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   27-MAR-2024, entry version 186.
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       Interacts with CDC20 (By similarity). {ECO:0000250|UniProtKB:O60566,
CC       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}.
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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; 10090-ENSMUSP00000037126; -.
DR   PeptideAtlas; Q9Z1S0; -.
DR   ProteomicsDB; 265320; -.
DR   Pumba; Q9Z1S0; -.
DR   Antibodypedia; 1214; 849 antibodies from 41 providers.
DR   DNASU; 12236; -.
DR   Ensembl; ENSMUST00000038341.8; ENSMUSP00000037126.8; ENSMUSG00000040084.10.
DR   GeneID; 12236; -.
DR   KEGG; mmu:12236; -.
DR   UCSC; uc008lse.2; mouse.
DR   AGR; MGI:1333889; -.
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; QPWMAPP; -.
DR   OrthoDB; 5479089at2759; -.
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 81 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 234 other cell types or tissues.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
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:0005634; C:nucleus; IBA:GO_Central.
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: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; ISS:UniProtKB.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   GO; GO:0071459; P:protein localization to chromosome, centromeric region; IMP:MGI.
DR   Gene3D; 1.25.40.430; -; 1.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
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; MITOTIC CHECKPOINT SERINE/THREONINE-PROTEIN KINASE BUB1; 1.
DR   PANTHER; PTHR14030:SF25; MITOTIC CHECKPOINT SERINE_THREONINE-PROTEIN KINASE BUB1 BETA; 1.
DR   Pfam; PF08311; Mad3_BUB1_I; 1.
DR   SMART; SM00777; Mad3_BUB1_I; 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR   PROSITE; PS51489; BUB1_N; 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   Genevisible; Q9Z1S0; MM.
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   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         762..770
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         784
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
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
//