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O60566 (BUB1B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 148. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1050 AA.
Sequence statusComplete.
Protein existenceEvidence 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.28 Ref.31

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.29 Ref.30 Ref.31

Subcellular location

Cytoplasm. Nucleus. Chromosomecentromerekinetochore. Cytoplasmcytoskeletonmicrotubule organizing centercentrosome. 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.29 Ref.31

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. Ref.30

Ubiquitinated. Degraded by the proteasome. Ref.14 Ref.30

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.37

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.36

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 processApoptosis
Cell cycle
Cell division
Mitosis
   Cellular componentCentromere
Chromosome
Cytoplasm
Cytoskeleton
Kinetochore
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
Tumor suppressor
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMAcetylation
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processanaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process

Traceable author statement. Source: Reactome

apoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

cell cycle

Non-traceable author statement PubMed 15504738. Source: UniProtKB

cell proliferation

Traceable author statement Ref.12. Source: ProtInc

metaphase/anaphase transition of mitotic cell cycle

Inferred from electronic annotation. Source: Ensembl

mitotic cell cycle

Traceable author statement. Source: Reactome

mitotic cell cycle checkpoint

Traceable author statement Ref.12. Source: ProtInc

mitotic nuclear division

Non-traceable author statement Ref.3. Source: UniProtKB

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: Ensembl

protein localization to kinetochore

Inferred from physical interaction Ref.2. Source: UniProtKB

regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle

Traceable author statement. Source: Reactome

spindle organization

Non-traceable author statement PubMed 15504738. Source: UniProtKB

   Cellular_componentanaphase-promoting complex

Traceable author statement Ref.12. Source: ProtInc

condensed chromosome kinetochore

Inferred from direct assay PubMed 19465021. Source: UniProtKB

condensed chromosome outer kinetochore

Inferred from direct assay PubMed 19468067. Source: UniProtKB

condensed nuclear chromosome kinetochore

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from direct assay. Source: LIFEdb

cytosol

Traceable author statement. Source: Reactome

kinetochore

Inferred from direct assay Ref.2. Source: UniProtKB

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_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction PubMed 15525512Ref.18Ref.20Ref.2Ref.3. Source: UniProtKB

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...

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10501050Mitotic checkpoint serine/threonine-protein kinase BUB1 beta
PRO_0000085673

Regions

Domain62 – 226165BUB1 N-terminal
Domain766 – 1050285Protein kinase
Nucleotide binding772 – 7809ATP By similarity
Region152 – 18534Necessary for interaction with CASC5
Motif111 – 1188Nuclear localization signal Potential
Motif224 – 2329D-box
Compositional bias209 – 2157Poly-Glu

Sites

Active site8821Proton acceptor By similarity
Binding site7951ATP By similarity
Site579 – 5802Cleavage; by caspase-3
Site610 – 6112Cleavage; by caspase-3

Amino acid modifications

Modified residue2501N6-acetyllysine; by PCAF Ref.30
Modified residue4351Phosphoserine Ref.23
Modified residue5431Phosphoserine Ref.23 Ref.34
Modified residue6701Phosphoserine Ref.23 Ref.25 Ref.26 Ref.32
Modified residue6761Phosphoserine; by PLK1 Ref.21
Modified residue7921Phosphothreonine; by PLK1 Ref.22
Modified residue10081Phosphothreonine; by PLK1 Ref.22
Modified residue10421Phosphothreonine Ref.32
Modified residue10431Phosphoserine Ref.23

Natural variations

Alternative sequence801R → RWVFLFHKDNRNINR in isoform 3.
VSP_036473
Alternative sequence113 – 16654Missing in isoform 2.
VSP_036474
Alternative sequence5221K → KVSLSL in isoform 2.
VSP_036475
Alternative sequence608 – 67568Missing in isoform 2.
VSP_036476
Natural variant151M → T in a colorectal cancer cell line. Ref.4
VAR_008852
Natural variant361R → Q in PCS. Ref.37
VAR_028921
Natural variant401T → M. Ref.38
Corresponds to variant rs56079734 [ dbSNP | Ensembl ].
VAR_040402
Natural variant3491R → Q. Ref.1 Ref.2 Ref.3 Ref.4 Ref.6 Ref.8 Ref.10 Ref.35 Ref.38
Corresponds to variant rs1801376 [ dbSNP | Ensembl ].
VAR_008853
Natural variant3781P → S. Ref.10
Corresponds to variant rs17851677 [ dbSNP | Ensembl ].
VAR_054549
Natural variant3901E → D. Ref.38
Corresponds to variant rs1017842 [ dbSNP | Ensembl ].
VAR_028922
Natural variant5501R → Q in MVA1; heterozygous compound with nonsense mutation. Ref.36
Corresponds to variant rs28989187 [ dbSNP | Ensembl ].
VAR_028923
Natural variant6181V → A in colorectal cancer. Ref.35 Ref.38
Corresponds to variant rs1801528 [ dbSNP | Ensembl ].
VAR_008854
Natural variant8141R → H in MVA1; heterozygous compound with nonsense mutation. Ref.36
Corresponds to variant rs28989182 [ dbSNP | Ensembl ].
VAR_028924
Natural variant8441L → F in MVA1; associated with H-921; heterozygous compound with nonsense mutation. Ref.36
Corresponds to variant rs28989181 [ dbSNP | Ensembl ].
VAR_028925
Natural variant9091I → T in MVA1; heterozygous compound with nonsense mutation. Ref.36
Corresponds to variant rs28989184 [ dbSNP | Ensembl ].
VAR_028926
Natural variant9211Q → H in MVA1; associated with F-844; heterozygous compound with nonsense mutation. Ref.36
Corresponds to variant rs28989183 [ dbSNP | Ensembl ].
VAR_028927
Natural variant10121L → P in MVA1; heterozygous compound with nonsense mutation. Ref.36
Corresponds to variant rs28989185 [ dbSNP | Ensembl ].
VAR_028928

Experimental info

Mutagenesis1591A → W: Loss of interaction with CASC5. Ref.20
Mutagenesis1751F → A: Loss of interaction with CASC5. Ref.20
Mutagenesis5791D → E: Abolishes the cleavage by caspase-3. Ref.17
Mutagenesis6101D → E: Abolishes the cleavage by caspase-3. Ref.17
Mutagenesis6201T → A: Induces chromosome congression defects and mitotic delay. Ref.21
Mutagenesis7951K → A: Does not abolish the capacity to inhibit APC/CDC20. Ref.13 Ref.15
Mutagenesis7951K → R: Inhibits kinase activity. Ref.13 Ref.15
Sequence conflict248 – 2492AL → VF in AAC23736. Ref.1
Sequence conflict2831S → P in BAG35587. Ref.8
Sequence conflict7881S → F in AAC06260. Ref.2
Sequence conflict10181E → K in AAC33435. Ref.3

Secondary structure

........................ 1050
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified April 3, 2007. Version 3.
Checksum: F7871103A56E6B46

FASTA1,050119,545
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 81D1307E360D7B67
Show »

FASTA933105,890
Isoform 3 [UniParc].

Checksum: FB6C9F104164FBEB
Show »

FASTA1,064121,386

References

« Hide '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. expand/collapse author list , 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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[27]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[28]"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.
[29]"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.
[30]"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.
[31]"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.
[32]"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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[33]"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].
[34]"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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[35]"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.
[36]"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.
[37]"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.
[38]"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. expand/collapse author list , 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.

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 expand/collapse EMBL AC list , 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.
CCDSCCDS10053.1. [O60566-1]
PIRJW0092.
RefSeqNP_001202.4. NM_001211.5.
UniGeneHs.513645.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2WVIX-ray1.80A57-220[»]
3SI5X-ray2.20A/B57-220[»]
4GGDX-ray2.44C/D20-42[»]
ProteinModelPortalO60566.
SMRO60566. Positions 20-203, 720-1033.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107166. 58 interactions.
DIPDIP-24203N.
IntActO60566. 39 interactions.
MINTMINT-2796866.

PTM databases

PhosphoSiteO60566.

Proteomic databases

MaxQBO60566.
PaxDbO60566.
PRIDEO60566.

Protocols and materials databases

DNASU701.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000287598; ENSP00000287598; ENSG00000156970. [O60566-1]
ENST00000412359; ENSP00000398470; ENSG00000156970. [O60566-3]
GeneID701.
KEGGhsa:701.
UCSCuc001zkx.4. human. [O60566-1]

Organism-specific databases

CTD701.
GeneCardsGC15P040453.
H-InvDBHIX0012121.
HGNCHGNC:1149. BUB1B.
HPAHPA008419.
MIM176430. phenotype.
257300. phenotype.
602860. gene.
neXtProtNX_O60566.
Orphanet1052. Mosaic variegated aneuploidy syndrome.
PharmGKBPA82.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG317001.
HOVERGENHBG050748.
InParanoidO60566.
KOK06637.
OMAATHSSGF.
OrthoDBEOG7DFXCB.
PhylomeDBO60566.
TreeFamTF105456.

Enzyme and pathway databases

BRENDA2.7.11.1. 2681.
ReactomeREACT_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.
SignaLinkO60566.

Gene expression databases

ArrayExpressO60566.
BgeeO60566.
CleanExHS_BUB1B.
GenevestigatorO60566.

Family and domain databases

InterProIPR015661. Bub1/Mad3.
IPR011009. Kinase-like_dom.
IPR013212. Mad3_BUB1_I.
IPR000719. Prot_kinase_dom.
[Graphical view]
PANTHERPTHR14030. PTHR14030. 1 hit.
PfamPF08311. Mad3_BUB1_I. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00777. Mad3_BUB1_I. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS51489. BUB1_N. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceO60566.
GeneWikiBUB1B.
GenomeRNAi701.
NextBio2866.
PROO60566.
SOURCESearch...

Entry information

Entry nameBUB1B_HUMAN
AccessionPrimary (citable) accession number: O60566
Secondary accession number(s): B2R6U0 expand/collapse secondary AC list , 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: July 9, 2014
This is version 148 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM