAG→GAT	E36→D	TPR domain	Colorectal cancer	Cahill et al., 1999
	Deletion	Δ76-141, frameshift		Colorectal cancer	Cahill et al., 1998
	GCT→TCT	A130→S		Lymph node metastasis	Shichiri et al., 2002
	G→A	140, transition of the splicing donor site		Colorectal cancer	Cahill et al., 1998
GLEBS motif	CGA→CAA	R209→Q		Lung cancer	Sato et al., 2000
	GGT→GAT	G250→N		ATLL	Ohshima et al., 2000*
	TAT→TGT	Y259→C		Pancreatic cancer	Hempen et al., 2003
	CAC→AAC	H265→N		Pancreatic cancer	Hempen et al., 2003
Middle region of low structural complexity	TCC→TTC	S375→F		Colorectal cancer	Saeki et al., 2002
	TCT→TAT	S492→Y		Colorectal cancer	Cahill et al., 1998
	AAG→AGG	K566→R		Colorectal cancer	Saeki et al., 2002
	CCC→CGC	P648→R		Colorectal cancer	Cahill et al., 1999
C-terminal	Deletion	Δ827, frameshift		Tyroid follicular adenoma	Ouyang et al., 2002
		S950→G	Kinase domain	Colorectal cancer	Imai et al., 1999

Table 1. Human bub1 mutations associated with cancer. *These authors incorrectly number these residues; the numbering shown here is the correct.

The following somatic mutations have been reported to date: A130->S (Shichiri et al., 2002); deletion delta76-141 (Cahill et al., 1998); 140, transition of the splicing donor site (Cahill et al., 1998); S492->Y (Cahill et al., 1998); deletion delta827 (Ouyang et al., 2002); G250->N (Ohshima et al., 2000); S950->G (Imai et al., 1999); Y259->C (Hempen et al., 2003); H265->N (Hempen et al., 2003). It could not be determined whether the R209->Q substitution was the result of a somatic mutation or due to a rare polymorphism because constitutional DNA from the patient harbouring this mutation was not available (Sato et al., 2000). The clinical condition associated to each mutation is described in Table 1. The mapping of residues substitutions onto the BUB1 domains is depicted in Figure 3.