PLK3_HUMAN
ID PLK3_HUMAN Reviewed; 646 AA.
AC Q9H4B4; Q15767; Q5JR99; Q96CV1;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2004, sequence version 2.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=Serine/threonine-protein kinase PLK3;
DE EC=2.7.11.21;
DE AltName: Full=Cytokine-inducible serine/threonine-protein kinase;
DE AltName: Full=FGF-inducible kinase;
DE AltName: Full=Polo-like kinase 3;
DE Short=PLK-3;
DE AltName: Full=Proliferation-related kinase;
GN Name=PLK3; Synonyms=CNK, FNK, PRK;
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=Embryo;
RX PubMed=11039900; DOI=10.1038/sj.onc.1203845;
RA Holtrich U., Wolf G., Yuan J., Bereiter-Hahn J., Karn T., Weiler M.,
RA Kauselmann G., Rehli M., Andreesen R., Kaufmann M., Kuhl D., Strebhardt K.;
RT "Adhesion induced expression of the serine/threonine kinase Fnk in human
RT macrophages.";
RL Oncogene 19:4832-4839(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-61; PHE-68; PHE-283;
RP CYS-483; LEU-498 AND PRO-618.
RG NIEHS SNPs program;
RL Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASN-491.
RC TISSUE=Brain;
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 [MRNA] OF 28-646.
RC TISSUE=Placenta;
RX PubMed=8702627; DOI=10.1074/jbc.271.32.19402;
RA Li B., Ouyang B., Pan H., Reissmann P.T., Slamon D.J., Arceci R., Lu L.,
RA Dai W.;
RT "Prk, a cytokine-inducible human protein serine/threonine kinase whose
RT expression appears to be down-regulated in lung carcinomas.";
RL J. Biol. Chem. 271:19402-19408(1996).
RN [7]
RP INDUCTION.
RX PubMed=11746980; DOI=10.1002/gcc.1204;
RA Wiest J., Clark A.M., Dai W.;
RT "Intron/exon organization and polymorphisms of the PLK3/PRK gene in human
RT lung carcinoma cell lines.";
RL Genes Chromosomes Cancer 32:384-389(2001).
RN [8]
RP FUNCTION IN PHOSPHORYLATION OF TP53 AND CHEK2, AND PHOSPHORYLATION.
RX PubMed=12242661; DOI=10.1038/sj.onc.1205850;
RA Bahassi el M., Conn C.W., Myer D.L., Hennigan R.F., McGowan C.H.,
RA Sanchez Y., Stambrook P.J.;
RT "Mammalian Polo-like kinase 3 (Plk3) is a multifunctional protein involved
RT in stress response pathways.";
RL Oncogene 21:6633-6640(2002).
RN [9]
RP FUNCTION.
RX PubMed=9353331; DOI=10.1074/jbc.272.45.28646;
RA Ouyang B., Pan H., Lu L., Li J., Stambrook P., Li B., Dai W.;
RT "Human Prk is a conserved protein serine/threonine kinase involved in
RT regulating M phase functions.";
RL J. Biol. Chem. 272:28646-28651(1997).
RN [10]
RP FUNCTION.
RX PubMed=10557092; DOI=10.1038/sj.onc.1202983;
RA Ouyang B., Li W., Pan H., Meadows J., Hoffmann I., Dai W.;
RT "The physical association and phosphorylation of Cdc25C protein phosphatase
RT by Prk.";
RL Oncogene 18:6029-6036(1999).
RN [11]
RP FUNCTION, AND MUTAGENESIS OF ASP-203.
RX PubMed=11156373;
RA Conn C.W., Hennigan R.F., Dai W., Sanchez Y., Stambrook P.J.;
RT "Incomplete cytokinesis and induction of apoptosis by overexpression of the
RT mammalian polo-like kinase, Plk3.";
RL Cancer Res. 60:6826-6831(2000).
RN [12]
RP FUNCTION IN PHOSPHORYLATION OF TP53, AND MUTAGENESIS OF LYS-91.
RX PubMed=11447225; DOI=10.1074/jbc.m104157200;
RA Xie S., Wang Q., Wu H., Cogswell J., Lu L., Jhanwar-Uniyal M., Dai W.;
RT "Reactive oxygen species-induced phosphorylation of p53 on serine 20 is
RT mediated in part by polo-like kinase-3.";
RL J. Biol. Chem. 276:36194-36199(2001).
RN [13]
RP FUNCTION IN PHOSPHORYLATION OF TP53.
RX PubMed=11551930; DOI=10.1074/jbc.m106050200;
RA Xie S., Wu H., Wang Q., Cogswell J.P., Husain I., Conn C., Stambrook P.,
RA Jhanwar-Uniyal M., Dai W.;
RT "Plk3 functionally links DNA damage to cell cycle arrest and apoptosis at
RT least in part via the p53 pathway.";
RL J. Biol. Chem. 276:43305-43312(2001).
RN [14]
RP FUNCTION.
RX PubMed=11971976; DOI=10.1128/mcb.22.10.3450-3459.2002;
RA Wang Q., Xie S., Chen J., Fukasawa K., Naik U., Traganos F.,
RA Darzynkiewicz Z., Jhanwar-Uniyal M., Dai W.;
RT "Cell cycle arrest and apoptosis induced by human Polo-like kinase 3 is
RT mediated through perturbation of microtubule integrity.";
RL Mol. Cell. Biol. 22:3450-3459(2002).
RN [15]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH GOLGB1, AND MUTAGENESIS OF
RP LYS-91.
RX PubMed=14980500; DOI=10.1016/j.yexcr.2003.10.022;
RA Ruan Q., Wang Q., Xie S., Fang Y., Darzynkiewicz Z., Guan K.,
RA Jhanwar-Uniyal M., Dai W.;
RT "Polo-like kinase 3 is Golgi localized and involved in regulating Golgi
RT fragmentation during the cell cycle.";
RL Exp. Cell Res. 294:51-59(2004).
RN [16]
RP FUNCTION IN PHOSPHORYLATION OF CDC25C.
RX PubMed=14968113; DOI=10.1038/sj.onc.1207425;
RA Bahassi el M., Hennigan R.F., Myer D.L., Stambrook P.J.;
RT "Cdc25C phosphorylation on serine 191 by Plk3 promotes its nuclear
RT translocation.";
RL Oncogene 23:2658-2663(2004).
RN [17]
RP FUNCTION.
RX PubMed=15021912; DOI=10.1038/sj.onc.1207479;
RA Xie S., Wang Q., Ruan Q., Liu T., Jhanwar-Uniyal M., Guan K., Dai W.;
RT "MEK1-induced Golgi dynamics during cell cycle progression is partly
RT mediated by Polo-like kinase-3.";
RL Oncogene 23:3822-3829(2004).
RN [18]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF THR-219 AND
RP 467-TRP-VAL-468.
RX PubMed=16478733; DOI=10.1074/jbc.m513156200;
RA Jiang N., Wang X., Jhanwar-Uniyal M., Darzynkiewicz Z., Dai W.;
RT "Polo box domain of Plk3 functions as a centrosome localization signal,
RT overexpression of which causes mitotic arrest, cytokinesis defects, and
RT apoptosis.";
RL J. Biol. Chem. 281:10577-10582(2006).
RN [19]
RP FUNCTION IN PHOSPHORYLATION OF TP53 AND CHEK2.
RX PubMed=16481012; DOI=10.1016/j.mrfmmm.2005.12.002;
RA Bahassi el M., Myer D.L., McKenney R.J., Hennigan R.F., Stambrook P.J.;
RT "Priming phosphorylation of Chk2 by polo-like kinase 3 (Plk3) mediates its
RT full activation by ATM and a downstream checkpoint in response to DNA
RT damage.";
RL Mutat. Res. 596:166-176(2006).
RN [20]
RP FUNCTION IN PHOSPHORYLATION OF JUN, AND MUTAGENESIS OF LYS-91.
RX PubMed=17804415; DOI=10.1074/jbc.m702791200;
RA Wang L., Dai W., Lu L.;
RT "Stress-induced c-Jun activation mediated by Polo-like kinase 3 in corneal
RT epithelial cells.";
RL J. Biol. Chem. 282:32121-32127(2007).
RN [21]
RP FUNCTION, SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=17264206; DOI=10.1073/pnas.0610856104;
RA Zimmerman W.C., Erikson R.L.;
RT "Polo-like kinase 3 is required for entry into S phase.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1847-1852(2007).
RN [22]
RP FUNCTION IN PHOSPHORYLATION OF TOP2A.
RX PubMed=18062778; DOI=10.1042/bj20071394;
RA Iida M., Matsuda M., Komatani H.;
RT "Plk3 phosphorylates topoisomerase IIalpha at Thr(1342), a site that is not
RT recognized by Plk1.";
RL Biochem. J. 411:27-32(2008).
RN [23]
RP FUNCTION IN PHOSPHORYLATION OF JUN, AND SUBCELLULAR LOCATION.
RX PubMed=18650425; DOI=10.1074/jbc.m801326200;
RA Wang L., Gao J., Dai W., Lu L.;
RT "Activation of Polo-like kinase 3 by hypoxic stresses.";
RL J. Biol. Chem. 283:25928-25935(2008).
RN [24]
RP FUNCTION IN PHOSPHORYLATION OF TP73, SUBCELLULAR LOCATION, AND MUTAGENESIS
RP OF LYS-91.
RX PubMed=19490146; DOI=10.1111/j.1365-2443.2009.01309.x;
RA Sang M., Ando K., Okoshi R., Koida N., Li Y., Zhu Y., Shimozato O.,
RA Geng C., Shan B., Nakagawara A., Ozaki T.;
RT "Plk3 inhibits pro-apoptotic activity of p73 through physical interaction
RT and phosphorylation.";
RL Genes Cells 14:775-788(2009).
RN [25]
RP FUNCTION IN PHOSPHORYLATION OF VRK1, AND MUTAGENESIS OF LYS-91.
RX PubMed=19103756; DOI=10.1128/mcb.01341-08;
RA Lopez-Sanchez I., Sanz-Garcia M., Lazo P.A.;
RT "Plk3 interacts with and specifically phosphorylates VRK1 in Ser342, a
RT downstream target in a pathway that induces Golgi fragmentation.";
RL Mol. Cell. Biol. 29:1189-1201(2009).
RN [26]
RP FUNCTION IN PHOSPHORYLATION OF HIF1A, AND MUTAGENESIS OF LYS-91.
RX PubMed=20889502; DOI=10.1074/jbc.m110.160325;
RA Xu D., Yao Y., Lu L., Costa M., Dai W.;
RT "Plk3 functions as an essential component of the hypoxia regulatory pathway
RT by direct phosphorylation of HIF-1alpha.";
RL J. Biol. Chem. 285:38944-38950(2010).
RN [27]
RP FUNCTION IN PHOSPHORYLATION OF PTEN, AND MUTAGENESIS OF LYS-91.
RX PubMed=20940307; DOI=10.1074/jbc.m110.166462;
RA Xu D., Yao Y., Jiang X., Lu L., Dai W.;
RT "Regulation of PTEN stability and activity by Plk3.";
RL J. Biol. Chem. 285:39935-39942(2010).
RN [28]
RP FUNCTION, INTERACTION WITH CIB1, AND SUBCELLULAR LOCATION.
RX PubMed=20951827; DOI=10.1016/j.biocel.2010.10.003;
RA Naik M.U., Naik U.P.;
RT "Calcium- and integrin-binding protein 1 regulates microtubule organization
RT and centrosome segregation through polo like kinase 3 during cell cycle
RT progression.";
RL Int. J. Biochem. Cell Biol. 43:120-129(2011).
RN [29]
RP INTERACTION WITH CIB1.
RX PubMed=20473878; DOI=10.1002/ijc.25388;
RA Naik M.U., Pham N.T., Beebe K., Dai W., Naik U.P.;
RT "Calcium-dependent inhibition of polo-like kinase 3 activity by CIB1 in
RT breast cancer cells.";
RL Int. J. Cancer 128:587-596(2011).
RN [30]
RP FUNCTION IN PHOSPHORYLATION OF ATF2, AND SUBCELLULAR LOCATION.
RX PubMed=21098032; DOI=10.1074/jbc.m110.166009;
RA Wang L., Payton R., Dai W., Lu L.;
RT "Hyperosmotic stress-induced ATF-2 activation through Polo-like kinase 3 in
RT human corneal epithelial cells.";
RL J. Biol. Chem. 286:1951-1958(2011).
RN [31]
RP FUNCTION IN PHOSPHORYLATION OF BCL2L1.
RX PubMed=21840391; DOI=10.1016/j.cellsig.2011.07.017;
RA Wang J., Beauchemin M., Bertrand R.;
RT "Bcl-xL phosphorylation at Ser49 by polo kinase 3 during cell cycle
RT progression and checkpoints.";
RL Cell. Signal. 23:2030-2038(2011).
RN [32]
RP FUNCTION IN PHOSPHORYLATION OF CDC25A.
RX PubMed=21376736; DOI=10.1016/j.mrfmmm.2011.02.006;
RA Myer D.L., Robbins S.B., Yin M., Boivin G.P., Liu Y., Greis K.D.,
RA Bahassi el M., Stambrook P.J.;
RT "Absence of polo-like kinase 3 in mice stabilizes Cdc25A after DNA damage
RT but is not sufficient to produce tumors.";
RL Mutat. Res. 714:1-10(2011).
RN [33]
RP FUNCTION, AND INTERACTION WITH CIB1.
RX PubMed=21264284; DOI=10.1371/journal.pone.0014513;
RA Kostyak J.C., Naik U.P.;
RT "Calcium- and integrin-binding protein 1 regulates endomitosis and its
RT interaction with Polo-like kinase 3 is enhanced in endomitotic Dami
RT cells.";
RL PLoS ONE 6:E14513-E14513(2011).
RN [34]
RP REVIEW ON FUNCTION.
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).
CC -!- FUNCTION: Serine/threonine-protein kinase involved in cell cycle
CC regulation, response to stress and Golgi disassembly. Polo-like kinases
CC act by binding and phosphorylating proteins are that already
CC phosphorylated on a specific motif recognized by the POLO box domains.
CC Phosphorylates ATF2, BCL2L1, CDC25A, CDC25C, CHEK2, HIF1A, JUN,
CC p53/TP53, p73/TP73, PTEN, TOP2A and VRK1. Involved in cell cycle
CC regulation: required for entry into S phase and cytokinesis.
CC Phosphorylates BCL2L1, leading to regulate the G2 checkpoint and
CC progression to cytokinesis during mitosis. Plays a key role in response
CC to stress: rapidly activated upon stress stimulation, such as ionizing
CC radiation, reactive oxygen species (ROS), hyperosmotic stress, UV
CC irradiation and hypoxia. Involved in DNA damage response and G1/S
CC transition checkpoint by phosphorylating CDC25A, p53/TP53 and p73/TP73.
CC Phosphorylates p53/TP53 in response to reactive oxygen species (ROS),
CC thereby promoting p53/TP53-mediated apoptosis. Phosphorylates CHEK2 in
CC response to DNA damage, promoting the G2/M transition checkpoint.
CC Phosphorylates the transcription factor p73/TP73 in response to DNA
CC damage, leading to inhibit p73/TP73-mediated transcriptional activation
CC and pro-apoptotic functions. Phosphorylates HIF1A and JUN is response
CC to hypoxia. Phosphorylates ATF2 following hyperosmotic stress in
CC corneal epithelium. Also involved in Golgi disassembly during the cell
CC cycle: part of a MEK1/MAP2K1-dependent pathway that induces Golgi
CC fragmentation during mitosis by mediating phosphorylation of VRK1. May
CC participate in endomitotic cell cycle, a form of mitosis in which both
CC karyokinesis and cytokinesis are interrupted and is a hallmark of
CC megakaryocyte differentiation, via its interaction with CIB1.
CC {ECO:0000269|PubMed:10557092, ECO:0000269|PubMed:11156373,
CC ECO:0000269|PubMed:11447225, ECO:0000269|PubMed:11551930,
CC ECO:0000269|PubMed:11971976, ECO:0000269|PubMed:12242661,
CC ECO:0000269|PubMed:14968113, ECO:0000269|PubMed:14980500,
CC ECO:0000269|PubMed:15021912, ECO:0000269|PubMed:16478733,
CC ECO:0000269|PubMed:16481012, ECO:0000269|PubMed:17264206,
CC ECO:0000269|PubMed:17804415, ECO:0000269|PubMed:18062778,
CC ECO:0000269|PubMed:18650425, ECO:0000269|PubMed:19103756,
CC ECO:0000269|PubMed:19490146, ECO:0000269|PubMed:20889502,
CC ECO:0000269|PubMed:20940307, ECO:0000269|PubMed:20951827,
CC ECO:0000269|PubMed:21098032, ECO:0000269|PubMed:21264284,
CC ECO:0000269|PubMed:21376736, ECO:0000269|PubMed:21840391,
CC ECO:0000269|PubMed:9353331}.
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 -!- 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;
CC -!- SUBUNIT: Interacts (via the POLO-box domain) with CIB1; leading to
CC inhibit PLK3 kinase activity. Interacts with GOLGB1.
CC {ECO:0000269|PubMed:14980500, ECO:0000269|PubMed:20473878,
CC ECO:0000269|PubMed:20951827, ECO:0000269|PubMed:21264284}.
CC -!- INTERACTION:
CC Q9H4B4; Q9Y4Y9: LSM5; NbExp=3; IntAct=EBI-751877, EBI-373007;
CC Q9H4B4; Q9GZY8-5: MFF; NbExp=3; IntAct=EBI-751877, EBI-11956541;
CC Q9H4B4; P14859: POU2F1; NbExp=3; IntAct=EBI-751877, EBI-624770;
CC Q9H4B4; P04156: PRNP; NbExp=4; IntAct=EBI-751877, EBI-977302;
CC Q9H4B4; P43351: RAD52; NbExp=3; IntAct=EBI-751877, EBI-706448;
CC Q9H4B4; Q8WVD5: RNF141; NbExp=3; IntAct=EBI-751877, EBI-4308142;
CC Q9H4B4; Q99986: VRK1; NbExp=12; IntAct=EBI-751877, EBI-1769146;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Nucleus, nucleolus. Golgi
CC apparatus. Cytoplasm, cytoskeleton, microtubule organizing center,
CC centrosome. Note=Translocates to the nucleus upon cisplatin treatment.
CC Localizes to the Golgi apparatus during interphase. According to a
CC report, PLK3 localizes only in the nucleolus and not in the centrosome,
CC or in any other location in the cytoplasm (PubMed:17264206). The
CC discrepancies in results may be explained by the PLK3 antibody
CC specificity, by cell line-specific expression or post-translational
CC modifications. {ECO:0000269|PubMed:17264206}.
CC -!- TISSUE SPECIFICITY: Transcripts are highly detected in placenta, lung,
CC followed by skeletal muscle, heart, pancreas, ovaries and kidney and
CC weakly detected in liver and brain. May have a short half-live. In
CC cells of hematopoietic origin, strongly and exclusively detected in
CC terminally differentiated macrophages. Transcript expression appears to
CC be down-regulated in primary lung tumor.
CC -!- DEVELOPMENTAL STAGE: Expression is cell cycle regulated with a peak in
CC G1 phase. {ECO:0000269|PubMed:17264206}.
CC -!- INDUCTION: Cytokine and cellular adhesion trigger induction. Down-
CC regulated in a majority of lung carcinoma samples.
CC {ECO:0000269|PubMed:11746980}.
CC -!- DOMAIN: The POLO box domains act as phosphopeptide-binding module that
CC recognize and bind serine-[phosphothreonine/phosphoserine]-(proline/X)
CC motifs. PLK3 recognizes and binds docking proteins that are already
CC phosphorylated on these motifs, and then phosphorylates them (By
CC similarity). The POLO box domains mediates localization to the
CC centrosome. {ECO:0000250}.
CC -!- PTM: Phosphorylated in an ATM-dependent manner following DNA damage.
CC Phosphorylated as cells enter mitosis and dephosphorylated as cells
CC exit mitosis. {ECO:0000269|PubMed:12242661}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. CDC5/Polo subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC50637.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/plk3/";
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DR EMBL; AJ293866; CAC10659.1; -; mRNA.
DR EMBL; AY764184; AAU88146.1; -; Genomic_DNA.
DR EMBL; AL592166; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471059; EAX07021.1; -; Genomic_DNA.
DR EMBL; BC013899; AAH13899.1; -; mRNA.
DR EMBL; U56998; AAC50637.1; ALT_INIT; mRNA.
DR CCDS; CCDS515.1; -.
DR RefSeq; NP_004064.2; NM_004073.3.
DR PDB; 4B6L; X-ray; 1.90 A; A=52-332.
DR PDBsum; 4B6L; -.
DR AlphaFoldDB; Q9H4B4; -.
DR SMR; Q9H4B4; -.
DR BioGRID; 107663; 26.
DR IntAct; Q9H4B4; 19.
DR STRING; 9606.ENSP00000361275; -.
DR BindingDB; Q9H4B4; -.
DR ChEMBL; CHEMBL4897; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q9H4B4; -.
DR GuidetoPHARMACOLOGY; 2170; -.
DR iPTMnet; Q9H4B4; -.
DR PhosphoSitePlus; Q9H4B4; -.
DR BioMuta; PLK3; -.
DR DMDM; 51338822; -.
DR jPOST; Q9H4B4; -.
DR MassIVE; Q9H4B4; -.
DR MaxQB; Q9H4B4; -.
DR PaxDb; Q9H4B4; -.
DR PeptideAtlas; Q9H4B4; -.
DR PRIDE; Q9H4B4; -.
DR Antibodypedia; 32550; 282 antibodies from 34 providers.
DR DNASU; 1263; -.
DR Ensembl; ENST00000372201.5; ENSP00000361275.4; ENSG00000173846.13.
DR GeneID; 1263; -.
DR KEGG; hsa:1263; -.
DR MANE-Select; ENST00000372201.5; ENSP00000361275.4; NM_004073.4; NP_004064.2.
DR UCSC; uc001cmn.4; human.
DR CTD; 1263; -.
DR DisGeNET; 1263; -.
DR GeneCards; PLK3; -.
DR HGNC; HGNC:2154; PLK3.
DR HPA; ENSG00000173846; Low tissue specificity.
DR MIM; 602913; gene.
DR neXtProt; NX_Q9H4B4; -.
DR OpenTargets; ENSG00000173846; -.
DR PharmGKB; PA26664; -.
DR VEuPathDB; HostDB:ENSG00000173846; -.
DR eggNOG; KOG0575; Eukaryota.
DR GeneTree; ENSGT00940000159121; -.
DR HOGENOM; CLU_000288_46_1_1; -.
DR InParanoid; Q9H4B4; -.
DR OMA; KKSKNHA; -.
DR OrthoDB; 1417203at2759; -.
DR PhylomeDB; Q9H4B4; -.
DR TreeFam; TF101089; -.
DR BRENDA; 2.7.11.21; 2681.
DR BRENDA; 2.7.11.23; 2681.
DR PathwayCommons; Q9H4B4; -.
DR Reactome; R-HSA-6804115; TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain.
DR Reactome; R-HSA-6804756; Regulation of TP53 Activity through Phosphorylation.
DR SignaLink; Q9H4B4; -.
DR SIGNOR; Q9H4B4; -.
DR BioGRID-ORCS; 1263; 13 hits in 1110 CRISPR screens.
DR ChiTaRS; PLK3; human.
DR GeneWiki; PLK3; -.
DR GenomeRNAi; 1263; -.
DR Pharos; Q9H4B4; Tchem.
DR PRO; PR:Q9H4B4; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9H4B4; protein.
DR Bgee; ENSG00000173846; Expressed in oocyte and 122 other tissues.
DR Genevisible; Q9H4B4; HS.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR GO; GO:0005795; C:Golgi stack; IDA:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000922; C:spindle pole; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0002039; F:p53 binding; IDA: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:0006915; P:apoptotic process; TAS:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0031122; P:cytoplasmic microtubule organization; IMP:UniProtKB.
DR GO; GO:0006977; P:DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; TAS:Reactome.
DR GO; GO:0007113; P:endomitotic cell cycle; TAS:UniProtKB.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; TAS:UniProtKB.
DR GO; GO:0090166; P:Golgi disassembly; IDA:UniProtKB.
DR GO; GO:0000278; P:mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0044819; P:mitotic G1/S transition checkpoint signaling; ISS:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:1904716; P:positive regulation of chaperone-mediated autophagy; IDA:ParkinsonsUK-UCL.
DR GO; GO:0090316; P:positive regulation of intracellular protein transport; IMP:UniProtKB.
DR GO; GO:2000777; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process involved in cellular response to hypoxia; IDA:UniProtKB.
DR GO; GO:0043491; P:protein kinase B signaling; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; TAS:ProtInc.
DR GO; GO:0051302; P:regulation of cell division; IDA:UniProtKB.
DR GO; GO:0032465; P:regulation of cytokinesis; IMP:UniProtKB.
DR GO; GO:1901796; P:regulation of signal transduction by p53 class mediator; TAS:Reactome.
DR GO; GO:0006970; P:response to osmotic stress; IDA:UniProtKB.
DR GO; GO:0009314; P:response to radiation; IDA:UniProtKB.
DR GO; GO:0000302; P:response to reactive oxygen species; IDA:UniProtKB.
DR CDD; cd13118; POLO_box_1; 1.
DR CDD; cd13117; POLO_box_2; 1.
DR CDD; cd14189; STKc_PLK3; 1.
DR Gene3D; 3.30.1120.30; -; 2.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR042703; PLK3_STKc.
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 InterPro; IPR020658; Ser/Thr_kinase_PLK3.
DR PANTHER; PTHR24345:SF42; PTHR24345:SF42; 1.
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; Apoptosis; ATP-binding; Cell cycle; Cytoplasm; Cytoskeleton;
KW DNA damage; Golgi apparatus; Kinase; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..646
FT /note="Serine/threonine-protein kinase PLK3"
FT /id="PRO_0000086564"
FT DOMAIN 62..314
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 470..537
FT /note="POLO box 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00154"
FT DOMAIN 567..637
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 381..417
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 16..33
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 185
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 68..76
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 91
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT VARIANT 61
FT /note="T -> S (in dbSNP:rs17884581)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_021091"
FT VARIANT 68
FT /note="L -> F (in dbSNP:rs17884316)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_021092"
FT VARIANT 283
FT /note="L -> F (in dbSNP:rs17880471)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_021093"
FT VARIANT 483
FT /note="R -> C (in dbSNP:rs17884653)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_021094"
FT VARIANT 491
FT /note="D -> N (in dbSNP:rs17855444)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_062384"
FT VARIANT 498
FT /note="S -> L (in dbSNP:rs17880829)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_021095"
FT VARIANT 618
FT /note="S -> P (in dbSNP:rs17881786)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_021096"
FT MUTAGEN 91
FT /note="K->R: Kinase defective mutant, abolishes activity."
FT /evidence="ECO:0000269|PubMed:11447225,
FT ECO:0000269|PubMed:14980500, ECO:0000269|PubMed:17804415,
FT ECO:0000269|PubMed:19103756, ECO:0000269|PubMed:19490146,
FT ECO:0000269|PubMed:20889502, ECO:0000269|PubMed:20940307"
FT MUTAGEN 203
FT /note="D->A: Kinase defective mutant, abolishes activity."
FT /evidence="ECO:0000269|PubMed:11156373"
FT MUTAGEN 219
FT /note="T->E: Kinase-defective mutant."
FT /evidence="ECO:0000269|PubMed:16478733"
FT MUTAGEN 467..468
FT /note="WV->FA: Abolishes localization to the centrosome and
FT ability to induce the G2/M arrest."
FT /evidence="ECO:0000269|PubMed:16478733"
FT CONFLICT 16
FT /note="A -> T (in Ref. 1; CAC10659)"
FT /evidence="ECO:0000305"
FT CONFLICT 20
FT /note="P -> T (in Ref. 1; CAC10659)"
FT /evidence="ECO:0000305"
FT CONFLICT 99
FT /note="A -> V (in Ref. 1; CAC10659)"
FT /evidence="ECO:0000305"
FT CONFLICT 353
FT /note="G -> V (in Ref. 1; CAC10659)"
FT /evidence="ECO:0000305"
FT CONFLICT 419
FT /note="D -> H (in Ref. 1; CAC10659)"
FT /evidence="ECO:0000305"
FT CONFLICT 464..470
FT /note="VSKWVDY -> FSEWVGF (in Ref. 1; CAC10659)"
FT /evidence="ECO:0000305"
FT CONFLICT 522
FT /note="P -> R (in Ref. 1; CAC10659)"
FT /evidence="ECO:0000305"
FT STRAND 62..69
FT /evidence="ECO:0007829|PDB:4B6L"
FT STRAND 75..81
FT /evidence="ECO:0007829|PDB:4B6L"
FT TURN 82..84
FT /evidence="ECO:0007829|PDB:4B6L"
FT STRAND 87..94
FT /evidence="ECO:0007829|PDB:4B6L"
FT HELIX 95..98
FT /evidence="ECO:0007829|PDB:4B6L"
FT HELIX 101..114
FT /evidence="ECO:0007829|PDB:4B6L"
FT STRAND 125..130
FT /evidence="ECO:0007829|PDB:4B6L"
FT STRAND 132..139
FT /evidence="ECO:0007829|PDB:4B6L"
FT HELIX 147..154
FT /evidence="ECO:0007829|PDB:4B6L"
FT HELIX 159..178
FT /evidence="ECO:0007829|PDB:4B6L"
FT HELIX 188..190
FT /evidence="ECO:0007829|PDB:4B6L"
FT STRAND 191..193
FT /evidence="ECO:0007829|PDB:4B6L"
FT STRAND 199..201
FT /evidence="ECO:0007829|PDB:4B6L"
FT TURN 213..215
FT /evidence="ECO:0007829|PDB:4B6L"
FT TURN 224..226
FT /evidence="ECO:0007829|PDB:4B6L"
FT HELIX 229..232
FT /evidence="ECO:0007829|PDB:4B6L"
FT HELIX 239..255
FT /evidence="ECO:0007829|PDB:4B6L"
FT HELIX 265..273
FT /evidence="ECO:0007829|PDB:4B6L"
FT HELIX 285..294
FT /evidence="ECO:0007829|PDB:4B6L"
FT HELIX 299..301
FT /evidence="ECO:0007829|PDB:4B6L"
FT HELIX 305..309
FT /evidence="ECO:0007829|PDB:4B6L"
FT HELIX 312..315
FT /evidence="ECO:0007829|PDB:4B6L"
FT HELIX 325..328
FT /evidence="ECO:0007829|PDB:4B6L"
SQ SEQUENCE 646 AA; 71629 MW; 324CA3E9DE482514 CRC64;
MEPAAGFLSP RPFQRAAAAP APPAGPGPPP SALRGPELEM LAGLPTSDPG RLITDPRSGR
TYLKGRLLGK GGFARCYEAT DTETGSAYAV KVIPQSRVAK PHQREKILNE IELHRDLQHR
HIVRFSHHFE DADNIYIFLE LCSRKSLAHI WKARHTLLEP EVRYYLRQIL SGLKYLHQRG
ILHRDLKLGN FFITENMELK VGDFGLAARL EPPEQRKKTI CGTPNYVAPE VLLRQGHGPE
ADVWSLGCVM YTLLCGSPPF ETADLKETYR CIKQVHYTLP ASLSLPARQL LAAILRASPR
DRPSIDQILR HDFFTKGYTP DRLPISSCVT VPDLTPPNPA RSLFAKVTKS LFGRKKKSKN
HAQERDEVSG LVSGLMRTSV GHQDARPEAP AASGPAPVSL VETAPEDSSP RGTLASSGDG
FEEGLTVATV VESALCALRN CIAFMPPAEQ NPAPLAQPEP LVWVSKWVDY SNKFGFGYQL
SSRRVAVLFN DGTHMALSAN RKTVHYNPTS TKHFSFSVGA VPRALQPQLG ILRYFASYME
QHLMKGGDLP SVEEVEVPAP PLLLQWVKTD QALLMLFSDG TVQVNFYGDH TKLILSGWEP
LLVTFVARNR SACTYLASHL RQLGCSPDLR QRLRYALRLL RDRSPA
