O43684 (BUB3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Mitotic checkpoint protein BUB3

Gene names

Name:

BUB3

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	328 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Has a dual function in spindle-assembly checkpoint signaling and in promoting the establishment of correct kinetochore-microtubule (K-MT) attachments. Promotes the formation of stable end-on bipolar attachments. Necessary for kinetochore localization of BUB1. Regulates chromosome segregation during oocyte meiosis. The BUB1/BUB3 complex plays a role in the inhibition of anaphase-promoting complex or cyclosome (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. Ref.1 Ref.8 Ref.10
Subunit structure	Interacts with BUB1 and BUBR1. The BUB1/BUB3 complex interacts with MAD1L1. Ref.1 Ref.8
Subcellular location	Nucleus. Chromosome › centromere › kinetochore By similarity. Note: Starts to localize at kinetochores in prometaphase I (Pro-MI) stage and maintains the localization until the metaphase I-anaphase I (MI-AI) transition By similarity.
Post-translational modification	Poly-ADP-ribosylated by PARP1 By similarity.
Sequence similarities	Belongs to the WD repeat BUB3 family. Contains 5 WD repeats.

Ontologies

Keywords
Biological process	Cell cycle Cell division Chromosome partition Meiosis Mitosis
Cellular component	Centromere Chromosome Kinetochore Nucleus
Coding sequence diversity	Alternative splicing
Domain	Repeat WD repeat
PTM	ADP-ribosylation Acetylation Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	M phase of mitotic cell cycle Traceable author statement. Source: Reactome anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process Traceable author statement. Source: Reactome attachment of spindle microtubules to kinetochore Inferred from direct assay Ref.10. Source: UniProtKB cell division Inferred from electronic annotation. Source: UniProtKB-KW meiosis Inferred from electronic annotation. Source: UniProtKB-KW mitotic anaphase Traceable author statement. Source: Reactome mitotic prometaphase Traceable author statement. Source: Reactome mitotic sister chromatid segregation Inferred from electronic annotation. Source: Compara 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 regulation of chromosome segregation Inferred from electronic annotation. Source: Compara
Cellular_component	condensed chromosome kinetochore Inferred from electronic annotation. Source: UniProtKB-SubCell cytosol Traceable author statement. Source: Reactome kinetochore Inferred from direct assay Ref.2. Source: UniProtKB nucleus Inferred from direct assay. Source: HPA
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Dynlt3	Q5XI90	2	EBI-1050987,EBI-1781818	From a different organism.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O43684-1)

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: O43684-2)

The sequence of this isoform differs from the canonical sequence as follows:
     326-328: PCT → T

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 328	328	Mitotic checkpoint protein BUB3		PRO_0000050891
Regions
	Repeat	5 – 43	39	WD 1
	Repeat	46 – 83	38	WD 2
	Repeat	86 – 124	39	WD 3
	Repeat	128 – 163	36	WD 4
	Repeat	223 – 262	40	WD 5
Amino acid modifications
	Modified residue	179	1	N6-acetyllysine Ref.12
	Modified residue	211	1	Phosphoserine Ref.11
	Cross-link	216		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.9
Natural variations
	Alternative sequence	326 – 328	3	PCT → T in isoform 2.		VSP_038655

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 1, 1998. Version 1. Checksum: 2915572A57368E5A	FASTA	328	37,155
	10 20 30 40 50 60 MTGSNEFKLN QPPEDGISSV KFSPNTSQFL LVSSWDTSVR LYDVPANSMR LKYQHTGAVL 70 80 90 100 110 120 DCAFYDPTHA WSGGLDHQLK MHDLNTDQEN LVGTHDAPIR CVEYCPEVNV MVTGSWDQTV 130 140 150 160 170 180 KLWDPRTPCN AGTFSQPEKV YTLSVSGDRL IVGTAGRRVL VWDLRNMGYV QQRRESSLKY 190 200 210 220 230 240 QTRCIRAFPN KQGYVLSSIE GRVAVEYLDP SPEVQKKKYA FKCHRLKENN IEQIYPVNAI 250 260 270 280 290 300 SFHNIHNTFA TGGSDGFVNI WDPFNKKRLC QFHRYPTSIA SLAFSNDGTT LAIASSYMYE 310 320 MDDTEHPEDG IFIRQVTDAE TKPKSPCT
	Isoform 2 [UniParc]. Checksum: F1EA57368E5A6345	FASTA	326	36,955
	10 20 30 40 50 60 MTGSNEFKLN QPPEDGISSV KFSPNTSQFL LVSSWDTSVR LYDVPANSMR LKYQHTGAVL 70 80 90 100 110 120 DCAFYDPTHA WSGGLDHQLK MHDLNTDQEN LVGTHDAPIR CVEYCPEVNV MVTGSWDQTV 130 140 150 160 170 180 KLWDPRTPCN AGTFSQPEKV YTLSVSGDRL IVGTAGRRVL VWDLRNMGYV QQRRESSLKY 190 200 210 220 230 240 QTRCIRAFPN KQGYVLSSIE GRVAVEYLDP SPEVQKKKYA FKCHRLKENN IEQIYPVNAI 250 260 270 280 290 300 SFHNIHNTFA TGGSDGFVNI WDPFNKKRLC QFHRYPTSIA SLAFSNDGTT LAIASSYMYE 310 320 MDDTEHPEDG IFIRQVTDAE TKPKST

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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] (ISOFORMS 1 AND 2), FUNCTION, INTERACTION WITH BUB1 AND MAD1L1. Tissue: Spleen and Testis.
[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).
[3]	"Human BUB3 is a kinetochore protein that interacts with hBUB1 and hBUBR1." Chan G.K.T., Yen T.J. Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Tongue.
[5]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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). Tissue: Brain and Placenta.
[8]	"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, INTERACTION WITH BUB1.
[9]	"Quantitative analysis of global ubiquitination in HeLa cells by mass spectrometry." Meierhofer D., Wang X., Huang L., Kaiser P. J. Proteome Res. 7:4566-4576(2008) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-216, MASS SPECTROMETRY.
[10]	"The human spindle assembly checkpoint protein Bub3 is required for the establishment of efficient kinetochore-microtubule attachments." Logarinho E., Resende T., Torres C., Bousbaa H. Mol. Biol. Cell 19:1798-1813(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[11]	"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-211, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-179, MASS SPECTROMETRY.
[13]	"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].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF047472 mRNA. Translation: AAC28438.1. AF047473 mRNA. Translation: AAC28439.1. AF053304 mRNA. Translation: AAC06258.1. AF081496 mRNA. Translation: AAC36307.1. AK312546 mRNA. Translation: BAG35444.1. AC012391 Genomic DNA. No translation available. CH471066 Genomic DNA. Translation: EAW49284.1. CH471066 Genomic DNA. Translation: EAW49285.1. CH471066 Genomic DNA. Translation: EAW49286.1. BC005138 mRNA. Translation: AAH05138.1. BC022438 mRNA. Translation: AAH22438.1.
IPI	IPI00013468. IPI00514701.
RefSeq	NP_001007794.1. NM_001007793.2. NP_004716.1. NM_004725.3.
UniGene	Hs.418533.
3D structure databases
ProteinModelPortal	O43684.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-24205N.
IntAct	O43684. 25 interactions.
MINT	MINT-5005850.
STRING	9606.ENSP00000357858.
PTM databases
PhosphoSite	O43684.
Proteomic databases
PaxDb	O43684.
PRIDE	O43684.
Protocols and materials databases
DNASU	9184.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000368858; ENSP00000357851; ENSG00000154473. ENST00000368865; ENSP00000357858; ENSG00000154473.
GeneID	9184.
KEGG	hsa:9184.
UCSC	uc001lhd.2. human. uc001lhe.2. human.
Organism-specific databases
CTD	9184.
GeneCards	GC10P124903.
HGNC	HGNC:1151. BUB3.
HPA	HPA003601.
MIM	603719. gene.
neXtProt	NX_O43684.
PharmGKB	PA25467.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG2319.
HOGENOM	HOG000208822.
HOVERGEN	HBG002942.
InParanoid	O43684.
KO	K02180.
OMA	NAISFHS.
OrthoDB	EOG4R7VB2.
PhylomeDB	O43684.
Enzyme and pathway databases
Reactome	REACT_115566. Cell Cycle. REACT_21300. Mitotic M-M/G1 phases. REACT_6850. Cdc20:Phospho-APC/C mediated degradation of Cyclin A. REACT_8017. APC-Cdc20 mediated degradation of Nek2A.
SignaLink	O43684.
Gene expression databases
ArrayExpress	O43684.
Bgee	O43684.
CleanEx	HS_BUB3.
Genevestigator	O43684.
GermOnline	ENSG00000154473. Homo sapiens.
Family and domain databases
Gene3D	2.130.10.10. 1 hit.
InterPro	IPR020472. G-protein_beta_WD-40_rep. IPR015943. WD40/YVTN_repeat-like_dom. IPR001680. WD40_repeat. IPR017986. WD40_repeat_dom. [Graphical view]
Pfam	PF00400. WD40. 3 hits. [Graphical view]
PRINTS	PR00320. GPROTEINBRPT.
SMART	SM00320. WD40. 6 hits. [Graphical view]
SUPFAM	SSF50978. WD40_like. 1 hit.
PROSITE	PS00678. WD_REPEATS_1. False negative. PS50082. WD_REPEATS_2. 2 hits. PS50294. WD_REPEATS_REGION. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	Bub3. human.
GenomeRNAi	9184.
NextBio	34433.
SOURCE	Search...

Entry information

Entry name

BUB3_HUMAN

Accession

Primary (citable) accession number: O43684
Secondary accession number(s): A6NJ42 , B2R6E7, D3DRE9, O43685

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	June 1, 1998
Last modified:	May 29, 2013
This is version 124 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.