PKN2

Summary

PKN2 (protein kinase N2, HGNC:9406) is a protein-coding gene on chromosome 1p22.2, encoding Serine/threonine-protein kinase N2 (Q16513). PKC-related serine/threonine-protein kinase and Rho/Rac effector protein that participates in specific signal transduction responses in the cell. It is a selective cancer dependency (DepMap: 27.1% of cell lines).

Enables RNA polymerase binding activity; histone deacetylase binding activity; and protein serine/threonine kinase activity. Involved in several processes, including apical junction assembly; positive regulation of cell cycle; and positive regulation of viral genome replication. Located in several cellular components, including cleavage furrow; cytoskeleton; and midbody. Part of protein-containing complex.

Source: NCBI Gene 5586 — RefSeq curated summary.

At a glance

• GWAS associations: 43
• Clinical variants (ClinVar): 112 total
• Druggable target: yes — 38 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 27.1% of screened cell lines
• MANE Select transcript: NM_006256

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9406
Approved symbol	PKN2
Name	protein kinase N2
Location	1p22.2
Locus type	gene with protein product
Status	Approved
Aliases	PRK2, Pak-2, STK7
Ensembl gene	ENSG00000065243
Ensembl biotype	protein_coding
OMIM	602549
Entrez	5586

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 13 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000316005, ENST00000370513, ENST00000370521, ENST00000436111, ENST00000449189, ENST00000495119, ENST00000866343, ENST00000866344, ENST00000866345, ENST00000866346, ENST00000866347, ENST00000932757, ENST00000932758, ENST00000953595

RefSeq mRNA: 4 — MANE Select: NM_006256 NM_001320707, NM_001320708, NM_001320709, NM_006256

CCDS: CCDS714, CCDS81350

Canonical transcript exons

ENST00000370521 — 22 exons

Exon	Start	End
ENSE00000464350	88771663	88771879
ENSE00000776277	88784639	88784824
ENSE00000776278	88786104	88786213
ENSE00001274666	88804391	88804534
ENSE00001592041	88807529	88807604
ENSE00001625739	88805497	88805671
ENSE00001633414	88805891	88806017
ENSE00001656730	88833077	88833157
ENSE00001673758	88770352	88770469
ENSE00001675560	88807684	88807775
ENSE00001687287	88824310	88824386
ENSE00001700083	88832744	88832851
ENSE00001702051	88771421	88771566
ENSE00001705588	88813557	88813733
ENSE00001707510	88740988	88741288
ENSE00001713357	88828481	88828623
ENSE00001735993	88833245	88836255
ENSE00001789306	88821941	88822003
ENSE00001803024	88807313	88807443
ENSE00003657696	88760222	88760376
ENSE00003752048	88804846	88804921
ENSE00003845712	88684273	88684628

Expression profiles

Bgee: expression breadth ubiquitous, 300 present calls, max score 97.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 43.9522 / max 692.0845, expressed in 1822 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
3919	35.3124	1819
3920	4.6780	1384
3922	1.5881	860
3923	1.4416	834
3921	0.5756	348
3924	0.2425	86
3927	0.1139	57

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tongue squamous epithelium	UBERON:0006919	97.91	gold quality
nipple	UBERON:0002030	96.60	gold quality
secondary oocyte	CL:0000655	96.47	gold quality
parotid gland	UBERON:0001831	96.42	gold quality
pylorus	UBERON:0001166	96.20	gold quality
jejunal mucosa	UBERON:0000399	96.00	gold quality
calcaneal tendon	UBERON:0003701	95.60	gold quality
visceral pleura	UBERON:0002401	95.59	gold quality
amniotic fluid	UBERON:0000173	95.21	gold quality
cervix squamous epithelium	UBERON:0006922	95.18	gold quality
cardia of stomach	UBERON:0001162	94.68	gold quality
trabecular bone tissue	UBERON:0002483	94.66	gold quality
renal medulla	UBERON:0000362	94.59	gold quality
squamous epithelium	UBERON:0006914	94.56	gold quality
adrenal tissue	UBERON:0018303	94.56	gold quality
caput epididymis	UBERON:0004358	94.53	gold quality
parietal pleura	UBERON:0002400	94.48	gold quality
oral cavity	UBERON:0000167	94.44	gold quality
pharyngeal mucosa	UBERON:0000355	94.30	gold quality
cranial nerve II	UBERON:0000941	94.27	gold quality
esophagus squamous epithelium	UBERON:0006920	94.21	gold quality
jejunum	UBERON:0002115	94.20	gold quality
pleura	UBERON:0000977	94.08	gold quality
mucosa of sigmoid colon	UBERON:0004993	94.02	gold quality
urethra	UBERON:0000057	93.85	gold quality
duodenum	UBERON:0002114	93.84	gold quality
gingival epithelium	UBERON:0001949	93.77	gold quality
cauda epididymis	UBERON:0004360	93.72	gold quality
inferior vagus X ganglion	UBERON:0005363	93.70	gold quality
oviduct epithelium	UBERON:0004804	93.67	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.70

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4

miRNA regulators (miRDB)

213 targeting PKN2, 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-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-340-5P	100.00	72.50	4437
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 27.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 21)

• PRK2/PKN2, is an essential regulator of both entry into mitosis and exit from cytokinesis in HeLa S3 cells, required for abscission of the midbody at the end of the cell division cycle and for phosphorylation and activation of Cdc25B. (PMID:17332740)
• These observations highlight elements of Nef’s functional complexity and demonstrate previously unsuspected structural requirements for PAK-2 activation and MHC-1 down-modulation in Nef’s flexible N- and C-terminal regions. (PMID:17632197)
• Little evidence of association was observed between SNPs in PKN2 and type 2 diabetes in African Americans. (PMID:18443202)
• the last seven amino acid residues at the C-terminus of PRK2 are not required for the activation of the kinase by RhoA in vitro, however, the extreme C-terminal segment is critical for the full activation of PRK2 by RhoA in cells (PMID:18835241)
• Protein kinase C-related kinase targets nuclear localization signals in a subset of class IIa histone deacetylases. (PMID:20188095)
• Rho binding is essential for PRK2 function and facilitates PRK2 recruitment to junctions. Kinase-dead PRK2 acts as a dominant-negative mutant and prevents apical junction formation. (PMID:20974804)
• PKN isoforms are not simply redundant in supporting migration, but appear to be linked through isoform specific regulatory domain properties to selective upstream signals. It (PMID:21754995)
• these findings suggest that Hsp90 plays a critical role in the regulation of HCV RNA polymerase phosphorylation via the PDK1-PRK2 signaling pathway. (PMID:22490666)
• Regulation of protein kinase C-related protein kinase 2 (PRK2) by an intermolecular PRK2-PRK2 interaction mediated by Its N-terminal domain. (PMID:22511787)
• findings demonstrate that Yersinia enterocolitica rYopM interacts with RSK1 and PRK2 following cell-penetration (PMID:25513777)
• Helicobacter pylori CagA interacts with PRK2 and inhibits its kinase activity. (PMID:26041307)
• TXA2-mediated neoplastic responses in prostate adenocarcinoma PC-3 cells occur through a PRK1/PRK2-dependent mechanism. (PMID:26296974)
• Steady-state kinetic analysis revealed that PKN1-3 follows a sequential ordered Bi-Bi kinetic mechanism, where peptide substrate binding is preceded by ATP binding. This kinetic mechanism was confirmed by additional kinetic studies for product inhibition and affinity of small molecule inhibitors. (PMID:27919031)
• PKN2 knockdown in vitro decreased insulin-stimulated glucose uptake, incorporation into glycogen, and oxidation. Thus, PKN2 alters key signaling pathways and transcriptional networks to regulate glucose and lipid metabolism. (PMID:28720584)
• The expression of PKN2 in colon cancer cells suppresses tumor associated M2 macrophage polarization and tumor growth. (PMID:29368606)
• Novel roles of PRK1 and PRK2 in cilia and cancer biology. (PMID:32127582)
• LINC00668 cooperated with HuR dependent upregulation of PKN2 to facilitate gastric cancer metastasis. (PMID:33879018)
• Protein kinase N2 mediates flow-induced endothelial NOS activation and vascular tone regulation. (PMID:34499618)
• Role of PKM2-Mediated Immunometabolic Reprogramming on Development of Cytokine Storm. (PMID:34759927)
• Genome-Wide Association Study for Idiopathic Ventricular Tachyarrhythmias Identifies Key Role of CCR7 and PKN2 in Calcium Homeostasis and Cardiac Rhythm Maintenance. (PMID:35895078)
• Increased PKN2 and M2-Polarized Macrophages Promote HCT116 Cell Invasion. (PMID:38505918)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	pkn2b	ENSDARG00000101293
danio_rerio	pkn2a	ENSDARG00000101983
mus_musculus	Pkn2	ENSMUSG00000004591
rattus_norvegicus	Pkn2	ENSRNOG00000011317
drosophila_melanogaster	Pkc53E	FBGN0003091
drosophila_melanogaster	inaC	FBGN0004784
drosophila_melanogaster	Pkn	FBGN0020621
drosophila_melanogaster	Pkcdelta	FBGN0287828
caenorhabditis_elegans		WBGENE00004033
caenorhabditis_elegans		WBGENE00006599
caenorhabditis_elegans		WBGENE00009793

Paralogs (9): PRKCH (ENSG00000027075), PRKCZ (ENSG00000067606), PKN1 (ENSG00000123143), PRKCG (ENSG00000126583), PRKCA (ENSG00000154229), PKN3 (ENSG00000160447), PRKCI (ENSG00000163558), PRKCB (ENSG00000166501), PRKCE (ENSG00000171132)

Protein

Protein identifiers

Serine/threonine-protein kinase N2 — Q16513 (reviewed: Q16513)

Alternative names: PKN gamma, Protein kinase C-like 2, Protein-kinase C-related kinase 2

All UniProt accessions (4): Q16513, B1AL79, H0Y429, H0Y5V5

UniProt curated annotations — full annotation on UniProt →

Function. PKC-related serine/threonine-protein kinase and Rho/Rac effector protein that participates in specific signal transduction responses in the cell. Plays a role in the regulation of cell cycle progression, actin cytoskeleton assembly, cell migration, cell adhesion, tumor cell invasion and transcription activation signaling processes. Phosphorylates CTTN in hyaluronan-induced astrocytes and hence decreases CTTN ability to associate with filamentous actin. Phosphorylates HDAC5, therefore lead to impair HDAC5 import. Direct RhoA target required for the regulation of the maturation of primordial junctions into apical junction formation in bronchial epithelial cells. Required for G2/M phases of the cell cycle progression and abscission during cytokinesis in a ECT2-dependent manner. Stimulates FYN kinase activity that is required for establishment of skin cell-cell adhesion during keratinocytes differentiation. Regulates epithelial bladder cells speed and direction of movement during cell migration and tumor cell invasion. Inhibits Akt pro-survival-induced kinase activity. Mediates Rho protein-induced transcriptional activation via the c-fos serum response factor (SRF). Involved in the negative regulation of ciliogenesis. (Microbial infection) Phosphorylates HCV NS5B leading to stimulation of HCV RNA replication.

Subunit / interactions. Interacts (via the REM repeats) with RHOA (GTP-bound form preferentially) and interacts (via the REM repeats) with RAC1 (GTP-bound form preferentially); the interactions induce its autophosphorylation. Interacts with RHOC. Interacts with NCK1 and NCK2. Interacts with NCK1 (via SH3 domains). Interacts with CD44. Interacts (via C-terminal kinase domain) with PDPK1; the interaction stimulates PDPK1 kinase activity. Interacts with MAP3K2; the interaction activates PRK2 kinase activity in a MAP3K2-independent kinase activity. Interacts (via C-terminal domain) with AKT1; the interaction occurs with the C-terminal cleavage product of PRK2 in apoptotic cells. Interacts (via C-terminus) with PTPN13 (via PDZ 3 domain). Interacts with CDK10. (Microbial infection) Interacts with HCV NS5B (via N-terminal finger domain).

Subcellular location. Cytoplasm. Nucleus. Membrane. Cell projection. Lamellipodium. Cytoskeleton. Cleavage furrow. Midbody. Cell junction.

Tissue specificity. Ubiquitous. Expressed in numerous tumor cell lines, especially in bladder tumor cells.

Post-translational modifications. Autophosphorylated. Phosphorylated during mitosis. Phosphorylated by CDK10. Activated by limited proteolysis with trypsin. Proteolytically cleaved by caspase-3 during the induction of apoptotic cell death.

Activity regulation. Kinase activity is activated upon binding to GTP-bound Rhoa/Rac1 GTPases. Activated by caspase-3 (CASP3) cleavage during apoptosis. Activated by lipids, particularly cardiolipin and to a lesser extent by other acidic phospholipids and unsaturated fatty acids. Two specific sites, Thr-816 (activation loop of the kinase domain) and Thr-958 (turn motif), need to be phosphorylated for its full activation.

Domain organisation. The N-terminal regioninterferes with the interaction between AKT1 and the C-terminal regionof PKN2. The C1 domain does not bind the diacylglycerol (DAG). The apoptotic C-terminal cleavage product inhibits EGF-induced kinase activity of AKT1 phosphorylation at ‘Thr-308’ and ‘Ser-473’ sites, PDPK1 autophosphorylation and kinases PRKCD and PRKCZ phosphorylations.

Induction. Up-regulated during keratinocyte differentiation.

Similarity. Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.

Isoforms (5)

UniProt ID	Names	Canonical?
Q16513-1	1	yes
Q16513-2	2
Q16513-3	3
Q16513-4	4
Q16513-5	5

RefSeq proteins (4): NP_001307636, NP_001307637, NP_001307638, NP_006247* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR000719	Prot_kinase_dom	Domain
IPR000961	AGC-kinase_C	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR011072	HR1_rho-bd	Domain
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR017892	Pkinase_C	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR036274	HR1_rpt_sf	Homologous_superfamily
IPR037313	PKN_HR1_1	Domain
IPR037784	C2_PKN	Domain

Pfam: PF00069, PF00433, PF02185

Enzyme classification (BRENDA):

• EC 2.7.11.13 — protein kinase C (BRENDA: 25 organisms, 203 substrates, 258 inhibitors, 20 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
FKKQGSFAKKK	0.0166–0.0599	10
ATP	0.0001–0.0828	4
N6-PHENYL-ATP	0.0124	1
S6-(229-239) PEPTIDE	0.0036	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 (94 total): modified residue 17, mutagenesis site 16, helix 16, strand 11, domain 6, region of interest 6, splice variant 5, sequence conflict 4, sequence variant 3, compositionally biased region 2, binding site 2, site 2, turn 2, chain 1, active site 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
4RRV	X-RAY DIFFRACTION	1.41
6CCY	X-RAY DIFFRACTION	2.18
4CRS	X-RAY DIFFRACTION	2.75
6GBE	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16513-F1	72.06	0.33

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 (3): 782 (proton acceptor); 117–118 (cleavage; by caspase-3); 700–701 (cleavage; by caspase-3)

Ligand- & substrate-binding residues (2): 663–671; 686

Post-translational modifications (17): 21, 77, 110, 121, 124, 302, 306, 360, 362, 535, 583, 620, 628, 631, 816, 952, 958

Mutagenesis-validated functional residues (16):

Position	Phenotype
117	prevents proteolytic processing by caspase-3 during apoptosis. diminishes pro-apoptotic function; when associated with e
121	does not suppress ciliogenesis; when associated with a-124.
124	does not suppress ciliogenesis; when associated with a-121.
686	does not inhibit interaction with ptpn13.
700	prevents proteolytic processing by caspase-3 during apoptosis. diminishes pro-apoptotic function; when associated with a
816	reduces catalytic activity.
958	abolishes catalytic activity.
974	abolishes interaction with pdpk1 and prevents the phosphorylation of akt1 at ‘ser-473’.
977	abolishes interaction with pdpk1 and prevents the phosphorylation of akt1 at ‘ser-473’. reduces catalytic activity by 90
977	reduces catalytic activity by 50%.
978	abolishes interaction with pdpk1 and prevents the phosphorylation of akt1 at ‘ser-473’.
978	does not inhibit catalytic activity.
979	abolishes interaction with pdpk1 and prevents the phosphorylation of akt1 at ‘ser-473’.
979	reduces catalytic activity by 50%.
979	reduces catalytic activity by 25%.
984	inhibits interaction with ptpn13.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-5625740	RHO GTPases activate PKNs
R-HSA-8980692	RHOA GTPase cycle
R-HSA-9013026	RHOB GTPase cycle
R-HSA-9013106	RHOC GTPase cycle
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9856530	High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells

MSigDB gene sets: 266 (showing top): MULLIGHAN_NPM1_SIGNATURE_3_UP, LU_IL4_SIGNALING, GOBP_RESPONSE_TO_FLUID_SHEAR_STRESS, GOBP_CELLULAR_RESPONSE_TO_FLUID_SHEAR_STRESS, GOBP_APICAL_JUNCTION_ASSEMBLY, GOBP_POSITIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, GOBP_POSITIVE_REGULATION_OF_VIRAL_GENOME_REPLICATION, GOMF_GTPASE_BINDING, GOBP_AMEBOIDAL_TYPE_CELL_MIGRATION, PID_RHOA_PATHWAY, IRF7_01, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_CYTOKINESIS, GOBP_POSITIVE_REGULATION_OF_CELL_DIVISION, GOBP_TISSUE_MIGRATION

GO Biological Process (14): protein phosphorylation (GO:0006468), apoptotic process (GO:0006915), cell adhesion (GO:0007155), signal transduction (GO:0007165), epithelial cell migration (GO:0010631), cell projection organization (GO:0030030), positive regulation of cytokinesis (GO:0032467), intracellular signal transduction (GO:0035556), apical junction assembly (GO:0043297), positive regulation of viral genome replication (GO:0045070), positive regulation of mitotic cell cycle (GO:0045931), cell division (GO:0051301), vascular endothelial cell response to laminar fluid shear stress (GO:0097700), regulation of cell motility (GO:2000145)

GO Molecular Function (15): RNA binding (GO:0003723), protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), diacylglycerol-dependent serine/threonine kinase activity (GO:0004697), protein tyrosine kinase activity (GO:0004713), ATP binding (GO:0005524), kinase activity (GO:0016301), small GTPase binding (GO:0031267), histone deacetylase binding (GO:0042826), cadherin binding (GO:0045296), RNA polymerase binding (GO:0070063), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (18): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), plasma membrane (GO:0005886), nuclear body (GO:0016604), lamellipodium (GO:0030027), midbody (GO:0030496), cleavage furrow (GO:0032154), protein-containing complex (GO:0032991), apical junction complex (GO:0043296), intermediate filament cytoskeleton (GO:0045111), perinuclear region of cytoplasm (GO:0048471), cytoskeleton (GO:0005856), membrane (GO:0016020), cell projection (GO:0042995), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
RHO GTPase cycle	4
RHO GTPase Effectors	1
Response of endothelial cells to shear stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
cellular process	3
protein kinase activity	3
regulation of cellular process	2
intracellular anatomical structure	2
enzyme binding	2
cytoplasm	2
intracellular membraneless organelle	2
phosphorylation	1
protein modification process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell communication	1
signaling	1
cellular response to stimulus	1
ameboidal-type cell migration	1
epithelium migration	1
cellular component organization	1
cytokinesis	1
regulation of cytokinesis	1
positive regulation of cell division	1
positive regulation of cell cycle process	1
signal transduction	1
cell-cell junction assembly	1
viral genome replication	1
regulation of viral genome replication	1
positive regulation of viral process	1
mitotic cell cycle	1
regulation of mitotic cell cycle	1
positive regulation of cell cycle	1
cellular response to laminar fluid shear stress	1
vascular endothelial cell response to fluid shear stress	1
regulation of locomotion	1
cell motility	1
nucleic acid binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
protein serine/threonine kinase activity	1

Protein interactions and networks

STRING

2224 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PKN2	RHOA	P06749	747
PKN2	AKT1	P31749	739
PKN2	RPS6KA1	Q15418	669
PKN2	RHOC	P08134	597
PKN2	SNW1	Q13573	594
PKN2	MEFV	O15553	584
PKN2	NCK1	P16333	497
PKN2	RAC1	P15154	481
PKN2	NCK2	O43639	474
PKN2	FAM241A	Q8N8J7	472
PKN2	ASH1L	Q9NR48	469
PKN2	CCNQ	Q8N1B3	461
PKN2	PLCG2	P16885	451
PKN2	GTF2B	Q00403	439
PKN2	S100A8	P05109	434

IntAct

243 interactions, top by confidence:

A	B	Type	Score
RHOA	ARHGEF11	psi-mi:“MI:0914”(association)	0.900
MOB1B	LATS1	psi-mi:“MI:0914”(association)	0.840
CETN2	SFI1	psi-mi:“MI:0914”(association)	0.740
RHOA	CTSA	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CETN1	SFI1	psi-mi:“MI:0914”(association)	0.640
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640
PKN2	CETN2	psi-mi:“MI:0915”(physical association)	0.600
PKN2	GOPC	psi-mi:“MI:0407”(direct interaction)	0.590
PKN2	FRMPD2	psi-mi:“MI:0407”(direct interaction)	0.590
HAVCR2	TCAF2	psi-mi:“MI:0914”(association)	0.530
TGFBR2	PIK3R2	psi-mi:“MI:0914”(association)	0.530
DFFB	UBB	psi-mi:“MI:0914”(association)	0.530
PPIAL4G	ACTB	psi-mi:“MI:0914”(association)	0.530
ABLIM2	AFDN	psi-mi:“MI:0914”(association)	0.530
PNMA2	CCDC85C	psi-mi:“MI:0914”(association)	0.530

BioGRID (243): PKN2 (Affinity Capture-MS), PKN2 (Affinity Capture-MS), PKN2 (Affinity Capture-MS), PKN2 (Affinity Capture-MS), PKN2 (Affinity Capture-MS), PKN2 (Affinity Capture-RNA), ACBD3 (Co-fractionation), LSM2 (Co-fractionation), LSM3 (Co-fractionation), LSM4 (Co-fractionation), LSM6 (Co-fractionation), LSM7 (Co-fractionation), PKN2 (Co-fractionation), PPM1B (Co-fractionation), RPE (Co-fractionation)

ESM2 similar proteins: A1A4I4, A1A5B6, A4D2P6, B2DCZ9, B4F7F3, O00192, O08773, O08874, O08908, O35465, O43566, O62683, O75808, O95049, P70268, P97492, Q0QWG9, Q12851, Q14164, Q14318, Q16512, Q16513, Q3B7U9, Q3KR56, Q3MII6, Q3UFB7, Q5FVC2, Q60875, Q61161, Q63433, Q63788, Q6P5Z2, Q6PFQ7, Q6V7V2, Q6ZT62, Q7Z5H3, Q865S3, Q8BWW9, Q8IYK8, Q8K045

Diamond homologs: A0A509AKL0, A1A4I4, A5K0N4, A7MBL8, A8XJQ6, A8XNJ6, A8XW88, F4HYG2, G1X456, J9W0G9, O42632, O43930, O77676, P00516, P00517, P04409, P05131, P05132, P05383, P05696, P05986, P06244, P06245, P0C605, P10102, P10665, P10666, P11792, P12370, P12688, P16911, P16912, P17252, P17612, P18652, P18654, P18961, P20444, P21137, P22612

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
PDK1	“up-regulates activity”	PKN2	phosphorylation
PDPK1	up-regulates	PKN2	phosphorylation
PKN2	“down-regulates activity”	MEFV	phosphorylation
RHOA	“up-regulates activity”	PKN2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 184 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	5	23.0×	4e-04
Unblocking of NMDA receptors, glutamate binding and activation	5	21.9×	4e-04
Negative regulation of NMDA receptor-mediated neuronal transmission	5	21.9×	4e-04
Chaperone Mediated Autophagy	5	20.0×	6e-04
Long-term potentiation	5	19.2×	6e-04
Assembly and cell surface presentation of NMDA receptors	8	16.4×	1e-05
Neurexins and neuroligins	9	14.3×	9e-06
EPHB-mediated forward signaling	5	10.7×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	9	29.9×	1e-08
receptor clustering	8	28.5×	1e-07
protein localization to synapse	6	26.3×	2e-05
regulation of postsynaptic membrane neurotransmitter receptor levels	7	19.8×	2e-05
cell-cell adhesion	11	6.4×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	78
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4375 predictions. Top by Δscore:

Variant	Effect	Δscore
1:88687163:G:GG	donor_gain	1.0000
1:88741150:A:T	donor_gain	1.0000
1:88741284:TACAG:T	donor_loss	1.0000
1:88741285:ACAG:A	donor_loss	1.0000
1:88741286:CAGGT:C	donor_loss	1.0000
1:88741287:AGGT:A	donor_loss	1.0000
1:88741288:GGT:G	donor_loss	1.0000
1:88741289:G:T	donor_loss	1.0000
1:88741290:T:A	donor_loss	1.0000
1:88760214:A:AG	acceptor_gain	1.0000
1:88760215:T:G	acceptor_gain	1.0000
1:88760217:TACA:T	acceptor_loss	1.0000
1:88760218:ACAG:A	acceptor_loss	1.0000
1:88760219:CAGAT:C	acceptor_loss	1.0000
1:88760220:A:AG	acceptor_gain	1.0000
1:88760220:AGATT:A	acceptor_gain	1.0000
1:88760221:G:GA	acceptor_gain	1.0000
1:88760221:GA:G	acceptor_gain	1.0000
1:88760221:GAT:G	acceptor_gain	1.0000
1:88760221:GATT:G	acceptor_gain	1.0000
1:88760221:GATTG:G	acceptor_gain	1.0000
1:88760374:AAG:A	donor_gain	1.0000
1:88760375:AG:A	donor_gain	1.0000
1:88760375:AGGTA:A	donor_loss	1.0000
1:88760376:GG:G	donor_gain	1.0000
1:88760376:GGTA:G	donor_loss	1.0000
1:88760377:G:GG	donor_gain	1.0000
1:88760378:T:A	donor_loss	1.0000
1:88771564:G:GT	donor_gain	1.0000
1:88771564:GAA:G	donor_gain	1.0000

AlphaMissense

6507 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:88741145:T:C	L69P	1.000
1:88771703:T:C	L270P	1.000
1:88771879:G:C	G329R	1.000
1:88771879:G:T	G329C	1.000
1:88784639:G:A	G329D	1.000
1:88784639:G:T	G329V	1.000
1:88784645:T:C	L331S	1.000
1:88784645:T:G	L331W	1.000
1:88784651:T:A	V333D	1.000
1:88784657:T:A	L335H	1.000
1:88784657:T:C	L335P	1.000
1:88784662:G:C	G337R	1.000
1:88784662:G:T	G337C	1.000
1:88784663:G:A	G337D	1.000
1:88784663:G:T	G337V	1.000
1:88786116:C:A	A395D	1.000
1:88786122:T:C	L397S	1.000
1:88786128:T:C	L399P	1.000
1:88786181:T:A	W417R	1.000
1:88786181:T:C	W417R	1.000
1:88786183:G:C	W417C	1.000
1:88786183:G:T	W417C	1.000
1:88804401:T:C	L431P	1.000
1:88804413:T:A	V435D	1.000
1:88804455:T:C	L449P	1.000
1:88804461:T:C	L451S	1.000
1:88804470:T:C	F454S	1.000
1:88804512:C:A	P468Q	1.000
1:88804517:G:C	G470R	1.000
1:88804852:T:C	F478L	1.000

dbSNP variants (sampled 300 via entrez): RS1000032077 (1:88734764 T>C), RS1000078927 (1:88786312 A>G), RS1000132576 (1:88794902 C>T), RS1000143057 (1:88782128 C>T), RS1000153114 (1:88825152 G>C,T), RS1000162990 (1:88729048 C>G,T), RS1000185255 (1:88794702 T>A), RS1000185757 (1:88815337 C>T), RS1000192931 (1:88826736 A>G), RS1000193527 (1:88773169 G>C), RS1000207372 (1:88762622 G>T), RS1000236531 (1:88706833 G>C), RS1000245837 (1:88772769 A>G), RS1000253662 (1:88832025 T>G), RS1000331308 (1:88765614 T>G)

Disease associations

OMIM: gene MIM:602549 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

43 associations (top):

Study	Trait	p-value
GCST000817_16	Height	5.000000e-09
GCST001277_8	Liver enzyme levels (gamma-glutamyl transferase)	4.000000e-11
GCST001588_2	Periodontal microbiota	1.000000e-06
GCST002166_12	Serum protein levels (sST2)	4.000000e-07
GCST002647_86	Height	6.000000e-20
GCST003486_8	Response to fenofibrate (LDL cholesterol levels)	5.000000e-06
GCST003992_3	Photic sneeze reflex	1.000000e-10
GCST005196_184	Coronary artery disease	2.000000e-06
GCST005352_21	Paclitaxel disposition in epithelial ovarian cancer	2.000000e-07
GCST005522_6	Narcolepsy	2.000000e-06
GCST005580_314	Intraocular pressure	5.000000e-09
GCST005790_80	Rosacea symptom severity	2.000000e-06
GCST006288_605	Heel bone mineral density	1.000000e-11
GCST006288_710	Heel bone mineral density	1.000000e-06
GCST006628_31	Systolic blood pressure	1.000000e-10
GCST006979_990	Heel bone mineral density	1.000000e-23
GCST007094_118	Diastolic blood pressure	4.000000e-06
GCST007096_54	Pulse pressure	2.000000e-09
GCST007099_12	Systolic blood pressure	1.000000e-11
GCST007325_105	General risk tolerance (MTAG)	2.000000e-10
GCST007611_10	Chronic obstructive pulmonary disease or high blood pressure (pleiotropy)	3.000000e-12
GCST008839_122	Height	5.000000e-29
GCST009277_2	Subjective response to placebo treatment in childhood asthma (change in cough/wheeze)	8.000000e-07
GCST009723_96	Vertical cup-disc ratio (adjusted for vertical disc diameter)	2.000000e-07
GCST009724_85	Vertical cup-disc ratio (multi-trait analysis)	6.000000e-09
GCST010002_361	Refractive error	3.000000e-08
GCST010170_7	Neonatal total 25-hydroxyvitamin D levels (maternal genetic effect)	4.000000e-06
GCST011946_6	White matter hyperintensity volume	4.000000e-06
GCST011947_57	White matter hyperintensity volume	3.000000e-07
GCST011949_24	White matter hyperintensity volume (adjusted for hypertension)	4.000000e-07

EFO canonical traits (20, from GWAS)

EFO ID	Trait name
EFO:0004532	serum gamma-glutamyl transferase measurement
EFO:0007804	LDL cholesterol change measurement
EFO:0007887	autosomal dominant compelling helio-ophthalmic outburst syndrome
EFO:0004695	intraocular pressure measurement
EFO:0009180	rosacea severity measurement
EFO:0009270	heel bone mineral density
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0008579	risk-taking behaviour
EFO:0008344	response to placebo
EFO:0010068	respiratory symptom change measurement
EFO:0006939	cup-to-disc ratio measurement
EFO:0005939	parental genotype effect measurement
EFO:0005665	white matter hyperintensity measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0004980	appendicular lean mass
EFO:0009749	age at first sexual intercourse measurement
EFO:0004305	erythrocyte count
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3032 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

38 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 277,543 (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
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL1983268	ENTRECTINIB	4	3,510
CHEMBL2103743	TOFACITINIB CITRATE	4	1,672
CHEMBL2105759	BARICITINIB	4	6,741
CHEMBL221959	TOFACITINIB	4	10,408
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL5416410	DASATINIB	4	655
CHEMBL553	ERLOTINIB	4	108,300
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL2105728	CRENOLANIB	3	2,167
CHEMBL3426621	RIPASUDIL	3	870
CHEMBL38380	FASUDIL	3	11,953
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3	77
CHEMBL1667969	SAR-407899 FREE BASE	2	157
CHEMBL1721885	SU-014813	2	363
CHEMBL1944698	ZOTIRACICLIB	2	2,915
CHEMBL1967878	CENISERTIB	2
CHEMBL1980297	ILORASERTIB	2
CHEMBL362558	LY-2090314	2
CHEMBL384304	RG-547	2
CHEMBL475251	R-406	2
CHEMBL495727	AT-9283	2
CHEMBL565612	SOTRASTAURIN	2
CHEMBL572878	TOZASERTIB	2
CHEMBL574737	UCN-01	2
CHEMBL1084546	PF-00562271	1

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Protein kinase N (PKN) family

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
compound 32 [PMID: 20471253]	Inhibition	7.85	pIC50
ninvosudil	Inhibition	7.15	pIC50

Binding affinities (BindingDB)

8 measured of 8 human assays (8 total across all organisms); most potent 8 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Staurosporine	KD	1.7 nM
CHEMBL5175087	KI	25 nM
PKC-412	KD	190 nM
(3Z)-4-amino-5-fluoro-3-[5-(4-methylpiperazino)-1,3-dihydrobenzimidazol-2-ylidene]carbostyril	KD	520 nM
(18S)-18-[(dimethylamino)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.1^{7,14}.0^{2,6}.0^{8,13}.0^{22,27}]nonacosa-1(28),2(6),7(29),8(13),9,11,22(27),23,25-nonaene-3,5-dione	KD	700 nM
5-[(Z)-(5-fluoranyl-2-oxidanylidene-1H-indol-3-ylidene)methyl]-2,4-dimethyl-N-[(2S)-3-morpholin-4-yl-2-oxidanyl-propyl]-1H-pyrrole-3-carboxamide	KD	2600 nM
1-Acyl-1H-[1,2,4]triazole-3,5-diamine Analogue 3b	KD	3100 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

ChEMBL bioactivities

430 potent at pChembl≥5 of 444 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.10	Ki	0.7943	nM	CHEMBL1980995
8.74	Kd	1.8	nM	LESTAURTINIB
8.71	IC50	1.97	nM	STAUROSPORINE
8.66	IC50	2.2	nM	STAUROSPORINE
8.60	Kd	2.5	nM	STAUROSPORINE
8.60	Ki	2.512	nM	CHEMBL1998432
8.60	Ki	2.512	nM	CHEMBL1969588
8.60	Ki	2.512	nM	CHEMBL1968930
8.40	Kd	4	nM	CHEMBL4576489
8.30	Ki	5.012	nM	CHEMBL1972290
8.30	Ki	5.012	nM	CHEMBL225519
8.30	Ki	5.012	nM	CHEMBL1970903
8.30	Ki	5.012	nM	CHEMBL2001751
8.22	Kd	6	nM	CHEMBL4465866
8.21	IC50	6.09	nM	STAUROSPORINE
8.20	Ki	6.31	nM	CHEMBL1994977
8.20	Ki	6.31	nM	CHEMBL1973540
8.15	IC50	7	nM	CHEMBL1214929
8.15	Ki	7	nM	CHEMBL5182936
8.10	Kd	8	nM	SAR-407899 FREE BASE
8.10	Ki	8	nM	CHEMBL225519
8.10	Ki	8	nM	CHEMBL250870
8.10	Ki	7.943	nM	CHEMBL1986943
8.05	Kd	9	nM	AT-13148
8.05	IC50	9	nM	CHEMBL5557426
8.00	Ki	10	nM	CHEMBL2006456
8.00	Ki	10	nM	CHEMBL1969151
7.92	IC50	11.9	nM	STAUROSPORINE
7.90	Ki	12.59	nM	CHEMBL1991674
7.85	IC50	14	nM	CHEMBL1082821
7.82	Ki	15	nM	CHEMBL250871
7.82	IC50	15	nM	CHEMBL5182936
7.82	Kd	15	nM	MIDOSTAURIN
7.80	IC50	16	nM	CHEMBL225519
7.80	IC50	16	nM	CHEMBL250870
7.80	Ki	15.85	nM	CHEMBL1996980
7.80	Ki	15.85	nM	CHEMBL1997534
7.80	Ki	15.85	nM	CHEMBL1974870
7.78	IC50	16.8	nM	STAUROSPORINE
7.77	IC50	17	nM	CHEMBL2147538
7.70	Ki	19.95	nM	CHEMBL1987261
7.70	Ki	19.95	nM	CHEMBL1985723
7.70	Ki	19.95	nM	CHEMBL1965660
7.70	Ki	19.95	nM	CHEMBL1976936
7.70	Ki	19.95	nM	CHEMBL1974935
7.70	Ki	19.95	nM	CHEMBL1998121
7.70	Ki	19.95	nM	CHEMBL1991063
7.60	Ki	25	nM	CHEMBL5175087
7.60	Ki	25.12	nM	CHEMBL1964290
7.60	Ki	25.12	nM	CHEMBL1998159

PubChem BioAssay actives

134 with measured affinity, of 1259 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
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	508038: Binding affinity to PKN2	kd	0.0018	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-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	1612687: Inhibition of human PKN2 using KKLNRTLSVA as substrate by [gamma-33P]-ATP assay	ic50	0.0020	uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-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-4-yl]-methylamino]ethoxy]ethoxy]ethoxy]ethyl]propanamide	1526293: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged PKN2 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.0040	uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-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-4-yl]amino]ethoxy]ethoxy]ethoxy]ethyl]propanamide	1526293: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged PKN2 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.0060	uM
1-propyl-2-pyridin-4-yl-6,7-dihydro-5H-pyrrolo[3,2-c]pyridin-4-one	1879129: Inhibition of PKN2 (unknown origin) by TR-FRET-based tracer displacement assay dependent Cheng-Prusoff equation analysis	ki	0.0070	uM
N’-(3-pyridin-4-yl-2,6-naphthyridin-1-yl)ethane-1,2-diamine	1165791: Inhibition of human recombinant PKN-2 using AKRRRLSSLRA as substrate after 40 mins by scintillation counting analysis	ic50	0.0070	uM
2-pyridin-4-yl-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one	1879129: Inhibition of PKN2 (unknown origin) by TR-FRET-based tracer displacement assay dependent Cheng-Prusoff equation analysis	ki	0.0080	uM
6-piperidin-4-yloxy-2H-isoquinolin-1-one	1425118: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0080	uM
1-ethyl-2-pyridin-4-yl-6,7-dihydro-5H-pyrrolo[3,2-c]pyridin-4-one	1879129: Inhibition of PKN2 (unknown origin) by TR-FRET-based tracer displacement assay dependent Cheng-Prusoff equation analysis	ki	0.0080	uM
N-methyl-3-(3,12,13,23-tetrazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1(16),2,4,6,8,10,14,17,19,21-decaen-23-yl)propan-1-amine;dihydrochloride	2075598: Inhibition of human PRK2 using ISDELMDATFADQEAKKK as substrate in presence of ATP	ic50	0.0090	uM
(1S)-2-amino-1-(4-chlorophenyl)-1-[4-(1H-pyrazol-4-yl)phenyl]ethanol	1425118: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0090	uM
(3S,4R)-N-(7-chloro-1-oxo-2H-isoquinolin-6-yl)-4-(4-chlorophenyl)pyrrolidine-3-carboxamide	483960: Inhibition of PRKCL2	ic50	0.0140	uM
1-(2-hydroxyethyl)-2-pyridin-4-yl-6,7-dihydro-5H-pyrrolo[3,2-c]pyridin-4-one	1879129: Inhibition of PKN2 (unknown origin) by TR-FRET-based tracer displacement assay dependent Cheng-Prusoff equation analysis	ki	0.0150	uM
Midostaurin	435933: Binding constant for PKN2 kinase domain	kd	0.0150	uM
2-methyl-1-N-(3-pyridin-4-yl-2,6-naphthyridin-1-yl)propane-1,2-diamine	1165791: Inhibition of human recombinant PKN-2 using AKRRRLSSLRA as substrate after 40 mins by scintillation counting analysis	ic50	0.0170	uM
6-phenyl-2-pyridin-4-yl-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one	1879129: Inhibition of PKN2 (unknown origin) by TR-FRET-based tracer displacement assay dependent Cheng-Prusoff equation analysis	ki	0.0250	uM
4-[(1R)-1-aminoethyl]-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)benzamide	1425118: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0280	uM
2-pyridin-4-yl-1,5,6,7-tetrahydroindol-4-one	1879129: Inhibition of PKN2 (unknown origin) by TR-FRET-based tracer displacement assay dependent Cheng-Prusoff equation analysis	ki	0.0300	uM
2-pyridin-4-yl-1H-benzimidazole-4-carboxamide	1667210: Displacement of tracer from PKN2 (unknown origin) by TR-FRET assay	ki	0.0300	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149019: Binding affinity to human PKN2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0413	uM
N-[(1S)-2-amino-1-phenylethyl]-4-pyridin-4-ylbenzamide	1948869: Inhibition of PKN2 (unknown origin)	ic50	0.0501	uM
2-methyl-1-N-(2-pyridin-4-ylpyrido[3,4-d]pyrimidin-4-yl)propane-1,2-diamine	1165791: Inhibition of human recombinant PKN-2 using AKRRRLSSLRA as substrate after 40 mins by scintillation counting analysis	ic50	0.0580	uM
1-propan-2-yl-2-pyridin-4-yl-6,7-dihydro-5H-pyrrolo[3,2-c]pyridin-4-one	1879129: Inhibition of PKN2 (unknown origin) by TR-FRET-based tracer displacement assay dependent Cheng-Prusoff equation analysis	ki	0.0700	uM
4-[(1R)-1-aminoethyl]-N-pyridin-4-ylcyclohexane-1-carboxamide;dihydrochloride	483717: Inhibition of Prkcl2	ic50	0.0700	uM
2-[3-(methanesulfonamido)phenyl]-N-[4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1,3-thiazol-2-yl]acetamide	1398951: Inhibition of PRK2 (unknown origin)	ki	0.0770	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149019: Binding affinity to human PKN2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0790	uM
6-bromo-2-pyridin-4-yl-1H-benzimidazole-4-carboxamide	1667210: Displacement of tracer from PKN2 (unknown origin) by TR-FRET assay	ki	0.0800	uM
N-(7-chloro-1-oxo-2H-isoquinolin-6-yl)-2-(methylamino)-2-phenylacetamide	483717: Inhibition of Prkcl2	ic50	0.1100	uM
1-methyl-2-pyridin-4-yl-6,7-dihydro-5H-pyrrolo[3,2-c]pyridin-4-one	1879129: Inhibition of PKN2 (unknown origin) by TR-FRET-based tracer displacement assay dependent Cheng-Prusoff equation analysis	ki	0.1300	uM
methyl N-[4-[5-[(2S)-2-amino-2,4-dimethylpentoxy]-6-chloro-2-pyridinyl]-2-pyridinyl]carbamate	1904676: Inhibition of PKN2 (unknown origin)	ic50	0.1400	uM
(16E)-14-methyl-20-oxa-5,7,14,27-tetrazatetracyclo[19.3.1.12,6.18,12]heptacosa-1(25),2(27),3,5,8,10,12(26),16,21,23-decaene	1425118: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.1410	uM
(2S,3R,4R,6R,18S)-18-hydroxy-3-methoxy-2-methyl-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	1425118: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.1420	uM
1-ethyl-5-methyl-2-pyridin-4-yl-6,7-dihydropyrrolo[3,2-c]pyridin-4-one	1879129: Inhibition of PKN2 (unknown origin) by TR-FRET-based tracer displacement assay dependent Cheng-Prusoff equation analysis	ki	0.1700	uM
Baricitinib	1425118: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.2690	uM
4-fluoro-5-[[(2S)-2-methyl-1,4-diazepan-1-yl]sulfonyl]isoquinoline	1425118: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.2850	uM
7,8-dichloro-9-methyl-1-oxospiro[2,4-dihydropyrido[3,4-b]indole-3,4’-piperidine]-4-carbonitrile	643865: Inhibition of PKN2 using ATP as substrate	ic50	0.3000	uM
1-benzyl-2-pyridin-4-yl-6,7-dihydro-5H-pyrrolo[3,2-c]pyridin-4-one	1879129: Inhibition of PKN2 (unknown origin) by TR-FRET-based tracer displacement assay dependent Cheng-Prusoff equation analysis	ki	0.3200	uM
methyl (15S,16R,18R)-16-hydroxy-15-methyl-3-oxo-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaene-16-carboxylate	1425118: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.3610	uM
(2S)-1-[2-(difluoromethyl)-4-[2-(difluoromethyl)-4-pyridinyl]phenoxy]-2,4-dimethylpentan-2-amine	1826926: Inhibition of PRK2 (unknown origin)	ic50	0.4400	uM
2-amino-N-(7-chloro-1-oxo-2H-isoquinolin-6-yl)-2-phenylacetamide	483717: Inhibition of Prkcl2	ic50	0.5100	uM
(2S)-1-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine	625050: Binding constant for PKN2 kinase domain	kd	0.5900	uM
4-[(1R)-1-aminoethyl]-N-pyridin-4-ylcyclohexane-1-carboxamide	164175: Inhibition of Protein kinase C related kinase 2 (PRK2)	ic50	0.6000	uM
5-[6-[(4-methylpiperazin-1-yl)methyl]benzimidazol-1-yl]-3-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide	625050: Binding constant for PKN2 kinase domain	kd	0.6200	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	625050: Binding constant for PKN2 kinase domain	kd	0.6800	uM
1-N-[2-(1H-indazol-5-yl)pyrido[3,4-d]pyrimidin-4-yl]-2-methylpropane-1,2-diamine	1165791: Inhibition of human recombinant PKN-2 using AKRRRLSSLRA as substrate after 40 mins by scintillation counting analysis	ic50	0.7420	uM
3-[[(4-carbamoylphenyl)carbamoylamino]methyl]-N-(1,2,3,4-tetrahydroisoquinolin-7-yl)benzamide	456639: Inhibition of PKN2	ic50	0.7700	uM
5-(1,4-diazepan-1-ylsulfonyl)isoquinoline	456639: Inhibition of PKN2	ic50	0.7800	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	625050: Binding constant for PKN2 kinase domain	kd	0.8800	uM
4-[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-[[(3S)-piperidin-3-yl]methoxy]imidazo[4,5-c]pyridin-4-yl]-2-methylbut-3-yn-2-ol	1425118: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.8920	uM
3-(1H-indazol-5-yl)-1-piperazin-1-ylisoquinoline	1165791: Inhibition of human recombinant PKN-2 using AKRRRLSSLRA as substrate after 40 mins by scintillation counting analysis	ic50	0.9200	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
arsenite	affects expression, affects binding, decreases reaction	2
Cadmium Chloride	increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
coumarin	decreases phosphorylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
fasudil	decreases activity	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
Y 27632	decreases activity	1
jinfukang	decreases expression	1
Resveratrol	decreases expression	1
Temozolomide	increases expression	1
Glyphosate	decreases expression	1
Caffeine	affects phosphorylation	1
Chelating Agents	affects binding, increases expression	1
Copper	affects binding, increases expression	1
Endosulfan	decreases expression	1
Folic Acid	decreases expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Nicotine	increases expression	1
Quercetin	decreases phosphorylation	1
Selenium	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Dronabinol	increases expression	1

ChEMBL screening assays

327 unique, capped per target: 326 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1003322	Binding	Inhibition of PRK2 at 1 uM relative to control	Novel potent BRAF inhibitors: toward 1 nM compounds through optimization of the central phenyl ring. — J Med Chem
CHEMBL1963748	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: PKN2	PubChem BioAssay data set

Cellosaurus cell lines

7 cell lines: 6 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1DY	Abcam HCT 116 PKN2 KO	Cancer cell line	Male
CVCL_B2AY	Abcam HeLa PKN2 KO	Cancer cell line	Female
CVCL_D7XP	Ubigene A-549 PKN2 KO	Cancer cell line	Male
CVCL_D8T5	Ubigene HCT 116 PKN2 KO	Cancer cell line	Male
CVCL_D9NP	Ubigene HEK293 PKN2 KO	Transformed cell line	Female
CVCL_E0L1	Ubigene HeLa PKN2 KO	Cancer cell line	Female
CVCL_TE02	HAP1 PKN2 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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