PLK3_MOUSE
ID PLK3_MOUSE Reviewed; 631 AA.
AC Q60806; Q60822; Q9R009;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 27-APR-2001, sequence version 2.
DT 03-AUG-2022, entry version 164.
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;
GN Name=Plk3; Synonyms=Cnk, Fnk;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
RC STRAIN=NIH Swiss;
RX PubMed=7730342; DOI=10.1074/jbc.270.17.10351;
RA Donohue P.J., Alberts G.F., Guo Y., Winkles J.A.;
RT "Identification by targeted differential display of an immediate early gene
RT encoding a putative serine/threonine kinase.";
RL J. Biol. Chem. 270:10351-10357(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 333-437 (ISOFORM 2).
RC STRAIN=NIH Swiss;
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 [3]
RP FUNCTION, AND PHOSPHORYLATION.
RX PubMed=9677325; DOI=10.1042/bj3330655;
RA Chase D., Feng Y., Hanshew B., Winkles J.A., Longo D.L., Ferris D.K.;
RT "Expression and phosphorylation of fibroblast-growth-factor-inducible
RT kinase (Fnk) during cell-cycle progression.";
RL Biochem. J. 333:655-660(1998).
RN [4]
RP DISRUPTION PHENOTYPE.
RX PubMed=18519666; DOI=10.1158/0008-5472.can-07-6182;
RA Yang Y., Bai J., Shen R., Brown S.A., Komissarova E., Huang Y., Jiang N.,
RA Alberts G.F., Costa M., Lu L., Winkles J.A., Dai W.;
RT "Polo-like kinase 3 functions as a tumor suppressor and is a negative
RT regulator of hypoxia-inducible factor-1 alpha under hypoxic conditions.";
RL Cancer Res. 68:4077-4085(2008).
RN [5]
RP INDUCTION.
RX PubMed=19188452; DOI=10.1128/mcb.00982-08;
RA Horner T.J., Lai W.S., Stumpo D.J., Blackshear P.J.;
RT "Stimulation of polo-like kinase 3 mRNA decay by tristetraprolin.";
RL Mol. Cell. Biol. 29:1999-2010(2009).
RN [6]
RP FUNCTION IN PHOSPHORYLATION OF PTEN.
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 [7]
RP FUNCTION IN PHOSPHORYLATION OF CDC25A, AND DISRUPTION PHENOTYPE.
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).
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:20940307, ECO:0000269|PubMed:21376736,
CC ECO:0000269|PubMed:9677325}.
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 (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC Nucleus, nucleolus {ECO:0000250}. Golgi apparatus {ECO:0000250}.
CC Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
CC {ECO:0000250}. Note=Translocates to the nucleus upon cisplatin
CC treatment. Localizes to the Golgi apparatus during interphase (By
CC similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q60806-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q60806-2; Sequence=VSP_004927;
CC -!- TISSUE SPECIFICITY: Expressed in skin.
CC -!- INDUCTION: Negatively regulated by TTP family members: TTP binds to the
CC 3'-untranslated region (3'-UTR) of PLK3 mRNAs, contributing to the
CC rapid degradation of transcripts. {ECO:0000269|PubMed:19188452}.
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. The POLO
CC box domains mediates localization to the centrosome (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Phosphorylated in an ATM-dependent manner following DNA damage (By
CC similarity). Phosphorylated as cells enter mitosis and dephosphorylated
CC as cells exit mitosis. {ECO:0000250, ECO:0000269|PubMed:9677325}.
CC -!- DISRUPTION PHENOTYPE: Aging mice display increased weight. Cells
CC display defects in the G1/S cell cycle checkpoint and CDC25A protein is
CC more stable. According to a report, they also develop tumors with the
CC highest incidence in the lung but also in the kidney, the liver and the
CC uterus (PubMed:18519666). However, increased tumorigenesis was not
CC observed by another report (PubMed:21376736;). The differences observed
CC might be due to the different mouse strain background used in the 2
CC experiments. {ECO:0000269|PubMed:18519666,
CC ECO:0000269|PubMed:21376736}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. CDC5/Polo subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
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DR EMBL; U21392; AAC52191.1; -; mRNA.
DR EMBL; U22434; AAC52192.1; -; Genomic_DNA.
DR EMBL; AF136586; AAF08369.1; -; mRNA.
DR CCDS; CCDS18529.1; -. [Q60806-2]
DR PIR; A57286; A57286.
DR AlphaFoldDB; Q60806; -.
DR SMR; Q60806; -.
DR STRING; 10090.ENSMUSP00000076130; -.
DR iPTMnet; Q60806; -.
DR PhosphoSitePlus; Q60806; -.
DR MaxQB; Q60806; -.
DR PaxDb; Q60806; -.
DR PRIDE; Q60806; -.
DR ProteomicsDB; 289546; -. [Q60806-1]
DR ProteomicsDB; 289547; -. [Q60806-2]
DR MGI; MGI:109604; Plk3.
DR eggNOG; KOG0575; Eukaryota.
DR InParanoid; Q60806; -.
DR BRENDA; 2.7.11.21; 3474.
DR Reactome; R-MMU-6804115; TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain.
DR Reactome; R-MMU-6804756; Regulation of TP53 Activity through Phosphorylation.
DR PRO; PR:Q60806; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q60806; protein.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0000785; C:chromatin; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0005795; C:Golgi stack; ISS:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005730; C:nucleolus; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS: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; ISS: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; IEA:UniProtKB-KW.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IMP:UniProtKB.
DR GO; GO:0031122; P:cytoplasmic microtubule organization; ISS:UniProtKB.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; ISS:UniProtKB.
DR GO; GO:0090166; P:Golgi disassembly; ISS:UniProtKB.
DR GO; GO:0000278; P:mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0044819; P:mitotic G1/S transition checkpoint signaling; IMP:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:1904716; P:positive regulation of chaperone-mediated autophagy; ISO:MGI.
DR GO; GO:0090316; P:positive regulation of intracellular protein transport; ISS:UniProtKB.
DR GO; GO:2000777; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process involved in cellular response to hypoxia; ISS:UniProtKB.
DR GO; GO:0043491; P:protein kinase B signaling; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0051302; P:regulation of cell division; ISS:UniProtKB.
DR GO; GO:0032465; P:regulation of cytokinesis; ISO:MGI.
DR GO; GO:0006970; P:response to osmotic stress; ISS:UniProtKB.
DR GO; GO:0009314; P:response to radiation; ISS:UniProtKB.
DR GO; GO:0000302; P:response to reactive oxygen species; ISS: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 Alternative splicing; Apoptosis; ATP-binding; Cell cycle; Cytoplasm;
KW Cytoskeleton; DNA damage; Golgi apparatus; Kinase; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..631
FT /note="Serine/threonine-protein kinase PLK3"
FT /id="PRO_0000086565"
FT DOMAIN 63..315
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 455..518
FT /note="POLO box 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00154"
FT DOMAIN 552..622
FT /note="POLO box 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00154"
FT REGION 1..59
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 15..33
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 186
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 69..77
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 92
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT VAR_SEQ 373
FT /note="L -> LVSGLMRTSIGHPDVRPE (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11039900"
FT /id="VSP_004927"
FT CONFLICT 386
FT /note="I -> V (in Ref. 2; AAF08369)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 631 AA; 70012 MW; 20857341870DB1D2 CRC64;
MEPAAGFLSP RPFPRAAVPS APPAGPGPPA NASPRSEPEV LAGPRAPDPP GRLITDPLSG
RTYTKGRLLG KGGFARCYEA TDTESGIAYA VKVIPQSRVA KPHQREKILN EIELHRDLQH
RHIVRFSHHF EDADNIYIFL ELCSRKSLAH IWKARHTLLE PEVRYYLRQI LSGLKYLHQR
GILHRDLKLG NFFITDNMEL KVGDFGLAAR LEPPEQRKKT ICGTPNYVAP EVLLRQGHGP
EADVWSLGCV MYTLLCGSPP FETADLKETY RCIKQVHYTL PASLSLPARQ LLAAILRASP
RDRPSIEQIL RHDFFTKGYT PDRLPVSSCV TVPDLTPPNP ARSLFAKVTK SLFGRKKNKN
KNHSEDQDNV SCLAPVVSGQ APASLIETAA EDSSPRGTLA SSGDGFEEGL TVATVVESAL
CALRNCVAFM PPAEQNPAPL AQPEPLVWVS KWVDYSNKFG FGYQLSSRRV AVLFNDGTHM
ALSANRKTVH YNPTSTKHFS FSMGSVPRAL QPQLGILRYF ASYMEQHLMK GGDLPSVEEA
EVPAPPLLLQ WVKTDQALLM LFSDGTVQVN FYGDHTKLIL SGWEPLLVTF VARNRSACTY
LASHLRQLGC SPDLRQRLRY ALRLLRDQSP A
