PLK2

Summary

PLK2 (polo like kinase 2, HGNC:19699) is a protein-coding gene on chromosome 5q11.2, encoding Serine/threonine-protein kinase PLK2 (Q9NYY3). Tumor suppressor serine/threonine-protein kinase involved in synaptic plasticity, centriole duplication and G1/S phase transition.

The protein encoded by this gene is a member of the polo family of serine/threonine protein kinases that have a role in normal cell division. This gene is most abundantly expressed in testis, spleen and fetal tissues, and its expression is inducible by serum, suggesting that it may also play an important role in cells undergoing rapid cell division. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 10769 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 50 total
• Phenotypes (HPO): 2
• Druggable target: yes — 12 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_006622

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19699
Approved symbol	PLK2
Name	polo like kinase 2
Location	5q11.2
Locus type	gene with protein product
Status	Approved
Aliases	SNK
Ensembl gene	ENSG00000145632
Ensembl biotype	protein_coding
OMIM	607023
Entrez	10769

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 12 retained_intron, 6 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000274289, ENST00000502671, ENST00000503115, ENST00000503378, ENST00000503713, ENST00000504196, ENST00000505244, ENST00000508300, ENST00000509422, ENST00000509555, ENST00000510629, ENST00000511326, ENST00000514306, ENST00000515415, ENST00000617412, ENST00000862409, ENST00000932191, ENST00000971658, ENST00000971659

RefSeq mRNA: 2 — MANE Select: NM_006622 NM_001252226, NM_006622

CCDS: CCDS3974, CCDS75250

Canonical transcript exons

ENST00000274289 — 14 exons

Exon	Start	End
ENSE00001001081	58459690	58460086
ENSE00001592709	58453982	58454774
ENSE00001599141	58454911	58455021
ENSE00001739399	58456026	58456155
ENSE00003466000	58457488	58457583
ENSE00003509338	58458084	58458171
ENSE00003538270	58455285	58455414
ENSE00003568624	58458399	58458528
ENSE00003591624	58458725	58458841
ENSE00003602138	58456492	58456589
ENSE00003602624	58456945	58457092
ENSE00003618806	58457181	58457379
ENSE00003642809	58458985	58459092
ENSE00003682361	58455539	58455779

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 98.28.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 81.7533 / max 873.6556, expressed in 1648 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
61777	80.5813	1647
61775	0.6160	275
61774	0.5094	265
61776	0.0466	13

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
spleen	UBERON:0002106	98.28	gold quality
apex of heart	UBERON:0002098	97.29	gold quality
cortical plate	UBERON:0005343	97.28	gold quality
endometrium epithelium	UBERON:0004811	97.25	gold quality
endocervix	UBERON:0000458	97.16	gold quality
ectocervix	UBERON:0012249	97.07	gold quality
islet of Langerhans	UBERON:0000006	96.93	gold quality
colonic epithelium	UBERON:0000397	96.86	gold quality
skin of abdomen	UBERON:0001416	96.86	gold quality
adrenal tissue	UBERON:0018303	96.85	gold quality
calcaneal tendon	UBERON:0003701	96.83	gold quality
gall bladder	UBERON:0002110	96.61	gold quality
tibial nerve	UBERON:0001323	96.36	gold quality
skin of leg	UBERON:0001511	96.01	gold quality
penis	UBERON:0000989	95.74	gold quality
mammary duct	UBERON:0001765	95.62	gold quality
primary visual cortex	UBERON:0002436	95.58	gold quality
zone of skin	UBERON:0000014	95.45	gold quality
nucleus accumbens	UBERON:0001882	95.37	gold quality
esophagus mucosa	UBERON:0002469	95.35	gold quality
epithelium of mammary gland	UBERON:0003244	95.35	gold quality
tongue squamous epithelium	UBERON:0006919	95.32	gold quality
body of uterus	UBERON:0009853	95.13	gold quality
dorsal root ganglion	UBERON:0000044	95.10	gold quality
middle temporal gyrus	UBERON:0002771	95.06	gold quality
thoracic mammary gland	UBERON:0005200	95.06	gold quality
mammary gland	UBERON:0001911	95.00	gold quality
upper lobe of left lung	UBERON:0008952	94.99	gold quality
smooth muscle tissue	UBERON:0001135	94.98	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.97	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-GEOD-114530	yes	1230.77
E-MTAB-7008	yes	672.98
E-MTAB-6701	yes	75.35
E-HCAD-10	yes	33.98
E-MTAB-8271	yes	15.95
E-HCAD-5	yes	13.99
E-CURD-112	yes	7.88
E-GEOD-84465	yes	6.30
E-MTAB-9689	no	794.06
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, ESRRG, GATA1, TP53

miRNA regulators (miRDB)

61 targeting PLK2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-584-3P	99.35	67.69	1082
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-3085-3P	99.26	66.16	1490
HSA-MIR-6504-5P	99.26	65.95	1487
HSA-MIR-2054	99.20	68.89	1699
HSA-MIR-505-3P	99.19	69.71	896

Literature-anchored findings (GeneRIF, showing 40)

• there is a mitotic checkpoint wherein p53-dependent activation of Snk/Plk2 prevents mitotic catastrophe following spindle damage (PMID:12897130)
• hVPS18 may play an important role in regulation of SNK activity through its ubiquitin ligase (PMID:16203730)
• Calcipotriol affects proliferation of keratinocytes by decreasing the expression of EGR1 and PLK2 (PMID:17671831)
• increased cell death observed after aphidicolin treatment and release in Plk2-deficient cells may result from both higher levels of replication stress-induced DNA damage and a dysfunctional S-phase checkpoint (PMID:17912033)
• Plk2 mediated centriole duplication is dependent on Plk4 function (PMID:19001868)
• PLK2 directly phosphorylates alpha-synuclein at Ser-129 in an in vitro biochemical assay (PMID:19004816)
• overexpression of PLK2 in bladder carcinomas, suggesting a possible role of PLK2 in the pathogenesis of bladder carcinomas (PMID:19506885)
• Data show that PLK2 as a kinase that phosphorylates Ser-137 of PLK1, which is sufficient to mediate this survival signal. (PMID:19706541)
• Our results point to a novel Plk2-TSC1 interaction with effects on mTOR signaling during hypoxia, and tumor growth that may enable targeting Plk2 signaling in cancer therapy. (PMID:20054236)
• NPM/B23 is a direct target of Plk2 in the regulation of centriole duplication and that phosphorylation on serine 4 can trigger this process (PMID:20352051)
• Results identify centrosomal P4.1-associated protein (CPAP), a human homologue of SAS-4, as a substrate of PLK2 whose activity oscillates during the cell cycle. (PMID:20531387)
• Identification of Snk/Plk2 as a novel methylated gene in multiple myeloma. (PMID:21067440)
• Polo-like kinase 2 (SNK/PLK2) is a novel epigenetically regulated gene in acute myeloid leukemia and myelodysplastic syndromes. (PMID:21340720)
• Results implicate Plk2 as a clinically important determinant of chemosensitivity. (PMID:21402713)
• phosphorylation sites could play an important role in the rapid activation, expansion, and prolongation of Plk2 signaling (PMID:22100274)
• Mutant p53 oncogenic functions are sustained by Plk2 kinase through an autoregulatory feedback loop. (PMID:22134238)
• Acetylation of GATA-1 responsive elements in Polo-like kinase 2 plays a crucial role in Plk2 transcription and protein expression in MG-63 cells. (PMID:22138223)
• PLK2 and to a lesser extent PLK3 are superior over CK2, as catalysts of Ser-129 phosphorylation both in full length alpha-synuclein and in a peptide reproducing the C-terminal segment of the protein. (PMID:22248692)
• The methylation status of the PLK2 CpG island predicts outcomes in patients treated with carboplatin and paclitaxel chemotherapy. (PMID:22289679)
• Phosphorylation of Fbxw7 by Plk2 induces destabilization of the F-box protein resulting in accumulation of cyclin E and increased potential for centriole reproduction (PMID:22399798)
• have identified and validated as in vitro PLK2 and PLK3 substrates HSP90, GRP-94, beta-tubulin, calumenin, and 14-3-3 epsilon (PMID:22828320)
• PLK2 inhibition is a tractable CNS pharmacological target that does not cause genotoxicity at doses and exposures that engage the target in the sensory retina. (PMID:23466428)
• This study supports a role for PLK2 in the generation of aSyn inclusions by a mechanism that does not depend directly on serine 129 phosphorylation. (PMID:23677647)
• Polo-like kinase 2 is a mediator of hedgehog survival signaling in cholangiocarcinoma. (PMID:23703673)
• Our findings suggest a new role for PLK2 in the regulation of inflammatory diseases by modulating ADAM17 activity. (PMID:24338472)
• PLK2 SNPs were associated with Alzheimer disease and mild cognitive impairment. PLK2-rs15009 CC and GG genotypes and CC genotype at PLK2-rs702723 were protective for AD. (PMID:24384746)
• the regulation of redox homeostasis by PLK2 promotes the survival of cells with dysfunctional mitochondria (PMID:24887096)
• Study indicates that miR-126 is a tumor suppressor that inhibits gastric cancer cells proliferation by targeting PI3KR2, Crk and PLK2. (PMID:24969300)
• Data shows that PLK2 mRNA is a direct target of miR-27a in laryngeal squamous cell carcinoma. (PMID:25239093)
• Unique PLK2-dependent protein phosphorylation sites identified by mass spectrometry. (PMID:25338102)
• Decreased PLK2 protein expression due to promoter hypermethylation was negatively correlated with JAK2 overexpression, a common occurrence in hematological malignancies. (PMID:25347426)
• Silencing of polo-like kinase 2 increases cell proliferation and decreases apoptosis in SGC-7901 gastric cancer cells. (PMID:25501818)
• this study reports the first crystal structure of the C-terminal polo-box domain of PLK2. (PMID:25511705)
• PLK2 indirectly activates ROCK2 via phosphorylating nucleophosmin during centrosome amplification. (PMID:25590559)
• Structural analysis of the polo-box domain of human PLK2 has been presented. (PMID:25846005)
• these findings reveal a conserved PLK2-RAP1 pathway that is crucial to regulate endothelial tip cell behavior in order to ensure proper vascular development and patterning in vertebrates. (PMID:26004360)
• our study demonstrates a novel mechanism of PLK2 in promoting tumor progression, whereby it directly binds to enriched TAp73, catalyzes Ser48 phosphorylation of TAp73, and inhibits TAp73 transcriptional activity (PMID:26625870)
• Data suggest wild-type SNCA (alpha-synuclein) binding to synaptosome membrane is not affected by phosphorylation by PLK2; A30P SNCA, a Parkinson disease mutation, binding is greatly increased; endocytosis of SNCA fibrils follows similar pattern. (PMID:26719332)
• Findings indicate the interaction network of viral oncogene HPV16 E7, miR-27b and PLK2, and support the potential strategies using antisense nucleic acid of miR-27b for therapy of cervical cancer. (PMID:26910911)
• Plk2 represents an independent prognostic marker and regulates tumor growth and apoptosis by targeting Fbxw7/Cyclin E pathway in colorectal carcinoma. (PMID:27423313)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	plk2b	ENSDARG00000019130
danio_rerio	plk2a	ENSDARG00000090752
mus_musculus	Plk2	ENSMUSG00000021701
rattus_norvegicus	Plk2	ENSRNOG00000011951

Paralogs (4): PLK4 (ENSG00000142731), PLK1 (ENSG00000166851), PLK3 (ENSG00000173846), PLK5 (ENSG00000185988)

Protein

Protein identifiers

Serine/threonine-protein kinase PLK2 — Q9NYY3 (reviewed: Q9NYY3)

Alternative names: Polo-like kinase 2, Serine/threonine-protein kinase SNK, Serum-inducible kinase

All UniProt accessions (2): A0A087WUH9, Q9NYY3

UniProt curated annotations — full annotation on UniProt →

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 that are already phosphorylated on a specific motif recognized by the POLO box domains. Phosphorylates CPAP, 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 CPAP and NPM1, respectively. Its induction by p53/TP53 suggests that it may participate in the mitotic checkpoint following stress.

Subunit / interactions. Interacts with NSF; causing NSF dissociation from GRIA2. Interacts with CIB1.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Centriole. Cell projection. Dendrite.

Tissue specificity. Expressed at higher level in the fetal lung, kidney, spleen and heart.

Post-translational modifications. Catalytic activity is enhanced by phosphorylation of Thr-239.

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

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

Induction. Directly regulated by p53/TP53. Negatively regulated by miR-126.

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. 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.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NYY3-1	1	yes
Q9NYY3-2	2

RefSeq proteins (2): NP_001239155, NP_006613* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR000959	POLO_box_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR033695	POLO_box_2	Domain
IPR033701	POLO_box_1	Domain
IPR036947	POLO_box_dom_sf	Homologous_superfamily
IPR042825	PLK2_STKc	Domain

Pfam: PF00069, PF00659

Enzyme classification (BRENDA):

• EC 2.7.11.21 — polo kinase (BRENDA: 16 organisms, 193 substrates, 436 inhibitors, 20 Km, 14 kcat entries)

Substrate kinetics (BRENDA)

3 substrates with measured Km, best-characterized 3. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0002–0.0076	13
CDC25C	0.0006–0.0008	6
CASEIN	0.0014	1

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (64 total): strand 19, helix 19, turn 5, sequence variant 4, mutagenesis site 4, domain 3, region of interest 2, binding site 2, chain 1, modified residue 1, splice variant 1, sequence conflict 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
4I5P	X-RAY DIFFRACTION	1.74
4I6B	X-RAY DIFFRACTION	1.8
4I5M	X-RAY DIFFRACTION	1.8
4I6H	X-RAY DIFFRACTION	1.91
4RS6	X-RAY DIFFRACTION	2.6
4XB0	X-RAY DIFFRACTION	2.7
4I6F	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NYY3-F1	76.64	0.47

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 205 (proton acceptor)

Ligand- & substrate-binding residues (2): 88–96; 111

Post-translational modifications (1): 239

Mutagenesis-validated functional residues (4):

Position	Phenotype
210	loss of kinase activity.
503	impairs localization to the centrosome and centriole duplication; when associated with a-629 and m-631.
629	impairs localization to the centrosome and centriole duplication; when associated with f-503 and m-631.
631	impairs localization to the centrosome and centriole duplication; when associated with f-503 and a-631.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6804115	TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain
R-HSA-9662834	CD163 mediating an anti-inflammatory response
R-HSA-9768919	NPAS4 regulates expression of target genes

MSigDB gene sets: 452 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_MEMORY, MODULE_52, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, LEE_NEURAL_CREST_STEM_CELL_DN, GOBP_REGULATION_OF_AUTOPHAGY, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_REGULATION_OF_INFLAMMATORY_RESPONSE_TO_ANTIGENIC_STIMULUS, BOYLAN_MULTIPLE_MYELOMA_PCA1_DN, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_INFLAMMATORY_RESPONSE, DORN_ADENOVIRUS_INFECTION_12HR_UP

GO Biological Process (22): G1/S transition of mitotic cell cycle (GO:0000082), negative regulation of inflammatory response to antigenic stimulus (GO:0002862), protein phosphorylation (GO:0006468), mitotic spindle organization (GO:0007052), Ras protein signal transduction (GO:0007265), memory (GO:0007613), positive regulation of autophagy (GO:0010508), negative regulation of angiogenesis (GO:0016525), DNA damage response, signal transduction by p53 class mediator (GO:0030330), Rap protein signal transduction (GO:0032486), negative regulation of apoptotic process (GO:0043066), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), positive regulation of protein catabolic process (GO:0045732), regulation of centriole replication (GO:0046599), regulation of synaptic plasticity (GO:0048167), long-term synaptic potentiation (GO:0060291), long-term synaptic depression (GO:0060292), negative regulation of apoptotic process in bone marrow cell (GO:0071866), positive regulation of cell migration involved in sprouting angiogenesis (GO:0090050), negative regulation of cellular senescence (GO:2000773), mitotic cell cycle (GO:0000278), regulation of cell cycle process (GO:0010564)

GO Molecular Function (9): protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), ATP-dependent protein binding (GO:0043008), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (11): kinetochore (GO:0000776), chromatin (GO:0000785), spindle pole (GO:0000922), nucleus (GO:0005634), cytoplasm (GO:0005737), centrosome (GO:0005813), centriole (GO:0005814), cytosol (GO:0005829), dendrite (GO:0030425), cytoskeleton (GO:0005856), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
TP53 Regulates Transcription of Cell Cycle Genes	1
Anti-inflammatory response favouring Leishmania parasite infection	1
Transcriptional Regulation by NPAS4	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
intracellular membraneless organelle	3
mitotic cell cycle	2
small GTPase-mediated signal transduction	2
positive regulation of catabolic process	2
regulation of synaptic plasticity	2
protein kinase activity	2
microtubule organizing center	2
mitotic cell cycle phase transition	1
cell cycle G1/S phase transition	1
inflammatory response to antigenic stimulus	1
regulation of inflammatory response to antigenic stimulus	1
negative regulation of inflammatory response	1
negative regulation of immune response	1
phosphorylation	1
protein modification process	1
spindle organization	1
microtubule cytoskeleton organization involved in mitosis	1
learning or memory	1
autophagy	1
regulation of autophagy	1
angiogenesis	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
signal transduction in response to DNA damage	1
signal transduction by p53 class mediator	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
protein catabolic process	1
regulation of protein catabolic process	1
positive regulation of protein metabolic process	1
centriole replication	1
regulation of centrosome duplication	1
regulation of organelle assembly	1
modulation of chemical synaptic transmission	1
regulation of biological quality	1

Protein interactions and networks

STRING

3025 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLK2	CPAP	Q9HC77	599
PLK2	CIB1	Q99828	576
PLK2	CDC5L	Q99459	569
PLK2	HOMER1	Q86YM7	497
PLK2	PICK1	Q9NRD5	496
PLK2	SUN1	O94901	475
PLK2	CNTD1	Q8N815	471
PLK2	NPTX2	P47972	469
PLK2	NABP1	Q96AH0	453
PLK2	TP53	P04637	447
PLK2	TSC1	Q92574	444
PLK2	TSC2	P49815	430
PLK2	PLK1	P53350	426
PLK2	AEN	Q8WTP8	422
PLK2	INS	P01308	418

IntAct

29 interactions, top by confidence:

A	B	Type	Score
CDC20B	PLK2	psi-mi:“MI:0915”(physical association)	0.560
PLK1	PLK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
CPAP	PLK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
PLK2	Plk2	psi-mi:“MI:0915”(physical association)	0.400
YWHAE	PLK2	psi-mi:“MI:0915”(physical association)	0.400
SFN	PLK2	psi-mi:“MI:0915”(physical association)	0.400
PLK2	E2	psi-mi:“MI:0915”(physical association)	0.370
PLK2	E6	psi-mi:“MI:0915”(physical association)	0.370
CASK	PLK2	psi-mi:“MI:0915”(physical association)	0.370
PLK2	C1orf226	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
PLK2	ANKRD28	psi-mi:“MI:0914”(association)	0.350
PLK2	H2AZ1	psi-mi:“MI:0914”(association)	0.350
PLK2	E2	psi-mi:“MI:0915”(physical association)	0.000
y1093	PLK2	psi-mi:“MI:0915”(physical association)	0.000
fhuB	PLK2	psi-mi:“MI:0915”(physical association)	0.000
NRIP1	PLK2	psi-mi:“MI:0915”(physical association)	0.000
MPP3	PLK2	psi-mi:“MI:0915”(physical association)	0.000
PLK2	ELP1	psi-mi:“MI:0915”(physical association)	0.000
DLGAP4	PLK2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (110): CDC20B (Two-hybrid), KLK7 (Affinity Capture-MS), IGKC (Affinity Capture-MS), IGHG2 (Affinity Capture-MS), CTSV (Affinity Capture-MS), RNASE7 (Affinity Capture-MS), POF1B (Affinity Capture-MS), EIF5B (Affinity Capture-MS), SUGP1 (Affinity Capture-MS), TAF8 (Affinity Capture-MS), CCDC12 (Affinity Capture-MS), EEF1A2 (Affinity Capture-MS), RABL6 (Affinity Capture-MS), ANKRD44 (Affinity Capture-MS), ANKRD28 (Affinity Capture-MS)

ESM2 similar proteins: A2AHJ4, A2AQW0, A7MBL8, A9JRL3, F1ND48, O00418, O08796, O08874, O35099, P15056, P28028, P32866, P34908, P53350, P53351, P62205, P70032, P70531, Q07832, Q16513, Q21029, Q2TA25, Q3TWN3, Q4U2V3, Q5E9N5, Q5R4L1, Q5R9R1, Q5ZKK7, Q62673, Q641K1, Q6DD21, Q6RI45, Q6ZN16, Q80V94, Q8AYK6, Q8BPM2, Q8IVH8, Q8QGV2, Q921C3, Q99683

Diamond homologs: A0A509AH51, A0QNG1, A3B529, A3LUB9, A5D791, A6ZU08, A7E3S4, A8X0C4, A8XSC1, D0Z5N4, D4A7V9, E2QWQ2, O19004, P00531, P00532, P04049, P04627, P05625, P07527, P0CS76, P0CS77, P10398, P11345, P14056, P17157, P19525, P27636, P32490, P33279, P34331, P38990, P41676, P43637, P50750, P52304, P53351, P54666, Q03957, Q03963, Q04770

SIGNOR signaling

14 interactions.

A	Effect	B	Mechanism
PLK2	up-regulates	NPM1	phosphorylation
PLK2	up-regulates	CENPJ	phosphorylation
PLK2	“down-regulates activity”	SNCA	phosphorylation
PLK2	“down-regulates activity”	SNCB	phosphorylation
PLK2	down-regulates	FBXW7	phosphorylation
VPS18	“down-regulates quantity by destabilization”	PLK2	ubiquitination
DYRK1A	“up-regulates quantity by stabilization”	PLK2	phosphorylation
PLK2	“down-regulates activity”	TP73	phosphorylation
PLK2	“up-regulates activity”	TP53	phosphorylation
PLK2	“up-regulates activity”	APP	phosphorylation
PLK2	“up-regulates activity”	LRPAP1	phosphorylation
PLK2	“up-regulates activity”	RAPGEF2	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

50 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	36
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

940 predictions. Top by Δscore:

Variant	Effect	Δscore
5:58454770:TTCAC:T	acceptor_gain	1.0000
5:58454771:TCAC:T	acceptor_gain	1.0000
5:58454772:CAC:C	acceptor_gain	1.0000
5:58454772:CACC:C	acceptor_gain	1.0000
5:58454773:ACC:A	acceptor_loss	1.0000
5:58454774:CCT:C	acceptor_gain	1.0000
5:58454775:C:CA	acceptor_loss	1.0000
5:58454775:C:CC	acceptor_gain	1.0000
5:58454775:C:T	acceptor_gain	1.0000
5:58454776:T:C	acceptor_gain	1.0000
5:58454776:T:TC	acceptor_gain	1.0000
5:58454909:A:C	donor_loss	1.0000
5:58454942:AGGG:A	donor_gain	1.0000
5:58454951:T:C	donor_gain	1.0000
5:58455017:CCACC:C	acceptor_gain	1.0000
5:58455018:CACC:C	acceptor_gain	1.0000
5:58455018:CACCC:C	acceptor_gain	1.0000
5:58455019:ACC:A	acceptor_gain	1.0000
5:58455020:CC:C	acceptor_gain	1.0000
5:58455020:CCC:C	acceptor_gain	1.0000
5:58455021:CC:C	acceptor_gain	1.0000
5:58455022:C:CC	acceptor_gain	1.0000
5:58455022:C:T	acceptor_gain	1.0000
5:58455279:ACTT:A	donor_loss	1.0000
5:58455280:CTT:C	donor_loss	1.0000
5:58455281:TTAC:T	donor_loss	1.0000
5:58455282:TAC:T	donor_loss	1.0000
5:58455283:A:AC	donor_gain	1.0000
5:58455283:ACA:A	donor_loss	1.0000
5:58455283:ACAT:A	donor_gain	1.0000

AlphaMissense

4550 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:58454626:C:G	R672P	1.000
5:58454691:C:A	R650S	1.000
5:58454691:C:G	R650S	1.000
5:58454692:C:A	R650M	1.000
5:58454692:C:G	R650T	1.000
5:58454748:T:A	K631N	1.000
5:58454748:T:G	K631N	1.000
5:58454749:T:A	K631I	1.000
5:58454754:A:C	H629Q	1.000
5:58454754:A:T	H629Q	1.000
5:58454756:G:C	H629D	1.000
5:58454758:T:A	D628V	1.000
5:58454758:T:G	D628A	1.000
5:58454759:C:G	D628H	1.000
5:58454766:G:C	F625L	1.000
5:58454766:G:T	F625L	1.000
5:58454768:A:G	F625L	1.000
5:58454769:A:C	N624K	1.000
5:58454769:A:T	N624K	1.000
5:58454771:T:C	N624D	1.000
5:58454771:T:G	N624H	1.000
5:58454912:T:G	Q622P	1.000
5:58454933:A:G	L615P	1.000
5:58454936:A:C	M614R	1.000
5:58454936:A:G	M614T	1.000
5:58454942:A:G	L612P	1.000
5:58454942:A:T	L612Q	1.000
5:58454945:G:T	A611D	1.000
5:58454946:C:G	A611P	1.000
5:58454955:A:G	S608P	1.000

dbSNP variants (sampled 300 via entrez): RS1000096381 (5:58460471 C>G,T), RS1001482201 (5:58456342 T>C,G), RS1001510011 (5:58456010 A>T), RS1002401072 (5:58460497 C>A), RS1002483719 (5:58458002 C>T), RS1003818066 (5:58461920 T>C), RS1004105387 (5:58461709 T>G), RS1004557249 (5:58458314 A>G), RS1005258862 (5:58454943 G>C), RS1005340577 (5:58461134 G>A), RS1005598276 (5:58459322 G>C), RS1005878007 (5:58457100 A>G), RS1006566150 (5:58460969 G>A), RS1006717001 (5:58453532 G>A), RS1006965307 (5:58460794 C>T)

Disease associations

OMIM: gene MIM:607023 | disease phenotypes:

GenCC curated gene-disease

Mondo (2): esophageal atresia (MONDO:0001044), pyloric stenosis (MONDO:0001561)

Orphanet (0):

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPO	Term
HP:0002032	Esophageal atresia
HP:0002021	Pyloric stenosis

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST004125_17	Type 2 diabetes (age of onset)	4.000000e-06
GCST006530_2	Esophageal adenocarcinoma x smoking interaction	7.000000e-07
GCST006627_32	Diastolic blood pressure	4.000000e-12
GCST006988_70	Blond vs. brown/black hair color	4.000000e-10
GCST008892_8	Working memory	5.000000e-06
GCST010244_144	Triglyceride levels	1.000000e-12
GCST012334_5	Multisite chronic pain	3.000000e-08

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0006527	smoking status measurement
EFO:0006336	diastolic blood pressure
EFO:0003924	hair color
EFO:0004335	short-term memory
EFO:0004530	triglyceride measurement
EFO:0010100	multisite chronic pain

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D004933	Esophageal Atresia	C06.198.330; C06.405.117.260; C16.131.314.330
D017219	Gastric Outlet Obstruction	C06.405.748.340
D011707	Pyloric Stenosis	C06.405.748.340.690

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5938 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

12 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 117,858 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL535	SUNITINIB	4	79,020
CHEMBL1233528	VOLASERTIB	3	1,511
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL1672002	THYMOQUINONE	2	1,497
CHEMBL1738758	ONVANSERTIB	2	780
CHEMBL475251	R-406	2	762
CHEMBL513909	BI-2536	2	895
CHEMBL1908394	GSK-461364	1	1,093

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Polo-like kinase (PLK) family

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
BI-2536	Inhibition	8.46	pIC50
rucaparib metabolite M324	Inhibition	6.23	pIC50
onvansertib	Inhibition	5.0	pIC50

Binding affinities (BindingDB)

25 measured of 31 human assays (33 total across all organisms); most potent 25 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
BMCL191018 Compound 2	IC50	2 nM
(3R,4R)-3-methoxy-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	IC50	3.93 nM	US-10189849: CDK inhibitors
4-{[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-5,6,7,8-tetrahydropteridin-2-yl]amino}-N-(1-methylpiperidin-4-yl)benzamide	IC50	5 nM
Biochemistry 469551 Compound 12	IC50	5.4 nM
H-1152	KI	6 nM
1-tert-butyl-3-(4-methylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine	IC50	6 nM
4-{[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-5,6,7,8-tetrahydropteridin-2-yl]amino}-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide	IC50	8 nM	US-8598172: Substituted dihydropteridin-6-one derivatives, process for their preparation and their use as kinase inhibitors
3-[(4-bromo-2,6-difluorophenyl)methoxy]-5-({[4-(pyrrolidin-1-yl)butyl]carbamoyl}amino)-1,2-thiazole-4-carboxamide	IC50	10.1 nM	US-9446026: Ocular formulations for drug-delivery to the posterior segment of the eye
Biochemistry 469551 Compound 11	IC50	14 nM
(7R)-8-cyclopentyl-7-ethyl-5-methyl-2-[5-(4-methylpiperazin-1-yl)-2-(trifluoromethoxy)anilino]-7H-pteridin-6-one	IC50	32 nM	US-8598172: Substituted dihydropteridin-6-one derivatives, process for their preparation and their use as kinase inhibitors
3-[3-chloro-5-(5-{[(1S)-1-phenylethyl]amino}pyrido[4,3-d][1,2]oxazol-3-yl)phenyl]propanamide	IC50	51 nM
1-[4-(cyclopentylamino)-2-{[2-methoxy-4-(4-methylpiperazin-1-yl)phenyl]amino}pyrimidin-5-yl]ethan-1-one	IC50	145 nM
3-(2H-1,3-benzodioxol-5-yl)-N-[(1S)-1-phenylethyl]pyrido[4,3-d][1,2]oxazol-5-amine	IC50	214 nM
1-[4-(cyclopentylamino)-2-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrimidin-5-yl]ethan-1-one	IC50	345 nM
4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]-N-methylpyridine-2-carboxamide	KD	370 nM
(3Z)-4-amino-5-fluoro-3-[5-(4-methylpiperazino)-1,3-dihydrobenzimidazol-2-ylidene]carbostyril	KD	520 nM
3-(3-methylphenyl)-N-[(1S)-1-phenylethyl]pyrido[4,3-d][1,2]oxazol-5-amine	IC50	549 nM
3-(4-{4-aminothieno[2,3-d]pyrimidin-5-yl}phenyl)-1-(3-methylphenyl)urea	IC50	720 nM
4-[(4-methylpiperazin-1-yl)methyl]-N-[4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl]benzamide	KD	1000 nM
N-[4-({4-[(3-methyl-1H-pyrazol-5-yl)amino]-6-(4-methylpiperazin-1-yl)pyrimidin-2-yl}sulfanyl)phenyl]cyclopropanecarboxamide	KD	1100 nM
N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	KD	3500 nM
N-{2-[3-chloro-5-(3-methyl-6-{[(1S)-1-phenylethyl]amino}-1H-pyrazolo[4,3-c]pyridin-1-yl)phenyl]phenyl}acetamide	IC50	6800 nM
2-(4-Morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	IC50	13100 nM	US-9505780: Thienopyranones as kinase and epigenetic inhibitors
(3E)-5-{5-[(2S)-2-amino-3-(1H-indol-3-yl)propoxy]pyridin-3-yl}-3-(furan-2-ylmethylidene)-2,3-dihydro-1H-indol-2-one	KI	31000 nM
CHEMBL5197718	IC50	51900 nM

ChEMBL bioactivities

247 potent at pChembl≥5 of 254 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.09	Kd	0.81	nM	BI-2536
8.70	Ki	2	nM	CHEMBL2205426
8.70	IC50	2	nM	CHEMBL1094477
8.54	IC50	2.92	nM	BI-2536
8.47	IC50	3.4	nM	CHEMBL4166771
8.46	IC50	3.5	nM	BI-2536
8.40	IC50	3.98	nM	CHEMBL4592698
8.40	IC50	4	nM	CHEMBL522618
8.33	IC50	4.72	nM	CHEMBL4454222
8.31	IC50	4.88	nM	CHEMBL4171770
8.30	IC50	5	nM	CHEMBL2401963
8.30	IC50	5	nM	VOLASERTIB
8.30	IC50	5	nM	CHEMBL5276995
8.24	IC50	5.73	nM	CHEMBL5430344
8.20	IC50	6.32	nM	CHEMBL5435085
8.15	IC50	7	nM	CHEMBL2402081
8.15	IC50	7.06	nM	CHEMBL4175722
8.11	IC50	7.86	nM	CHEMBL4176983
8.10	IC50	8	nM	CHEMBL2401971
8.10	IC50	7.98	nM	CHEMBL4548940
8.09	IC50	8.16	nM	CHEMBL4169129
8.07	IC50	8.6	nM	CHEMBL4163892
8.05	IC50	9	nM	CHEMBL2402079
8.05	IC50	9	nM	CHEMBL2401966
8.05	IC50	9	nM	CHEMBL559845
7.99	IC50	10.17	nM	CHEMBL4168155
7.96	EC50	11	nM	VOLASERTIB
7.95	IC50	11.35	nM	CHEMBL4164012
7.92	IC50	12	nM	CHEMBL2402078
7.92	IC50	12	nM	CHEMBL2401969
7.92	IC50	12	nM	CHEMBL1095457
7.92	IC50	12	nM	CHEMBL1097022
7.90	IC50	12.72	nM	CHEMBL6173341
7.89	IC50	13	nM	CHEMBL2401968
7.87	IC50	13.55	nM	BI-2536
7.85	IC50	14	nM	CHEMBL1094478
7.82	IC50	15	nM	CHEMBL2401975
7.78	IC50	16.52	nM	CHEMBL4160611
7.78	IC50	16.8	nM	BI-2536
7.77	IC50	17	nM	CHEMBL2401974
7.76	IC50	17.41	nM	CHEMBL4174667
7.75	IC50	17.77	nM	CHEMBL4177399
7.73	IC50	18.62	nM	CHEMBL4171224
7.70	IC50	19.85	nM	CHEMBL4170176
7.68	IC50	21	nM	CHEMBL2402080
7.68	IC50	21	nM	CHEMBL2401972
7.68	IC50	21	nM	CHEMBL551079
7.66	IC50	21.77	nM	CHEMBL4162262
7.62	IC50	23.87	nM	CHEMBL4173620
7.62	IC50	24	nM	CHEMBL1094135

PubChem BioAssay actives

242 with measured affinity, of 993 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide	625063: Binding constant for PLK2 kinase domain	kd	0.0008	uM
1-methyl-8-(2-methylanilino)-4,5-dihydropyrazolo[4,5-h]quinazoline-3-carboxamide	480527: Inhibition of Plk2 assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting	ic50	0.0020	uM
3-(tert-butylamino)-4-[[2-(4-pyridin-4-ylanilino)pyrimidin-4-yl]amino]cyclobut-3-ene-1,2-dione	719093: Inhibition of recombinant PLK2 after 1 hr by scintillation counter analysis in presence of gamma-[33P]ATP	ki	0.0020	uM
4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-N-methylbenzenesulfonamide	1348849: Inhibition human recombinant full length GST-tagged Plk2 expressed in baculovirus expression system after 1 hr by FRET-based Z’-Lyte assay	ic50	0.0034	uM
5-(5,6-dimethoxybenzimidazol-1-yl)-3-[[2-(trifluoromethyl)phenyl]methoxy]thiophene-2-carboxamide	1798514: PLK Kinase Assay from Article 10.1021/bi7008745: “Pharmacological and functional comparison of the polo-like kinase family: insight into inhibitor and substrate specificity.”	ki	0.0038	uM
N-cyclopentyl-4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-3-methoxybenzamide	1610356: Inhibition of recombinant full length human GST-tagged PLK2 expressed in baculovirus expression system using ser/thr 16 as substrate incubated for 1 hr by Z’-LYTE assay	ic50	0.0040	uM
3-(1,3-benzodioxol-5-yl)-N-[(1S)-1-phenylethyl]-[1,2]oxazolo[5,4-c]pyridin-5-amine	1798481: Plk in Vitro Assay from Article 10.1016/j.bmcl.2008.08.091: “Design and synthesis of 2-amino-isoxazolopyridines as Polo-like kinase inhibitors.”	ic50	0.0040	uM
N-cyclopentyl-4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-3-methylbenzamide	1610356: Inhibition of recombinant full length human GST-tagged PLK2 expressed in baculovirus expression system using ser/thr 16 as substrate incubated for 1 hr by Z’-LYTE assay	ic50	0.0047	uM
1-[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]-N-ethylindole-5-carboxamide	1348849: Inhibition human recombinant full length GST-tagged Plk2 expressed in baculovirus expression system after 1 hr by FRET-based Z’-Lyte assay	ic50	0.0049	uM
N-[4-[4-(cyclopropylmethyl)piperazin-1-yl]cyclohexyl]-4-[[(7R)-7-ethyl-5-methyl-6-oxo-8-propan-2-yl-7H-pteridin-2-yl]amino]-3-methoxybenzamide	1949827: Inhibition of PLK2 (unknown origin)	ic50	0.0050	uM
(7R)-8-cyclopentyl-7-ethyl-5-methyl-2-(2-phenylimidazol-1-yl)-7H-pteridin-6-one	757393: Inhibition of GST-tagged Plk2 (unknown origin) assessed as inhibition of DEKTDDED phosphorylation at Thr1342 after 60 mins by TR-FRET assay	ic50	0.0050	uM
(7R)-8-cyclopentyl-7-ethyl-2-[2-methoxy-4-[5-(piperazin-1-ylmethyl)-1,2,4-oxadiazol-3-yl]anilino]-5-methyl-7H-pteridin-6-one	2007990: Inhibition of PLK2 (unknown origin) preincubated for 10 mins followed by substrate addition measured after 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0057	uM
(7R)-8-cyclopentyl-2-[4-[5-(1,4-diazepan-1-ylmethyl)-1,2,4-oxadiazol-3-yl]-2-methoxyanilino]-7-ethyl-5-methyl-7H-pteridin-6-one	2007990: Inhibition of PLK2 (unknown origin) preincubated for 10 mins followed by substrate addition measured after 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0063	uM
(7R)-7-ethyl-2-[2-(4-fluorophenyl)imidazol-1-yl]-5-methyl-8-(1-methylpyrazol-3-yl)-7H-pteridin-6-one	757393: Inhibition of GST-tagged Plk2 (unknown origin) assessed as inhibition of DEKTDDED phosphorylation at Thr1342 after 60 mins by TR-FRET assay	ic50	0.0070	uM
N-cyclopentyl-1-[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]indole-5-carboxamide	1348849: Inhibition human recombinant full length GST-tagged Plk2 expressed in baculovirus expression system after 1 hr by FRET-based Z’-Lyte assay	ic50	0.0071	uM
4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-N-(2-hydroxyethyl)benzenesulfonamide	1348849: Inhibition human recombinant full length GST-tagged Plk2 expressed in baculovirus expression system after 1 hr by FRET-based Z’-Lyte assay	ic50	0.0079	uM
N-cyclopentyl-4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-3-hydroxybenzamide	1610356: Inhibition of recombinant full length human GST-tagged PLK2 expressed in baculovirus expression system using ser/thr 16 as substrate incubated for 1 hr by Z’-LYTE assay	ic50	0.0080	uM
(7R)-7-ethyl-5-methyl-8-[(3S)-oxolan-3-yl]-2-(2-phenylimidazol-1-yl)-7H-pteridin-6-one	757393: Inhibition of GST-tagged Plk2 (unknown origin) assessed as inhibition of DEKTDDED phosphorylation at Thr1342 after 60 mins by TR-FRET assay	ic50	0.0080	uM
4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-N-(3-hydroxypropyl)benzenesulfonamide	1348849: Inhibition human recombinant full length GST-tagged Plk2 expressed in baculovirus expression system after 1 hr by FRET-based Z’-Lyte assay	ic50	0.0082	uM
1-[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]-N-methylindole-5-carboxamide	1348849: Inhibition human recombinant full length GST-tagged Plk2 expressed in baculovirus expression system after 1 hr by FRET-based Z’-Lyte assay	ic50	0.0086	uM
8-anilino-1-methyl-4,5-dihydropyrazolo[4,5-h]quinazoline-3-carboxamide	480527: Inhibition of Plk2 assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting	ic50	0.0090	uM
(7R)-7-ethyl-5-methyl-2-(2-phenylimidazol-1-yl)-8-(3,3,3-trifluoropropyl)-7H-pteridin-6-one	757393: Inhibition of GST-tagged Plk2 (unknown origin) assessed as inhibition of DEKTDDED phosphorylation at Thr1342 after 60 mins by TR-FRET assay	ic50	0.0090	uM
7-ethyl-2-[2-(4-fluorophenyl)imidazol-1-yl]-5-methyl-8-(1H-pyrazol-5-yl)-7H-pteridin-6-one	757393: Inhibition of GST-tagged Plk2 (unknown origin) assessed as inhibition of DEKTDDED phosphorylation at Thr1342 after 60 mins by TR-FRET assay	ic50	0.0090	uM
4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]benzenesulfonamide	1348849: Inhibition human recombinant full length GST-tagged Plk2 expressed in baculovirus expression system after 1 hr by FRET-based Z’-Lyte assay	ic50	0.0102	uM
1-[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]-N-propylindole-5-carboxamide	1348849: Inhibition human recombinant full length GST-tagged Plk2 expressed in baculovirus expression system after 1 hr by FRET-based Z’-Lyte assay	ic50	0.0114	uM
4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-N-(1-methylpiperidin-4-yl)benzamide	1798697: Enzymatic Activity Assay from Article 10.1111/j.1747-0285.2007.00594.x: “Selectivity-determining residues in Plk1.”	ic50	0.0115	uM
1-methyl-8-[2-(methylamino)anilino]-4,5-dihydropyrazolo[4,5-h]quinazoline-3-carboxamide	480527: Inhibition of Plk2 assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting	ic50	0.0120	uM
8-(2-aminoanilino)-1-methyl-4,5-dihydropyrazolo[4,5-h]quinazoline-3-carboxamide	480527: Inhibition of Plk2 assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting	ic50	0.0120	uM
(7R)-7-ethyl-2-[2-(4-fluorophenyl)imidazol-1-yl]-5-methyl-8-(1H-pyrazol-4-yl)-7H-pteridin-6-one	757393: Inhibition of GST-tagged Plk2 (unknown origin) assessed as inhibition of DEKTDDED phosphorylation at Thr1342 after 60 mins by TR-FRET assay	ic50	0.0120	uM
(7R)-8-(3,3-difluorocyclobutyl)-7-ethyl-2-[2-(4-fluorophenyl)imidazol-1-yl]-5-methyl-7H-pteridin-6-one	757393: Inhibition of GST-tagged Plk2 (unknown origin) assessed as inhibition of DEKTDDED phosphorylation at Thr1342 after 60 mins by TR-FRET assay	ic50	0.0120	uM
8-(3,3-difluorocyclopentyl)-7-ethyl-2-[2-(4-fluorophenyl)imidazol-1-yl]-5-methyl-7H-pteridin-6-one	757393: Inhibition of GST-tagged Plk2 (unknown origin) assessed as inhibition of DEKTDDED phosphorylation at Thr1342 after 60 mins by TR-FRET assay	ic50	0.0130	uM
1-methyl-8-(2-methylsulfanylanilino)-4,5-dihydropyrazolo[4,5-h]quinazoline-3-carboxamide	480527: Inhibition of Plk2 assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting	ic50	0.0140	uM
7-ethyl-8-(4-fluorophenyl)-2-[2-(4-fluorophenyl)imidazol-1-yl]-5-methyl-7H-pteridin-6-one	757393: Inhibition of GST-tagged Plk2 (unknown origin) assessed as inhibition of DEKTDDED phosphorylation at Thr1342 after 60 mins by TR-FRET assay	ic50	0.0150	uM
N-butyl-1-[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]indole-5-carboxamide	1348849: Inhibition human recombinant full length GST-tagged Plk2 expressed in baculovirus expression system after 1 hr by FRET-based Z’-Lyte assay	ic50	0.0165	uM
7-ethyl-5-methyl-8-phenyl-2-(2-phenylimidazol-1-yl)-7H-pteridin-6-one	757393: Inhibition of GST-tagged Plk2 (unknown origin) assessed as inhibition of DEKTDDED phosphorylation at Thr1342 after 60 mins by TR-FRET assay	ic50	0.0170	uM
1-[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]-N-propan-2-ylindole-5-carboxamide	1348849: Inhibition human recombinant full length GST-tagged Plk2 expressed in baculovirus expression system after 1 hr by FRET-based Z’-Lyte assay	ic50	0.0174	uM
4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-N-propylbenzenesulfonamide	1348849: Inhibition human recombinant full length GST-tagged Plk2 expressed in baculovirus expression system after 1 hr by FRET-based Z’-Lyte assay	ic50	0.0178	uM
1-[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]-N-(2-methylpropyl)indole-5-carboxamide	1348849: Inhibition human recombinant full length GST-tagged Plk2 expressed in baculovirus expression system after 1 hr by FRET-based Z’-Lyte assay	ic50	0.0186	uM
N-butyl-4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]benzenesulfonamide	1348849: Inhibition human recombinant full length GST-tagged Plk2 expressed in baculovirus expression system after 1 hr by FRET-based Z’-Lyte assay	ic50	0.0198	uM
3-[(1R)-1-[4-[(tert-butylamino)methyl]-2-(difluoromethoxy)phenyl]ethoxy]-5-imidazo[1,2-a]pyridin-3-ylthiophene-2-carboxamide	433283: Inhibition of PLK2	ic50	0.0210	uM
(7R)-7-ethyl-2-[2-(4-fluorophenyl)imidazol-1-yl]-5-methyl-8-(1-methylpyrazol-4-yl)-7H-pteridin-6-one	757393: Inhibition of GST-tagged Plk2 (unknown origin) assessed as inhibition of DEKTDDED phosphorylation at Thr1342 after 60 mins by TR-FRET assay	ic50	0.0210	uM
(7R)-7-ethyl-5-methyl-8-[(3R)-oxolan-3-yl]-2-(2-phenylimidazol-1-yl)-7H-pteridin-6-one	757393: Inhibition of GST-tagged Plk2 (unknown origin) assessed as inhibition of DEKTDDED phosphorylation at Thr1342 after 60 mins by TR-FRET assay	ic50	0.0210	uM
4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-N-(2-methylpropyl)benzenesulfonamide	1348849: Inhibition human recombinant full length GST-tagged Plk2 expressed in baculovirus expression system after 1 hr by FRET-based Z’-Lyte assay	ic50	0.0218	uM
N-cyclopentyl-4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]benzenesulfonamide	1348849: Inhibition human recombinant full length GST-tagged Plk2 expressed in baculovirus expression system after 1 hr by FRET-based Z’-Lyte assay	ic50	0.0239	uM
8-(2-methoxyanilino)-1-methyl-4,5-dihydropyrazolo[4,5-h]quinazoline-3-carboxamide	480527: Inhibition of Plk2 assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting	ic50	0.0240	uM
(7R)-7-ethyl-5-methyl-2-(2-phenylimidazol-1-yl)-8-propan-2-yl-7H-pteridin-6-one	757393: Inhibition of GST-tagged Plk2 (unknown origin) assessed as inhibition of DEKTDDED phosphorylation at Thr1342 after 60 mins by TR-FRET assay	ic50	0.0250	uM
8-(2-fluoroanilino)-1-methyl-4,5-dihydropyrazolo[4,5-h]quinazoline-3-carboxamide	480527: Inhibition of Plk2 assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting	ic50	0.0270	uM
1-[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]indole-5-carboxamide	1348849: Inhibition human recombinant full length GST-tagged Plk2 expressed in baculovirus expression system after 1 hr by FRET-based Z’-Lyte assay	ic50	0.0285	uM
7-ethyl-2-[2-(4-fluorophenyl)imidazol-1-yl]-5,7-dimethyl-8-(3,3,3-trifluoropropyl)pteridin-6-one	757393: Inhibition of GST-tagged Plk2 (unknown origin) assessed as inhibition of DEKTDDED phosphorylation at Thr1342 after 60 mins by TR-FRET assay	ic50	0.0300	uM
N-cyclopentyl-4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2-fluoro-5-(2-hydroxyethoxy)benzamide	1610356: Inhibition of recombinant full length human GST-tagged PLK2 expressed in baculovirus expression system using ser/thr 16 as substrate incubated for 1 hr by Z’-LYTE assay	ic50	0.0305	uM

CTD chemical–gene interactions

113 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression	8
Estradiol	decreases expression, decreases reaction, affects expression, affects binding, increases expression (+1 more)	7
sodium arsenite	decreases expression, increases abundance, increases expression	6
Valproic Acid	affects cotreatment, increases expression, decreases expression	6
methylmercuric chloride	decreases expression, increases expression, affects cotreatment	5
Tretinoin	increases expression	4
Aflatoxin B1	affects expression, increases expression	4
trichostatin A	increases expression, affects cotreatment	3
Particulate Matter	increases abundance, affects cotreatment, increases expression, decreases expression	3
potassium chromate(VI)	affects cotreatment, decreases expression, increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
chromium hexavalent ion	affects expression, increases abundance, increases expression	2
perfluorooctane sulfonic acid	decreases expression, increases expression	2
Troglitazone	decreases expression	2
Air Pollutants	decreases expression, increases abundance	2
Cisplatin	increases expression	2
Fluorouracil	increases expression, affects reaction, increases reaction	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	increases expression	2
Cyclosporine	decreases expression, increases expression	2
Sodium Selenite	decreases expression, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
echimidine	affects expression, increases metabolic processing	1
dicrotophos	decreases expression	1
beta-N-methylamino-L-alanine	decreases expression	1
lasiocarpine	increases expression, increases metabolic processing	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1

ChEMBL screening assays

270 unique, capped per target: 268 binding, 1 admet, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1043816	Binding	Residual activity of SNK at 1 uM by microplate scintillation counting	Substituted 2-arylbenzothiazoles as kinase inhibitors: hit-to-lead optimization. — Bioorg Med Chem
CHEMBL4677357	ADMET	Inhibition of FITC-Ahx-DPPLHSpTAI-NH2 binding to Plk2 PBD (unknown origin) expressed in bacterial expression system measured after 30 mins by fluorescence polarization assay	Identification of a New Heterocyclic Scaffold for Inhibitors of the Polo-Box Domain of Polo-like Kinase 1. — J Med Chem
CHEMBL5209953	Functional	Affinity Phenotypic Cellular interaction (Alamar blue proliferation assay (growth inhibiton of BRO cancer cells)) EUB0000669a PLK2	Affinity Phenotypic Cellular Literature for EUbOPEN Chemogenomics Library wave 3

Cellosaurus cell lines

11 cell lines: 10 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1DZ	Abcam HCT 116 PLK2 KO	Cancer cell line	Male
CVCL_B2B7	Abcam HeLa PLK2 KO	Cancer cell line	Female
CVCL_D7XW	Ubigene A-549 PLK2 KO	Cancer cell line	Male
CVCL_D8TD	Ubigene HCT 116 PLK2 KO	Cancer cell line	Male
CVCL_D9NU	Ubigene HEK293 PLK2 KO	Transformed cell line	Female
CVCL_E0L9	Ubigene HeLa PLK2 KO	Cancer cell line	Female
CVCL_TE62	HAP1 PLK2 (-)	Cancer cell line	Male
CVCL_TE63	HAP1 PLK2 (-) 1	Cancer cell line	Male
CVCL_TE64	HAP1 PLK2 (-) 2	Cancer cell line	Male
CVCL_TE65	HAP1 PLK2 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

59 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00556283	PHASE4	COMPLETED	RCT: STARR vs Biofeedback
NCT00226044	PHASE3	COMPLETED	Rectal and Oral Omeprazole Treatment of Reflux Disease in Infants.
NCT03127345	PHASE2	WITHDRAWN	Omega 3 Fatty Acid Treatment for Pediatric Musculoskeletal Health
NCT02033772	Not specified	COMPLETED	Prospective Data Collection of Patients < 6 Months of Age Undergoing Thoracoscopic Surgery
NCT02466451	Not specified	COMPLETED	Study in Children With the Diagnosis of Congenital Diaphragmatic Hernia (CDH) and Oesophageal Atresia (EA)
NCT02525705	Not specified	COMPLETED	Dumping Syndrome After Operation of Esophageal Atresia Type III
NCT02883725	Not specified	COMPLETED	National Register of Oesophageal Atresia
NCT03023865	Not specified	UNKNOWN	Individualized Management for Long Gap Esophageal Atresia
NCT03415893	Not specified	COMPLETED	High-resolution Esophageal Manometry
NCT03455881	Not specified	UNKNOWN	Phenotypic and Genetic Assessment of Tracheal and Esophageal Birth Defects in Patients
NCT03615495	Not specified	COMPLETED	Flourish™ Pediatric Esophageal Atresia
NCT03619408	Not specified	UNKNOWN	Management of Esophagitis Following Repair of Esophageal Atresia
NCT03666767	Not specified	COMPLETED	Management and Outcomes of Congenital Anomalies in Low-, Middle- and High-Income Countries
NCT03730454	Not specified	ACTIVE_NOT_RECRUITING	Transanastomotic Tube for Proximal Esophageal Atresia With Distal Tracheoesophageal Fistula Repair
NCT03767673	Not specified	UNKNOWN	Cardiorespiratory Performance and Pulmonary Microbiome in Patients After Repair of Esophageal Atresia
NCT03999008	Not specified	UNKNOWN	Oral Viscous Budesonide in Anastomotic Stricture After Esophageal Atresia Repair (OVB in EA)
NCT04072419	Not specified	UNKNOWN	Application of Enhanced Recovery After Surgery for Congenital Esophageal Atresia During Perioperative Period
NCT04136795	Not specified	UNKNOWN	Evaluation of the Respiratory Impact After Conventional or Minimally Invasive Esophageal Atresia Surgery
NCT04259528	Not specified	UNKNOWN	Endoscopic Ultrasound Findings in Esophageal Atresia Following Surgical Repair
NCT04522193	Not specified	RECRUITING	Dumping Syndrome and Esophageal Atresia
NCT04901546	Not specified	COMPLETED	Esophageal Atresia: a Natural Experiment of the Effects of Oral Inoculation on the Gut Microbiome
NCT04932746	Not specified	COMPLETED	The Effect of Dexmedetomidine on Oxygen During One Lung Ventilation in Pediatric Surgery.
NCT05129930	Not specified	COMPLETED	Fluid Overload and Pulmonary Function
NCT05527873	Not specified	COMPLETED	Respiratory Complications of Operated Esophageal Atresia in Children
NCT05995171	Not specified	RECRUITING	Long Term Outcome of Easophageal Atresia : Transmics Profiles in Adolescence
NCT06073158	Not specified	COMPLETED	Molecular Signatures of Esophageal Atresia
NCT06208449	Not specified	UNKNOWN	Robotic Versus Thoracoscopy Versus Thoracotomy Repair for Congenital Esophageal Atresia
NCT06335862	Not specified	ENROLLING_BY_INVITATION	Primary Posterior Tracheopexy Prevents Tracheal Collapse
NCT06731855	Not specified	RECRUITING	An Exploratory Physiological Study of Post-operative Recovery in Surgical Neonates and Dimethylarginine:Arginine Levels
NCT06860919	Not specified	RECRUITING	Prospective Evaluation of the Results of Multidisciplinary Follow-up After a Transitional Consultation for Esophageal Atresia
NCT06975982	Not specified	RECRUITING	Symptoms, Pulmonary Function, Muscle Strength, Exercise Capacity, and Frailty in Esophageal Atresia vs. Healthy Peers
NCT07100379	Not specified	RECRUITING	Balloon Inflation Time for Esophageal Strictures (BITES): A Randomized Multi-Center Study
NCT07210736	Not specified	NOT_YET_RECRUITING	Brazilian Multicenter Study on Esophageal Atresia
NCT03223480	PHASE2/PHASE3	COMPLETED	EUS - Guided Balloon-occluded Gastrojejunostomy Bypass
NCT01139853	EARLY_PHASE1	COMPLETED	Post-Operative Impact of Nasogastric Tubes on Rates of Emesis in Infants Diagnosed With Pyloric Stenosis
NCT00144924	Not specified	TERMINATED	Open vs Laparoscopic Pyloromyotomy for Pyloric Stenosis
NCT00409734	Not specified	COMPLETED	Frequency of Formula Change Prior to the Accurate Diagnosis of Pyloric Stenosis
NCT00487552	Not specified	TERMINATED	Magnetic Anastomosis Device Relief of Malignant Gastric Outlet Obstruction
NCT00991614	Not specified	COMPLETED	EVOLUTION® Duodenal Stent for Duodenal or Gastric Outlet Obstruction Caused by Malignant Neoplasms
NCT01839292	Not specified	COMPLETED	ComVi and D-type Stent in Malignant GOO