PLK2_MOUSE
ID PLK2_MOUSE Reviewed; 682 AA.
AC P53351;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Serine/threonine-protein kinase PLK2;
DE EC=2.7.11.21;
DE AltName: Full=Polo-like kinase 2;
DE Short=PLK-2;
DE AltName: Full=Serine/threonine-protein kinase SNK;
DE AltName: Full=Serum-inducible kinase;
GN Name=Plk2; Synonyms=Snk;
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 [MRNA], TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=1508211; DOI=10.1128/mcb.12.9.4164-4169.1992;
RA Simmons D.L., Neel B.G., Stevens R., Evett G., Erikson R.L.;
RT "Identification of an early-growth-response gene encoding a novel putative
RT protein kinase.";
RL Mol. Cell. Biol. 12:4164-4169(1992).
RN [2]
RP FUNCTION, DEVELOPMENTAL STAGE, PHOSPHORYLATION AT THR-236, AND MUTAGENESIS
RP OF LYS-108 AND THR-236.
RX PubMed=12651910;
RA Ma S., Liu M.A., Yuan Y.L., Erikson R.L.;
RT "The serum-inducible protein kinase Snk is a G1 phase polo-like kinase that
RT is inhibited by the calcium- and integrin-binding protein CIB.";
RL Mol. Cancer Res. 1:376-384(2003).
RN [3]
RP FUNCTION, INDUCTION, AND MUTAGENESIS OF THR-236.
RX PubMed=12897130; DOI=10.1128/mcb.23.16.5556-5571.2003;
RA Burns T.F., Fei P., Scata K.A., Dicker D.T., El-Deiry W.S.;
RT "Silencing of the novel p53 target gene Snk/Plk2 leads to mitotic
RT catastrophe in paclitaxel (taxol)-exposed cells.";
RL Mol. Cell. Biol. 23:5556-5571(2003).
RN [4]
RP DISRUPTION PHENOTYPE.
RX PubMed=12972611; DOI=10.1128/mcb.23.19.6936-6943.2003;
RA Ma S., Charron J., Erikson R.L.;
RT "Role of Plk2 (Snk) in mouse development and cell proliferation.";
RL Mol. Cell. Biol. 23:6936-6943(2003).
RN [5]
RP FUNCTION IN PHOSPHORYLATION OF SNCA.
RX PubMed=19004816; DOI=10.1074/jbc.c800206200;
RA Inglis K.J., Chereau D., Brigham E.F., Chiou S.S., Schobel S., Frigon N.L.,
RA Yu M., Caccavello R.J., Nelson S., Motter R., Wright S., Chian D.,
RA Santiago P., Soriano F., Ramos C., Powell K., Goldstein J.M., Babcock M.,
RA Yednock T., Bard F., Basi G.S., Sham H., Chilcote T.J., McConlogue L.,
RA Griswold-Prenner I., Anderson J.P.;
RT "Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in
RT central nervous system.";
RL J. Biol. Chem. 284:2598-2602(2009).
RN [6]
RP FUNCTION, MUTAGENESIS OF LYS-108, AND DISRUPTION PHENOTYPE.
RX PubMed=21382555; DOI=10.1016/j.neuron.2011.02.004;
RA Lee K.J., Lee Y., Rozeboom A., Lee J.Y., Udagawa N., Hoe H.S., Pak D.T.;
RT "Requirement for Plk2 in orchestrated ras and rap signaling, homeostatic
RT structural plasticity, and memory.";
RL Neuron 69:957-973(2011).
CC -!- FUNCTION: Tumor suppressor serine/threonine-protein kinase involved in
CC synaptic plasticity, centriole duplication and G1/S phase transition.
CC Polo-like kinases act by binding and phosphorylating proteins are that
CC already phosphorylated on a specific motif recognized by the POLO box
CC domains. Phosphorylates CENPJ, NPM1, RAPGEF2, RASGRF1, SNCA, SIPA1L1
CC and SYNGAP1. Plays a key role in synaptic plasticity and memory by
CC regulating the Ras and Rap protein signaling: required for
CC overactivity-dependent spine remodeling by phosphorylating the Ras
CC activator RASGRF1 and the Rap inhibitor SIPA1L1 leading to their
CC degradation by the proteasome. Conversely, phosphorylates the Rap
CC activator RAPGEF2 and the Ras inhibitor SYNGAP1, promoting their
CC activity. Also regulates synaptic plasticity independently of kinase
CC activity, via its interaction with NSF that disrupts the interaction
CC between NSF and the GRIA2 subunit of AMPARs, leading to a rapid rundown
CC of AMPAR-mediated current that occludes long term depression. Required
CC for procentriole formation and centriole duplication by phosphorylating
CC CENPJ and NPM1, respectively. Its induction by p53/TP53 suggests that
CC it may participate in the mitotic checkpoint following stress.
CC {ECO:0000269|PubMed:12651910, ECO:0000269|PubMed:12897130,
CC ECO:0000269|PubMed:19004816, ECO:0000269|PubMed:21382555}.
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 -!- ACTIVITY REGULATION: Activated by phosphorylation of Thr-236. Once
CC activated, activity is stimulated by binding target proteins (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with NSF; causing NSF dissociation from GRIA2 (By
CC similarity). Interacts with CIB1. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule organizing
CC center, centrosome, centriole {ECO:0000250}. Cell projection, dendrite
CC {ECO:0000250}. Note=Localizes to centrosomes during early G1 phase
CC where it only associates to the mother centriole and then distributes
CC equally to both mother and daughter centrioles at the onset of S phase.
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Brain, lung and heart.
CC {ECO:0000269|PubMed:1508211}.
CC -!- DEVELOPMENTAL STAGE: Expressed in early G1, during G0-G1 transition as
CC well as in cycling cells. {ECO:0000269|PubMed:12651910}.
CC -!- INDUCTION: Directly regulated by p53/TP53. Induced by serum and phorbol
CC ester. {ECO:0000269|PubMed:12897130, ECO:0000269|PubMed:1508211}.
CC -!- DOMAIN: The POLO box domains act as phosphopeptide-binding module that
CC recognize and bind serine-[phosphothreonine/phosphoserine]-(proline/X)
CC motifs. PLK2 recognizes and binds docking proteins that are already
CC phosphorylated on these motifs, and then phosphorylates them (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Catalytic activity is enhanced by phosphorylation of Thr-236.
CC {ECO:0000269|PubMed:12651910}.
CC -!- DISRUPTION PHENOTYPE: Embryos display a delay in skeletal development
CC and retarded growth. Embryonic fibroblasts proliferated slowly and
CC displayed a delayed entry into S phase. Mice display loss of dendritic
CC spines and impaired memory formation. {ECO:0000269|PubMed:12972611,
CC ECO:0000269|PubMed:21382555}.
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; M96163; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS26767.1; -.
DR PIR; A44493; A44493.
DR RefSeq; NP_690017.2; NM_152804.2.
DR AlphaFoldDB; P53351; -.
DR SMR; P53351; -.
DR BioGRID; 203368; 10.
DR IntAct; P53351; 9.
DR STRING; 10090.ENSMUSP00000022212; -.
DR iPTMnet; P53351; -.
DR PhosphoSitePlus; P53351; -.
DR PaxDb; P53351; -.
DR PRIDE; P53351; -.
DR ProteomicsDB; 289545; -.
DR Antibodypedia; 4042; 265 antibodies from 32 providers.
DR DNASU; 20620; -.
DR Ensembl; ENSMUST00000022212; ENSMUSP00000022212; ENSMUSG00000021701.
DR GeneID; 20620; -.
DR KEGG; mmu:20620; -.
DR UCSC; uc007rvs.2; mouse.
DR CTD; 10769; -.
DR MGI; MGI:1099790; Plk2.
DR VEuPathDB; HostDB:ENSMUSG00000021701; -.
DR eggNOG; KOG0575; Eukaryota.
DR GeneTree; ENSGT00940000158739; -.
DR HOGENOM; CLU_000288_46_1_1; -.
DR InParanoid; P53351; -.
DR OMA; MPEADSN; -.
DR OrthoDB; 507604at2759; -.
DR PhylomeDB; P53351; -.
DR TreeFam; TF101089; -.
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 BioGRID-ORCS; 20620; 3 hits in 76 CRISPR screens.
DR ChiTaRS; Plk2; mouse.
DR PRO; PR:P53351; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; P53351; protein.
DR Bgee; ENSMUSG00000021701; Expressed in CA3 field of hippocampus and 274 other tissues.
DR ExpressionAtlas; P53351; baseline and differential.
DR Genevisible; P53351; MM.
DR GO; GO:0005814; C:centriole; ISS:UniProtKB.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0000785; C:chromatin; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0000922; C:spindle pole; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0043008; F:ATP-dependent protein binding; ISO:MGI.
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:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; ISS:UniProtKB.
DR GO; GO:0060292; P:long-term synaptic depression; ISS:UniProtKB.
DR GO; GO:0060291; P:long-term synaptic potentiation; ISS:UniProtKB.
DR GO; GO:0007613; P:memory; IMP:UniProtKB.
DR GO; GO:0000278; P:mitotic cell cycle; IMP:MGI.
DR GO; GO:0007052; P:mitotic spindle organization; IMP:UniProtKB.
DR GO; GO:0016525; P:negative regulation of angiogenesis; IMP:BHF-UCL.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0071866; P:negative regulation of apoptotic process in bone marrow cell; IMP:BHF-UCL.
DR GO; GO:2000773; P:negative regulation of cellular senescence; IMP:BHF-UCL.
DR GO; GO:0061000; P:negative regulation of dendritic spine development; ISO:MGI.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISO:MGI.
DR GO; GO:0010508; P:positive regulation of autophagy; ISO:MGI.
DR GO; GO:0090050; P:positive regulation of cell migration involved in sprouting angiogenesis; IMP:BHF-UCL.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; ISO:MGI.
DR GO; GO:0032092; P:positive regulation of protein binding; ISO:MGI.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0032486; P:Rap protein signal transduction; ISS:UniProtKB.
DR GO; GO:0007265; P:Ras protein signal transduction; ISS:UniProtKB.
DR GO; GO:0046599; P:regulation of centriole replication; ISS:UniProtKB.
DR GO; GO:0032465; P:regulation of cytokinesis; IBA:GO_Central.
DR GO; GO:0048167; P:regulation of synaptic plasticity; IMP:UniProtKB.
DR CDD; cd13118; POLO_box_1; 1.
DR CDD; cd13117; POLO_box_2; 1.
DR CDD; cd14188; STKc_PLK2; 1.
DR Gene3D; 3.30.1120.30; -; 2.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR042825; PLK2_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 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 ATP-binding; Cell projection; Cytoplasm; Cytoskeleton; Kinase;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Transferase; Tumor suppressor.
FT CHAIN 1..682
FT /note="Serine/threonine-protein kinase PLK2"
FT /id="PRO_0000086562"
FT DOMAIN 79..331
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 507..570
FT /note="POLO box 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00154"
FT DOMAIN 603..674
FT /note="POLO box 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00154"
FT REGION 25..67
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 403..432
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 403..417
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 202
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 85..93
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 108
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305"
FT MOD_RES 236
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:12651910"
FT MUTAGEN 108
FT /note="K->M: In DN mutant; Loss of kinase activity; leading
FT to disrupted Ras and Rap protein signaling, altered spine
FT morphology and aberrant memory formation in mice."
FT /evidence="ECO:0000269|PubMed:12651910,
FT ECO:0000269|PubMed:21382555"
FT MUTAGEN 236
FT /note="T->D,V: Does not significantly affect kinase
FT activity."
FT /evidence="ECO:0000269|PubMed:12651910,
FT ECO:0000269|PubMed:12897130"
FT MUTAGEN 236
FT /note="T->E: Mimicks phosphorylation state, leading to
FT increased activity."
FT /evidence="ECO:0000269|PubMed:12651910,
FT ECO:0000269|PubMed:12897130"
SQ SEQUENCE 682 AA; 77812 MW; 586DEABFD7208A9D CRC64;
MELLRTITYQ PAAGTKMCEQ ALGKACGGDS KKKRPQQPSE DGQPQAQVTP AAPHHHHHHS
HSGPEISRII VDPTTGKRYC RGKVLGKGGF AKCYEMTDLT NNKVYAAKII PHSRVAKPHQ
REKIDKEIEL HRLLHHKHVV QFYHYFEDKE NIYILLEYCS RRSMAHILKA RKVLTEPEVR
YYLRQIVSGL KYLHEQEILH RDLKLGNFFI NEAMELKVGD FGLAARLEPL EHRRRTICGT
PNYLSPEVLN KQGHGCESDI WALGCVMYTM LLGRPPFETT NLKETYRCIR EARYTMPSSL
LAPAKHLIAS MLSKNPEDRP SLDDIIRHDF FLQGFTPDRL SSSCCHTVPD FHLSSPAKNF
FKKAAAALFG GKKDKARYND THNKVSKEDE DIYKLRHDLK KVSITQQPSK HRADEEPQPP
PTTVARSGTS AVENKQQIGD AIRMIVRGTL GSCSSSSECL EDSTMGSVAD TVARVLRGCL
ENMPEADCIP KEQLSTSFQW VTKWVDYSNK YGFGYQLSDH TVGVLFNNGA HMSLLPDKKT
VHYYAELGQC SVFPATDAPE QFISQVTVLK YFSHYMEENL MDGGDLPSVT DIRRPRLYLL
QWLKSDKALM MLFNDGTFQV NFYHDHTKII ICNQSEEYLL TYINEDRIST TFRLTTLLMS
GCSLELKNRM EYALNMLLQR CN
