BUB1B_MOUSE
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 03-AUG-2022, entry version 177.
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}.
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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; Q9Z1S0; -.
DR PeptideAtlas; Q9Z1S0; -.
DR PRIDE; Q9Z1S0; -.
DR ProteomicsDB; 265320; -.
DR Antibodypedia; 1214; 746 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 231 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: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 GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
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 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
