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Updated November 2019

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Nomenclature

Short Name:
PLK2
Full Name:
Serine-threonine-protein kinase PLK2
Alias:
  • EC 2.7.11.21
  • SNK
  • Polo-like kinase 2
  • Serine/threonine-protein kinase SNK
  • Serum inducible kinase
  • Serum-inducible kinase

Classification

Type:
Protein-serine/threonine kinase
Group:
Other
Family:
PLK
SubFamily:
NA
 
 

Specific Links

Entrez-Gene Entry: 10769
Entrez-Protein Entry: NP_006613
GeneCards Entry: SNK
KinBASE Entry: PLK2
OMIM Entry: 607023
Pfam Entry: Q9NYY3
PhosphoNET Entry: Q9NYY3
Phosphosite Plus Entry: 815
Source Entry: SNK
UCSD-Nature Entry: A001848
UniProt Entry: Q9NYY3

General Links

ClustalW2
GPS-Cuckoo
Human Protein Atlas
Kinase.com
Kinase Research
Kinasource
Kinomer
Netphorest
NetworKIN
Phosida
PhosphoElm
Protein Blast
ScanSite
String

Structure

Mol. Mass (Da):
78,237
# Amino Acids:
685
# mRNA Isoforms:
1
mRNA Isoforms:
78,237 Da (685 AA; Q9NYY3)
4D Structure:
NA
1D Structure:
Retrieve Gene Sequence
Retrieve Full Protein Sequence
Retrieve Catalytic Domain Sequence
 
3D Image (rendered using PV Viewer):

PDB ID
4I5M

Subfamily Alignment
subfamily domain
 
Domain Distribution:
Start End Domain
82 334 Pkinase
510 573 POLO_box
606 677 POLO_box
 

Post-translation Modifications

For detailed information on phosphorylation of this kinase go to PhosphoNET
Methylated:
K366.
Threonine phosphorylated:

T100+, T239+, T243-.
Tyrosine phosphorylated:

Y108, Y184, Y185+, Y246-, Y271, Y297.
Ubiquitinated:
K207, K317, K375, K390, K438.
 

Distribution

Based on gene microarray analysis from the NCBI
Human Tissue Distribution
% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:
% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:
  • adipose
    11

    822

    16

    970

  • adrenal
    0.3

    24

    10

    11

  • bladder
    23

    1672

    13

    3479

  • brain
    15

    1076

    58

    1160

  • breast
    17

    1207

    14

    796

  • cervix
    2

    147

    41

    158

  • colon
    4

    279

    19

    476

  • heart
    14

    1040

    32

    1589

  • intestine
    4

    325

    10

    317

  • kidney
    5

    375

    57

    2024

  • liver
    11

    779

    25

    2662

  • lung
    13

    929

    107

    1188

  • lymphnode
    11

    817

    24

    2428

  • ovary
    0.8

    61

    9

    25

  • pancreas
    9

    669

    23

    1294

  • pituitary
    0.4

    31

    8

    21

  • prostate
    3

    217

    113

    1196

  • salivarygland
    14

    1030

    20

    1977

  • skeletalmuscle"
    3

    192

    55

    685

  • skin
    12

    860

    56

    817

  • spinalcord
    11

    784

    22

    2716

  • spleen
    30

    2204

    24

    3761

  • stomach
    17

    1228

    14

    2605

  • testis
    21

    1494

    20

    2192

  • thymus
    10

    699

    22

    2283

  • thyroid
    12

    899

    40

    1514

  • tonsil
    9

    624

    27

    1933

  • trachea
    20

    1431

    20

    2688

  • uterus
    21

    1555

    20

    2736

  • reticulocytes"
    0.2

    15

    14

    9

  • t-lymphocytes
    5

    398

    18

    292

  • b-lymphocytes
    100

    7273

    21

    11775

  • neutrophils
    11

    782

    52

    1060

  • macrophages
    12

    876

    26

    762

  • sperm
    6

    416

    22

    432

 

Evolution

Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
  • tableheader
    100

    100

    100
  • tableheader
    0

    0

    100
  • tableheader
    97.3

    97.3

    100
  • tableheader
    -

    -

    98
  • tableheader
    -

    -

    99
  • tableheader
    97.6

    98.2

    97
  • tableheader
    -

    -

    -
  • tableheader
    96.7

    97.5

    97
  • tableheader
    97

    97.8

    97
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    86.7

    91.2

    89
  • tableheader
    37.5

    57.3

    84
  • tableheader
    -

    -

    77
  • tableheader
    -

    -

    -
  • tableheader
    33.2

    54.8

    -
  • tableheader
    -

    -

    -
  • tableheader
    27

    44.9

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    31

    50.6

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    31.7

    50

    -
  • tableheader
    -

    -

    -
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
 

Regulation

Activation:
NA
Inhibition:
NA
Synthesis:
NA
Degradation:
NA
 

Known Downstream Substrates

For further details on these substrates click on the Substrate Short Name or UniProt ID. Phosphosite Location is hyperlinked to PhosphoNET predictions.
Based on in vitro and/or in vivo phosphorylation data

Substrate Short Name UniProt ID (Human) Phosphosite Location Phosphosite Sequence Effect of Phosphorylation
SNCA P37840 S129 NEAYEMPSEEGYQDY
 

Protein Kinase Specificity

Matrix of observed frequency (%) of amino acids in aligned protein substrate phosphosites

Kinections GIF
Matrix Type:
Predicted from the application of the Kinexus Kinase Substrate Predictor Version 2.0 algorithm, which was trained with over 10,000 kinase-protein substrate pairs and 8,000 kinase-peptide substrate pairs.
Domain #:
1
 

Inhibitors

For further details on these inhibitors click on the Compound Name and enter it into DrugKiNET or click on the ID's
Based on in vitro and/or in vivo phosphorylation data
Compound Name KD, Ki or IC50 (nM) PubChem ID ChEMBL ID PubMed ID
BI2536 Kd = 810 pM 11364421 513909 22037378
Volasertib IC50 = 5 nM 10461508 19383823
R406 Kd = 34 nM 11984591 22037378
Staurosporine IC50 = 197 nM 5279 19397322
PDK1/Akt/Flt Dual Pathway Inhibitor IC50 > 250 nM 5113385 599894 22037377
Novonex IC50 = 260 nM 23696523 15766665
Lestaurtinib Kd = 330 nM 126565 22037378
TBCA IC50 = 500 nM 1095828 22037377
Wortmannin IC50 = 500 nM 312145 428496 22037377
Dovitinib Kd = 570 nM 57336746 22037378
Bosutinib Kd = 960 nM 5328940 288441 22037378
AG-E-60384 IC50 > 1 µM 6419741 413188 22037377
Icotinib IC50 > 1 µM 22024915 22112293
SB218078 IC50 > 1 µM 447446 289422 22037377
WZ3146 Kd > 1 µM 44607360 20033049
WZ4002 Kd > 1 µM 44607530 20033049
NVP-TAE684 Kd = 1.2 µM 16038120 509032 22037378
Ruxolitinib Kd = 1.5 µM 25126798 1789941 22037378
CHEMBL1240703 Kd = 2 µM 52945601 1240703 19654408
TG101348 Kd = 2.4 µM 16722836 1287853 22037378
MK5108 IC50 > 3 µM 24748204 20053775
SureCN4875304 IC50 > 3.5 µM 46871765 20472445
Sunitinib Kd = 4.7 µM 5329102 535 19654408
 

Disease Linkage

General Disease Association:

Cancer
Specific Cancer Types:
Burkitt lymphomas (BL); B-cell lymphomas
Comments:
PLK2 might be a tumour suppressor protein (TSP) that has a role in the duplication of centrioles, G1/S phase transition, and synaptic plasticity. The synaptic plasticity modulation is a kinase phosphotransferase activity-independent activity. Burkitt Lymphoma (BL) is a B-cell lymphoma where cells in the tumour originally arise from one cell. All of the resulting B cells would theoretically have the same IgH gene.
 
Gene Expression in Cancers:

TranscriptoNET (www.transcriptonet.ca) analysis with mRNA expression data retrieved from the National Center for Biotechnology Information's Gene Expression Omnibus (GEO) database, which was normalized against 60 abundantly and commonly found proteins, indicated altered expression for this protein kinase as shown here as the percent change from normal tissue controls (%CFC) as supported with the Student T-test in the following types of human cancers: Bladder carcinomas (%CFC= +93, p<0.034); Cervical epithelial cancer (%CFC= +52, p<0.047); Cervical cancer (%CFC= +175, p<(0.0003); Clear cell renal cell carcinomas (cRCC) (%CFC= +204, p<0.024); Colorectal adenocarcinomas (early onset) (%CFC= +53, p<0.026); Malignant pleural mesotheliomas (MPM) tumours (%CFC= +233, p<0.0001); Ovary adenocarcinomas (%CFC= -45, p<0.004); Skin melanomas - malignant (%CFC= -53, p<0.012); and Skin squamous cell carcinomas (%CFC= +67, p<0.073). The COSMIC website notes an up-regulated expression score for PLK2 in diverse human cancers of 310, which is 0.7-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 0 for this protein kinase in human cancers was 100% lower than the average score of 60 for the human protein kinases.
Mutagenesis Experiments:

Insertional mutagenesis studies in mice have not yet revealed a role for this protein kinase in mouse cancer oncogenesis. PLK2 phosphotransferase activity can be abrogated with an N210A mutation. The W503F, H629A, and K631M mutations, in conjunction, lead to impaired centrosome localization of PLK2 and impaired centriole duplication.
Mutation Rate in All Cancers:

Percent mutation rates per 100 amino acids length in human cancers: 0.08 % in 24802 diverse cancer specimens. This rate is very similar (+ 3% higher) to the average rate of 0.075 % calculated for human protein kinases in general.
Mutation Rate in Specific Cancers:

Highest percent mutation rates per 100 amino acids length in human cancers: 0.45 % in 1093 large intestine cancers tested; 0.34 % in 602 endometrium cancers tested; 0.29 % in 805 skin cancers tested; 0.12 % in 1670 lung cancers tested; 0.11 % in 1270 liver cancers tested.
Frequency of Mutated Sites:

None > 7 in 20,085 cancer specimens
Comments:
Eleven deletion mutations as well as 3 insertions mutations observed at L335, which is at the end of the protein kinase catalytic domain.
 
COSMIC Entry:
PLK2
OMIM Entry:
607023
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