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 25-MAY-2022, entry version 176. 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; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC 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, is RT 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., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [3] RP ACTIVITY 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 mitotic RT checkpoint to prevent aneuploidy due to single chromosome 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., Yang Y.M., RA Xu M., Rao C.V.; RT "Slippage of mitotic arrest and enhanced tumor development in mice with RT 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 and RT 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 BY RP 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 expression."; RL Cell 143:1174-1189(2010). CC -!- FUNCTION: Essential component of the mitotic checkpoint. Required for CC normal mitosis progression and tumor suppression. The mitotic CC checkpoint delays anaphase until all chromosomes are properly attached CC to the mitotic spindle. One of its checkpoint functions is to inhibit CC the activity of the anaphase-promoting complex/cyclosome (APC/C) by CC blocking the binding of CDC20 to APC/C, independently of its kinase CC activity. The other is to monitor kinetochore activities that depend on CC the kinetochore motor CENPE. Required for kinetochore localization of CC CENPE. 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 arrest. CC Essential for tumor suppression. May play a role in regulating aging CC and fertility (By similarity). {ECO:0000250, CC ECO:0000269|PubMed:14744753, ECO:0000269|PubMed:15208629}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; CC EC=2.7.11.1; CC -!- ACTIVITY REGULATION: Kinase activity stimulated by CENPE. CC {ECO:0000269|PubMed:12925705}. CC -!- SUBUNIT: Interacts with CENPE (PubMed:12925705). Interacts with PLK1 CC (By similarity). Part of a complex containing BUB3, CDC20 and BUB1B (By CC similarity). Interacts with anaphase-promoting complex/cyclosome CC (APC/C) (By similarity). Interacts with KNL1 (By similarity). Interacts CC with KAT2B (By similarity). Interacts with RIPK3 (By similarity). CC Interacts with the closed conformation form of MAD2L1 (By similarity). CC {ECO:0000250|UniProtKB:O60566, ECO:0000269|PubMed:12925705}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}. CC Chromosome, centromere, kinetochore {ECO:0000269|PubMed:12925705, CC ECO:0000269|PubMed:17925231}. Note=Cytoplasmic in interphase cells (By CC similarity). Associates with the kinetochores in early prophase. CC Kinetochore localization requires BUB1, PLK1 and KNL1 (By similarity). CC {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 to CC interphase. {ECO:0000305}. CC -!- DOMAIN: The BUB1 N-terminal domain directs kinetochore localization and CC 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 cell CC cycle delay. {ECO:0000250}. CC -!- PTM: Acetylation at Lys-243 regulates its degradation and timing in CC 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 autophosphorylation CC stimulated by CENPE. Phosphorylated during mitosis and CC hyperphosphorylated in mitotically arrested cells. Phosphorylation at CC Ser-659 and Ser-1033 occurs at kinetochores upon mitotic entry with CC dephosphorylation at the onset of anaphase. {ECO:0000250}. CC -!- DISEASE: Note=Defects in Bub1b are involved in the development of lung CC and intestinal adenocarcinomas after exposure to a carcinogen. CC -!- DISRUPTION PHENOTYPE: Mice die in utero. {ECO:0000269|PubMed:15208629}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein CC kinase family. BUB1 subfamily. {ECO:0000255|PROSITE-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; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL929381; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS16579.1; -. DR RefSeq; NP_033903.2; NM_009773.3. DR AlphaFoldDB; Q9Z1S0; -. DR SMR; Q9Z1S0; -. DR BioGRID; 198405; 62. DR ComplexPortal; CPX-3968; Mitotic Checkpoint Complex. DR IntAct; Q9Z1S0; 47. DR STRING; 10090.ENSMUSP00000037126; -. DR iPTMnet; Q9Z1S0; -. DR PhosphoSitePlus; Q9Z1S0; -. DR EPD; Q9Z1S0; -. DR jPOST; Q9Z1S0; -. DR MaxQB; Q9Z1S0; -. DR PaxDb; Q9Z1S0; -. DR PeptideAtlas; Q9Z1S0; -. DR PRIDE; Q9Z1S0; -. DR ProteomicsDB; 265320; -. DR Antibodypedia; 1214; 708 antibodies from 41 providers. DR DNASU; 12236; -. 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 VEuPathDB; HostDB:ENSMUSG00000040084; -. DR eggNOG; KOG1166; Eukaryota. DR GeneTree; ENSGT00940000158912; -. DR HOGENOM; CLU_010890_0_0_1; -. DR InParanoid; Q9Z1S0; -. DR OMA; CAKETSL; -. DR OrthoDB; 1411806at2759; -. DR PhylomeDB; Q9Z1S0; -. 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-141444; Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal. 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 Reactome; R-MMU-9648025; EML4 and NUDC in mitotic spindle formation. DR BioGRID-ORCS; 12236; 25 hits in 76 CRISPR screens. DR ChiTaRS; Bub1b; mouse. DR PRO; PR:Q9Z1S0; -. DR Proteomes; UP000000589; Chromosome 2. DR RNAct; Q9Z1S0; protein. DR Bgee; ENSMUSG00000040084; Expressed in secondary oocyte and 257 other tissues. DR Genevisible; Q9Z1S0; MM. 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:0033597; C:mitotic checkpoint complex; ISO:MGI. DR GO; GO:0000940; C:outer kinetochore; IDA:MGI. DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI. DR GO; GO:0005819; C:spindle; 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:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW. DR GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; IEA:RHEA. 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 signaling; ISO:MGI. DR GO; GO:0051444; P:negative regulation of ubiquitin-protein transferase activity; ISO:MGI. DR GO; GO:0071459; P:protein localization to chromosome, centromeric region; IMP:MGI. DR InterPro; IPR015661; Bub1/Mad3. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR013212; Mad3/Bub1_I. DR InterPro; IPR000719; Prot_kinase_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; Centromere; KW Chromosome; Cytoplasm; Kinase; Kinetochore; Mitosis; Nucleotide-binding; KW Nucleus; Phosphoprotein; Reference proteome; KW Serine/threonine-protein kinase; Transferase; Tumor suppressor; KW Ubl conjugation. FT CHAIN 1..1052 FT /note="Mitotic checkpoint serine/threonine-protein kinase FT BUB1 beta" FT /id="PRO_0000085674" FT DOMAIN 56..219 FT /note="BUB1 N-terminal" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00822" FT DOMAIN 756..1040 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT NP_BIND 762..770 FT /note="ATP" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 146..179 FT /note="Necessary for interaction with KNL1" FT /evidence="ECO:0000250" FT REGION 206..256 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 272..327 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 361..381 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 496..552 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 105..112 FT /note="Nuclear localization signal" FT /evidence="ECO:0000255" FT MOTIF 217..225 FT /note="D-box" FT COMPBIAS 496..524 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 871 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 784 FT /note="ATP" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT SITE 572..573 FT /note="Cleavage; by caspase-3" FT /evidence="ECO:0000250" FT SITE 603..604 FT /note="Cleavage; by caspase-3" FT /evidence="ECO:0000250" FT MOD_RES 243 FT /note="N6-acetyllysine; by PCAF" FT /evidence="ECO:0000250|UniProtKB:O60566" FT MOD_RES 360 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O60566" FT MOD_RES 428 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O60566" FT MOD_RES 535 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O60566" FT MOD_RES 659 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O60566" FT MOD_RES 665 FT /note="Phosphoserine; by PLK1" FT /evidence="ECO:0000250|UniProtKB:O60566" FT MOD_RES 686 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O60566" FT MOD_RES 781 FT /note="Phosphothreonine; by PLK1" FT /evidence="ECO:0000250|UniProtKB:O60566" FT MOD_RES 998 FT /note="Phosphothreonine; by PLK1" FT /evidence="ECO:0000250|UniProtKB:O60566" FT MOD_RES 1033 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O60566" FT MOD_RES 1050 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT CONFLICT 275 FT /note="A -> T (in Ref. 1; AAD11940)" FT /evidence="ECO:0000305" FT CONFLICT 278 FT /note="T -> P (in Ref. 1; AAD11940)" FT /evidence="ECO:0000305" FT CONFLICT 664 FT /note="E -> D (in Ref. 1; AAD11940)" FT /evidence="ECO:0000305" FT CONFLICT 705 FT /note="D -> N (in Ref. 1; AAD11940)" FT /evidence="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 //