O43683 (BUB1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Mitotic checkpoint serine/threonine-protein kinase BUB1
Short name=hBUB1
EC=2.7.11.1

Alternative name(s):
BUB1A

Gene names

Name:	BUB1
Synonyms:	BUB1L

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	1085 AA.
Sequence status	Complete.
Protein existence	Evidence at protein 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. Ref.4 Ref.10 Ref.11 Ref.12 Ref.13 Ref.15 Ref.20
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	Autophosphorylated when the cells enters mitosis.
Subunit structure	Interacts with BUB3 and CASC5. Interacts (when phosphorylated) with PLK1. The BUB1-BUB3 complex interacts with MAD1L1. Interacts with SV40 Large T antigen; this interaction induces activation of a DNA damage response and promotes p53/TP53 stabilization and phosphorylation Probable. Ref.4 Ref.11 Ref.13 Ref.14 Ref.19
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. Ref.10 Ref.13 Ref.14 Ref.15
Tissue specificity	High expression in testis and thymus, less in colon, spleen, lung and small intestine. Expressed in fetal thymus, bone marrow, heart, liver, spleen and thymus. Expression is associated with cells/tissues with a high mitotic index.
Induction	Inhibited by phorbol 12-myristate 13-acetate (PMA).
Domain	The KEN box is required for its ubiquitination and degradation. Ref.15 BUB1 N-terminal domain directs kinetochore localization and binding to BUB3. Ref.15
Post-translational modification	Upon spindle-assembly checkpoint activation it is hyperphosphorylated and its kinase activity toward CDC20 is stimulated. Phosphorylation at Thr-609 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. Ref.4 Ref.11 Ref.13 Ubiquitinated and degraded during mitotic exit by APC/C-Cdh1. Ref.15
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 Chromosome partition Host-virus interaction Mitosis
Cellular component	Centromere Chromosome Kinetochore Nucleus
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure 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 cell proliferation Inferred from electronic annotation. Source: Compara chromosome segregation Inferred from electronic annotation. Source: UniProtKB-KW mitotic prometaphase Traceable author statement. Source: Reactome mitotic spindle assembly checkpoint Traceable author statement Ref.2. Source: ProtInc regulation of sister chromatid cohesion Inferred from direct assay Ref.12. Source: UniProtKB virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	condensed chromosome kinetochore Inferred from direct assay PubMed 19465021. Source: UniProtKB condensed nuclear chromosome, centromeric region Inferred from electronic annotation. Source: Compara cytosol Traceable author statement. Source: Reactome
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein kinase activity Traceable author statement Ref.4. Source: ProtInc 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 – 1085

1085

Mitotic checkpoint serine/threonine-protein kinase BUB1

PRO_0000085671

Regions

Domain

11 – 182

172

BUB1 N-terminal

Domain

787 – 1085

299

Protein kinase

Nucleotide binding

793 – 801

9

ATP By similarity

Region

1 – 146

146

Necessary for kinetochore localization

Region

99 – 132

34

Necessary for interaction with CASC5

Region

229 – 256

28

Necessary for interaction with BUB3

Region

458 – 476

19

Essential for loading of BUBR1, MAD1L1 and MAD2L1 to kinetochores

Motif

58 – 65

8

Nuclear localization signal Potential

Motif

535 – 537

3

KEN box 1

Motif

625 – 627

3

KEN box 2

Sites

Active site

917

1

Proton acceptor By similarity

Binding site

821

1

ATP By similarity

Amino acid modifications

Modified residue

314

1

Phosphoserine Ref.16 Ref.21

Modified residue

375

1

Phosphoserine Ref.21

Modified residue

563

1

Phosphoserine Ref.21 Ref.22

Modified residue

593

1

Phosphoserine Ref.18 Ref.22 Ref.23

Modified residue

596

1

Phosphoserine Ref.17 Ref.18 Ref.21 Ref.22 Ref.23 Ref.25

Modified residue

609

1

Phosphothreonine; by CDK1 Ref.13

Modified residue

655

1

Phosphoserine Ref.17 Ref.21

Natural variations

Natural variant

20

1

G → D. Ref.27
Corresponds to variant rs35890336 [ dbSNP | Ensembl ].

VAR_040400

Natural variant

36

1

E → D in colorectal cancer. Ref.5
Corresponds to variant rs1801328 [ dbSNP | Ensembl ].

VAR_008849

Natural variant

259

1

Y → C in pancreatic cancer; associated with N-265; failure to rescue the spindle-assembly checkpoint activity as a result of a deficient recruitment of MAD2L1 and BUBR1 to kinetochores; efficient restoration of chromosome congression; reduced binding to BUB3; rescue of the ability of kinetochores to bind SGOL1 and CENPF but not MCAK. Ref.20 Ref.26

VAR_015687

Natural variant

265

1

H → N in pancreatic cancer; associated with C-259; complete rescue of the spindle-assembly checkpoint activity; increased rate of chromosome congression errors. Ref.20 Ref.26

VAR_015688

Natural variant

492

1

S → Y in colorectal cancer. Ref.1

VAR_008850

Natural variant

534

1

N → D. Ref.27
Corresponds to variant rs36109304 [ dbSNP | Ensembl ].

VAR_040401

Natural variant

648

1

P → R in colorectal cancer. Ref.5

VAR_008851

Experimental info

Mutagenesis

106

1

A → D or W: Loss of interaction with CASC5. Ref.14

Mutagenesis

122

1

L → G: Loss of interaction with CASC5. Ref.14

Mutagenesis

130

1

A → S: Partial rescue of the spindle-assembly checkpoint activity. Increased rate of chromosome congression errors. Impaired localization to kinetochores and loss of kinetochore binding of CENPF, SGOL1 and BUBR1 but not of MCAK, MAD1L1 or MAD2L1. Ref.20

Mutagenesis

535

1

K → A: Loss of ubiquitination and CDH1-dependent degradation; when associated with A-536 and A-537. Ref.15

Mutagenesis

536

1

E → A: Loss of ubiquitination and CDH1-dependent degradation; when associated with A-535 and A-537. Ref.15

Mutagenesis

537

1

N → A: Loss of ubiquitination and CDH1-dependent degradation; when associated with A-535 and A-536. Ref.15

Mutagenesis

609

1

T → A: Diminished interaction with PLK1. Ref.13

Mutagenesis

625

1

K → A: Loss of ubiquitination and CDH1-dependent degradation; when associated with A-626 and A-627. Ref.15

Mutagenesis

626

1

E → A: Loss of ubiquitination and CDH1-dependent degradation; when associated with A-625 and A-627. Ref.15

Mutagenesis

627

1

N → A: Loss of ubiquitination and CDH1-dependent degradation; when associated with A-625 and A-626. Ref.15

Mutagenesis

821

1

K → A: Loss of activity. Ref.4

Sequence conflict

70

1

S → T in AAC06259. Ref.5

Sequence conflict

276 – 279

4

MKRK → IRHE in AAC39546. Ref.9

Secondary structure

1

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1085

Helix Strand Turn

Details...

Helix

3 – 14

12

Helix

23 – 35

13

Helix

43 – 56

14

Helix

60 – 62

3

Helix

66 – 76

11

Helix

82 – 90

9

Turn

91 – 97

7

Helix

99 – 111

13

Helix

115 – 127

13

Helix

133 – 145

13

Beta strand

736 – 739

4

Helix

744 – 752

9

Helix

758 – 760

3

Beta strand

764 – 766

3

Beta strand

779 – 781

3

Beta strand

783 – 795

13

Beta strand

797 – 805

9

Beta strand

818 – 825

8

Helix

828 – 840

13

Helix

843 – 848

6

Beta strand

852 – 857

6

Beta strand

862 – 866

5

Helix

874 – 882

9

Helix

891 – 909

19

Turn

910 – 912

3

Helix

920 – 922

3

Beta strand

923 – 925

3

Helix

927 – 929

3

Beta strand

942 – 944

3

Helix

953 – 955

3

Beta strand

960 – 962

3

Helix

974 – 977

4

Helix

985 – 1000

16

Beta strand

1006 – 1009

4

Beta strand

1012 – 1015

4

Helix

1025 – 1036

12

Helix

1047 – 1061

15

Turn

1062 – 1065

4

Helix

1066 – 1079

14

Sequences

	Sequence		Length	Mass (Da)
	O43683 [UniParc]. Last modified June 1, 1998. Version 1. Checksum: 38AE5E1F88C53BDC	FASTA	1,085	122,375
	10 20 30 40 50 60 MDTPENVLQM LEAHMQSYKG NDPLGEWERY IQWVEENFPE NKEYLITLLE HLMKEFLDKK 70 80 90 100 110 120 KYHNDPRFIS YCLKFAEYNS DLHQFFEFLY NHGIGTLSSP LYIAWAGHLE AQGELQHASA 130 140 150 160 170 180 VLQRGIQNQA EPREFLQQQY RLFQTRLTET HLPAQARTSE PLHNVQVLNQ MITSKSNPGN 190 200 210 220 230 240 NMACISKNQG SELSGVISSA CDKESNMERR VITISKSEYS VHSSLASKVD VEQVVMYCKE 250 260 270 280 290 300 KLIRGESEFS FEELRAQKYN QRRKHEQWVN EDRHYMKRKE ANAFEEQLLK QKMDELHKKL 310 320 330 340 350 360 HQVVETSHED LPASQERSEV NPARMGPSVG SQQELRAPCL PVTYQQTPVN MEKNPREAPP 370 380 390 400 410 420 VVPPLANAIS AALVSPATSQ SIAPPVPLKA QTVTDSMFAV ASKDAGCVNK STHEFKPQSG 430 440 450 460 470 480 AEIKEGCETH KVANTSSFHT TPNTSLGMVQ ATPSKVQPSP TVHTKEALGF IMNMFQAPTL 490 500 510 520 530 540 PDISDDKDEW QSLDQNEDAF EAQFQKNVRS SGAWGVNKII SSLSSAFHVF EDGNKENYGL 550 560 570 580 590 600 PQPKNKPTGA RTFGERSVSR LPSKPKEEVP HAEEFLDDST VWGIRCNKTL APSPKSPGDF 610 620 630 640 650 660 TSAAQLASTP FHKLPVESVH ILEDKENVVA KQCTQATLDS CEENMVVPSR DGKFSPIQEK 670 680 690 700 710 720 SPKQALSSHM YSASLLRLSQ PAAGGVLTCE AELGVEACRL TDTDAAIAED PPDAIAGLQA 730 740 750 760 770 780 EWMQMSSLGT VDAPNFIVGN PWDDKLIFKL LSGLSKPVSS YPNTFEWQCK LPAIKPKTEF 790 800 810 820 830 840 QLGSKLVYVH HLLGEGAFAQ VYEATQGDLN DAKNKQKFVL KVQKPANPWE FYIGTQLMER 850 860 870 880 890 900 LKPSMQHMFM KFYSAHLFQN GSVLVGELYS YGTLLNAINL YKNTPEKVMP QGLVISFAMR 910 920 930 940 950 960 MLYMIEQVHD CEIIHGDIKP DNFILGNGFL EQDDEDDLSA GLALIDLGQS IDMKLFPKGT 970 980 990 1000 1010 1020 IFTAKCETSG FQCVEMLSNK PWNYQIDYFG VAATVYCMLF GTYMKVKNEG GECKPEGLFR 1030 1040 1050 1060 1070 1080 RLPHLDMWNE FFHVMLNIPD CHHLPSLDLL RQKLKKVFQQ HYTNKIRALR NRLIVLLLEC KRSRK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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], VARIANT TYR-492.
[2]	"Human Bub1: a putative spindle checkpoint kinase closely linked to cell proliferation." Ouyang B., Lan Z., Meadows J., Pan H., Fukasawa K., Li W., Dai W. Cell Growth Differ. 9:877-885(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"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].
[4]	"Phosphorylation of human MAD1 by the BUB1 kinase in vitro." Seeley T.W., Wang L., Zhen J.Y. Biochem. Biophys. Res. Commun. 257:589-595(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, PHOSPHORYLATION, INTERACTION WITH BUB3 AND MAD1L1, MUTAGENESIS OF LYS-821. Tissue: Testis.
[5]	"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: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ASP-36 AND ARG-648.
[6]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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]. Tissue: Lung.
[9]	"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] OF 276-1085.
[10]	"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, SUBCELLULAR LOCATION.
[11]	"Phosphorylation of Cdc20 by Bub1 provides a catalytic mechanism for APC/C inhibition by the spindle checkpoint." Tang Z., Shu H., Oncel D., Chen S., Yu H. Mol. Cell 16:387-397(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION, INTERACTION WITH BUB3.
[12]	"Human Bub1 defines the persistent cohesion site along the mitotic chromosome by affecting Shugoshin localization." Kitajima T.S., Hauf S., Ohsugi M., Yamamoto T., Watanabe Y. Curr. Biol. 15:353-359(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[13]	"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: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PLK1, PHOSPHORYLATION AT THR-609, MUTAGENESIS OF THR-609.
[14]	"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: SUBCELLULAR LOCATION, INTERACTION WITH CASC5, MUTAGENESIS OF ALA-106 AND LEU-122.
[15]	"KEN-box-dependent degradation of the Bub1 spindle checkpoint kinase by the anaphase-promoting complex/cyclosome." Qi W., Yu H. J. Biol. Chem. 282:3672-3679(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, UBIQUITINATION, DOMAIN KEN BOX, MUTAGENESIS OF LYS-535; GLU-536; ASN-537; LYS-625; GLU-626 AND ASN-627.
[16]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-314, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[17]	"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-596 AND SER-655, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[18]	"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-593 AND SER-596, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[19]	"Simian virus 40 large T antigen disrupts genome integrity and activates a DNA damage response via Bub1 binding." Hein J., Boichuk S., Wu J., Cheng Y., Freire R., Jat P.S., Roberts T.M., Gjoerup O.V. J. Virol. 83:117-127(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SV40 LARGE T ANTIGEN.
[20]	"Bub1 regulates chromosome segregation in a kinetochore-independent manner." Klebig C., Korinth D., Meraldi P. J. Cell Biol. 185:841-858(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF ALA-130, CHARACTERIZATION OF VARIANTS CYS-259 AND ASN-265.
[21]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-314; SER-375; SER-563; SER-596 AND SER-655, MASS SPECTROMETRY.
[22]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-563; SER-593 AND SER-596, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[23]	"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-593 AND SER-596, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[24]	"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].
[25]	"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-596, MASS SPECTROMETRY.
[26]	"A double missense variation of the BUB1 gene and a defective mitotic spindle checkpoint in the pancreatic cancer cell line Hs766T." Hempen P.M., Kurpad H., Calhoun E.S., Abraham S., Kern S.E. Hum. Mutat. 21:445-445(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PANCREATIC CANCER CYS-259 AND ASN-265.
[27]	"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] ASP-20 AND ASP-534.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF046078 mRNA. Translation: AAC12729.1.
AF043294 mRNA. Translation: AAB97855.2.
AF053305 mRNA. Translation: AAC06259.1.
AF047471 mRNA. Translation: AAC03122.1.
AF139363 , AF139349, AF139350, AF139351, AF139352, AF139353, AF139354, AF139355, AF139356, AF139357, AF139358, AF139359, AF139360, AF139361, AF139362 Genomic DNA. Translation: AAD43675.1.
AC114776 Genomic DNA. Translation: AAY14706.1.
CH471237 Genomic DNA. Translation: EAW50355.1.
BC028201 mRNA. Translation: AAH28201.1.
AF011387 mRNA. Translation: AAC39546.1.

IPI

IPI00783305.

RefSeq

NP_004327.1. NM_004336.3.

UniGene

Hs.469649.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2LAH	NMR	-	A	1-150	[»]
3E7E	X-ray	2.31	A	724-1085	[»]
4A1G	X-ray	2.60	A/B/C/D	1-150	[»]

ProteinModelPortal

O43683.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-24206N.

IntAct

O43683. 24 interactions.

MINT

MINT-1460788.

STRING

9606.ENSP00000302530.

PTM databases

PhosphoSite

O43683.

Proteomic databases

PaxDb

O43683.

PRIDE

O43683.

Protocols and materials databases

DNASU

699.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000302759; ENSP00000302530; ENSG00000169679.

GeneID

699.

KEGG

hsa:699.

UCSC

uc002tgc.3. human.

Organism-specific databases

CTD

699.

GeneCards

GC02M111395.

HGNC

HGNC:1148. BUB1.

HPA

HPA006123.

MIM

602452. gene.

neXtProt

NX_O43683.

PharmGKB

PA81.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG317001.

HOGENOM

HOG000231751.

HOVERGEN

HBG003709.

InParanoid

O43683.

KO

K02178.

OMA

HEQWVNE.

Enzyme and pathway databases

BRENDA

2.7.11.1. 2681.

Pathway_Interaction_DB

aurora_b_pathway. Aurora B signaling.

Reactome

REACT_115566. Cell Cycle.
REACT_21300. Mitotic M-M/G1 phases.

Gene expression databases

ArrayExpress

O43683.

Bgee

O43683.

CleanEx

HS_BUB1.

Genevestigator

O43683.

GermOnline

ENSG00000169679. Homo sapiens.

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

BindingDB

O43683.

ChEMBL

CHEMBL1772932.

ChiTaRS

Bub1. human.

EvolutionaryTrace

O43683.

GenomeRNAi

699.

NextBio

2860.

SOURCE

Search...

Entry information

Entry name

BUB1_HUMAN

Accession

Primary (citable) accession number: O43683
Secondary accession number(s): O43430 , O43643, O60626, Q53QE4

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	June 1, 1998
Last modified:	May 1, 2013
This is version 126 of the entry and version 1 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.