PLK1_HUMAN
ID PLK1_HUMAN Reviewed; 603 AA.
AC P53350; Q15153; Q99746;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 237.
DE RecName: Full=Serine/threonine-protein kinase PLK1;
DE EC=2.7.11.21 {ECO:0000269|PubMed:11202906, ECO:0000269|PubMed:12207013, ECO:0000269|PubMed:21880710};
DE AltName: Full=Polo-like kinase 1;
DE Short=PLK-1;
DE AltName: Full=Serine/threonine-protein kinase 13;
DE Short=STPK13;
GN Name=PLK1; Synonyms=PLK;
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].
RC TISSUE=Placenta;
RX PubMed=8018557;
RA Hamanaka R., Maloid S., Smith M.R., O'Connell C.D., Longo D.L.,
RA Ferris D.K.;
RT "Cloning and characterization of human and murine homologues of the
RT Drosophila polo serine-threonine kinase.";
RL Cell Growth Differ. 5:249-257(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7902533; DOI=10.1128/mcb.13.12.7793-7801.1993;
RA Lake R.J., Jelinek W.R.;
RT "Cell cycle- and terminal differentiation-associated regulation of the
RT mouse mRNA encoding a conserved mitotic protein kinase.";
RL Mol. Cell. Biol. 13:7793-7801(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7962193; DOI=10.1242/jcs.107.6.1509;
RA Golsteyn R.M., Schultz S.J., Bartek J., Ziemiecki A., Ried T., Nigg E.A.;
RT "Cell cycle analysis and chromosomal localization of human Plk1, a putative
RT homologue of the mitotic kinases Drosophila polo and Saccharomyces
RT cerevisiae Cdc5.";
RL J. Cell Sci. 107:1509-1517(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lung;
RX PubMed=8127874; DOI=10.1073/pnas.91.5.1736;
RA Holtrich U., Wolf G., Braeuninger A., Karn T., Boehme B.,
RA Ruebsamen-Waigmann H., Strebhardt K.;
RT "Induction and down-regulation of PLK, a human serine/threonine kinase
RT expressed in proliferating cells and tumors.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:1736-1740(1994).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon, and Lung;
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 [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-136.
RX PubMed=7478607;
RA Brauninger A., Strebhardt K., Rubsamen-Waigmann H.;
RT "Identification and functional characterization of the human and murine
RT polo-like kinase (Plk) promoter.";
RL Oncogene 11:1793-1800(1995).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-136.
RX PubMed=9083047; DOI=10.1074/jbc.272.14.9166;
RA Uchiumi T., Longo D.L., Ferris D.K.;
RT "Cell cycle regulation of the human polo-like kinase (PLK) promoter.";
RL J. Biol. Chem. 272:9166-9174(1997).
RN [8]
RP FUNCTION IN CENTROSOME MATURATION, AND SUBCELLULAR LOCATION.
RX PubMed=8991084; DOI=10.1083/jcb.135.6.1701;
RA Lane H.A., Nigg E.A.;
RT "Antibody microinjection reveals an essential role for human polo-like
RT kinase 1 (Plk1) in the functional maturation of mitotic centrosomes.";
RL J. Cell Biol. 135:1701-1713(1996).
RN [9]
RP FUNCTION IN PHOSPHORYLATION OF CDC25C.
RX PubMed=11202906; DOI=10.1016/s0898-6568(00)00080-2;
RA Roshak A.K., Capper E.A., Imburgia C., Fornwald J., Scott G.,
RA Marshall L.A.;
RT "The human polo-like kinase, PLK, regulates cdc2/cyclin B through
RT phosphorylation and activation of the cdc25C phosphatase.";
RL Cell. Signal. 12:405-411(2000).
RN [10]
RP FUNCTION, PHOSPHORYLATION AT SER-137 AND THR-210, AND MUTAGENESIS OF
RP LYS-82; SER-137 AND THR-210.
RX PubMed=12207013; DOI=10.1074/jbc.m202172200;
RA Jang Y.-J., Ma S., Terada Y., Erikson R.L.;
RT "Phosphorylation of threonine 210 and the role of serine 137 in the
RT regulation of mammalian polo-like kinase.";
RL J. Biol. Chem. 277:44115-44120(2002).
RN [11]
RP FUNCTION IN PHOSPHORYLATION OF CCNB1, SUBCELLULAR LOCATION, AND MUTAGENESIS
RP OF LYS-82 AND THR-210.
RX PubMed=12447691; DOI=10.1038/sj.onc.1206011;
RA Yuan J., Eckerdt F., Bereiter-Hahn J., Kurunci-Csacsko E., Kaufmann M.,
RA Strebhardt K.;
RT "Cooperative phosphorylation including the activity of polo-like kinase 1
RT regulates the subcellular localization of cyclin B1.";
RL Oncogene 21:8282-8292(2002).
RN [12]
RP PHOSPHORYLATION AT SER-335.
RX PubMed=12442251;
RX DOI=10.1002/1615-9861(200211)2:11<1516::aid-prot1516>3.0.co;2-y;
RA Wind M., Kelm O., Nigg E.A., Lehmann W.D.;
RT "Identification of phosphorylation sites in the polo-like kinases Plx1 and
RT Plk1 by a novel strategy based on element and electrospray high resolution
RT mass spectrometry.";
RL Proteomics 2:1516-1523(2002).
RN [13]
RP FUNCTION IN PHOSPHORYLATION OF NINL.
RX PubMed=12852856; DOI=10.1016/s1534-5807(03)00193-x;
RA Casenghi M., Meraldi P., Weinhart U., Duncan P.I., Korner R., Nigg E.A.;
RT "Polo-like kinase 1 regulates Nlp, a centrosome protein involved in
RT microtubule nucleation.";
RL Dev. Cell 5:113-125(2003).
RN [14]
RP PHOSPHORYLATION BY STK10.
RX PubMed=12639966; DOI=10.1074/jbc.m212556200;
RA Walter S.A., Cutler R.E. Jr., Martinez R., Gishizky M., Hill R.J.;
RT "Stk10, a new member of the polo-like kinase kinase family highly expressed
RT in hematopoietic tissue.";
RL J. Biol. Chem. 278:18221-18228(2003).
RN [15]
RP FUNCTION IN PHOSPHORYLATION OF PKMYT1.
RX PubMed=12738781; DOI=10.1074/jbc.c300126200;
RA Nakajima H., Toyoshima-Morimoto F., Taniguchi E., Nishida E.;
RT "Identification of a consensus motif for Plk (Polo-like kinase)
RT phosphorylation reveals Myt1 as a Plk1 substrate.";
RL J. Biol. Chem. 278:25277-25280(2003).
RN [16]
RP FUNCTION IN PHOSPHORYLATION OF KIF20A, DOMAIN POLO BOX, SUBCELLULAR
RP LOCATION, AND INTERACTION WITH KIF20A.
RX PubMed=12939256; DOI=10.1083/jcb.200306009;
RA Neef R., Preisinger C., Sutcliffe J., Kopajtich R., Nigg E.A., Mayer T.U.,
RA Barr F.A.;
RT "Phosphorylation of mitotic kinesin-like protein 2 by polo-like kinase 1 is
RT required for cytokinesis.";
RL J. Cell Biol. 162:863-875(2003).
RN [17]
RP FUNCTION IN PHOSPHORYLATION OF CCNB1, AND SUBCELLULAR LOCATION.
RX PubMed=12524548; DOI=10.1038/ncb918;
RA Jackman M., Lindon C., Nigg E.A., Pines J.;
RT "Active cyclin B1-Cdk1 first appears on centrosomes in prophase.";
RL Nat. Cell Biol. 5:143-148(2003).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Lymphoblast;
RX PubMed=14654843; DOI=10.1038/nature02166;
RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., Mann M.;
RT "Proteomic characterization of the human centrosome by protein correlation
RT profiling.";
RL Nature 426:570-574(2003).
RN [19]
RP FUNCTION, PROTEASOMAL DEGRADATION, DOMAIN D-BOX MOTIF, AND MUTAGENESIS OF
RP ARG-337 AND LEU-340.
RX PubMed=14734534; DOI=10.1083/jcb.200309035;
RA Lindon C., Pines J.;
RT "Ordered proteolysis in anaphase inactivates Plk1 to contribute to proper
RT mitotic exit in human cells.";
RL J. Cell Biol. 164:233-241(2004).
RN [20]
RP FUNCTION IN PHOSPHORYLATION OF FBXO5.
RX PubMed=15469984; DOI=10.1091/mbc.e04-07-0598;
RA Hansen D.V., Loktev A.V., Ban K.H., Jackson P.K.;
RT "Plk1 regulates activation of the anaphase promoting complex by
RT phosphorylating and triggering SCFbetaTrCP-dependent destruction of the APC
RT inhibitor Emi1.";
RL Mol. Biol. Cell 15:5623-5634(2004).
RN [21]
RP FUNCTION IN PHOSPHORYLATION OF WEE1.
RX PubMed=15070733; DOI=10.1073/pnas.0307700101;
RA Watanabe N., Arai H., Nishihara Y., Taniguchi M., Watanabe N., Hunter T.,
RA Osada H.;
RT "M-phase kinases induce phospho-dependent ubiquitination of somatic Wee1 by
RT SCFbeta-TrCP.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:4419-4424(2004).
RN [22]
RP FUNCTION IN PHOSPHORYLATION OF FBXO5.
RX PubMed=15148369; DOI=10.1073/pnas.0402442101;
RA Moshe Y., Boulaire J., Pagano M., Hershko A.;
RT "Role of Polo-like kinase in the degradation of early mitotic inhibitor 1,
RT a regulator of the anaphase promoting complex/cyclosome.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:7937-7942(2004).
RN [23]
RP FUNCTION IN PHOSPHORYLATION OF CEP55.
RX PubMed=16198290; DOI=10.1016/j.devcel.2005.09.003;
RA Fabbro M., Zhou B.-B., Takahashi M., Sarcevic B., Lal P., Graham M.E.,
RA Gabrielli B.G., Robinson P.J., Nigg E.A., Ono Y., Khanna K.K.;
RT "Cdk1/Erk2- and Plk1-dependent phosphorylation of a centrosome protein,
RT Cep55, is required for its recruitment to midbody and cytokinesis.";
RL Dev. Cell 9:477-488(2005).
RN [24]
RP FUNCTION IN PHOSPHORYLATION OF HSF1, AND INTERACTION WITH HSF1.
RX PubMed=15661742; DOI=10.1074/jbc.m411908200;
RA Kim S.A., Yoon J.H., Lee S.H., Ahn S.G.;
RT "Polo-like kinase 1 phosphorylates heat shock transcription factor 1 and
RT mediates its nuclear translocation during heat stress.";
RL J. Biol. Chem. 280:12653-12657(2005).
RN [25]
RP INTERACTION WITH CEP170.
RX PubMed=15616186; DOI=10.1091/mbc.e04-10-0939;
RA Guarguaglini G., Duncan P.I., Stierhof Y.D., Holmstroem T., Duensing S.,
RA Nigg E.A.;
RT "The forkhead-associated domain protein Cep170 interacts with Polo-like
RT kinase 1 and serves as a marker for mature centrioles.";
RL Mol. Biol. Cell 16:1095-1107(2005).
RN [26]
RP INTERACTION WITH EVI5.
RX PubMed=16439210; DOI=10.1016/j.cell.2005.10.038;
RA Eldridge A.G., Loktev A.V., Hansen D.V., Verschuren E.W., Reimann J.D.R.,
RA Jackson P.K.;
RT "The evi5 oncogene regulates cyclin accumulation by stabilizing the
RT anaphase-promoting complex inhibitor emi1.";
RL Cell 124:367-380(2006).
RN [27]
RP SUBCELLULAR LOCATION, INTERACTION WITH BUB1 AND BUB1B, AND MUTAGENESIS OF
RP HIS-538 AND LYS-540.
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 [28]
RP FUNCTION IN PHOSPHORYLATION OF KIZ.
RX PubMed=16980960; DOI=10.1038/ncb1474;
RA Oshimori N., Ohsugi M., Yamamoto T.;
RT "The Plk1 target Kizuna stabilizes mitotic centrosomes to ensure spindle
RT bipolarity.";
RL Nat. Cell Biol. 8:1095-1101(2006).
RN [29]
RP FUNCTION IN PHOSPHORYLATION OF ECT2, AND INTERACTION WITH ECT2.
RX PubMed=16247472; DOI=10.1038/sj.onc.1209124;
RA Niiya F., Tatsumoto T., Lee K.S., Miki T.;
RT "Phosphorylation of the cytokinesis regulator ECT2 at G2/M phase stimulates
RT association of the mitotic kinase Plk1 and accumulation of GTP-bound
RT RhoA.";
RL Oncogene 25:827-837(2006).
RN [30]
RP FUNCTION IN PHOSPHORYLATION OF CENPU.
RX PubMed=17081991; DOI=10.1016/j.molcel.2006.10.016;
RA Kang Y.H., Park J.-E., Yu L.-R., Soung N.-K., Yun S.-M., Bang J.K.,
RA Seong Y.-S., Yu H., Garfield S., Veenstra T.D., Lee K.S.;
RT "Self-regulated Plk1 recruitment to kinetochores by the Plk1-PBIP1
RT interaction is critical for proper chromosome segregation.";
RL Mol. Cell 24:409-422(2006).
RN [31]
RP INVOLVEMENT IN CANCER.
RX PubMed=16645325; DOI=10.1159/000093003;
RA Kanaji S., Saito H., Tsujitani S., Matsumoto S., Tatebe S., Kondo A.,
RA Ozaki M., Ito H., Ikeguchi M.;
RT "Expression of polo-like kinase 1 (PLK1) protein predicts the survival of
RT patients with gastric carcinoma.";
RL Oncology 70:126-133(2006).
RN [32]
RP INVOLVEMENT IN CANCER.
RX PubMed=17981789; DOI=10.1158/0008-5472.can-07-1887;
RA Salvatore G., Nappi T.C., Salerno P., Jiang Y., Garbi C., Ugolini C.,
RA Miccoli P., Basolo F., Castellone M.D., Cirafici A.M., Melillo R.M.,
RA Fusco A., Bittner M.L., Santoro M.;
RT "A cell proliferation and chromosomal instability signature in anaplastic
RT thyroid carcinoma.";
RL Cancer Res. 67:10148-10158(2007).
RN [33]
RP INTERACTION WITH ERCC6L.
RX PubMed=17218258; DOI=10.1016/j.cell.2006.11.041;
RA Baumann C., Koerner R., Hofmann K., Nigg E.A.;
RT "PICH, a centromere-associated SNF2 family ATPase, is regulated by Plk1 and
RT required for the spindle checkpoint.";
RL Cell 128:101-114(2007).
RN [34]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=17617734; DOI=10.4161/cc.6.13.4442;
RA Pouwels J., Kukkonen A.M., Lan W., Daum J.R., Gorbsky G.J., Stukenberg T.,
RA Kallio M.J.;
RT "Shugoshin 1 plays a central role in kinetochore assembly and is required
RT for kinetochore targeting of Plk1.";
RL Cell Cycle 6:1579-1585(2007).
RN [35]
RP INTERACTION WITH TTDN1.
RX PubMed=17310276; DOI=10.1007/s00018-007-6501-8;
RA Zhang Y., Tian Y., Chen Q., Chen D., Zhai Z., Shu H.-B.;
RT "TTDN1 is a Plk1-interacting protein involved in maintenance of cell cycle
RT integrity.";
RL Cell. Mol. Life Sci. 64:632-640(2007).
RN [36]
RP FUNCTION IN PHOSPHORYLATION OF BUB1B.
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 [37]
RP INVOLVEMENT IN CANCER.
RX PubMed=17943598; DOI=10.1080/10428190701615918;
RA Liu L., Zhang M., Zou P.;
RT "Expression of PLK1 and survivin in diffuse large B-cell lymphoma.";
RL Leuk. Lymphoma 48:2179-2183(2007).
RN [38]
RP FUNCTION IN PHOSPHORYLATION OF PRC1, AND DOMAIN POLO BOX.
RX PubMed=17351640; DOI=10.1038/ncb1557;
RA Neef R., Gruneberg U., Kopajtich R., Li X., Nigg E.A., Sillje H.,
RA Barr F.A.;
RT "Choice of Plk1 docking partners during mitosis and cytokinesis is
RT controlled by the activation state of Cdk1.";
RL Nat. Cell Biol. 9:436-444(2007).
RN [39]
RP INTERACTION WITH CYLD, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=17495026; DOI=10.1073/pnas.0703268104;
RA Stegmeier F., Sowa M.E., Nalepa G., Gygi S.P., Harper J.W., Elledge S.J.;
RT "The tumor suppressor CYLD regulates entry into mitosis.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:8869-8874(2007).
RN [40]
RP FUNCTION IN PHOSPHORYLATION OF HSF1, INTERACTION WITH HSF1, AND SUBCELLULAR
RP LOCATION.
RX PubMed=18794143; DOI=10.1158/0008-5472.can-08-0129;
RA Lee Y.J., Kim E.H., Lee J.S., Jeoung D., Bae S., Kwon S.H., Lee Y.S.;
RT "HSF1 as a mitotic regulator: phosphorylation of HSF1 by Plk1 is essential
RT for mitotic progression.";
RL Cancer Res. 68:7550-7560(2008).
RN [41]
RP UBIQUITINATION BY THE APC/C COMPLEX, INTERACTION WITH FZR1, AND MUTAGENESIS
RP OF ARG-337 AND LEU-340.
RX PubMed=18662541; DOI=10.1016/j.cell.2008.05.043;
RA Bassermann F., Frescas D., Guardavaccaro D., Busino L., Peschiaroli A.,
RA Pagano M.;
RT "The Cdc14B-Cdh1-Plk1 axis controls the G2 DNA-damage-response
RT checkpoint.";
RL Cell 134:256-267(2008).
RN [42]
RP INTERACTION WITH BIRC6/BRUCE.
RX PubMed=18329369; DOI=10.1016/j.cell.2008.01.012;
RA Pohl C., Jentsch S.;
RT "Final stages of cytokinesis and midbody ring formation are controlled by
RT BRUCE.";
RL Cell 132:832-845(2008).
RN [43]
RP FUNCTION IN PHOSPHORYLATION OF TP73.
RX PubMed=18418051; DOI=10.4161/cc.7.9.5777;
RA Soond S.M., Barry S.P., Melino G., Knight R.A., Latchman D.S.,
RA Stephanou A.;
RT "p73-mediated transcriptional activity is negatively regulated by polo-like
RT kinase 1.";
RL Cell Cycle 7:1214-1223(2008).
RN [44]
RP FUNCTION, AND INTERACTION WITH PHOSPHORYLATED BORA.
RX PubMed=18521620; DOI=10.1007/s00412-008-0165-5;
RA Chan E.H., Santamaria A., Sillje H.H., Nigg E.A.;
RT "Plk1 regulates mitotic Aurora A function through betaTrCP-dependent
RT degradation of hBora.";
RL Chromosoma 117:457-469(2008).
RN [45]
RP FUNCTION IN PHOSPHORYLATION OF SGO1, AND INTERACTION WITH SGO1.
RX PubMed=18331714; DOI=10.1016/j.devcel.2007.12.007;
RA Wang X., Yang Y., Duan Q., Jiang N., Huang Y., Darzynkiewicz Z., Dai W.;
RT "sSgo1, a major splice variant of Sgo1, functions in centriole cohesion
RT where it is regulated by Plk1.";
RL Dev. Cell 14:331-341(2008).
RN [46]
RP FUNCTION IN PHOSPHORYLATION OF PPP1R12A, PHOSPHORYLATION AT THR-210,
RP DEPHOSPHORYLATION BY PPP1C, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP HIS-538 AND LYS-540.
RX PubMed=18477460; DOI=10.1016/j.devcel.2008.02.013;
RA Yamashiro S., Yamakita Y., Totsukawa G., Goto H., Kaibuchi K., Ito M.,
RA Hartshorne D.J., Matsumura F.;
RT "Myosin phosphatase-targeting subunit 1 regulates mitosis by antagonizing
RT polo-like kinase 1.";
RL Dev. Cell 14:787-797(2008).
RN [47]
RP FUNCTION IN PHOSPHORYLATION OF TP73, AND MUTAGENESIS OF LYS-82.
RX PubMed=18174154; DOI=10.1074/jbc.m710608200;
RA Koida N., Ozaki T., Yamamoto H., Ono S., Koda T., Ando K., Okoshi R.,
RA Kamijo T., Omura K., Nakagawara A.;
RT "Inhibitory role of Plk1 in the regulation of p73-dependent apoptosis
RT through physical interaction and phosphorylation.";
RL J. Biol. Chem. 283:8555-8563(2008).
RN [48]
RP INTERACTION WITH FAM29A.
RX PubMed=19029337; DOI=10.1083/jcb.200807046;
RA Zhu H., Coppinger J.A., Jang C.-Y., Yates J.R. III, Fang G.;
RT "FAM29A promotes microtubule amplification via recruitment of the NEDD1-
RT gamma-tubulin complex to the mitotic spindle.";
RL J. Cell Biol. 183:835-848(2008).
RN [49]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-6; SER-103; THR-210; THR-214;
RP SER-375; SER-450 AND THR-498, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [50]
RP FUNCTION IN PHOSPHORYLATION OF FOXM1, AND MUTAGENESIS OF LYS-82 AND
RP THR-210.
RX PubMed=19160488; DOI=10.1038/ncb1767;
RA Fu Z., Malureanu L., Huang J., Wang W., Li H., van Deursen J.M.,
RA Tindall D.J., Chen J.;
RT "Plk1-dependent phosphorylation of FoxM1 regulates a transcriptional
RT programme required for mitotic progression.";
RL Nat. Cell Biol. 10:1076-1082(2008).
RN [51]
RP FUNCTION, ACTIVITY REGULATION, PHOSPHORYLATION AT THR-210 BY AURKA,
RP SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-82; SER-137; ASP-176 AND THR-210,
RP AND ACTIVE SITE.
RX PubMed=18615013; DOI=10.1038/nature07185;
RA Macurek L., Lindqvist A., Lim D., Lampson M.A., Klompmaker R., Freire R.,
RA Clouin C., Taylor S.S., Yaffe M.B., Medema R.H.;
RT "Polo-like kinase-1 is activated by aurora A to promote checkpoint
RT recovery.";
RL Nature 455:119-123(2008).
RN [52]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-210 AND THR-214, AND
RP IDENTIFICATION BY 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 [53]
RP INTERACTION WITH SLX4.
RX PubMed=19596235; DOI=10.1016/j.cell.2009.06.030;
RA Svendsen J.M., Smogorzewska A., Sowa M.E., O'Connell B.C., Gygi S.P.,
RA Elledge S.J., Harper J.W.;
RT "Mammalian BTBD12/SLX4 assembles a Holliday junction resolvase and is
RT required for DNA repair.";
RL Cell 138:63-77(2009).
RN [54]
RP FUNCTION IN PHOSPHORYLATION OF TOPORS, AND INTERACTION WITH TOPORS.
RX PubMed=19473992; DOI=10.1074/jbc.c109.001560;
RA Yang X., Li H., Zhou Z., Wang W.H., Deng A., Andrisani O., Liu X.;
RT "Plk1-mediated phosphorylation of Topors regulates p53 stability.";
RL J. Biol. Chem. 284:18588-18592(2009).
RN [55]
RP FUNCTION AS NEDD1 KINASE.
RX PubMed=19509060; DOI=10.1242/jcs.042747;
RA Zhang X., Chen Q., Feng J., Hou J., Yang F., Liu J., Jiang Q., Zhang C.;
RT "Sequential phosphorylation of Nedd1 by Cdk1 and Plk1 is required for
RT targeting of the gammaTuRC to the centrosome.";
RL J. Cell Sci. 122:2240-2251(2009).
RN [56]
RP FUNCTION, INTERACTION WITH KIF2A, AND SUBCELLULAR LOCATION.
RX PubMed=19351716; DOI=10.1242/jcs.044321;
RA Jang C.Y., Coppinger J.A., Seki A., Yates J.R. III, Fang G.;
RT "Plk1 and Aurora A regulate the depolymerase activity and the cellular
RT localization of Kif2a.";
RL J. Cell Sci. 122:1334-1341(2009).
RN [57]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-210 AND THR-214, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [58]
RP FUNCTION IN PHOSPHORYLATION OF RACGAP1, INTERACTION WITH PRC1, AND
RP SUBCELLULAR LOCATION.
RX PubMed=19468300; DOI=10.1371/journal.pbio.1000110;
RA Wolfe B.A., Takaki T., Petronczki M., Glotzer M.;
RT "Polo-like kinase 1 directs assembly of the HsCyk-4 RhoGAP/Ect2 RhoGEF
RT complex to initiate cleavage furrow formation.";
RL PLoS Biol. 7:E1000110-E1000110(2009).
RN [59]
RP FUNCTION IN PHOSPHORYLATION OF RACGAP1, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF CYS-67; LEU-130; HIS-538 AND LYS-540.
RX PubMed=19468302; DOI=10.1371/journal.pbio.1000111;
RA Burkard M.E., Maciejowski J., Rodriguez-Bravo V., Repka M., Lowery D.M.,
RA Clauser K.R., Zhang C., Shokat K.M., Carr S.A., Yaffe M.B.,
RA Jallepalli P.V.;
RT "Plk1 self-organization and priming phosphorylation of HsCYK-4 at the
RT spindle midzone regulate the onset of division in human cells.";
RL PLoS Biol. 7:E1000111-E1000111(2009).
RN [60]
RP REVIEW ON FUNCTION, AND REVIEW ON ACTIVITY REGULATION.
RX PubMed=20671765; DOI=10.1038/nrd3184;
RA Strebhardt K.;
RT "Multifaceted polo-like kinases: drug targets and antitargets for cancer
RT therapy.";
RL Nat. Rev. Drug Discov. 9:643-660(2010).
RN [61]
RP FUNCTION IN PHOSPHORYLATION OF DCTN1, AND INTERACTION WITH DCTN1.
RX PubMed=20679239; DOI=10.1073/pnas.1006615107;
RA Li H., Liu X.S., Yang X., Song B., Wang Y., Liu X.;
RT "Polo-like kinase 1 phosphorylation of p150Glued facilitates nuclear
RT envelope breakdown during prophase.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:14633-14638(2010).
RN [62]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-210, AND IDENTIFICATION BY
RP 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 [63]
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 [64]
RP FUNCTION IN PHOSPHORYLATION OF RIOK2, AND MUTAGENESIS OF LYS-82.
RX PubMed=21880710; DOI=10.1074/jbc.m111.250175;
RA Liu T., Deng M., Li J., Tong X., Wei Q., Ye X.;
RT "Phosphorylation of right open reading frame 2 (Rio2) protein kinase by
RT polo-like kinase 1 regulates mitotic progression.";
RL J. Biol. Chem. 286:36352-36360(2011).
RN [65]
RP IDENTIFICATION IN A COMPLEX WITH KNSTRN; SPAG5; DYNLL1 AND SGO2.
RX PubMed=21402792; DOI=10.1083/jcb.201008023;
RA Dunsch A.K., Linnane E., Barr F.A., Gruneberg U.;
RT "The astrin-kinastrin/SKAP complex localizes to microtubule plus ends and
RT facilitates chromosome alignment.";
RL J. Cell Biol. 192:959-968(2011).
RN [66]
RP INTERACTION WITH FRY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ASP-194.
RX PubMed=22753416; DOI=10.1074/jbc.m112.378968;
RA Ikeda M., Chiba S., Ohashi K., Mizuno K.;
RT "Furry protein promotes Aurora A-mediated polo-like kinase 1 activation.";
RL J. Biol. Chem. 287:27670-27681(2012).
RN [67]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [68]
RP INTERACTION WITH KLHL22.
RX PubMed=24067371; DOI=10.4161/cc.25369;
RA Metzger T., Kleiss C., Sumara I.;
RT "CUL3 and protein kinases: insights from PLK1/KLHL22 interaction.";
RL Cell Cycle 12:2291-2296(2013).
RN [69]
RP INTERACTION WITH CEP20, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-82;
RP TRP-414; VAL-415 AND LEU-427.
RX PubMed=24018379; DOI=10.1038/cr.2013.127;
RA Shen M., Cai Y., Yang Y., Yan X., Liu X., Zhou T.;
RT "Centrosomal protein FOR20 is essential for S-phase progression by
RT recruiting Plk1 to centrosomes.";
RL Cell Res. 23:1284-1295(2013).
RN [70]
RP INTERACTION WITH DCTN6, AND SUBCELLULAR LOCATION.
RX PubMed=23455152; DOI=10.1038/emboj.2013.30;
RA Yeh T.Y., Kowalska A.K., Scipioni B.R., Cheong F.K., Zheng M.,
RA Derewenda U., Derewenda Z.S., Schroer T.A.;
RT "Dynactin helps target Polo-like kinase 1 to kinetochores via its left-
RT handed beta-helical p27 subunit.";
RL EMBO J. 32:1023-1035(2013).
RN [71]
RP FUNCTION IN PHOSPHORYLATION OF MISP.
RX PubMed=23509069; DOI=10.1083/jcb.201207050;
RA Zhu M., Settele F., Kotak S., Sanchez-Pulido L., Ehret L., Ponting C.P.,
RA Goenczy P., Hoffmann I.;
RT "MISP is a novel Plk1 substrate required for proper spindle orientation and
RT mitotic progression.";
RL J. Cell Biol. 200:773-787(2013).
RN [72]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-210, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [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 [73]
RP FUNCTION, INTERACTION WITH KLHL22, SUBCELLULAR LOCATION, UBIQUITINATION AT
RP LYS-9 AND LYS-492, AND MUTAGENESIS OF LYS-492.
RX PubMed=23455478; DOI=10.1038/ncb2695;
RA Beck J., Maerki S., Posch M., Metzger T., Persaud A., Scheel H.,
RA Hofmann K., Rotin D., Pedrioli P., Swedlow J.R., Peter M., Sumara I.;
RT "Ubiquitylation-dependent localization of PLK1 in mitosis.";
RL Nat. Cell Biol. 15:430-439(2013).
RN [74]
RP INTERACTION WITH HNRNPU, AND FUNCTION IN PHOSPHORYLATION OF HNRNPU.
RX PubMed=25986610; DOI=10.1128/mcb.01312-14;
RA Douglas P., Ye R., Morrice N., Britton S., Trinkle-Mulcahy L.,
RA Lees-Miller S.P.;
RT "Phosphorylation of SAF-A/hnRNP-U serine 59 by polo-like kinase 1 is
RT required for mitosis.";
RL Mol. Cell. Biol. 35:2699-2713(2015).
RN [75]
RP FUNCTION, AND INTERACTION WITH CEP68.
RX PubMed=25503564; DOI=10.1038/ncb3076;
RA Pagan J.K., Marzio A., Jones M.J., Saraf A., Jallepalli P.V., Florens L.,
RA Washburn M.P., Pagano M.;
RT "Degradation of Cep68 and PCNT cleavage mediate Cep215 removal from the PCM
RT to allow centriole separation, disengagement and licensing.";
RL Nat. Cell Biol. 17:31-43(2015).
RN [76]
RP FUNCTION.
RX PubMed=27979967; DOI=10.1074/jbc.m116.765438;
RA Zhang B., Wang G., Xu X., Yang S., Zhuang T., Wang G., Ren H., Cheng S.Y.,
RA Jiang Q., Zhang C.;
RT "DAZ-interacting Protein 1 (Dzip1) Phosphorylation by Polo-like Kinase 1
RT (Plk1) Regulates the Centriolar Satellite Localization of the BBSome
RT Protein during the Cell Cycle.";
RL J. Biol. Chem. 292:1351-1360(2017).
RN [77]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-338, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [78]
RP SUBCELLULAR LOCATION.
RX PubMed=30715179; DOI=10.1093/brain/awz004;
RA Perez Y., Bar-Yaacov R., Kadir R., Wormser O., Shelef I., Birk O.S.,
RA Flusser H., Birnbaum R.Y.;
RT "Mutations in the microtubule-associated protein MAP11 (C7orf43) cause
RT microcephaly in humans and zebrafish.";
RL Brain 142:574-585(2019).
RN [79]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 367-603 IN COMPLEX WITH
RP PHOSPHORYLATED PEPTIDE, FUNCTION, SUBCELLULAR LOCATION, DOMAIN POLO BOX,
RP INTERACTION WITH CDC25C, AND MUTAGENESIS OF HIS-538 AND LYS-540.
RX PubMed=14532005; DOI=10.1016/s0092-8674(03)00725-6;
RA Elia A.E., Rellos P., Haire L.F., Chao J.W., Ivins F.J., Hoepker K.,
RA Mohammad D., Cantley L.C., Smerdon S.J., Yaffe M.B.;
RT "The molecular basis for phosphodependent substrate targeting and
RT regulation of Plks by the Polo-box domain.";
RL Cell 115:83-95(2003).
RN [80]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 367-603 IN COMPLEX WITH
RP PHOSPHORYLATED PEPTIDE.
RX PubMed=14592974; DOI=10.1093/emboj/cdg558;
RA Cheng K.Y., Lowe E.D., Sinclair J., Nigg E.A., Johnson L.N.;
RT "The crystal structure of the human polo-like kinase-1 polo box domain and
RT its phospho-peptide complex.";
RL EMBO J. 22:5757-5768(2003).
RN [81]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 13-345 OF MUTANT VAL-210 IN
RP COMPLEXES WITH ATP ANALOGS, AND MUTAGENESIS OF THR-210.
RX PubMed=17461553; DOI=10.1021/bi602474j;
RA Kothe M., Kohls D., Low S., Coli R., Cheng A.C., Jacques S.L.,
RA Johnson T.L., Lewis C., Loh C., Nonomiya J., Sheils A.L., Verdries K.A.,
RA Wynn T.A., Kuhn C., Ding Y.H.;
RT "Structure of the catalytic domain of human polo-like kinase 1.";
RL Biochemistry 46:5960-5971(2007).
RN [82]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 37-330 IN COMPLEX WITH SYNTHETIC
RP INHIBITOR BI 2536.
RX PubMed=18005335; DOI=10.1111/j.1747-0285.2007.00594.x;
RA Kothe M., Kohls D., Low S., Coli R., Rennie G.R., Feru F., Kuhn C.,
RA Ding Y.H.;
RT "Selectivity-determining residues in Plk1.";
RL Chem. Biol. Drug Des. 70:540-546(2007).
RN [83]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 365-603 IN COMPLEX WITH CDC25C,
RP SUBCELLULAR LOCATION, INTERACTION WITH CDC25C, ACTIVITY REGULATION, AND
RP MUTAGENESIS OF TRP-414.
RX PubMed=17307877; DOI=10.1073/pnas.0609131104;
RA Garcia-Alvarez B., de Carcer G., Ibanez S., Bragado-Nilsson E., Montoya G.;
RT "Molecular and structural basis of polo-like kinase 1 substrate
RT recognition: Implications in centrosomal localization.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:3107-3112(2007).
RN [84]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 33-345 IN COMPLEX WITH A DARPIN.
RX PubMed=18391401; DOI=10.1107/s0907444907068217;
RA Bandeiras T.M., Hillig R.C., Matias P.M., Eberspaecher U., Fanghanel J.,
RA Thomaz M., Miranda S., Crusius K., Putter V., Amstutz P.,
RA Gulotti-Georgieva M., Binz H.K., Holz C., Schmitz A.A., Lang C., Donner P.,
RA Egner U., Carrondo M.A., Muller-Tiemann B.;
RT "Structure of wild-type Plk-1 kinase domain in complex with a selective
RT DARPin.";
RL Acta Crystallogr. D 64:339-353(2008).
RN [85]
RP X-RAY CRYSTALLOGRAPHY (1.58 ANGSTROMS) OF 371-603 IN COMPLEX WITH
RP PHOSPHOPEPTIDE, FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP PHOSPHORYLATED CENPU.
RX PubMed=19597481; DOI=10.1038/nsmb.1628;
RA Yun S.M., Moulaei T., Lim D., Bang J.K., Park J.E., Shenoy S.R., Liu F.,
RA Kang Y.H., Liao C., Soung N.K., Lee S., Yoon D.Y., Lim Y., Lee D.H.,
RA Otaka A., Appella E., McMahon J.B., Nicklaus M.C., Burke T.R. Jr.,
RA Yaffe M.B., Wlodawer A., Lee K.S.;
RT "Structural and functional analyses of minimal phosphopeptides targeting
RT the polo-box domain of polo-like kinase 1.";
RL Nat. Struct. Mol. Biol. 16:876-882(2009).
RN [86]
RP VARIANTS [LARGE SCALE ANALYSIS] LEU-12; PHE-261; VAL-332; HIS-463 AND
RP HIS-518.
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: Serine/threonine-protein kinase that performs several
CC important functions throughout M phase of the cell cycle, including the
CC regulation of centrosome maturation and spindle assembly, the removal
CC of cohesins from chromosome arms, the inactivation of anaphase-
CC promoting complex/cyclosome (APC/C) inhibitors, and the regulation of
CC mitotic exit and cytokinesis. Polo-like kinase proteins acts by binding
CC and phosphorylating proteins are that already phosphorylated on a
CC specific motif recognized by the POLO box domains. Phosphorylates BORA,
CC BUB1B/BUBR1, CCNB1, CDC25C, CEP55, ECT2, ERCC6L, FBXO5/EMI1, FOXM1,
CC KIF20A/MKLP2, CENPU, NEDD1, NINL, NPM1, NUDC, PKMYT1/MYT1, KIZ,
CC PPP1R12A/MYPT1, PRC1, RACGAP1/CYK4, SGO1, STAG2/SA2, TEX14, TOPORS,
CC p73/TP73, TPT1, WEE1 and HNRNPU. Plays a key role in centrosome
CC functions and the assembly of bipolar spindles by phosphorylating KIZ,
CC NEDD1 and NINL. NEDD1 phosphorylation promotes subsequent targeting of
CC the gamma-tubulin ring complex (gTuRC) to the centrosome, an important
CC step for spindle formation. Phosphorylation of NINL component of the
CC centrosome leads to NINL dissociation from other centrosomal proteins.
CC Involved in mitosis exit and cytokinesis by phosphorylating CEP55,
CC ECT2, KIF20A/MKLP2, CENPU, PRC1 and RACGAP1. Recruited at the central
CC spindle by phosphorylating and docking PRC1 and KIF20A/MKLP2; creates
CC its own docking sites on PRC1 and KIF20A/MKLP2 by mediating
CC phosphorylation of sites subsequently recognized by the POLO box
CC domains. Phosphorylates RACGAP1, thereby creating a docking site for
CC the Rho GTP exchange factor ECT2 that is essential for the cleavage
CC furrow formation. Promotes the central spindle recruitment of ECT2.
CC Plays a central role in G2/M transition of mitotic cell cycle by
CC phosphorylating CCNB1, CDC25C, FOXM1, CENPU, PKMYT1/MYT1,
CC PPP1R12A/MYPT1 and WEE1. Part of a regulatory circuit that promotes the
CC activation of CDK1 by phosphorylating the positive regulator CDC25C and
CC inhibiting the negative regulators WEE1 and PKMYT1/MYT1. Also acts by
CC mediating phosphorylation of cyclin-B1 (CCNB1) on centrosomes in
CC prophase. Phosphorylates FOXM1, a key mitotic transcription regulator,
CC leading to enhance FOXM1 transcriptional activity. Involved in
CC kinetochore functions and sister chromatid cohesion by phosphorylating
CC BUB1B/BUBR1, FBXO5/EMI1 and STAG2/SA2. PLK1 is high on non-attached
CC kinetochores suggesting a role of PLK1 in kinetochore attachment or in
CC spindle assembly checkpoint (SAC) regulation. Required for kinetochore
CC localization of BUB1B. Regulates the dissociation of cohesin from
CC chromosomes by phosphorylating cohesin subunits such as STAG2/SA2.
CC Phosphorylates SGO1: required for spindle pole localization of isoform
CC 3 of SGO1 and plays a role in regulating its centriole cohesion
CC function. Mediates phosphorylation of FBXO5/EMI1, a negative regulator
CC of the APC/C complex during prophase, leading to FBXO5/EMI1
CC ubiquitination and degradation by the proteasome. Acts as a negative
CC regulator of p53 family members: phosphorylates TOPORS, leading to
CC inhibit the sumoylation of p53/TP53 and simultaneously enhance the
CC ubiquitination and subsequent degradation of p53/TP53. Phosphorylates
CC the transactivation domain of the transcription factor p73/TP73,
CC leading to inhibit p73/TP73-mediated transcriptional activation and
CC pro-apoptotic functions. Phosphorylates BORA, and thereby promotes the
CC degradation of BORA. Contributes to the regulation of AURKA function.
CC Also required for recovery after DNA damage checkpoint and entry into
CC mitosis. Phosphorylates MISP, leading to stabilization of cortical and
CC astral microtubule attachments required for proper spindle positioning
CC (PubMed:8991084, PubMed:11202906, PubMed:12207013, PubMed:12447691,
CC PubMed:12524548, PubMed:12738781, PubMed:12852856, PubMed:12939256,
CC PubMed:14532005, PubMed:14734534, PubMed:15070733, PubMed:15148369,
CC PubMed:15469984, PubMed:16198290, PubMed:16247472, PubMed:16980960,
CC PubMed:17081991, PubMed:17351640, PubMed:17376779, PubMed:17617734,
CC PubMed:18174154, PubMed:18331714, PubMed:18418051, PubMed:18477460,
CC PubMed:18521620, PubMed:18615013, PubMed:19160488, PubMed:19351716,
CC PubMed:19468300, PubMed:19468302, PubMed:19473992, PubMed:19509060,
CC PubMed:19597481, PubMed:23455478, PubMed:23509069). Together with
CC MEIKIN, acts as a regulator of kinetochore function during meiosis I:
CC required both for mono-orientation of kinetochores on sister
CC chromosomes and protection of centromeric cohesin from separase-
CC mediated cleavage (By similarity). Phosphorylates CEP68 and is required
CC for its degradation (PubMed:25503564). Regulates nuclear envelope
CC breakdown during prophase by phosphorylating DCTN1 resulting in its
CC localization in the nuclear envelope (PubMed:20679239). Phosphorylates
CC the heat shock transcription factor HSF1, promoting HSF1 nuclear
CC translocation upon heat shock (PubMed:15661742). Phosphorylates HSF1
CC also in the early mitotic period; this phosphorylation regulates HSF1
CC localization to the spindle pole, the recruitment of the SCF(BTRC)
CC ubiquitin ligase complex induicing HSF1 degradation, and hence mitotic
CC progression (PubMed:18794143). Regulates mitotic progression by
CC phosphorylating RIOK2 (PubMed:21880710). Through the phosphorylation of
CC DZIP1 regulates the localization during mitosis of the BBSome, a
CC ciliary protein complex involved in cilium biogenesis
CC (PubMed:27979967). {ECO:0000250|UniProtKB:Q5F2C3,
CC ECO:0000269|PubMed:11202906, ECO:0000269|PubMed:12207013,
CC ECO:0000269|PubMed:12447691, ECO:0000269|PubMed:12524548,
CC ECO:0000269|PubMed:12738781, ECO:0000269|PubMed:12852856,
CC ECO:0000269|PubMed:12939256, ECO:0000269|PubMed:14532005,
CC ECO:0000269|PubMed:14734534, ECO:0000269|PubMed:15070733,
CC ECO:0000269|PubMed:15148369, ECO:0000269|PubMed:15469984,
CC ECO:0000269|PubMed:15661742, ECO:0000269|PubMed:16198290,
CC ECO:0000269|PubMed:16247472, ECO:0000269|PubMed:16980960,
CC ECO:0000269|PubMed:17081991, ECO:0000269|PubMed:17351640,
CC ECO:0000269|PubMed:17376779, ECO:0000269|PubMed:17617734,
CC ECO:0000269|PubMed:18174154, ECO:0000269|PubMed:18331714,
CC ECO:0000269|PubMed:18418051, ECO:0000269|PubMed:18477460,
CC ECO:0000269|PubMed:18521620, ECO:0000269|PubMed:18615013,
CC ECO:0000269|PubMed:18794143, ECO:0000269|PubMed:19160488,
CC ECO:0000269|PubMed:19351716, ECO:0000269|PubMed:19468300,
CC ECO:0000269|PubMed:19468302, ECO:0000269|PubMed:19473992,
CC ECO:0000269|PubMed:19509060, ECO:0000269|PubMed:19597481,
CC ECO:0000269|PubMed:20679239, ECO:0000269|PubMed:21880710,
CC ECO:0000269|PubMed:23455478, ECO:0000269|PubMed:23509069,
CC ECO:0000269|PubMed:25503564, ECO:0000269|PubMed:25986610,
CC ECO:0000269|PubMed:27979967, ECO:0000269|PubMed:8991084}.
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=2.7.11.21;
CC Evidence={ECO:0000269|PubMed:11202906, ECO:0000269|PubMed:12207013,
CC ECO:0000269|PubMed:21880710};
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=2.7.11.21; Evidence={ECO:0000269|PubMed:11202906,
CC ECO:0000269|PubMed:12207013, ECO:0000269|PubMed:21880710};
CC -!- ACTIVITY REGULATION: Activated by phosphorylation of Thr-210 by AURKA;
CC phosphorylation by AURKA is enhanced by BORA. Once activated, activity
CC is stimulated by binding target proteins. Binding of target proteins
CC has no effect on the non-activated kinase. Several inhibitors targeting
CC PLKs are currently in development and are under investigation in a
CC growing number of clinical trials, such as BI 2536, an ATP-competitive
CC PLK1 inhibitor or BI 6727, a dihydropteridinone that specifically
CC inhibits the catalytic activity of PLK1. {ECO:0000269|PubMed:17307877,
CC ECO:0000269|PubMed:18615013}.
CC -!- SUBUNIT: Interacts with CEP170 and EVI5. Interacts and phosphorylates
CC ERCC6L. Interacts with FAM29A. Interacts with SLX4/BTBD12 and TTDN1.
CC Interacts with BUB1B. Interacts (via POLO-box domain) with the
CC phosphorylated form of BUB1, CENPU and CDC25C. Interacts with isoform 3
CC of SGO1. Interacts with BORA, KIF2A and AURKA. Interacts with TOPORS
CC and CYLD. Interacts with ECT2; the interaction is stimulated upon
CC phosphorylation of ECT2 on 'Thr-444'. Interacts with PRC1. Interacts
CC with KIF20A/MKLP2 (when phosphorylated), leading to the recruitment at
CC the central spindle. Interacts (via POLO box domains) with
CC PPP1R12A/MYPT1 (when previously phosphorylated by CDK1). Part of an
CC astrin (SPAG5)-kinastrin (SKAP) complex containing KNSTRN, SPAG5, PLK1,
CC DYNLL1 and SGO2. Interacts with BIRC6/bruce. Interacts with CDK1-
CC phosphorylated FRY; this interaction occurs in mitotic cells, but not
CC in interphase cells. FRY interaction facilitates AURKA-mediated PLK1
CC phosphorylation. Interacts with CDK1-phosphorylated DCTN6 during
CC mitotic prometaphase; the interaction facilitates recruitment to
CC kinetochores. Interacts with CEP68; the interaction phosphorylates
CC CEP68 (PubMed:25503564). Interacts (via POLO-box domain) with DCTN1
CC (PubMed:20679239). Interacts with CEP20 in later G1, S, G2 and M phases
CC of the cell cycle; this interaction recruits PLK1 to centrosomes, a
CC step required for S phase progression (PubMed:24018379). Interacts with
CC HSF1; this interaction increases upon heat shock but does not modulate
CC neither HSF1 homotrimerization nor DNA-binding activities
CC (PubMed:15661742, PubMed:18794143). Interacts with HNRNPU; this
CC interaction induces phosphorylation of HNRNPU in mitosis
CC (PubMed:25986610). Interacts (via its N-terminus) to RIOK2
CC (PubMed:21880710). Interacts with KLHL22 (PubMed:24067371,
CC PubMed:23455478). {ECO:0000269|PubMed:12939256,
CC ECO:0000269|PubMed:14532005, ECO:0000269|PubMed:14592974,
CC ECO:0000269|PubMed:15616186, ECO:0000269|PubMed:15661742,
CC ECO:0000269|PubMed:16247472, ECO:0000269|PubMed:16439210,
CC ECO:0000269|PubMed:16760428, ECO:0000269|PubMed:17218258,
CC ECO:0000269|PubMed:17307877, ECO:0000269|PubMed:17310276,
CC ECO:0000269|PubMed:17495026, ECO:0000269|PubMed:18005335,
CC ECO:0000269|PubMed:18329369, ECO:0000269|PubMed:18331714,
CC ECO:0000269|PubMed:18391401, ECO:0000269|PubMed:18521620,
CC ECO:0000269|PubMed:18662541, ECO:0000269|PubMed:18794143,
CC ECO:0000269|PubMed:19029337, ECO:0000269|PubMed:19351716,
CC ECO:0000269|PubMed:19468300, ECO:0000269|PubMed:19473992,
CC ECO:0000269|PubMed:19596235, ECO:0000269|PubMed:19597481,
CC ECO:0000269|PubMed:20679239, ECO:0000269|PubMed:21402792,
CC ECO:0000269|PubMed:21880710, ECO:0000269|PubMed:22753416,
CC ECO:0000269|PubMed:23455152, ECO:0000269|PubMed:23455478,
CC ECO:0000269|PubMed:24018379, ECO:0000269|PubMed:24067371,
CC ECO:0000269|PubMed:25503564, ECO:0000269|PubMed:25986610}.
CC -!- INTERACTION:
CC P53350; P05067: APP; NbExp=3; IntAct=EBI-476768, EBI-77613;
CC P53350; O14965: AURKA; NbExp=4; IntAct=EBI-476768, EBI-448680;
CC P53350; Q9Y2T1: AXIN2; NbExp=2; IntAct=EBI-476768, EBI-4400025;
CC P53350; Q9NR09: BIRC6; NbExp=4; IntAct=EBI-476768, EBI-1765160;
CC P53350; P54132: BLM; NbExp=4; IntAct=EBI-476768, EBI-621372;
CC P53350; Q6PGQ7: BORA; NbExp=5; IntAct=EBI-476768, EBI-719836;
CC P53350; Q14790: CASP8; NbExp=3; IntAct=EBI-476768, EBI-78060;
CC P53350; P30307: CDC25C; NbExp=5; IntAct=EBI-476768, EBI-974439;
CC P53350; Q99741: CDC6; NbExp=6; IntAct=EBI-476768, EBI-374862;
CC P53350; Q71F23-1: CENPU; NbExp=5; IntAct=EBI-476768, EBI-15793375;
CC P53350; Q76N32: CEP68; NbExp=2; IntAct=EBI-476768, EBI-9051024;
CC P53350; O96017: CHEK2; NbExp=7; IntAct=EBI-476768, EBI-1180783;
CC P53350; O14641: DVL2; NbExp=2; IntAct=EBI-476768, EBI-740850;
CC P53350; P23588: EIF4B; NbExp=3; IntAct=EBI-476768, EBI-970310;
CC P53350; Q2NKX8: ERCC6L; NbExp=4; IntAct=EBI-476768, EBI-1042535;
CC P53350; O60447: EVI5; NbExp=3; IntAct=EBI-476768, EBI-852291;
CC P53350; Q13158: FADD; NbExp=9; IntAct=EBI-476768, EBI-494804;
CC P53350; Q9NYZ3: GTSE1; NbExp=6; IntAct=EBI-476768, EBI-2511327;
CC P53350; P08107: HSPA1B; NbExp=5; IntAct=EBI-476768, EBI-629985;
CC P53350; O95251: KAT7; NbExp=6; IntAct=EBI-476768, EBI-473199;
CC P53350; P49736: MCM2; NbExp=2; IntAct=EBI-476768, EBI-374819;
CC P53350; P33993: MCM7; NbExp=4; IntAct=EBI-476768, EBI-355924;
CC P53350; Q00987: MDM2; NbExp=7; IntAct=EBI-476768, EBI-389668;
CC P53350; Q8TD19: NEK9; NbExp=5; IntAct=EBI-476768, EBI-1044009;
CC P53350; Q5HYW2: NHSL2; NbExp=3; IntAct=EBI-476768, EBI-2859639;
CC P53350; O75665: OFD1; NbExp=4; IntAct=EBI-476768, EBI-716327;
CC P53350; Q8IXK0: PHC2; NbExp=2; IntAct=EBI-476768, EBI-713786;
CC P53350; P53350: PLK1; NbExp=3; IntAct=EBI-476768, EBI-476768;
CC P53350; P49768-2: PSEN1; NbExp=3; IntAct=EBI-476768, EBI-11047108;
CC P53350; Q9H0H5: RACGAP1; NbExp=4; IntAct=EBI-476768, EBI-717233;
CC P53350; Q8IY92: SLX4; NbExp=8; IntAct=EBI-476768, EBI-2370740;
CC P53350; Q92844: TANK; NbExp=3; IntAct=EBI-476768, EBI-356349;
CC P53350; Q15583: TGIF1; NbExp=3; IntAct=EBI-476768, EBI-714215;
CC P53350; P04637: TP53; NbExp=6; IntAct=EBI-476768, EBI-366083;
CC P53350; Q12888: TP53BP1; NbExp=6; IntAct=EBI-476768, EBI-396540;
CC P53350; P30291: WEE1; NbExp=2; IntAct=EBI-476768, EBI-914695;
CC P53350; Q60838: Dvl2; Xeno; NbExp=12; IntAct=EBI-476768, EBI-641940;
CC P53350; P23804: Mdm2; Xeno; NbExp=2; IntAct=EBI-476768, EBI-641788;
CC P53350; P70399-1: Tp53bp1; Xeno; NbExp=2; IntAct=EBI-476768, EBI-15790796;
CC P53350; PRO_0000045602 [Q99IB8]; Xeno; NbExp=4; IntAct=EBI-476768, EBI-6927873;
CC -!- SUBCELLULAR LOCATION: Nucleus. Chromosome, centromere, kinetochore.
CC Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
CC {ECO:0000269|PubMed:14654843, ECO:0000269|PubMed:24018379}. Cytoplasm,
CC cytoskeleton, spindle {ECO:0000269|PubMed:18794143,
CC ECO:0000269|PubMed:30715179}. Midbody {ECO:0000269|PubMed:30715179}.
CC Note=localization at the centrosome starts at the G1/S transition
CC (PubMed:24018379). During early stages of mitosis, the phosphorylated
CC form is detected on centrosomes and kinetochores. Localizes to the
CC outer kinetochore. Presence of SGO1 and interaction with the
CC phosphorylated form of BUB1 is required for the kinetochore
CC localization. Localizes onto the central spindle by phosphorylating and
CC docking at midzone proteins KIF20A/MKLP2 and PRC1. Colocalizes with FRY
CC to separating centrosomes and spindle poles from prophase to metaphase
CC in mitosis, but not in other stages of the cell cycle. Localization to
CC the centrosome is required for S phase progression (PubMed:24018379).
CC Colocalizes with HSF1 at the spindle poles during prometaphase
CC (PubMed:18794143). {ECO:0000269|PubMed:18794143,
CC ECO:0000269|PubMed:24018379}.
CC -!- TISSUE SPECIFICITY: Placenta and colon.
CC -!- DEVELOPMENTAL STAGE: Accumulates to a maximum during the G2 and M
CC phases, declines to a nearly undetectable level following mitosis and
CC throughout G1 phase, and then begins to accumulate again during S
CC phase.
CC -!- INDUCTION: By growth-stimulating agents.
CC -!- DOMAIN: The POLO box domains act as phosphopeptide-binding module that
CC recognize and bind serine-[phosphothreonine/phosphoserine]-(proline/X)
CC motifs. PLK1 recognizes and binds docking proteins that are already
CC phosphorylated on these motifs, and then phosphorylates them. PLK1 can
CC also create its own docking sites by mediating phosphorylation of
CC serine-[phosphothreonine/phosphoserine]-(proline/X) motifs subsequently
CC recognized by the POLO box domains. {ECO:0000269|PubMed:12939256,
CC ECO:0000269|PubMed:14532005, ECO:0000269|PubMed:14734534,
CC ECO:0000269|PubMed:17351640}.
CC -!- PTM: Catalytic activity is enhanced by phosphorylation of Thr-210.
CC Phosphorylation at Thr-210 is first detected on centrosomes in the G2
CC phase of the cell cycle, peaks in prometaphase and gradually disappears
CC from centrosomes during anaphase. Dephosphorylation at Thr-210 at
CC centrosomes is probably mediated by protein phosphatase 1C (PP1C), via
CC interaction with PPP1R12A/MYPT1. Autophosphorylation and
CC phosphorylation of Ser-137 may not be significant for the activation of
CC PLK1 during mitosis, but may enhance catalytic activity during recovery
CC after DNA damage checkpoint. Phosphorylated in vitro by STK10.
CC {ECO:0000269|PubMed:12207013, ECO:0000269|PubMed:12442251,
CC ECO:0000269|PubMed:12639966, ECO:0000269|PubMed:18477460,
CC ECO:0000269|PubMed:18615013}.
CC -!- PTM: Ubiquitinated by the anaphase promoting complex/cyclosome (APC/C)
CC in anaphase and following DNA damage, leading to its degradation by the
CC proteasome. Ubiquitination is mediated via its interaction with
CC FZR1/CDH1. Ubiquitination and subsequent degradation prevents entry
CC into mitosis and is essential to maintain an efficient G2 DNA damage
CC checkpoint. Monoubiquitination at Lys-492 by the BCR(KLHL22) ubiquitin
CC ligase complex does not lead to degradation: it promotes PLK1
CC dissociation from phosphoreceptor proteins and subsequent removal from
CC kinetochores, allowing silencing of the spindle assembly checkpoint
CC (SAC) and chromosome segregation. {ECO:0000269|PubMed:18662541,
CC ECO:0000269|PubMed:23455478}.
CC -!- DISEASE: Note=Defects in PLK1 are associated with some cancers, such as
CC gastric, thyroid or B-cell lymphomas. Expression is cancer increased in
CC tumor tissues with a poor prognosis, suggesting a role in malignant
CC transformations and carcinogenesis.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. CDC5/Polo subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/PLK1ID41747ch16p12.html";
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DR EMBL; U01038; AAA56634.1; -; mRNA.
DR EMBL; L19559; AAA36659.1; -; mRNA.
DR EMBL; X73458; CAA51837.1; -; mRNA.
DR EMBL; X75932; CAA53536.1; -; mRNA.
DR EMBL; BC002369; AAH02369.1; -; mRNA.
DR EMBL; BC003002; AAH03002.1; -; mRNA.
DR EMBL; BC014846; AAH14846.1; -; mRNA.
DR EMBL; X90725; CAA62260.1; -; Genomic_DNA.
DR EMBL; U78073; AAB36946.1; -; Genomic_DNA.
DR CCDS; CCDS10616.1; -.
DR PIR; S34130; S34130.
DR RefSeq; NP_005021.2; NM_005030.5.
DR PDB; 1Q4K; X-ray; 2.30 A; A/B/C=345-603.
DR PDB; 1Q4O; X-ray; 2.20 A; A/B=367-603.
DR PDB; 1UMW; X-ray; 1.90 A; A/B=367-603.
DR PDB; 2OGQ; X-ray; 1.95 A; A=365-603.
DR PDB; 2OJX; X-ray; 2.85 A; A=365-603.
DR PDB; 2OU7; X-ray; 2.40 A; A=13-345.
DR PDB; 2OWB; X-ray; 2.10 A; A=13-345.
DR PDB; 2RKU; X-ray; 1.95 A; A=37-330.
DR PDB; 2V5Q; X-ray; 2.30 A; A/B=33-345.
DR PDB; 2YAC; X-ray; 2.20 A; A=36-345.
DR PDB; 3BZI; X-ray; 2.10 A; A=365-603.
DR PDB; 3C5L; X-ray; 2.33 A; A=373-593.
DR PDB; 3FC2; X-ray; 2.45 A; A=13-345.
DR PDB; 3FVH; X-ray; 1.58 A; A=371-603.
DR PDB; 3HIH; X-ray; 1.70 A; A/B=371-593.
DR PDB; 3HIK; X-ray; 1.77 A; A=367-603.
DR PDB; 3KB7; X-ray; 2.50 A; A=36-345.
DR PDB; 3P2W; X-ray; 1.66 A; A=371-594.
DR PDB; 3P2Z; X-ray; 1.79 A; A=371-594.
DR PDB; 3P34; X-ray; 1.40 A; A=371-594.
DR PDB; 3P35; X-ray; 2.09 A; A/B/C=371-594.
DR PDB; 3P36; X-ray; 1.59 A; A=371-594.
DR PDB; 3P37; X-ray; 2.38 A; A/B/C=371-594.
DR PDB; 3Q1I; X-ray; 1.40 A; A=371-594.
DR PDB; 3RQ7; X-ray; 1.55 A; A=371-603.
DR PDB; 3THB; X-ray; 2.50 A; A=13-345.
DR PDB; 4A4L; X-ray; 2.35 A; A=36-345.
DR PDB; 4A4O; X-ray; 2.70 A; A=36-345.
DR PDB; 4DFW; X-ray; 1.55 A; A=367-603.
DR PDB; 4E67; X-ray; 2.10 A; A=371-594.
DR PDB; 4E9C; X-ray; 1.70 A; A=371-594.
DR PDB; 4E9D; X-ray; 2.75 A; A=371-594.
DR PDB; 4H5X; X-ray; 1.95 A; A/B=367-603.
DR PDB; 4H71; X-ray; 1.93 A; A/B=367-603.
DR PDB; 4HAB; X-ray; 2.65 A; A/B/C=371-593.
DR PDB; 4HCO; X-ray; 2.75 A; A/B=367-603.
DR PDB; 4HY2; X-ray; 2.00 A; A=371-595.
DR PDB; 4J52; X-ray; 2.30 A; A=38-330.
DR PDB; 4J53; X-ray; 2.50 A; A=38-330.
DR PDB; 4LKL; X-ray; 1.58 A; A=372-593.
DR PDB; 4LKM; X-ray; 2.00 A; A/C=371-601.
DR PDB; 4O56; X-ray; 1.80 A; A=367-603.
DR PDB; 4O6W; X-ray; 1.45 A; A=371-603.
DR PDB; 4O9W; X-ray; 1.69 A; A=373-594.
DR PDB; 4RCP; X-ray; 1.60 A; A=372-599.
DR PDB; 4WHH; X-ray; 1.90 A; A=371-603.
DR PDB; 4WHK; X-ray; 1.80 A; A=371-603.
DR PDB; 4WHL; X-ray; 2.71 A; A=371-603.
DR PDB; 4X9R; X-ray; 1.40 A; A=371-603.
DR PDB; 4X9V; X-ray; 1.43 A; A=371-603.
DR PDB; 4X9W; X-ray; 1.80 A; A=371-603.
DR PDB; 5J19; X-ray; 2.00 A; A/B=367-594.
DR PDB; 5NEI; X-ray; 2.68 A; A=371-603.
DR PDB; 5NFU; X-ray; 1.81 A; A=371-602.
DR PDB; 5NJE; X-ray; 1.98 A; A=371-603.
DR PDB; 5NMM; X-ray; 2.02 A; A=371-603.
DR PDB; 5NN1; X-ray; 1.78 A; A=371-603.
DR PDB; 5NN2; X-ray; 1.81 A; A=371-594.
DR PDB; 5TA6; X-ray; 2.50 A; A=13-345.
DR PDB; 5TA8; X-ray; 2.60 A; A=13-345.
DR PDB; 6AX4; X-ray; 1.45 A; A=371-603.
DR PDB; 6GY2; X-ray; 3.11 A; A/B=365-603.
DR PDB; 7MSO; X-ray; 1.85 A; A/B=371-603.
DR PDB; 7MX1; X-ray; 1.64 A; A/B=371-603.
DR PDBsum; 1Q4K; -.
DR PDBsum; 1Q4O; -.
DR PDBsum; 1UMW; -.
DR PDBsum; 2OGQ; -.
DR PDBsum; 2OJX; -.
DR PDBsum; 2OU7; -.
DR PDBsum; 2OWB; -.
DR PDBsum; 2RKU; -.
DR PDBsum; 2V5Q; -.
DR PDBsum; 2YAC; -.
DR PDBsum; 3BZI; -.
DR PDBsum; 3C5L; -.
DR PDBsum; 3FC2; -.
DR PDBsum; 3FVH; -.
DR PDBsum; 3HIH; -.
DR PDBsum; 3HIK; -.
DR PDBsum; 3KB7; -.
DR PDBsum; 3P2W; -.
DR PDBsum; 3P2Z; -.
DR PDBsum; 3P34; -.
DR PDBsum; 3P35; -.
DR PDBsum; 3P36; -.
DR PDBsum; 3P37; -.
DR PDBsum; 3Q1I; -.
DR PDBsum; 3RQ7; -.
DR PDBsum; 3THB; -.
DR PDBsum; 4A4L; -.
DR PDBsum; 4A4O; -.
DR PDBsum; 4DFW; -.
DR PDBsum; 4E67; -.
DR PDBsum; 4E9C; -.
DR PDBsum; 4E9D; -.
DR PDBsum; 4H5X; -.
DR PDBsum; 4H71; -.
DR PDBsum; 4HAB; -.
DR PDBsum; 4HCO; -.
DR PDBsum; 4HY2; -.
DR PDBsum; 4J52; -.
DR PDBsum; 4J53; -.
DR PDBsum; 4LKL; -.
DR PDBsum; 4LKM; -.
DR PDBsum; 4O56; -.
DR PDBsum; 4O6W; -.
DR PDBsum; 4O9W; -.
DR PDBsum; 4RCP; -.
DR PDBsum; 4WHH; -.
DR PDBsum; 4WHK; -.
DR PDBsum; 4WHL; -.
DR PDBsum; 4X9R; -.
DR PDBsum; 4X9V; -.
DR PDBsum; 4X9W; -.
DR PDBsum; 5J19; -.
DR PDBsum; 5NEI; -.
DR PDBsum; 5NFU; -.
DR PDBsum; 5NJE; -.
DR PDBsum; 5NMM; -.
DR PDBsum; 5NN1; -.
DR PDBsum; 5NN2; -.
DR PDBsum; 5TA6; -.
DR PDBsum; 5TA8; -.
DR PDBsum; 6AX4; -.
DR PDBsum; 6GY2; -.
DR PDBsum; 7MSO; -.
DR PDBsum; 7MX1; -.
DR AlphaFoldDB; P53350; -.
DR SMR; P53350; -.
DR BioGRID; 111362; 436.
DR CORUM; P53350; -.
DR DIP; DIP-29696N; -.
DR ELM; P53350; -.
DR IntAct; P53350; 264.
DR MINT; P53350; -.
DR STRING; 9606.ENSP00000300093; -.
DR BindingDB; P53350; -.
DR ChEMBL; CHEMBL3024; -.
DR DrugBank; DB07789; 1-[5-Methyl-2-(trifluoromethyl)furan-3-yl]-3-[5-[2-[[6-(1H-1,2,4-triazol-5-ylamino)pyrimidin-4-yl]amino]ethyl]-1,3-thiazol-2-yl]urea.
DR DrugBank; DB06963; 3-[3-(3-methyl-6-{[(1S)-1-phenylethyl]amino}-1H-pyrazolo[4,3-c]pyridin-1-yl)phenyl]propanamide.
DR DrugBank; DB06897; 3-[3-chloro-5-(5-{[(1S)-1-phenylethyl]amino}isoxazolo[5,4-c]pyridin-3-yl)phenyl]propan-1-ol.
DR DrugBank; DB07186; 4-(4-METHYLPIPERAZIN-1-YL)-N-[5-(2-THIENYLACETYL)-1,5-DIHYDROPYRROLO[3,4-C]PYRAZOL-3-YL]BENZAMIDE.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB08059; Wortmannin.
DR DrugCentral; P53350; -.
DR GuidetoPHARMACOLOGY; 2168; -.
DR MoonDB; P53350; Curated.
DR GlyGen; P53350; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P53350; -.
DR PhosphoSitePlus; P53350; -.
DR SwissPalm; P53350; -.
DR BioMuta; PLK1; -.
DR DMDM; 1709658; -.
DR CPTAC; CPTAC-1264; -.
DR CPTAC; CPTAC-1326; -.
DR CPTAC; CPTAC-1327; -.
DR EPD; P53350; -.
DR jPOST; P53350; -.
DR MassIVE; P53350; -.
DR MaxQB; P53350; -.
DR PaxDb; P53350; -.
DR PeptideAtlas; P53350; -.
DR PRIDE; P53350; -.
DR ProteomicsDB; 56569; -.
DR Antibodypedia; 12634; 1231 antibodies from 48 providers.
DR DNASU; 5347; -.
DR Ensembl; ENST00000300093.9; ENSP00000300093.4; ENSG00000166851.15.
DR GeneID; 5347; -.
DR KEGG; hsa:5347; -.
DR MANE-Select; ENST00000300093.9; ENSP00000300093.4; NM_005030.6; NP_005021.2.
DR UCSC; uc002dlz.2; human.
DR CTD; 5347; -.
DR DisGeNET; 5347; -.
DR GeneCards; PLK1; -.
DR HGNC; HGNC:9077; PLK1.
DR HPA; ENSG00000166851; Tissue enhanced (bone marrow, lymphoid tissue, testis).
DR MIM; 602098; gene.
DR neXtProt; NX_P53350; -.
DR OpenTargets; ENSG00000166851; -.
DR PharmGKB; PA33410; -.
DR VEuPathDB; HostDB:ENSG00000166851; -.
DR eggNOG; KOG0575; Eukaryota.
DR GeneTree; ENSGT00940000157752; -.
DR HOGENOM; CLU_000288_46_1_1; -.
DR InParanoid; P53350; -.
DR OMA; LKHFERY; -.
DR OrthoDB; 507604at2759; -.
DR PhylomeDB; P53350; -.
DR TreeFam; TF101089; -.
DR BRENDA; 2.7.11.21; 2681.
DR PathwayCommons; P53350; -.
DR Reactome; R-HSA-141444; Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal.
DR Reactome; R-HSA-156711; Polo-like kinase mediated events.
DR Reactome; R-HSA-162658; Golgi Cisternae Pericentriolar Stack Reorganization.
DR Reactome; R-HSA-174178; APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1.
DR Reactome; R-HSA-176412; Phosphorylation of the APC/C.
DR Reactome; R-HSA-176417; Phosphorylation of Emi1.
DR Reactome; R-HSA-2299718; Condensation of Prophase Chromosomes.
DR Reactome; R-HSA-2467813; Separation of Sister Chromatids.
DR Reactome; R-HSA-2500257; Resolution of Sister Chromatid Cohesion.
DR Reactome; R-HSA-2565942; Regulation of PLK1 Activity at G2/M Transition.
DR Reactome; R-HSA-2980767; Activation of NIMA Kinases NEK9, NEK6, NEK7.
DR Reactome; R-HSA-380259; Loss of Nlp from mitotic centrosomes.
DR Reactome; R-HSA-380270; Recruitment of mitotic centrosome proteins and complexes.
DR Reactome; R-HSA-380284; Loss of proteins required for interphase microtubule organization from the centrosome.
DR Reactome; R-HSA-380320; Recruitment of NuMA to mitotic centrosomes.
DR Reactome; R-HSA-5620912; Anchoring of the basal body to the plasma membrane.
DR Reactome; R-HSA-5663220; RHO GTPases Activate Formins.
DR Reactome; R-HSA-68877; Mitotic Prometaphase.
DR Reactome; R-HSA-68881; Mitotic Metaphase/Anaphase Transition.
DR Reactome; R-HSA-68884; Mitotic Telophase/Cytokinesis.
DR Reactome; R-HSA-69273; Cyclin A/B1/B2 associated events during G2/M transition.
DR Reactome; R-HSA-8852276; The role of GTSE1 in G2/M progression after G2 checkpoint.
DR Reactome; R-HSA-8854518; AURKA Activation by TPX2.
DR Reactome; R-HSA-9648025; EML4 and NUDC in mitotic spindle formation.
DR SignaLink; P53350; -.
DR SIGNOR; P53350; -.
DR BioGRID-ORCS; 5347; 839 hits in 1107 CRISPR screens.
DR ChiTaRS; PLK1; human.
DR EvolutionaryTrace; P53350; -.
DR GeneWiki; PLK1; -.
DR GenomeRNAi; 5347; -.
DR Pharos; P53350; Tchem.
DR PRO; PR:P53350; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; P53350; protein.
DR Bgee; ENSG00000166851; Expressed in ventricular zone and 101 other tissues.
DR ExpressionAtlas; P53350; baseline and differential.
DR Genevisible; P53350; HS.
DR GO; GO:0034451; C:centriolar satellite; IEA:Ensembl.
DR GO; GO:0005814; C:centriole; IEA:Ensembl.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0000785; C:chromatin; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0000776; C:kinetochore; IDA:UniProtKB.
DR GO; GO:0015630; C:microtubule cytoskeleton; IDA:BHF-UCL.
DR GO; GO:0030496; C:midbody; IDA:UniProtKB.
DR GO; GO:0097431; C:mitotic spindle pole; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000940; C:outer kinetochore; IDA:BHF-UCL.
DR GO; GO:0005819; C:spindle; IDA:UniProtKB.
DR GO; GO:0051233; C:spindle midzone; IDA:UniProtKB.
DR GO; GO:0000922; C:spindle pole; IDA:BHF-UCL.
DR GO; GO:0000795; C:synaptonemal complex; IEA:Ensembl.
DR GO; GO:0010997; F:anaphase-promoting complex binding; IPI:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IMP:CAFA.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0000287; F:magnesium ion binding; IMP:CAFA.
DR GO; GO:0008017; F:microtubule binding; IDA:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0007098; P:centrosome cycle; IMP:UniProtKB.
DR GO; GO:0000132; P:establishment of mitotic spindle orientation; IDA:UniProtKB.
DR GO; GO:0045184; P:establishment of protein localization; IMP:MGI.
DR GO; GO:0016321; P:female meiosis chromosome segregation; IEA:Ensembl.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; IDA:UniProtKB.
DR GO; GO:0045143; P:homologous chromosome segregation; IEA:Ensembl.
DR GO; GO:0001578; P:microtubule bundle formation; IDA:UniProtKB.
DR GO; GO:0000278; P:mitotic cell cycle; IDA:UniProtKB.
DR GO; GO:0007076; P:mitotic chromosome condensation; TAS:Reactome.
DR GO; GO:0000281; P:mitotic cytokinesis; IDA:UniProtKB.
DR GO; GO:0007095; P:mitotic G2 DNA damage checkpoint signaling; IDA:UniProtKB.
DR GO; GO:0007077; P:mitotic nuclear membrane disassembly; TAS:Reactome.
DR GO; GO:0000070; P:mitotic sister chromatid segregation; IMP:UniProtKB.
DR GO; GO:0007094; P:mitotic spindle assembly checkpoint signaling; IMP:UniProtKB.
DR GO; GO:0007052; P:mitotic spindle organization; TAS:Reactome.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0045736; P:negative regulation of cyclin-dependent protein serine/threonine kinase activity; IMP:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0051081; P:nuclear membrane disassembly; IMP:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB.
DR GO; GO:0010800; P:positive regulation of peptidyl-threonine phosphorylation; IMP:BHF-UCL.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; TAS:Reactome.
DR GO; GO:0045862; P:positive regulation of proteolysis; IDA:UniProtKB.
DR GO; GO:1904668; P:positive regulation of ubiquitin protein ligase activity; IDA:UniProtKB.
DR GO; GO:0051443; P:positive regulation of ubiquitin-protein transferase activity; IMP:UniProtKB.
DR GO; GO:0031648; P:protein destabilization; IDA:UniProtKB.
DR GO; GO:0071168; P:protein localization to chromatin; IDA:UniProtKB.
DR GO; GO:0090435; P:protein localization to nuclear envelope; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
DR GO; GO:1905784; P:regulation of anaphase-promoting complex-dependent catabolic process; TAS:Reactome.
DR GO; GO:0051726; P:regulation of cell cycle; TAS:Reactome.
DR GO; GO:0032465; P:regulation of cytokinesis; IDA:UniProtKB.
DR GO; GO:0007346; P:regulation of mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:1901990; P:regulation of mitotic cell cycle phase transition; TAS:Reactome.
DR GO; GO:0030071; P:regulation of mitotic metaphase/anaphase transition; IDA:UniProtKB.
DR GO; GO:1901673; P:regulation of mitotic spindle assembly; IDA:CACAO.
DR GO; GO:0043393; P:regulation of protein binding; IMP:BHF-UCL.
DR GO; GO:1904776; P:regulation of protein localization to cell cortex; IDA:UniProtKB.
DR GO; GO:0007062; P:sister chromatid cohesion; TAS:Reactome.
DR GO; GO:0070194; P:synaptonemal complex disassembly; IEA:Ensembl.
DR CDD; cd13118; POLO_box_1; 1.
DR CDD; cd13117; POLO_box_2; 1.
DR CDD; cd14187; STKc_PLK1; 1.
DR Gene3D; 3.30.1120.30; -; 2.
DR IDEAL; IID00200; -.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR033702; PLK1_cat.
DR InterPro; IPR033701; POLO_box_1.
DR InterPro; IPR033695; POLO_box_2.
DR InterPro; IPR000959; POLO_box_dom.
DR InterPro; IPR036947; POLO_box_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00659; POLO_box; 2.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50078; POLO_BOX; 2.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ATP-binding; Cell cycle; Cell division;
KW Centromere; Chromosome; Cytoplasm; Cytoskeleton; Isopeptide bond; Kinase;
KW Kinetochore; Mitosis; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Serine/threonine-protein kinase; Transferase;
KW Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22814378"
FT CHAIN 2..603
FT /note="Serine/threonine-protein kinase PLK1"
FT /id="PRO_0000086556"
FT DOMAIN 53..305
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 417..480
FT /note="POLO box 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00154"
FT DOMAIN 515..584
FT /note="POLO box 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00154"
FT REGION 1..35
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 194..221
FT /note="Activation loop"
FT REGION 338..364
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 493..507
FT /note="Linker"
FT REGION 538..540
FT /note="Important for interaction with phosphorylated
FT proteins"
FT /evidence="ECO:0000250"
FT MOTIF 337..340
FT /note="D-box that targets the protein for proteasomal
FT degradation in anaphase"
FT COMPBIAS 350..364
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 176
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:18615013"
FT BINDING 59..67
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 82
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 131
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 178..181
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 194
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 6
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 103
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 137
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:12207013"
FT MOD_RES 210
FT /note="Phosphothreonine; by AURKA"
FT /evidence="ECO:0000269|PubMed:12207013,
FT ECO:0000269|PubMed:18477460, ECO:0000269|PubMed:18615013,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 214
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195"
FT MOD_RES 269
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 335
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:12442251"
FT MOD_RES 375
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 450
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 498
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT CROSSLNK 19
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:18662541"
FT CROSSLNK 338
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 492
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:23455478"
FT VARIANT 12
FT /note="R -> L (in a lung squamous cell carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041018"
FT VARIANT 261
FT /note="L -> F (in dbSNP:rs35056440)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041019"
FT VARIANT 297
FT /note="N -> D (in dbSNP:rs16972799)"
FT /id="VAR_051659"
FT VARIANT 332
FT /note="L -> V (in dbSNP:rs45489499)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041020"
FT VARIANT 463
FT /note="L -> H (in dbSNP:rs45569335)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041021"
FT VARIANT 518
FT /note="R -> H (in dbSNP:rs56027600)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041022"
FT VARIANT 595
FT /note="S -> L (in dbSNP:rs34001032)"
FT /id="VAR_051660"
FT VARIANT 599
FT /note="R -> H (in dbSNP:rs34954545)"
FT /id="VAR_051661"
FT MUTAGEN 67
FT /note="C->V: In analog-sensitive mutant; enlarged catalytic
FT pocket to accommodate purine analogs; when associated with
FT G-130."
FT /evidence="ECO:0000269|PubMed:19468302"
FT MUTAGEN 82
FT /note="K->M: Loss of kinase activity. No effect on S-phase
FT progression."
FT /evidence="ECO:0000269|PubMed:12207013,
FT ECO:0000269|PubMed:12447691, ECO:0000269|PubMed:18174154,
FT ECO:0000269|PubMed:24018379"
FT MUTAGEN 82
FT /note="K->R: Loss of kinase activity. No effect on RIOK2-
FT binding."
FT /evidence="ECO:0000269|PubMed:18615013,
FT ECO:0000269|PubMed:19160488, ECO:0000269|PubMed:21880710"
FT MUTAGEN 130
FT /note="L->G: In analog-sensitive mutant; enlarged catalytic
FT pocket to accommodate purine analogs; when associated with
FT V-67."
FT /evidence="ECO:0000269|PubMed:19468302"
FT MUTAGEN 137
FT /note="S->A: No change in activity. Increases activity and
FT restores recovery after DNA damage checkpoint; when
FT associated with D-210."
FT /evidence="ECO:0000269|PubMed:12207013,
FT ECO:0000269|PubMed:18615013"
FT MUTAGEN 137
FT /note="S->D: Increases activity. Results in a block in
FT G1/S."
FT /evidence="ECO:0000269|PubMed:12207013,
FT ECO:0000269|PubMed:18615013"
FT MUTAGEN 176
FT /note="D->N: Abolishes kinase activity."
FT /evidence="ECO:0000269|PubMed:18615013"
FT MUTAGEN 194
FT /note="D->A: Does not interfere with FRY-binding."
FT /evidence="ECO:0000269|PubMed:22753416"
FT MUTAGEN 210
FT /note="T->A: Abolishes activity. Abolishes checkpoint
FT recovery."
FT /evidence="ECO:0000269|PubMed:12207013,
FT ECO:0000269|PubMed:12447691, ECO:0000269|PubMed:17461553,
FT ECO:0000269|PubMed:18615013, ECO:0000269|PubMed:19160488"
FT MUTAGEN 210
FT /note="T->D: Increases activity and restores recovery after
FT DNA damage checkpoint."
FT /evidence="ECO:0000269|PubMed:12207013,
FT ECO:0000269|PubMed:12447691, ECO:0000269|PubMed:17461553,
FT ECO:0000269|PubMed:18615013, ECO:0000269|PubMed:19160488"
FT MUTAGEN 210
FT /note="T->V: Reduced catalytic activity, but no effect on
FT affinity for ATP."
FT /evidence="ECO:0000269|PubMed:12207013,
FT ECO:0000269|PubMed:12447691, ECO:0000269|PubMed:17461553,
FT ECO:0000269|PubMed:18615013, ECO:0000269|PubMed:19160488"
FT MUTAGEN 337
FT /note="R->A: Interferes with ubiquitination and subsequent
FT proteasomal degradation in anaphase; when associated with
FT A-340."
FT /evidence="ECO:0000269|PubMed:14734534,
FT ECO:0000269|PubMed:18662541"
FT MUTAGEN 340
FT /note="L->A: Interferes with ubiquitination and subsequent
FT proteasomal degradation in anaphase; when associated with
FT A-337."
FT /evidence="ECO:0000269|PubMed:14734534,
FT ECO:0000269|PubMed:18662541"
FT MUTAGEN 414
FT /note="W->F: Abolishes interaction with CDC25C and reduces
FT centrosomal localization."
FT /evidence="ECO:0000269|PubMed:17307877"
FT MUTAGEN 414
FT /note="W->F: No effect on centrosomal localization, nor on
FT S-phase progression; when asscociated with A-427. Loss of
FT centrosomal localization and of S-phase progression; when
FT associated with A- 415 and A-427."
FT /evidence="ECO:0000269|PubMed:24018379"
FT MUTAGEN 415
FT /note="V->A: Loss of centrosomal localization and of S-
FT phase progression; when associated with A- 414 and A-427."
FT /evidence="ECO:0000269|PubMed:24018379"
FT MUTAGEN 427
FT /note="L->A: No effect on centrosomal localization, nor on
FT S-phase progression; when associated with A-414. Loss of
FT centrosomal localization and of S-phase progression; when
FT associated with A- 414 and A-415."
FT /evidence="ECO:0000269|PubMed:24018379"
FT MUTAGEN 492
FT /note="K->R: Severe mitotic defects leading to prometaphase
FT delay. Increased localization at kinetochores leading to
FT increased levels of phosphorylated BUBR1."
FT /evidence="ECO:0000269|PubMed:23455478"
FT MUTAGEN 538
FT /note="H->A: In pincer mutant; loss of centrosomal location
FT and decreased interaction with phosphorylated CDC25C and
FT BUB1; when associated with M-540."
FT /evidence="ECO:0000269|PubMed:14532005,
FT ECO:0000269|PubMed:16760428, ECO:0000269|PubMed:18477460,
FT ECO:0000269|PubMed:19468302"
FT MUTAGEN 540
FT /note="K->M: In pincer mutant; loss of centrosomal location
FT and decreased interaction with phosphorylated CDC25C and
FT BUB1; when associated with A-538."
FT /evidence="ECO:0000269|PubMed:14532005,
FT ECO:0000269|PubMed:16760428, ECO:0000269|PubMed:18477460,
FT ECO:0000269|PubMed:19468302"
FT CONFLICT 2
FT /note="S -> T (in Ref. 1; AAA56634)"
FT /evidence="ECO:0000305"
FT CONFLICT 11
FT /note="A -> P (in Ref. 1; AAA56634)"
FT /evidence="ECO:0000305"
FT CONFLICT 58
FT /note="F -> L (in Ref. 1; AAA56634)"
FT /evidence="ECO:0000305"
FT CONFLICT 60
FT /note="G -> S (in Ref. 1; AAA56634)"
FT /evidence="ECO:0000305"
FT CONFLICT 73
FT /note="A -> V (in Ref. 2; AAA36659 and 7; AAB36946)"
FT /evidence="ECO:0000305"
FT CONFLICT 123
FT /note="N -> T (in Ref. 6; CAA62260)"
FT /evidence="ECO:0000305"
FT CONFLICT 141
FT /note="L -> P (in Ref. 4; CAA53536)"
FT /evidence="ECO:0000305"
FT CONFLICT 227
FT /note="G -> E (in Ref. 4; CAA53536)"
FT /evidence="ECO:0000305"
FT CONFLICT 301
FT /note="N -> G (in Ref. 2; AAA36659)"
FT /evidence="ECO:0000305"
FT CONFLICT 495
FT /note="A -> G (in Ref. 2; AAA36659)"
FT /evidence="ECO:0000305"
FT CONFLICT 501
FT /note="E -> Q (in Ref. 2; AAA36659)"
FT /evidence="ECO:0000305"
FT STRAND 42..46
FT /evidence="ECO:0007829|PDB:2RKU"
FT TURN 47..50
FT /evidence="ECO:0007829|PDB:2RKU"
FT STRAND 51..62
FT /evidence="ECO:0007829|PDB:2RKU"
FT STRAND 65..72
FT /evidence="ECO:0007829|PDB:2RKU"
FT TURN 73..75
FT /evidence="ECO:0007829|PDB:2RKU"
FT STRAND 78..85
FT /evidence="ECO:0007829|PDB:2RKU"
FT HELIX 86..88
FT /evidence="ECO:0007829|PDB:2RKU"
FT HELIX 92..106
FT /evidence="ECO:0007829|PDB:2RKU"
FT STRAND 116..121
FT /evidence="ECO:0007829|PDB:2RKU"
FT STRAND 123..131
FT /evidence="ECO:0007829|PDB:2RKU"
FT HELIX 138..145
FT /evidence="ECO:0007829|PDB:2RKU"
FT HELIX 150..169
FT /evidence="ECO:0007829|PDB:2RKU"
FT HELIX 179..181
FT /evidence="ECO:0007829|PDB:2RKU"
FT STRAND 182..184
FT /evidence="ECO:0007829|PDB:2RKU"
FT STRAND 190..192
FT /evidence="ECO:0007829|PDB:2RKU"
FT HELIX 220..223
FT /evidence="ECO:0007829|PDB:2RKU"
FT STRAND 224..226
FT /evidence="ECO:0007829|PDB:2V5Q"
FT HELIX 231..246
FT /evidence="ECO:0007829|PDB:2RKU"
FT HELIX 256..264
FT /evidence="ECO:0007829|PDB:2RKU"
FT HELIX 276..285
FT /evidence="ECO:0007829|PDB:2RKU"
FT HELIX 290..292
FT /evidence="ECO:0007829|PDB:2RKU"
FT HELIX 296..301
FT /evidence="ECO:0007829|PDB:2RKU"
FT HELIX 303..306
FT /evidence="ECO:0007829|PDB:2RKU"
FT HELIX 316..319
FT /evidence="ECO:0007829|PDB:2RKU"
FT HELIX 367..370
FT /evidence="ECO:0007829|PDB:5J19"
FT HELIX 374..386
FT /evidence="ECO:0007829|PDB:4X9R"
FT HELIX 389..391
FT /evidence="ECO:0007829|PDB:4X9R"
FT STRAND 392..394
FT /evidence="ECO:0007829|PDB:3P34"
FT HELIX 397..400
FT /evidence="ECO:0007829|PDB:4X9R"
FT HELIX 403..405
FT /evidence="ECO:0007829|PDB:4X9R"
FT STRAND 411..417
FT /evidence="ECO:0007829|PDB:4X9R"
FT TURN 418..421
FT /evidence="ECO:0007829|PDB:4X9R"
FT STRAND 422..427
FT /evidence="ECO:0007829|PDB:4X9R"
FT STRAND 432..436
FT /evidence="ECO:0007829|PDB:4X9R"
FT STRAND 441..444
FT /evidence="ECO:0007829|PDB:4X9R"
FT STRAND 448..454
FT /evidence="ECO:0007829|PDB:4X9R"
FT STRAND 460..464
FT /evidence="ECO:0007829|PDB:4X9R"
FT TURN 465..467
FT /evidence="ECO:0007829|PDB:3Q1I"
FT HELIX 470..472
FT /evidence="ECO:0007829|PDB:4X9R"
FT HELIX 473..488
FT /evidence="ECO:0007829|PDB:4X9R"
FT TURN 493..496
FT /evidence="ECO:0007829|PDB:4X9R"
FT TURN 503..505
FT /evidence="ECO:0007829|PDB:3P34"
FT STRAND 511..516
FT /evidence="ECO:0007829|PDB:4X9R"
FT STRAND 518..525
FT /evidence="ECO:0007829|PDB:4X9R"
FT TURN 526..528
FT /evidence="ECO:0007829|PDB:4WHL"
FT STRAND 530..534
FT /evidence="ECO:0007829|PDB:4X9R"
FT TURN 535..537
FT /evidence="ECO:0007829|PDB:4X9R"
FT STRAND 540..544
FT /evidence="ECO:0007829|PDB:4X9R"
FT TURN 545..548
FT /evidence="ECO:0007829|PDB:4X9R"
FT STRAND 549..553
FT /evidence="ECO:0007829|PDB:4X9R"
FT STRAND 559..563
FT /evidence="ECO:0007829|PDB:4X9R"
FT HELIX 564..570
FT /evidence="ECO:0007829|PDB:4X9R"
FT HELIX 574..591
FT /evidence="ECO:0007829|PDB:4X9R"
FT STRAND 593..595
FT /evidence="ECO:0007829|PDB:4O56"
FT STRAND 598..602
FT /evidence="ECO:0007829|PDB:4O56"
SQ SEQUENCE 603 AA; 68255 MW; 178C2F13C10E8206 CRC64;
MSAAVTAGKL ARAPADPGKA GVPGVAAPGA PAAAPPAKEI PEVLVDPRSR RRYVRGRFLG
KGGFAKCFEI SDADTKEVFA GKIVPKSLLL KPHQREKMSM EISIHRSLAH QHVVGFHGFF
EDNDFVFVVL ELCRRRSLLE LHKRRKALTE PEARYYLRQI VLGCQYLHRN RVIHRDLKLG
NLFLNEDLEV KIGDFGLATK VEYDGERKKT LCGTPNYIAP EVLSKKGHSF EVDVWSIGCI
MYTLLVGKPP FETSCLKETY LRIKKNEYSI PKHINPVAAS LIQKMLQTDP TARPTINELL
NDEFFTSGYI PARLPITCLT IPPRFSIAPS SLDPSNRKPL TVLNKGLENP LPERPREKEE
PVVRETGEVV DCHLSDMLQQ LHSVNASKPS ERGLVRQEEA EDPACIPIFW VSKWVDYSDK
YGLGYQLCDN SVGVLFNDST RLILYNDGDS LQYIERDGTE SYLTVSSHPN SLMKKITLLK
YFRNYMSEHL LKAGANITPR EGDELARLPY LRTWFRTRSA IILHLSNGSV QINFFQDHTK
LILCPLMAAV TYIDEKRDFR TYRLSLLEEY GCCKELASRL RYARTMVDKL LSSRSASNRL
KAS
