BUB1

BUB1

<div class="infobox infobox-gene">
<span class="infobox-title">BUB1</span>
<table>
<tr><th>Full Name</th><td>Mitotic Checkpoint Kinase BUB1 (Budding Uninhibited by Benzimidazoles 1)</td></tr>
<tr><th>Chromosomal Location</th><td>2q14</td></tr>
<tr><th>NCBI Gene ID</th><td>699</td></tr>
<tr><th>OMIM</th><td>602452</td></tr>
<tr><th>Ensembl ID</th><td>ENSG00000169679</td></tr>
<tr><th>UniProt ID</th><td>O43683</td></tr>
<tr><th>Protein</th><td>BUB1 protein</td></tr>
<tr><th>Associated Diseases</th><td>Cancer (multiple types), Mosaic variegated aneuploidy (MVA), Microcephaly, Growth retardation</td></tr>
</table>
</div>

Overview

BUBR1 is a human gene whose product bUB1 (Budding Uninhibited by Benzimidazoles 1) is a serine/threonine-protein kinase that plays a critical role in the mitotic checkpoint (spindle assembly checkpoint), ensuring proper chromosome segregation during cell division[@yu2007]. Variants in BUBR1 have been implicated in Cancer, Congenital Disorders, Neurodegeneration. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.

Function

BUB1 (Budding Uninhibited by Benzimidazoles 1) is a serine/threonine-protein kinase that plays a critical role in the mitotic checkpoint (spindle assembly checkpoint), ensuring proper chromosome segregation during cell division[@yu2007].

Key Molecular Functions

BUB1

<div class="infobox infobox-gene">
<span class="infobox-title">BUB1</span>
<table>
<tr><th>Full Name</th><td>Mitotic Checkpoint Kinase BUB1 (Budding Uninhibited by Benzimidazoles 1)</td></tr>
<tr><th>Chromosomal Location</th><td>2q14</td></tr>
<tr><th>NCBI Gene ID</th><td>699</td></tr>
<tr><th>OMIM</th><td>602452</td></tr>
<tr><th>Ensembl ID</th><td>ENSG00000169679</td></tr>
<tr><th>UniProt ID</th><td>O43683</td></tr>
<tr><th>Protein</th><td>BUB1 protein</td></tr>
<tr><th>Associated Diseases</th><td>Cancer (multiple types), Mosaic variegated aneuploidy (MVA), Microcephaly, Growth retardation</td></tr>
</table>
</div>

Overview

BUBR1 is a human gene whose product bUB1 (Budding Uninhibited by Benzimidazoles 1) is a serine/threonine-protein kinase that plays a critical role in the mitotic checkpoint (spindle assembly checkpoint), ensuring proper chromosome segregation during cell division[@yu2007]. Variants in BUBR1 have been implicated in Cancer, Congenital Disorders, Neurodegeneration. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.

Function

BUB1 (Budding Uninhibited by Benzimidazoles 1) is a serine/threonine-protein kinase that plays a critical role in the mitotic checkpoint (spindle assembly checkpoint), ensuring proper chromosome segregation during cell division[@yu2007].

Key Molecular Functions

• Checkpoint signaling: BUB1 phosphorylates MAD3/BUBR1 to generate the mitotic checkpoint complex (MCC)[@chen1999]
• Kinetochore localization: BUB1 localizes to kinetochores and recruits other checkpoint proteins[@sharpbaker2001]
• Chromosome alignment: Ensures proper kinetochore-microtubule attachments[@li2009]
• Centromere function: Regulates Aurora B kinase localization and activity[@ruchaud2007]

• N-terminal kinetochore-targeting domain
• C-terminal kinase domain
• Multiple phosphorylation sites[@kang2008]

Disease Associations

Cancer

• Colorectal cancer: BUB1 mutations in microsatellite instability-high tumors[@shichiri2002]
• Breast cancer: Altered expression in aggressive subtypes[@yuan2006]
• Hematologic malignancies: Mutations in B-cell lymphomas and leukemias[@cai2009]

Congenital Disorders

• Mosaic Variegated Aneuploidy (MVA): Biallelic BUB1 mutations cause MVA syndrome[@matsuura2006]
• Microcephaly: Associated with BUB1 haploinsufficiency[@suijkerbuijk2010]

Neurodegeneration

• [Alzheimer's disease](/diseases/alzheimers-disease): Mitotic checkpoint defects in AD [neurons](/entities/neurons); aneuploidy increases[@yang2001]
• Tauopathies: BUB1 dysregulation in neurodegenerative diseases[@liu2014]
• Aging: Declining checkpoint function contributes to genomic instability[@baker2014]

Expression

BUB1 is expressed in proliferating cells:

• Highest: Bone marrow, testis, embryonic tissues[@gtex]
• Cell cycle-regulated: Peak in G2/M phase
• Low/undetectable: Most differentiated tissues

• Neural progenitor cells
• Developing neurons
• Low in mature neurons

Therapeutic Implications

• Cancer therapy: BUB1 as target for anti-mitotic drugs[@kops2004]
• Checkpoint inhibition: Synthetic lethality with microtubule poisons[@janssen2009]
• Biomarker: Checkpoint status predicts chemotherapy response[@holland2012]

See Also

• [BUBR1](/genes/bub1b) - Partner checkpoint kinase
• [MAD2](/genes/mad2l1) - Checkpoint complex component
• [Aurora B](/genes/aurkb) - Kinase partner
• [Mitotic Checkpoint](/mechanisms/mitosis) - Pathway

External Links

• [NCBI Gene: BUB1](https://www.ncbi.nlm.nih.gov/gene/699)
• [UniProt: O43683](https://www.uniprot.org/uniprot/O43683)
• [OMIM: 602452](https://www.omim.org/entry/602452)

References

Pathway Diagram

The following diagram shows the key molecular relationships involving BUB1 discovered through SciDEX knowledge graph analysis: