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mitotic checkpoint serine/threonine protein kinase BUB1 beta; EC=2.7.11.1; MAD3/BUB1-related protein kinase; hBUBR1; mitotic checkpoint kinase MAD3L; protein SSK1 (BUB1B BUBR1 MAD3L SSK1)

Function: - essential component of the mitotic checkpoint - required for normal mitosis progression - the mitotic checkpoint delays anaphase until all chromosomes are properly attached to the mitotic spindle - checkpoint functions a) 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 b) to monitor kinetochore activities that depend on the kinetochore motor CENPE - required for kinetochore localization of CENPE - negatively regulates PLK1 activity in interphase cells & suppresses centrosome amplification - implicated in triggering apoptosis in polyploid cells that exit aberrantly from mitotic arrest - may play a role for tumor suppression - kinase activity stimulated by CENPE - proteolytically cleaved by caspase-3 (cell cycle specific); cleavage might be involved in the durability of the cell cycle delay - caspase-3 cleavage is associated with abrogation of the mitotic checkpoint - the major site of cleavage is at Asp-610 - acetylation at Lys-250 regulates its degradation & timing in anaphase entry - ubiquitinated - degradated by the proteasome - sumoylated by SUMO2 & SUMO3 - sumoylation mediates the association with CENPE at the kinetochore - autophosphorylated in vitro - intramolecular autophosphorylation is stimulated by CENPE - phosphorylated during mitosis & hyperphosphorylated in mitotically arrested cells - phosphorylation at Ser-670 & Ser-1043 occurs at kinetochores upon mitotic entry with dephosphorylation at the onset of anaphase - interacts with CENPE, CENPF, mitosin, PLK1 & BUB3 - part of a complex containing BUB3, CDC20 & BUB1B - interacts with anaphase-promoting complex/cyclosome (APC/C) - interacts with CASC5 Structure: - the CD1 domain directs kinetochore localization & binding to BUB3 - the D-box targets the protein for rapid degradation by ubiquitin-dependent proteolysis during the transition from mitosis to interphase (putative) - belongs to the protein kinase superfamily, Ser/Thr protein kinase family, BUB1 subfamily - contains 1 CD1 domain - contains 1 protein kinase domain Compartment: - cytoplasm, nucleus, kinetochore, cytoplasm, cytoskeleton, centrosome - cytoplasmic in interphase cells - associates with the kinetochores in early prophase - kinetochore localization requires BUB1, PLK1 & CASC5 Alternative splicing: named isoforms=3 Expression: - highly expressed in thymus followed by spleen - preferentially expressed in tissues with a high mitotic index - induced during mitosis Pathology: - defects in BUB1B are associated with tumor formation - defects in BUB1B are the cause a) premature chromatid separation trait b) mosaic variegated aneuploidy syndrome

General

nuclear protein phosphoprotein serine/threonine kinase

Properties

SIZE: entity length = 1050 aa MW = 120 kD COMPARTMENT: cytoplasm cell nucleus STATE: active state MOTIF: Thr phosphorylation site {T54} CD1 {62-213} MOTIF: nuclear translocation signal {111-118} Necessary for interaction with CASC5 {152-185} glutamate-rich region {209-215} MOTIF: glutamate residue (SEVERAL) ubiquitination site (destruction box, D-box) SITE: 224-232 FOR-BINDING-OF: ubiquitin Ser phosphorylation site {S435} Ser phosphorylation site {S543} proteolytic site {579-580} proteolytic site {610-611} Ser phosphorylation site {S670} Ser phosphorylation site {S676} kinase domain SITE: 766-1050 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 772-780 Thr phosphorylation site {T792} ATP-binding site NAME: ATP-binding site SITE: 795-795 aspartate residue {D882} Thr phosphorylation site {T1008} Ser phosphorylation site {S1043}

Database Correlations

OMIM correlations MORBIDMAP 602860 UniProt O60566 PFAM correlations Entrez Gene 701 Kegg hsa:701 ENZYME 2.7.11.1

References

  1. UniProt :accession O60566
  2. Atlas of Genetics & Cytogenetics in Oncology & Haematology http://atlasgeneticsoncology.org/genes/BUB1BID854ch15q15.html