BUB3: A Key Mitotic Checkpoint Protein in Chromosome Segregation
Comprehensive genomic and functional analysis of BUB3, a component of the spindle assembly checkpoint complex.
Gene Information Card
| Symbol | BUB3 |
|---|---|
| Full Name | BUB3 mitotic checkpoint protein |
| Gene Type | protein-coding |
| Chromosomal Location | 10q26.13 |
| NCBI Gene ID | 9184 ncbi.nlm.nih.gov/gene/9184 |
| Ensembl ID | ENSG00000154473 |
| UniProt ID | O43684 |
| OMIM ID | 603719 |
| HGNC ID | 1151 |
| Aliases | BUB3L, hBUB3, BUB3 (S. cerevisiae homolog) |
Description
BUB3 (BUB3 mitotic checkpoint protein) is a protein-coding gene that encodes a key component of the spindle assembly checkpoint (SAC). This protein binds to BUB1 and BUBR1 to form the mitotic checkpoint complex (MCC), which delays anaphase until all chromosomes are properly attached to the mitotic spindle. BUB3 is essential for accurate chromosome segregation and genomic stability.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer | Loss of BUB3 function leads to chromosomal instability and aneuploidy, promoting tumorigenesis. | PMID: 10655551, COSMIC |
| Mosaic variegated aneuploidy syndrome 1 (MVA1) | Biallelic mutations in BUB3 cause premature chromatid separation and aneuploidy. | OMIM #257300, PMID: 25533962 |
| Breast cancer | Reduced BUB3 expression correlates with poor prognosis and chromosomal instability. | PMID: 20023638 |
| Lung cancer | BUB3 downregulation contributes to aneuploidy and tumor progression. | PMID: 21804529 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 28.5 | High |
| Bone marrow | 22.1 | High |
| Lymph node | 18.7 | Medium |
| Brain | 12.3 | Medium |
| Liver | 8.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 35.2 | Cervical cancer cell line |
| K562 | 29.8 | Leukemia cell line |
| A549 | 24.5 | Lung cancer cell line |
| MCF7 | 20.1 | Breast cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Loss of start codon, likely loss of function |
| c.697C>T (p.Arg233*) | Nonsense | Rare | Premature stop, loss of function |
| c.1066G>A (p.Glu356Lys) | Missense | Rare | Unknown significance, possibly damaging |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations that truncate the protein or disrupt the WD40 domain impair SAC function, leading to aneuploidy.
Gain of Function (GOF)
No documented gain-of-function mutations in BUB3.
Dominant Negative (DN)
Some missense mutations may interfere with MCC assembly, acting in a dominant-negative manner, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • chromosome (GO:0000775) | • condensed chromosome kinetochore (GO:0000777) |
| • protein binding (GO:0005515) | • chromosome segregation (GO:0007059) |
| • mitotic spindle assembly checkpoint (GO:0007094) | • spindle checkpoint (GO:0031577) |
Pathways
• Cell cycle - KEGG hsa04110
• Mitotic spindle checkpoint - Reactome R-HSA-69618
• M Phase - Reactome R-HSA-68886
Protein Summary
BUB3 is a 328-amino acid protein containing seven WD40 repeats that form a beta-propeller structure. It localizes to kinetochores during mitosis and is required for the recruitment of BUB1 and BUBR1. BUB3 is a core component of the mitotic checkpoint complex (MCC) that inhibits the anaphase-promoting complex/cyclosome (APC/C) until all chromosomes are bioriented. Loss of BUB3 function leads to chromosomal instability and is implicated in various cancers.
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