ID BUB1B_MOUSE Reviewed; 1052 AA. AC Q9Z1S0; A2ARS1; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 27-JUL-2011, sequence version 2. DT 30-AUG-2017, entry version 150. DE RecName: Full=Mitotic checkpoint serine/threonine-protein kinase BUB1 beta; DE EC=2.7.11.1; DE AltName: Full=MAD3/BUB1-related protein kinase; DE Short=BubR1; DE AltName: Full=Mitotic checkpoint kinase MAD3L; GN Name=Bub1b; Synonyms=Mad3l; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; OC Muroidea; Muridae; Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=NIH Swiss; TISSUE=Embryo; RX PubMed=9889005; DOI=10.1006/geno.1998.5629; RA Davenport J.W., Fernandes E.R., Harris L.D., Neale G.A.M., Goorha R.; RT "The mouse mitotic checkpoint gene bub1b, a novel bub1 family member, RT is expressed in a cell cycle-dependent manner."; RL Genomics 55:113-117(1999). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., RA She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., RA Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., RA Zhou S., Teague B., Potamousis K., Churas C., Place M., Herschleb J., RA Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., RA Lindblad-Toh K., Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of RT the mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [3] RP ENZYME REGULATION, INTERACTION WITH CENPE, AND SUBCELLULAR LOCATION. RX PubMed=12925705; DOI=10.1083/jcb.200303167; RA Weaver B.A., Bonday Z.Q., Putkey F.R., Kops G.J., Silk A.D., RA Cleveland D.W.; RT "Centromere-associated protein-E is essential for the mammalian RT mitotic checkpoint to prevent aneuploidy due to single chromosome RT loss."; RL J. Cell Biol. 162:551-563(2003). RN [4] RP FUNCTION. RX PubMed=14744753; DOI=10.1158/0008-5472.CAN-03-3119; RA Dai W., Wang Q., Liu T., Swamy M., Fang Y., Xie S., Mahmood R., RA Yang Y.M., Xu M., Rao C.V.; RT "Slippage of mitotic arrest and enhanced tumor development in mice RT with BubR1 haploinsufficiency."; RL Cancer Res. 64:440-445(2004). RN [5] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=15208629; DOI=10.1038/ng1382; RA Baker D.J., Jeganathan K.B., Cameron J.D., Thompson M., Juneja S., RA Kopecka A., Kumar R., Jenkins R.B., de Groen P.C., Roche P., RA van Deursen J.M.; RT "BubR1 insufficiency causes early onset of aging-associated phenotypes RT and infertility in mice."; RL Nat. Genet. 36:744-749(2004). RN [6] RP SUBCELLULAR LOCATION. RX PubMed=17925231; DOI=10.1016/j.devcel.2007.08.008; RA Perera D., Tilston V., Hopwood J.A., Barchi M., Boot-Handford R.P., RA Taylor S.S.; RT "Bub1 maintains centromeric cohesion by activation of the spindle RT checkpoint."; RL Dev. Cell 13:566-579(2007). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1050, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and RT expression."; RL Cell 143:1174-1189(2010). CC -!- FUNCTION: Essential component of the mitotic checkpoint. Required CC for normal mitosis progression and tumor suppression. The mitotic CC checkpoint delays anaphase until all chromosomes are properly CC attached to the mitotic spindle. One of its checkpoint functions CC is to inhibit the activity of the anaphase-promoting CC complex/cyclosome (APC/C) by blocking the binding of CDC20 to CC APC/C, independently of its kinase activity. The other is to CC monitor kinetochore activities that depend on the kinetochore CC motor CENPE. Required for kinetochore localization of CENPE. CC Negatively regulates PLK1 activity in interphase cells and CC suppresses centrosome amplification. Also implicated in triggering CC apoptosis in polyploid cells that exit aberrantly from mitotic CC arrest. Essential for tumor suppression. May play a role in CC regulating aging and fertility (By similarity). {ECO:0000250, CC ECO:0000269|PubMed:14744753, ECO:0000269|PubMed:15208629}. CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CC -!- ENZYME REGULATION: Kinase activity stimulated by CENPE. CC {ECO:0000269|PubMed:12925705}. CC -!- SUBUNIT: Interacts with CENPE, CENPF, mitosin, PLK1 and BUB3. Part CC of a complex containing BUB3, CDC20 and BUB1B. Interacts with CC anaphase-promoting complex/cyclosome (APC/C). Interacts with KNL1 CC (By similarity). {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus CC {ECO:0000250}. Chromosome, centromere, kinetochore CC {ECO:0000269|PubMed:12925705, ECO:0000269|PubMed:17925231}. CC Note=Cytoplasmic in interphase cells (By similarity). Associates CC with the kinetochores in early prophase. Kinetochore localization CC requires BUB1, PLK1 and KNL1 (By similarity). {ECO:0000250}. CC -!- TISSUE SPECIFICITY: Highly expressed in thymus followed by spleen. CC -!- DOMAIN: The D-box targets the protein for rapid degradation by CC ubiquitin-dependent proteolysis during the transition from mitosis CC to interphase. {ECO:0000305}. CC -!- DOMAIN: The BUB1 N-terminal domain directs kinetochore CC localization and binding to BUB3. CC -!- PTM: Proteolytically cleaved by caspase-3 in a cell cycle specific CC manner. The cleavage might be involved in the durability of the CC cell cycle delay. {ECO:0000250}. CC -!- PTM: Acetylation at Lys-243 regulates its degradation and timing CC in anaphase entry. {ECO:0000250}. CC -!- PTM: Ubiquitinated. Degraded by the proteasome (By similarity). CC {ECO:0000250}. CC -!- PTM: Sumoylated with SUMO2 and SUMO3. The sumoylation mediates the CC association with CENPE at the kinetochore (By similarity). CC {ECO:0000250}. CC -!- PTM: Autophosphorylated in vitro. Intramolecular CC autophosphorylation stimulated by CENPE. Phosphorylated during CC mitosis and hyperphosphorylated in mitotically arrested cells. CC Phosphorylation at Ser-659 and Ser-1033 occurs at kinetochores CC upon mitotic entry with dephosphorylation at the onset of CC anaphase. {ECO:0000250}. CC -!- DISEASE: Note=Defects in Bub1b are involved in the development of CC lung and intestinal adenocarcinomas after exposure to a CC carcinogen. CC -!- DISRUPTION PHENOTYPE: Mice die in utero. CC {ECO:0000269|PubMed:15208629}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr CC protein kinase family. BUB1 subfamily. {ECO:0000255|PROSITE- CC ProRule:PRU00159}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF107296; AAD11940.1; -; mRNA. DR EMBL; AL845470; CAM17418.1; -; Genomic_DNA. DR EMBL; AL929381; CAM17418.1; JOINED; Genomic_DNA. DR EMBL; AL929381; CAM19078.1; -; Genomic_DNA. DR EMBL; AL845470; CAM19078.1; JOINED; Genomic_DNA. DR CCDS; CCDS16579.1; -. DR RefSeq; NP_033903.2; NM_009773.3. DR UniGene; Mm.29133; -. DR ProteinModelPortal; Q9Z1S0; -. DR SMR; Q9Z1S0; -. DR BioGrid; 198405; 50. DR IntAct; Q9Z1S0; 47. DR STRING; 10090.ENSMUSP00000037126; -. DR iPTMnet; Q9Z1S0; -. DR PhosphoSitePlus; Q9Z1S0; -. DR EPD; Q9Z1S0; -. DR MaxQB; Q9Z1S0; -. DR PaxDb; Q9Z1S0; -. DR PeptideAtlas; Q9Z1S0; -. DR PRIDE; Q9Z1S0; -. DR Ensembl; ENSMUST00000038341; ENSMUSP00000037126; ENSMUSG00000040084. DR GeneID; 12236; -. DR KEGG; mmu:12236; -. DR UCSC; uc008lse.2; mouse. DR CTD; 701; -. DR MGI; MGI:1333889; Bub1b. DR eggNOG; ENOG410IQA2; Eukaryota. DR eggNOG; ENOG410XUW7; LUCA. DR GeneTree; ENSGT00520000055622; -. DR HOGENOM; HOG000231849; -. DR HOVERGEN; HBG050748; -. DR InParanoid; Q9Z1S0; -. DR KO; K06637; -. DR OMA; ATHSSGF; -. DR OrthoDB; EOG091G01MC; -. DR TreeFam; TF105456; -. DR BRENDA; 2.7.11.1; 3474. DR Reactome; R-MMU-141430; Inactivation of APC/C via direct inhibition of the APC/C complex. DR Reactome; R-MMU-174184; Cdc20:Phospho-APC/C mediated degradation of Cyclin A. DR Reactome; R-MMU-176409; APC/C:Cdc20 mediated degradation of mitotic proteins. DR Reactome; R-MMU-179409; APC-Cdc20 mediated degradation of Nek2A. DR Reactome; R-MMU-2467813; Separation of Sister Chromatids. DR Reactome; R-MMU-2500257; Resolution of Sister Chromatid Cohesion. DR Reactome; R-MMU-5663220; RHO GTPases Activate Formins. DR Reactome; R-MMU-68877; Mitotic Prometaphase. DR ChiTaRS; Bub1b; mouse. DR PRO; PR:Q9Z1S0; -. DR Proteomes; UP000000589; Chromosome 2. DR Bgee; ENSMUSG00000040084; -. DR Genevisible; Q9Z1S0; MM. DR GO; GO:0000777; C:condensed chromosome kinetochore; ISO:MGI. DR GO; GO:0000940; C:condensed chromosome outer kinetochore; IDA:MGI. DR GO; GO:0000778; C:condensed nuclear chromosome kinetochore; IDA:MGI. DR GO; GO:0005737; C:cytoplasm; ISO:MGI. DR GO; GO:0005829; C:cytosol; ISO:MGI. DR GO; GO:0000776; C:kinetochore; IDA:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004672; F:protein kinase activity; IBA:GO_Central. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0051754; P:meiotic sister chromatid cohesion, centromeric; IBA:GO_Central. DR GO; GO:0007091; P:metaphase/anaphase transition of mitotic cell cycle; IGI:MGI. DR GO; GO:0007094; P:mitotic spindle assembly checkpoint; IBA:GO_Central. DR GO; GO:0071459; P:protein localization to chromosome, centromeric region; IMP:MGI. DR GO; GO:0034501; P:protein localization to kinetochore; ISO:MGI. DR Gene3D; 1.25.40.10; -; 1. DR InterPro; IPR015661; Bub1/Mad3. DR InterPro; IPR011009; Kinase-like_dom. DR InterPro; IPR013212; Mad3/Bub1_I. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR011990; TPR-like_helical_dom. DR PANTHER; PTHR14030; PTHR14030; 1. DR Pfam; PF08311; Mad3_BUB1_I; 1. DR SMART; SM00777; Mad3_BUB1_I; 1. DR SUPFAM; SSF56112; SSF56112; 1. DR PROSITE; PS51489; BUB1_N; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. PE 1: Evidence at protein level; KW Acetylation; Apoptosis; ATP-binding; Cell cycle; Cell division; KW Centromere; Chromosome; Complete proteome; Cytoplasm; Kinase; KW Kinetochore; Mitosis; Nucleotide-binding; Nucleus; Phosphoprotein; KW Reference proteome; Serine/threonine-protein kinase; Transferase; KW Tumor suppressor; Ubl conjugation. FT CHAIN 1 1052 Mitotic checkpoint serine/threonine- FT protein kinase BUB1 beta. FT /FTId=PRO_0000085674. FT DOMAIN 56 219 BUB1 N-terminal. {ECO:0000255|PROSITE- FT ProRule:PRU00822}. FT DOMAIN 756 1040 Protein kinase. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT NP_BIND 762 770 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT REGION 146 179 Necessary for interaction with KNL1. FT {ECO:0000250}. FT MOTIF 105 112 Nuclear localization signal. FT {ECO:0000255}. FT MOTIF 217 225 D-box. FT COMPBIAS 205 208 Poly-Glu. FT COMPBIAS 675 680 Poly-Ser. FT ACT_SITE 871 871 Proton acceptor. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT BINDING 784 784 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT SITE 572 573 Cleavage; by caspase-3. {ECO:0000250}. FT SITE 603 604 Cleavage; by caspase-3. {ECO:0000250}. FT MOD_RES 243 243 N6-acetyllysine; by PCAF. FT {ECO:0000250|UniProtKB:O60566}. FT MOD_RES 360 360 Phosphoserine. FT {ECO:0000250|UniProtKB:O60566}. FT MOD_RES 428 428 Phosphoserine. FT {ECO:0000250|UniProtKB:O60566}. FT MOD_RES 535 535 Phosphoserine. FT {ECO:0000250|UniProtKB:O60566}. FT MOD_RES 659 659 Phosphoserine. FT {ECO:0000250|UniProtKB:O60566}. FT MOD_RES 665 665 Phosphoserine; by PLK1. FT {ECO:0000250|UniProtKB:O60566}. FT MOD_RES 686 686 Phosphoserine. FT {ECO:0000250|UniProtKB:O60566}. FT MOD_RES 781 781 Phosphothreonine; by PLK1. FT {ECO:0000250|UniProtKB:O60566}. FT MOD_RES 998 998 Phosphothreonine; by PLK1. FT {ECO:0000250|UniProtKB:O60566}. FT MOD_RES 1033 1033 Phosphoserine. FT {ECO:0000250|UniProtKB:O60566}. FT MOD_RES 1050 1050 Phosphoserine. FT {ECO:0000244|PubMed:21183079}. FT CONFLICT 275 275 A -> T (in Ref. 1; AAD11940). FT {ECO:0000305}. FT CONFLICT 278 278 T -> P (in Ref. 1; AAD11940). FT {ECO:0000305}. FT CONFLICT 664 664 E -> D (in Ref. 1; AAD11940). FT {ECO:0000305}. FT CONFLICT 705 705 D -> N (in Ref. 1; AAD11940). FT {ECO:0000305}. SQ SEQUENCE 1052 AA; 118392 MW; 9EF1ECF3735DD1F4 CRC64; MAEASEAMCL EGAEWELSKE NIQPLRHGRV MSTLQGALAK QESAGHTALQ QQKRAFESEI RFYSGDDPLD VWDRYINWTE QNYPQGGKES NMSALVERAI EALQGETRYY NDPRFLSLWI KLGHLCNEPL DMYSYLQSQG IGVSLAQFYI SWAEEYEARE NFKKADIIFQ EGIERKAEPL DRLQSQHRQF QSRVSRQAFL ALGNEEEEAL EPSEPQRSSL AELKSRGKKM ARAPISRVGG ALKAPGQSRG FLNAVPQPVH GNRRITVFDE NADTASRTEL SKPVAQPWMA PPVPRAKENE LQPGPWSTDR PAGRRPHDNP ASVTSIPSVL PSFTPYVEES AQQTVMTPCK IEPSINHVLS TRKPGREEGD PLQRVQSHQQ GCEEKKEKMM YCKEKIYAGV GEFSFEEIRA EVFRKKLKER REAELLTSAK KREEMQKQIE EMERRLKAMQ AVQQEGAGGQ QEEKMPTEDP ARLQIASGPQ EMSGVPLSCS ICPLSSNPRE ISPAENILQE QPDSKGSSMP FSIFDESLSD KKDKSPATGG PQVLNAQRRP LSVLKTTEVG TTNEDVSPDI CDELTELEPL SEDAIITGFR NVTLCPNPED TCDFARAARL ASTPFHEILS SKGIAADPEG LLQEEDLDGK AAEAHHTVHH QALIIKKLSP IIEESREATH SSGFSRSSSS APSTSSIKGF QLLEKLELTN DGAEDAIQSP WCSQYRLQLL KSLLELSAFA EFSVEDRPMP VLEIGKEIEL GPEDYVIKQE HLTCDDYRLF WVAPRSSAEL TMIKASSQPI PWDFYINLKL KERLNEDYDQ LCSCCQYQDG HVVWYQYINC STLQNLLQHS EFVTHEIIVL IIYNLLTIVE KLHRAEIVHG DLSPRSLILR NRIHDPYDYV NKDDHAVRIM DFSYSVDLRV QLDAFAYSGF RTAQILEGQK ILANCSSPYH VDLLGIADLA HLLLFKEHLH VFWDGLLWKL SQSTSELKDS ELWNKFFVRI LNASDKSTVS VLGELAAEMG GAFDATFHSH LNRALWKLGK TISPEALLTQ QDKQPGGSQS PA //