BUB1_MOUSE
ID BUB1_MOUSE Reviewed; 1058 AA.
AC O08901; O09007;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Mitotic checkpoint serine/threonine-protein kinase BUB1;
DE Short=mBUB1;
DE EC=2.7.11.1;
DE AltName: Full=BUB1A;
GN Name=Bub1;
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].
RX PubMed=9182760; DOI=10.1016/s0092-8674(00)80255-x;
RA Taylor S.S., McKeon F.;
RT "Kinetochore localization of murine Bub1 is required for normal mitotic
RT timing and checkpoint response to spindle damage.";
RL Cell 89:727-735(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J;
RX PubMed=9441741; DOI=10.1006/geno.1997.5068;
RA Pangilinan F., Li Q., Weaver T., Lewis B.C., Dang C.V., Spencer F.;
RT "Mammalian BUB1 protein kinases: map positions and in vivo expression.";
RL Genomics 46:379-388(1997).
RN [3]
RP FUNCTION, AND TISSUE SPECIFICITY.
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 [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17938250; DOI=10.1083/jcb.200706015;
RA Jeganathan K., Malureanu L., Baker D.J., Abraham S.C., van Deursen J.M.;
RT "Bub1 mediates cell death in response to chromosome missegregation and acts
RT to suppress spontaneous tumorigenesis.";
RL J. Cell Biol. 179:255-267(2007).
RN [5]
RP FUNCTION.
RX PubMed=19772675; DOI=10.1186/1756-0500-2-190;
RA Tilston V., Taylor S.S., Perera D.;
RT "Inactivating the spindle checkpoint kinase Bub1 during embryonic
RT development results in a global shutdown of proliferation.";
RL BMC Res. Notes 2:190-190(2009).
RN [6]
RP IDENTIFICATION 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 expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Serine/threonine-protein kinase that performs 2 crucial
CC functions during mitosis: it is essential for spindle-assembly
CC checkpoint signaling and for correct chromosome alignment. Has a key
CC role in the assembly of checkpoint proteins at the kinetochore, being
CC required for the subsequent localization of CENPF, BUB1B, CENPE and
CC MAD2L1. Required for the kinetochore localization of PLK1. Required for
CC centromeric enrichment of AUKRB in prometaphase. Plays an important
CC role in defining SGO1 localization and thereby affects sister chromatid
CC cohesion. Acts as a substrate for anaphase-promoting complex or
CC cyclosome (APC/C) in complex with its activator CDH1 (APC/C-Cdh1).
CC Necessary for ensuring proper chromosome segregation and binding to
CC BUB3 is essential for this function. Can regulate chromosome
CC segregation in a kinetochore-independent manner. Can phosphorylate
CC BUB3. The BUB1-BUB3 complex plays a role in the inhibition of APC/C
CC when spindle-assembly checkpoint is activated and inhibits the
CC ubiquitin ligase activity of APC/C by phosphorylating its activator
CC CDC20. This complex can also phosphorylate MAD1L1. Kinase activity is
CC essential for inhibition of APC/CCDC20 and for chromosome alignment but
CC does not play a major role in the spindle-assembly checkpoint activity.
CC Mediates cell death in response to chromosome missegregation and acts
CC to suppress spontaneous tumorigenesis. Essential during early and later
CC stages of embryonic development. Necessary for postimplantation
CC embryogenesis and proliferation of primary embryonic fibroblasts and
CC plays an important role in spermatogenesis and fertility.
CC {ECO:0000250|UniProtKB:O43683, ECO:0000269|PubMed:17925231,
CC ECO:0000269|PubMed:17938250, ECO:0000269|PubMed:19772675}.
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: Autophosphorylated when the cells enters mitosis.
CC {ECO:0000250}.
CC -!- SUBUNIT: Interacts with BUB3 and KNL1. Interacts (when phosphorylated)
CC with PLK1. The BUB1-BUB3 complex interacts with MAD1L1 (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus. Chromosome, centromere, kinetochore.
CC Note=Nuclear in interphase cells. Accumulates gradually during G1 and S
CC phase of the cell cycle, peaks at G2/M, and drops dramatically after
CC mitosis. Localizes to the outer kinetochore. Kinetochore localization
CC is required for normal mitotic timing and checkpoint response to
CC spindle damage and occurs very early in prophase. AURKB, KNL1 and
CC INCENP are required for kinetochore localization (By similarity).
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Highly expressed in testis. Weakly expressed in
CC spleen and lung. {ECO:0000269|PubMed:17925231}.
CC -!- DOMAIN: The KEN box is required for its ubiquitination and degradation.
CC {ECO:0000250}.
CC -!- DOMAIN: BUB1 N-terminal domain directs kinetochore localization and
CC binding to BUB3.
CC -!- PTM: Upon spindle-assembly checkpoint activation it is
CC hyperphosphorylated and its kinase activity toward CDC20 is stimulated.
CC Phosphorylation at Thr-595 is required for interaction with PLK1,
CC phosphorylation at this site probably creates a binding site for the
CC POLO-box domain of PLK1, thus enhancing the PLK1-BUB1 interaction (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Ubiquitinated and degraded during mitotic exit by APC/C-Cdh1.
CC {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Early embryonic lethality.
CC {ECO:0000269|PubMed:17938250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. BUB1 subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC53533.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF002823; AAC53226.1; -; mRNA.
DR EMBL; U89795; AAC53533.1; ALT_INIT; mRNA.
DR PIR; T30178; T30178.
DR PIR; T31004; T31004.
DR RefSeq; NP_001106650.1; NM_001113179.1.
DR RefSeq; NP_033902.2; NM_009772.2.
DR AlphaFoldDB; O08901; -.
DR SMR; O08901; -.
DR BioGRID; 198404; 61.
DR IntAct; O08901; 15.
DR STRING; 10090.ENSMUSP00000028858; -.
DR iPTMnet; O08901; -.
DR PhosphoSitePlus; O08901; -.
DR SwissPalm; O08901; -.
DR EPD; O08901; -.
DR MaxQB; O08901; -.
DR PaxDb; O08901; -.
DR PRIDE; O08901; -.
DR ProteomicsDB; 273779; -.
DR DNASU; 12235; -.
DR GeneID; 12235; -.
DR KEGG; mmu:12235; -.
DR UCSC; uc008mgd.2; mouse.
DR CTD; 699; -.
DR MGI; MGI:1100510; Bub1.
DR eggNOG; KOG1166; Eukaryota.
DR InParanoid; O08901; -.
DR OrthoDB; 1411806at2759; -.
DR BRENDA; 2.7.11.1; 3474.
DR Reactome; R-MMU-141444; Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal.
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; 12235; 15 hits in 74 CRISPR screens.
DR ChiTaRS; Bub1; mouse.
DR PRO; PR:O08901; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; O08901; protein.
DR GO; GO:0000775; C:chromosome, centromeric region; IDA:MGI.
DR GO; GO:0000779; C:condensed chromosome, centromeric region; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0000776; C:kinetochore; IDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; 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:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0007059; P:chromosome segregation; IMP:MGI.
DR GO; GO:0097193; P:intrinsic apoptotic signaling pathway; IMP:MGI.
DR GO; GO:0051754; P:meiotic sister chromatid cohesion, centromeric; IBA:GO_Central.
DR GO; GO:0007094; P:mitotic spindle assembly checkpoint signaling; IBA:GO_Central.
DR GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; IMP:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0051983; P:regulation of chromosome segregation; ISO:MGI.
DR GO; GO:0007063; P:regulation of sister chromatid cohesion; ISS:UniProtKB.
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 InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR PANTHER; PTHR14030; PTHR14030; 1.
DR Pfam; PF08311; Mad3_BUB1_I; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00777; Mad3_BUB1_I; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51489; BUB1_N; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW Apoptosis; ATP-binding; Cell cycle; Cell division; Centromere; Chromosome;
KW Chromosome partition; Kinase; Kinetochore; Mitosis; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Ubl conjugation.
FT CHAIN 1..1058
FT /note="Mitotic checkpoint serine/threonine-protein kinase
FT BUB1"
FT /id="PRO_0000085672"
FT DOMAIN 11..182
FT /note="BUB1 N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00822"
FT DOMAIN 761..1058
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..146
FT /note="Necessary for kinetochore localization"
FT /evidence="ECO:0000250"
FT REGION 99..132
FT /note="Necessary for interaction with KNL1"
FT /evidence="ECO:0000250"
FT REGION 229..255
FT /note="Necessary for interaction with BUB3"
FT /evidence="ECO:0000250"
FT REGION 334..359
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 446..464
FT /note="Essential for loading of BUBR1, MAD1L1 and MAD2L1 to
FT kinetochores"
FT /evidence="ECO:0000250"
FT MOTIF 58..65
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT MOTIF 522..524
FT /note="KEN box 1"
FT /evidence="ECO:0000250"
FT MOTIF 611..613
FT /note="KEN box 2"
FT /evidence="ECO:0000250"
FT COMPBIAS 334..354
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 891
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 767..775
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 795
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 306
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43683"
FT MOD_RES 313
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43683"
FT MOD_RES 330
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43683"
FT MOD_RES 512
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43683"
FT MOD_RES 550
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43683"
FT MOD_RES 579
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43683"
FT MOD_RES 582
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43683"
FT MOD_RES 595
FT /note="Phosphothreonine; by CDK1"
FT /evidence="ECO:0000250|UniProtKB:O43683"
FT MOD_RES 648
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43683"
FT CONFLICT 187
FT /note="K -> R (in Ref. 2; AAC53533)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1058 AA; 119563 MW; D179DAD4583A2C2F CRC64;
MDNLENVFRM FEAHMQSYTG NDPLGEWESF IKWVEENFPD NKEYLMTLLE HLMKEFLHKK
NYHNDSRFIN YCLKFAEYNS DRHQFFEFLY NQGIGTKSSY IYMSWAGHLE AQGELQHASA
IFQTGIHNEA EPKELLQQQY RLFQARLTGI HLPAQATTSE PLHSAQILNQ VMMTNSSPEK
NSACVPKSQG SECSGVASST CDEKSNMEQR VIMISKSECS VSSSVAPKPE AQQVMYCKEK
LIRGDSEFSF EELRAQKYNQ RKKHEQWVSE DRNYMKRKEA NAFEEQLLKQ KMDELHKKLH
QVVELSHKDL PASENRPDVS LVCVGQNTCS QQELRGPSLS SISHQTSESS GEKPQEEPSV
PLMVNAVNST LLFPAANLPA LPVPVSGQSL TDSRCVNQSV HEFMPQCGPE TKEVCETNKV
ASINDFHTTP NTSLGMVQGT PCKVQPSPTV HTKEALGFIM DMFQAPTLPD ISDDKDEWPS
LDQNEDAFEA QFQKNAVSSG DWGVKKIMTL SSAFPIFEDG NKENYGLPQP KNKPLGARTF
GERSLSKYSS RSNEMPHTDE FMDDSTVCGI RCNKTLAPSP KSIGDFTSAA QLSSTPFHKF
PADLVQIPED KENVVATQYT HMALDSCKEN IVDLSKGRKL GPIQEKISAS LPCPSQPATG
GLFTQEAVFG LEAFKCTGID HATVEDLSDA NAGLQVECVQ TLGNVNAPSF TVENPWDDEL
ILKLLSGLSK PVTSYSNTFE WQSKLPAIKT KTEYQLGSLL VYVNHLLGEG AFAQVFEAIH
GDVRNAKSEQ KCILKVQRPA NSWEFYIGMQ LMERLKPEVH HMFIKFYSAH LFKNGSILVG
ELYSYGTLLN VINLYKNTSE KVMPQALVLT FAIRMLYMVE QVHSCEIIHG DIKPDNFILG
HRFLEQADED LATGLALIDL GQSIDMKLFP KGTVFTGKCE TSGFQCPEML SNKPWNYQID
YFGVAATIYC MLFGSYMKVK NEGGVWKPEG LFRRLPHLDM WEEFFHIMLN IPDCHNLPSL
DFLRQNMKKL LEQQYSNKIK TLRNRLIVML SEYKRSRK
