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Q9NYY3 (PLK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 134. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Serine/threonine-protein kinase PLK2

EC=2.7.11.21
Alternative name(s):
Polo-like kinase 2
Short name=PLK-2
Short name=hPlk2
Serine/threonine-protein kinase SNK
Short name=hSNK
Serum-inducible kinase
Gene names
Name:PLK2
Synonyms:SNK
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length685 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Tumor suppressor serine/threonine-protein kinase involved in synaptic plasticity, centriole duplication and G1/S phase transition. Polo-like kinases act by binding and phosphorylating proteins are that already phosphorylated on a specific motif recognized by the POLO box domains. Phosphorylates CENPJ, NPM1, RAPGEF2, RASGRF1, SNCA, SIPA1L1 and SYNGAP1. Plays a key role in synaptic plasticity and memory by regulating the Ras and Rap protein signaling: required for overactivity-dependent spine remodeling by phosphorylating the Ras activator RASGRF1 and the Rap inhibitor SIPA1L1 leading to their degradation by the proteasome. Conversely, phosphorylates the Rap activator RAPGEF2 and the Ras inhibitor SYNGAP1, promoting their activity. Also regulates synaptic plasticity independently of kinase activity, via its interaction with NSF that disrupts the interaction between NSF and the GRIA2 subunit of AMPARs, leading to a rapid rundown of AMPAR-mediated current that occludes long term depression. Required for procentriole formation and centriole duplication by phosphorylating CENPJ and NPM1, respectively. Its induction by p53/TP53 suggests that it may participate in the mitotic checkpoint following stress. Ref.7 Ref.9 Ref.11 Ref.12

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation

Activated by phosphorylation of Thr-239. Once activated, activity is stimulated by binding target proteins By similarity.

Subunit structure

Interacts with NSF; causing NSF dissociation from GRIA2. Interacts with CIB1 By similarity.

Subcellular location

Cytoplasmcytoskeletonmicrotubule organizing centercentrosomecentriole. Cell projectiondendrite By similarity. Note: Localizes to centrosomes during early G1 phase where it only associates to the mother centriole and then distributes equally to both mother and daughter centrioles at the onset of S phase. Ref.7 Ref.9

Tissue specificity

Expressed at higher level in the fetal lung, kidney, spleen and heart. Ref.1

Induction

Directly regulated by p53/TP53. Negatively regulated by miR-126. Ref.6 Ref.8 Ref.10 Ref.13

Domain

The POLO box domains act as phosphopeptide-binding module that recognize and bind serine-[phosphothreonine/phosphoserine]-(proline/X) motifs. PLK2 recognizes and binds docking proteins that are already phosphorylated on these motifs, and then phosphorylates them By similarity.

Post-translational modification

Catalytic activity is enhanced by phosphorylation of Thr-239 By similarity.

Miscellaneous

There are indications that PLK2 might act as a tumor suppressor: PLK2 is significantly down-regulated in a wide range of acute myeloid leukemias (AMLs) and B-cell lymphomas due to aberrant cytosine methylation in the CpG island located at the 5' of the PLK2 gene (Ref.8, Ref.13). Moreover, miR-126, a microRNA that negatively regulates PLK2 is up-regulated in AMLs, suggesting that PLK2 down-regulation by miR-126 could also contribute to leukemogenesis (Ref.10).

Sequence similarities

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. CDC5/Polo subfamily.

Contains 2 POLO box domains.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Cellular componentCell projection
Cytoplasm
Cytoskeleton
   Coding sequence diversityPolymorphism
   DiseaseTumor suppressor
   DomainRepeat
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG1/S transition of mitotic cell cycle

Inferred from mutant phenotype Ref.7. Source: UniProtKB

Rap protein signal transduction

Inferred from sequence or structural similarity. Source: UniProtKB

Ras protein signal transduction

Inferred from sequence or structural similarity. Source: UniProtKB

long term synaptic depression

Inferred from sequence or structural similarity. Source: UniProtKB

long-term synaptic potentiation

Inferred from sequence or structural similarity. Source: UniProtKB

memory

Inferred from sequence or structural similarity. Source: UniProtKB

mitotic cell cycle checkpoint

Inferred from sequence or structural similarity. Source: UniProtKB

mitotic spindle organization

Inferred from direct assay Ref.9. Source: UniProtKB

negative regulation of apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of I-kappaB kinase/NF-kappaB signaling

Inferred from mutant phenotype PubMed 12761501. Source: UniProtKB

positive regulation of proteasomal ubiquitin-dependent protein catabolic process

Inferred from electronic annotation. Source: Ensembl

protein phosphorylation

Inferred from direct assay Ref.12. Source: UniProtKB

regulation of centriole replication

Inferred from direct assay Ref.9Ref.12Ref.11. Source: UniProtKB

regulation of synaptic plasticity

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcentriole

Inferred from direct assay Ref.9. Source: UniProtKB

centrosome

Inferred from direct assay Ref.7. Source: UniProtKB

dendrite

Inferred from sequence or structural similarity. Source: UniProtKB

intracellular

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction Ref.12Ref.11. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from direct assay Ref.9Ref.12Ref.11. Source: UniProtKB

signal transducer activity

Inferred from mutant phenotype PubMed 12761501. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CENPJQ9HC773EBI-721354,EBI-946194

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 685685Serine/threonine-protein kinase PLK2
PRO_0000086561

Regions

Domain82 – 334253Protein kinase
Domain510 – 57364POLO box 1
Domain606 – 67772POLO box 2
Nucleotide binding88 – 969ATP By similarity
Compositional bias57 – 648Poly-His

Sites

Active site2051Proton acceptor By similarity
Binding site1111ATP By similarity

Amino acid modifications

Modified residue2391Phosphothreonine By similarity

Natural variations

Natural variant141S → T in an ovarian Endometrioid carcinoma sample; somatic mutation. Ref.15
VAR_041023
Natural variant921G → S in a lung adenocarcinoma sample; somatic mutation. Ref.15
VAR_041024
Natural variant4361E → K. Ref.15
Corresponds to variant rs55768901 [ dbSNP | Ensembl ].
VAR_041025
Natural variant4871P → L. Ref.15
Corresponds to variant rs55645589 [ dbSNP | Ensembl ].
VAR_041026

Experimental info

Mutagenesis2101N → A: Loss of kinase activity. Ref.9
Mutagenesis5031W → F: Impairs localization to the centrosome and centriole duplication; when associated with A-629 and M-631. Ref.9
Mutagenesis6291H → A: Impairs localization to the centrosome and centriole duplication; when associated with F-503 and M-631. Ref.9
Mutagenesis6311K → M: Impairs localization to the centrosome and centriole duplication; when associated with F-503 and A-631. Ref.9
Sequence conflict281A → G in AAC14573. Ref.1

Secondary structure

................................................ 685
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9NYY3 [UniParc].

Last modified August 2, 2002. Version 3.
Checksum: 6429F6EFD830B333

FASTA68578,237
        10         20         30         40         50         60 
MELLRTITYQ PAASTKMCEQ ALGKGCGADS KKKRPPQPPE ESQPPQSQAQ VPPAAPHHHH 

        70         80         90        100        110        120 
HHSHSGPEIS RIIVDPTTGK RYCRGKVLGK GGFAKCYEMT DLTNNKVYAA KIIPHSRVAK 

       130        140        150        160        170        180 
PHQREKIDKE IELHRILHHK HVVQFYHYFE DKENIYILLE YCSRRSMAHI LKARKVLTEP 

       190        200        210        220        230        240 
EVRYYLRQIV SGLKYLHEQE ILHRDLKLGN FFINEAMELK VGDFGLAARL EPLEHRRRTI 

       250        260        270        280        290        300 
CGTPNYLSPE VLNKQGHGCE SDIWALGCVM YTMLLGRPPF ETTNLKETYR CIREARYTMP 

       310        320        330        340        350        360 
SSLLAPAKHL IASMLSKNPE DRPSLDDIIR HDFFLQGFTP DRLSSSCCHT VPDFHLSSPA 

       370        380        390        400        410        420 
KNFFKKAAAA LFGGKKDKAR YIDTHNRVSK EDEDIYKLRH DLKKTSITQQ PSKHRTDEEL 

       430        440        450        460        470        480 
QPPTTTVARS GTPAVENKQQ IGDAIRMIVR GTLGSCSSSS ECLEDSTMGS VADTVARVLR 

       490        500        510        520        530        540 
GCLENMPEAD CIPKEQLSTS FQWVTKWVDY SNKYGFGYQL SDHTVGVLFN NGAHMSLLPD 

       550        560        570        580        590        600 
KKTVHYYAEL GQCSVFPATD APEQFISQVT VLKYFSHYME ENLMDGGDLP SVTDIRRPRL 

       610        620        630        640        650        660 
YLLQWLKSDK ALMMLFNDGT FQVNFYHDHT KIIICSQNEE YLLTYINEDR ISTTFRLTTL 

       670        680 
LMSGCSSELK NRMEYALNML LQRCN 

« Hide

References

« Hide 'large scale' references
[1]"Identification of the human homologue of the early-growth response gene Snk, encoding a serum-inducible kinase."
Liby K., Wu H., Ouyang B., Wu S., Chen J., Dai W.
DNA Seq. 11:527-533(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
[2]"Identification and characterization of human serum-inducible kinase (SNK), a novel member of the polo-kinase family of cell cycle regulators: potential implication for regulation of vascular smooth muscle proliferation."
Anderson K.M., Nerurkar S.S., Hansbury M.J., Fornwald J., Scott G., Bouzyk M., Mui P., Imbrugia C.S., Carlson K., Marshall L.A., Roshak A.K.
Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Colon.
[3]"The DNA sequence and comparative analysis of human chromosome 5."
Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. expand/collapse author list , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Skin.
[5]Fidler C., Boultwood J., Wang Jabs E., Wainscoat J.S.
Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 110-408.
[6]"Radiation-inducible hSNK gene is transcriptionally regulated by p53 binding homology element in human thyroid cells."
Shimizu-Yoshida Y., Sugiyama K., Rogounovitch T., Ohtsuru A., Namba H., Saenko V., Yamashita S.
Biochem. Biophys. Res. Commun. 289:491-498(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[7]"Polo-like kinase-2 is required for centriole duplication in mammalian cells."
Warnke S., Kemmler S., Hames R.S., Tsai H.L., Hoffmann-Rohrer U., Fry A.M., Hoffmann I.
Curr. Biol. 14:1200-1207(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[8]"Transcriptional silencing of Polo-like kinase 2 (SNK/PLK2) is a frequent event in B-cell malignancies."
Syed N., Smith P., Sullivan A., Spender L.C., Dyer M., Karran L., O'Nions J., Allday M., Hoffmann I., Crawford D., Griffin B., Farrell P.J., Crook T.
Blood 107:250-256(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: DOWN-REGULATION IN B-CELL LYMPHOMAS.
[9]"Plk2 regulated centriole duplication is dependent on its localization to the centrioles and a functional polo-box domain."
Cizmecioglu O., Warnke S., Arnold M., Duensing S., Hoffmann I.
Cell Cycle 7:3548-3555(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF ASN-210; TRP-503; HIS-629 AND LYS-631.
[10]"Distinct microRNA expression profiles in acute myeloid leukemia with common translocations."
Li Z., Lu J., Sun M., Mi S., Zhang H., Luo R.T., Chen P., Wang Y., Yan M., Qian Z., Neilly M.B., Jin J., Zhang Y., Bohlander S.K., Zhang D.E., Larson R.A., Le Beau M.M., Thirman M.J. expand/collapse author list , Golub T.R., Rowley J.D., Chen J.
Proc. Natl. Acad. Sci. U.S.A. 105:15535-15540(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[11]"PLK2 phosphorylation is critical for CPAP function in procentriole formation during the centrosome cycle."
Chang J., Cizmecioglu O., Hoffmann I., Rhee K.
EMBO J. 29:2395-2406(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF CENPJ.
[12]"Polo-like kinase 2-dependent phosphorylation of NPM/B23 on serine 4 triggers centriole duplication."
Krause A., Hoffmann I.
PLoS ONE 5:E9849-E9849(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF NPM.
[13]"Polo-like kinase 2 (SNK/PLK2) is a novel epigenetically regulated gene in acute myeloid leukemia and myelodysplastic syndromes: genetic and epigenetic interactions."
Benetatos L., Dasoula A., Hatzimichael E., Syed N., Voukelatou M., Dranitsaris G., Bourantas K.L., Crook T.
Ann. Hematol. 90:1037-1045(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: DOWN-REGULATION IN ACUTE MYELOID LEUKEMIA.
[14]"Multifaceted polo-like kinases: drug targets and antitargets for cancer therapy."
Strebhardt K.
Nat. Rev. Drug Discov. 9:643-660(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[15]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] THR-14; SER-92; LYS-436 AND LEU-487.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF059617 mRNA. Translation: AAC14573.1.
AF223574 mRNA. Translation: AAF62897.1.
U85755 mRNA. Translation: AAD00575.1.
AC008814 Genomic DNA. No translation available.
BC013879 mRNA. Translation: AAH13879.1.
CCDSCCDS3974.1.
RefSeqNP_001239155.1. NM_001252226.1.
NP_006613.2. NM_006622.3.
UniGeneHs.398157.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4I5MX-ray1.80A57-360[»]
4I5PX-ray1.74A57-360[»]
4I6BX-ray1.80A57-360[»]
4I6FX-ray2.90A57-360[»]
4I6HX-ray1.91A57-360[»]
ProteinModelPortalQ9NYY3.
SMRQ9NYY3. Positions 71-354, 503-680.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115988. 11 interactions.
DIPDIP-48943N.
IntActQ9NYY3. 8 interactions.
MINTMINT-1397390.
STRING9606.ENSP00000274289.

Chemistry

BindingDBQ9NYY3.
ChEMBLCHEMBL5938.
GuidetoPHARMACOLOGY2169.

PTM databases

PhosphoSiteQ9NYY3.

Polymorphism databases

DMDM22096374.

Proteomic databases

MaxQBQ9NYY3.
PaxDbQ9NYY3.
PRIDEQ9NYY3.

Protocols and materials databases

DNASU10769.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000274289; ENSP00000274289; ENSG00000145632.
GeneID10769.
KEGGhsa:10769.
UCSCuc003jrn.3. human.

Organism-specific databases

CTD10769.
GeneCardsGC05M057749.
HGNCHGNC:19699. PLK2.
HPACAB009624.
MIM607023. gene.
neXtProtNX_Q9NYY3.
PharmGKBPA134940798.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000248546.
HOVERGENHBG001843.
InParanoidQ9NYY3.
KOK08861.
OMARHEFFLQ.
OrthoDBEOG78M01K.
PhylomeDBQ9NYY3.
TreeFamTF101089.

Enzyme and pathway databases

BRENDA2.7.11.21. 2681.
SignaLinkQ9NYY3.

Gene expression databases

BgeeQ9NYY3.
CleanExHS_PLK2.
GenevestigatorQ9NYY3.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000959. POLO_box_duplicated_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
PF00659. POLO_box. 2 hits.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS50078. POLO_BOX. 2 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiPLK2.
GenomeRNAi10769.
NextBio40893.
PROQ9NYY3.
SOURCESearch...

Entry information

Entry namePLK2_HUMAN
AccessionPrimary (citable) accession number: Q9NYY3
Secondary accession number(s): O60679, Q96CV7, Q9UE61
Entry history
Integrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: August 2, 2002
Last modified: July 9, 2014
This is version 134 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM