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Database: UniProt
Entry: O60566
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Original site: O60566 
ID   BUB1B_HUMAN             Reviewed;        1050 AA.
AC   O60566; B2R6U0; B4DL09; B4DLG3; O60501; O60627; O60758; O75389; Q59HH6;
AC   Q8WV50; Q96KM4;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   03-APR-2007, sequence version 3.
DT   29-SEP-2021, entry version 212.
DE   RecName: Full=Mitotic checkpoint serine/threonine-protein kinase BUB1 beta;
DE            EC=2.7.11.1;
DE   AltName: Full=MAD3/BUB1-related protein kinase;
DE            Short=hBUBR1;
DE   AltName: Full=Mitotic checkpoint kinase MAD3L;
DE   AltName: Full=Protein SSK1;
GN   Name=BUB1B; Synonyms=BUBR1, MAD3L, SSK1;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT GLN-349.
RC   TISSUE=Umbilical vein;
RX   PubMed=9618306; DOI=10.1006/bbrc.1998.8713;
RA   Donadelli R., Benatti L., Remuzzi A., Morigi M., Gullans S.R., Benigni A.,
RA   Remuzzi G., Noris M.;
RT   "Identification of a novel gene -- SSK1 -- in human endothelial cells
RT   exposed to shear stress.";
RL   Biochem. Biophys. Res. Commun. 246:881-887(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT GLN-349.
RX   PubMed=9660858; DOI=10.1083/jcb.142.1.1;
RA   Taylor S.S., Ha E., McKeon F.;
RT   "The human homologue of Bub3 is required for kinetochore localization of
RT   Bub1 and a Mad3/Bub1-related protein kinase.";
RL   J. Cell Biol. 142:1-11(1998).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH CENPE, SUBCELLULAR
RP   LOCATION, AND VARIANT GLN-349.
RX   PubMed=9763420; DOI=10.1083/jcb.143.1.49;
RA   Chan G.K.T., Schaar B.T., Yen T.J.;
RT   "Characterization of the kinetochore binding domain of CENP-E reveals
RT   interactions with the kinetochore proteins CENP-F and hBUBR1.";
RL   J. Cell Biol. 143:49-63(1998).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS THR-15 AND GLN-349.
RX   PubMed=9521327; DOI=10.1038/32688;
RA   Cahill D.P., Lengauer C., Yu J., Riggins G.J., Willson J.K.V.,
RA   Markowitz S.D., Kinzler K.W., Vogelstein B.;
RT   "Mutations of mitotic checkpoint genes in human cancers.";
RL   Nature 392:300-303(1998).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   PubMed=9889005; DOI=10.1006/geno.1998.5629;
RA   Davenport J.W., Fernandes E.R., Harris L.D., Neale G.A.M., Goorha R.;
RT   "The mouse mitotic checkpoint gene bub1b, a novel bub1 family member, is
RT   expressed in a cell cycle-dependent manner.";
RL   Genomics 55:113-117(1999).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT GLN-349.
RA   Dai W., Ouyang B., Lan Z., Pan H.;
RT   "Human MAD3-like protein kinase (hmad3).";
RL   Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA   Seike M., Gemma A., Hosoya Y., Kurimoto F., Yoshimura A., Kudoh S.;
RL   Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases.
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3), AND VARIANT
RP   GLN-349.
RC   TISSUE=Tongue;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [9]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Brain;
RA   Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA   Ohara O., Nagase T., Kikuno R.F.;
RL   Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN   [10]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS GLN-349
RP   AND SER-378.
RC   TISSUE=Placenta;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [11]
RP   PHOSPHORYLATION, TISSUE SPECIFICITY, AND INDUCTION.
RX   PubMed=10593653;
RA   Li W., Lan Z., Wu H., Wu S., Meadows J., Chen J., Zhu V., Dai W.;
RT   "BUBR1 phosphorylation is regulated during mitotic checkpoint activation.";
RL   Cell Growth Differ. 10:769-775(1999).
RN   [12]
RP   FUNCTION, SUBCELLULAR LOCATION, INDUCTION, PHOSPHORYLATION, AND INTERACTION
RP   WITH APC/C.
RX   PubMed=10477750; DOI=10.1083/jcb.146.5.941;
RA   Chan G.K., Jablonski S.A., Sudakin V., Hittle J.C., Yen T.J.;
RT   "Human BUBR1 is a mitotic checkpoint kinase that monitors CENP-E functions
RT   at kinetochores and binds the cyclosome/APC.";
RL   J. Cell Biol. 146:941-954(1999).
RN   [13]
RP   FUNCTION, IDENTIFICATION IN A COMPLEX WITH CDC20 AND BUB3, AND MUTAGENESIS
RP   OF LYS-795.
RX   PubMed=11702782; DOI=10.1016/s1534-5807(01)00019-3;
RA   Tang Z., Bharadwaj R., Li B., Yu H.;
RT   "Mad2-independent inhibition of APC/Cdc20 by the mitotic checkpoint protein
RT   BubR1.";
RL   Dev. Cell 1:227-237(2001).
RN   [14]
RP   FUNCTION, SUBCELLULAR LOCATION, AND DEGRADATION BY THE PROTEASOME.
RX   PubMed=14706340; DOI=10.1016/s1535-6108(03)00302-7;
RA   Shin H.J., Baek K.H., Jeon A.H., Park M.T., Lee S.J., Kang C.M., Lee H.S.,
RA   Yoo S.H., Chung D.H., Sung Y.C., McKeon F., Lee C.W.;
RT   "Dual roles of human BubR1, a mitotic checkpoint kinase, in the monitoring
RT   of chromosomal instability.";
RL   Cancer Cell 4:483-497(2003).
RN   [15]
RP   ACTIVITY REGULATION, INTERACTION WITH CENPE, AUTOPHOSPHORYLATION, AND
RP   MUTAGENESIS OF LYS-795.
RX   PubMed=12925705; DOI=10.1083/jcb.200303167;
RA   Weaver B.A., Bonday Z.Q., Putkey F.R., Kops G.J., Silk A.D.,
RA   Cleveland D.W.;
RT   "Centromere-associated protein-E is essential for the mammalian mitotic
RT   checkpoint to prevent aneuploidy due to single chromosome loss.";
RL   J. Cell Biol. 162:551-563(2003).
RN   [16]
RP   FUNCTION.
RX   PubMed=15020684; DOI=10.1242/jcs.01006;
RA   Johnson V.L., Scott M.I., Holt S.V., Hussein D., Taylor S.S.;
RT   "Bub1 is required for kinetochore localization of BubR1, Cenp-E, Cenp-F and
RT   Mad2, and chromosome congression.";
RL   J. Cell Sci. 117:1577-1589(2004).
RN   [17]
RP   PROTEOLYTIC CLEAVAGE AT ASP-579 AND ASP-610 BY CASPASE-3, INDUCTION, AND
RP   MUTAGENESIS OF ASP-579 AND ASP-610.
RX   PubMed=16227576; DOI=10.1128/mcb.25.21.9232-9248.2005;
RA   Kim M., Murphy K., Liu F., Parker S.E., Dowling M.L., Baff W., Kao G.D.;
RT   "Caspase-mediated specific cleavage of BubR1 is a determinant of mitotic
RT   progression.";
RL   Mol. Cell. Biol. 25:9232-9248(2005).
RN   [18]
RP   SUBCELLULAR LOCATION, AND INTERACTION WITH PLK1.
RX   PubMed=16760428; DOI=10.1091/mbc.e06-03-0240;
RA   Qi W., Tang Z., Yu H.;
RT   "Phosphorylation- and polo-box-dependent binding of Plk1 to Bub1 is
RT   required for the kinetochore localization of Plk1.";
RL   Mol. Biol. Cell 17:3705-3716(2006).
RN   [19]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=16964243; DOI=10.1038/nbt1240;
RA   Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT   "A probability-based approach for high-throughput protein phosphorylation
RT   analysis and site localization.";
RL   Nat. Biotechnol. 24:1285-1292(2006).
RN   [20]
RP   INTERACTION WITH KNL1, AND MUTAGENESIS OF ALA-159 AND PHE-175.
RX   PubMed=17981135; DOI=10.1016/j.devcel.2007.09.005;
RA   Kiyomitsu T., Obuse C., Yanagida M.;
RT   "Human Blinkin/AF15q14 is required for chromosome alignment and the mitotic
RT   checkpoint through direct interaction with Bub1 and BubR1.";
RL   Dev. Cell 13:663-676(2007).
RN   [21]
RP   INTERACTION WITH PLK1, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-676,
RP   AND MUTAGENESIS OF THR-620.
RX   PubMed=17785528; DOI=10.1101/gad.436007;
RA   Elowe S., Huemmer S., Uldschmid A., Li X., Nigg E.A.;
RT   "Tension-sensitive Plk1 phosphorylation on BubR1 regulates the stability of
RT   kinetochore microtubule interactions.";
RL   Genes Dev. 21:2205-2219(2007).
RN   [22]
RP   INTERACTION WITH PLK1, SUBCELLULAR LOCATION, AND PHOSPHORYLATION AT THR-792
RP   AND THR-1008.
RX   PubMed=17376779; DOI=10.1074/jbc.m611053200;
RA   Matsumura S., Toyoshima F., Nishida E.;
RT   "Polo-like kinase 1 facilitates chromosome alignment during prometaphase
RT   through BubR1.";
RL   J. Biol. Chem. 282:15217-15227(2007).
RN   [23]
RP   PHOSPHORYLATION AT SER-435; SER-543; SER-670 AND SER-1043.
RX   PubMed=19015317; DOI=10.1083/jcb.200805163;
RA   Huang H., Hittle J., Zappacosta F., Annan R.S., Hershko A., Yen T.J.;
RT   "Phosphorylation sites in BubR1 that regulate kinetochore attachment,
RT   tension, and mitotic exit.";
RL   J. Cell Biol. 183:667-680(2008).
RN   [24]
RP   SUMOYLATION.
RX   PubMed=18374647; DOI=10.1016/j.molcel.2008.01.013;
RA   Zhang X.-D., Goeres J., Zhang H., Yen T.J., Porter A.C.G., Matunis M.J.;
RT   "SUMO-2/3 modification and binding regulate the association of CENP-E with
RT   kinetochores and progression through mitosis.";
RL   Mol. Cell 29:729-741(2008).
RN   [25]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-670, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA   Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA   Greff Z., Keri G., Stemmann O., Mann M.;
RT   "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT   kinome across the cell cycle.";
RL   Mol. Cell 31:438-448(2008).
RN   [26]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-670, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN   [27]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19413330; DOI=10.1021/ac9004309;
RA   Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT   "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT   refined SCX-based approach.";
RL   Anal. Chem. 81:4493-4501(2009).
RN   [28]
RP   FUNCTION.
RX   PubMed=19411850; DOI=10.4161/cc.8.11.8671;
RA   Park S.-Y., Kim S., Cho H., Kwon S.-H., Chae S., Kang D., Seong Y.-S.,
RA   Cho H.;
RT   "Depletion of BubR1 promotes premature centrosomal localization of cyclin
RT   B1 and accelerates mitotic entry.";
RL   Cell Cycle 8:1754-1764(2009).
RN   [29]
RP   INTERACTION WITH CENPE, AND SUBCELLULAR LOCATION.
RX   PubMed=19625775; DOI=10.4161/cc.8.16.9366;
RA   Huang Y., Yao Y., Xu H.-Z., Wang Z.-G., Lu L., Dai W.;
RT   "Defects in chromosome congression and mitotic progression in KIF18A-
RT   deficient cells are partly mediated through impaired functions of CENP-E.";
RL   Cell Cycle 8:2643-2649(2009).
RN   [30]
RP   INTERACTION WITH KAT2B, ACETYLATION AT LYS-250, AND UBIQUITINATION.
RX   PubMed=19407811; DOI=10.1038/emboj.2009.123;
RA   Choi E., Choe H., Min J., Choi J.Y., Kim J., Lee H.;
RT   "BubR1 acetylation at prometaphase is required for modulating APC/C
RT   activity and timing of mitosis.";
RL   EMBO J. 28:2077-2089(2009).
RN   [31]
RP   FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH PLK1.
RX   PubMed=19503101; DOI=10.1038/onc.2009.141;
RA   Izumi H., Matsumoto Y., Ikeuchi T., Saya H., Kajii T., Matsuura S.;
RT   "BubR1 localizes to centrosomes and suppresses centrosome amplification via
RT   regulating Plk1 activity in interphase cells.";
RL   Oncogene 28:2806-2820(2009).
RN   [32]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-670 AND THR-1042, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA   Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA   Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT   "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT   site occupancy during mitosis.";
RL   Sci. Signal. 3:RA3-RA3(2010).
RN   [33]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [34]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-543, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA   Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA   Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT   "System-wide temporal characterization of the proteome and phosphoproteome
RT   of human embryonic stem cell differentiation.";
RL   Sci. Signal. 4:RS3-RS3(2011).
RN   [35]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-367; SER-435; SER-543;
RP   SER-665; SER-670 AND SER-697, AND IDENTIFICATION BY MASS SPECTROMETRY
RP   [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma, and Erythroleukemia;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [36]
RP   INTERACTION WITH MAD2L1.
RX   PubMed=29162720; DOI=10.1074/jbc.ra117.000555;
RA   Ji W., Luo Y., Ahmad E., Liu S.T.;
RT   "Direct interactions of mitotic arrest deficient 1 (MAD1) domains with each
RT   other and MAD2 conformers are required for mitotic checkpoint signaling.";
RL   J. Biol. Chem. 293:484-496(2018).
RN   [37]
RP   INTERACTION WITH RIPK3.
RX   PubMed=29883609; DOI=10.1016/j.molcel.2018.05.016;
RA   Choi S.W., Park H.H., Kim S., Chung J.M., Noh H.J., Kim S.K., Song H.K.,
RA   Lee C.W., Morgan M.J., Kang H.C., Kim Y.S.;
RT   "PELI1 selectively targets kinase-active RIP3 for ubiquitylation-dependent
RT   proteasomal degradation.";
RL   Mol. Cell 70:920-935(2018).
RN   [38]
RP   VARIANTS GLN-349 AND ALA-618.
RX   PubMed=10366450; DOI=10.1006/geno.1999.5831;
RA   Cahill D.P., da Costa L.T., Carson-Walter E.B., Kinzler K.W.,
RA   Vogelstein B., Lengauer C.;
RT   "Characterization of MAD2B and other mitotic spindle checkpoint genes.";
RL   Genomics 58:181-187(1999).
RN   [39]
RP   VARIANTS MVA1 GLN-550; HIS-814; PHE-844; THR-909; HIS-921 AND PRO-1012.
RX   PubMed=15475955; DOI=10.1038/ng1449;
RA   Hanks S., Coleman K., Reid S., Plaja A., Firth H., Fitzpatrick D., Kidd A.,
RA   Mehes K., Nash R., Robin N., Shannon N., Tolmie J., Swansbury J.,
RA   Irrthum A., Douglas J., Rahman N.;
RT   "Constitutional aneuploidy and cancer predisposition caused by biallelic
RT   mutations in BUB1B.";
RL   Nat. Genet. 36:1159-1161(2004).
RN   [40]
RP   VARIANT PCS GLN-36.
RX   PubMed=16411201; DOI=10.1002/ajmg.a.31069;
RA   Matsuura S., Matsumoto Y., Morishima K., Izumi H., Matsumoto H., Ito E.,
RA   Tsutsui K., Kobayashi J., Tauchi H., Kajiwara Y., Hama S., Kurisu K.,
RA   Tahara H., Oshimura M., Komatsu K., Ikeuchi T., Kajii T.;
RT   "Monoallelic BUB1B mutations and defective mitotic-spindle checkpoint in
RT   seven families with premature chromatid separation (PCS) syndrome.";
RL   Am. J. Med. Genet. A 140:358-367(2006).
RN   [41]
RP   VARIANTS [LARGE SCALE ANALYSIS] MET-40; GLN-349; ASP-390 AND ALA-618.
RX   PubMed=17344846; DOI=10.1038/nature05610;
RA   Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA   Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA   Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA   Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA   Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA   Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA   Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA   Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA   Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA   Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA   Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA   Futreal P.A., Stratton M.R.;
RT   "Patterns of somatic mutation in human cancer genomes.";
RL   Nature 446:153-158(2007).
CC   -!- FUNCTION: Essential component of the mitotic checkpoint. Required for
CC       normal mitosis progression. The mitotic checkpoint delays anaphase
CC       until all chromosomes are properly attached to the mitotic spindle. One
CC       of its checkpoint functions is to inhibit the activity of the anaphase-
CC       promoting complex/cyclosome (APC/C) by blocking the binding of CDC20 to
CC       APC/C, independently of its kinase activity. The other is to monitor
CC       kinetochore activities that depend on the kinetochore motor CENPE.
CC       Required for kinetochore localization of CENPE. Negatively regulates
CC       PLK1 activity in interphase cells and suppresses centrosome
CC       amplification. Also implicated in triggering apoptosis in polyploid
CC       cells that exit aberrantly from mitotic arrest. May play a role for
CC       tumor suppression. {ECO:0000269|PubMed:10477750,
CC       ECO:0000269|PubMed:11702782, ECO:0000269|PubMed:14706340,
CC       ECO:0000269|PubMed:15020684, ECO:0000269|PubMed:19411850,
CC       ECO:0000269|PubMed:19503101}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC         [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC         COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC         threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC         Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC         EC=2.7.11.1;
CC   -!- ACTIVITY REGULATION: Kinase activity stimulated by CENPE.
CC       {ECO:0000269|PubMed:12925705}.
CC   -!- SUBUNIT: Interacts with CENPE (PubMed:12925705, PubMed:19625775).
CC       Interacts with PLK1 (PubMed:16760428, PubMed:17785528, PubMed:17376779,
CC       PubMed:19503101). Part of a complex containing BUB3, CDC20 and BUB1B
CC       (PubMed:11702782). Interacts with anaphase-promoting complex/cyclosome
CC       (APC/C) (PubMed:10477750). Interacts with KNL1 (PubMed:17981135).
CC       Interacts with KAT2B (PubMed:19407811). Interacts with RIPK3
CC       (PubMed:29883609). Interacts with the closed conformation form of
CC       MAD2L1 (PubMed:29162720). {ECO:0000269|PubMed:10477750,
CC       ECO:0000269|PubMed:11702782, ECO:0000269|PubMed:12925705,
CC       ECO:0000269|PubMed:16760428, ECO:0000269|PubMed:17376779,
CC       ECO:0000269|PubMed:17785528, ECO:0000269|PubMed:17981135,
CC       ECO:0000269|PubMed:19407811, ECO:0000269|PubMed:19503101,
CC       ECO:0000269|PubMed:19625775, ECO:0000269|PubMed:29162720,
CC       ECO:0000269|PubMed:29883609}.
CC   -!- INTERACTION:
CC       O60566; O43683: BUB1; NbExp=3; IntAct=EBI-1001438, EBI-748936;
CC       O60566; O43684: BUB3; NbExp=9; IntAct=EBI-1001438, EBI-1050987;
CC       O60566; Q12834: CDC20; NbExp=32; IntAct=EBI-1001438, EBI-367462;
CC       O60566; Q02224: CENPE; NbExp=4; IntAct=EBI-1001438, EBI-1375040;
CC       O60566; Q92831: KAT2B; NbExp=14; IntAct=EBI-1001438, EBI-477430;
CC       O60566; Q8NG31-2: KNL1; NbExp=10; IntAct=EBI-1001438, EBI-10973816;
CC       O60566; Q13257: MAD2L1; NbExp=14; IntAct=EBI-1001438, EBI-78203;
CC       O60566; Q8IXJ6: SIRT2; NbExp=3; IntAct=EBI-1001438, EBI-477232;
CC       O60566; P0CG48: UBC; NbExp=3; IntAct=EBI-1001438, EBI-3390054;
CC       O60566; P45481: Crebbp; Xeno; NbExp=3; IntAct=EBI-1001438, EBI-296306;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Chromosome, centromere,
CC       kinetochore. Cytoplasm, cytoskeleton, microtubule organizing center,
CC       centrosome. Note=Cytoplasmic in interphase cells. Associates with the
CC       kinetochores in early prophase. Kinetochore localization requires BUB1,
CC       PLK1 and KNL1.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=O60566-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=O60566-2; Sequence=VSP_036474, VSP_036475, VSP_036476;
CC       Name=3;
CC         IsoId=O60566-3; Sequence=VSP_036473;
CC   -!- TISSUE SPECIFICITY: Highly expressed in thymus followed by spleen.
CC       Preferentially expressed in tissues with a high mitotic index.
CC       {ECO:0000269|PubMed:10593653}.
CC   -!- INDUCTION: Induced during mitosis. {ECO:0000269|PubMed:10477750,
CC       ECO:0000269|PubMed:10593653, ECO:0000269|PubMed:16227576}.
CC   -!- DOMAIN: The D-box targets the protein for rapid degradation by
CC       ubiquitin-dependent proteolysis during the transition from mitosis to
CC       interphase. {ECO:0000305}.
CC   -!- DOMAIN: The BUB1 N-terminal domain directs kinetochore localization and
CC       binding to BUB3.
CC   -!- PTM: Proteolytically cleaved by caspase-3 in a cell cycle specific
CC       manner. The cleavage might be involved in the durability of the cell
CC       cycle delay. Caspase-3 cleavage is associated with abrogation of the
CC       mitotic checkpoint. The major site of cleavage is at Asp-610.
CC       {ECO:0000269|PubMed:16227576}.
CC   -!- PTM: Acetylation at Lys-250 regulates its degradation and timing in
CC       anaphase entry. {ECO:0000269|PubMed:19407811}.
CC   -!- PTM: Ubiquitinated. Degraded by the proteasome.
CC       {ECO:0000269|PubMed:19407811}.
CC   -!- PTM: Sumoylated with SUMO2 and SUMO3. The sumoylation mediates the
CC       association with CENPE at the kinetochore.
CC       {ECO:0000269|PubMed:18374647}.
CC   -!- PTM: Autophosphorylated in vitro. Intramolecular autophosphorylation is
CC       stimulated by CENPE. Phosphorylated during mitosis and
CC       hyperphosphorylated in mitotically arrested cells. Phosphorylation at
CC       Ser-670 and Ser-1043 occurs at kinetochores upon mitotic entry with
CC       dephosphorylation at the onset of anaphase.
CC       {ECO:0000269|PubMed:10477750, ECO:0000269|PubMed:10593653,
CC       ECO:0000269|PubMed:17376779, ECO:0000269|PubMed:17785528,
CC       ECO:0000269|PubMed:19015317}.
CC   -!- DISEASE: Note=Defects in BUB1B are associated with tumor formation.
CC   -!- DISEASE: Premature chromatid separation trait (PCS) [MIM:176430]:
CC       Consists of separate and splayed chromatids with discernible
CC       centromeres and involves all or most chromosomes of a metaphase. It is
CC       found in up to 2% of metaphases in cultured lymphocytes from
CC       approximately 40% of normal individuals. When PCS is present in 5% or
CC       more of cells, it is known as the heterozygous PCS trait and has no
CC       obvious phenotypic effect, although some have reported decreased
CC       fertility. Inheritance is autosomal dominant.
CC       {ECO:0000269|PubMed:16411201}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- DISEASE: Mosaic variegated aneuploidy syndrome 1 (MVA1) [MIM:257300]: A
CC       severe developmental disorder characterized by mosaic aneuploidies,
CC       predominantly trisomies and monosomies, involving multiple different
CC       chromosomes and tissues. Affected individuals typically present with
CC       severe intrauterine growth retardation and microcephaly. Eye anomalies,
CC       mild dysmorphism, variable developmental delay, and a broad spectrum of
CC       additional congenital abnormalities and medical conditions may also
CC       occur. The risk of malignancy is high, with rhabdomyosarcoma, Wilms
CC       tumor and leukemia reported in several cases.
CC       {ECO:0000269|PubMed:15475955}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry. MVA1 is caused by
CC       biallelic mutations in the BUB1B gene.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC       kinase family. BUB1 subfamily. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAD92019.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC       Haematology;
CC       URL="http://atlasgeneticsoncology.org/Genes/BUB1BID854ch15q15.html";
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DR   EMBL; AF053306; AAC06260.1; -; mRNA.
DR   EMBL; AF046918; AAC33435.1; -; mRNA.
DR   EMBL; AF046079; AAC12730.2; -; mRNA.
DR   EMBL; AF107297; AAD11941.1; -; mRNA.
DR   EMBL; AF035933; AAC23736.1; -; mRNA.
DR   EMBL; AF068760; AAC19118.1; -; mRNA.
DR   EMBL; AF310214; AAL10712.1; -; Genomic_DNA.
DR   EMBL; AF310192; AAL10712.1; JOINED; Genomic_DNA.
DR   EMBL; AF310193; AAL10712.1; JOINED; Genomic_DNA.
DR   EMBL; AF310194; AAL10712.1; JOINED; Genomic_DNA.
DR   EMBL; AF310195; AAL10712.1; JOINED; Genomic_DNA.
DR   EMBL; AF310196; AAL10712.1; JOINED; Genomic_DNA.
DR   EMBL; AF310197; AAL10712.1; JOINED; Genomic_DNA.
DR   EMBL; AF310198; AAL10712.1; JOINED; Genomic_DNA.
DR   EMBL; AF310199; AAL10712.1; JOINED; Genomic_DNA.
DR   EMBL; AF310200; AAL10712.1; JOINED; Genomic_DNA.
DR   EMBL; AF310201; AAL10712.1; JOINED; Genomic_DNA.
DR   EMBL; AF310202; AAL10712.1; JOINED; Genomic_DNA.
DR   EMBL; AF310203; AAL10712.1; JOINED; Genomic_DNA.
DR   EMBL; AF310204; AAL10712.1; JOINED; Genomic_DNA.
DR   EMBL; AF310205; AAL10712.1; JOINED; Genomic_DNA.
DR   EMBL; AF310206; AAL10712.1; JOINED; Genomic_DNA.
DR   EMBL; AF310207; AAL10712.1; JOINED; Genomic_DNA.
DR   EMBL; AF310208; AAL10712.1; JOINED; Genomic_DNA.
DR   EMBL; AF310209; AAL10712.1; JOINED; Genomic_DNA.
DR   EMBL; AF310210; AAL10712.1; JOINED; Genomic_DNA.
DR   EMBL; AF310211; AAL10712.1; JOINED; Genomic_DNA.
DR   EMBL; AF310212; AAL10712.1; JOINED; Genomic_DNA.
DR   EMBL; AF310213; AAL10712.1; JOINED; Genomic_DNA.
DR   EMBL; AK296795; BAG59371.1; -; mRNA.
DR   EMBL; AK296984; BAG59525.1; -; mRNA.
DR   EMBL; AK312709; BAG35587.1; -; mRNA.
DR   EMBL; AB208782; BAD92019.1; ALT_INIT; mRNA.
DR   EMBL; BC018739; AAH18739.1; -; mRNA.
DR   CCDS; CCDS10053.1; -. [O60566-1]
DR   PIR; JW0092; JW0092.
DR   RefSeq; NP_001202.4; NM_001211.5. [O60566-1]
DR   PDB; 2WVI; X-ray; 1.80 A; A=57-220.
DR   PDB; 3SI5; X-ray; 2.20 A; A/B=57-220.
DR   PDB; 4GGD; X-ray; 2.44 A; C/D=20-42.
DR   PDB; 5JJA; X-ray; 2.35 A; C/D=647-720.
DR   PDB; 5K6S; X-ray; 2.79 A; B=663-681.
DR   PDB; 5KHU; EM; 4.80 A; Q=1-1050.
DR   PDB; 5LCW; EM; 4.00 A; S=1-560.
DR   PDB; 5SWF; X-ray; 2.82 A; B=668-676.
DR   PDB; 6TLJ; EM; 3.80 A; S=1-1050.
DR   PDBsum; 2WVI; -.
DR   PDBsum; 3SI5; -.
DR   PDBsum; 4GGD; -.
DR   PDBsum; 5JJA; -.
DR   PDBsum; 5K6S; -.
DR   PDBsum; 5KHU; -.
DR   PDBsum; 5LCW; -.
DR   PDBsum; 5SWF; -.
DR   PDBsum; 6TLJ; -.
DR   BMRB; O60566; -.
DR   SMR; O60566; -.
DR   BioGRID; 107166; 136.
DR   ComplexPortal; CPX-3946; Mitotic Checkpoint Complex.
DR   CORUM; O60566; -.
DR   DIP; DIP-24203N; -.
DR   ELM; O60566; -.
DR   IntAct; O60566; 80.
DR   MINT; O60566; -.
DR   STRING; 9606.ENSP00000287598; -.
DR   ChEMBL; CHEMBL4295998; -.
DR   GlyConnect; 1516; 11 N-Linked glycans (1 site).
DR   GlyGen; O60566; 2 sites, 11 N-linked glycans (1 site), 1 O-linked glycan (1 site).
DR   iPTMnet; O60566; -.
DR   MetOSite; O60566; -.
DR   PhosphoSitePlus; O60566; -.
DR   BioMuta; BUB1B; -.
DR   EPD; O60566; -.
DR   jPOST; O60566; -.
DR   MassIVE; O60566; -.
DR   MaxQB; O60566; -.
DR   PaxDb; O60566; -.
DR   PeptideAtlas; O60566; -.
DR   PRIDE; O60566; -.
DR   ProteomicsDB; 49471; -. [O60566-1]
DR   ProteomicsDB; 49472; -. [O60566-2]
DR   ProteomicsDB; 49473; -. [O60566-3]
DR   Antibodypedia; 1214; 704 antibodies.
DR   DNASU; 701; -.
DR   Ensembl; ENST00000287598; ENSP00000287598; ENSG00000156970. [O60566-1]
DR   Ensembl; ENST00000412359; ENSP00000398470; ENSG00000156970. [O60566-3]
DR   GeneID; 701; -.
DR   KEGG; hsa:701; -.
DR   UCSC; uc001zkx.5; human. [O60566-1]
DR   CTD; 701; -.
DR   DisGeNET; 701; -.
DR   GeneCards; BUB1B; -.
DR   HGNC; HGNC:1149; BUB1B.
DR   HPA; ENSG00000156970; Tissue enhanced (lymphoid tissue, testis).
DR   MalaCards; BUB1B; -.
DR   MIM; 176430; phenotype.
DR   MIM; 257300; phenotype.
DR   MIM; 602860; gene.
DR   neXtProt; NX_O60566; -.
DR   OpenTargets; ENSG00000156970; -.
DR   Orphanet; 1052; Mosaic variegated aneuploidy syndrome.
DR   PharmGKB; PA82; -.
DR   VEuPathDB; HostDB:ENSG00000156970; -.
DR   eggNOG; KOG1166; Eukaryota.
DR   GeneTree; ENSGT00940000158912; -.
DR   HOGENOM; CLU_010890_0_0_1; -.
DR   InParanoid; O60566; -.
DR   OMA; CAKETSL; -.
DR   OrthoDB; 1411806at2759; -.
DR   PhylomeDB; O60566; -.
DR   TreeFam; TF105456; -.
DR   BRENDA; 2.7.11.1; 2681.
DR   PathwayCommons; O60566; -.
DR   Reactome; R-HSA-141430; Inactivation of APC/C via direct inhibition of the APC/C complex.
DR   Reactome; R-HSA-141444; Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal.
DR   Reactome; R-HSA-174184; Cdc20:Phospho-APC/C mediated degradation of Cyclin A.
DR   Reactome; R-HSA-176409; APC/C:Cdc20 mediated degradation of mitotic proteins.
DR   Reactome; R-HSA-179409; APC-Cdc20 mediated degradation of Nek2A.
DR   Reactome; R-HSA-2467813; Separation of Sister Chromatids.
DR   Reactome; R-HSA-2500257; Resolution of Sister Chromatid Cohesion.
DR   Reactome; R-HSA-5663220; RHO GTPases Activate Formins.
DR   Reactome; R-HSA-68877; Mitotic Prometaphase.
DR   Reactome; R-HSA-9648025; EML4 and NUDC in mitotic spindle formation.
DR   SignaLink; O60566; -.
DR   SIGNOR; O60566; -.
DR   BioGRID-ORCS; 701; 685 hits in 1057 CRISPR screens.
DR   ChiTaRS; BUB1B; human.
DR   EvolutionaryTrace; O60566; -.
DR   GeneWiki; BUB1B; -.
DR   GenomeRNAi; 701; -.
DR   Pharos; O60566; Tbio.
DR   PRO; PR:O60566; -.
DR   Proteomes; UP000005640; Chromosome 15.
DR   RNAct; O60566; protein.
DR   Bgee; ENSG00000156970; Expressed in secondary oocyte and 164 other tissues.
DR   ExpressionAtlas; O60566; baseline and differential.
DR   Genevisible; O60566; HS.
DR   GO; GO:0005680; C:anaphase-promoting complex; TAS:ProtInc.
DR   GO; GO:0005737; C:cytoplasm; IDA:LIFEdb.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0000776; C:kinetochore; IDA:UniProtKB.
DR   GO; GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
DR   GO; GO:0000940; C:outer kinetochore; IDA:UniProtKB.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:BHF-UCL.
DR   GO; GO:0005819; C:spindle; IDA:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0004672; F:protein kinase activity; IBA:GO_Central.
DR   GO; GO:0106310; F:protein serine kinase activity; IEA:UniProtKB-EC.
DR   GO; GO:0106311; F:protein threonine kinase activity; IEA:UniProtKB-EC.
DR   GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR   GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR   GO; GO:0051754; P:meiotic sister chromatid cohesion, centromeric; IBA:GO_Central.
DR   GO; GO:0007091; P:metaphase/anaphase transition of mitotic cell cycle; IEA:Ensembl.
DR   GO; GO:0000278; P:mitotic cell cycle; TAS:ProtInc.
DR   GO; GO:0007093; P:mitotic cell cycle checkpoint signaling; TAS:ProtInc.
DR   GO; GO:0007094; P:mitotic spindle assembly checkpoint signaling; IBA:GO_Central.
DR   GO; GO:0071459; P:protein localization to chromosome, centromeric region; IEA:Ensembl.
DR   DisProt; DP01117; -.
DR   IDEAL; IID00407; -.
DR   InterPro; IPR015661; Bub1/Mad3.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR013212; Mad3/Bub1_I.
DR   PANTHER; PTHR14030; PTHR14030; 1.
DR   Pfam; PF08311; Mad3_BUB1_I; 1.
DR   SMART; SM00777; Mad3_BUB1_I; 1.
DR   SUPFAM; SSF56112; SSF56112; 1.
DR   PROSITE; PS51489; BUB1_N; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Alternative splicing; Apoptosis; ATP-binding;
KW   Cell cycle; Cell division; Centromere; Chromosome; Cytoplasm; Cytoskeleton;
KW   Disease variant; Kinase; Kinetochore; Mitosis; Nucleotide-binding; Nucleus;
KW   Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW   Transferase; Tumor suppressor; Ubl conjugation.
FT   CHAIN           1..1050
FT                   /note="Mitotic checkpoint serine/threonine-protein kinase
FT                   BUB1 beta"
FT                   /id="PRO_0000085673"
FT   DOMAIN          62..226
FT                   /note="BUB1 N-terminal"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00822"
FT   DOMAIN          766..1050
FT                   /note="Protein kinase"
FT   NP_BIND         772..780
FT                   /note="ATP"
FT                   /evidence="ECO:0000250"
FT   REGION          152..185
FT                   /note="Necessary for interaction with KNL1"
FT                   /evidence="ECO:0000269|PubMed:17981135"
FT   REGION          368..393
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          456..480
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           111..118
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000255"
FT   MOTIF           224..232
FT                   /note="D-box"
FT   ACT_SITE        882
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250"
FT   BINDING         795
FT                   /note="ATP"
FT                   /evidence="ECO:0000250"
FT   SITE            579..580
FT                   /note="Cleavage; by caspase-3"
FT                   /evidence="ECO:0000269|PubMed:16227576"
FT   SITE            610..611
FT                   /note="Cleavage; by caspase-3"
FT                   /evidence="ECO:0000269|PubMed:16227576"
FT   MOD_RES         250
FT                   /note="N6-acetyllysine; by PCAF"
FT                   /evidence="ECO:0000269|PubMed:19407811"
FT   MOD_RES         367
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         435
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:19015317,
FT                   ECO:0007744|PubMed:23186163"
FT   MOD_RES         543
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:19015317,
FT                   ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT   MOD_RES         665
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         670
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:19015317,
FT                   ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976,
FT                   ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT   MOD_RES         676
FT                   /note="Phosphoserine; by PLK1"
FT                   /evidence="ECO:0000269|PubMed:17785528"
FT   MOD_RES         697
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         792
FT                   /note="Phosphothreonine; by PLK1"
FT                   /evidence="ECO:0000269|PubMed:17376779"
FT   MOD_RES         1008
FT                   /note="Phosphothreonine; by PLK1"
FT                   /evidence="ECO:0000269|PubMed:17376779"
FT   MOD_RES         1042
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:20068231"
FT   MOD_RES         1043
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:19015317"
FT   VAR_SEQ         80
FT                   /note="R -> RWVFLFHKDNRNINR (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_036473"
FT   VAR_SEQ         113..166
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_036474"
FT   VAR_SEQ         522
FT                   /note="K -> KVSLSL (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_036475"
FT   VAR_SEQ         608..675
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_036476"
FT   VARIANT         15
FT                   /note="M -> T (in a colorectal cancer cell line;
FT                   dbSNP:rs1392369693)"
FT                   /evidence="ECO:0000269|PubMed:9521327"
FT                   /id="VAR_008852"
FT   VARIANT         36
FT                   /note="R -> Q (in PCS; dbSNP:rs534297115)"
FT                   /evidence="ECO:0000269|PubMed:16411201"
FT                   /id="VAR_028921"
FT   VARIANT         40
FT                   /note="T -> M (in dbSNP:rs56079734)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_040402"
FT   VARIANT         349
FT                   /note="R -> Q (in dbSNP:rs1801376)"
FT                   /evidence="ECO:0000269|PubMed:10366450,
FT                   ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334,
FT                   ECO:0000269|PubMed:17344846, ECO:0000269|PubMed:9521327,
FT                   ECO:0000269|PubMed:9618306, ECO:0000269|PubMed:9660858,
FT                   ECO:0000269|PubMed:9763420, ECO:0000269|Ref.6"
FT                   /id="VAR_008853"
FT   VARIANT         378
FT                   /note="P -> S (in dbSNP:rs17851677)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_054549"
FT   VARIANT         390
FT                   /note="E -> D (in dbSNP:rs1017842)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_028922"
FT   VARIANT         550
FT                   /note="R -> Q (in MVA1; heterozygous compound with nonsense
FT                   mutation; dbSNP:rs28989187)"
FT                   /evidence="ECO:0000269|PubMed:15475955"
FT                   /id="VAR_028923"
FT   VARIANT         618
FT                   /note="V -> A (in dbSNP:rs1801528)"
FT                   /evidence="ECO:0000269|PubMed:10366450,
FT                   ECO:0000269|PubMed:17344846"
FT                   /id="VAR_008854"
FT   VARIANT         814
FT                   /note="R -> H (in MVA1; heterozygous compound with nonsense
FT                   mutation; dbSNP:rs28989182)"
FT                   /evidence="ECO:0000269|PubMed:15475955"
FT                   /id="VAR_028924"
FT   VARIANT         844
FT                   /note="L -> F (in MVA1; associated with H-921; heterozygous
FT                   compound with nonsense mutation; dbSNP:rs28989181)"
FT                   /evidence="ECO:0000269|PubMed:15475955"
FT                   /id="VAR_028925"
FT   VARIANT         909
FT                   /note="I -> T (in MVA1; heterozygous compound with nonsense
FT                   mutation; dbSNP:rs28989184)"
FT                   /evidence="ECO:0000269|PubMed:15475955"
FT                   /id="VAR_028926"
FT   VARIANT         921
FT                   /note="Q -> H (in MVA1; associated with F-844; heterozygous
FT                   compound with nonsense mutation; dbSNP:rs28989183)"
FT                   /evidence="ECO:0000269|PubMed:15475955"
FT                   /id="VAR_028927"
FT   VARIANT         1012
FT                   /note="L -> P (in MVA1; heterozygous compound with nonsense
FT                   mutation; dbSNP:rs28989185)"
FT                   /evidence="ECO:0000269|PubMed:15475955"
FT                   /id="VAR_028928"
FT   MUTAGEN         159
FT                   /note="A->W: Loss of interaction with KNL1."
FT                   /evidence="ECO:0000269|PubMed:17981135"
FT   MUTAGEN         175
FT                   /note="F->A: Loss of interaction with KNL1."
FT                   /evidence="ECO:0000269|PubMed:17981135"
FT   MUTAGEN         579
FT                   /note="D->E: Abolishes the cleavage by caspase-3."
FT                   /evidence="ECO:0000269|PubMed:16227576"
FT   MUTAGEN         610
FT                   /note="D->E: Abolishes the cleavage by caspase-3."
FT                   /evidence="ECO:0000269|PubMed:16227576"
FT   MUTAGEN         620
FT                   /note="T->A: Induces chromosome congression defects and
FT                   mitotic delay."
FT                   /evidence="ECO:0000269|PubMed:17785528"
FT   MUTAGEN         795
FT                   /note="K->A: Does not abolish the capacity to inhibit
FT                   APC/CDC20."
FT                   /evidence="ECO:0000269|PubMed:11702782,
FT                   ECO:0000269|PubMed:12925705"
FT   MUTAGEN         795
FT                   /note="K->R: Inhibits kinase activity."
FT                   /evidence="ECO:0000269|PubMed:11702782,
FT                   ECO:0000269|PubMed:12925705"
FT   CONFLICT        248..249
FT                   /note="AL -> VF (in Ref. 1; AAC23736)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        283
FT                   /note="S -> P (in Ref. 8; BAG35587)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        788
FT                   /note="S -> F (in Ref. 2; AAC06260)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1018
FT                   /note="E -> K (in Ref. 3; AAC33435)"
FT                   /evidence="ECO:0000305"
FT   TURN            26..28
FT                   /evidence="ECO:0007829|PDB:4GGD"
FT   HELIX           60..65
FT                   /evidence="ECO:0007829|PDB:2WVI"
FT   HELIX           75..88
FT                   /evidence="ECO:0007829|PDB:2WVI"
FT   HELIX           94..96
FT                   /evidence="ECO:0007829|PDB:3SI5"
FT   HELIX           98..108
FT                   /evidence="ECO:0007829|PDB:2WVI"
FT   TURN            109..111
FT                   /evidence="ECO:0007829|PDB:2WVI"
FT   HELIX           113..115
FT                   /evidence="ECO:0007829|PDB:2WVI"
FT   HELIX           119..131
FT                   /evidence="ECO:0007829|PDB:2WVI"
FT   HELIX           135..144
FT                   /evidence="ECO:0007829|PDB:2WVI"
FT   HELIX           152..164
FT                   /evidence="ECO:0007829|PDB:2WVI"
FT   HELIX           168..180
FT                   /evidence="ECO:0007829|PDB:2WVI"
FT   HELIX           186..218
FT                   /evidence="ECO:0007829|PDB:2WVI"
SQ   SEQUENCE   1050 AA;  119545 MW;  F7871103A56E6B46 CRC64;
     MAAVKKEGGA LSEAMSLEGD EWELSKENVQ PLRQGRIMST LQGALAQESA CNNTLQQQKR
     AFEYEIRFYT GNDPLDVWDR YISWTEQNYP QGGKESNMST LLERAVEALQ GEKRYYSDPR
     FLNLWLKLGR LCNEPLDMYS YLHNQGIGVS LAQFYISWAE EYEARENFRK ADAIFQEGIQ
     QKAEPLERLQ SQHRQFQARV SRQTLLALEK EEEEEVFESS VPQRSTLAEL KSKGKKTARA
     PIIRVGGALK APSQNRGLQN PFPQQMQNNS RITVFDENAD EASTAELSKP TVQPWIAPPM
     PRAKENELQA GPWNTGRSLE HRPRGNTASL IAVPAVLPSF TPYVEETARQ PVMTPCKIEP
     SINHILSTRK PGKEEGDPLQ RVQSHQQASE EKKEKMMYCK EKIYAGVGEF SFEEIRAEVF
     RKKLKEQREA ELLTSAEKRA EMQKQIEEME KKLKEIQTTQ QERTGDQQEE TMPTKETTKL
     QIASESQKIP GMTLSSSVCQ VNCCARETSL AENIWQEQPH SKGPSVPFSI FDEFLLSEKK
     NKSPPADPPR VLAQRRPLAV LKTSESITSN EDVSPDVCDE FTGIEPLSED AIITGFRNVT
     ICPNPEDTCD FARAARFVST PFHEIMSLKD LPSDPERLLP EEDLDVKTSE DQQTACGTIY
     SQTLSIKKLS PIIEDSREAT HSSGFSGSSA SVASTSSIKC LQIPEKLELT NETSENPTQS
     PWCSQYRRQL LKSLPELSAS AELCIEDRPM PKLEIEKEIE LGNEDYCIKR EYLICEDYKL
     FWVAPRNSAE LTVIKVSSQP VPWDFYINLK LKERLNEDFD HFCSCYQYQD GCIVWHQYIN
     CFTLQDLLQH SEYITHEITV LIIYNLLTIV EMLHKAEIVH GDLSPRCLIL RNRIHDPYDC
     NKNNQALKIV DFSYSVDLRV QLDVFTLSGF RTVQILEGQK ILANCSSPYQ VDLFGIADLA
     HLLLFKEHLQ VFWDGSFWKL SQNISELKDG ELWNKFFVRI LNANDEATVS VLGELAAEMN
     GVFDTTFQSH LNKALWKVGK LTSPGALLFQ
//
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