Mitotic checkpoint serine/threonine-protein kinase BUB1

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O08901 (BUB1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 102. 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
Short name=mBUB1
EC=2.7.11.1

Alternative name(s):
BUB1A

Gene names

Name:

Bub1

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	1058 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Serine/threonine-protein kinase that performs 2 crucial functions during mitosis: it is essential for spindle-assembly checkpoint signaling and for correct chromosome alignment. Has a key role in the assembly of checkpoint proteins at the kinetochore, being required for the subsequent localization of CENPF, BUB1B, CENPE and MAD2L1. Required for the kinetochore localization of PLK1. Plays an important role in defining SGOL1 localization and thereby affects sister chromatid cohesion. Acts as a substrate for anaphase-promoting complex or cyclosome (APC/C) in complex with its activator CDH1 (APC/C-Cdh1). Necessary for ensuring proper chromosome segregation and binding to BUB3 is essential for this function. Can regulate chromosome segregation in a kinetochore-independent manner. Can phosphorylate BUB3. The BUB1-BUB3 complex plays a role in the inhibition of APC/C when spindle-assembly checkpoint is activated and inhibits the ubiquitin ligase activity of APC/C by phosphorylating its activator CDC20. This complex can also phosphorylate MAD1L1. Kinase activity is essential for inhibition of APC/CCDC20 and for chromosome alignment but does not play a major role in the spindle-assembly checkpoint activity. Mediates cell death in response to chromosome missegregation and acts to suppress spontaneous tumorigenesis. Essential during early and later stages of embryonic development. Necessary for postimplantation embryogenesis and proliferation of primary embryonic fibroblasts and plays an important role in spermatogenesis and fertility. Ref.3 Ref.4 Ref.5
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	Autophosphorylated when the cells enters mitosis By similarity.
Subunit structure	Interacts with BUB3 and CASC5. Interacts (when phosphorylated) with PLK1. The BUB1-BUB3 complex interacts with MAD1L1 By similarity.
Subcellular location	Nucleus. Chromosome › centromere › kinetochore. Note: Nuclear in interphase cells. Accumulates gradually during G1 and S phase of the cell cycle, peaks at G2/M, and drops dramatically after mitosis. Localizes to the outer kinetochore. Kinetochore localization is required for normal mitotic timing and checkpoint response to spindle damage and occurs very early in prophase. AURKB, CASC5 and INCENP are required for kinetochore localization By similarity.
Tissue specificity	Highly expressed in testis. Weakly expressed in spleen and lung. Ref.3
Domain	The KEN box is required for its ubiquitination and degradation By similarity. BUB1 N-terminal domain directs kinetochore localization and binding to BUB3.
Post-translational modification	Upon spindle-assembly checkpoint activation it is hyperphosphorylated and its kinase activity toward CDC20 is stimulated. Phosphorylation at Thr-595 is required for interaction with PLK1, phosphorylation at this site probably creates a binding site for the POLO-box domain of PLK1, thus enhancing the PLK1-BUB1 interaction By similarity. Ubiquitinated and degraded during mitotic exit by APC/C-Cdh1 By similarity.
Disruption phenotype	Early embryonic lethality. Ref.4
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.
Sequence caution	The sequence AAC53533.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Apoptosis Cell cycle Cell division Chromosome partition Mitosis
Cellular component	Centromere Chromosome Kinetochore Nucleus
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Inferred from mutant phenotype Ref.4. Source: UniProtKB cell division Inferred from electronic annotation. Source: UniProtKB-KW chromosome segregation Inferred from electronic annotation. Source: UniProtKB-KW embryo development Inferred from direct assay Ref.5. Source: UniProtKB mitosis Inferred from electronic annotation. Source: UniProtKB-KW regulation of sister chromatid cohesion Inferred from sequence or structural similarity. Source: UniProtKB spindle assembly checkpoint Inferred from direct assay Ref.3. Source: UniProtKB
Cellular_component	condensed chromosome kinetochore Inferred from electronic annotation. Source: UniProtKB-SubCell condensed nuclear chromosome, centromeric region Inferred from direct assay PubMed 18084284 PubMed 19965387. Source: MGI kinetochore Inferred from direct assay PubMed 15226446 PubMed 17227893. Source: MGI
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 – 1058

1058

Mitotic checkpoint serine/threonine-protein kinase BUB1

PRO_0000085672

Regions

Domain

11 – 182

172

BUB1 N-terminal

Domain

761 – 1058

298

Protein kinase

Nucleotide binding

767 – 775

ATP By similarity

Region

1 – 146

146

Necessary for kinetochore localization By similarity

Region

99 – 132

Necessary for interaction with CASC5 By similarity

Region

229 – 255

Necessary for interaction with BUB3 By similarity

Region

446 – 464

Essential for loading of BUBR1, MAD1L1 and MAD2L1 to kinetochores By similarity

Motif

58 – 65

Nuclear localization signal Potential

Motif

522 – 524

KEN box 1 By similarity

Motif

611 – 613

KEN box 2 By similarity

Sites

Active site

891

Proton acceptor By similarity

Binding site

795

ATP By similarity

Amino acid modifications

Modified residue

313

Phosphoserine By similarity

Modified residue

550

Phosphoserine By similarity

Modified residue

579

Phosphoserine By similarity

Modified residue

582

Phosphoserine By similarity

Modified residue

595

Phosphothreonine; by CDK1 By similarity

Experimental info

Sequence conflict

187

K → R in AAC53533. Ref.2

Sequences

Sequence

Length

Mass (Da)

Tools

O08901 [UniParc].

Last modified July 1, 1997. Version 1.
Checksum: D179DAD4583A2C2F
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FASTA

1,058

119,563

        10         20         30         40         50         60 
MDNLENVFRM FEAHMQSYTG NDPLGEWESF IKWVEENFPD NKEYLMTLLE HLMKEFLHKK 

        70         80         90        100        110        120 
NYHNDSRFIN YCLKFAEYNS DRHQFFEFLY NQGIGTKSSY IYMSWAGHLE AQGELQHASA 

       130        140        150        160        170        180 
IFQTGIHNEA EPKELLQQQY RLFQARLTGI HLPAQATTSE PLHSAQILNQ VMMTNSSPEK 

       190        200        210        220        230        240 
NSACVPKSQG SECSGVASST CDEKSNMEQR VIMISKSECS VSSSVAPKPE AQQVMYCKEK 

       250        260        270        280        290        300 
LIRGDSEFSF EELRAQKYNQ RKKHEQWVSE DRNYMKRKEA NAFEEQLLKQ KMDELHKKLH 

       310        320        330        340        350        360 
QVVELSHKDL PASENRPDVS LVCVGQNTCS QQELRGPSLS SISHQTSESS GEKPQEEPSV 

       370        380        390        400        410        420 
PLMVNAVNST LLFPAANLPA LPVPVSGQSL TDSRCVNQSV HEFMPQCGPE TKEVCETNKV 

       430        440        450        460        470        480 
ASINDFHTTP NTSLGMVQGT PCKVQPSPTV HTKEALGFIM DMFQAPTLPD ISDDKDEWPS 

       490        500        510        520        530        540 
LDQNEDAFEA QFQKNAVSSG DWGVKKIMTL SSAFPIFEDG NKENYGLPQP KNKPLGARTF 

       550        560        570        580        590        600 
GERSLSKYSS RSNEMPHTDE FMDDSTVCGI RCNKTLAPSP KSIGDFTSAA QLSSTPFHKF 

       610        620        630        640        650        660 
PADLVQIPED KENVVATQYT HMALDSCKEN IVDLSKGRKL GPIQEKISAS LPCPSQPATG 

       670        680        690        700        710        720 
GLFTQEAVFG LEAFKCTGID HATVEDLSDA NAGLQVECVQ TLGNVNAPSF TVENPWDDEL 

       730        740        750        760        770        780 
ILKLLSGLSK PVTSYSNTFE WQSKLPAIKT KTEYQLGSLL VYVNHLLGEG AFAQVFEAIH 

       790        800        810        820        830        840 
GDVRNAKSEQ KCILKVQRPA NSWEFYIGMQ LMERLKPEVH HMFIKFYSAH LFKNGSILVG 

       850        860        870        880        890        900 
ELYSYGTLLN VINLYKNTSE KVMPQALVLT FAIRMLYMVE QVHSCEIIHG DIKPDNFILG 

       910        920        930        940        950        960 
HRFLEQADED LATGLALIDL GQSIDMKLFP KGTVFTGKCE TSGFQCPEML SNKPWNYQID 

       970        980        990       1000       1010       1020 
YFGVAATIYC MLFGSYMKVK NEGGVWKPEG LFRRLPHLDM WEEFFHIMLN IPDCHNLPSL 

      1030       1040       1050 
DFLRQNMKKL LEQQYSNKIK TLRNRLIVML SEYKRSRK

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References

[1]	"Kinetochore localization of murine Bub1 is required for normal mitotic timing and checkpoint response to spindle damage." Taylor S.S., McKeon F. Cell 89:727-735(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Mammalian BUB1 protein kinases: map positions and in vivo expression." Pangilinan F., Li Q., Weaver T., Lewis B.C., Dang C.V., Spencer F. Genomics 46:379-388(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: C57BL/6J.
[3]	"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: FUNCTION, TISSUE SPECIFICITY.
[4]	"Bub1 mediates cell death in response to chromosome missegregation and acts to suppress spontaneous tumorigenesis." Jeganathan K., Malureanu L., Baker D.J., Abraham S.C., van Deursen J.M. J. Cell Biol. 179:255-267(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[5]	"Inactivating the spindle checkpoint kinase Bub1 during embryonic development results in a global shutdown of proliferation." Tilston V., Taylor S.S., Perera D. BMC Res. Notes 2:190-190(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF002823 mRNA. Translation: AAC53226.1. U89795 mRNA. Translation: AAC53533.1. Different initiation.
IPI	IPI00882019.
PIR	T30178. T31004.
RefSeq	NP_001106650.1. NM_001113179.1. NP_033902.2. NM_009772.2.
UniGene	Mm.2185.
3D structure databases
ProteinModelPortal	O08901.
SMR	O08901. Positions 1-148, 709-1052.
ModBase	Search...
Protein-protein interaction databases
IntAct	O08901. 15 interactions.
PTM databases
PhosphoSite	O08901.
Proteomic databases
PaxDb	O08901.
PRIDE	O08901.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	12235.
KEGG	mmu:12235.
UCSC	uc008mgd.2. mouse.
Organism-specific databases
CTD	699.
MGI	MGI:1100510. Bub1.
Phylogenomic databases
eggNOG	NOG317001.
HOVERGEN	HBG003709.
InParanoid	O08901.
KO	K02178.
OrthoDB	EOG4JM7P7.
Enzyme and pathway databases
BRENDA	2.7.11.1. 3474.
Gene expression databases
Genevestigator	O08901.
GermOnline	ENSMUSG00000027379. Mus musculus.
Family and domain databases
InterPro	IPR015661. Bub1/Mad3. IPR011009. Kinase-like_dom. IPR013212. Mad3_BUB1_I. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
PANTHER	PTHR14030. PTHR14030. 1 hit.
Pfam	PF08311. Mad3_BUB1_I. 1 hit. PF00069. Pkinase. 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. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	280662.
SOURCE	Search...

Entry information

Entry name

BUB1_MOUSE

Accession

Primary (citable) accession number: O08901
Secondary accession number(s): O09007

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	July 1, 1997
Last modified:	April 3, 2013
This is version 102 of the entry and version 1 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