PRKD3

Summary

PRKD3 (protein kinase D3, HGNC:9408) is a protein-coding gene on chromosome 2p22.2, encoding Serine/threonine-protein kinase D3 (O94806). Converts transient diacylglycerol (DAG) signals into prolonged physiological effects, downstream of PKC.

This gene belongs to the multigene protein kinase D family of serine/threonine kinases, which bind diacylglycerol and phorbol esters. Members of this family are characterized by an N-terminal regulatory domain comprised of a tandem repeat of cysteine-rich zinc-finger motifs and a pleckstrin domain. The C-terminal region contains the catalytic domain and is distantly related to calcium-regulated kinases. Catalytic activity of this enzyme promotes its nuclear localization. This protein has been implicated in a variety of functions including negative regulation of human airway epithelial barrier formation, growth regulation of breast and prostate cancer cells, and vesicle trafficking.

Source: NCBI Gene 23683 — RefSeq curated summary.

At a glance

• GWAS associations: 14
• Clinical variants (ClinVar): 84 total
• Druggable target: yes — 62 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_005813

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9408
Approved symbol	PRKD3
Name	protein kinase D3
Location	2p22.2
Locus type	gene with protein product
Status	Approved
Aliases	PKD3, EPK2
Ensembl gene	ENSG00000115825
Ensembl biotype	protein_coding
OMIM	607077
Entrez	23683

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 12 protein_coding, 4 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000234179, ENST00000379066, ENST00000443187, ENST00000443977, ENST00000452104, ENST00000464552, ENST00000469275, ENST00000475912, ENST00000477132, ENST00000494667, ENST00000887822, ENST00000933385, ENST00000933386, ENST00000933387, ENST00000933388, ENST00000933389, ENST00000933390

RefSeq mRNA: 1 — MANE Select: NM_005813 NM_005813

CCDS: CCDS1789

Canonical transcript exons

ENST00000234179 — 19 exons

Exon	Start	End
ENSE00001479694	37316237	37317179
ENSE00003535964	37272380	37272432
ENSE00003544987	37293133	37293271
ENSE00003553892	37290868	37290999
ENSE00003568681	37277866	37277989
ENSE00003573308	37267430	37267536
ENSE00003583881	37260223	37260384
ENSE00003598470	37269615	37269687
ENSE00003624331	37289356	37289513
ENSE00003638671	37286177	37286369
ENSE00003641683	37282542	37282619
ENSE00003649347	37275767	37275844
ENSE00003650125	37274421	37274697
ENSE00003654574	37256662	37256929
ENSE00003670761	37279746	37279929
ENSE00003676063	37259583	37259681
ENSE00003892067	37250502	37253350
ENSE00003896164	37254204	37254289
ENSE00003901272	37324681	37324833

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 96.35.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.2560 / max 197.0390, expressed in 1731 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
27783	13.3356	1717
27784	0.7577	521
27779	0.4622	234
27782	0.3611	163
27778	0.0893	24
27777	0.0753	21
27781	0.0689	16
27776	0.0579	9
27780	0.0481	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	96.35	gold quality
buccal mucosa cell	CL:0002336	94.95	gold quality
sperm	CL:0000019	94.23	gold quality
tendon	UBERON:0000043	93.05	gold quality
corpus epididymis	UBERON:0004359	92.23	gold quality
cauda epididymis	UBERON:0004360	92.18	gold quality
skin of hip	UBERON:0001554	92.12	gold quality
parietal pleura	UBERON:0002400	91.64	gold quality
male germ cell	CL:0000015	91.38	gold quality
tibia	UBERON:0000979	90.98	gold quality
cartilage tissue	UBERON:0002418	90.96	gold quality
superficial temporal artery	UBERON:0001614	90.84	gold quality
pleura	UBERON:0000977	90.45	gold quality
colonic epithelium	UBERON:0000397	90.20	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.14	gold quality
ventricular zone	UBERON:0003053	90.00	gold quality
caput epididymis	UBERON:0004358	89.95	gold quality
stromal cell of endometrium	CL:0002255	89.94	gold quality
endometrium	UBERON:0001295	89.62	gold quality
blood vessel layer	UBERON:0004797	89.53	gold quality
visceral pleura	UBERON:0002401	89.28	gold quality
adrenal tissue	UBERON:0018303	89.18	gold quality
right adrenal gland cortex	UBERON:0035827	89.13	gold quality
ganglionic eminence	UBERON:0004023	88.90	gold quality
vermiform appendix	UBERON:0001154	88.86	gold quality
lymph node	UBERON:0000029	88.82	gold quality
tonsil	UBERON:0002372	88.66	gold quality
tendon of biceps brachii	UBERON:0008188	88.51	gold quality
adrenal cortex	UBERON:0001235	88.36	gold quality
adrenal gland	UBERON:0002369	88.33	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.24
E-GEOD-100618	no	467.01

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, GATA4, NFKB, NKX2-5, RELA

miRNA regulators (miRDB)

174 targeting PRKD3, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4775	99.98	75.00	6394
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-4725-3P	99.96	69.53	2520

Literature-anchored findings (GeneRIF, showing 35)

• Novel isoforms regulate human keratinocyte differentiation by activating a p38 delta mitogen-activated protein kinase cascade that targets CCAAT/enhancer-binding protein alpha. (PMID:12080077)
• PKCnu is an important component of signaling pathways downstream from novel PKC enzymes after B-cell receptor engagement (PMID:12506120)
• the effect of G protein-coupled receptor agonists on the regulatory properties, continuous shuttling, and intracellular distribution of Protein kinase C nu/protein kinase D3 (PMID:12676944)
• specificity of different PKD isoforms in regulating protein trafficking from the trans-Golgi network (PMID:14743217)
• PKD3 directly contributes to insulin-independent basal glucose uptake in L6 skeletal muscle cells. (PMID:15496505)
• Expression of constitutively activated PKCeta caused Golgi fragmentation. (PMID:15824133)
• the catalytic activity of PKD3 may regulate its nuclear import through autophosphorylation and/or interaction with another protein (PMID:16380377)
• The vesicular distribution may be attributed in part to the direct interaction between PKD3 and vesicle-associated membrane protein VAMP2, through which PKD3 may regulate VAMP2 vesicle trafficking by facilitating its recruitment to the target membrane. (PMID:17196367)
• A pathway comprising PKCs>Raf-1>MEK-1>ERK-1/-2 mediates the effect of gastrin on the CgA promoter, and strongly suggests that enhanced phosphorylation of Sp1 and CREB is crucial for CgA transactivation through the G protein-coupled CCK-B/gastrin receptor. (PMID:17889508)
• The data suggest that protein kinase C contributes to the phosphorylation of influenza PB1 and NS1 proteins which appears to be functionally relevant for both viral RNA polymerase activity and efficient viral replication. (PMID:19264651)
• Data demonstrate the functional role of protein kinase D1 and protein kinase D3 in modulating physiological responses to Ox1R activation. (PMID:20621130)
• PKD3 may contribute to the malignant progression of prostate cancer cells through negative regulation of MMP-7 expression. (PMID:20813660)
• PKD3 contributes to the proliferation and malignant growth of androgen-dependent prostate cancer cells in part by upregulating PSA expression. (PMID:20813663)
• phosphorylation of GIT1 on serine 46 by PKD3 represents a molecular switch by which GIT1 localization, paxillin trafficking, and cellular protrusive activity are regulated. (PMID:22893698)
• PKD antagonists inhibited differentiation and viability of human hematopoietic stem cells, and had less HDAC phosphorylation, confirming the need for PKD-HDAC signaling in erythropoiesis. (PMID:22983445)
• We have identified PKD2 and PKD3, especially PKD3, as novel cell growth regulators in HCC1806 triple-negative breast cancer cells (PMID:23393329)
• PKD3 negatively regulates human airway epithelial barrier formation and integrity through down-regulation of claudin-1, which is a key component of tight junctions. (PMID:24265314)
• PKD3 in TNBC cells provides a molecular connection between the Golgi and endolysosomal compartments to enhance proliferative mTORC1-S6K1 signaling. (PMID:24337579)
• Activation of PKD2 and further increase of PKD3 activity leads to additional phosphorylation and inhibition of endogenous phosphatase slingshot 1L. (PMID:24840177)
• for the first time, PKD3 is implicated in the transcription activation of latent HIV-1 provirus, and our results revealed a molecular mechanism of prostratin-induced HIV-1 transcription via PKCepsilon/PKD3/NF-kappaB signaling pathway. (PMID:25136641)
• Loss of PKD2 enhanced KC proliferative potential while loss of PKD3 resulted in a progressive proliferation defect, loss of clonogenicity and diminished tissue regenerative ability. (PMID:25802335)
• Studies indicate that the loss of protein kinase D PKD1 is thought to promote invasion and metastasis, while PKD2 and upregulated PKD3 to be positive regulators of proliferation. (PMID:26253275)
• None of the Polymorphous low-grade adenocarcinoma (PLGA) lacking PRKD1 somatic mutations or PRKD gene family rearrangements harboured somatic mutations in the kinase domains of the PRKD2 or PRKD3 genes. (PMID:26426580)
• This study discovered and characterized a novel, highly conserved N-terminal domain, comprising 92 amino acids, which mediates dimerization of Protein Kinase D (PKD) isoforms, PKD1, PKD2, and PKD3 monomers. (PMID:27662904)
• Our findings suggest that abnormal PKD3 expression might contribute to hepatocellular carcinoma progression. Furthermore, high PKD3 expression predicts a poor prognosis in hepatocellular carcinoma patients after hepatectomy (PMID:28363424)
• The enriched pathway analysis reveals that PRKD3 regulates pathways contributing to multiple cancer related events, including cell cycle, migration and others. (PMID:28656000)
• KD2 and PKD3 were the two major isoforms of PKD overexpressed in breast cancer. Suppressing either PKD2 or PKD3 was able to reduce breast cancer cell proliferation and metastasis. (PMID:30652415)
• exogenous SCF, CCL5 and CCL11 reversed the effect on MCs migration inhibited by PKD2/3 silencing. Mechanistically, PKD2/3 interacted with Erk1/2 and activated Erk1/2 or NF-kappaB signaling pathway, leading to AP-1 or NF-kappaB binding to the promoter of scf, ccl5 and ccl11. (PMID:30841931)
• The PRKD3 up-regulated 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) and activated glycolysis as shown by increased glucose consumption and lactate production. (PMID:31026442)
• The GEF-H1/PKD3 signaling pathway promotes the maintenance of triple-negative breast cancer stem cells. (PMID:31745977)
• Protein Kinase D3 promotes the cell proliferation by activating the ERK1/c-MYC axis in breast cancer. (PMID:31944568)
• Deletion of Protein Kinase D3 Promotes Liver Fibrosis in Mice. (PMID:32048304)
• Protein kinase D3 regulates the expression of the immunosuppressive protein, PDL1, through STAT1/STAT3 signaling. (PMID:32319563)
• PRKD3 promotes malignant progression of OSCC by downregulating KLF16 expression. (PMID:33378018)
• Protein Kinase D3 (PKD3) Requires Hsp90 for Stability and Promotion of Prostate Cancer Cell Migration. (PMID:36672148)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	prkd3	ENSDARG00000079967
mus_musculus	Prkd3	ENSMUSG00000024070
rattus_norvegicus	Prkd3	ENSRNOG00000005289
drosophila_melanogaster	PKD	FBGN0038603
caenorhabditis_elegans		WBGENE00012019
caenorhabditis_elegans	dkf-1	WBGENE00012352

Paralogs (2): PRKD2 (ENSG00000105287), PRKD1 (ENSG00000184304)

Protein

Protein identifiers

Serine/threonine-protein kinase D3 — O94806 (reviewed: O94806)

Alternative names: Protein kinase C nu type, Protein kinase EPK2, nPKC-nu

All UniProt accessions (4): O94806, C9JKP8, H0Y5M6, H7C172

UniProt curated annotations — full annotation on UniProt →

Function. Converts transient diacylglycerol (DAG) signals into prolonged physiological effects, downstream of PKC. Involved in resistance to oxidative stress.

Subcellular location. Cytoplasm. Membrane.

Tissue specificity. Ubiquitous.

Activity regulation. Activated by DAG and phorbol esters. Phorbol-ester/DAG-type domains 1 and 2 bind both DAG and phorbol ester with high affinity and mediate translocation to the cell membrane. Autophosphorylation of Ser-735 and phosphorylation of Ser-731 by PKC relieves auto-inhibition by the PH domain.

Similarity. Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. PKD subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
O94806-1	1	yes
O94806-2	2

RefSeq proteins (1): NP_005804* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR001849	PH_domain	Domain
IPR002219	PKC_DAG/PE	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR015727	Protein_Kinase_C_mu-related	Family
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR020454	DAG/PE-bd	Domain
IPR046349	C1-like_sf	Homologous_superfamily
IPR057764	Ubiquitin_PRKD1-3_N	Domain

Pfam: PF00069, PF00130, PF00169, PF25525

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 (52 total): modified residue 18, mutagenesis site 8, sequence variant 6, strand 6, domain 2, splice variant 2, zinc finger region 2, turn 2, binding site 2, chain 1, region of interest 1, helix 1, active site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2D9Z	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O94806-F1	69.57	0.26

Functional residue map

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

Catalytic / active sites (1): 699 (proton acceptor)

Ligand- & substrate-binding residues (2): 582–590; 605

Post-translational modifications (18): 27, 37, 41, 44, 213, 216, 364, 391, 395, 426, 442, 457, 535, 539, 731, 735, 742, 6

Mutagenesis-validated functional residues (8):

Position	Phenotype
156	slight loss in ability to bind dag and phorbol-ester; when associated with f-158.
158	slight loss in ability to bind dag and phorbol-ester; when associated with a-156.
165	no effect on ability to bind phorbol ester, loss of ability to bind dag, reduced dag-induced membrane translocation.
166	slight loss in ability to bind dag and phorbol-ester.
170	slight loss in ability to bind dag and phorbol-ester.
282	no effect on ability to bind phorbol ester, increase in ability to bind dag.
284	slight increase in ability to bind dag, no effect on phorbol-ester binding.
293	increased ability to bind dag, no effect on phorbol-ester binding.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-1660661	Sphingolipid de novo biosynthesis
R-HSA-1430728	Metabolism
R-HSA-428157	Sphingolipid metabolism
R-HSA-556833	Metabolism of lipids

MSigDB gene sets: 258 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, VICENT_METASTASIS_UP, AAGCCAT_MIR135A_MIR135B, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, YANG_BREAST_CANCER_ESR1_LASER_DN, BROWNE_HCMV_INFECTION_16HR_UP, HERNANDEZ_ABERRANT_MITOSIS_BY_DOCETACEL_2NM_UP, HERNANDEZ_MITOTIC_ARREST_BY_DOCETAXEL_2_UP, BROWNE_HCMV_INFECTION_48HR_DN, MARTINEZ_RB1_TARGETS_UP, MODULE_289, GOBP_SPHINGOLIPID_METABOLIC_PROCESS, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_UP, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN

GO Biological Process (4): protein phosphorylation (GO:0006468), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), sphingolipid biosynthetic process (GO:0030148), intracellular signal transduction (GO:0035556)

GO Molecular Function (11): protein serine/threonine kinase activity (GO:0004674), diacylglycerol-dependent serine/threonine kinase activity (GO:0004697), ATP binding (GO:0005524), zinc ion binding (GO:0008270), kinase activity (GO:0016301), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (6): nucleoplasm (GO:0005654), cytosol (GO:0005829), plasma membrane (GO:0005886), ciliary basal body (GO:0036064), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Sphingolipid metabolism	1
Metabolism of lipids	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
intracellular anatomical structure	2
protein kinase activity	2
phosphorylation	1
protein modification process	1
G protein-coupled receptor signaling pathway	1
phospholipase C activator activity	1
sphingolipid metabolic process	1
lipid biosynthetic process	1
signal transduction	1
protein serine/threonine kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
transition metal ion binding	1
transferase activity, transferring phosphorus-containing groups	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
catalytic activity	1
cation binding	1
nuclear lumen	1
cytoplasm	1
membrane	1
cell periphery	1
microtubule organizing center	1
cilium	1

Protein interactions and networks

STRING

976 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRKD3	ARF1	P10947	831
PRKD3	AKAP13	Q12802	773
PRKD3	PLEK2	Q9NYT0	768
PRKD3	PLEK	P08567	767
PRKD3	KIDINS220	Q9ULH0	706
PRKD3	HCLS1	P14317	623
PRKD3	PI4KB	P78405	621
PRKD3	CTTN	Q14247	617
PRKD3	HDAC5	Q9UQL6	613
PRKD3	CERT1	Q9Y5P4	602
PRKD3	TCAP	O15273	597
PRKD3	PXN	P49023	572
PRKD3	RYR2	Q92736	550
PRKD3	SSH1	Q8WYL5	546
PRKD3	OSBP	P22059	545

IntAct

31 interactions, top by confidence:

A	B	Type	Score
PRKD2	PRKD3	psi-mi:“MI:0914”(association)	0.730
PRKD3	PRKD1	psi-mi:“MI:0914”(association)	0.640
PRKD1	PRKD3	psi-mi:“MI:0914”(association)	0.640
PRKD3	VAMP2	psi-mi:“MI:0915”(physical association)	0.620
VAMP2	PRKD3	psi-mi:“MI:0407”(direct interaction)	0.620
PRKD3	VAMP2	psi-mi:“MI:0407”(direct interaction)	0.620
PRKD3	VAMP2	psi-mi:“MI:0403”(colocalization)	0.620
MED29	POLR2D	psi-mi:“MI:0914”(association)	0.530
PRKD3	PKM	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
DLAT	PRKD3	psi-mi:“MI:0915”(physical association)	0.370
PRKD3	SKA2	psi-mi:“MI:0915”(physical association)	0.370
PRKD3	NUDT3	psi-mi:“MI:0915”(physical association)	0.370
Ctnnbl1	LCMT2	psi-mi:“MI:0914”(association)	0.350
PRKD2		psi-mi:“MI:0914”(association)	0.350
CHM	POLR3A	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
PRKD3	NDUFA4	psi-mi:“MI:0914”(association)	0.350
PRKD2	ACOT7	psi-mi:“MI:0914”(association)	0.350
FKBP5	IFT56	psi-mi:“MI:0914”(association)	0.350
HDAC2		psi-mi:“MI:0914”(association)	0.350
PRKD2	PRPF40A	psi-mi:“MI:0914”(association)	0.350
RAN	NUP214	psi-mi:“MI:0914”(association)	0.350
EXTL3	CCDC85C	psi-mi:“MI:0914”(association)	0.350
FECH	POTEF	psi-mi:“MI:0914”(association)	0.350
PRKD3	malS	psi-mi:“MI:0915”(physical association)	0.000
PRKD3	MYH3	psi-mi:“MI:0915”(physical association)	0.000
PRKD3	TAF1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (61): PRKD3 (Affinity Capture-MS), PRKD3 (Affinity Capture-MS), PRKD3 (Affinity Capture-RNA), PRKD3 (Affinity Capture-RNA), POLL (Two-hybrid), PRKD3 (Affinity Capture-MS), PRKD3 (Proximity Label-MS), PRKD3 (Proximity Label-MS), PRKD3 (Proximity Label-MS), PRKD3 (Proximity Label-MS), PRKD3 (Proximity Label-MS), MYH3 (Two-hybrid), TAF1 (Two-hybrid), PRKD3 (Affinity Capture-MS), PRKD3 (Affinity Capture-MS)

ESM2 similar proteins: A0A8C0TYJ0, A0A8I5ZNK2, A5D7H2, O55047, O88506, O94806, O95747, P00535, P11273, P32298, P34947, P43249, P49137, Q08CW1, Q12959, Q13033, Q15139, Q15700, Q16644, Q1ECX4, Q28C55, Q3SYZ2, Q3UMW7, Q5PYH5, Q5PYH6, Q5R372, Q5R495, Q5RCW6, Q5XIS9, Q62101, Q62696, Q62833, Q63622, Q66H84, Q6P9R2, Q811D0, Q863I2, Q86UE8, Q8BZ03, Q8C0V0

Diamond homologs: A2ASS6, A2CG49, A4IFM7, A8C984, A8WXF6, E9PT87, F1M0Z1, G4SLH0, O02827, O08875, O43293, O44997, O54784, O60229, O62305, O70150, O75962, O88764, O94768, O94806, P07313, P08414, P10911, P13234, P18652, P18653, P18654, P20689, P22216, P25323, P29294, P51812, P53355, P97924, Q00168, Q0KHT7, Q0KL02, Q14012, Q15139, Q15418

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
PRKD3	unknown	GIT1	phosphorylation
PKA	“up-regulates activity”	PRKD3	phosphorylation
PRKD3	“up-regulates activity”	HDAC5	phosphorylation
PRKD3	“up-regulates activity”	PAK4	phosphorylation
PRKD3	“up-regulates activity”	HDAC7	phosphorylation
PRKD3	“down-regulates activity”	SSH1	phosphorylation
PRKD3	“up-regulates activity”	MFF	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	64
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3616 predictions. Top by Δscore:

Variant	Effect	Δscore
2:37254201:TACCT:T	donor_loss	1.0000
2:37254202:A:C	donor_loss	1.0000
2:37254203:CCT:C	donor_loss	1.0000
2:37254285:AATTG:A	acceptor_gain	1.0000
2:37254286:ATTG:A	acceptor_gain	1.0000
2:37254287:TTG:T	acceptor_gain	1.0000
2:37254287:TTGC:T	acceptor_loss	1.0000
2:37254288:TG:T	acceptor_gain	1.0000
2:37254290:C:CC	acceptor_gain	1.0000
2:37254290:C:T	acceptor_loss	1.0000
2:37267426:TTAC:T	donor_loss	1.0000
2:37267427:TACC:T	donor_loss	1.0000
2:37267428:ACC:A	donor_loss	1.0000
2:37267429:C:A	donor_loss	1.0000
2:37269610:CTTA:C	donor_loss	1.0000
2:37269611:TTAC:T	donor_loss	1.0000
2:37269612:TA:T	donor_loss	1.0000
2:37269613:A:AC	donor_gain	1.0000
2:37269613:ACCT:A	donor_gain	1.0000
2:37269614:C:CC	donor_gain	1.0000
2:37269614:C:G	donor_loss	1.0000
2:37269614:CCT:C	donor_gain	1.0000
2:37269614:CCTC:C	donor_gain	1.0000
2:37269684:TATC:T	acceptor_gain	1.0000
2:37269686:TC:T	acceptor_gain	1.0000
2:37269687:CC:C	acceptor_gain	1.0000
2:37269688:C:CC	acceptor_gain	1.0000
2:37269688:CTG:C	acceptor_loss	1.0000
2:37269691:G:GC	acceptor_gain	1.0000
2:37272374:ACTT:A	donor_loss	1.0000

AlphaMissense

5901 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:37253266:A:G	W862R	1.000
2:37253266:A:T	W862R	1.000
2:37253328:A:G	L841P	1.000
2:37254245:G:T	R820S	1.000
2:37254265:A:G	L813P	1.000
2:37254268:A:G	L812P	1.000
2:37254280:A:G	L808P	1.000
2:37256683:A:G	W798R	1.000
2:37256683:A:T	W798R	1.000
2:37256702:A:C	F791L	1.000
2:37256702:A:T	F791L	1.000
2:37256704:A:G	F791L	1.000
2:37256747:A:C	F776L	1.000
2:37256747:A:T	F776L	1.000
2:37256748:A:G	F776S	1.000
2:37256749:A:G	F776L	1.000
2:37256751:G:T	P775H	1.000
2:37256752:G:A	P775S	1.000
2:37256753:A:C	F774L	1.000
2:37256753:A:T	F774L	1.000
2:37256754:A:C	F774C	1.000
2:37256755:A:G	F774L	1.000
2:37256760:C:T	G772D	1.000
2:37256768:G:C	S769R	1.000
2:37256768:G:T	S769R	1.000
2:37256770:T:G	S769R	1.000
2:37256787:C:A	G763V	1.000
2:37256787:C:T	G763E	1.000
2:37256788:C:G	G763R	1.000
2:37256788:C:T	G763R	1.000

dbSNP variants (sampled 300 via entrez): RS1000027274 (2:37250290 G>A), RS1000082960 (2:37271991 C>A), RS1000100824 (2:37281998 C>A), RS1000217341 (2:37304569 C>T), RS1000247481 (2:37303171 G>A), RS1000255267 (2:37308341 C>G), RS1000263070 (2:37255452 C>G), RS1000269075 (2:37312360 T>C), RS1000365546 (2:37307209 C>A,T), RS1000371138 (2:37323070 A>T), RS1000401779 (2:37265574 C>T), RS1000439142 (2:37307420 G>T), RS1000460126 (2:37264054 C>A,T), RS1000560435 (2:37277760 A>G), RS1000572872 (2:37313363 T>A)

Disease associations

OMIM: gene MIM:607077 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST002149_12	Schizophrenia	7.000000e-09
GCST002299_6	Chronic lymphocytic leukemia	9.000000e-06
GCST004146_1	Chronic lymphocytic leukemia	5.000000e-08
GCST004279_18	Systolic blood pressure	7.000000e-11
GCST004904_221	Body mass index	3.000000e-12
GCST004904_252	Body mass index	3.000000e-09
GCST006979_917	Heel bone mineral density	4.000000e-10
GCST007094_94	Diastolic blood pressure	1.000000e-06
GCST007096_144	Pulse pressure	5.000000e-08
GCST007099_251	Systolic blood pressure	1.000000e-10
GCST011769_9	Schizophrenia	9.000000e-09
GCST012182_14	Alzheimer’s disease	1.000000e-09
GCST90002389_108	Lymphocyte percentage of white cells	2.000000e-12
GCST90002399_138	Neutrophil percentage of white cells	4.000000e-10

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0004340	body mass index
EFO:0009270	heel bone mineral density
EFO:0006336	diastolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2093867 (PROTEIN FAMILY), CHEMBL2096620 (PROTEIN FAMILY), CHEMBL2595 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

62 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 570,946 (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
CHEMBL1863513	INGENOL MEBUTATE	4	1,475
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL83	TAMOXIFEN	4	171,635
CHEMBL1078178	MOMELOTINIB	4	3,481
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL180022	NERATINIB	4	9,404
CHEMBL189963	PALBOCICLIB	4	13,102
CHEMBL2028663	DABRAFENIB	4	12,430
CHEMBL2325741	CAPIVASERTIB	4	2,157
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL31	GATIFLOXACIN	4	25,151
CHEMBL3301610	ABEMACICLIB	4	7,045
CHEMBL3545311	BRIGATINIB	4	5,634
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL939	GEFITINIB	4	117,814
CHEMBL265502	SURAMIN	3	36,848
CHEMBL38380	FASUDIL	3	11,953
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL2105728	CRENOLANIB	3
CHEMBL522892	DOVITINIB	3
CHEMBL603469	LESTAURTINIB	3
CHEMBL279115	PHORBOL MYRISTATE ACETATE	2
CHEMBL28509	EDELFOSINE	2
CHEMBL3137336	UPROSERTIB	2
CHEMBL574737	UCN-01	2
CHEMBL1090090	VX-702	2
CHEMBL1230609	FORETINIB	2
CHEMBL1614713	CC-401	2

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Protein kinase D (PKD) family

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

Ligand	Action	Affinity	Parameter
BPKDi	Inhibition	9.0	pIC50
CRT 0066101	Inhibition	8.7	pIC50

Binding affinities (BindingDB)

24 measured of 48 human assays (48 total across all organisms); most potent 24 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL4442196	IC50	0.09 nM
CHEMBL3741746	IC50	0.13 nM
CHEMBL4528495	IC50	0.15 nM
CHEMBL4538431	IC50	0.17 nM
CHEMBL4443190	IC50	0.18 nM
CHEMBL4435580	IC50	0.22 nM
CHEMBL4587471	IC50	0.36 nM
CHEMBL4575056	EC50	0.6 nM
Staurosporine	KD	1.7 nM
kb-NB142-70	IC50	28.3 nM
PD-146626	IC50	82.5 nM
kb-NB165-92	IC50	111 nM
kb-NB165-31	IC50	114 nM
PKC-412	KD	190 nM
kb-NB184-02	IC50	193 nM
1-[4-[(4-ethyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[[6-(methylamino)-4-pyrimidinyl]oxy]phenyl]urea	KD	1400 nM
BMS-387072	KD	1800 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
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S)-3-hydroxy-1-methyl-4-piperidinyl]-1-benzopyran-4-one	KD	5300 nM
CHEMBL411351	IC50	15000 nM
CHEMBL3215313	IC50	17000 nM
CHEMBL81478	IC50	30000 nM

ChEMBL bioactivities

780 potent at pChembl≥5 of 887 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.10	IC50	0.08	nM	STAUROSPORINE
10.05	IC50	0.09	nM	CHEMBL4442196
9.89	IC50	0.13	nM	CHEMBL3741746
9.85	IC50	0.14	nM	CHEMBL4575056
9.82	IC50	0.15	nM	CHEMBL4528495
9.77	IC50	0.17	nM	CHEMBL4538431
9.74	IC50	0.18	nM	CHEMBL4443190
9.72	EC50	0.19	nM	CHEMBL3741746
9.66	IC50	0.22	nM	CHEMBL4435580
9.44	IC50	0.36	nM	CHEMBL4587471
9.26	EC50	0.55	nM	CHEMBL4587471
9.22	EC50	0.6	nM	CHEMBL4575056
9.22	IC50	0.6	nM	STAUROSPORINE
9.00	IC50	1	nM	STAUROSPORINE
9.00	IC50	1	nM	CHEMBL5440043
8.83	IC50	1.49	nM	STAUROSPORINE
8.82	IC50	1.52	nM	STAUROSPORINE
8.82	IC50	1.5	nM	CHEMBL5419827
8.77	IC50	1.7	nM	CHEMBL291126
8.70	IC50	2	nM	CHEMBL162621
8.70	IC50	2	nM	STAUROSPORINE
8.70	IC50	2	nM	CHEMBL5428541
8.68	IC50	2.07	nM	STAUROSPORINE
8.68	IC50	2.1	nM	SOTRASTAURIN
8.66	IC50	2.2	nM	CHEMBL83790
8.57	IC50	2.7	nM	STAUROSPORINE
8.52	IC50	3	nM	STAUROSPORINE
8.52	Kd	3	nM	CHEMBL400402
8.40	Ki	3.981	nM	CHEMBL1986263
8.40	Ki	3.981	nM	CHEMBL1997129
8.40	Ki	3.981	nM	CHEMBL1974870
8.40	Ki	3.981	nM	CHEMBL1991063
8.39	IC50	4.1	nM	UCN-01
8.34	IC50	4.6	nM	CHEMBL6144731
8.30	IC50	5	nM	CHEMBL538718
8.30	Ki	5.012	nM	CHEMBL1994669
8.30	Ki	5.012	nM	CHEMBL1970903
8.30	Ki	5.012	nM	CHEMBL1973720
8.30	Ki	5.012	nM	CHEMBL2005509
8.28	Ki	5.3	nM	BALANOL
8.22	IC50	6	nM	CHEMBL4515390
8.22	Kd	6	nM	CHEMBL27768
8.22	IC50	6	nM	STAUROSPORINE
8.20	Ki	6.31	nM	CHEMBL1966628
8.20	Ki	6.31	nM	CHEMBL2001751
8.19	IC50	6.5	nM	STAUROSPORINE
8.15	IC50	7	nM	STAUROSPORINE
8.12	IC50	7.5	nM	STAUROSPORINE
8.10	IC50	8	nM	STAUROSPORINE
8.10	IC50	7.9	nM	STAUROSPORINE

PubChem BioAssay actives

239 with measured affinity, of 2450 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
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,22R,25R)-12-benzoyloxy-10,11,22-trihydroxy-9-(hydroxymethyl)-13,15-dimethyl-4-prop-1-en-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-2-yl]methyl benzoate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0001	uM
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,22R,25R)-22-acetyloxy-12-benzoyloxy-10,11-dihydroxy-9-(hydroxymethyl)-13,15-dimethyl-4-prop-1-en-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-2-yl]methyl benzoate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0001	uM
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,22R,25R)-2-(benzoyloxymethyl)-10,11,22-trihydroxy-9-(hydroxymethyl)-13,15-dimethyl-4-prop-1-en-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-12-yl] naphthalene-2-carboxylate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0001	uM
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,25R)-12-benzoyloxy-10,11-dihydroxy-9-(hydroxymethyl)-13,15-dimethyl-22-oxo-4-prop-1-en-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-2-yl]methyl benzoate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0001	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	165147: Inhibition Protein kinase C (PKC)	ic50	0.0001	uM
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,22R,25R)-2-(benzoyloxymethyl)-10,11,22-trihydroxy-9-(hydroxymethyl)-13,15-dimethyl-4-prop-1-en-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-12-yl] 4-nitrobenzoate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0002	uM
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,22R,25R)-12-benzoyloxy-10,11,22-trihydroxy-9-(hydroxymethyl)-13,15-dimethyl-4-propan-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-2-yl]methyl benzoate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0002	uM
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,22R,25R)-2-(benzoyloxymethyl)-10,11,22-trihydroxy-9-(hydroxymethyl)-13,15-dimethyl-4-prop-1-en-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-12-yl] 4-methoxybenzoate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0002	uM
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,22R,25R)-2-(benzoyloxymethyl)-10,11,22-trihydroxy-9-(hydroxymethyl)-13,15-dimethyl-4-prop-1-en-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-12-yl] pyridine-4-carboxylate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0004	uM
2-piperazin-1-yl-6-(2-piperidin-1-yl-4-pyridinyl)pyridine-4-carboxamide	1964578: Inhibition of PKD3 (unknown origin)	ic50	0.0010	uM
3-[6-amino-5-(6-ethoxynaphthalen-2-yl)-3-pyridinyl]-N-[2-(dimethylamino)ethyl]benzamide	1964578: Inhibition of PKD3 (unknown origin)	ic50	0.0015	uM
(15R,16R,18S)-16-(hydroxymethyl)-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-3,5-dione	155717: In vitro inhibition of protein kinase C (PKC)	ic50	0.0017	uM
2-[4-[[(2S)-2-aminobutyl]amino]pyrimidin-2-yl]-4-(1-methylpyrazol-4-yl)phenol	1964578: Inhibition of PKD3 (unknown origin)	ic50	0.0020	uM
3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione	1902442: Inhibition of PKCnu (unknown origin) by IMAP kinase assay	ic50	0.0021	uM
4-chloro-3-[5-methyl-3-[4-(2-pyrrolidin-1-ylethoxy)anilino]-1,2,4-benzotriazin-7-yl]phenol	1425137: 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	0.0030	uM
2-[2,6-dihydroxy-4-[(3R,4R)-3-[(4-hydroxybenzoyl)amino]azepan-4-yl]oxycarbonylbenzoyl]-3-hydroxybenzoic acid	254306: Inhibitory constant against protein kinase C	ki	0.0053	uM
2-[4-[[(2R)-2-aminobutyl]amino]pyrimidin-2-yl]-4-(1-methylpyrazol-4-yl)phenol	1742911: Inhibition of recombinant FLAG-tagged PKD3 (unknown origin) expressed in HEK293T cells using Syntide-2 as substrate measured after 15 mins by ADP-Glo assay	ic50	0.0060	uM
[(1S,2S,6R,10S,11R,13S,14R,15R)-13-butanoyloxy-1,6-dihydroxy-8-(hydroxymethyl)-4,12,12,15-tetramethyl-5-oxo-14-tetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dienyl] butanoate	2150891: Binding affinity to PKC (unknown origin) assessed as dissociation constant	kd	0.0060	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	508049: Binding affinity to PRKD3	kd	0.0089	uM
[(1S,2S,6R,10S,11R,13S,14R,15R)-13-acetyloxy-1,6-dihydroxy-8-(hydroxymethyl)-4,12,12,15-tetramethyl-5-oxo-14-tetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dienyl] tetradecanoate	1459482: Activation of PKC in human platelet assessed as induction of platelet aggregation measured within 15 mins by tribidimetric method	ec50	0.0095	uM
5-chloro-4-(4-chloro-1-methylpyrazol-5-yl)-N-[(3S,4S,6S)-4-(3,4-difluorophenyl)-6-(2-hydroxyethyl)piperidin-3-yl]furan-2-carboxamide	1608042: Inhibition of PKC (unknown origin)	ic50	0.0160	uM
3-(1H-indol-3-yl)-1-(piperidin-4-ylmethyl)pyrazolo[3,4-d]pyrimidin-4-amine	1742911: Inhibition of recombinant FLAG-tagged PKD3 (unknown origin) expressed in HEK293T cells using Syntide-2 as substrate measured after 15 mins by ADP-Glo assay	ic50	0.0170	uM
N-[(1R)-1-cyanoethyl]-3-[5-[4-[(oxan-4-ylamino)methyl]phenyl]-1,2-oxazol-3-yl]benzamide	580272: Inhibition of human PKD3	ic50	0.0170	uM
(2S,5S)-9-decyl-5-(hydroxymethyl)-1-methyl-2-propan-2-yl-2,4,5,6-tetrahydro-1,4-benzodiazocin-3-one	2163933: Activation of PKC in human ACH-2 cells infected with latent HIV-1 assessed as reversal of HIV-1 latency by measuring increase in p24 antigen level incubated for 48 hrs by chemiluminescent enzyme immunoassay	ec50	0.0250	uM
4-[[[6-methoxy-4-methyl-5-[3-(trifluoromethyl)phenoxy]quinolin-8-yl]amino]methyl]phenol	1180278: Inhibition of PKC (unknown origin) using C1 peptide substrate	ic50	0.0350	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	1425137: 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	0.0380	uM
3-(2-ethoxyquinolin-6-yl)-1-[(1-methylpiperidin-4-yl)methyl]pyrazolo[3,4-d]pyrimidin-4-amine	1742911: Inhibition of recombinant FLAG-tagged PKD3 (unknown origin) expressed in HEK293T cells using Syntide-2 as substrate measured after 15 mins by ADP-Glo assay	ic50	0.0430	uM
(10S,13S)-13-(hydroxymethyl)-9-methyl-10-propan-2-yl-3,9,12-triazatricyclo[6.6.1.04,15]pentadeca-1,4(15),5,7-tetraen-11-one	2163933: Activation of PKC in human ACH-2 cells infected with latent HIV-1 assessed as reversal of HIV-1 latency by measuring increase in p24 antigen level incubated for 48 hrs by chemiluminescent enzyme immunoassay	ec50	0.0470	uM
9-hydroxy-3,4-dihydro-2H-[1]benzothiolo[2,3-f][1,4]thiazepin-5-one	1964578: Inhibition of PKD3 (unknown origin)	ic50	0.0530	uM
10-hydroxy-2,3,4,5-tetrahydro-[1]benzothiolo[3,2-b][1,5]thiazocin-6-one	1799562: In Vitro Radiometric Kinase Assay from Article 10.1186/1472-6769-10-5: “Novel protein kinase D inhibitors cause potent arrest in prostate cancer cell growth and motility.”	ic50	0.0588	uM
N-[6,6-dimethyl-5-(1-methylpiperidine-4-carbonyl)-1,4-dihydropyrrolo[3,4-d]pyrazol-3-yl]-3-methylbutanamide	1425137: 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	0.0650	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149084: Binding affinity to human PRKD3 incubated for 45 mins by Kinobead based pull down assay	kd	0.0724	uM
[(1S,4S,5S,6R,9S,10R,12R,14R)-5,6-dihydroxy-7-(hydroxymethyl)-3,11,11,14-tetramethyl-15-oxo-4-tetracyclo[7.5.1.01,5.010,12]pentadeca-2,7-dienyl] (Z)-2-methylbut-2-enoate	1459482: Activation of PKC in human platelet assessed as induction of platelet aggregation measured within 15 mins by tribidimetric method	ec50	0.0725	uM
3-[4-amino-3-(1H-indol-3-yl)pyrazolo[3,4-d]pyrimidin-1-yl]-2,2-dimethylpropan-1-ol	1742911: Inhibition of recombinant FLAG-tagged PKD3 (unknown origin) expressed in HEK293T cells using Syntide-2 as substrate measured after 15 mins by ADP-Glo assay	ic50	0.0760	uM
3-naphthalen-1-yl-1-(piperidin-4-ylmethyl)pyrazolo[3,4-d]pyrimidin-4-amine	1742911: Inhibition of recombinant FLAG-tagged PKD3 (unknown origin) expressed in HEK293T cells using Syntide-2 as substrate measured after 15 mins by ADP-Glo assay	ic50	0.0780	uM
bis(3,3-bis[4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl]-2-phenylprop-2-enenitrile);pentahydrochloride	1323681: Inhibition of PKC in human SH-SY5Y cells assessed as inhibition of PMA-stimulated MARCKS phosphorylation preincubated for 1 hr followed by PMA-stimulation for 15 mins by Western blot analysis	ic50	0.0800	uM
3-hydroxy-2-[4-[(3R,4R)-3-[(4-hydroxybenzoyl)amino]azepan-4-yl]oxycarbonylbenzoyl]benzoic acid	254303: Inhibitory activity against protein kinase C	ki	0.0800	uM
3,13-diazahexacyclo[14.8.0.02,10.04,9.011,15.017,22]tetracosa-1(16),2(10),4,6,8,11(15),17,19,21-nonaene-12,14-dione	277640: Inhibition of PKC	ic50	0.0830	uM
3-[3-(2-piperidin-1-ylethoxy)phenyl]-5-(1H-1,2,4-triazol-5-yl)-1H-indazole	1425137: 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	0.0900	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	625024: Binding constant for PRKD3 kinase domain	kd	0.0900	uM
9-hydroxy-10-iodo-3,4-dihydro-2H-[1]benzothiolo[2,3-f][1,4]thiazepin-5-one	1799562: In Vitro Radiometric Kinase Assay from Article 10.1186/1472-6769-10-5: “Novel protein kinase D inhibitors cause potent arrest in prostate cancer cell growth and motility.”	ic50	0.0911	uM
1-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[4-[(dimethylamino)methyl]cyclohexyl]amino]-1,5-naphthyridin-3-yl]ethanone	1425137: 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	0.0930	uM
5-chloro-4-(4-chloro-1-methylpyrazol-5-yl)-N-[(3S,4S,6S)-4-(3,4-difluorophenyl)-6-[2-(methylamino)-2-oxoethyl]piperidin-3-yl]furan-2-carboxamide	1608042: Inhibition of PKC (unknown origin)	ic50	0.0940	uM
Brigatinib	2182828: Inhibition of human PRKD3 using KKLNRTLSVA as substrate in presence of [gamma33P]-ATP by HotSpot assay	ic50	0.0950	uM
9-methoxy-3,4-dihydro-2H-[1]benzothiolo[2,3-f][1,4]thiazepin-5-one	1799562: In Vitro Radiometric Kinase Assay from Article 10.1186/1472-6769-10-5: “Novel protein kinase D inhibitors cause potent arrest in prostate cancer cell growth and motility.”	ic50	0.0985	uM
(2S)-5-(diaminomethylideneamino)-2-[[(2S)-5-(diaminomethylideneamino)-2-[[(2S)-5-(diaminomethylideneamino)-2-[[(2S)-5-(diaminomethylideneamino)-2-[[(2S)-5-(diaminomethylideneamino)-2-[[(2S)-5-(diaminomethylideneamino)-2-[[(2S)-3-hydroxy-2-[3-[2-(isoquinolin-5-ylsulfonylamino)ethylamino]propanoylamino]propanoyl]amino]pentanoyl]amino]pentanoyl]amino]pentanoyl]amino]pentanoyl]amino]pentanoyl]amino]pentanoic acid	164148: Displacement of ATP from protein kinase C (PKC)	ki	0.1000	uM
Momelotinib	2183877: Inhibition of PRKCN (unknown origin)	ic50	0.1000	uM
1-tert-butyl-3-naphthalen-1-ylpyrazolo[3,4-d]pyrimidin-4-amine	1964578: Inhibition of PKD3 (unknown origin)	ic50	0.1040	uM
2-(5-chloro-2-fluorophenyl)-N-pyridin-4-ylpteridin-4-amine	1964578: Inhibition of PKD3 (unknown origin)	ic50	0.1050	uM
1-tert-butyl-3-(1H-indol-3-yl)pyrazolo[3,4-d]pyrimidin-4-amine	1742911: Inhibition of recombinant FLAG-tagged PKD3 (unknown origin) expressed in HEK293T cells using Syntide-2 as substrate measured after 15 mins by ADP-Glo assay	ic50	0.1080	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation	5
Acetaminophen	decreases expression, affects cotreatment, increases expression	2
Arsenic	increases response to substance, decreases expression, increases abundance	2
Benzo(a)pyrene	decreases expression, increases methylation	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
6-hydroxy-5-((p- sulfophenyl)azo)-2-naphthalenesulfonic acid disodium salt	affects cotreatment, increases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
trichostatin A	increases expression	1
sodium arsenite	decreases expression, increases abundance	1
cobaltous chloride	decreases expression	1
coumarin	increases phosphorylation	1
perfluorooctane sulfonic acid	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
asparanin A	decreases expression	1
jinfukang	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Carbamazepine	affects expression	1
Catechin	affects cotreatment, increases expression	1
Chenodeoxycholic Acid	affects cotreatment, increases expression	1
Cisplatin	increases expression	1
Deoxycholic Acid	increases expression, affects cotreatment	1
Diclofenac	affects expression	1
Doxorubicin	decreases expression	1
Folic Acid	decreases expression	1
Glycochenodeoxycholic Acid	affects cotreatment, increases expression	1

ChEMBL screening assays

557 unique, capped per target: 546 binding, 11 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1000235	Binding	Activation of PKC in PMA-stimulated human LNCAP cells assessed as ERK phosphorylation at 1 nM to 10 uM by Western blot relative to PMA	Conformationally constrained analogues of diacylglycerol (DAG). 31. Modulation of the biological properties of diacylgycerol lactones (DAG-lactones) containing rigid-rod acyl groups separated from the core lactone by spacer units of different lengths. — J Med Chem
CHEMBL688555	Functional	Retained protein kinase C activity in the presence of 1.25 uM compound	Synthesis and biological activity of novel quaternary ammonium derivatives of alkylglycerols as potent inhibitors of protein kinase C. — J Med Chem

Cellosaurus cell lines

6 cell lines: 5 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2C7	Abcam HeLa PRKD3 KO	Cancer cell line	Female
CVCL_D7YP	Ubigene A-549 PRKD3 KO	Cancer cell line	Male
CVCL_D8U2	Ubigene HCT 116 PRKD3 KO	Cancer cell line	Male
CVCL_D9PT	Ubigene HEK293 PRKD3 KO	Transformed cell line	Female
CVCL_E0M0	Ubigene HeLa PRKD3 KO	Cancer cell line	Female
CVCL_TH00	HAP1 PRKD3 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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