UniProt Accession

 BUB1B_HUMAN; O60566; B2R6U0; B4DL09; B4DLG3; O60501; O60627; O60758; O75389; Q59HH6; Q8WV50; Q96KM4 

Genbank Protein ID

 AF053306; AF046918; AF046079; AF107297; AF035933; AF068760; AF310214; AF310192; AF310193; AF310194; AF310195; AF310196; AF310197; AF310198; AF310199; AF310200; AF310201; AF310202; AF310203; AF310204; AF310205; AF310206; AF310207; AF310208; AF310209; AF310210; AF310211; AF310212; AF310213; AK296795; AK296984; AK312709; AB208782; BC018739 

Genbank Nucleotide ID

 AAC06260.1; AAC33435.1; AAC12730.2; AAD11941.1; AAC23736.1; AAC19118.1; AAL10712.1; AAL10712.1; AAL10712.1; AAL10712.1; AAL10712.1; AAL10712.1; AAL10712.1; AAL10712.1; AAL10712.1; AAL10712.1; AAL10712.1; AAL10712.1; AAL10712.1; AAL10712.1; AAL10712.1; AAL10712.1; AAL10712.1; AAL10712.1; AAL10712.1; AAL10712.1; AAL10712.1; AAL10712.1; AAL10712.1; BAG59371.1; BAG59525.1; BAG35587.1; BAD92019.1; AAH18739.1 

Protein Name

 Mitotic checkpoint serine/threonine-protein kinase BUB1 beta 

Protein Synonyms/Alias

 MAD3/BUB1-related protein kinase; hBUBR1; Mitotic checkpoint kinase MAD3L; Protein SSK1 

Gene Name

 BUB1B 

Gene Synonyms/Alias

 BUBR1; MAD3L; SSK1 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
113	VEALQGEKRYYSDPR	ubiquitination	[1]
182	FQEGIQQKAEPLERL	ubiquitination	[1]
210	QTLLALEKEEEEEVF	ubiquitination	[2]
250	IRVGGALKAPSQNRG	acetylation	[3]
250	IRVGGALKAPSQNRG	sumoylation	[4]
250	IRVGGALKAPSQNRG	ubiquitination	[1, 5]
304	APPMPRAKENELQAG	ubiquitination	[5]
370	NHILSTRKPGKEEGD	ubiquitination	[1]
454	EEMEKKLKEIQTTQQ	ubiquitination	[1]
475	QEETMPTKETTKLQI	ubiquitination	[1, 2, 5]
488	QIASESQKIPGMTLS	ubiquitination	[1]
540	EFLLSEKKNKSPPAD	ubiquitination	[1]
629	FHEIMSLKDLPSDPE	ubiquitination	[1, 2]
668	SQTLSIKKLSPIIED	ubiquitination	[1]
757	MPKLEIEKEIELGNE	ubiquitination	[1]
769	GNEDYCIKREYLICE	ubiquitination	[1]
995	KDGELWNKFFVRILN	ubiquitination	[2, 6]
1037	HLNKALWKVGKLTSP	ubiquitination	[1]
1040	KALWKVGKLTSPGAL	ubiquitination	[1]

Reference

 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [3] BubR1 acetylation at prometaphase is required for modulating APC/C activity and timing of mitosis.
 Choi E, Choe H, Min J, Choi JY, Kim J, Lee H.
 EMBO J. 2009 Jul 22;28(14):2077-89. [PMID: 19407811]
 [4] BubR1 is modified by sumoylation during mitotic progression.
 Yang F, Hu L, Chen C, Yu J, O'Connell CB, Khodjakov A, Pagano M, Dai W.
 J Biol Chem. 2012 Feb 10;287(7):4875-82. [PMID: 22167194]
 [5] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [6] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473] 

Functional Description

 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. 

Sequence Annotation

 DOMAIN 62 226 BUB1 N-terminal.
 DOMAIN 766 1050 Protein kinase.
 NP_BIND 772 780 ATP (By similarity).
 REGION 152 185 Necessary for interaction with CASC5.
 MOTIF 111 118 Nuclear localization signal (Potential).
 MOTIF 224 232 D-box.
 ACT_SITE 882 882 Proton acceptor (By similarity).
 BINDING 795 795 ATP (By similarity).
 MOD_RES 250 250 N6-acetyllysine; by PCAF.
 MOD_RES 435 435 Phosphoserine.
 MOD_RES 543 543 Phosphoserine.
 MOD_RES 670 670 Phosphoserine.
 MOD_RES 676 676 Phosphoserine; by PLK1.
 MOD_RES 792 792 Phosphothreonine; by PLK1.
 MOD_RES 1008 1008 Phosphothreonine; by PLK1.
 MOD_RES 1042 1042 Phosphothreonine.
 MOD_RES 1043 1043 Phosphoserine.  

Keyword

 3D-structure; Acetylation; Alternative splicing; Apoptosis; ATP-binding; Cell cycle; Cell division; Centromere; Chromosome; Complete proteome; Cytoplasm; Cytoskeleton; Disease mutation; Kinase; Kinetochore; Mitosis; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Serine/threonine-protein kinase; Transferase; Tumor suppressor; Ubl conjugation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 1050 AA 

Protein Sequence

Gene Ontology

 GO:0005680; C:anaphase-promoting complex; TAS:ProtInc.
 GO:0000940; C:condensed chromosome outer kinetochore; IDA:UniProtKB.
 GO:0000778; C:condensed nuclear chromosome kinetochore; IEA:Compara.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
 GO:0048471; C:perinuclear region of cytoplasm; IDA:BHF-UCL.
 GO:0051233; C:spindle midzone; NAS:UniProtKB.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004672; F:protein kinase activity; NAS:UniProtKB.
 GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
 GO:0031145; P:anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process; TAS:Reactome.
 GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
 GO:0051301; P:cell division; IEA:UniProtKB-KW.
 GO:0008283; P:cell proliferation; TAS:ProtInc.
 GO:0007091; P:metaphase/anaphase transition of mitotic cell cycle; IEA:Compara.
 GO:0007067; P:mitosis; NAS:UniProtKB.
 GO:0007094; P:mitotic spindle assembly checkpoint; TAS:Reactome.
 GO:0051436; P:negative regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle; TAS:Reactome.
 GO:0048015; P:phosphatidylinositol-mediated signaling; NAS:UniProtKB.
 GO:0071459; P:protein localization to chromosome, centromeric region; IEA:Compara.
 GO:0034501; P:protein localization to kinetochore; IPI:UniProtKB.
 GO:0007051; P:spindle organization; NAS:UniProtKB. 

Interpro

 IPR015661; Bub1/Mad3.
 IPR011009; Kinase-like_dom.
 IPR013212; Mad3_BUB1_I.
 IPR000719; Prot_kinase_cat_dom. 

Pfam

 PF08311; Mad3_BUB1_I
 PF00069; Pkinase 

SMART

 SM00777; Mad3_BUB1_I 

PROSITE

 PS51489; BUB1_N
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST 

PRINTS