P53351 (PLK2_MOUSE) 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
Serine/threonine-protein kinase SNK
Serum-inducible kinase

Gene names

Name:	Plk2
Synonyms:	Snk

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	682 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.2 Ref.3 Ref.5 Ref.6
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	Activated by phosphorylation of Thr-236. Once activated, activity is stimulated by binding target proteins By similarity.
Subunit structure	Interacts with NSF; causing NSF dissociation from GRIA2 By similarity. Interacts with CIB1.
Subcellular location	Cytoplasm › cytoskeleton › centrosome › centriole By similarity. 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 By similarity.
Tissue specificity	Brain, lung and heart. Ref.1
Developmental stage	Expressed in early G1, during G0-G1 transition as well as in cycling cells. Ref.2
Induction	Directly regulated by p53/TP53. Induced by serum and phorbol ester. Ref.1 Ref.3
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-236.
Disruption phenotype	Embryos display a delay in skeletal development and retarded growth. Embryonic fibroblasts proliferated slowly and displayed a delayed entry into S phase. Mice display loss of dendritic spines and impaired memory formation. Ref.4 Ref.6
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
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 sequence or structural similarity. 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 mutant phenotype Ref.6. Source: UniProtKB mitotic cell cycle checkpoint Inferred from mutant phenotype Ref.3. Source: UniProtKB mitotic spindle organization Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of apoptotic process Inferred from mutant phenotype Ref.3. Source: UniProtKB positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from electronic annotation. Source: Compara regulation of centriole replication Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	centriole Inferred from sequence or structural similarity. 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.3. Source: UniProtKB signal transducer activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 682	682	Serine/threonine-protein kinase PLK2		PRO_0000086562
Regions
	Domain	79 – 331	253	Protein kinase
	Domain	507 – 570	64	POLO box 1
	Domain	603 – 674	72	POLO box 2
	Nucleotide binding	85 – 93	9	ATP By similarity
	Compositional bias	54 – 59	6	Poly-His
Sites
	Active site	202	1	Proton acceptor By similarity
	Binding site	108	1	ATP Probable
Amino acid modifications
	Modified residue	236	1	Phosphothreonine Ref.2
Experimental info
	Mutagenesis	108	1	K → M in DN mutant; Loss of kinase activity; leading to disrupted Ras and Rap protein signaling, altered spine morphology and aberrant memory formation in mice. Ref.2 Ref.6
	Mutagenesis	236	1	T → D or V: Does not significantely affect kinase activity. Ref.2 Ref.3
	Mutagenesis	236	1	T → E: Mimicks phosphorylation state, leading to increased activity. Ref.2 Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P53351 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 586DEABFD7208A9D	FASTA	682	77,812
	10 20 30 40 50 60 MELLRTITYQ PAAGTKMCEQ ALGKACGGDS KKKRPQQPSE DGQPQAQVTP AAPHHHHHHS 70 80 90 100 110 120 HSGPEISRII VDPTTGKRYC RGKVLGKGGF AKCYEMTDLT NNKVYAAKII PHSRVAKPHQ 130 140 150 160 170 180 REKIDKEIEL HRLLHHKHVV QFYHYFEDKE NIYILLEYCS RRSMAHILKA RKVLTEPEVR 190 200 210 220 230 240 YYLRQIVSGL KYLHEQEILH RDLKLGNFFI NEAMELKVGD FGLAARLEPL EHRRRTICGT 250 260 270 280 290 300 PNYLSPEVLN KQGHGCESDI WALGCVMYTM LLGRPPFETT NLKETYRCIR EARYTMPSSL 310 320 330 340 350 360 LAPAKHLIAS MLSKNPEDRP SLDDIIRHDF FLQGFTPDRL SSSCCHTVPD FHLSSPAKNF 370 380 390 400 410 420 FKKAAAALFG GKKDKARYND THNKVSKEDE DIYKLRHDLK KVSITQQPSK HRADEEPQPP 430 440 450 460 470 480 PTTVARSGTS AVENKQQIGD AIRMIVRGTL GSCSSSSECL EDSTMGSVAD TVARVLRGCL 490 500 510 520 530 540 ENMPEADCIP KEQLSTSFQW VTKWVDYSNK YGFGYQLSDH TVGVLFNNGA HMSLLPDKKT 550 560 570 580 590 600 VHYYAELGQC SVFPATDAPE QFISQVTVLK YFSHYMEENL MDGGDLPSVT DIRRPRLYLL 610 620 630 640 650 660 QWLKSDKALM MLFNDGTFQV NFYHDHTKII ICNQSEEYLL TYINEDRIST TFRLTTLLMS 670 680 GCSLELKNRM EYALNMLLQR CN

References

[1]	"Identification of an early-growth-response gene encoding a novel putative protein kinase." Simmons D.L., Neel B.G., Stevens R., Evett G., Erikson R.L. Mol. Cell. Biol. 12:4164-4169(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, INDUCTION.
[2]	"The serum-inducible protein kinase Snk is a G1 phase polo-like kinase that is inhibited by the calcium- and integrin-binding protein CIB." Ma S., Liu M.A., Yuan Y.L., Erikson R.L. Mol. Cancer Res. 1:376-384(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DEVELOPMENTAL STAGE, PHOSPHORYLATION AT THR-236, MUTAGENESIS OF LYS-108 AND THR-236.
[3]	"Silencing of the novel p53 target gene Snk/Plk2 leads to mitotic catastrophe in paclitaxel (taxol)-exposed cells." Burns T.F., Fei P., Scata K.A., Dicker D.T., El-Deiry W.S. Mol. Cell. Biol. 23:5556-5571(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INDUCTION, MUTAGENESIS OF THR-236.
[4]	"Role of Plk2 (Snk) in mouse development and cell proliferation." Ma S., Charron J., Erikson R.L. Mol. Cell. Biol. 23:6936-6943(2003) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE.
[5]	"Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system." Inglis K.J., Chereau D., Brigham E.F., Chiou S.S., Schobel S., Frigon N.L., Yu M., Caccavello R.J., Nelson S., Motter R., Wright S., Chian D., Santiago P., Soriano F., Ramos C., Powell K., Goldstein J.M., Babcock M. , Yednock T., Bard F., Basi G.S., Sham H., Chilcote T.J., McConlogue L., Griswold-Prenner I., Anderson J.P. J. Biol. Chem. 284:2598-2602(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF SNCA.
[6]	"Requirement for Plk2 in orchestrated ras and rap signaling, homeostatic structural plasticity, and memory." Lee K.J., Lee Y., Rozeboom A., Lee J.Y., Udagawa N., Hoe H.S., Pak D.T. Neuron 69:957-973(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF LYS-108, DISRUPTION PHENOTYPE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M96163 mRNA. No translation available.
IPI	IPI00314845.
PIR	A44493.
RefSeq	NP_690017.2. NM_152804.2.
UniGene	Mm.380.
3D structure databases
ProteinModelPortal	P53351.
SMR	P53351. Positions 65-350, 500-677.
ModBase	Search...
Protein-protein interaction databases
IntAct	P53351. 1 interaction.
PTM databases
PhosphoSite	P53351.
Proteomic databases
PRIDE	P53351.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000022212; ENSMUSP00000022212; ENSMUSG00000021701.
GeneID	20620.
KEGG	mmu:20620.
UCSC	uc007rvs.2. mouse.
Organism-specific databases
CTD	10769.
MGI	MGI:1099790. Plk2.
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000248546.
HOVERGEN	HBG001843.
InParanoid	P53351.
KO	K08861.
OMA	DDIIRHE.
OrthoDB	EOG480HW8.
Enzyme and pathway databases
BRENDA	2.7.11.21. 3474.
Gene expression databases
ArrayExpress	P53351.
Bgee	P53351.
CleanEx	MM_PLK2.
Genevestigator	P53351.
GermOnline	ENSMUSG00000021701. Mus musculus.
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
NextBio	299009.
SOURCE	Search...

Entry information

Entry name

PLK2_MOUSE

Accession

Primary (citable) accession number: P53351

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	May 29, 2013
This is version 111 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program