ID:BUB1B_HUMAN DESCRIPTION: RecName: Full=Mitotic checkpoint serine/threonine-protein kinase BUB1 beta; EC=2.7.11.1; AltName: Full=MAD3/BUB1-related protein kinase; Short=hBUBR1; AltName: Full=Mitotic checkpoint kinase MAD3L; AltName: Full=Protein 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. 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. May play a role for tumor suppression. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. ENZYME REGULATION: Kinase activity stimulated by CENPE. SUBUNIT: 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. INTERACTION: Q12834:CDC20; NbExp=8; IntAct=EBI-1001438, EBI-367462; Q02224:CENPE; NbExp=4; IntAct=EBI-1001438, EBI-1375040; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Chromosome, centromere, kinetochore. Cytoplasm, cytoskeleton, centrosome. Note=Cytoplasmic in interphase cells. Associates with the kinetochores in early prophase. Kinetochore localization requires BUB1, PLK1 and CASC5. TISSUE SPECIFICITY: Highly expressed in thymus followed by spleen. Preferentially expressed in tissues with a high mitotic index. INDUCTION: Induced during mitosis. DOMAIN: The D-box targets the protein for rapid degradation by ubiquitin-dependent proteolysis during the transition from mitosis to interphase (Potential). DOMAIN: The BUB1 N-terminal domain directs kinetochore localization and binding to BUB3. PTM: Proteolytically cleaved by caspase-3 in a cell cycle specific manner. The 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. PTM: Acetylation at Lys-250 regulates its degradation and timing in anaphase entry. PTM: Ubiquitinated. Degradated by the proteasome. PTM: Sumoylated with SUMO2 and SUMO3. The sumoylation mediates the association with CENPE at the kinetochore. PTM: Autophosphorylated in vitro. Intramolecular autophosphorylation is stimulated by CENPE. Phosphorylated during mitosis and hyperphosphorylated in mitotically arrested cells. Phosphorylation at Ser-670 and Ser-1043 occurs at kinetochores upon mitotic entry with dephosphorylation at the onset of anaphase. DISEASE: Note=Defects in BUB1B are associated with tumor formation. DISEASE: Defects in BUB1B are the cause of premature chromatid separation trait (PCS) [MIM:176430]. PCS consists of separate and splayed chromatids with discernible centromeres and involves all or most chromosomes of a metaphase. It is found in up to 2% of metaphases in cultured lymphocytes from approximately 40% of normal individuals. When PCS is present in 5% or more of cells, it is known as the heterozygous PCS trait and has no obvious phenotypic effect, although some have reported decreased fertility. Inheritance is autosomal dominant. DISEASE: Defects in BUB1B are the cause of mosaic variegated aneuploidy syndrome type 1 (MVA1) [MIM:257300]. A severe autosomal recessive developmental disorder characterized by mosaic aneuploidies, predominantly trisomies and monosomies, involving multiple different chromosomes and tissues. The proportion of aneuploid cells varies but is usually more than 25% and is substantially greater than in normal individuals. Affected individuals typically present with severe intrauterine growth retardation and microcephaly. Eye anomalies, mild dysmorphism, variable developmental delay, and a broad spectrum of additional congenital abnormalities and medical conditions may also occur. The risk of malignancy is high, with rhabdomyosarcoma, Wilms tumor and leukemia reported in several cases. Note=MVA1 is caused by biallelic mutations in the BUB1B gene. SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. BUB1 subfamily. SIMILARITY: Contains 1 BUB1 N-terminal domain. SIMILARITY: Contains 1 protein kinase domain. SEQUENCE CAUTION: Sequence=BAD92019.1; Type=Erroneous initiation; WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/BUB1BID854ch15q15.html";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on O60566
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
AF053306 - Homo sapiens mitotic checkpoint kinase Mad3L (MAD3L) mRNA, complete cds. AK312709 - Homo sapiens cDNA, FLJ93109, highly similar to Homo sapiens BUB1 budding uninhibited by benzimidazoles 1 homologbeta (yeast) (BUB1B), mRNA. AK296795 - Homo sapiens cDNA FLJ55899 complete cds, moderately similar to Mitotic checkpoint serine/threonine-proteinkinase BUB1 beta (EC 2.7.11.1). AK296984 - Homo sapiens cDNA FLJ51891 complete cds, highly similar to Mitotic checkpoint serine/threonine-proteinkinase BUB1 beta (EC 2.7.11.1). AF107297 - Homo sapiens mitotic checkpoint protein kinase BUB1B (BUB1B) mRNA, complete cds. BC018739 - Homo sapiens budding uninhibited by benzimidazoles 1 homolog beta (yeast), mRNA (cDNA clone MGC:31884 IMAGE:4649881), complete cds. AF046918 - Homo sapiens mitotic checkpoint protein kinase Bub1A mRNA, complete cds. AB208782 - Homo sapiens mRNA for Mitotic checkpoint serine/threonine-protein kinase BUB1 beta variant protein. AF035933 - Homo sapiens protein kinase mRNA, complete cds. AF068760 - Homo sapiens MAD3-like protein kinase mRNA, complete cds. AF046079 - Homo sapiens similar to protein kinase (BUBR1) mRNA, complete cds. AB384719 - Synthetic construct DNA, clone: pF1KB3004, Homo sapiens BUB1B gene for mitotic checkpoint serine/threonine-protein kinase BUB1 beta, complete cds, without stop codon, in Flexi system. JF432304 - Synthetic construct Homo sapiens clone IMAGE:100073486 budding uninhibited by benzimidazoles 1 homolog beta (yeast) (BUB1B) gene, encodes complete protein. KJ896513 - Synthetic construct Homo sapiens clone ccsbBroadEn_05907 BUB1B gene, encodes complete protein. KJ905152 - Synthetic construct Homo sapiens clone ccsbBroadEn_14556 BUB1B gene, encodes complete protein. KR710587 - Synthetic construct Homo sapiens clone CCSBHm_00014158 BUB1B (BUB1B) mRNA, encodes complete protein. KR710588 - Synthetic construct Homo sapiens clone CCSBHm_00014161 BUB1B (BUB1B) mRNA, encodes complete protein. KR710589 - Synthetic construct Homo sapiens clone CCSBHm_00014162 BUB1B (BUB1B) mRNA, encodes complete protein. KR710590 - Synthetic construct Homo sapiens clone CCSBHm_00014166 BUB1B (BUB1B) mRNA, encodes complete protein. JD180697 - Sequence 161721 from Patent EP1572962. JD282279 - Sequence 263303 from Patent EP1572962. JD487877 - Sequence 468901 from Patent EP1572962. JD462179 - Sequence 443203 from Patent EP1572962. JD044981 - Sequence 26005 from Patent EP1572962. JD339207 - Sequence 320231 from Patent EP1572962. CU676304 - Synthetic construct Homo sapiens gateway clone IMAGE:100020495 5' read BUB1B mRNA. AK315817 - Homo sapiens cDNA, FLJ79466 complete cds, highly similar to Serine/threonine-protein kinase PAK 6 (EC2.7.11.1). AK315813 - Homo sapiens cDNA, FLJ79462 complete cds, highly similar to Serine/threonine-protein kinase PAK 6 (EC2.7.11.1). AK290227 - Homo sapiens cDNA FLJ75021 complete cds, highly similar to Homo sapiens p21(CDKN1A)-activated kinase 6 (PAK6), mRNA. JD047101 - Sequence 28125 from Patent EP1572962. JD137607 - Sequence 118631 from Patent EP1572962. JD332808 - Sequence 313832 from Patent EP1572962. JD061967 - Sequence 42991 from Patent EP1572962.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein O60566 (Reactome details) participates in the following event(s):
R-HSA-141437 Formation of the MCC complex R-HSA-141423 Binding of the MCC complex to the APC/C complex R-HSA-174238 Activation of APC/C:Cdc20 by dissociation of Cdc20:phospho-APC/C from Cdc20:phospho-APC/C:Mad2:Bub3:BubR1 R-HSA-174171 Association of Cyclin A with the APC/C R-HSA-179410 Association of Nek2A with MCC:APC/C R-HSA-141409 Mad1 binds kinetochore R-HSA-375302 Kinetochore capture of astral microtubules R-HSA-5666129 CDC42:GTP recruits DIAPH2-2 to kinetochores R-HSA-5666169 Kinetochore capture of astral microtubules is positively regulated by CDC42:GTP:p-S196-DIAPH2-2 R-HSA-174104 Ubiquitination of Cyclin A by APC/C:Cdc20 complex R-HSA-179417 Multiubiquitination of Nek2A R-HSA-141431 MAD2 associates with the Mad1 kinetochore complex R-HSA-141439 Release of activated MAD2 from kinetochores R-HSA-2467811 Separation of sister chromatids R-HSA-2467809 ESPL1 (Separase) cleaves centromeric cohesin R-HSA-5666160 AURKB phosphorylates DIAPH2-2 at kinetochores R-HSA-141422 MAD2 converted to an inhibitory state via interaction with Mad1 R-HSA-1638821 PP2A-B56 dephosphorylates centromeric cohesin R-HSA-1638803 Phosphorylation of cohesin by PLK1 at centromeres R-HSA-2468287 CDK1 phosphorylates CDCA5 (Sororin) at centromeres R-HSA-141430 Inactivation of APC/C via direct inhibition of the APC/C complex R-HSA-176409 APC/C:Cdc20 mediated degradation of mitotic proteins R-HSA-141405 Inhibition of the proteolytic activity of APC/C required for the onset of anaphase by mitotic spindle checkpoint components R-HSA-174184 Cdc20:Phospho-APC/C mediated degradation of Cyclin A R-HSA-179409 APC-Cdc20 mediated degradation of Nek2A R-HSA-176814 Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins R-HSA-141444 Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal R-HSA-68877 Mitotic Prometaphase R-HSA-5663220 RHO GTPases Activate Formins R-HSA-69618 Mitotic Spindle Checkpoint R-HSA-176408 Regulation of APC/C activators between G1/S and early anaphase R-HSA-179419 APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint R-HSA-174143 APC/C-mediated degradation of cell cycle proteins R-HSA-2500257 Resolution of Sister Chromatid Cohesion R-HSA-2467813 Separation of Sister Chromatids R-HSA-141424 Amplification of signal from the kinetochores R-HSA-68886 M Phase R-HSA-195258 RHO GTPase Effectors R-HSA-69620 Cell Cycle Checkpoints R-HSA-453276 Regulation of mitotic cell cycle R-HSA-68882 Mitotic Anaphase R-HSA-69278 Cell Cycle (Mitotic) R-HSA-194315 Signaling by Rho GTPases R-HSA-1640170 Cell Cycle R-HSA-2555396 Mitotic Metaphase and Anaphase R-HSA-162582 Signal Transduction
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
