Q9NYY3 (PLK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	685 AA.
Sequence status	Complete.
Protein existence	Evidence 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	Cytoplasm › cytoskeleton › centrosome › centriole. Cell projection › dendrite 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 component	Cell projection Cytoplasm Cytoskeleton
Coding sequence diversity	Polymorphism
Disease	Tumor suppressor
Domain	Repeat
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G1/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 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 cascade Inferred from mutant phenotype PubMed 12761501. Source: UniProtKB regulation of centriole replication Inferred from direct assay Ref.9Ref.12Ref.11. Source: UniProtKB
Cellular_component	centriole Inferred from direct assay Ref.9. Source: UniProtKB dendrite Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW 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...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 685	685	Serine/threonine-protein kinase PLK2		PRO_0000086561
Regions
	Domain	82 – 334	253	Protein kinase
	Domain	510 – 573	64	POLO box 1
	Domain	606 – 677	72	POLO box 2
	Nucleotide binding	88 – 96	9	ATP By similarity
	Compositional bias	57 – 64	8	Poly-His
Sites
	Active site	205	1	Proton acceptor By similarity
	Binding site	111	1	ATP By similarity
Amino acid modifications
	Modified residue	239	1	Phosphothreonine By similarity
Natural variations
	Natural variant	14	1	S → T in an ovarian Endometrioid carcinoma sample; somatic mutation. Ref.15		VAR_041023
	Natural variant	92	1	G → S in a lung adenocarcinoma sample; somatic mutation. Ref.15		VAR_041024
	Natural variant	436	1	E → K. Ref.15 Corresponds to variant rs55768901 [ dbSNP | Ensembl ].		VAR_041025
	Natural variant	487	1	P → L. Ref.15 Corresponds to variant rs55645589 [ dbSNP | Ensembl ].		VAR_041026
Experimental info
	Mutagenesis	210	1	N → A: Loss of kinase activity. Ref.9
	Mutagenesis	503	1	W → F: Impairs localization to the centrosome and centriole duplication; when associated with A-629 and M-631. Ref.9
	Mutagenesis	629	1	H → A: Impairs localization to the centrosome and centriole duplication; when associated with F-503 and M-631. Ref.9
	Mutagenesis	631	1	K → M: Impairs localization to the centrosome and centriole duplication; when associated with F-503 and A-631. Ref.9
	Sequence conflict	28	1	A → G in AAC14573. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q9NYY3 [UniParc]. Last modified August 2, 2002. Version 3. Checksum: 6429F6EFD830B333	FASTA	685	78,237
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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.
IPI	IPI00302787.
RefSeq	NP_001239155.1. NM_001252226.1. NP_006613.2. NM_006622.3.
UniGene	Hs.398157. Hs.658132.
3D structure databases
ProteinModelPortal	Q9NYY3.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-48943N.
IntAct	Q9NYY3. 7 interactions.
MINT	MINT-1397390.
STRING	9606.ENSP00000274289.
PTM databases
PhosphoSite	Q9NYY3.
Polymorphism databases
DMDM	22096374.
Proteomic databases
PaxDb	Q9NYY3.
PRIDE	Q9NYY3.
Protocols and materials databases
DNASU	10769.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000274289; ENSP00000274289; ENSG00000145632.
GeneID	10769.
KEGG	hsa:10769.
UCSC	uc003jrn.3. human.
Organism-specific databases
CTD	10769.
GeneCards	GC05M057749.
HGNC	HGNC:19699. PLK2.
HPA	CAB009624.
MIM	607023. gene.
neXtProt	NX_Q9NYY3.
PharmGKB	PA134940798.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000248546.
HOVERGEN	HBG001843.
InParanoid	Q9NYY3.
KO	K08861.
OMA	DDIIRHE.
OrthoDB	EOG480HW8.
PhylomeDB	Q9NYY3.
Enzyme and pathway databases
BRENDA	2.7.11.21. 2681.
SignaLink	Q9NYY3.
Gene expression databases
Bgee	Q9NYY3.
CleanEx	HS_PLK2.
Genevestigator	Q9NYY3.
GermOnline	ENSG00000145632. Homo sapiens.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000959. POLO_box_duplicated_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR002290. Ser/Thr_dual-sp_kinase_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. PF00659. POLO_box. 2 hits. [Graphical view]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS50078. POLO_BOX. 2 hits. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q9NYY3.
ChEMBL	CHEMBL5938.
GenomeRNAi	10769.
NextBio	40893.
SOURCE	Search...

Entry information

Entry name

PLK2_HUMAN

Accession

Primary (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:	May 29, 2013
This is version 122 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.