O60566 (BUB1B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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=hBUBR1
Mitotic checkpoint kinase MAD3L
Protein SSK1

Gene names

Name:	BUB1B
Synonyms:	BUBR1, MAD3L, SSK1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1050 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. 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. May play a role for tumor suppression. Ref.12 Ref.13 Ref.14 Ref.16 Ref.27 Ref.30
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	Kinase activity stimulated by CENPE. Ref.15
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. Ref.3 Ref.12 Ref.13 Ref.15 Ref.18 Ref.20 Ref.21 Ref.22 Ref.28 Ref.29 Ref.30
Subcellular location	Cytoplasm. Nucleus. Chromosome › centromere › kinetochore. Cytoplasm › cytoskeleton › centrosome. Note: Cytoplasmic in interphase cells. Associates with the kinetochores in early prophase. Kinetochore localization requires BUB1, PLK1 and CASC5. Ref.3 Ref.12 Ref.14 Ref.18 Ref.21 Ref.22 Ref.28 Ref.30
Tissue specificity	Highly expressed in thymus followed by spleen. Preferentially expressed in tissues with a high mitotic index. Ref.11
Induction	Induced during mitosis. Ref.11 Ref.12 Ref.15 Ref.17
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. The cleavage might be involved in the durability of the cell cycle delay. Caspase-3 cleavage is associated with abrogation of the mitotic checkpoint. The major site of cleavage is at Asp-610. Ref.17 Acetylation at Lys-250 regulates its degradation and timing in anaphase entry. Ubiquitinated. Degraded by the proteasome. Ref.14 Ref.29 Sumoylated with SUMO2 and SUMO3. The sumoylation mediates the association with CENPE at the kinetochore. Ref.24 Autophosphorylated in vitro. Intramolecular autophosphorylation is stimulated by CENPE. Phosphorylated during mitosis and hyperphosphorylated in mitotically arrested cells. Phosphorylation at Ser-670 and Ser-1043 occurs at kinetochores upon mitotic entry with dephosphorylation at the onset of anaphase. Ref.11 Ref.12 Ref.15 Ref.21 Ref.22 Ref.23
Involvement in disease	Defects in BUB1B are associated with tumor formation. Premature chromatid separation trait (PCS) [MIM:176430]: Consists of separate and splayed chromatids with discernible centromeres and involves all or most chromosomes of a metaphase. It is found in up to 2% of metaphases in cultured lymphocytes from approximately 40% of normal individuals. When PCS is present in 5% or more of cells, it is known as the heterozygous PCS trait and has no obvious phenotypic effect, although some have reported decreased fertility. Inheritance is autosomal dominant. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.36 Mosaic variegated aneuploidy syndrome 1 (MVA1) [MIM:257300]: A severe developmental disorder characterized by mosaic aneuploidies, predominantly trisomies and monosomies, involving multiple different chromosomes and tissues. Affected individuals typically present with severe intrauterine growth retardation and microcephaly. Eye anomalies, mild dysmorphism, variable developmental delay, and a broad spectrum of additional congenital abnormalities and medical conditions may also occur. The risk of malignancy is high, with rhabdomyosarcoma, Wilms tumor and leukemia reported in several cases. Note: The disease is caused by mutations affecting the gene represented in this entry. MVA1 is caused by biallelic mutations in the BUB1B gene. Ref.35
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 BAD92019.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Apoptosis Cell cycle Cell division Mitosis
Cellular component	Centromere Chromosome Cytoplasm Cytoskeleton Kinetochore Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Tumor suppressor
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process Traceable author statement. Source: Reactome apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW cell division Inferred from electronic annotation. Source: UniProtKB-KW cell proliferation Traceable author statement Ref.12. Source: ProtInc mitotic metaphase/anaphase transition Inferred from electronic annotation. Source: Compara mitotic prometaphase Traceable author statement. Source: Reactome mitotic spindle assembly checkpoint Traceable author statement. Source: Reactome negative regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle Traceable author statement. Source: Reactome phosphatidylinositol-mediated signaling Non-traceable author statement PubMed 15504738. Source: UniProtKB protein localization to chromosome, centromeric region Inferred from electronic annotation. Source: Compara protein localization to kinetochore Inferred from physical interaction Ref.2. Source: UniProtKB spindle organization Non-traceable author statement PubMed 15504738. Source: UniProtKB
Cellular_component	anaphase-promoting complex Traceable author statement Ref.12. Source: ProtInc condensed chromosome outer kinetochore Inferred from direct assay PubMed 19468067. Source: UniProtKB condensed nuclear chromosome kinetochore Inferred from electronic annotation. Source: Compara cytosol Traceable author statement. Source: Reactome microtubule organizing center Inferred from electronic annotation. Source: UniProtKB-SubCell perinuclear region of cytoplasm Inferred from direct assay PubMed 20531406. Source: BHF-UCL spindle midzone Non-traceable author statement Ref.3. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein kinase activity Non-traceable author statement Ref.3. Source: UniProtKB protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CDC20	Q12834	8	EBI-1001438,EBI-367462
CENPE	Q02224	4	EBI-1001438,EBI-1375040

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O60566-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O60566-2)

The sequence of this isoform differs from the canonical sequence as follows:
     113-166: Missing.
     522-522: K → KVSLSL
     608-675: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: O60566-3)

The sequence of this isoform differs from the canonical sequence as follows:
     80-80: R → RWVFLFHKDNRNINR

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1050

1050

Mitotic checkpoint serine/threonine-protein kinase BUB1 beta

PRO_0000085673

Regions

Domain

62 – 226

165

BUB1 N-terminal

Domain

766 – 1050

285

Protein kinase

Nucleotide binding

772 – 780

9

ATP By similarity

Region

152 – 185

34

Necessary for interaction with CASC5

Motif

111 – 118

8

Nuclear localization signal Potential

Motif

224 – 232

9

D-box

Compositional bias

209 – 215

7

Poly-Glu

Sites

Active site

882

1

Proton acceptor By similarity

Binding site

795

1

ATP By similarity

Site

579 – 580

2

Cleavage; by caspase-3

Site

610 – 611

2

Cleavage; by caspase-3

Amino acid modifications

Modified residue

250

1

N6-acetyllysine; by PCAF Ref.29

Modified residue

435

1

Phosphoserine Ref.23

Modified residue

543

1

Phosphoserine Ref.23 Ref.33

Modified residue

670

1

Phosphoserine Ref.23 Ref.25 Ref.26 Ref.31

Modified residue

676

1

Phosphoserine; by PLK1 Ref.21

Modified residue

792

1

Phosphothreonine; by PLK1 Ref.22

Modified residue

1008

1

Phosphothreonine; by PLK1 Ref.22

Modified residue

1042

1

Phosphothreonine Ref.31

Modified residue

1043

1

Phosphoserine Ref.23

Natural variations

Alternative sequence

80

1

R → RWVFLFHKDNRNINR in isoform 3.

VSP_036473

Alternative sequence

113 – 166

54

Missing in isoform 2.

VSP_036474

Alternative sequence

522

1

K → KVSLSL in isoform 2.

VSP_036475

Alternative sequence

608 – 675

68

Missing in isoform 2.

VSP_036476

Natural variant

15

1

M → T in a colorectal cancer cell line. Ref.4

VAR_008852

Natural variant

36

1

R → Q in PCS. Ref.36

VAR_028921

Natural variant

40

1

T → M. Ref.37
Corresponds to variant rs56079734 [ dbSNP | Ensembl ].

VAR_040402

Natural variant

349

1

R → Q. Ref.1 Ref.2 Ref.3 Ref.4 Ref.6 Ref.8 Ref.10 Ref.34 Ref.37
Corresponds to variant rs1801376 [ dbSNP | Ensembl ].

VAR_008853

Natural variant

378

1

P → S. Ref.10
Corresponds to variant rs17851677 [ dbSNP | Ensembl ].

VAR_054549

Natural variant

390

1

E → D. Ref.37
Corresponds to variant rs1017842 [ dbSNP | Ensembl ].

VAR_028922

Natural variant

550

1

R → Q in MVA1; heterozygous compound with nonsense mutation. Ref.35
Corresponds to variant rs28989187 [ dbSNP | Ensembl ].

VAR_028923

Natural variant

618

1

V → A in colorectal cancer. Ref.34 Ref.37
Corresponds to variant rs1801528 [ dbSNP | Ensembl ].

VAR_008854

Natural variant

814

1

R → H in MVA1; heterozygous compound with nonsense mutation. Ref.35
Corresponds to variant rs28989182 [ dbSNP | Ensembl ].

VAR_028924

Natural variant

844

1

L → F in MVA1; associated with H-921; heterozygous compound with nonsense mutation. Ref.35
Corresponds to variant rs28989181 [ dbSNP | Ensembl ].

VAR_028925

Natural variant

909

1

I → T in MVA1; heterozygous compound with nonsense mutation. Ref.35
Corresponds to variant rs28989184 [ dbSNP | Ensembl ].

VAR_028926

Natural variant

921

1

Q → H in MVA1; associated with F-844; heterozygous compound with nonsense mutation. Ref.35
Corresponds to variant rs28989183 [ dbSNP | Ensembl ].

VAR_028927

Natural variant

1012

1

L → P in MVA1; heterozygous compound with nonsense mutation. Ref.35
Corresponds to variant rs28989185 [ dbSNP | Ensembl ].

VAR_028928

Experimental info

Mutagenesis

159

1

A → W: Loss of interaction with CASC5. Ref.20

Mutagenesis

175

1

F → A: Loss of interaction with CASC5. Ref.20

Mutagenesis

579

1

D → E: Abolishes the cleavage by caspase-3. Ref.17

Mutagenesis

610

1

D → E: Abolishes the cleavage by caspase-3. Ref.17

Mutagenesis

620

1

T → A: Induces chromosome congression defects and mitotic delay. Ref.21

Mutagenesis

795

1

K → A: Does not abolish the capacity to inhibit APC/CDC20. Ref.13 Ref.15

Mutagenesis

795

1

K → R: Inhibits kinase activity. Ref.13 Ref.15

Sequence conflict

248 – 249

2

AL → VF in AAC23736. Ref.1

Sequence conflict

283

1

S → P in BAG35587. Ref.8

Sequence conflict

788

1

S → F in AAC06260. Ref.2

Sequence conflict

1018

1

E → K in AAC33435. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

1050

Helix Strand Turn

Details...

Turn

26 – 28

3

Helix

60 – 65

6

Helix

75 – 88

14

Helix

94 – 96

3

Helix

98 – 108

11

Turn

109 – 111

3

Helix

113 – 115

3

Helix

119 – 131

13

Helix

135 – 144

10

Helix

152 – 164

13

Helix

168 – 180

13

Helix

186 – 218

33

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified April 3, 2007. Version 3. Checksum: F7871103A56E6B46	FASTA	1,050	119,545
	10 20 30 40 50 60 MAAVKKEGGA LSEAMSLEGD EWELSKENVQ PLRQGRIMST LQGALAQESA CNNTLQQQKR 70 80 90 100 110 120 AFEYEIRFYT GNDPLDVWDR YISWTEQNYP QGGKESNMST LLERAVEALQ GEKRYYSDPR 130 140 150 160 170 180 FLNLWLKLGR LCNEPLDMYS YLHNQGIGVS LAQFYISWAE EYEARENFRK ADAIFQEGIQ 190 200 210 220 230 240 QKAEPLERLQ SQHRQFQARV SRQTLLALEK EEEEEVFESS VPQRSTLAEL KSKGKKTARA 250 260 270 280 290 300 PIIRVGGALK APSQNRGLQN PFPQQMQNNS RITVFDENAD EASTAELSKP TVQPWIAPPM 310 320 330 340 350 360 PRAKENELQA GPWNTGRSLE HRPRGNTASL IAVPAVLPSF TPYVEETARQ PVMTPCKIEP 370 380 390 400 410 420 SINHILSTRK PGKEEGDPLQ RVQSHQQASE EKKEKMMYCK EKIYAGVGEF SFEEIRAEVF 430 440 450 460 470 480 RKKLKEQREA ELLTSAEKRA EMQKQIEEME KKLKEIQTTQ QERTGDQQEE TMPTKETTKL 490 500 510 520 530 540 QIASESQKIP GMTLSSSVCQ VNCCARETSL AENIWQEQPH SKGPSVPFSI FDEFLLSEKK 550 560 570 580 590 600 NKSPPADPPR VLAQRRPLAV LKTSESITSN EDVSPDVCDE FTGIEPLSED AIITGFRNVT 610 620 630 640 650 660 ICPNPEDTCD FARAARFVST PFHEIMSLKD LPSDPERLLP EEDLDVKTSE DQQTACGTIY 670 680 690 700 710 720 SQTLSIKKLS PIIEDSREAT HSSGFSGSSA SVASTSSIKC LQIPEKLELT NETSENPTQS 730 740 750 760 770 780 PWCSQYRRQL LKSLPELSAS AELCIEDRPM PKLEIEKEIE LGNEDYCIKR EYLICEDYKL 790 800 810 820 830 840 FWVAPRNSAE LTVIKVSSQP VPWDFYINLK LKERLNEDFD HFCSCYQYQD GCIVWHQYIN 850 860 870 880 890 900 CFTLQDLLQH SEYITHEITV LIIYNLLTIV EMLHKAEIVH GDLSPRCLIL RNRIHDPYDC 910 920 930 940 950 960 NKNNQALKIV DFSYSVDLRV QLDVFTLSGF RTVQILEGQK ILANCSSPYQ VDLFGIADLA 970 980 990 1000 1010 1020 HLLLFKEHLQ VFWDGSFWKL SQNISELKDG ELWNKFFVRI LNANDEATVS VLGELAAEMN 1030 1040 1050 GVFDTTFQSH LNKALWKVGK LTSPGALLFQ
	Isoform 2 [UniParc]. Checksum: 81D1307E360D7B67	FASTA	933	105,890
	10 20 30 40 50 60 MAAVKKEGGA LSEAMSLEGD EWELSKENVQ PLRQGRIMST LQGALAQESA CNNTLQQQKR 70 80 90 100 110 120 AFEYEIRFYT GNDPLDVWDR YISWTEQNYP QGGKESNMST LLERAVEALQ GENFRKADAI 130 140 150 160 170 180 FQEGIQQKAE PLERLQSQHR QFQARVSRQT LLALEKEEEE EVFESSVPQR STLAELKSKG 190 200 210 220 230 240 KKTARAPIIR VGGALKAPSQ NRGLQNPFPQ QMQNNSRITV FDENADEAST AELSKPTVQP 250 260 270 280 290 300 WIAPPMPRAK ENELQAGPWN TGRSLEHRPR GNTASLIAVP AVLPSFTPYV EETARQPVMT 310 320 330 340 350 360 PCKIEPSINH ILSTRKPGKE EGDPLQRVQS HQQASEEKKE KMMYCKEKIY AGVGEFSFEE 370 380 390 400 410 420 IRAEVFRKKL KEQREAELLT SAEKRAEMQK QIEEMEKKLK EIQTTQQERT GDQQEETMPT 430 440 450 460 470 480 KETTKLQIAS ESQKIPGMTL SSSVCQVNCC ARETSLAENI WQEQPHSKVS LSLGPSVPFS 490 500 510 520 530 540 IFDEFLLSEK KNKSPPADPP RVLAQRRPLA VLKTSESITS NEDVSPDVCD EFTGIEPLSE 550 560 570 580 590 600 DAIITGFRNV TICPNPEDSR EATHSSGFSG SSASVASTSS IKCLQIPEKL ELTNETSENP 610 620 630 640 650 660 TQSPWCSQYR RQLLKSLPEL SASAELCIED RPMPKLEIEK EIELGNEDYC IKREYLICED 670 680 690 700 710 720 YKLFWVAPRN SAELTVIKVS SQPVPWDFYI NLKLKERLNE DFDHFCSCYQ YQDGCIVWHQ 730 740 750 760 770 780 YINCFTLQDL LQHSEYITHE ITVLIIYNLL TIVEMLHKAE IVHGDLSPRC LILRNRIHDP 790 800 810 820 830 840 YDCNKNNQAL KIVDFSYSVD LRVQLDVFTL SGFRTVQILE GQKILANCSS PYQVDLFGIA 850 860 870 880 890 900 DLAHLLLFKE HLQVFWDGSF WKLSQNISEL KDGELWNKFF VRILNANDEA TVSVLGELAA 910 920 930 EMNGVFDTTF QSHLNKALWK VGKLTSPGAL LFQ
	Isoform 3 [UniParc]. Checksum: FB6C9F104164FBEB	FASTA	1,064	121,386
	10 20 30 40 50 60 MAAVKKEGGA LSEAMSLEGD EWELSKENVQ PLRQGRIMST LQGALAQESA CNNTLQQQKR 70 80 90 100 110 120 AFEYEIRFYT GNDPLDVWDR WVFLFHKDNR NINRYISWTE QNYPQGGKES NMSTLLERAV 130 140 150 160 170 180 EALQGEKRYY SDPRFLNLWL KLGRLCNEPL DMYSYLHNQG IGVSLAQFYI SWAEEYEARE 190 200 210 220 230 240 NFRKADAIFQ EGIQQKAEPL ERLQSQHRQF QARVSRQTLL ALEKEEEEEV FESSVPQRST 250 260 270 280 290 300 LAELKSKGKK TARAPIIRVG GALKAPSQNR GLQNPFPQQM QNNSRITVFD ENADEASTAE 310 320 330 340 350 360 LSKPTVQPWI APPMPRAKEN ELQAGPWNTG RSLEHRPRGN TASLIAVPAV LPSFTPYVEE 370 380 390 400 410 420 TARQPVMTPC KIEPSINHIL STRKPGKEEG DPLQRVQSHQ QASEEKKEKM MYCKEKIYAG 430 440 450 460 470 480 VGEFSFEEIR AEVFRKKLKE QREAELLTSA EKRAEMQKQI EEMEKKLKEI QTTQQERTGD 490 500 510 520 530 540 QQEETMPTKE TTKLQIASES QKIPGMTLSS SVCQVNCCAR ETSLAENIWQ EQPHSKGPSV 550 560 570 580 590 600 PFSIFDEFLL SEKKNKSPPA DPPRVLAQRR PLAVLKTSES ITSNEDVSPD VCDEFTGIEP 610 620 630 640 650 660 LSEDAIITGF RNVTICPNPE DTCDFARAAR FVSTPFHEIM SLKDLPSDPE RLLPEEDLDV 670 680 690 700 710 720 KTSEDQQTAC GTIYSQTLSI KKLSPIIEDS REATHSSGFS GSSASVASTS SIKCLQIPEK 730 740 750 760 770 780 LELTNETSEN PTQSPWCSQY RRQLLKSLPE LSASAELCIE DRPMPKLEIE KEIELGNEDY 790 800 810 820 830 840 CIKREYLICE DYKLFWVAPR NSAELTVIKV SSQPVPWDFY INLKLKERLN EDFDHFCSCY 850 860 870 880 890 900 QYQDGCIVWH QYINCFTLQD LLQHSEYITH EITVLIIYNL LTIVEMLHKA EIVHGDLSPR 910 920 930 940 950 960 CLILRNRIHD PYDCNKNNQA LKIVDFSYSV DLRVQLDVFT LSGFRTVQIL EGQKILANCS 970 980 990 1000 1010 1020 SPYQVDLFGI ADLAHLLLFK EHLQVFWDGS FWKLSQNISE LKDGELWNKF FVRILNANDE 1030 1040 1050 1060 ATVSVLGELA AEMNGVFDTT FQSHLNKALW KVGKLTSPGA LLFQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of a novel gene -- SSK1 -- in human endothelial cells exposed to shear stress." Donadelli R., Benatti L., Remuzzi A., Morigi M., Gullans S.R., Benigni A., Remuzzi G., Noris M. Biochem. Biophys. Res. Commun. 246:881-887(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT GLN-349. Tissue: Umbilical vein.
[2]	"The human homologue of Bub3 is required for kinetochore localization of Bub1 and a Mad3/Bub1-related protein kinase." Taylor S.S., Ha E., McKeon F. J. Cell Biol. 142:1-11(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT GLN-349.
[3]	"Characterization of the kinetochore binding domain of CENP-E reveals interactions with the kinetochore proteins CENP-F and hBUBR1." Chan G.K.T., Schaar B.T., Yen T.J. J. Cell Biol. 143:49-63(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH CENPE, SUBCELLULAR LOCATION, VARIANT GLN-349.
[4]	"Mutations of mitotic checkpoint genes in human cancers." Cahill D.P., Lengauer C., Yu J., Riggins G.J., Willson J.K.V., Markowitz S.D., Kinzler K.W., Vogelstein B. Nature 392:300-303(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS THR-15 AND GLN-349.
[5]	"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] (ISOFORM 1).
[6]	"Human MAD3-like protein kinase (hmad3)." Dai W., Ouyang B., Lan Z., Pan H. Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT GLN-349.
[7]	Seike M., Gemma A., Hosoya Y., Kurimoto F., Yoshimura A., Kudoh S. Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[8]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3), VARIANT GLN-349. Tissue: Tongue.
[9]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[10]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANTS GLN-349 AND SER-378. Tissue: Placenta.
[11]	"BUBR1 phosphorylation is regulated during mitotic checkpoint activation." Li W., Lan Z., Wu H., Wu S., Meadows J., Chen J., Zhu V., Dai W. Cell Growth Differ. 10:769-775(1999) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION, TISSUE SPECIFICITY, INDUCTION.
[12]	"Human BUBR1 is a mitotic checkpoint kinase that monitors CENP-E functions at kinetochores and binds the cyclosome/APC." Chan G.K., Jablonski S.A., Sudakin V., Hittle J.C., Yen T.J. J. Cell Biol. 146:941-954(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INDUCTION, PHOSPHORYLATION, INTERACTION WITH APC/C.
[13]	"Mad2-independent inhibition of APC/Cdc20 by the mitotic checkpoint protein BubR1." Tang Z., Bharadwaj R., Li B., Yu H. Dev. Cell 1:227-237(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, IDENTIFICATION IN A COMPLEX WITH CDC20 AND BUB3, MUTAGENESIS OF LYS-795.
[14]	"Dual roles of human BubR1, a mitotic checkpoint kinase, in the monitoring of chromosomal instability." Shin H.J., Baek K.H., Jeon A.H., Park M.T., Lee S.J., Kang C.M., Lee H.S., Yoo S.H., Chung D.H., Sung Y.C., McKeon F., Lee C.W. Cancer Cell 4:483-497(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, DEGRADATION BY THE PROTEASOME.
[15]	"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, AUTOPHOSPHORYLATION, MUTAGENESIS OF LYS-795.
[16]	"Bub1 is required for kinetochore localization of BubR1, Cenp-E, Cenp-F and Mad2, and chromosome congression." Johnson V.L., Scott M.I., Holt S.V., Hussein D., Taylor S.S. J. Cell Sci. 117:1577-1589(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[17]	"Caspase-mediated specific cleavage of BubR1 is a determinant of mitotic progression." Kim M., Murphy K., Liu F., Parker S.E., Dowling M.L., Baff W., Kao G.D. Mol. Cell. Biol. 25:9232-9248(2005) [PubMed] [Europe PMC] [Abstract] Cited for: CASPASE-3 CLEAVAGE AT ASP-579 AND ASP-610, INDUCTION, MUTAGENESIS OF ASP-579 AND ASP-610.
[18]	"Phosphorylation- and polo-box-dependent binding of Plk1 to Bub1 is required for the kinetochore localization of Plk1." Qi W., Tang Z., Yu H. Mol. Biol. Cell 17:3705-3716(2006) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH PLK1.
[19]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[20]	"Human Blinkin/AF15q14 is required for chromosome alignment and the mitotic checkpoint through direct interaction with Bub1 and BubR1." Kiyomitsu T., Obuse C., Yanagida M. Dev. Cell 13:663-676(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CASC5, MUTAGENESIS OF ALA-159 AND PHE-175.
[21]	"Tension-sensitive Plk1 phosphorylation on BubR1 regulates the stability of kinetochore microtubule interactions." Elowe S., Huemmer S., Uldschmid A., Li X., Nigg E.A. Genes Dev. 21:2205-2219(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PLK1, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-676, MUTAGENESIS OF THR-620.
[22]	"Polo-like kinase 1 facilitates chromosome alignment during prometaphase through BubR1." Matsumura S., Toyoshima F., Nishida E. J. Biol. Chem. 282:15217-15227(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PLK1, SUBCELLULAR LOCATION, PHOSPHORYLATION AT THR-792 AND THR-1008.
[23]	"Phosphorylation sites in BubR1 that regulate kinetochore attachment, tension, and mitotic exit." Huang H., Hittle J., Zappacosta F., Annan R.S., Hershko A., Yen T.J. J. Cell Biol. 183:667-680(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-435; SER-543; SER-670 AND SER-1043.
[24]	"SUMO-2/3 modification and binding regulate the association of CENP-E with kinetochores and progression through mitosis." Zhang X.-D., Goeres J., Zhang H., Yen T.J., Porter A.C.G., Matunis M.J. Mol. Cell 29:729-741(2008) [PubMed] [Europe PMC] [Abstract] Cited for: SUMOYLATION.
[25]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-670, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[26]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-670, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[27]	"Depletion of BubR1 promotes premature centrosomal localization of cyclin B1 and accelerates mitotic entry." Park S.-Y., Kim S., Cho H., Kwon S.-H., Chae S., Kang D., Seong Y.-S., Cho H. Cell Cycle 8:1754-1764(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[28]	"Defects in chromosome congression and mitotic progression in KIF18A-deficient cells are partly mediated through impaired functions of CENP-E." Huang Y., Yao Y., Xu H.-Z., Wang Z.-G., Lu L., Dai W. Cell Cycle 8:2643-2649(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CENPE, SUBCELLULAR LOCATION.
[29]	"BubR1 acetylation at prometaphase is required for modulating APC/C activity and timing of mitosis." Choi E., Choe H., Min J., Choi J.Y., Kim J., Lee H. EMBO J. 28:2077-2089(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PCAF, ACETYLATION AT LYS-250, UBIQUITINATION.
[30]	"BubR1 localizes to centrosomes and suppresses centrosome amplification via regulating Plk1 activity in interphase cells." Izumi H., Matsumoto Y., Ikeuchi T., Saya H., Kajii T., Matsuura S. Oncogene 28:2806-2820(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PLK1.
[31]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-670 AND THR-1042, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[32]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[33]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-543, MASS SPECTROMETRY.
[34]	"Characterization of MAD2B and other mitotic spindle checkpoint genes." Cahill D.P., da Costa L.T., Carson-Walter E.B., Kinzler K.W., Vogelstein B., Lengauer C. Genomics 58:181-187(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS GLN-349 AND ALA-618.
[35]	"Constitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B." Hanks S., Coleman K., Reid S., Plaja A., Firth H., Fitzpatrick D., Kidd A., Mehes K., Nash R., Robin N., Shannon N., Tolmie J., Swansbury J., Irrthum A., Douglas J., Rahman N. Nat. Genet. 36:1159-1161(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MVA1 GLN-550; HIS-814; PHE-844; THR-909; HIS-921 AND PRO-1012.
[36]	"Monoallelic BUB1B mutations and defective mitotic-spindle checkpoint in seven families with premature chromatid separation (PCS) syndrome." Matsuura S., Matsumoto Y., Morishima K., Izumi H., Matsumoto H., Ito E., Tsutsui K., Kobayashi J., Tauchi H., Kajiwara Y., Hama S., Kurisu K., Tahara H., Oshimura M., Komatsu K., Ikeuchi T., Kajii T. Am. J. Med. Genet. A 140:358-367(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT PCS GLN-36.
[37]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] MET-40; GLN-349; ASP-390 AND ALA-618.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF053306 mRNA. Translation: AAC06260.1.
AF046918 mRNA. Translation: AAC33435.1.
AF046079 mRNA. Translation: AAC12730.2.
AF107297 mRNA. Translation: AAD11941.1.
AF035933 mRNA. Translation: AAC23736.1.
AF068760 mRNA. Translation: AAC19118.1.
AF310214 , AF310192, AF310193, AF310194, AF310195, AF310196, AF310197, AF310198, AF310199, AF310200, AF310201, AF310202, AF310203, AF310204, AF310205, AF310206, AF310207, AF310208, AF310209, AF310210, AF310211, AF310212, AF310213 Genomic DNA. Translation: AAL10712.1.
AK296795 mRNA. Translation: BAG59371.1.
AK296984 mRNA. Translation: BAG59525.1.
AK312709 mRNA. Translation: BAG35587.1.
AB208782 mRNA. Translation: BAD92019.1. Different initiation.
BC018739 mRNA. Translation: AAH18739.1.

IPI

IPI00141933.
IPI00921844.
IPI00922915.

PIR

JW0092.

RefSeq

NP_001202.4. NM_001211.5.

UniGene

Hs.513645.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2WVI	X-ray	1.80	A	57-220	[»]
3SI5	X-ray	2.20	A/B	57-220	[»]
4GGD	X-ray	2.44	C/D	20-42	[»]

ProteinModelPortal

O60566.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-24203N.

IntAct

O60566. 28 interactions.

PTM databases

PhosphoSite

O60566.

Proteomic databases

PaxDb

O60566.

PRIDE

O60566.

Protocols and materials databases

DNASU

701.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000287598; ENSP00000287598; ENSG00000156970.
ENST00000412359; ENSP00000398470; ENSG00000156970.

GeneID

701.

KEGG

hsa:701.

UCSC

uc001zkx.4. human.

Organism-specific databases

CTD

701.

GeneCards

GC15P040453.

H-InvDB

HIX0012121.

HGNC

HGNC:1149. BUB1B.

HPA

HPA008419.

MIM

176430. phenotype.
257300. phenotype.
602860. gene.

neXtProt

NX_O60566.

Orphanet

1052. Mosaic variegated aneuploidy syndrome.

PharmGKB

PA82.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG317001.

HOVERGEN

HBG050748.

InParanoid

O60566.

KO

K06637.

OMA

ASTPFHE.

OrthoDB

EOG4FR0QT.

PhylomeDB

O60566.

Enzyme and pathway databases

BRENDA

2.7.11.1. 2681.

Reactome

REACT_115566. Cell Cycle.
REACT_21300. Mitotic M-M/G1 phases.
REACT_6850. Cdc20:Phospho-APC/C mediated degradation of Cyclin A.
REACT_8017. APC-Cdc20 mediated degradation of Nek2A.

Gene expression databases

ArrayExpress

O60566.

Bgee

O60566.

CleanEx

HS_BUB1B.

Genevestigator

O60566.

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.
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. False negative.
PS50011. PROTEIN_KINASE_DOM. False negative.
PS00108. PROTEIN_KINASE_ST. False negative.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

O60566.

GenomeRNAi

701.

NextBio

2866.

SOURCE

Search...

Entry information

Entry name

BUB1B_HUMAN

Accession

Primary (citable) accession number: O60566
Secondary accession number(s): B2R6U0 , B4DL09, B4DLG3, O60501, O60627, O60758, O75389, Q59HH6, Q8WV50, Q96KM4

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	April 3, 2007
Last modified:	May 1, 2013
This is version 136 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.