mitotic checkpoint serine/threonine protein kinase BUB1; hBUB1; BUB1A (BUB1, BUB1L)

Function: - serine/threonine protein kinase - performs 2 crucial functions during mitosis a) essential for spindle-assembly checkpoint signaling b) correct chromosome alignment - role in assembly of checkpoint proteins at the kinetochore a) required for the subsequent localization of CENPF, BUB1B, CENPE & MAD2L1 b) required for the kinetochore localization of PLK1 - role in SGOL1 localization & thus affects sister chromatid cohesion - substrate for anaphase-promoting complex or cyclosome (APC/C) in complex with its activator CDH1 (APC/C-Cdh1) - necessary for ensuring proper chromosome segregation as component of BUB1/BUB3 complex - can regulate chromosome segregation (kinetochore-independent) - can phosphorylate BUB3 - component of BUB1/BUB3 complex - mediates cell death in response to chromosome missegregation & acts to suppress spontaneous tumorigenesis - autophosphorylated when the cells enters mitosis - phosphorylated upon DNA damage, probably by ATM or ATR - upon spindle-assembly checkpoint activation, it is hyperphosphorylated & its kinase activity toward CDC20 is stimulated - phosphorylation at Thr-609 is required for interaction with PLK1; phosphorylation probably creates a binding site for the POLO-box domain of PLK1, thus enhancing the PLK1-BUB1 interaction - ubiquitinated & degraded during mitotic exit by APC/C-Cdh1 - interacts with BUB3 & CASC5 - interacts (when phosphorylated) with PLK1 Structure: - CD1 domain directs kinetochore localization & binding to BUB3 - the KEN box is required for its ubiquitination & degradation - belongs to the protein kinase superfamily, Ser/Thr protein kinase family, BUB1 subfamily - contains 1 CD1 domain - contains 1 protein kinase domain Compartment: - nucleus - kinetochore - nuclear in interphase cells - accumulates gradually during G1 & S phase of the cell cycle, peaks at G2/M, & drops dramatically after mitosis - localizes to the outer kinetochore - kinetochore localization is required for normal mitotic timing & checkpoint response to spindle damage & occurs very early in prophase - AURKB, CASC5 & INCENP are required for kinetochore localization Expression: - high expression in testis & thymus - less in colon, spleen, lung & small intestine - expressed in fetal thymus, bone marrow, heart, liver, spleen & thymus - expression is associated with cells/tissues with a high mitotic index - inhibited by phorbol 12-myristate 13-acetate (PMA)

General

nuclear protein phosphoprotein serine/threonine kinase

Properties

SIZE: entity length = 1085 aa MW = 122 kD COMPARTMENT: cell nucleus STATE: active state MOTIF: domain {1-146} CD1 {11-160} MOTIF: nuclear translocation signal {58-65} domain {99-132} Ser phosphorylation site {S159} domain {229-256} Ser phosphorylation site {S314} Ser phosphorylation site {S331} Ser phosphorylation site {S375} Thr phosphorylation site {T452} domain {458-476} MOTIF: Thr phosphorylation site {T461} KEN box 1 {535-537} Ser phosphorylation site {S563} Ser phosphorylation site {S593} Ser phosphorylation site {S596} Thr phosphorylation site {T609} KEN box 2 {625-627} Ser phosphorylation site {S655} Ser phosphorylation site {S661} kinase domain SITE: 787-1085 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 793-801 ATP-binding site NAME: ATP-binding site SITE: 821-821 aspartate residue {D917}

Database Correlations

OMIM 602452 MORBIDMAP 602452 UniProt O43683 PFAM correlations Entrez Gene 699 Kegg hsa:699 ENZYME 2.7.11.1

References

UniProt :accession O43683