Reviewed, UniProtKB/Swiss-Prot O60566 (BUB1B_HUMAN)

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)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1050 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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. 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
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	Kinase activity stimulated by CENPE. Ref.15
Subunit structure	Interacts with CENPE, CENPF, mitosin and BUB3. Part of a complex containing BUB3, CDC20 and BUB1B. Interacts with anaphase-promoting complex/cyclosome (APC/C). Ref.12 Ref.15 Ref.3
Subcellular location	Cytoplasm. Nucleus. Kinetochore. Note: Cytoplasmic in interphase cells. Associates with the kinetochores in early prophase. Ref.12 Ref.14 Ref.3
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.12 Ref.11 Ref.16
Domain	The CD1 domain directs kinetochore localization and binding to BUB3. The D-box targets the protein for rapid degradation by ubiquitin-dependent proteolysis during the transition from mitosis to interphase Potential.
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.16 Ubiquitinated Probable. Degradated by the proteasome. Autophosphorylated in vitro. Intramolecular autophosphorylation is stimulated by CENPE. Phosphorylated during mitosis and hyperphosphorylated in mitotically arrested cells. Ref.12 Ref.15 Ref.11 Ref.17 Ref.18 Ref.19
Involvement in disease	Defects in BUB1B are associated with tumor formation. Defects in BUB1B are the cause of premature chromatid separation trait (PCS) [MIM:176430]. PCS 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. Ref.23 Defects in BUB1B are the cause of mosaic variegated aneuploidy syndrome (MVA) [MIM:257300]. MVA is a severe autosomal recessive developmental disorder characterized by mosaic aneuploidies, predominantly trisomies and monosomies, involving multiple different chromosomes and tissues. The proportion of aneuploid cells varies but is usually more than 25% and is substantially greater than in normal individuals. 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. MVA is caused by biallelic mutations in the BUB1B gene. Ref.22
Sequence similarities	Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. BUB1 subfamily. Contains 1 CD1 domain. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Apoptosis Cell cycle Cell division Mitosis
Cellular component	Cytoplasm Kinetochore Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Ligand	ATP-binding Nucleotide-binding
Molecular function	Anti-oncogene Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein Ubl conjugation
Gene Ontology (GO)
Biological process	anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process Inferred from Experiment. Source: Reactome apoptosis Inferred from electronic annotation. Source: UniProtKB-KW cell division Inferred from electronic annotation. Source: UniProtKB-KW cell proliferation Ref.12 Traceable author statement. Source: ProtInc mitotic cell cycle checkpoint Ref.12 Traceable author statement. Source: ProtInc negative regulation of cell cycle Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of ubiquitin-protein ligase activity during mitotic cell cycle Inferred from Experiment. Source: Reactome phosphoinositide-mediated signaling Non-traceable author statement. Source: UniProtKB spindle organization Non-traceable author statement. Source: UniProtKB
Cellular component	anaphase-promoting complex Ref.12 Traceable author statement. Source: ProtInc cytosol Inferred from Experiment. Source: Reactome spindle midzone Ref.3 Non-traceable author statement. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Ref.3 Inferred from physical interaction. 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	4	EBI-1001438,EBI-367462
CENPE	Q02224	2	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 – 213	152	CD1
	Domain	766 – 1050	285	Protein kinase
	Nucleotide binding	772 – 780	9	ATP By similarity
	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	54	1	Phosphothreonine Ref.17
	Modified residue	435	1	Phosphoserine Ref.19
	Modified residue	670	1	Phosphoserine Ref.18 Ref.19
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.23		VAR_028921
	Natural variant	40	1	T → M Ref.24		VAR_040402
	Natural variant	349	1	R → Q: dbSNP rs1801376. Ref.3 Ref.4 Ref.24 Ref.1 Ref.2 Ref.6 Ref.8 Ref.10 Ref.21		VAR_008853
	Natural variant	378	1	P → S: dbSNP rs17851677. Ref.10		VAR_054549
	Natural variant	390	1	E → D: dbSNP rs1017842. Ref.24		VAR_028922
	Natural variant	550	1	R → Q in MVA; heterozygous compound with nonsense mutation. dbSNP rs28989187. Ref.22		VAR_028923
	Natural variant	618	1	V → A in colorectal cancer. dbSNP rs1801528. Ref.24 Ref.21		VAR_008854
	Natural variant	814	1	R → H in MVA; heterozygous compound with nonsense mutation. dbSNP rs28989182. Ref.22		VAR_028924
	Natural variant	844	1	L → F in MVA; associated with H-921; heterozygous compound with nonsense mutation. dbSNP rs28989181. Ref.22		VAR_028925
	Natural variant	909	1	I → T in MVA; heterozygous compound with nonsense mutation. dbSNP rs28989184. Ref.22		VAR_028926
	Natural variant	921	1	Q → H in MVA; associated with F-844; heterozygous compound with nonsense mutation. dbSNP rs28989183. Ref.22		VAR_028927
	Natural variant	1012	1	L → P in MVA; heterozygous compound with nonsense mutation. dbSNP rs28989185. Ref.22		VAR_028928
Experimental info
	Mutagenesis	579	1	D → E: Abolishes the cleavage by caspase-3. Ref.16
	Mutagenesis	610	1	D → E: Abolishes the cleavage by caspase-3. Ref.16
	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

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. 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. 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: 9618306] [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: 9660858] [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: 9763420] [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: 9521327] [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: 9889005] [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: 14702039] [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: 15489334] [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: 10593653] [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: 10477750] [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: 11702782] [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: 14706340] [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: 12925705] [Abstract] Cited for: ENZYME REGULATION, INTERACTION WITH CENPE, AUTOPHOSPHORYLATION, MUTAGENESIS OF LYS-795.
[16]	"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: 16227576] [Abstract] Cited for: CASPASE-3 CLEAVAGE AT ASP-579 AND ASP-610, INDUCTION, MUTAGENESIS OF ASP-579 AND ASP-610.
[17]	"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column." Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y. Anal. Sci. 24:161-166(2008) [PubMed: 18187866] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-54, MASS SPECTROMETRY.
[18]	"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: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-670, MASS SPECTROMETRY.
[19]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-435 AND SER-670, MASS SPECTROMETRY.
[20]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[21]	"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: 10366450] [Abstract] Cited for: VARIANTS GLN-349 AND ALA-618.
[22]	"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: 15475955] [Abstract] Cited for: VARIANTS MVA GLN-550; HIS-814; PHE-844; THR-909; HIS-921 AND PRO-1012.
[23]	"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: 16411201] [Abstract] Cited for: VARIANT PCS GLN-36.
[24]	"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: 17344846] [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
EMBLGenBankDDBJ	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.
UniGene	Hs.631699
3D structure databases
ModBase	Search...
Protein-protein interaction databases
DIP	DIP:24203N.
IntAct	O60566. 6 interactions.
PTM databases
PhosphoSite	O60566.
Proteomic databases
PRIDE	O60566.
Genome annotation databases
Ensembl	ENSG00000156970. Homo sapiens. [Contig view]
GeneID	701.
KEGG	hsa:701.
Organism-specific databases
GeneCards	GC15P038240.
H-InvDB	HIX0012121.
HGNC	HGNC:1149. BUB1B.
HPA	HPA008419.
MIM	176430. phenotype. 257300. phenotype. 602860. gene.
Orphanet	1052. Mosaic variegated aneuploidy syndrome.
PharmGKB	PA82.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	O60566.
OMA	O60566. CLQIPEK.
Enzyme and pathway databases
BRENDA	2.7.11.1. 247.
Reactome	REACT_152. Cell Cycle, Mitotic. REACT_1538. Cell Cycle Checkpoints. 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.
Family and domain databases
InterPro	IPR015661. Bub1. IPR013212. Mad3_BUB1_I. IPR017441. Protein_kinase_ATP_BS. IPR008271. Ser_thr_pkin_AS. [Graphical view]
PANTHER	PTHR14030. Bub1. 1 hit.
Pfam	PF08311. Mad3_BUB1_I. 1 hit. [Graphical view]
ProDom	PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00777. Mad3_BUB1_I. 1 hit. [Graphical view]
PROSITE	PS00107. PROTEIN_KINASE_ATP. False negative. PS50011. PROTEIN_KINASE_DOM. False negative. PS00108. PROTEIN_KINASE_ST. False negative. [Graphical view]
ProtoNet	Search...
Other Resources
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:	June 16, 2009
This is version 93 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)