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   27-MAR-2024, entry version 183.
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 that are
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       recognizes and binds serine-[phosphothreonine/phosphoserine]-
CC       (proline/X) motifs. PLK2 recognizes and binds docking proteins that are
CC       already phosphorylated on these motifs, and then phosphorylates them
CC       (By 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; 10090-ENSMUSP00000022212; -.
DR   ProteomicsDB; 289545; -.
DR   Antibodypedia; 4042; 298 antibodies from 32 providers.
DR   DNASU; 20620; -.
DR   Ensembl; ENSMUST00000022212.9; ENSMUSP00000022212.8; ENSMUSG00000021701.9.
DR   GeneID; 20620; -.
DR   KEGG; mmu:20620; -.
DR   UCSC; uc007rvs.2; mouse.
DR   AGR; MGI:1099790; -.
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; QRRRTIC; -.
DR   OrthoDB; 5471704at2759; -.
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 81 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 278 other cell types or tissues.
DR   ExpressionAtlas; P53351; baseline and differential.
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:0000776; C:kinetochore; IBA:GO_Central.
DR   GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
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:0051117; F:ATPase binding; ISO:MGI.
DR   GO; GO:0032050; F:clathrin heavy chain binding; ISO:MGI.
DR   GO; GO:0051020; F:GTPase binding; ISO:MGI.
DR   GO; GO:0019901; F:protein kinase 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:0090394; P:negative regulation of excitatory postsynaptic potential; ISO:MGI.
DR   GO; GO:2000009; P:negative regulation of protein localization to cell surface; 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:0045732; P:positive regulation of protein catabolic process; ISO:MGI.
DR   GO; GO:0002092; P:positive regulation of receptor internalization; 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: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; POLO box domain; 2.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
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   PANTHER; PTHR24345; SERINE/THREONINE-PROTEIN KINASE PLK; 1.
DR   PANTHER; PTHR24345:SF44; SERINE_THREONINE-PROTEIN KINASE PLK2; 1.
DR   Pfam; PF00069; Pkinase; 1.
DR   Pfam; PF00659; POLO_box; 2.
DR   SMART; SM00220; S_TKc; 1.
DR   SUPFAM; SSF82615; Polo-box domain; 2.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 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.
DR   Genevisible; P53351; MM.
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          500..578
FT                   /note="POLO box 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00154"
FT   DOMAIN          598..682
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
//