PKN1

Summary

PKN1 (protein kinase N1, HGNC:9405) is a protein-coding gene on chromosome 19p13.12, encoding Serine/threonine-protein kinase N1 (Q16512). PKC-related serine/threonine-protein kinase involved in various processes such as regulation of the intermediate filaments of the actin cytoskeleton, cell migration, tumor cell invasion and transcription regulation.

The protein encoded by this gene belongs to the protein kinase C superfamily. This kinase is activated by Rho family of small G proteins and may mediate the Rho-dependent signaling pathway. This kinase can be activated by phospholipids and by limited proteolysis. The 3-phosphoinositide dependent protein kinase-1 (PDPK1/PDK1) is reported to phosphorylate this kinase, which may mediate insulin signals to the actin cytoskeleton. The proteolytic activation of this kinase by caspase-3 or related proteases during apoptosis suggests its role in signal transduction related to apoptosis. Alternatively spliced transcript variants encoding distinct isoforms have been observed.

Source: NCBI Gene 5585 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 223 total — 1 pathogenic
• Phenotypes (HPO): 24
• Druggable target: yes — 46 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002741

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9405
Approved symbol	PKN1
Name	protein kinase N1
Location	19p13.12
Locus type	gene with protein product
Status	Approved
Aliases	DBK, PRK1, PKN, MGC46204, PAK1
Ensembl gene	ENSG00000123143
Ensembl biotype	protein_coding
OMIM	601032
Entrez	5585

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 15 protein_coding, 5 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000242783, ENST00000342216, ENST00000585619, ENST00000585839, ENST00000586039, ENST00000586237, ENST00000586557, ENST00000586900, ENST00000587215, ENST00000587429, ENST00000588200, ENST00000590097, ENST00000591461, ENST00000592794, ENST00000592960, ENST00000900936, ENST00000934913, ENST00000934914, ENST00000934915, ENST00000944771, ENST00000944772, ENST00000944773, ENST00000944774

RefSeq mRNA: 2 — MANE Select: NM_002741 NM_002741, NM_213560

CCDS: CCDS42513, CCDS42514

Canonical transcript exons

ENST00000242783 — 22 exons

Exon	Start	End
ENSE00000836606	14467565	14467641
ENSE00000836607	14467718	14467793
ENSE00000836609	14469341	14469517
ENSE00000836610	14469752	14469814
ENSE00001313986	14433306	14433542
ENSE00001648194	14469912	14469988
ENSE00001826047	14471581	14471859
ENSE00003486759	14470575	14470682
ENSE00003488868	14470771	14470851
ENSE00003491778	14441143	14441443
ENSE00003513865	14463667	14463742
ENSE00003542623	14463828	14463969
ENSE00003542967	14451829	14452023
ENSE00003543291	14464060	14464153
ENSE00003545642	14450896	14451109
ENSE00003545909	14467876	14467967
ENSE00003557517	14446426	14446561
ENSE00003560892	14458232	14458375
ENSE00003606734	14470163	14470305
ENSE00003616406	14458031	14458140
ENSE00003617844	14450318	14450463
ENSE00003668170	14443470	14443621

Expression profiles

Bgee: expression breadth ubiquitous, 228 present calls, max score 98.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.0897 / max 446.2443, expressed in 1808 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
174253	27.0114	1797
174255	4.0892	527
174258	0.4926	284
208706	0.2578	91
174252	0.1216	26
174257	0.1171	29

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	98.58	gold quality
granulocyte	CL:0000094	98.19	gold quality
ventricular zone	UBERON:0003053	97.18	gold quality
right lung	UBERON:0002167	96.69	gold quality
stromal cell of endometrium	CL:0002255	96.59	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.54	gold quality
cortical plate	UBERON:0005343	96.40	gold quality
ganglionic eminence	UBERON:0004023	96.38	gold quality
monocyte	CL:0000576	96.35	gold quality
upper lobe of left lung	UBERON:0008952	96.28	gold quality
mucosa of stomach	UBERON:0001199	96.19	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.07	gold quality
lower esophagus	UBERON:0013473	96.02	gold quality
leukocyte	CL:0000738	95.99	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.88	gold quality
mononuclear cell	CL:0000842	95.87	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.67	gold quality
upper lobe of lung	UBERON:0008948	95.48	gold quality
metanephros cortex	UBERON:0010533	95.37	gold quality
body of uterus	UBERON:0009853	95.29	gold quality
right atrium auricular region	UBERON:0006631	95.28	gold quality
spleen	UBERON:0002106	95.22	gold quality
adenohypophysis	UBERON:0002196	95.07	gold quality
right coronary artery	UBERON:0001625	94.93	gold quality
left testis	UBERON:0004533	94.89	gold quality
left uterine tube	UBERON:0001303	94.86	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.81	gold quality
left coronary artery	UBERON:0001626	94.75	gold quality
nerve	UBERON:0001021	94.65	gold quality
tibial nerve	UBERON:0001323	94.65	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HESX1, NEUROD2

Literature-anchored findings (GeneRIF, showing 29)

• Data show that stimulation of the RhoA effector protein kinase C-related kinase (PRK) signalling cascade results in a ligand-dependent superactivation of androgen receptors both in vivo and in vitro. (PMID:12514133)
• PKNalpha functions as not only an upstream activator of MLTKalpha but also a putative scaffold protein for the p38gamma MAPK signaling pathway (PMID:12761180)
• analysis of the interaction between the small G proteins Rac1 and RhoA and protein kinase C-related kinase 1 (PMID:14514689)
• Data suggest that hyaluronan-CD44 interaction with Rac1-protein kinase N gamma plays a pivotal role in phospholipase C gamma1-regulated calcium signaling and cortactin-cytoskeleton function required for keratinocyte cell-cell adhesion and differentiation. (PMID:15123640)
• PKN1 mediates arsenite-induced delay of the G(2)/M transition by binding to and phosphorylating Cdc25C (PMID:15791647)
• Data strengthen the hypothesis that Cyclin T2a plays a role in muscle differentiation, and propose PKNalpha as a novel partner of Cyclin T2a in this process. (PMID:16331689)
• Human pregnancy is characterized by increases in PKN1 expression in the myometrium. (PMID:17301291)
• Study identifies TRAF1 as a substrate of PKN1 kinase activity in vitro and in vivo, and show that this phosphorylation event is required for attenuating downstream kinase activities. (PMID:18429822)
• Deregulation of PKN1 may contribute to the pathogenic process in amyotrophic lateral sclerosis. (PMID:18519042)
• Protein kinase C-related kinase and ROCK are required for thrombin-induced endothelial cell permeability downstream from Galpha12/13 and Galpha11/q (PMID:18713748)
• PRK1 is present in various malignancies, but especially in ovarian serous carcinomas (PMID:19427017)
• Protein kinase C-related kinase targets nuclear localization signals in a subset of class IIa histone deacetylases. (PMID:20188095)
• A-kinase anchoring protein (AKAP)-Lbc anchors a PKN-based signaling complex involved in alpha1-adrenergic receptor-induced p38 activation. (PMID:21224381)
• Data show that just one contact site as being relevant for binding of RhoA and domain from PRK1, and the HR1b domain was found not to contribute to RhoA binding. (PMID:21351730)
• 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)
• Protein kinase N1 is a novel substrate of NFATc1-mediated cyclin D1-CDK6 activity and modulates vascular smooth muscle cell division and migration leading to inward blood vessel wall remodeling. (PMID:22893700)
• Protein kinase N1 inhibits Wnt/b-catenin signaling and apoptosis in melanoma cells. (PMID:24114839)
• Data indicate that Salmonella SspH1 catalyzes the ubiquitination and proteasome-dependent degradation of PKN1 in cells. (PMID:24248594)
• Transcriptome and interactome analyses uncover that PRK1 regulates expression of migration-relevant genes by interacting with the scaffold protein sperm-associated antigen 9 (SPAG9/JIP4). (PMID:25504435)
• 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)
• PKN1 activity was up-regulated by the active RhoA mutant (G14V) and suppressed by RhoA T19N. PKN1 siRNA interrupted the ability of RhoA to promote ESC proliferation and DNA synthesis. The effect of RhoA on ESC proliferation is mediated by activation of the PKN1-cyclin D1 pathway in vitro. (PMID:28222172)
• Pkn1 is not required for tumorigenesis initiated by loss of Pten. Triple knockout of Pten, Pkn1, and Pkn2 in mouse prostate results in squamous cell carcinoma, an uncommon but therapy-resistant form of prostate cancer. (PMID:28875501)
• PKN1 transduces androgen-responsiveness to serum response factor in prostate neoplasms (PMID:30742064)
• Secretory carcinoma of the skin associated with the presence of novel NFIX-PKN1 translocation. (PMID:31045890)
• Characterization of the novel cardiolipin binding regions identified on the protease and lipid activated PKC-related kinase 1 (PMID:31125460)
• Cyclin-dependent kinase 1-mediated phosphorylation of protein kinase N1 promotes anchorage-independent growth and migration. (PMID:31981797)
• Novel roles of PRK1 and PRK2 in cilia and cancer biology. (PMID:32127582)
• Upregulation of PKN1 as a Prognosis Biomarker for Endometrial Cancer. (PMID:35533253)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	pkn1a	ENSDARG00000060184
danio_rerio	pkn1b	ENSDARG00000062748
mus_musculus	Pkn1	ENSMUSG00000057672
rattus_norvegicus	Pkn1	ENSRNOG00000004131
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), PKN2 (ENSG00000065243), PRKCZ (ENSG00000067606), PRKCG (ENSG00000126583), PRKCA (ENSG00000154229), PKN3 (ENSG00000160447), PRKCI (ENSG00000163558), PRKCB (ENSG00000166501), PRKCE (ENSG00000171132)

Protein

Protein identifiers

Serine/threonine-protein kinase N1 — Q16512 (reviewed: Q16512)

Alternative names: Protease-activated kinase 1, Protein kinase C-like 1, Protein kinase C-like PKN, Protein kinase PKN-alpha, Protein-kinase C-related kinase 1, Serine-threonine protein kinase N

All UniProt accessions (7): Q16512, K7EKY9, K7EL10, K7EM57, K7EN76, K7EPK3, K7ES10

UniProt curated annotations — full annotation on UniProt →

Function. PKC-related serine/threonine-protein kinase involved in various processes such as regulation of the intermediate filaments of the actin cytoskeleton, cell migration, tumor cell invasion and transcription regulation. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14. Regulates the cytoskeletal network by phosphorylating proteins such as VIM and neurofilament proteins NEFH, NEFL and NEFM, leading to inhibit their polymerization. Phosphorylates ‘Ser-575’, ‘Ser-637’ and ‘Ser-669’ of MAPT/Tau, lowering its ability to bind to microtubules, resulting in disruption of tubulin assembly. Acts as a key coactivator of androgen receptor (AR)-dependent transcription, by being recruited to AR target genes and specifically mediating phosphorylation of ‘Thr-11’ of histone H3 (H3T11ph), a specific tag for epigenetic transcriptional activation that promotes demethylation of histone H3 ‘Lys-9’ (H3K9me) by KDM4C/JMJD2C. Phosphorylates HDAC5, HDAC7 and HDAC9, leading to impair their import in the nucleus. Phosphorylates ‘Thr-38’ of PPP1R14A, ‘Ser-159’, ‘Ser-163’ and ‘Ser-170’ of MARCKS, and GFAP. Able to phosphorylate RPS6 in vitro.

Subunit / interactions. Interacts with ZFAND6. Interacts with AR. Interacts with PRKCB. Interacts (via REM 1 and REM 2 repeats) with RAC1. Interacts (via REM 1 repeat) with RHOA. Interacts with RHOB. Interacts (via C-terminus) with PDPK1. Interacts with CCNT2; enhances MYOD1-dependent transcription. Component of a signaling complex containing at least AKAP13, PKN1, MAPK14, ZAK and MAP2K3. Within this complex, AKAP13 interacts directly with PKN1, which in turn recruits MAPK14, MAP2K3 and ZAK. (Microbial infection) Interacts (via the second REM repeat) with S.typhimurium E3 ubiquitin-protein ligase SspH1 (via the leucine-rich repeat region).

Subcellular location. Cytoplasm. Nucleus. Endosome. Cell membrane. Cleavage furrow. Midbody.

Tissue specificity. Found ubiquitously. Expressed in heart, brain, placenta, lung, skeletal muscle, kidney and pancreas. Expressed in numerous tumor cell lines, especially in breast tumor cells.

Post-translational modifications. Autophosphorylated; preferably on serine. Phosphorylated during mitosis. Activated by limited proteolysis with trypsin. (Microbial infection) In case of infection, polyubiquitinated by the bacterial E3 ubiquitin-protein ligase SspH1, leading to its proteasomal degradation.

Activity regulation. Kinase activity is activated upon binding to Rho proteins (RHOA, RHOB and RAC1). Activated by lipids, particularly cardiolipin and to a lesser extent by other acidic phospholipids. Activated by caspase-3 (CASP3) cleavage during apoptosis. Two specific sites, Thr-774 (activation loop of the kinase domain) and Ser-916 (turn motif), need to be phosphorylated for its full activation.

Domain organisation. The C1 domain does not bind the diacylglycerol (DAG).

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q16512-1	1	yes
Q16512-2	2
Q16512-3	3

RefSeq proteins (2): NP_002732, NP_998725 (=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
IPR037317	PKN1_HR1_2	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 (104 total): helix 21, modified residue 15, strand 11, sequence variant 10, mutagenesis site 10, turn 8, sequence conflict 7, domain 6, region of interest 4, site 3, splice variant 3, binding site 2, initiator methionine 1, chain 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
4OTH	X-RAY DIFFRACTION	1.8
4OTI	X-RAY DIFFRACTION	1.93
4OTD	X-RAY DIFFRACTION	2
1CXZ	X-RAY DIFFRACTION	2.2
4OTG	X-RAY DIFFRACTION	2.6
4NKG	X-RAY DIFFRACTION	2.9
1URF	SOLUTION NMR
2RMK	SOLUTION NMR
9RXE	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16512-F1	73.16	0.28

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 (4): 740 (proton acceptor); 108–109 (cleavage; by caspase-3); 454–455 (cleavage; by caspase-3); 558–559 (cleavage; by caspase-3)

Ligand- & substrate-binding residues (2): 621–629; 644

Post-translational modifications (15): 2, 69, 205, 374, 448, 533, 537, 540, 559, 562, 608, 774, 778, 914, 916

Mutagenesis-validated functional residues (10):

Position	Phenotype
108	abolishes cleavage by caspase-3 and formation of af1 fragment.
181	abolishes interaction with bacterial ssph1.
181	decreases interaction with bacterial ssph1.
185	abolishes interaction with bacterial ssph1.
451	abolishes cleavage by caspase-3 and formation of 70 kda fragment.
454	abolishes cleavage by caspase-3 and formation of 70 kda fragment.
558	abolishes cleavage by caspase-3 and formation of af3 fragment.
560	abolishes cleavage by caspase-3 and formation of af3 fragment.
644	abolishes serine/threonine-protein kinase activity.
644	substantial reduction of autophosphorylation.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-5625740	RHO GTPases activate PKNs
R-HSA-5625886	Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3
R-HSA-8980692	RHOA GTPase cycle
R-HSA-9013026	RHOB GTPase cycle
R-HSA-9013106	RHOC GTPase cycle
R-HSA-9013149	RAC1 GTPase cycle

MSigDB gene sets: 938 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, GSE45365_NK_CELL_VS_CD8A_DC_DN, ATF_B, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_HINDBRAIN_DEVELOPMENT, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_EPITHELIUM_DEVELOPMENT, BIOCARTA_FMLP_PATHWAY, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, FREAC2_01, GOBP_METENCEPHALON_DEVELOPMENT, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, REACTOME_INNATE_IMMUNE_SYSTEM

GO Biological Process (19): B cell homeostasis (GO:0001782), B cell apoptotic process (GO:0001783), regulation of germinal center formation (GO:0002634), regulation of immunoglobulin production (GO:0002637), renal system process (GO:0003014), regulation of transcription by RNA polymerase II (GO:0006357), protein phosphorylation (GO:0006468), hyperosmotic response (GO:0006972), signal transduction (GO:0007165), epithelial cell migration (GO:0010631), negative regulation of B cell proliferation (GO:0030889), intracellular signal transduction (GO:0035556), post-translational protein modification (GO:0043687), spleen development (GO:0048536), regulation of androgen receptor signaling pathway (GO:0060765), regulation of cell motility (GO:2000145), chromatin organization (GO:0006325), chromatin remodeling (GO:0006338), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (17): chromatin binding (GO:0003682), transcription coactivator activity (GO:0003713), protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), diacylglycerol-dependent serine/threonine kinase activity (GO:0004697), protein kinase C binding (GO:0005080), ATP binding (GO:0005524), small GTPase binding (GO:0031267), histone H3T11 kinase activity (GO:0035402), histone binding (GO:0042393), histone deacetylase binding (GO:0042826), nuclear androgen receptor binding (GO:0050681), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (11): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), endosome (GO:0005768), cytosol (GO:0005829), midbody (GO:0030496), cleavage furrow (GO:0032154), protein-containing complex (GO:0032991), plasma membrane (GO:0005886), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
RHO GTPase cycle	4
RHO GTPase Effectors	1
RHO GTPases activate PKNs	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
regulation of DNA-templated transcription	2
protein modification process	2
regulation of cellular process	2
intracellular anatomical structure	2
binding	2
protein kinase activity	2
protein serine/threonine kinase activity	2
cytoplasm	2
lymphocyte homeostasis	1
lymphocyte apoptotic process	1
germinal center formation	1
regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	1
regulation of anatomical structure morphogenesis	1
immunoglobulin production	1
regulation of production of molecular mediator of immune response	1
system process	1
transcription by RNA polymerase II	1
phosphorylation	1
response to osmotic stress	1
cell communication	1
cellular process	1
signaling	1
cellular response to stimulus	1
ameboidal-type cell migration	1
epithelium migration	1
regulation of B cell proliferation	1
B cell proliferation	1
negative regulation of lymphocyte proliferation	1
negative regulation of B cell activation	1
signal transduction	1
hematopoietic or lymphoid organ development	1
androgen receptor signaling pathway	1
regulation of intracellular steroid hormone receptor signaling pathway	1
regulation of locomotion	1
cell motility	1
cellular component organization	1
chromatin organization	1
DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1

Protein interactions and networks

STRING

1834 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PKN1	MAP2K3	P46734	952
PKN1	MAP3K20	Q9NYL2	939
PKN1	RHOA	P06749	915
PKN1	RHPN1	Q8TCX5	872
PKN1	RTKN	Q9BST9	796
PKN1	CDC42	P21181	729
PKN1	AKAP9	Q99996	697
PKN1	MAPK14	Q16539	690
PKN1	RHOC	P08134	660
PKN1	RHOB	P01121	651
PKN1	MEFV	O15553	617
PKN1	ZFAND6	Q6FIF0	615
PKN1	AR	P10275	590
PKN1	ZFAND5	O76080	548
PKN1	KDM4C	Q9H3R0	494

IntAct

290 interactions, top by confidence:

A	B	Type	Score
HOMER3	PKN1	psi-mi:“MI:0915”(physical association)	0.780
PKN1	HOMER3	psi-mi:“MI:0915”(physical association)	0.780
PKN1	CDR2	psi-mi:“MI:0915”(physical association)	0.720
PKN1	GOLGA2	psi-mi:“MI:0915”(physical association)	0.720
PKN1	KRT31	psi-mi:“MI:0915”(physical association)	0.720
GOLGA2	PKN1	psi-mi:“MI:0915”(physical association)	0.720
CDR2	PKN1	psi-mi:“MI:0915”(physical association)	0.720
KRT31	PKN1	psi-mi:“MI:0915”(physical association)	0.720
MID1	PKN1	psi-mi:“MI:0915”(physical association)	0.560
VIM	PKN1	psi-mi:“MI:0915”(physical association)	0.560
KRT15	PKN1	psi-mi:“MI:0915”(physical association)	0.560
PKN1	CEP57L1	psi-mi:“MI:0915”(physical association)	0.560
SSX2IP	PKN1	psi-mi:“MI:0915”(physical association)	0.560
PKN1	MID1	psi-mi:“MI:0915”(physical association)	0.560
PKN1	VIM	psi-mi:“MI:0915”(physical association)	0.560
PKN1	KRT15	psi-mi:“MI:0915”(physical association)	0.560
CEP57L1	PKN1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (200): PKN1 (Affinity Capture-MS), PKN1 (Two-hybrid), PKN1 (Two-hybrid), PKN1 (Two-hybrid), PKN1 (Two-hybrid), PKN1 (Two-hybrid), VIM (Two-hybrid), HOMER3 (Two-hybrid), SSX2IP (Two-hybrid), CEP57L1 (Two-hybrid), WDR5 (Co-localization), KMT2A (Co-localization), RBBP5 (Co-localization), ASH2L (Co-localization), PKN1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0B4J1F4, A0A0G2JXN2, A2AWP8, A2RRH5, C9J798, O43374, O70277, O95294, P04629, P59926, Q0GA42, Q13368, Q14318, Q16512, Q29RM4, Q2HY40, Q2T9P3, Q2TBA3, Q5BIM1, Q5M7W1, Q5R5M3, Q5R811, Q5T7P8, Q5XIS9, Q62746, Q6PFQ7, Q6PFY8, Q7TNM2, Q7TP90, Q7Z4K8, Q8BG60, Q8BHT7, Q8BQC3, Q8C6N3, Q8CIW5, Q8IZ69, Q8NCT1, Q920N2, Q92546, Q925B4

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

32 interactions.

A	Effect	B	Mechanism
PKN1	up-regulates	RAF1	phosphorylation
PKN1	down-regulates	ARHGEF2	phosphorylation
PKN1	up-regulates	PGM1	phosphorylation
PKN1	up-regulates	SNAI1	phosphorylation
PKN1	up-regulates	AR	phosphorylation
PKN1	up-regulates	MAPK14	phosphorylation
PKN1	up-regulates	MAP3K20	phosphorylation
PKN1	“down-regulates activity”	EGFR	phosphorylation
PKN1	unknown	CDC25C	phosphorylation
PKN1	down-regulates	FOXO	phosphorylation
IPA-3	“down-regulates activity”	PKN1	“chemical inhibition”
CDK1	“up-regulates activity”	PKN1	phosphorylation
PKN1	“down-regulates activity”	MRTFA	phosphorylation
PDPK1	up-regulates	PKN1	phosphorylation
PKN1	down-regulates	MAPT	phosphorylation
PKN1	down-regulates	FOXO1	phosphorylation
PKN1	“down-regulates activity”	MEFV	phosphorylation
RHOA	“up-regulates activity”	PKN1	binding
PKN1	“down-regulates activity”	MARCKS	phosphorylation
PKN1	unknown	MARCKS	phosphorylation
PKN1	“up-regulates activity”	PKN1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 69 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
AURKA Activation by TPX2	5	18.1×	9e-04
Formation of the cornified envelope	8	16.7×	7e-06
Regulation of PLK1 Activity at G2/M Transition	5	15.1×	2e-03
Anchoring of the basal body to the plasma membrane	5	13.5×	2e-03
Keratinization	8	10.6×	1e-04
Cell Cycle, Mitotic	6	6.9×	9e-03
Cell Cycle	7	6.0×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
morphogenesis of an epithelium	8	46.6×	2e-09
intermediate filament organization	10	40.8×	2e-11
epithelial cell differentiation	7	20.8×	8e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	170
Likely benign	8
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
443499	GRCh37/hg19 19p13.3-q13.43(chr19:260912-58956888)	Pathogenic

SpliceAI

3037 predictions. Top by Δscore:

Variant	Effect	Δscore
19:14433540:CAGGT:C	donor_loss	1.0000
19:14433541:AGGT:A	donor_loss	1.0000
19:14433542:GGTA:G	donor_loss	1.0000
19:14433543:G:T	donor_loss	1.0000
19:14433544:T:A	donor_loss	1.0000
19:14441140:CAG:C	acceptor_gain	1.0000
19:14441141:A:AG	acceptor_gain	1.0000
19:14441141:AGA:A	acceptor_gain	1.0000
19:14441141:AGAGT:A	acceptor_gain	1.0000
19:14441142:G:GG	acceptor_gain	1.0000
19:14441142:GA:G	acceptor_gain	1.0000
19:14441142:GAG:G	acceptor_gain	1.0000
19:14441142:GAGT:G	acceptor_gain	1.0000
19:14441142:GAGTG:G	acceptor_gain	1.0000
19:14441440:CACGG:C	donor_loss	1.0000
19:14441442:CGGT:C	donor_loss	1.0000
19:14441443:GGTG:G	donor_loss	1.0000
19:14441444:G:GA	donor_loss	1.0000
19:14441444:G:GG	donor_gain	1.0000
19:14441445:T:A	donor_loss	1.0000
19:14443619:AAG:A	donor_loss	1.0000
19:14443622:GTGAG:G	donor_loss	1.0000
19:14446408:GACT:G	acceptor_gain	1.0000
19:14446557:CCAAG:C	donor_gain	1.0000
19:14446558:CAAG:C	donor_gain	1.0000
19:14446559:AAG:A	donor_gain	1.0000
19:14446560:AG:A	donor_gain	1.0000
19:14446560:AGGT:A	donor_loss	1.0000
19:14446561:GG:G	donor_gain	1.0000
19:14446561:GGT:G	donor_loss	1.0000

AlphaMissense

6077 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:14451109:G:T	G324W	1.000
19:14451829:G:A	G324E	1.000
19:14467779:G:C	G624R	1.000
19:14467785:T:A	F626I	1.000
19:14467785:T:C	F626L	1.000
19:14467787:T:A	F626L	1.000
19:14467787:T:G	F626L	1.000
19:14467788:G:T	G627W	1.000
19:14467789:G:A	G627E	1.000
19:14467923:G:C	K644N	1.000
19:14467923:G:T	K644N	1.000
19:14469352:A:T	E663V	1.000
19:14469466:G:A	G701E	1.000
19:14469466:G:T	G701V	1.000
19:14469472:T:C	L703P	1.000
19:14469476:G:A	M704I	1.000
19:14469476:G:C	M704I	1.000
19:14469476:G:T	M704I	1.000
19:14469781:T:C	L728P	1.000
19:14469808:T:A	V737D	1.000
19:14469814:G:C	R739T	1.000
19:14469814:G:T	R739M	1.000
19:14469912:G:C	R739S	1.000
19:14469912:G:T	R739S	1.000
19:14469913:G:C	D740H	1.000
19:14469914:A:C	D740A	1.000
19:14469914:A:G	D740G	1.000
19:14469914:A:T	D740V	1.000
19:14469915:C:A	D740E	1.000
19:14469915:C:G	D740E	1.000

dbSNP variants (sampled 300 via entrez): RS1000050050 (19:14470052 G>A), RS1000065077 (19:14467321 C>T), RS1000092469 (19:14448094 C>T), RS1000100784 (19:14432120 C>T), RS1000210147 (19:14453724 C>T), RS1000327063 (19:14445121 T>C), RS1000378469 (19:14465218 G>C), RS1000431622 (19:14434438 G>A), RS1000461220 (19:14432113 G>T), RS1000465358 (19:14450582 C>A,T), RS1000493755 (19:14432469 G>C), RS1000520576 (19:14466754 G>C), RS1000528129 (19:14448304 C>G), RS1000608421 (19:14460573 C>T), RS1000626024 (19:14461442 C>G)

Disease associations

OMIM: gene MIM:601032 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

24 total (24 of 24 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000276	Long face
HP:0000337	Broad forehead
HP:0000490	Deeply set eye
HP:0000750	Delayed speech and language development
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001290	Generalized hypotonia
HP:0001988	Recurrent hypoglycemia
HP:0002007	Frontal bossing
HP:0002020	Gastroesophageal reflux
HP:0002066	Gait ataxia
HP:0002317	Unsteady gait
HP:0002465	Poor speech
HP:0003593	Infantile onset
HP:0005490	Postnatal macrocephaly
HP:0008551	Microtia
HP:0010863	Receptive language delay
HP:0010864	Severe intellectual disability
HP:0012448	Delayed myelination
HP:0020045	Esodeviation
HP:0030891	Periventricular white matter hyperintensities
HP:0031936	Delayed ability to walk

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST007833_14	Urolithiasis	5.000000e-15
GCST009895_1	Pancreatic cancer	5.000000e-10

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3384 (SINGLE PROTEIN), CHEMBL4523644 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

46 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 270,763 (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
CHEMBL2103743	TOFACITINIB CITRATE	4	1,672
CHEMBL2105759	BARICITINIB	4	6,741
CHEMBL221959	TOFACITINIB	4	10,408
CHEMBL2325741	CAPIVASERTIB	4	2,157
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL5416410	DASATINIB	4	655
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL2105728	CRENOLANIB	3	2,167
CHEMBL2219422	AFURESERTIB	3	1,467
CHEMBL300138	ENZASTAURIN	3	3,209
CHEMBL3426621	RIPASUDIL	3	870
CHEMBL38380	FASUDIL	3	11,953
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL50	QUERCETIN	3	74,559
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3
CHEMBL1230165	SILMITASERTIB	2
CHEMBL1667969	SAR-407899 FREE BASE	2
CHEMBL1721885	SU-014813	2
CHEMBL1944698	ZOTIRACICLIB	2
CHEMBL3039513	DECERNOTINIB	2
CHEMBL3137336	UPROSERTIB	2
CHEMBL3545396	BMS-690514	2
CHEMBL475251	R-406	2
CHEMBL495727	AT-9283	2

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 (4 total), top 4:

Ligand	Action	Affinity	Parameter
staurosporine	Inhibition	9.0	pIC50
RKI-1447	Inhibition	9.0	pIC50
tofacitinib	Inhibition	6.91	pIC50
compound 20 [PMID: 22136433]	Inhibition	6.51	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
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
N-[4-({4-[(3-methyl-1H-pyrazol-5-yl)amino]-6-(4-methylpiperazin-1-yl)pyrimidin-2-yl}sulfanyl)phenyl]cyclopropanecarboxamide	KD	1100 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
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
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S)-3-hydroxy-1-methyl-4-piperidinyl]-1-benzopyran-4-one	KD	5300 nM

ChEMBL bioactivities

147 potent at pChembl≥5 of 180 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.70	IC50	0.199	nM	STAUROSPORINE
9.22	IC50	0.6	nM	STAUROSPORINE
9.00	IC50	1	nM	STAUROSPORINE
9.00	IC50	1	nM	CHEMBL5687042
9.00	IC50	1	nM	CHEMBL3597011
8.92	IC50	1.2	nM	STAUROSPORINE
8.89	Kd	1.3	nM	STAUROSPORINE
8.80	IC50	1.6	nM	CHEMBL5687026
8.42	IC50	3.78	nM	STAUROSPORINE
8.40	IC50	4	nM	CHEMBL5687057
8.38	IC50	4.21	nM	STAUROSPORINE
8.30	IC50	5	nM	CHEMBL5687053
8.28	Kd	5.3	nM	LESTAURTINIB
8.22	Kd	6	nM	CHEMBL4576489
8.15	IC50	7	nM	CHEMBL1214929
8.11	IC50	7.7	nM	CHEMBL3609327
8.10	Kd	8	nM	UCN-01
8.10	IC50	8	nM	CHEMBL5687023
8.10	IC50	8	nM	CHEMBL3609326
8.03	Kd	9.3	nM	MIDOSTAURIN
8.00	IC50	10	nM	CHEMBL5687001
7.96	Kd	11	nM	XL-228
7.96	Kd	11	nM	CHEMBL4465866
7.86	Ki	13.7	nM	PF-03758309
7.85	IC50	14	nM	PF-03758309
7.72	Kd	19	nM	SAR-407899 FREE BASE
7.70	IC50	20	nM	CHEMBL5661914
7.70	IC50	20	nM	CHEMBL5686987
7.64	Ki	23	nM	CHEMBL3770186
7.60	Kd	25	nM	AT-13148
7.47	Kd	34	nM	GSK-690693
7.46	IC50	35	nM	CHEMBL2147538
7.41	Kd	39	nM	GSK-690693
7.24	Kd	58	nM	TOFACITINIB
7.24	Kd	57	nM	CGP-52421
7.22	Ki	60	nM	CHEMBL5182936
7.19	IC50	64	nM	CHEMBL3596912
7.12	Kd	76	nM	UPROSERTIB
7.09	Ki	81	nM	PF-03758309
7.09	IC50	81.9	nM	PF-03758309
7.00	IC50	99	nM	CHEMBL3338837
6.98	Kd	104	nM	BARICITINIB
6.97	Ki	108	nM	CHEMBL250870
6.92	Kd	119	nM	CHEMBL3990456
6.92	IC50	120	nM	CHEMBL5182936
6.82	Ki	150	nM	CHEMBL225519
6.78	Kd	165	nM	CRENOLANIB
6.77	Kd	170	nM	TOFACITINIB CITRATE
6.77	Kd	170	nM	TOFACITINIB
6.75	Kd	180	nM	DOVITINIB

PubChem BioAssay actives

146 with measured affinity, of 779 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
(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	2198390: Inhibition of human PKN1 using KKLNRTLSVA as substrate preincubated for 20 mins followed by [gamma-33P]-ATP addition and measured after 120 mins by radiometric Hot-SpotSM Kinase assay	ic50	0.0002	uM
(2-chlorophenyl)-[5-(2-methyl-3,4-dihydro-1H-isoquinolin-6-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]methanone	2171479: Inhibition of PAK1 (unknown origin)	ic50	0.0010	uM
(2S,3R,4R,6R)-11-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(13),9,11,14,19,21,23,25,27-nonaen-16-one	2171479: Inhibition of PAK1 (unknown origin)	ic50	0.0010	uM
1-[(3-hydroxyphenyl)methyl]-3-(4-pyridin-4-yl-1,3-thiazol-2-yl)urea;methanesulfonic acid	1119797: Inhibition of PKN1 (unknown origin)	ic50	0.0010	uM
2-N-[(4-chloro-1H-benzimidazol-5-yl)methyl]-2-N-ethyl-4-N-(5-propan-2-yl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine	2171479: Inhibition of PAK1 (unknown origin)	ic50	0.0016	uM
6-[2-chloro-4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]-8-ethyl-2-[4-(1-methylpiperidin-4-yl)anilino]pyrido[2,3-d]pyrimidin-7-one	2171479: Inhibition of PAK1 (unknown origin)	ic50	0.0040	uM
3-[[8-chloro-11-(2,2-difluoroethyl)-3-fluoro-5H-benzo[b][1,4]benzodiazepin-6-ylidene]amino]-N-propan-2-ylpyrrolidine-1-carboxamide	2171479: Inhibition of PAK1 (unknown origin)	ic50	0.0050	uM
(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	508037: Binding affinity to PKN1	kd	0.0053	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	1526301: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged PKN1 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.0060	uM
N’-(3-pyridin-4-yl-2,6-naphthyridin-1-yl)ethane-1,2-diamine	1165790: Inhibition of PKN-1 (unknown origin)	ic50	0.0070	uM
6-[2-chloro-4-(1,3-thiazol-5-yl)phenyl]-8-ethyl-2-[4-(4-methylpiperazin-1-yl)anilino]pyrido[2,3-d]pyrimidin-7-one	2171479: Inhibition of PAK1 (unknown origin)	ic50	0.0077	uM
4-N-[5-[(1R,2S)-2-fluorocyclopropyl]-1H-pyrazol-3-yl]-2-N-methyl-2-N-(1H-pyrrolo[3,2-b]pyridin-5-ylmethyl)pyrimidine-2,4-diamine	2171479: Inhibition of PAK1 (unknown origin)	ic50	0.0080	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	1425117: 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
6-(2,4-dichlorophenyl)-8-ethyl-2-(3-fluoro-4-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidin-7-one	2171479: Inhibition of PAK1 (unknown origin)	ic50	0.0080	uM
Midostaurin	435319: Binding constant for PKN1 kinase domain	kd	0.0093	uM
N-tert-butyl-3-[(8-chloro-11-ethyl-3-fluoro-5H-benzo[b][1,4]benzodiazepin-6-ylidene)amino]pyrrolidine-1-carboxamide	2171479: Inhibition of PAK1 (unknown origin)	ic50	0.0100	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	1526301: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged PKN1 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.0110	uM
4-N-(5-cyclopropyl-1H-pyrazol-3-yl)-6-(4-methylpiperazin-1-yl)-2-N-[(3-propan-2-yl-1,2-oxazol-5-yl)methyl]pyrimidine-2,4-diamine	1425117: 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	0.0110	uM
N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methylthieno[3,2-d]pyrimidin-4-yl)amino]-1,4-dihydropyrrolo[3,4-d]pyrazole-5-carboxamide	2171489: Inhibition of recombinant PAK1 (unknown origin) assessed as inhibition constant	ki	0.0137	uM
6-piperidin-4-yloxy-2H-isoquinolin-1-one	1425117: 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	0.0190	uM
6-(2,4-dichlorophenyl)-8-ethyl-2-[4-(4-methylpiperazin-1-yl)anilino]pyrido[2,3-d]pyrimidin-7-one	2171524: Inhibition of PAK1 (unknown origin) in presence of ATP by Z-LYTE enzymatic kinase assay	ic50	0.0200	uM
(2-chlorophenyl)-[5-(1-piperidin-4-ylpyrazol-4-yl)-2H-pyrazolo[3,4-b]pyridin-3-yl]methanone	2171526: Inhibition of PAK1 (unknown origin) using 5-FAM-KPDRKKRYTVVGNPY-amide as substrate incubated for 120 mins by caliper off-chip mobility shift assay	ic50	0.0200	uM
6-[2-chloro-4-(6-methylpyrazin-2-yl)phenyl]-8-ethyl-2-[2-(1-methylpiperidin-4-yl)ethylamino]pyrido[2,3-d]pyrimidin-7-one	2171479: Inhibition of PAK1 (unknown origin)	ki	0.0230	uM
(1S)-2-amino-1-(4-chlorophenyl)-1-[4-(1H-pyrazol-4-yl)phenyl]ethanol	1425117: 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	0.0250	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	624745: Binding constant for PKN1 kinase domain	kd	0.0340	uM
2-methyl-1-N-(3-pyridin-4-yl-2,6-naphthyridin-1-yl)propane-1,2-diamine	1165790: Inhibition of PKN-1 (unknown origin)	ic50	0.0350	uM
N-[(2S,3R,4R,6R,18S)-18-hydroxy-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]-N-methylbenzamide	508037: Binding affinity to PKN1	kd	0.0570	uM
Tofacitinib	1425117: 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	0.0580	uM
1-propyl-2-pyridin-4-yl-6,7-dihydro-5H-pyrrolo[3,2-c]pyridin-4-one	1879131: Inhibition of PKN1 (unknown origin) by TR-FRET-based tracer displacement assay dependent Cheng-Prusoff equation analysis	ki	0.0600	uM
[2-chloro-5-(hydroxymethyl)phenyl]-[5-(1-piperidin-4-ylpyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]methanone	2171479: Inhibition of PAK1 (unknown origin)	ic50	0.0640	uM
N-[(2S)-1-amino-3-(3,4-difluorophenyl)propan-2-yl]-5-chloro-4-(4-chloro-1-methylpyrazol-5-yl)furan-2-carboxamide	1425117: 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	0.0760	uM
2-methyl-1-N-(2-pyridin-4-ylpyrido[3,4-d]pyrimidin-4-yl)propane-1,2-diamine	1165790: Inhibition of PKN-1 (unknown origin)	ic50	0.0990	uM
Baricitinib	1425117: 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	0.1040	uM
1-ethyl-2-pyridin-4-yl-6,7-dihydro-5H-pyrrolo[3,2-c]pyridin-4-one	1879131: Inhibition of PKN1 (unknown origin) by TR-FRET-based tracer displacement assay dependent Cheng-Prusoff equation analysis	ki	0.1080	uM
2-amino-2-cyclohexyl-N-[2-(1-methylpyrazol-4-yl)-9-oxo-3,10,11-triazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13),11-pentaen-6-yl]acetamide	1425117: 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	0.1190	uM
2-pyridin-4-yl-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one	1879131: Inhibition of PKN1 (unknown origin) by TR-FRET-based tracer displacement assay dependent Cheng-Prusoff equation analysis	ki	0.1500	uM
1-[2-[5-[(3-methyloxetan-3-yl)methoxy]benzimidazol-1-yl]quinolin-8-yl]piperidin-4-amine	1425117: 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	0.1650	uM
4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one	435319: Binding constant for PKN1 kinase domain	kd	0.1800	uM
(2S)-1-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine	624745: Binding constant for PKN1 kinase domain	kd	0.2100	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149018: Binding affinity to human PKN1 incubated for 45 mins by Kinobead based pull down assay	kd	0.2141	uM
1-(2-hydroxyethyl)-2-pyridin-4-yl-6,7-dihydro-5H-pyrrolo[3,2-c]pyridin-4-one	1879131: Inhibition of PKN1 (unknown origin) by TR-FRET-based tracer displacement assay dependent Cheng-Prusoff equation analysis	ki	0.2200	uM
1-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[4-[(dimethylamino)methyl]cyclohexyl]amino]-1,5-naphthyridin-3-yl]ethanone	1425117: 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	0.2440	uM
N-[(1R,2S)-2-aminocyclohexyl]-4-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl]thiophene-2-carboxamide	1637123: Inhibition of full-length recombinant human GST-tagged PKN1 expressed in baculovirus expression system by Z’-LYTE assay	ic50	0.2500	uM
4-[(1R)-1-aminoethyl]-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)benzamide	1425117: 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	0.2530	uM
6-phenyl-2-pyridin-4-yl-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one	1879131: Inhibition of PKN1 (unknown origin) by TR-FRET-based tracer displacement assay dependent Cheng-Prusoff equation analysis	ki	0.2600	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	1425117: 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	0.2640	uM
7,8-dichloro-9-methyl-1-oxospiro[2,4-dihydropyrido[3,4-b]indole-3,4’-piperidine]-4-carbonitrile	643864: Inhibition of PKN1 using ATP as substrate	ic50	0.3100	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	624745: Binding constant for PKN1 kinase domain	kd	0.3400	uM
8-chloro-11-ethyl-3-fluoro-6-(4-methylpiperazin-1-yl)benzo[b][1,4]benzodiazepine	2171479: Inhibition of PAK1 (unknown origin)	ic50	0.3400	uM
(18S)-18-[(dimethylamino)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.17,14.02,6.08,13.022,27]nonacosa-1(28),2(6),7(29),8,10,12,22,24,26-nonaene-3,5-dione	435319: Binding constant for PKN1 kinase domain	kd	0.3500	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression	3
bisphenol A	affects cotreatment, increases methylation, increases expression	2
Arsenic	affects methylation, increases abundance, increases expression	2
Tretinoin	increases expression	2
FR900359	affects phosphorylation	1
methyleugenol	increases expression	1
cobaltous chloride	decreases expression	1
coumarin	decreases phosphorylation	1
testosterone-3-carboxymethyloxime-bovine serum albumin conjugate	increases expression	1
tamibarotene	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluoro-n-nonanoic acid	increases expression	1
3-nitrobenzanthrone	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants	increases abundance, decreases expression	1
Caffeine	affects phosphorylation	1
Chelating Agents	affects binding, increases expression	1
Cisplatin	increases expression	1
Copper	affects binding, increases expression	1
Ivermectin	decreases expression	1
Quercetin	decreases expression	1
Rotenone	increases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Valproic Acid	increases methylation	1
Vanadium	decreases expression	1
1-Methyl-4-phenylpyridinium	increases expression	1

ChEMBL screening assays

268 unique, capped per target: 268 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1017908	Binding	Inhibition of PKN1 assessed as enzyme activity relative to control	Examining the chirality, conformation and selective kinase inhibition of 3-((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile (CP-690,550). — J Med Chem

Cellosaurus cell lines

7 cell lines: 5 cancer cell line, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3DY	Abcam HEK293T PKN1 KO	Transformed cell line	Female
CVCL_D7XN	Ubigene A-549 PKN1 KO	Cancer cell line	Male
CVCL_D8T4	Ubigene HCT 116 PKN1 KO	Cancer cell line	Male
CVCL_D9NN	Ubigene HEK293 PKN1 KO	Transformed cell line	Female
CVCL_E0L0	Ubigene HeLa PKN1 KO	Cancer cell line	Female
CVCL_TE00	HAP1 PKN1 (-) 1	Cancer cell line	Male
CVCL_TE01	HAP1 PKN1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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