Protein: Mitotic checkpoint serine/threonine-protein kinase BUB1 (hBUB1) (EC 2.7.11.1) (BUB1A) (O43683)
Organism: Homo sapiens (Human)
Function: Serine/threonine-protein kinase that performs 2 crucial functions during mitosis: it is essential for spindle-assembly checkpoint signaling and for correct chromosome alignment. Has a key role in the assembly of checkpoint proteins at the kinetochore, being required for the subsequent localization of CENPF, BUB1B, CENPE and MAD2L1. Required for the kinetochore localization of PLK1. Required for centromeric enrichment of AUKRB in prometaphase. Plays an important role in defining SGO1 localization and thereby affects sister chromatid cohesion. Acts as a substrate for anaphase-promoting complex or cyclosome (APC/C) in complex with its activator CDH1 (APC/C-Cdh1). Necessary for ensuring proper chromosome segregation and binding to BUB3 is essential for this function. Can regulate chromosome segregation in a kinetochore-independent manner. Can phosphorylate BUB3. The BUB1-BUB3 complex plays a role in the inhibition of APC/C when spindle-assembly checkpoint is activated and inhibits the ubiquitin ligase activity of APC/C by phosphorylating its activator CDC20. This complex can also phosphorylate MAD1L1. Kinase activity is essential for inhibition of APC/CCDC20 and for chromosome alignment but does not play a major role in the spindle-assembly checkpoint activity. Mediates cell death in response to chromosome missegregation and acts to suppress spontaneous tumorigenesis.
Subcellular location: Nucleus. Chromosome, centromere, kinetochore. Note=Nuclear in interphase cells. Accumulates gradually during G1 and S phase of the cell cycle, peaks at G2/M, and drops dramatically after mitosis. Localizes to the outer kinetochore. Kinetochore localization is required for normal mitotic timing and checkpoint response to spindle damage and occurs very early in prophase. AURKB, KNL1 and INCENP are required for kinetochore localization (By similarity). {ECO:0000250}.
Sequence: MDTPENVLQMLEAHMQSYKGNDPLGEWERYIQWVEENFPENKEYLITLLEHLMKEFLDKKKYHNDPRFISYCLKFAEYNSDLHQFFEFLYNHGIGTLSSPLYIAWAGHLEAQGELQHASAVLQRGIQNQAEPREFLQQQYRLFQTRLTETHLPAQARTSEPLHNVQVLNQMITSKSNPGNNMACISKNQGSELSGVISSACDKESNMERRVITISKSEYSVHSSLASKVDVEQVVMYCKEKLIRGESEFSFEELRAQKYNQRRKHEQWVNEDRHYMKRKEANAFEEQLLKQKMDELHKKLHQVVETSHEDLPASQERSEVNPARMGPSVGSQQELRAPCLPVTYQQTPVNMEKNPREAPPVVPPLANAISAALVSPATSQSIAPPVPLKAQTVTDSMFAVASKDAGCVNKSTHEFKPQSGAEIKEGCETHKVANTSSFHTTPNTSLGMVQATPSKVQPSPTVHTKEALGFIMNMFQAPTLPDISDDKDEWQSLDQNEDAFEAQFQKNVRSSGAWGVNKIISSLSSAFHVFEDGNKENYGLPQPKNKPTGARTFGERSVSRLPSKPKEEVPHAEEFLDDSTVWGIRCNKTLAPSPKSPGDFTSAAQLASTPFHKLPVESVHILEDKENVVAKQCTQATLDSCEENMVVPSRDGKFSPIQEKSPKQALSSHMYSASLLRLSQPAAGGVLTCEAELGVEACRLTDTDAAIAEDPPDAIAGLQAEWMQMSSLGTVDAPNFIVGNPWDDKLIFKLLSGLSKPVSSYPNTFEWQCKLPAIKPKTEFQLGSKLVYVHHLLGEGAFAQVYEATQGDLNDAKNKQKFVLKVQKPANPWEFYIGTQLMERLKPSMQHMFMKFYSAHLFQNGSVLVGELYSYGTLLNAINLYKNTPEKVMPQGLVISFAMRMLYMIEQVHDCEIIHGDIKPDNFILGNGFLEQDDEDDLSAGLALIDLGQSIDMKLFPKGTIFTAKCETSGFQCVEMLSNKPWNYQIDYFGVAATVYCMLFGTYMKVKNEGGECKPEGLFRRLPHLDMWNEFFHVMLNIPDCHHLPSLDLLRQKLKKVFQQHYTNKIRALRNRLIVLLLECKRSRK
InterPro domains: - IPR011009: Protein kinase-like domain superfamily (homologous_superfamily) [789-1061]
- IPR008271: Serine/threonine-protein kinase, active site (active_site) [913-925]
- IPR013212: Mad3/Bub1 homology region 1 (domain) [4-182]
- IPR015661: Mitotic spindle checkpoint protein Bub1/Mad3 (family) [10-1068]
- IPR017441: Protein kinase, ATP binding site (binding_site) [793-821]
- IPR000719: Protein kinase domain (domain) [787-1085]
Interaction partners: - Mitotic checkpoint serine/threonine-protein kinase BUB1 beta
- Dual specificity protein kinase TTK
- Cell division cycle protein 20 homolog
- Outer kinetochore KNL1 complex subunit KNL1
- Mitotic checkpoint protein BUB3
- Mitotic spindle assembly checkpoint protein MAD2A
- Kinetochore protein NDC80 homolog
- Mitotic spindle assembly checkpoint protein MAD1
- G2/mitotic-specific cyclin-B2
- Cyclin-dependent kinase 1
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0016740 (transferase activity), GO:0140096 (catalytic activity, acting on a protein), GO:0005515 (protein binding), GO:0004672 (protein kinase activity), GO:0016772 (transferase activity, transferring phosphorus-containing groups), GO:0016773 (phosphotransferase activity, alcohol group as acceptor), GO:0016301 (kinase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0051179 (localization), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0023052 (signaling), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0009987 (cellular process), GO:0051641 (cellular localization), GO:0022402 (cell cycle process), GO:0006807 (nitrogen compound metabolic process), GO:0007049 (cell cycle), GO:0051234 (establishment of localization), GO:0071840 (cellular component organization or biogenesis), GO:0071704 (organic substance metabolic process), GO:0033036 (macromolecule localization), GO:0044237 (cellular metabolic process), GO:0050794 (regulation of cellular process), GO:0051716 (cellular response to stimulus), GO:0007154 (cell communication), GO:0007165 (signal transduction), GO:0044238 (primary metabolic process), GO:0048522 (positive regulation of cellular process), GO:1901564 (organonitrogen compound metabolic process), GO:1903047 (mitotic cell cycle process), GO:0051129 (negative regulation of cellular component organization), GO:0035556 (intracellular signal transduction), GO:0019538 (protein metabolic process), GO:0051649 (establishment of localization in cell), GO:0010948 (negative regulation of cell cycle process), GO:0043170 (macromolecule metabolic process), GO:0045184 (establishment of protein localization), GO:0051726 (regulation of cell cycle), GO:0007059 (chromosome segregation), GO:0046907 (intracellular transport), GO:0006810 (transport), GO:0070727 (cellular macromolecule localization), GO:0016043 (cellular component organization), GO:0045786 (negative regulation of cell cycle), GO:0051128 (regulation of cellular component organization), GO:0010564 (regulation of cell cycle process), GO:0000278 (mitotic cell cycle), GO:0098813 (nuclear chromosome segregation), GO:0007346 (regulation of mitotic cell cycle), GO:0007088 (regulation of mitotic nuclear division), GO:0000075 (cell cycle checkpoint signaling), GO:0045839 (negative regulation of mitotic nuclear division), GO:0072594 (establishment of protein localization to organelle), GO:0140014 (mitotic nuclear division), GO:1905818 (regulation of chromosome separation), GO:0007093 (mitotic cell cycle checkpoint signaling), GO:0036211 (protein modification process), GO:0010639 (negative regulation of organelle organization), GO:0051983 (regulation of chromosome segregation), GO:0043412 (macromolecule modification), GO:1901987 (regulation of cell cycle phase transition), GO:0045930 (negative regulation of mitotic cell cycle), GO:1905819 (negative regulation of chromosome separation), GO:0033043 (regulation of organelle organization), GO:0008104 (protein localization), GO:0051985 (negative regulation of chromosome segregation), GO:0006996 (organelle organization), GO:0000070 (mitotic sister chromatid segregation), GO:1901988 (negative regulation of cell cycle phase transition), GO:0051783 (regulation of nuclear division), GO:0033365 (protein localization to organelle), GO:0051784 (negative regulation of nuclear division), GO:0010965 (regulation of mitotic sister chromatid separation), GO:0033045 (regulation of sister chromatid segregation), GO:1901991 (negative regulation of mitotic cell cycle phase transition), GO:2000816 (negative regulation of mitotic sister chromatid separation), GO:0033046 (negative regulation of sister chromatid segregation), GO:0070647 (protein modification by small protein conjugation or removal), GO:0048285 (organelle fission), GO:0051276 (chromosome organization), GO:1902099 (regulation of metaphase/anaphase transition of cell cycle), GO:0033048 (negative regulation of mitotic sister chromatid segregation), GO:0031577 (spindle checkpoint signaling), GO:0045841 (negative regulation of mitotic metaphase/anaphase transition), GO:0033047 (regulation of mitotic sister chromatid segregation), GO:1901990 (regulation of mitotic cell cycle phase transition), GO:0000819 (sister chromatid segregation), GO:1902100 (negative regulation of metaphase/anaphase transition of cell cycle), GO:2001251 (negative regulation of chromosome organization), GO:0033044 (regulation of chromosome organization), GO:0071174 (mitotic spindle checkpoint signaling), GO:0034502 (protein localization to chromosome), GO:0000280 (nuclear division), GO:0007094 (mitotic spindle assembly checkpoint signaling), GO:0071173 (spindle assembly checkpoint signaling), GO:0030071 (regulation of mitotic metaphase/anaphase transition), GO:0032446 (protein modification by small protein conjugation), GO:0071459 (protein localization to chromosome, centromeric region), GO:1903083 (protein localization to condensed chromosome), GO:0034501 (protein localization to kinetochore)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0031974 (membrane-enclosed lumen), GO:0005654 (nucleoplasm), GO:0043229 (intracellular organelle), GO:0043233 (organelle lumen), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0070013 (intracellular organelle lumen), GO:0031981 (nuclear lumen), GO:0005634 (nucleus)