Target Information
| Target General Information | Top | |||||
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| Target ID |
T59654
(Former ID: TTDI02482)
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| Target Name |
Polo-like kinase 2 (PLK2)
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| Synonyms |
hSNK; hPlk2; Serum-inducible kinase; Serine/threonine-protein kinase SNK; Serine/threonine-protein kinase PLK2; SNK; PLK-2
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| Gene Name |
PLK2
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| Target Type |
Patented-recorded target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | |||||
| Function |
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. Tumor suppressor serine/threonine-protein kinase involved in synaptic plasticity, centriole duplication and G1/S phase transition.
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| BioChemical Class |
Kinase
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| UniProt ID | ||||||
| EC Number |
EC 2.7.11.21
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| Sequence |
MELLRTITYQPAASTKMCEQALGKGCGADSKKKRPPQPPEESQPPQSQAQVPPAAPHHHH
HHSHSGPEISRIIVDPTTGKRYCRGKVLGKGGFAKCYEMTDLTNNKVYAAKIIPHSRVAK PHQREKIDKEIELHRILHHKHVVQFYHYFEDKENIYILLEYCSRRSMAHILKARKVLTEP EVRYYLRQIVSGLKYLHEQEILHRDLKLGNFFINEAMELKVGDFGLAARLEPLEHRRRTI CGTPNYLSPEVLNKQGHGCESDIWALGCVMYTMLLGRPPFETTNLKETYRCIREARYTMP SSLLAPAKHLIASMLSKNPEDRPSLDDIIRHDFFLQGFTPDRLSSSCCHTVPDFHLSSPA KNFFKKAAAALFGGKKDKARYIDTHNRVSKEDEDIYKLRHDLKKTSITQQPSKHRTDEEL QPPTTTVARSGTPAVENKQQIGDAIRMIVRGTLGSCSSSSECLEDSTMGSVADTVARVLR GCLENMPEADCIPKEQLSTSFQWVTKWVDYSNKYGFGYQLSDHTVGVLFNNGAHMSLLPD KKTVHYYAELGQCSVFPATDAPEQFISQVTVLKYFSHYMEENLMDGGDLPSVTDIRRPRL YLLQWLKSDKALMMLFNDGTFQVNFYHDHTKIIICSQNEEYLLTYINEDRISTTFRLTTL LMSGCSSELKNRMEYALNMLLQRCN Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| ADReCS ID | BADD_A06440 | |||||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: BI 2536 | Ligand Info | |||||
| Structure Description | Selective & Brain-Permeable Polo-like Kinase-2 (Plk-2) Inhibitors that Reduce -Synuclein Phosphorylation in Rat Brain | PDB:4I5M | ||||
| Method | X-ray diffraction | Resolution | 1.80 Å | Mutation | Yes | [3] |
| PDB Sequence |
RIIVDPTTGK
51 RYSRGKTLGK61 GGFAKCYEMT71 DLTNNKVYAA81 KIIPHSRVSK91 PHQREKIDKE 101 IELHRILHHK111 HVVQFYHYFE121 DKENIYILLE131 YCSRRSMAHI141 LKARKVLTEP 151 EVRYYLRQIV161 SGLKYLHEQE171 ILHRDLKLGN181 FFINESMELK191 VGDFGLAARL 201 ETPNYLSPEV222 LNKQGHGAES232 DIWALGCVMY242 TMLLGRPPFE252 TTNLKETYRS 262 IREARYTMPS272 SLLAPAKHLI282 ASMLSKNPED292 RPSLDDIIRH302 DFFTQGFTPD 312 RLSSSCCHTV322 PDF
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| Ligand Name: (7r)-8-Cyclopentyl-7-Ethyl-5-Methyl-2-(1h-Pyrrol-2-Yl)-7,8-Dihydropteridin-6(5h)-One | Ligand Info | |||||
| Structure Description | Selective & Brain-Permeable Polo-like Kinase-2 (Plk-2) Inhibitors that Reduce -Synuclein Phosphorylation in Rat Brain | PDB:4I5P | ||||
| Method | X-ray diffraction | Resolution | 1.74 Å | Mutation | Yes | [3] |
| PDB Sequence |
RIIVDPTTGK
80 RYSRGKTLGK90 GGFAKCYEMT100 DLTNNKVYAA110 KIIPHSRVSK120 PHQREKIDKE 130 IELHRILHHK140 HVVQFYHYFE150 DKENIYILLE160 YCSRRSMAHI170 LKARKVLTEP 180 EVRYYLRQIV190 SGLKYLHEQE200 ILHRDLKLGN210 FFINESMELK220 VGDFGLAARL 230 EPLEHRRRTI240 CGTPNYLSPE250 VLNKQGHGAE260 SDIWALGCVM270 YTMLLGRPPF 280 ETTNLKETYR290 SIREARYTMP300 SSLLAPAKHL310 IASMLSKNPE320 DRPSLDDIIR 330 HDFFTQGFTP340 DRLSSSCCHT350 VPDF
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Pathway Affiliation
Biological Network Descriptors
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| FoxO signaling pathway | hsa04068 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Degree | 1 | Degree centrality | 1.07E-04 | Betweenness centrality | 0.00E+00 |
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| Closeness centrality | 1.51E-01 | Radiality | 1.20E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 1.00E+01 | Topological coefficient | 1.00E+00 | Eccentricity | 14 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 1 KEGG Pathways | + | ||||
| 1 | FoxO signaling pathway | |||||
| NetPath Pathway | [+] 4 NetPath Pathways | + | ||||
| 1 | IL1 Signaling Pathway | |||||
| 2 | TSH Signaling Pathway | |||||
| 3 | TGF_beta_Receptor Signaling Pathway | |||||
| 4 | TCR Signaling Pathway | |||||
| PID Pathway | [+] 2 PID Pathways | + | ||||
| 1 | PLK2 and PLK4 events | |||||
| 2 | Polo-like kinase signaling events in the cell cycle | |||||
| References | Top | |||||
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| REF 1 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2169). | |||||
| REF 2 | Substituted dihydropteridin-6-one derivatives, process for their preparation and their use as kinase inhibitors. US8598172. | |||||
| REF 3 | Selective and brain-permeable polo-like kinase-2 (Plk-2) inhibitors that reduce Alpha-synuclein phosphorylation in rat brain. ChemMedChem. 2013 Aug;8(8):1295-313. | |||||
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