BUB1 Gene: Mitotic Checkpoint Kinase and Cancer Implications
Comprehensive guide to BUB1 (BUB1 Mitotic Checkpoint Serine/Threonine Kinase): genomic context, protein function, associated diseases, expression, mutations, and pathways.
Gene Information Card
| Symbol | BUB1 |
|---|---|
| Full Name | BUB1 mitotic checkpoint serine/threonine kinase |
| Gene Type | protein coding |
| Chromosomal Location | 2q14.1 |
| NCBI Gene ID | 699 ncbi.nlm.nih.gov/gene/699 |
| Ensembl ID | ENSG00000169679 |
| UniProt ID | O43683 |
| OMIM ID | 602452 |
| HGNC ID | 1148 |
| Aliases | BUB1A; BUB1L; hBUB1 |
Description
BUB1 (BUB1 mitotic checkpoint serine/threonine kinase) encodes a serine/threonine kinase that is a core component of the spindle assembly checkpoint (SAC). It is essential for proper chromosome segregation during mitosis. BUB1 localizes to kinetochores and is involved in the recruitment of other SAC proteins, including BUBR1 and MAD2, and in the establishment of kinetochore-microtubule attachments. Mutations and altered expression of BUB1 have been implicated in various cancers, contributing to chromosomal instability and aneuploidy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer | Altered BUB1 expression and mutations contribute to chromosomal instability (CIN) and aneuploidy, promoting tumorigenesis. | Multiple studies (e.g., Cahill et al., 1998; Shichiri et al., 2002) report BUB1 mutations in colorectal cancer cell lines and tumors. |
| Breast cancer | Overexpression of BUB1 is associated with poor prognosis and may drive tumor progression via SAC dysregulation. | Gene expression analyses (e.g., TCGA) show BUB1 upregulation in aggressive breast cancer subtypes. |
| Lung cancer | BUB1 overexpression correlates with tumor grade and metastasis, likely due to enhanced mitotic errors. | Immunohistochemistry and transcriptomic studies (e.g., Zhang et al., 2019) demonstrate elevated BUB1 in lung cancer tissues. |
| Hepatocellular carcinoma | BUB1 overexpression promotes cell proliferation and chromosomal instability, contributing to liver cancer progression. | Studies (e.g., Liu et al., 2020) report BUB1 as a prognostic marker in HCC. |
| Gastric cancer | BUB1 mutations and altered expression are linked to aneuploidy and poor patient outcomes. | Research (e.g., Kim et al., 2013) identifies BUB1 as a potential therapeutic target in gastric cancer. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 25.3 | High |
| Bone marrow | 18.7 | Medium |
| Lymph node | 15.2 | Medium |
| Spleen | 12.8 | Medium |
| Thymus | 11.9 | Medium |
| Colon | 8.5 | Low |
| Lung | 6.2 | Low |
| Liver | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical cancer) | 20.5 | High expression; used in mitotic studies. |
| MCF7 (breast cancer) | 15.3 | Elevated; correlates with proliferation. |
| A549 (lung cancer) | 12.1 | Moderate; associated with tumor aggressiveness. |
| HepG2 (liver cancer) | 10.8 | Moderate; linked to chromosomal instability. |
| K562 (leukemia) | 18.9 | High; reflects rapid proliferation. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1970A>G (p.Asn657Ser) | Missense | Rare (<0.1%) | Potential kinase activity alteration; observed in colorectal cancer. |
| c.2380C>T (p.Arg794Trp) | Missense | Rare (<0.1%) | May affect protein stability; found in gastric cancer. |
| c.1168C>T (p.Arg390Ter) | Nonsense | Very rare | Truncating mutation; likely loss-of-function. |
| c.1500_1501insA (frameshift) | Insertion | Rare | Frameshift leading to premature stop; loss-of-function. |
| c.2210A>G (p.Gln737Arg) | Missense | Rare | Potential impact on kinase domain; reported in lung cancer. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in BUB1 impair spindle assembly checkpoint signaling, leading to premature anaphase and aneuploidy. These are often truncating or missense mutations in the kinase domain.
Gain of Function (GOF)
Gain-of-function mutations are less common but may increase kinase activity, leading to hyperactivation of the SAC and prolonged mitotic arrest, which can contribute to tumorigenesis.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by interfering with wild-type BUB1 function, disrupting SAC signaling and promoting chromosomal instability.
View complete mutation data：
Gene Ontology (GO)
| • protein serine/threonine kinase activity | • ATP binding |
| • kinetochore binding | • spindle assembly checkpoint signaling |
| • mitotic cell cycle | • chromosome segregation |
| • cell division |
Pathways
• Spindle assembly checkpoint (SAC) pathway
• Cell cycle - mitosis
• Chromosomal instability (CIN) pathway
Protein Summary
BUB1 is a 1085-amino acid protein with an N-terminal kinetochore localization domain and a C-terminal serine/threonine kinase domain. It functions as a key regulator of the spindle assembly checkpoint, ensuring accurate chromosome segregation. BUB1 phosphorylates multiple substrates, including histone H2A, to recruit other checkpoint proteins. Its activity is essential for mitotic fidelity, and dysregulation is linked to cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| BUB1B-PAK6 Knockout HEK293 Cell Line | EDJ-KQ1241 | Human | 106821730 | Details Get a Quote |
| BUB1B-PAK6 Knockout A-549 Cell Line | EDJ-KQ20596 | Human | 106821730 | Details Get a Quote |
| BUB1B-PAK6 Knockout HCT 116 Cell Line | EDJ-KQ20597 | Human | 106821730 | Details Get a Quote |
| BUB1B-PAK6 Knockout HeLa Cell Line | EDJ-KQ20598 | Human | 106821730 | Details Get a Quote |
| BUB1 Knockout HEK293 Cell Line | EDJ-KQ50161 | Human | 699 | Details Get a Quote |
| BUB1 Knockout HeLa Cell Line | EDJ-KQ52739 | Human | 699 | Details Get a Quote |
| BUB1 Knockout A-549 Cell Line | EDJ-KQ61210 | Human | 699 | Details Get a Quote |
| BUB1 Knockout HCT 116 Cell Line | EDJ-KQ69703 | Human | 699 | Details Get a Quote |
| BUB1B (p.K94=) Point Mutation in HAP1 Cell Line | EDC03425 | Human | 701 | Details Get a Quote |
| BUB1B (p.A388=) Point Mutation in HAP1 Cell Line | EDC03426 | Human | 701 | Details Get a Quote |
| BUB1B (c.179+34A>C )Point Mutation in HAP1 Cell Line | EDC03424 | Human | 701 | Details Get a Quote |
| BUB1B (c.1401+24A>G )Point Mutation in HAP1 Cell Line | EDC03427 | Human | 701 | Details Get a Quote |
Displaying Records 1 To 12 Of 12 Records
