Mitotic checkpoint kinase MAD3L

For Research Use Only. Not for use in diagnostic procedures.

Chromosome: 2; NC_000068.7 (118598211..118641592). Location: 2 E5; 2

Polyclonal

IgG

Sheep

Ammonium Sulfate Precipitation

Provided as solution in phosphate buffered saline with 0.08% sodium azide

Product should be stored at -20 degree C. Aliquot to avoid freeze/thaw cycles

Small volumes of anti-Bub1b antibody vial(s) may occasionally become entrapped in the seal of the product vial during shipment and storage. If necessary, briefly centrifuge the vial on a tabletop centrifuge to dislodge any liquid in the container`s cap. Certain products may require to ship with dry ice and additional dry ice fee may apply.

Bub1, a mitotic checkpoint gene first identified in yeast, ensures proper chromosome segregation by delaying anaphase until chromosomes are properly aligned on the mitotic spindle. Mutations in the mitotic spindle assembly checkpoint genes, like yeast Bub1, cause cells to exit mitosis without proper chromosome attachment/alignment, resulting in aneuploidy. Aneuploidy is a form of genetic instability involved in cancer. Recently, a novel homologue of the murine Bub1 gene has been identified and named Bub1b. The yeast mitotic checkpoint pathway is unresolved, but the mammalian pathway remains even less clear. It is important to investigate the role of the Bub1 genes in the mammalian checkpoint as they have been implicated in carcinogenesis, namely colon carcinomas. The aneuploidy and chromosome instability characterizing some tumors is thought to be caused by mutations in Bub1.

Polyclonal Antibody; Protein Kinases

Western Blot (WB), Immunohistochemistry (IHC)

Immunoprecipitation/

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Function: Essential component of the mitotic checkpoint. Required for normal mitosis progression and tumor suppression. The mitotic checkpoint delays anaphase until all chromosomes are properly attached to the mitotic spindle. One of its checkpoint functions is to inhibit the activity of the anaphase-promoting complex/cyclosome (APC/C) by blocking the binding of CDC20 to APC/C, independently of its kinase activity. The other is to monitor kinetochore activities that depend on the kinetochore motor CENPE. Required for kinetochore localization of CENPE. Negatively regulates PLK1 activity in interphase cells and suppresses centrosome amplification. Also implicated in triggering apoptosis in polyploid cells that exit aberrantly from mitotic arrest. Essential for tumor suppression. May play a role in regulating aging and fertility

By similarity. Ref.4 Ref.5

Catalytic activity: ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation: Kinase activity stimulated by CENPE. Ref.3

Subunit structure: Interacts with CENPE, CENPF, mitosin, PLK1 and BUB3. Part of a complex containing BUB3, CDC20 and BUB1B. Interacts with anaphase-promoting complex/cyclosome (APC/C). Interacts with CASC5

By similarity. Ref.3

Subcellular location: Cytoplasm

By similarity. Nucleus

By similarity. Chromosome ? centromere ? kinetochore. Note: Cytoplasmic in interphase cells

By similarity. Associates with the kinetochores in early prophase. Kinetochore localization requires BUB1, PLK1 and CASC5

By similarity. Ref.3 Ref.6

Tissue specificity: Highly expressed in thymus followed by spleen.

Domain: The D-box targets the protein for rapid degradation by ubiquitin-dependent proteolysis during the transition from mitosis to interphase

Potential.The BUB1 N-terminal domain directs kinetochore localization and binding to BUB3.

Post-translational modification: Proteolytically cleaved by caspase-3 in a cell cycle specific manner

By similarity. The cleavage might be involved in the durability of the cell cycle delay

By similarity.Acetylation at Lys-243 regulates its degradation and timing in anaphase entry

By similarity.Ubiquitinated. Degraded by the proteasome

By similarity.Sumoylated with SUMO2 and SUMO3. The sumoylation mediates the association with CENPE at the kinetochore

By similarity.Autophosphorylated in vitro

By similarity. Intramolecular autophosphorylation stimulated by CENPE

By similarity. Phosphorylated during mitosis and hyperphosphorylated in mitotically arrested cells

By similarity. Phosphorylation at Ser-659 and Ser-1033 occurs at kinetochores upon mitotic entry with dephosphorylation at the onset of anaphase

By similarity.

Involvement in disease: Defects in Bub1b are involved in the development of lung and intestinal adenocarcinomas after exposure to a carcinogen.

Disruption phenotype: Mice die in utero. Ref.5

Sequence similarities: Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. BUB1 subfamily.Contains 1 BUB1 N-terminal domain.Contains 1 protein kinase domain.

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