BUB1B

BUB1B
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2WVI, 3SI5, 4GGD, 5JJA
Identifiers
Aliases	BUB1B, BUB1beta, BUBR1, Bub1A, MAD3L, MVA1, SSK1, hBUBR1, BUB1 mitotic checkpoint serine/threonine kinase B
External IDs	OMIM: 602860; MGI: 1333889; HomoloGene: 933; GeneCards: BUB1B; OMA:BUB1B - orthologs
Gene location (Human) Chr. Chromosome 15 (human)[1] Band 15q15.1 Start 40,161,023 bp[1] End 40,221,123 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2|2 E5 Start 118,428,692 bp[2] End 118,472,072 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in secondary oocyte ventricular zone gonad embryo Epithelium of choroid plexus ganglionic eminence right testis bone marrow left testis trabecular bone Top expressed in secondary oocyte primary oocyte ectoderm otic vesicle primitive streak otic placode tail of embryo spermatocyte genital tubercle zygote More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein serine/threonine kinase activity ATP binding protein binding kinase activity nucleotide binding transferase activity protein kinase activity Cellular component kinetochore nucleus cytoskeleton outer kinetochore microtubule organizing center perinuclear region of cytoplasm chromosome, centromeric region anaphase-promoting complex chromosome cytoplasm spindle midzone cytosol spindle Biological process protein localization to chromosome, centromeric region anaphase-promoting complex-dependent catabolic process mitotic cell cycle checkpoint signaling protein phosphorylation metaphase cell cycle apoptotic process phosphorylation cell division cell population proliferation protein localization to kinetochore mitotic spindle assembly checkpoint signaling meiotic sister chromatid cohesion, centromeric mitotic cell cycle regulation of mitotic cell cycle phase transition ubiquitin-dependent protein catabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 701 12236 Ensembl ENSG00000156970 ENSMUSG00000040084 UniProt O60566 Q9Z1S0 RefSeq (mRNA) NM_001211 NM_009773 RefSeq (protein) NP_001202 NP_033903 Location (UCSC) Chr 15: 40.16 – 40.22 Mb Chr 2: 118.43 – 118.47 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Mitotic checkpoint serine/threonine-protein kinase BUB1 beta is an enzyme that in humans is encoded by the BUB1B gene.^[5] Also known as BubR1, this protein is recognized for its mitotic roles in the spindle assembly checkpoint (SAC) and kinetochore-microtubule interactions that facilitate chromosome migration and alignment. BubR1 promotes mitotic fidelity and protects against aneuploidy by ensuring proper chromosome segregation between daughter cells. BubR1 is proposed to prevent tumorigenesis.

Function

This gene encodes a kinase involved in spindle checkpoint function and chromosome segregation.^[6] The protein has been localized to the kinetochore and plays a role in the inhibition of the anaphase-promoting complex/cyclosome (APC/C), delaying the onset of anaphase and ensuring proper chromosome segregation. Impaired spindle checkpoint function has been found in many forms of cancer.^[7]

Increased expression of BubR1 in mice extends a healthy lifespan.^[8]

Clinical Significance

BubR1 has been implicated in a variety of biological processes and pathologies, including cancer, aging, mosaic variegated aneuploidy (MVA), and heart disease. BubR1 protein levels are shown to decline with age.^[8][9][10] Furthermore, loss of BubR1 in young organisms is associated with rapid aging and premature onset of age-related diseases and phenotypes such as cardiac dysfunction, poor wound healing, cataracts, kyphosis, fat loss and muscle wasting (cachexia), and cancer.^[9] This has been demonstrated in mice.

DNA repair

Chemoradiotherapy (CRT), the combination of chemotherapy and radiotherapy applied with curative intent, is used to treat a variety of cancers. CRT acts by inducing damage in the DNA of the cancer cells. Bladder cancer tumor samples were taken from patients before treatment and from the same patients after CRT treatment when the tumors had reoccurred.^[11] An increased level of BUB1B expression was found in the CRT-recurrent cells. This increased expression was considered to facilitate an inaccurate DNA repair process termed alternative non-homologous end joining (A-NHEJ) that inaccurately repairs DNA damages such as those caused by the CRT. This inaccurate repair could cause additional mutations in the tumor including mutations to CRT resistance.^[11]

Interactions

BUB1B has been shown to interact with:

• AP2B1^[12]
• BRCA2^[13]
• BUB3^[12][14][15]
• CDC20^{[16][17][18][19][20][21]}
• MAD2L1^[16]
• CBP^[22]
• SIRT2^[22][23][24]
• PLK1^{[25][26][27][28][29]}
• PP2A-B56^{[29][30][31][32]}
• HDAC1^[33]
• HDAC2 / HDAC3^[34]
• SNCG^[35]

References

Further reading

External links

• Human BUB1B genome location and BUB1B gene details page in the UCSC Genome Browser.