Mitotic checkpoint serine/threonine-protein kinase BUB1 beta

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Q9Z1S0 (BUB1B_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified May 29, 2013. Version 111. History...

Clusters with 100%, 90%, 50% identity |

Documents (3) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Mitotic checkpoint serine/threonine-protein kinase BUB1 beta
EC=2.7.11.1

Alternative name(s):
MAD3/BUB1-related protein kinase
Short name=BubR1
Mitotic checkpoint kinase MAD3L

Gene names

Name:	Bub1b
Synonyms:	Mad3l

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1052 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Essential component of the mitotic checkpoint. Required for normal mitosis progression and tumor suppression. The mitotic checkpoint delays anaphase until all chromosomes are properly attached to the mitotic spindle. One of its checkpoint functions is to inhibit the activity of the anaphase-promoting complex/cyclosome (APC/C) by blocking the binding of CDC20 to APC/C, independently of its kinase activity. The other is to monitor kinetochore activities that depend on the kinetochore motor CENPE. Required for kinetochore localization of CENPE. Negatively regulates PLK1 activity in interphase cells and suppresses centrosome amplification. Also implicated in triggering apoptosis in polyploid cells that exit aberrantly from mitotic arrest. Essential for tumor suppression. May play a role in regulating aging and fertility By similarity. Ref.4 Ref.5
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	Kinase activity stimulated by CENPE. Ref.3
Subunit structure	Interacts with CENPE, CENPF, mitosin, PLK1 and BUB3. Part of a complex containing BUB3, CDC20 and BUB1B. Interacts with anaphase-promoting complex/cyclosome (APC/C). Interacts with CASC5 By similarity. Ref.3
Subcellular location	Cytoplasm By similarity. Nucleus By similarity. Chromosome › centromere › kinetochore. Note: Cytoplasmic in interphase cells By similarity. Associates with the kinetochores in early prophase. Kinetochore localization requires BUB1, PLK1 and CASC5 By similarity. Ref.3 Ref.6
Tissue specificity	Highly expressed in thymus followed by spleen.
Domain	The D-box targets the protein for rapid degradation by ubiquitin-dependent proteolysis during the transition from mitosis to interphase Potential. The BUB1 N-terminal domain directs kinetochore localization and binding to BUB3.
Post-translational modification	Proteolytically cleaved by caspase-3 in a cell cycle specific manner By similarity. The cleavage might be involved in the durability of the cell cycle delay By similarity. Acetylation at Lys-243 regulates its degradation and timing in anaphase entry By similarity. Ubiquitinated. Degraded by the proteasome By similarity. Sumoylated with SUMO2 and SUMO3. The sumoylation mediates the association with CENPE at the kinetochore By similarity. Autophosphorylated in vitro By similarity. Intramolecular autophosphorylation stimulated by CENPE By similarity. Phosphorylated during mitosis and hyperphosphorylated in mitotically arrested cells By similarity. Phosphorylation at Ser-659 and Ser-1033 occurs at kinetochores upon mitotic entry with dephosphorylation at the onset of anaphase By similarity.
Involvement in disease	Defects in Bub1b are involved in the development of lung and intestinal adenocarcinomas after exposure to a carcinogen.
Disruption phenotype	Mice die in utero. Ref.5
Sequence similarities	Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. BUB1 subfamily. Contains 1 BUB1 N-terminal domain. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Apoptosis Cell cycle Cell division Mitosis
Cellular component	Centromere Chromosome Cytoplasm Kinetochore Nucleus
Disease	Tumor suppressor
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW cell division Inferred from electronic annotation. Source: UniProtKB-KW metaphase/anaphase transition of mitotic cell cycle Inferred from genetic interaction PubMed 15767571. Source: MGI protein localization to chromosome, centromeric region Inferred from mutant phenotype PubMed 19283064. Source: MGI protein localization to kinetochore Inferred from electronic annotation. Source: Compara
Cellular_component	condensed chromosome outer kinetochore Inferred from direct assay PubMed 14519686 PubMed 19283064. Source: MGI condensed nuclear chromosome kinetochore Inferred from direct assay PubMed 18765791. Source: MGI perinuclear region of cytoplasm Inferred from electronic annotation. Source: Compara
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1052

1052

Mitotic checkpoint serine/threonine-protein kinase BUB1 beta

PRO_0000085674

Regions

Domain

56 – 219

164

BUB1 N-terminal

Domain

756 – 1040

285

Protein kinase

Nucleotide binding

762 – 770

ATP By similarity

Region

146 – 179

Necessary for interaction with CASC5 By similarity

Motif

105 – 112

Nuclear localization signal Potential

Motif

217 – 225

D-box

Compositional bias

205 – 208

Poly-Glu

Compositional bias

675 – 680

Poly-Ser

Sites

Active site

871

Proton acceptor By similarity

Binding site

784

ATP By similarity

Site

572 – 573

Cleavage; by caspase-3 By similarity

Site

603 – 604

Cleavage; by caspase-3 By similarity

Amino acid modifications

Modified residue

243

N6-acetyllysine; by PCAF By similarity

Modified residue

428

Phosphoserine By similarity

Modified residue

535

Phosphoserine By similarity

Modified residue

659

Phosphoserine By similarity

Modified residue

665

Phosphoserine; by PLK1 By similarity

Modified residue

781

Phosphothreonine; by PLK1 By similarity

Modified residue

998

Phosphothreonine; by PLK1 By similarity

Modified residue

1033

Phosphoserine By similarity

Experimental info

Sequence conflict

275

A → T in AAD11940. Ref.1

Sequence conflict

278

T → P in AAD11940. Ref.1

Sequence conflict

664

E → D in AAD11940. Ref.1

Sequence conflict

705

D → N in AAD11940. Ref.1

Sequences

Sequence

Length

Mass (Da)

Tools

Q9Z1S0 [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: 9EF1ECF3735DD1F4
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FASTA

1,052

118,392

        10         20         30         40         50         60 
MAEASEAMCL EGAEWELSKE NIQPLRHGRV MSTLQGALAK QESAGHTALQ QQKRAFESEI 

        70         80         90        100        110        120 
RFYSGDDPLD VWDRYINWTE QNYPQGGKES NMSALVERAI EALQGETRYY NDPRFLSLWI 

       130        140        150        160        170        180 
KLGHLCNEPL DMYSYLQSQG IGVSLAQFYI SWAEEYEARE NFKKADIIFQ EGIERKAEPL 

       190        200        210        220        230        240 
DRLQSQHRQF QSRVSRQAFL ALGNEEEEAL EPSEPQRSSL AELKSRGKKM ARAPISRVGG 

       250        260        270        280        290        300 
ALKAPGQSRG FLNAVPQPVH GNRRITVFDE NADTASRTEL SKPVAQPWMA PPVPRAKENE 

       310        320        330        340        350        360 
LQPGPWSTDR PAGRRPHDNP ASVTSIPSVL PSFTPYVEES AQQTVMTPCK IEPSINHVLS 

       370        380        390        400        410        420 
TRKPGREEGD PLQRVQSHQQ GCEEKKEKMM YCKEKIYAGV GEFSFEEIRA EVFRKKLKER 

       430        440        450        460        470        480 
REAELLTSAK KREEMQKQIE EMERRLKAMQ AVQQEGAGGQ QEEKMPTEDP ARLQIASGPQ 

       490        500        510        520        530        540 
EMSGVPLSCS ICPLSSNPRE ISPAENILQE QPDSKGSSMP FSIFDESLSD KKDKSPATGG 

       550        560        570        580        590        600 
PQVLNAQRRP LSVLKTTEVG TTNEDVSPDI CDELTELEPL SEDAIITGFR NVTLCPNPED 

       610        620        630        640        650        660 
TCDFARAARL ASTPFHEILS SKGIAADPEG LLQEEDLDGK AAEAHHTVHH QALIIKKLSP 

       670        680        690        700        710        720 
IIEESREATH SSGFSRSSSS APSTSSIKGF QLLEKLELTN DGAEDAIQSP WCSQYRLQLL 

       730        740        750        760        770        780 
KSLLELSAFA EFSVEDRPMP VLEIGKEIEL GPEDYVIKQE HLTCDDYRLF WVAPRSSAEL 

       790        800        810        820        830        840 
TMIKASSQPI PWDFYINLKL KERLNEDYDQ LCSCCQYQDG HVVWYQYINC STLQNLLQHS 

       850        860        870        880        890        900 
EFVTHEIIVL IIYNLLTIVE KLHRAEIVHG DLSPRSLILR NRIHDPYDYV NKDDHAVRIM 

       910        920        930        940        950        960 
DFSYSVDLRV QLDAFAYSGF RTAQILEGQK ILANCSSPYH VDLLGIADLA HLLLFKEHLH 

       970        980        990       1000       1010       1020 
VFWDGLLWKL SQSTSELKDS ELWNKFFVRI LNASDKSTVS VLGELAAEMG GAFDATFHSH 

      1030       1040       1050 
LNRALWKLGK TISPEALLTQ QDKQPGGSQS PA

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The mouse mitotic checkpoint gene bub1b, a novel bub1 family member, is expressed in a cell cycle-dependent manner." Davenport J.W., Fernandes E.R., Harris L.D., Neale G.A.M., Goorha R. Genomics 55:113-117(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: NIH Swiss. Tissue: Embryo.
[2]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[3]	"Centromere-associated protein-E is essential for the mammalian mitotic checkpoint to prevent aneuploidy due to single chromosome loss." Weaver B.A., Bonday Z.Q., Putkey F.R., Kops G.J., Silk A.D., Cleveland D.W. J. Cell Biol. 162:551-563(2003) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION, INTERACTION WITH CENPE, SUBCELLULAR LOCATION.
[4]	"Slippage of mitotic arrest and enhanced tumor development in mice with BubR1 haploinsufficiency." Dai W., Wang Q., Liu T., Swamy M., Fang Y., Xie S., Mahmood R., Yang Y.M., Xu M., Rao C.V. Cancer Res. 64:440-445(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[5]	"BubR1 insufficiency causes early onset of aging-associated phenotypes and infertility in mice." Baker D.J., Jeganathan K.B., Cameron J.D., Thompson M., Juneja S., Kopecka A., Kumar R., Jenkins R.B., de Groen P.C., Roche P., van Deursen J.M. Nat. Genet. 36:744-749(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[6]	"Bub1 maintains centromeric cohesion by activation of the spindle checkpoint." Perera D., Tilston V., Hopwood J.A., Barchi M., Boot-Handford R.P., Taylor S.S. Dev. Cell 13:566-579(2007) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF107296 mRNA. Translation: AAD11940.1. AL845470, AL929381 Genomic DNA. Translation: CAM17418.1. AL929381, AL845470 Genomic DNA. Translation: CAM19078.1.
IPI	IPI00353560.
RefSeq	NP_033903.2. NM_009773.3.
UniGene	Mm.29133.
3D structure databases
ProteinModelPortal	Q9Z1S0.
SMR	Q9Z1S0. Positions 16-197, 707-1025.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9Z1S0. 29 interactions.
PTM databases
PhosphoSite	Q9Z1S0.
Proteomic databases
PaxDb	Q9Z1S0.
PRIDE	Q9Z1S0.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000038341; ENSMUSP00000037126; ENSMUSG00000040084.
GeneID	12236.
KEGG	mmu:12236.
UCSC	uc008lse.2. mouse.
Organism-specific databases
CTD	701.
MGI	MGI:1333889. Bub1b.
Phylogenomic databases
eggNOG	NOG317001.
GeneTree	ENSGT00520000055622.
HOGENOM	HOG000231849.
HOVERGEN	HBG050748.
InParanoid	A2ARS1.
KO	K06637.
OMA	ASTPFHE.
OrthoDB	EOG4FR0QT.
Enzyme and pathway databases
BRENDA	2.7.11.1. 3474.
Gene expression databases
ArrayExpress	Q9Z1S0.
Bgee	Q9Z1S0.
Genevestigator	Q9Z1S0.
GermOnline	ENSMUSG00000040084. Mus musculus.
Family and domain databases
InterPro	IPR015661. Bub1/Mad3. IPR011009. Kinase-like_dom. IPR013212. Mad3_BUB1_I. IPR000719. Prot_kinase_cat_dom. [Graphical view]
PANTHER	PTHR14030. PTHR14030. 1 hit.
Pfam	PF08311. Mad3_BUB1_I. 1 hit. [Graphical view]
SMART	SM00777. Mad3_BUB1_I. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS51489. BUB1_N. 1 hit. PS00107. PROTEIN_KINASE_ATP. False negative. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. False negative. [Graphical view]
ProtoNet	Search...
Other
NextBio	280666.
SOURCE	Search...

Entry information

Entry name

BUB1B_MOUSE

Accession

Primary (citable) accession number: Q9Z1S0
Secondary accession number(s): A2ARS1

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	July 27, 2011
Last modified:	May 29, 2013
This is version 111 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents