PRKCD

Summary

PRKCD (protein kinase C delta, HGNC:9399) is a protein-coding gene on chromosome 3p21.1, encoding Protein kinase C delta type (Q05655). Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays contrasting roles in cell death and cell survival by functioning as a pro-apoptotic protein during DNA damage-induced apoptosis, but acting as an anti-apoptotic prote….

The protein encoded by this gene is a member of the protein kinase C family of serine- and threonine-specific protein kinases. The encoded protein is activated by diacylglycerol and is both a tumor suppressor and a positive regulator of cell cycle progression. Also, this protein can positively or negatively regulate apoptosis. Defects in this gene are a cause of autoimmune lymphoproliferative syndrome.

Source: NCBI Gene 5580 — RefSeq curated summary.

At a glance

• Gene–disease (curated): systemic lupus erythematosus (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 11
• Clinical variants (ClinVar): 609 total — 13 pathogenic, 7 likely-pathogenic (top 5% of genes corpus-wide)
• Regional missense constraint (gnomAD): 1 of 5 regions constrained (≈2% of expected missense variation)
• GTEx eGene: eQTL in 25 tissues, sQTL in 48 (q < 0.05)
• Phenotypes (HPO): 42
• Drug target: yes — 1 curated mechanism-of-action drug; 49 molecules with ChEMBL bioactivity (top 1% of genes corpus-wide)
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types (inferred from mutation patterns)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.34 (highly constrained)
• MANE Select transcript: NM_006254
• Interaction hub: 2,304 STRING partners (top 5% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9399
Approved symbol	PRKCD
Name	protein kinase C delta
Location	3p21.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000163932
Ensembl biotype	protein_coding
OMIM	176977
Entrez	5580

Gene structure

Transcript identifiers

Ensembl transcripts: 47 — 38 protein_coding, 7 nonsense_mediated_decay, 2 retained_intron

MANE Select: ENST00000330452

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 3: 1, TSL 4: 2, TSL 5: 1

ENST00000330452, ENST00000394729, ENST00000464818, ENST00000477794, ENST00000478843, ENST00000487897, ENST00000650739, ENST00000650940, ENST00000651505, ENST00000652449, ENST00000654719, ENST00000697588, ENST00000697589, ENST00000697590, ENST00000883491, ENST00000883492, ENST00000883493, ENST00000928336, ENST00000928337, ENST00000928338, ENST00000928339, ENST00000928340, ENST00000949457, ENST00000949458, ENST00000949459, ENST00000949460, ENST00000949461, ENST00000949462, ENST00000949463, ENST00000949464, ENST00000949465, ENST00000949466, ENST00000949467, ENST00000949468, ENST00000949469, ENST00000949470, ENST00000949471, ENST00000949472, ENST00000949473, ENST00000949474, ENST00000949475, ENST00000949476, ENST00001053192, ENST00001053194, ENST00001053195, ENST00001053196, ENST00001053197

RefSeq mRNA: 7 — MANE Select: NM_006254 NM_001316327, NM_001354676, NM_001354678, NM_001354679, NM_001354680, NM_006254, NM_212539

CCDS: CCDS2870

Canonical transcript exons

ENST00000330452 — 19 exons

Exon	Start	End
ENSE00001079749	53181444	53181606
ENSE00001079750	53179577	53179776
ENSE00001079751	53186604	53186695
ENSE00001079752	53183121	53183206
ENSE00001079754	53187340	53187402
ENSE00001079755	53185927	53186027
ENSE00001079756	53181701	53181732
ENSE00001079757	53186167	53186340
ENSE00001079760	53188720	53188858
ENSE00001079761	53185604	53185700
ENSE00001079762	53184874	53184974
ENSE00001079764	53189873	53190001
ENSE00001079766	53189058	53189246
ENSE00001079767	53183452	53183581
ENSE00001297556	53161209	53161428
ENSE00001321750	53192108	53192717
ENSE00001339281	53165104	53165215
ENSE00003784881	53181207	53181267
ENSE00003851003	53178404	53178537

Expression profiles

Bgee: expression breadth ubiquitous, 229 present calls, max score 98.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.8011 / max 981.7375, expressed in 1799 samples.

Highest expression (Bgee): monocyte, mononuclear cell, leukocyte, granulocyte, adrenal gland cortex.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PRKCD is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 25 tissues and its splicing (sQTL) in 48 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 73 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	sqtl	9.3e-262	-1.46	3:53173500:C:G
Thyroid	sqtl	4.3e-174	-1.41	3:53173500:C:G
Adipose Subcutaneous	sqtl	3.4e-173	-1.36	3:53173500:C:G
Skin Not Sun Exposed Suprapubic	sqtl	2.1e-168	-1.33	3:53173500:C:G
Cells Cultured fibroblasts	sqtl	4.1e-156	-1.30	3:53173500:C:G
Lung	sqtl	3.0e-142	-1.39	3:53173500:C:G
Skin Sun Exposed Lower leg	sqtl	9.5e-137	-1.29	3:53173500:C:G
Artery Tibial	sqtl	5.3e-123	-1.26	3:53173500:C:G
Esophagus Mucosa	sqtl	6.2e-118	-1.33	3:53173500:C:G
Cells EBV-transformed lymphocytes	sqtl	6.1e-113	-1.45	3:53173500:C:G
Nerve Tibial	sqtl	3.4e-112	-1.19	3:53173500:C:G
Adipose Visceral Omentum	sqtl	3.2e-111	-1.33	3:53173500:C:G
Esophagus Muscularis	sqtl	1.4e-100	-1.23	3:53173500:C:G
Testis	sqtl	5.8e-88	-1.35	3:53173500:C:G
Colon Transverse	sqtl	2.7e-85	-1.27	3:53173500:C:G
Breast Mammary Tissue	sqtl	2.2e-82	-1.37	3:53173500:C:G
Artery Aorta	sqtl	4.7e-78	-1.28	3:53173500:C:G
Esophagus Gastroesophageal Junction	sqtl	4.3e-72	-1.21	3:53173500:C:G
Stomach	sqtl	5.1e-67	-1.25	3:53173500:C:G
Spleen	sqtl	3.2e-65	-1.39	3:53173500:C:G

FANTOM5 promoters

6 alternative TSS:

Promoter ID	TPM avg	Samples expressed
36913	21.7824	1793
36914	2.9025	971
36918	1.5323	211
36915	1.3837	286
36916	0.1785	46
36919	0.0217	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	98.31	gold quality
mononuclear cell	CL:0000842	98.00	gold quality
leukocyte	CL:0000738	97.96	gold quality
granulocyte	CL:0000094	97.73	gold quality
right adrenal gland cortex	UBERON:0035827	95.82	gold quality
right uterine tube	UBERON:0001302	95.74	gold quality
mucosa of transverse colon	UBERON:0004991	95.69	gold quality
right adrenal gland	UBERON:0001233	95.63	gold quality
left adrenal gland	UBERON:0001234	95.20	gold quality
left adrenal gland cortex	UBERON:0035825	95.03	gold quality
right lobe of thyroid gland	UBERON:0001119	94.90	gold quality
left lobe of thyroid gland	UBERON:0001120	94.53	gold quality
rectum	UBERON:0001052	93.83	gold quality
adrenal cortex	UBERON:0001235	93.68	gold quality
upper lobe of left lung	UBERON:0008952	93.66	gold quality
adrenal gland	UBERON:0002369	93.55	gold quality
blood	UBERON:0000178	93.36	gold quality
gall bladder	UBERON:0002110	93.28	gold quality
spleen	UBERON:0002106	93.22	gold quality
right lung	UBERON:0002167	93.10	gold quality
thyroid gland	UBERON:0002046	92.95	gold quality
upper lobe of lung	UBERON:0008948	92.77	gold quality
bone marrow cell	CL:0002092	92.65	gold quality
body of stomach	UBERON:0001161	92.59	gold quality
lower esophagus mucosa	UBERON:0035834	92.39	gold quality
endometrium epithelium	UBERON:0004811	92.19	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.14	gold quality
transverse colon	UBERON:0001157	91.98	gold quality
skin of abdomen	UBERON:0001416	91.60	gold quality
right coronary artery	UBERON:0001625	91.41	gold quality
skin of leg	UBERON:0001511	91.24	gold quality
esophagus mucosa	UBERON:0002469	91.09	gold quality
vermiform appendix	UBERON:0001154	91.04	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.94	gold quality
small intestine	UBERON:0002108	90.64	gold quality
omental fat pad	UBERON:0010414	90.53	gold quality
peritoneum	UBERON:0002358	90.46	gold quality
subcutaneous adipose tissue	UBERON:0002190	90.45	gold quality
minor salivary gland	UBERON:0001830	90.29	gold quality
adipose tissue of abdominal region	UBERON:0007808	90.25	gold quality
left coronary artery	UBERON:0001626	89.75	gold quality
adipose tissue	UBERON:0001013	89.73	gold quality
stomach	UBERON:0000945	89.56	gold quality
right atrium auricular region	UBERON:0006631	89.33	gold quality
duodenum	UBERON:0002114	89.21	gold quality
lymph node	UBERON:0000029	89.14	gold quality
ileal mucosa	UBERON:0000331	89.13	gold quality
descending thoracic aorta	UBERON:0002345	89.03	gold quality
body of pancreas	UBERON:0001150	88.92	gold quality
connective tissue	UBERON:0002384	88.70	gold quality
jejunal mucosa	UBERON:0000399	88.64	gold quality
zone of skin	UBERON:0000014	88.63	gold quality
esophagus	UBERON:0001043	88.57	gold quality
thoracic aorta	UBERON:0001515	88.56	gold quality
ascending aorta	UBERON:0001496	88.47	gold quality
coronary artery	UBERON:0001621	88.38	gold quality
aorta	UBERON:0000947	88.04	gold quality
mouth mucosa	UBERON:0003729	87.95	gold quality
tibial artery	UBERON:0007610	87.92	gold quality
popliteal artery	UBERON:0002250	87.91	gold quality
bone marrow	UBERON:0002371	87.91	gold quality
islet of Langerhans	UBERON:0000006	87.85	gold quality
prostate gland	UBERON:0002367	87.84	gold quality
intestine	UBERON:0000160	87.49	gold quality
metanephros cortex	UBERON:0010533	87.48	gold quality
cardiac atrium	UBERON:0002081	87.36	gold quality
endocervix	UBERON:0000458	87.35	gold quality
pancreas	UBERON:0001264	87.11	gold quality
colon	UBERON:0001155	86.96	gold quality
apex of heart	UBERON:0002098	86.96	gold quality
large intestine	UBERON:0000059	86.87	gold quality
saliva-secreting gland	UBERON:0001044	86.63	gold quality
tibial nerve	UBERON:0001323	86.49	gold quality
urinary bladder	UBERON:0001255	86.43	gold quality
caecum	UBERON:0001153	86.20	gold quality
lower esophagus	UBERON:0013473	86.04	gold quality
lower esophagus muscularis layer	UBERON:0035833	86.02	gold quality
left testis	UBERON:0004533	85.95	gold quality
ectocervix	UBERON:0012249	85.91	gold quality
lung	UBERON:0002048	85.88	gold quality
left uterine tube	UBERON:0001303	85.77	gold quality
stromal cell of endometrium	CL:0002255	85.61	gold quality
vagina	UBERON:0000996	85.42	gold quality
right testis	UBERON:0004534	85.39	gold quality
fundus of stomach	UBERON:0001160	85.36	gold quality
mucosa of stomach	UBERON:0001199	85.19	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	85.03	gold quality
right frontal lobe	UBERON:0002810	84.56	gold quality
cingulate cortex	UBERON:0003027	84.41	gold quality
anterior cingulate cortex	UBERON:0009835	84.33	gold quality
colonic mucosa	UBERON:0000317	84.20	gold quality
prefrontal cortex	UBERON:0000451	84.05	gold quality
caudate nucleus	UBERON:0001873	84.04	gold quality
right ovary	UBERON:0002118	84.03	gold quality
testis	UBERON:0000473	83.98	gold quality
adult mammalian kidney	UBERON:0000082	83.82	gold quality
multicellular organism	UBERON:0000468	83.49	gold quality
anatomical system	UBERON:0000467	83.46	gold quality
material anatomical entity	UBERON:0000465	83.44	gold quality
bronchial epithelial cell	CL:0002328	83.18	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-75367	yes	522.67
E-ANND-3	yes	17.79
E-MTAB-9067	yes	11.47

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Bone marrow	tissue	70.5	high
Tonsil	tissue	53.2	high
Stomach 1	tissue	51.8	high
Adrenal gland	tissue	50.3	medium
Small intestine	tissue	45.5	medium
Duodenum	tissue	42.7	medium
Adipose tissue	tissue	39.7	low
Appendix	tissue	37.8	high
Lung	tissue	37.7	high
Lymph node	tissue	37.4	high
Urinary bladder	tissue	36.7	high
Colon	tissue	36.4	high
Fallopian tube	tissue	36.4	high
Rectum	tissue	33.4	high
Epididymis	tissue	33.2	high
Thyroid gland	tissue	32.1	medium
Prostate	tissue	31.3	medium
Spleen	tissue	29.3	medium
Pancreas	tissue	27.9	medium
Hippocampal formation	tissue	27.1
Esophagus	tissue	26.7	medium
Seminal vesicle	tissue	26.1	high
Gallbladder	tissue	25.8	high
Cervix	tissue	22.2	medium
Kidney	tissue	22.2	medium
Skin 1	tissue	22.1	low
Vagina	tissue	21.6	low
Septum	tissue	21.5
Salivary gland	tissue	21.0	medium
Nucleus accumbens	tissue	19.4
Testis	tissue	18.2	medium
Parathyroid gland	tissue	18.0	medium
Hippocampus	tissue	16.6	low
Choroid plexus	tissue	16.4
Placenta	tissue	16.1	high
Hypothalamus	tissue	15.9
Putamen	tissue	15.4
Breast	tissue	14.8	low
Spinal cord	tissue	14.4
Heart muscle	tissue	13.7	low
Periaqueductal gray	tissue	13.6
Thymus	tissue	13.5
Smooth muscle	tissue	13.3	low
Substantia nigra	tissue	13.0
Medulla oblongata	tissue	12.6
Locus coeruleus	tissue	11.6
Corpus callosum	tissue	11.4
Ventral forebrain	tissue	11.4
Cerebellum	tissue	10.9	medium
Pons	tissue	10.8
Amygdala	tissue	10.8
Basal ganglia	tissue	10.6	medium
Midbrain	tissue	10.5
Superior colliculi	tissue	10.1
Olfactory bulb	tissue	9.6
Ovary	tissue	9.5	medium
Thalamus	tissue	8.5
Entorhinal cortex	tissue	8.4
Postcentral gyrus	tissue	8.1
Cerebral cortex	tissue	7.5	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Perirhinal gyrus (27.7), Subiculum (27.1), Mammillary body (26.5), Entorhinal gyrus (25.8), Olfactory area (25.8).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, ATF2, AZU1, ESR1, JUN, NFKB, PDGFB, SP1

miRNA regulators (miRDB)

Targeting PRKCD by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 47 miRNAs:

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-1277-5P	100.00	73.95	5056
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-510-3P	99.54	70.06	2965

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.344, missense Z 3.87 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000330452 splits into 5 regions with different missense tolerance; 1 is missense-constrained (≈2% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
3:53,178,423–53,181,554	161 / 227.0	0.71	no
3:53,181,555–53,181,596	1 / 16.4	0.06	yes (p 1.4e-04)
3:53,181,597–53,184,954	109 / 155.6	0.70	no
3:53,184,955–53,185,992	85 / 76.1	1.12	no
3:53,185,993–53,192,263	251 / 423.9	0.59	no

Literature-anchored findings (GeneRIF, showing 40)

• PKC-delta selectively inhibits H2 histamine receptor-mediated activation of nonselective cation channels in differentiating granulocytic cells. (PMID:11466390)
• Physical and functional interactions between protein tyrosine phosphatase alpha, PI 3-kinase, and PKCdelta. (PMID:11676480)
• role in regulation of eosinophil NADPH oxidase activity (PMID:11748588)
• that the PKC delta pathway plays an important role int the control of human keratinocyte migration (PMID:11822877)
• activation by type I interferons and mediation of Stat1 phosphorylation on serine 727 (PMID:11839738)
• Calcium-dependent involucrin expression is inversely regulated by protein kinase C (PKC)alpha and PKCdelta. (PMID:11864971)
• Switch chimeras, containing the C1B from epsilonPKC in the context of deltaPKC (delta(epsilonC1B)) and vice versa (epsilon(deltaC1B)), were generated and tested for their translocation in response to ceramide and arachidonic acid. (PMID:11877428)
• Phosphorylation of MUC1 by PKCdelta increases binding of MUC1 and beta-catenin in vitro and in vivo. (PMID:11877440)
• results indicate that PKCdelta plays a crucial role in activating anticancer drug-induced apoptosis signaling by amplifying the ceramide-mediated mitochondrial amplification loop. (PMID:11901191)
• PMA activated the promoter activity of the 12(S)-lipoxygenase gene in cells PKCdelta but not PKCalpha, indicating that PKCdelta played the functional role in mediating the gene activation of 12(S)-lipoxygenase induced by PMA. (PMID:11914583)
• intracellular Cl(-) (Cl) regulates the activity of protein kinase C (PKC)-delta and thus the activation of Na-K-Cl cotransport (PMID:11943682)
• PLD1 is threonine-phosphorylated in human-airway epithelial cells by a PKCdelta dependent mechanism (PMID:12014986)
• PKC delta expressed in human neutrophils can phosphorylate p47phox and induce both its translocation and NADPH oxidase activation as well as the binding of p47phox to the cytosolic fragment of p22phox. (PMID:12056906)
• 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)
• REVIEW:Interaction of protein kinase C isozymes with membranes containing anionic phospholipids utilizing fluorescent phorbol esters to probe the properties of the C1 domains (PMID:12093536)
• contributes to apoptosis by regulating p73beta protein (PMID:12097319)
• role for the PKC-delta isoenzyme in regulating HLA class II-mediated apoptosis of mature dendritic cells (PMID:12147630)
• Data show that protein kinase C delta (PKC delta) is located downstream of RhoA and that active RhoA and PKCdelta are both necessary for leukotriene D(4)-induced stress-fibre formation. (PMID:12154081)
• Role of nuclear PKC delta in mediating caspase-3-upregulation in Jurkat T leukemic cells exposed to ionizing radiation (PMID:12210761)
• Activation is required for oxidant-induced disruption of both the microtubule cytoskeleton and permeability barrier of intestinal epithelia (PMID:12235228)
• PKC delta associates with IL6ST via Stat3 and enhances Stat3-gp130 interaction (PMID:12361954)
• PKC mediates VEGF-induced Akt activation in a novel signal transduction pathway through which Akt can be regulated by growth factors acting through receptor protein tyrosine kinases, and may play an essential role in VEGF-stimulated angiogenesis. (PMID:12377207)
• PKCdelta functions in the activation of SAPK through a Lyn –> PKCdelta –> MEKK1 –> MKK7 –> SAPK signaling cascade in response to DNA damage (PMID:12377781)
• inhibits p300 intrinsic histone acetyltransferase activity after phosphorylation at serine 89 (PMID:12379484)
• tyrosine phosphorylation and activity of PKCdelta were dependent on PI-3K activity in B-CLL cells, and survival signals might be mediated via PKCdelta (PMID:12393602)
• Down-regulation of hydrogen peroxide-induced activation of this enzyme in N-acetylglucosaminyltransferase III-transfected HeLaS3 cells (PMID:12427758)
• Protein kinase C delta-NF-kappaB signaling regulates VCAM1 stimulation by thrombin in endothelial cells (PMID:12493764)
• selective modulation of PKC delta may regulate TNF-R1 signaling in intestinal epithelium. (PMID:12505880)
• protein kinase c delta regulates apoptosis [review] (PMID:12510148)
• affects on JunB expression and monocyte differentiation (PMID:12522006)
• Il-2 and polysaccharide K increased expression of protein kinase C delta. (PMID:12536241)
• This protein is responsible for constitutive and DNA damage-induced phosphorylation of rad9 protein. (PMID:12628935)
• Phosphorylated PKCdelta, but not total PKCdelta, in dorsal root ganglion was decreased in diabetic rats. Decrease in phosphorylated PKCdelta is partly causes impaired neurite outgrowth in diabetes, and PKCdelta plays role in diabetic neuropathy. (PMID:12634498)
• PLS3 is a downstream effector of PKC-delta in the mitochondria. (PMID:12649167)
• data suggest that nuclear translocation and kinase activity of protein kinase C-delta are both necessary for saturated fatty acid-induced apoptosis (PMID:12663471)
• Data suggest that phosphorylation of protein kinase C delta may act as a negative feedback mechanism to limit the overall activation of the CD98 pathway. (PMID:12729789)
• Mediation of tumor growth factor beta-1 induced collagen I expression in glomerular mesangial cells. (PMID:12759229)
• PKC delta regulates airway epithelial cell expression of NF-kappa B-dependent proinflammatory genes IL-8, GM-CSF, RANTES, and ICAM-1. (PMID:12759450)
• The novel varepsilon and eta and atypical zeta, but not the conventional alpha and beta and the novel delta PKCs, may be involved in the signaling pathways involved in thrombin-induced human platelet P-selectin expression (PMID:12783114)
• PKC-delta has a role in EGF protection of tumor cells from TNF-alpha-induced apoptosis (PMID:12795334)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	prkcda	ENSDARG00000009208
danio_rerio	prkcdb	ENSDARG00000070651
mus_musculus	Prkcd	ENSMUSG00000021948
rattus_norvegicus	Prkcd	ENSRNOG00000016346

Paralogs (5): PRKCQ (ENSG00000065675), AKT2 (ENSG00000105221), AKT3 (ENSG00000117020), PDPK1 (ENSG00000140992), AKT1 (ENSG00000142208)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:97598) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 44 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased IgM level	3
increased IgA level	3
increased IgG1 level	3
enlarged spleen	2
enlarged lymph nodes	2
decreased body weight	2
premature death	2
abnormal neutrophil physiology	2
increased B cell number	2
increased B cell proliferation	2
increased susceptibility to induced colitis	2
decreased neutrophil cell number	1
abnormal cardiovascular system physiology	1
abnormal Peyer’s patch germinal center morphology	1
abnormal immunoglobulin level	1
glomerulonephritis	1
increased insulin sensitivity	1
decreased insulin secretion	1
abnormal response to CNS ischemic injury	1
increased erythrocyte cell number	1
decreased width of hypertrophic chondrocyte zone	1
arteriosclerosis	1
increased anti-nuclear antigen antibody level	1
increased anti-chromatin antibody level	1
increased acute inflammation	1

+19 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5R4K9	99.7%	Diamond
Pan troglodytes	Q4VSN5	99.5%	Diamond
Oryctolagus cuniculus	P05772	99.4%	Diamond
Macaca fascicularis	Q4R4U2	99.4%	Diamond
Bos taurus	P05126	99.3%	Diamond
Macaca mulatta	Q20CR4	98.9%	Diamond
Drosophila sechellia	B4I4Y1	98.1%	Diamond
Drosophila simulans	B4R0A5	98.1%	Diamond
Xenopus laevis	Q6NU47	97.9%	Diamond
Drosophila yakuba	B4PRE2	97.6%	Diamond
Drosophila erecta	B3NYS4	97.1%	Diamond
Chlorocebus aethiops	P10650	96.5%	Diamond
Xenopus tropicalis	Q67E00	95.4%	Diamond
Drosophila melanogaster	A8JQ65	94.1%	Diamond
Takifugu rubripes	Q4VSN2	93.8%	Diamond
Tetraodon nigroviridis	Q4VSN3	93.8%	Diamond
Caenorhabditis briggsae	A8WUG4	93.5%	Diamond
Caenorhabditis elegans	Q19266	93.5%	Diamond
Canis lupus familiaris	Q4VSN4	92.9%	Diamond
Sus scrofa	Q8WP15	92.8%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
SNORD38C	snoRNA	109617024
DCP1A	protein-coding	55802
TKT	protein-coding	7086
RFT1	protein-coding	91869
SFMBT1	protein-coding	51460
STIMATE-MUSTN1	protein-coding	100526772
MIR8064	ncRNA	102465866
STIMATE	protein-coding	375346

Protein

Protein identifiers

Protein kinase C delta type — Q05655 (reviewed: Q05655)

Alternative names: Tyrosine-protein kinase PRKCD, nPKC-delta

All UniProt accessions (8): A0A494BZX2, A0A494C125, A0A494C1T7, Q05655, A0A8V8TMH8, C9J9P1, C9JZU8, C9K0E3

UniProt curated annotations — full annotation on UniProt →

Function. Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays contrasting roles in cell death and cell survival by functioning as a pro-apoptotic protein during DNA damage-induced apoptosis, but acting as an anti-apoptotic protein during cytokine receptor-initiated cell death, is involved in tumor suppression as well as survival of several cancers, is required for oxygen radical production by NADPH oxidase and acts as positive or negative regulator in platelet functional responses. Negatively regulates B cell proliferation and also has an important function in self-antigen induced B cell tolerance induction. Upon DNA damage, activates the promoter of the death-promoting transcription factor BCLAF1/Btf to trigger BCLAF1-mediated p53/TP53 gene transcription and apoptosis. In response to oxidative stress, interact with and activate CHUK/IKKA in the nucleus, causing the phosphorylation of p53/TP53. In the case of ER stress or DNA damage-induced apoptosis, can form a complex with the tyrosine-protein kinase ABL1 which trigger apoptosis independently of p53/TP53. In cytosol can trigger apoptosis by activating MAPK11 or MAPK14, inhibiting AKT1 and decreasing the level of X-linked inhibitor of apoptosis protein (XIAP), whereas in nucleus induces apoptosis via the activation of MAPK8 or MAPK9. Upon ionizing radiation treatment, is required for the activation of the apoptosis regulators BAX and BAK, which trigger the mitochondrial cell death pathway. Can phosphorylate MCL1 and target it for degradation which is sufficient to trigger for BAX activation and apoptosis. Is required for the control of cell cycle progression both at G1/S and G2/M phases. Mediates phorbol 12-myristate 13-acetate (PMA)-induced inhibition of cell cycle progression at G1/S phase by up-regulating the CDK inhibitor CDKN1A/p21 and inhibiting the cyclin CCNA2 promoter activity. In response to UV irradiation can phosphorylate CDK1, which is important for the G2/M DNA damage checkpoint activation. Can protect glioma cells from the apoptosis induced by TNFSF10/TRAIL, probably by inducing increased phosphorylation and subsequent activation of AKT1. Is highly expressed in a number of cancer cells and promotes cell survival and resistance against chemotherapeutic drugs by inducing cyclin D1 (CCND1) and hyperphosphorylation of RB1, and via several pro-survival pathways, including NF-kappa-B, AKT1 and MAPK1/3 (ERK1/2). Involved in antifungal immunity by mediating phosphorylation and activation of CARD9 downstream of C-type lectin receptors activation, promoting interaction between CARD9 and BCL10, followed by activation of NF-kappa-B and MAP kinase p38 pathways. Can also act as tumor suppressor upon mitogenic stimulation with PMA or TPA. In N-formyl-methionyl-leucyl-phenylalanine (fMLP)-treated cells, is required for NCF1 (p47-phox) phosphorylation and activation of NADPH oxidase activity, and regulates TNF-elicited superoxide anion production in neutrophils, by direct phosphorylation and activation of NCF1 or indirectly through MAPK1/3 (ERK1/2) signaling pathways. May also play a role in the regulation of NADPH oxidase activity in eosinophil after stimulation with IL5, leukotriene B4 or PMA. In collagen-induced platelet aggregation, acts a negative regulator of filopodia formation and actin polymerization by interacting with and negatively regulating VASP phosphorylation. Downstream of PAR1, PAR4 and CD36/GP4 receptors, regulates differentially platelet dense granule secretion; acts as a positive regulator in PAR-mediated granule secretion, whereas it negatively regulates CD36/GP4-mediated granule release. Phosphorylates MUC1 in the C-terminal and regulates the interaction between MUC1 and beta-catenin. The catalytic subunit phosphorylates 14-3-3 proteins (YWHAB, YWHAZ and YWHAH) in a sphingosine-dependent fashion. Phosphorylates ELAVL1 in response to angiotensin-2 treatment. Phosphorylates mitochondrial phospholipid scramblase 3 (PLSCR3), resulting in increased cardiolipin expression on the mitochondrial outer membrane which facilitates apoptosis. Phosphorylates SMPD1 which induces SMPD1 secretion. Acts as a negative regulator of smoothened signaling by mediating phosphorylation of GLI1, preventing its localization to the nucleus.

Subunit / interactions. Interacts with PDPK1 (via N-terminal region). Interacts with RAD9A. Interacts with CDCP1. Interacts with MUC1. Interacts with VASP. Interacts with CAVIN3. Interacts with PRKD2 (via N-terminus and zing-finger domain 1 and 2) in response to oxidative stress; the interaction is independent of PRKD2 tyrosine phosphorylation. Interacts with PLSC3; interaction is enhanced by UV irradiation. Interacts with PRKCH upstream open reading frame 2; the interaction leads to inhibition of kinase activity.

Subcellular location. Cytoplasm. Perinuclear region. Nucleus. Cell membrane. Mitochondrion. Endomembrane system.

Post-translational modifications. Autophosphorylated and/or phosphorylated at Thr-507, within the activation loop; phosphorylation at Thr-507 is not a prerequisite for enzymatic activity. Autophosphorylated at Ser-299, Ser-302 and Ser-304. Upon TNFSF10/TRAIL treatment, phosphorylated at Tyr-155; phosphorylation is required for its translocation to the endoplasmic reticulum and cleavage by caspase-3. Phosphorylated at Tyr-313, Tyr-334 and Tyr-567; phosphorylation of Tyr-313 and Tyr-567 following thrombin or zymosan stimulation potentiates its kinase activity. Phosphorylated by protein kinase PDPK1; phosphorylation is inhibited by the apoptotic C-terminal cleavage product of PKN2. Phosphorylated at Tyr-313 through a SYK and SRC mechanism downstream of C-type lectin receptors activation, promoting its activation. Proteolytically cleaved into a catalytic subunit and a regulatory subunit by caspase-3 during apoptosis which results in kinase activation.

Disease relevance. Autoimmune lymphoproliferative syndrome 3 (ALPS3) [MIM:615559] A primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B-cells is usually in the normal range, but can be low. CVID9 patients have B-cell deficiency and severe autoimmunity. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are calcium-insensitive, but activated by diacylglycerol (DAG) and phosphatidylserine. Three specific sites; Thr-507 (activation loop of the kinase domain), Ser-645 (turn motif) and Ser-664 (hydrophobic region), need to be phosphorylated for its full activation. Activated by caspase-3 (CASP3) cleavage during apoptosis. After cleavage, the pseudosubstrate motif in the regulatory subunit is released from the substrate recognition site of the catalytic subunit, which enables PRKCD to become constitutively activated. The catalytic subunit which displays properties of a sphingosine-dependent protein kinase is activated by D-erythro-sphingosine (Sph) or N,N-dimethyl-D-erythrosphingosine (DMS) or N,N,N-trimethyl-D-erythrosphingosine (TMS), but not by ceramide or Sph-1-P and is strongly inhibited by phosphatidylserine. Inhibited by PRKCH upstream open reading frame 2.

Domain organisation. The C1 domain, containing the phorbol ester/DAG-type region 1 (C1A) and 2 (C1B), is the diacylglycerol sensor. The C2 domain is a non-calcium binding domain. It binds proteins containing phosphotyrosine in a sequence-specific manner.

Miscellaneous. Antiapoptotic isoform, resistant to caspase-3 cleavage.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q05655-1	1	yes
Q05655-2	2, PKCdeltaVIII

RefSeq proteins (7): NP_001303256, NP_001341605, NP_001341607, NP_001341608, NP_001341609, NP_006245, NP_997704 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR000719	Prot_kinase_dom	Domain
IPR000961	AGC-kinase_C	Domain
IPR002219	PKC_DAG/PE	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR014376	Prot_kin_PKC_delta	Family
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR017892	Pkinase_C	Domain
IPR020454	DAG/PE-bd	Domain
IPR027436	PKC_delta	Family
IPR034667	nPKC_delta	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR046349	C1-like_sf	Homologous_superfamily

Pfam: PF00069, PF00130, PF00433, PF21494

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)

• L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) (RHEA:10596)
• 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 (69 total): modified residue 23, strand 14, sequence variant 6, site 5, chain 3, domain 3, helix 3, binding site 2, mutagenesis site 2, sequence conflict 2, turn 2, zinc finger region 2, splice variant 1, active site 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
1YRK	The C2 Domain of PKC is a new Phospho-Tyrosine Binding Domain	X-RAY DIFFRACTION	1.7
2YUU	Solution structure of the first Phorbol esters/diacylglycerol binding domain of human …	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q05655-F1	81.29	0.46

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Kinases, AGC Ser/Thr protein kinases, Predicted intracellular proteins, Cancer-related genes, Mutational cancer driver genes, Disease related genes, FDA approved drug targets, Small molecule drugs, Human disease related genes, Primary immunodeficiency

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; endoplasmic reticulum; golgi apparatus; vesicles

Antibody reliability (HPA): IH enhanced · IF enhanced

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 (6)

Position	Role
48	interaction with phosphotyrosine-containing peptide
62	interaction with phosphotyrosine-containing peptide
67	interaction with phosphotyrosine-containing peptide
123	interaction with phosphotyrosine-containing peptide
329–330	cleavage; by caspase-3
473	proton acceptor

Ligand- & substrate-binding residues (2)

Position	Role
378	ATP
355–363	ATP

Post-translational modifications (23)

Type	Positions
Phosphothreonine	43, 50, 141, 218, 451, 507
Phosphotyrosine	64, 155, 313, 334, 374, 567
Phosphoserine	130, 299, 302, 304, 307, 503, 506, 645, 654, 658, 664

Mutagenesis-validated functional residues (2)

Position	Phenotype
299	loss of phosphorylation.
507	no effect on kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

12 curated (TAS) of 48; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

48 pathways:

ID	Pathway	Evidence
R-HSA-111465	Apoptotic cleavage of cellular proteins	curated
R-HSA-5607764	CLEC7A (Dectin-1) signaling	curated
R-HSA-111933	Calmodulin induced events	curated
R-HSA-1489509	DAG and IP3 signaling	curated
R-HSA-114508	Effects of PIP2 hydrolysis	curated
R-HSA-450520	HuR (ELAVL1) binds and stabilizes mRNA	curated
R-HSA-877300	Interferon gamma signaling	curated
R-HSA-6798695	Neutrophil degranulation	curated
R-HSA-5668599	RHO GTPases Activate NADPH Oxidases	curated
R-HSA-2029485	Role of phospholipids in phagocytosis	curated
R-HSA-1250196	SHC1 events in ERBB2 signaling	curated
R-HSA-5218921	VEGFR2 mediated cell proliferation	curated
R-HSA-109581	Apoptosis	—
R-HSA-75153	Apoptotic execution phase	—
R-HSA-5621481	C-type lectin receptors (CLRs)	—
R-HSA-111996	Ca-dependent events	—
R-HSA-111997	CaM pathway	—
R-HSA-9711123	Cellular response to chemical stress	—
R-HSA-8953897	Cellular responses to stimuli	—
R-HSA-2262752	Cellular responses to stress	—
R-HSA-1280215	Cytokine Signaling in Immune system	—
R-HSA-2029480	Fcgamma receptor (FCGR) dependent phagocytosis	—
R-HSA-418594	G alpha (i) signalling events	—
R-HSA-416476	G alpha (q) signalling events	—
R-HSA-418597	G alpha (z) signalling events	electronic
R-HSA-112040	G-protein mediated events	—
R-HSA-388396	GPCR downstream signalling	—
R-HSA-109582	Hemostasis	—
R-HSA-168256	Immune System	—
R-HSA-168249	Innate Immune System	—
R-HSA-913531	Interferon Signaling	—
R-HSA-9006925	Intracellular signaling by second messengers	—
R-HSA-9755511	KEAP1-NFE2L2 pathway	electronic
R-HSA-8953854	Metabolism of RNA	—
R-HSA-111885	Opioid Signalling	—
R-HSA-112043	PLC beta mediated events	—
R-HSA-76002	Platelet activation, signaling and aggregation	—
R-HSA-5357801	Programmed Cell Death	—
R-HSA-195258	RHO GTPase Effectors	—
R-HSA-450531	Regulation of mRNA stability by proteins that bind AU-rich elements	—
R-HSA-162582	Signal Transduction	—
R-HSA-1227986	Signaling by ERBB2	—
R-HSA-372790	Signaling by GPCR	—
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases	—
R-HSA-194315	Signaling by Rho GTPases	—
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3	—
R-HSA-194138	Signaling by VEGF	—
R-HSA-4420097	VEGFA-VEGFR2 Pathway	—

MSigDB gene sets: 805 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_CERAMIDE_CATABOLIC_PROCESS, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_CELL_CHEMOTAXIS, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_UV, GOBP_INFLAMMATORY_RESPONSE, GOBP_CELLULAR_RESPONSE_TO_LIPID

GO Biological Process (42): protein phosphorylation (GO:0006468), apoptotic process (GO:0006915), DNA damage response (GO:0006974), signal transduction (GO:0007165), intrinsic apoptotic signaling pathway in response to oxidative stress (GO:0008631), peptidyl-serine phosphorylation (GO:0018105), peptidyl-threonine phosphorylation (GO:0018107), termination of signal transduction (GO:0023021), negative regulation of actin filament polymerization (GO:0030837), positive regulation of superoxide anion generation (GO:0032930), regulation of actin cytoskeleton organization (GO:0032956), negative regulation of glial cell apoptotic process (GO:0034351), cellular response to UV (GO:0034644), intracellular signal transduction (GO:0035556), Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096), neutrophil activation (GO:0042119), positive regulation of protein import into nucleus (GO:0042307), defense response to bacterium (GO:0042742), negative regulation of MAPK cascade (GO:0043409), regulation of mRNA stability (GO:0043488), positive regulation of DNA repair (GO:0045739), negative regulation of insulin receptor signaling pathway (GO:0046627), negative regulation of inflammatory response (GO:0050728), protein stabilization (GO:0050821), negative regulation of filopodium assembly (GO:0051490), cell chemotaxis (GO:0060326), cellular response to hydrogen peroxide (GO:0070301), protein kinase C signaling (GO:0070528), cellular response to fatty acid (GO:0071398), cellular response to hydroperoxide (GO:0071447), negative regulation of platelet aggregation (GO:0090331), cellular senescence (GO:0090398), phospholipase C/protein kinase C signal transduction (GO:0141212), positive regulation of phospholipid scramblase activity (GO:1900163), cellular response to angiotensin (GO:1904385), regulation of ceramide biosynthetic process (GO:2000303), positive regulation of ceramide biosynthetic process (GO:2000304), positive regulation of glucosylceramide catabolic process (GO:2000753), positive regulation of sphingomyelin catabolic process (GO:2000755), negative regulation of apoptotic process (GO:0043066), negative regulation of smoothened signaling pathway (GO:0045879), positive regulation of DNA metabolic process (GO:0051054)

GO Molecular Function (20): protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), diacylglycerol-dependent serine/threonine kinase activity (GO:0004697), calcium,diacylglycerol-dependent serine/threonine kinase activity (GO:0004698), diacylglycerol-dependent, calcium-independent serine/threonine kinase activity (GO:0004699), non-membrane spanning protein tyrosine kinase activity (GO:0004715), ATP binding (GO:0005524), enzyme activator activity (GO:0008047), zinc ion binding (GO:0008270), enzyme binding (GO:0019899), protein kinase binding (GO:0019901), protein tyrosine kinase activator activity (GO:0030296), insulin receptor substrate binding (GO:0043560), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein tyrosine kinase activity (GO:0004713), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (17): extracellular region (GO:0005576), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), nuclear matrix (GO:0016363), azurophil granule lumen (GO:0035578), endolysosome (GO:0036019), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), endomembrane system (GO:0012505), membrane (GO:0016020)

Reactome top-level categories

21 top-level categories:

Category	Pathways
Apoptotic execution phase	1
CaM pathway	1
G alpha (q) signalling events	1
Platelet activation, signaling and aggregation	1
Signaling by ERBB2	1
Intracellular signaling by second messengers	1
Fcgamma receptor (FCGR) dependent phagocytosis	1
GPCR downstream signalling	1
Regulation of mRNA stability by proteins that bind AU-rich elements	1
VEGFA-VEGFR2 Pathway	1
C-type lectin receptors (CLRs)	1
RHO GTPase Effectors	1
Innate Immune System	1
Interferon Signaling	1
Cellular response to chemical stress	1
Programmed Cell Death	1
G alpha (i) signalling events	1
PLC beta mediated events	1
Ca-dependent events	1
DAG and IP3 signaling	1
Opioid Signalling	1

GO top-level categories

showing 60 of 87 GO namespaces:

Category	Terms
cellular anatomical structure	8
cytoplasm	5
intracellular membrane-bounded organelle	4
protein kinase activity	3
protein phosphorylation	2
intracellular anatomical structure	2
diacylglycerol-dependent serine/threonine kinase activity	2
protein tyrosine kinase activity	2
catalytic activity	2
protein binding	2
nuclear lumen	2
endomembrane system	2
phosphorylation	1
protein modification process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cellular response to stress	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
intrinsic apoptotic signaling pathway	1
negative regulation of signal transduction	1
actin filament polymerization	1
regulation of actin filament polymerization	1
negative regulation of protein polymerization	1
negative regulation of cytoskeleton organization	1
negative regulation of supramolecular fiber organization	1
regulation of superoxide anion generation	1
superoxide anion generation	1
positive regulation of reactive oxygen species metabolic process	1
actin cytoskeleton organization	1
regulation of actin filament-based process	1
regulation of cytoskeleton organization	1
glial cell apoptotic process	1
regulation of glial cell apoptotic process	1
negative regulation of apoptotic process	1
response to UV	1
cellular response to light stimulus	1
signal transduction	1
Fc receptor mediated stimulatory signaling pathway	1
phagocytosis	1
Fc-gamma receptor signaling pathway	1
granulocyte activation	1
protein import into nucleus	1
regulation of protein import into nucleus	1
positive regulation of nucleocytoplasmic transport	1
positive regulation of intracellular protein transport	1
positive regulation of protein localization to nucleus	1
defense response	1
response to bacterium	1
MAPK cascade	1
regulation of MAPK cascade	1
negative regulation of intracellular signal transduction	1
regulation of RNA stability	1
regulation of mRNA catabolic process	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 43 of 79 annotations. The rest are phylogenetic / computational / electronic (IEA).

43 experimentally-supported GO terms:

GO term	NS	Evidence
DNA damage response	BP	mutant phenotype
apoptotic process	BP	direct assay
cell chemotaxis	BP	mutant phenotype
cellular response to UV	BP	direct assay
cellular response to angiotensin	BP	direct assay
cellular response to hydrogen peroxide	BP	direct assay
cellular response to hydroperoxide	BP	direct assay
cellular senescence	BP	mutant phenotype
negative regulation of MAPK cascade	BP	mutant phenotype
negative regulation of glial cell apoptotic process	BP	mutant phenotype
negative regulation of inflammatory response	BP	mutant phenotype
neutrophil activation	BP	direct assay
peptidyl-serine phosphorylation	BP	direct assay
peptidyl-threonine phosphorylation	BP	direct assay
phospholipase C/protein kinase C signal transduction	BP	direct assay
positive regulation of DNA repair	BP	direct assay
positive regulation of ceramide biosynthetic process	BP	mutant phenotype
positive regulation of glucosylceramide catabolic process	BP	mutant phenotype
positive regulation of phospholipid scramblase activity	BP	mutant phenotype
positive regulation of protein import into nucleus	BP	mutant phenotype
positive regulation of sphingomyelin catabolic process	BP	mutant phenotype
positive regulation of superoxide anion generation	BP	mutant phenotype
protein phosphorylation	BP	direct assay
regulation of actin cytoskeleton organization	BP	mutant phenotype
regulation of ceramide biosynthetic process	BP	direct assay
termination of signal transduction	BP	mutant phenotype
Golgi apparatus	CC	direct assay
cytoplasm	CC	direct assay
cytosol	CC	direct assay
endolysosome	CC	direct assay
endoplasmic reticulum	CC	direct assay
extracellular exosome	CC	high-throughput assay
nucleus	CC	direct assay
plasma membrane	CC	direct assay
calcium,diacylglycerol-dependent serine/threonine kinase activity	MF	experiment
diacylglycerol-dependent, calcium-independent serine/threonine kinase activity	MF	experiment
enzyme activator activity	MF	direct assay
enzyme binding	MF	physical interaction
protein kinase activity	MF	direct assay
protein kinase binding	MF	physical interaction
protein serine kinase activity	MF	direct assay
protein serine/threonine kinase activity	MF	direct assay
protein tyrosine kinase activator activity	MF	direct assay

Protein interactions and networks

STRING

showing 16 of 2,304 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRKCD	CEL	P19835	694
PRKCD	PTPN6	P29350	604
PRKCD	SST	P01166	594
PRKCD	NFKB1	P19838	580
PRKCD	RBCK1	Q9BYM8	554
PRKCD	CASP3	P42574	538
PRKCD	PDGFB	P01127	533
PRKCD	MARCKS	P29966	515
PRKCD	FCER1G	P30273	496
PRKCD	GRHL3	Q8TE85	491
PRKCD	GAB2	Q9UQC2	470
PRKCD	TNFSF13B	Q9Y275	465
PRKCD	PRKDC	P78527	455
PRKCD	HSPB1	P04792	452
PRKCD	SSH1	Q8WYL5	445
PRKCD	YWHAB	P31946	445

IntAct

Human interaction partners of PRKCD in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

27 partners by confidence:

Partner	Interaction type	MIscore	Records
FYN	physical association	0.740	5
IL32	colocalization	0.730	8
TOP2A	physical association	0.680	10
CDCP1	colocalization	0.670	7
CARD11	physical association	0.620	7
GAP43	phosphorylation reaction	0.600	4
TP53	phosphorylation reaction	0.600	4
APP	physical association	0.560	3
VPS29	physical association	0.560	3
NCF2	phosphorylation reaction	0.540	3
PRKCB	association	0.530	2
TRO	physical association	0.460	2
NCF1	phosphorylation reaction	0.440	1
PTPN22	direct interaction	0.440	1
DIABLO	physical association	0.400	4
SRC	physical association	0.400	2
TP63	physical association	0.400	2
ABL1	physical association	0.400	1
C1QBP	physical association	0.400	1
MALT1	physical association	0.400	1
POT1	physical association	0.400	1
SPI1	physical association	0.400	1
TP53INP1	physical association	0.400	1
TRAF6	physical association	0.400	1
DHX16	association	0.350	1
TRAPPC13	association	0.350	1
GRM5	proximity	0.270	1

BioGRID (276 interactions; top human partners by supporting records): STAT1 (Affinity Capture-Western; 11 records), ELAVL1 (Affinity Capture-Western; 6 records), SP1 (Affinity Capture-Western; 6 records), ATG7 (Affinity Capture-Western; 4 records), IKBKB (Reconstituted Complex; 4 records), PTPN6 (Affinity Capture-Western; 4 records), SHC1 (Affinity Capture-MS; 4 records), TP73 (Affinity Capture-Western; 4 records), VHL (Affinity Capture-Western; 4 records), CEACAM6 (Proximity Label-MS; 3 records), CHUK (Reconstituted Complex; 3 records), MUC1 (Affinity Capture-Western; 3 records), RASGRP3 (Biochemical Activity; 3 records), SPRY2 (Affinity Capture-Western; 3 records), SQSTM1 (Biochemical Activity; 3 records)

SIGNOR signaling

showing 43 of 200 signaling interactions:

A	Effect	B	Mechanism
PTPN1	down-regulates	PRKCD	dephosphorylation
PRKCD	“up-regulates activity”	ITGB2	phosphorylation
PRKCD	up-regulates	MUC1	phosphorylation
PRKCD	down-regulates	GSK3A	phosphorylation
PRKCD	up-regulates	PEBP1	phosphorylation
PRKCD	up-regulates	PRKD1	phosphorylation
PRKCD	down-regulates	IRS1	phosphorylation
PRKCD	“down-regulates activity”	IRS1	phosphorylation
PRKCD	down-regulates	DAB2	phosphorylation
PRKCD	up-regulates	PRKCD	phosphorylation
PRKCD	down-regulates	LIMK2	phosphorylation
PRKCD	up-regulates	RPS3	phosphorylation
PRKCD	down-regulates	YWHAB	phosphorylation
PRKCD	up-regulates	PLSCR3	phosphorylation
PRKCD	up-regulates	TP53	phosphorylation
PRKCD	up-regulates	STAT3	phosphorylation
PRKCD	up-regulates	SHC1	phosphorylation
PRKCD	unknown	SHC1	phosphorylation
PRKCD	up-regulates	MYBPC3	phosphorylation
PRKCD	down-regulates	C5AR1	phosphorylation
PRKCD	up-regulates	MAPK8	phosphorylation
PRKCD	up-regulates	DNM1L	phosphorylation
PRKCD	up-regulates	SMPD1	phosphorylation
PRKCD	up-regulates	STAT1	phosphorylation
PRKCD	down-regulates	PTPN22	phosphorylation
PRKCD	up-regulates	DBI	phosphorylation
PRKCD	up-regulates	DAP3	phosphorylation
PRKCD	up-regulates	ELAVL1	phosphorylation
PRKCD	down-regulates	CHN2	phosphorylation
PRKCD	up-regulates	G6PD	phosphorylation
PRKCD	up-regulates	PLD2	phosphorylation
PRKCD	up-regulates	PA2G4	phosphorylation
PRKCD	down-regulates	FLI1	phosphorylation
PRKCD	“up-regulates activity”	TNNI3	phosphorylation
PRKCD	down-regulates	TNNI3	phosphorylation
PRKCD	up-regulates	ITGB2	phosphorylation
PRKCD	down-regulates	TRIM28	phosphorylation
PRKCD	down-regulates	NR2F6	phosphorylation
PRKCD	“up-regulates activity”	H3C1	phosphorylation
PRKCD	unknown	PRKCD	phosphorylation
“bisindolylmaleimide i”	down-regulates	PRKCD	“chemical inhibition”
PRKCD	up-regulates	ENOX2	phosphorylation
PRKCD	up-regulates	BAG3	phosphorylation

Protein complexes (CORUM) (11)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

11 complexes by size:

Complex	Subunits	Members
★ IL32-PRKCD-STAT3 complex	3	IL32, PRKCD, STAT3
★ IL6ST-PRKCD-STAT3 complex	3	PRKCD, STAT3, IL6ST
★ CDCP1-PRKCD-SRC complex	3	SRC, CDCP1, PRKCD
★ BLVRA-MAPK1-PRKCD complex	3	BLVRA, MAPK1, PRKCD
★ MAP2K5-PRKCD-SQSTM1 complex	3	MAP2K5, PRKCD, SQSTM1
★ PDPK1-PRG2-PRKCD complex	3	PDPK1, PRG2, PRKCD
★ MUC1-PRKCD complex	2	MUC1, PRKCD
★ PLSCR3-PRKCD complex	2	PLSCR3, PRKCD
★ PRKCD-RAD9A complex	2	PRKCD, RAD9A
★ PRKCD-VASP complex	2	PRKCD, VASP
★ PRKCD-PRKD2 complex	2	PRKCD, PRKD2

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 27 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
VEGFA-VEGFR2 Pathway	5	27.9×	3e-04
Signaling by Rho GTPases	6	8.2×	3e-03
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	6	8.0×	3e-03
Hemostasis	5	7.2×	7e-03
Innate Immune System	6	6.1×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
T cell receptor signaling pathway	5	29.2×	1e-04
regulation of apoptotic process	5	16.0×	9e-04
positive regulation of canonical NF-kappaB signal transduction	5	14.0×	1e-03
negative regulation of gene expression	5	13.3×	2e-03
positive regulation of apoptotic process	6	13.1×	6e-04
DNA damage response	6	12.3×	6e-04
positive regulation of gene expression	5	7.5×	9e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — NHL.

intOGen’s role is a computational inference from cohort mutation patterns and may diverge from the gene’s curated/literature role; read it alongside the evidence above.

Genetic variants

Variant evidence for PRKCD: 609 ClinVar records (20 pathogenic / likely pathogenic); 11 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	13
Likely pathogenic	7
Uncertain significance	215
Likely benign	271
Benign	47

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 20 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
89076	NM_006254.4(PRKCD):c.1352+1G>A	Pathogenic	criteria provided, single submitter	3
958249	NM_006254.4(PRKCD):c.571C>T (p.Gln191Ter)	Pathogenic	criteria provided, single submitter	2
1072331	NM_006254.4(PRKCD):c.1301del (p.Asp434fs)	Pathogenic	criteria provided, single submitter	1
1454573	NM_006254.4(PRKCD):c.285C>A (p.Cys95Ter)	Pathogenic	criteria provided, single submitter	1
1458167	NM_006254.4(PRKCD):c.1300dup (p.Asp434fs)	Pathogenic	criteria provided, single submitter	1
2128407	NM_006254.4(PRKCD):c.1182del (p.Met395fs)	Pathogenic	criteria provided, single submitter	1
3650412	NM_006254.4(PRKCD):c.1542T>G (p.Tyr514Ter)	Pathogenic	criteria provided, single submitter	1
4713023	NM_006254.4(PRKCD):c.1318C>T (p.Gln440Ter)	Pathogenic	criteria provided, single submitter	1
541623	NM_006254.4(PRKCD):c.788-2A>G	Likely pathogenic	criteria provided, single submitter	1
2028257	NM_006254.4(PRKCD):c.1743+2T>A	Likely pathogenic	criteria provided, single submitter	1
2068571	NM_006254.4(PRKCD):c.788-1G>T	Likely pathogenic	criteria provided, single submitter	1
2909516	NM_006254.4(PRKCD):c.571+1G>A	Likely pathogenic	criteria provided, single submitter	1
3391052	NM_006254.4(PRKCD):c.1073G>A (p.Gly358Asp)	Likely pathogenic	criteria provided, single submitter	1
3652522	NM_006254.4(PRKCD):c.657+1G>A	Likely pathogenic	criteria provided, single submitter	1
4845698	NM_006254.4(PRKCD):c.769C>T (p.Gln257Ter)	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore PRKCD’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 22 predictions of 1,501):

Position(s)	Effect	Δscore	Sites
3:53161429	donor_loss	1.0000	2
3:53178538–53178539	donor_loss	1.0000	4
3:53179572	acceptor_gain	1.0000
3:53179576	acceptor_loss	1.0000
3:53179766	donor_gain	1.0000
3:53179777–53179778	donor_loss	1.0000	5
3:53181187–53181188	acceptor_gain	1.0000	2
3:53181194–53181195	acceptor_gain	1.0000	2
3:53181442	acceptor_loss	1.0000	2
3:53183101–53183102	acceptor_gain	1.0000	2

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	8.14e-06
Lung Adenocarcinoma (TCGA)	favorable	0.000127

Disease associations

OMIM: gene MIM:176977 | disease phenotypes: MIM:615559

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD	Strong	Autosomal recessive	2

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
systemic lupus erythematosus	Definitive	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (2 panels, 2 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

2 panels:

Panel	Rating
COVID-19 research	green
Primary immunodeficiency or monogenic inflammatory bowel disease	green

Mondo (1): autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD (MONDO:8000024)

Orphanet (2): Autoimmune lymphoproliferative syndrome (Orphanet:3261), EBV-induced lymphoproliferative disease due to PRKCD deficiency (Orphanet:664711)

HPO phenotypes

42 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000100	Nephrotic syndrome
HP:0000403	Recurrent otitis media
HP:0001369	Arthritis
HP:0001433	Hepatosplenomegaly
HP:0001596	Alopecia
HP:0001744	Splenomegaly
HP:0001890	Autoimmune hemolytic anemia
HP:0001954	Recurrent fever
HP:0001973	Autoimmune thrombocytopenia
HP:0002240	Hepatomegaly
HP:0002716	Lymphadenopathy
HP:0002719	Recurrent infections
HP:0002729	Follicular hyperplasia
HP:0002783	Recurrent lower respiratory tract infections
HP:0002788	Recurrent upper respiratory tract infections
HP:0002960	Autoimmunity
HP:0003493	Antinuclear antibody positivity
HP:0003565	Elevated erythrocyte sedimentation rate
HP:0003774	Stage 5 chronic kidney disease
HP:0005404	Increased total B cell count
HP:0005421	Decreased circulating complement C3 concentration
HP:0005523	Lymphoproliferative disorder
HP:0008940	Generalized lymphadenopathy
HP:0010702	Increased circulating immunoglobulin concentration
HP:0011108	Recurrent sinusitis
HP:0011227	Elevated circulating C-reactive protein concentration
HP:0012177	Abnormal natural killer cell physiology
HP:0012578	Membranous nephropathy
HP:0020072	Persistent EBV viremia
HP:0020136	Anticardiolipin IgG antibody positivity
HP:0025475	Erythematous macule
HP:0030374	Decreased memory B cell proportion
HP:0030388	Decreased class-switched memory B cell proportion
HP:0031041	Obstruction of the superior vena cava
HP:0031956	Elevated circulating aspartate aminotransferase concentration
HP:0031964	Elevated circulating alanine aminotransferase concentration
HP:0033207	Increased CD21low B cell proportion
HP:0045042	Decreased circulating complement C4 concentration
HP:0100721	Mediastinal lymphadenopathy
HP:0410293	Absent circulating isohemagglutinin

GWAS associations

11 associations:

Study	Trait	p-value
GCST90020024_370	A body shape index	5e-10
GCST90020029_793	Waist circumference adjusted for body mass index	6e-10
GCST001728_2	Ulcerative colitis	1e-8
GCST90020025_1743	Waist-to-hip ratio adjusted for BMI	2e-8
GCST90020025_1744	Waist-to-hip ratio adjusted for BMI	2e-8
GCST90020027_777	Waist-hip index	2e-8
GCST90020027_828	Waist-hip index	2e-8
GCST90020029_792	Waist circumference adjusted for body mass index	4e-8
GCST006396_5	Disrupted circadian rhythm (low relative amplitude of rest-activity cycles)	4e-7
GCST008161_115	Waist circumference adjusted for body mass index	8e-7
GCST001241_15	Bipolar disorder	2e-6

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2093867 (PROTEIN FAMILY), CHEMBL2096620 (PROTEIN FAMILY), CHEMBL2996 (SINGLE PROTEIN)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the PRKCD protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

1 curated-mechanism drugs:

Drug	Modality	Max phase
DELCASERTIB	Unknown	2

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 409,937 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

49 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL3301610	ABEMACICLIB	4	7,497
CHEMBL2105759	BARICITINIB	4	7,117
CHEMBL288441	BOSUTINIB	4	12,869
CHEMBL2325741	CAPIVASERTIB	4	2,281
CHEMBL1863513	INGENOL MEBUTATE	4	1,527
CHEMBL608533	MIDOSTAURIN	4	7,641
CHEMBL83	TAMOXIFEN	4	173,287
CHEMBL221959	TOFACITINIB	4	10,947
CHEMBL2103743	TOFACITINIB CITRATE	4	1,763
CHEMBL428690	ALVOCIDIB	3	28,145
CHEMBL2105728	CRENOLANIB	3	2,278
CHEMBL140	CURCUMIN	3	95,185
CHEMBL522892	DOVITINIB	3	5,162
CHEMBL300138	ENZASTAURIN	3	3,401
CHEMBL38380	FASUDIL	3	12,137
CHEMBL603469	LESTAURTINIB	3
CHEMBL3426621	RIPASUDIL	3	913
CHEMBL91829	RUBOXISTAURIN	3	78
CHEMBL265502	SURAMIN	3	37,133
CHEMBL3545396	BMS-690514	2	576
CHEMBL575448	BMS-754807	2
CHEMBL449158	BRYOSTATIN 1	2
CHEMBL1967878	CENISERTIB	2
CHEMBL3982723	DAROVASERTIB	2
CHEMBL3039513	DECERNOTINIB	2
CHEMBL103667	DORAMAPIMOD	2
CHEMBL28509	EDELFOSINE	2
CHEMBL1980297	ILORASERTIB	2
CHEMBL1980715	LAUROGUADINE	2
CHEMBL362558	LY-2090314	2
CHEMBL607707	PELITINIB	2
CHEMBL279115	PHORBOL MYRISTATE ACETATE	2
CHEMBL475251	R-406	2
CHEMBL1667969	SAR-407899 FREE BASE	2
CHEMBL2386889	SCH-900776	2
CHEMBL565612	SOTRASTAURIN	2
CHEMBL574737	UCN-01	2
CHEMBL3137336	UPROSERTIB	2
CHEMBL1944698	ZOTIRACICLIB	2
CHEMBL2140408	AMG-900	1
CHEMBL3544960	AT-13148	1
CHEMBL2041933	AZD-7762	1
CHEMBL1908394	GSK-461364	1
CHEMBL494089	GSK-690693	1
CHEMBL1084546	PF-00562271	1
CHEMBL3128043	PF-03758309	1
CHEMBL1980391	RG-1530	1
CHEMBL482767	SNS-314	1
CHEMBL571948	Y-39983	1

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Delta subfamily

Most potent curated ligand interactions (12 total), top 12:

Ligand	Action	Affinity	Parameter
ingenol mebutate	Activation	9.42	pKi
bryostatin 1	Activation	9.36	pKi
10-Me-Aplog-1	Activation	9.34	pKi
sotrastaurin	Inhibition	8.89	pIC50
Gö 6983	Inhibition	8.0	pIC50
balanol	Inhibition	7.8	pIC50
compound 23 [PMID: 35816678]	Inhibition	7.15	pIC50
ruboxistaurin	Inhibition	6.6	pIC50
7-hydroxystaurosporine	Inhibition	6.23	pIC50
enzastaurin	Inhibition	6.0	pIC50
rottlerin	Inhibition	5.52	pIC50
CC-90005	Inhibition	5.35	pIC50

Binding affinities (BindingDB)

910 measured of 1150 human assays (1178 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL4442196	IC50	0.09 nM
[(1S,4S,5S,6R,9S,10S,12R)-5,6-dihydroxy-7-(hydroxymethyl)-3,11,11-trimethyl-15-oxo-4-tetracyclo[7.5.1.01,5.010,12]pentadeca-2,7-dienyl] 1-methylcyclohexane-1-carboxylate	EC50	0.1 nM	US-9409931: 3-O-acyl-ingenol analogues
CHEMBL5172923	KI	0.11 nM
CHEMBL4528495	IC50	0.15 nM
CHEMBL4538431	IC50	0.17 nM
CHEMBL4443190	IC50	0.18 nM
CHEMBL3741746	EC50	0.19 nM
(1R)-N-(4-chloroisoquinolin-6-yl)-2-[4-(pyridin-2-ylsulfamoyl)phenyl]cyclopropane-1-carboxamide	IC50	0.2 nM	US-11427563: Aryl cyclopropyl-amino-isoquinolinyl amide compounds
CHEMBL4435580	IC50	0.22 nM
CHEMBL2148106	KI	0.26 nM
Butyric acid (1aS,1bS,4aS,7aS,8R,9S,9aR)-9-butyryloxy-4a,7b-dihydroxy-3-((R)-hydroxymethyl)-1,1,6,8-tetramethyl-5-oxo-1,1a,1b,4,4a,5,7a,7b,8,9-decahydro-cyclopropa[3,4]benzo[1,2-e]azulen-9a-yl ester	KD	0.28 nM
teleocidin B-4	KI	0.32 nM
NSC_105100	KI	0.35 nM
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
Aplysiatoxin	KI	0.4 nM
CHEMBL2151411	IC50	0.4 nM
NSC_4179	KI	0.43 nM
Bryostatin	KD	0.44 nM
CAS_159320	KI	0.45 nM
13-Hydroxymethyl-10-isopropyl-9-methyl-5-octyl-3,9,12-triaza-tricyclo[6.6.1.0*4,15*]pentadeca-1,4,6,8(15)-tetraen-11-one (n-octyl-ILV)	KI	0.5 nM
CHEMBL4102228	IC50	0.5 nM
CHEMBL4072879	IC50	0.5 nM
CHEMBL1996510	IC50	0.5 nM
CHEMBL4587471	EC50	0.55 nM
CHEMBL4575056	EC50	0.6 nM
bryostatin 1	KD	0.73 nM
[(1S,4S,5R,9S,10S,12R,14R)-5-hydroxy-7-(hydroxymethyl)-3,11,11,14-tetramethyl-15-oxo-4-tetracyclo[7.5.1.01,5.010,12]pentadeca-2,7-dienyl] 1-methylcyclohexane-1-carboxylate	EC50	0.8 nM	US-9409931: 3-O-acyl-ingenol analogues
(2S,5S)-2-Decyl-5-hydroxymethyl-1-methyl-1,4,5,6-tetrahydro-2H-benzo[e][1,4]diazocin-3-one	KI	0.8 nM
(2S,5S)-2-Dodecyl-5-hydroxymethyl-1-methyl-1,4,5,6-tetrahydro-2H-benzo[e][1,4]diazocin-3-one	KI	0.8 nM
(2S,5S)-5-Hydroxymethyl-1-methyl-2-tetradecyl-1,4,5,6-tetrahydro-2H-benzo[e][1,4]diazocin-3-one	KI	0.8 nM
maleimide derivative, 12	IC50	0.9 nM
CHEMBL2153750	IC50	1 nM
DEMETHOXYDEBROMOAPLYSIATOXIN	KI	1 nM
Compound K-252a(epi)	IC50	1.2 nM
CHEMBL2381165	KI	1.3 nM
CHEMBL4565484	KI	1.3 nM
CHEMBL2151415	IC50	1.4 nM
CHEMBL2153748	IC50	1.4 nM
Staurosporine	KD	1.7 nM
CHEMBL2153751	IC50	1.7 nM
CHEMBL4085837	IC50	1.8 nM
CHEMBL4533216	KI	1.9 nM
maleimide derivative, 10	IC50	2.2 nM
CHEMBL83790	IC50	2.2 nM
5-vinyl-3-pyridinecarbonitrile, 12b	IC50	2.5 nM
CHEMBL3105098	EC50	2.5 nM
CHEMBL4083319	IC50	2.7 nM
CHEMBL4574406	KI	2.7 nM
CHEMBL4101316	IC50	2.8 nM
CHEMBL4593581	KI	2.8 nM

ChEMBL bioactivities

1363 potent at pChembl≥5 of 1495 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
10.00	IC50	0.1	nM	CHEMBL2151411
9.96	Ki	0.11	nM	CHEMBL5172923
9.89	IC50	0.128	nM	STAUROSPORINE
9.89	IC50	0.13	nM	CHEMBL3741746
9.89	IC50	0.129	nM	STAUROSPORINE
9.89	Kd	0.129	nM	CHEMBL5653589
9.87	ED50	0.136	nM	CHEMBL5653589
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
9.71	Kd	0.193	nM	CHEMBL27768
9.71	IC50	0.193	nM	STAUROSPORINE
9.70	Ki	0.2	nM	DEBROMOAPLYSIATOXIN
9.66	IC50	0.22	nM	CHEMBL4435580
9.49	Ki	0.32	nM	DEMETHOXYDEBROMOAPLYSIATOXIN
9.49	Ki	0.32	nM	CHEMBL417692
9.44	IC50	0.36	nM	CHEMBL4587471
9.40	IC50	0.4	nM	CHEMBL1996510
9.39	Ki	0.41	nM	APLYSIATOXIN
9.36	Ki	0.44	nM	BRYOSTATIN 1
9.34	Ki	0.46	nM	CHEMBL2148108
9.34	Ki	0.46	nM	CHEMBL399981
9.28	Kd	0.53	nM	CHEMBL27768
9.26	EC50	0.55	nM	CHEMBL4587471
9.26	Ki	0.55	nM	CHEMBL265998
9.22	IC50	0.6	nM	CHEMBL2153750
9.22	EC50	0.6	nM	CHEMBL4575056
9.22	IC50	0.6	nM	STAUROSPORINE
9.10	Ki	0.8	nM	PHORBOL MYRISTATE ACETATE
9.10	Ki	0.8	nM	CHEMBL160375
9.10	Ki	0.8	nM	CHEMBL159233
9.10	Ki	0.8	nM	CHEMBL351103
9.10	Ki	0.8	nM	CHEMBL27768
9.10	Ki	0.8	nM	CHEMBL285801
9.05	IC50	0.9	nM	CHEMBL427118
9.05	IC50	0.9	nM	CHEMBL52529
9.05	Ki	0.9	nM	CHEMBL137386
9.05	IC50	0.9	nM	CHEMBL48636
9.00	IC50	1	nM	CHEMBL2151415
9.00	Kd	1	nM	CHEMBL27768
9.00	IC50	1	nM	CHEMBL48636
9.00	IC50	1	nM	STAUROSPORINE
9.00	IC50	1	nM	CHEMBL52529
9.00	IC50	1	nM	CHEMBL71331
9.00	Kd	1	nM	CHEMBL337834
8.99	Ki	1.03	nM	CHEMBL27768

PubChem BioAssay actives

986 with measured affinity, of 3760 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149078: Binding affinity to human PRKCD incubated for 45 mins by Kinobead based pull down assay	kd	0.0001	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-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	1531839: Inhibition of human PKCdelta using ERMRPRKRQGSVRRRV as substrate by [gamma-33P]-ATP assay	ic50	0.0001	uM
3-(7-methyl-1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione	690000: Inhibition of PKCdelta by scintillation proximity assay	ic50	0.0001	uM
(10S,13S)-5-[(3R)-3,7-dimethylocta-1,6-dien-3-yl]-13-(hydroxymethyl)-9-methyl-10-propan-2-yl-3,9,12-triazatricyclo[6.6.1.04,15]pentadeca-1,4,6,8(15)-tetraen-11-one	1942299: Inhibition of [3H]-PDBu binding to PKCdelta C1B domain (unknown origin) by competitive binding assay	ki	0.0001	uM
[(1R,6R,13R,14R,15S)-13-butanoyloxy-1,6-dihydroxy-4,12,12,15-tetramethyl-5,8-dioxo-14-tetracyclo[8.5.0.02,6.011,13]pentadec-3-enyl] 2-(methylamino)benzoate	1799804: Binding Assay from Article 10.1074/jbc.M707463200: “Characterization of the interaction of phorbol esters with the C1 domain of MRCK (myotonic dystrophy kinase-related Cdc42 binding kinase) alpha/beta.”	ki	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
[(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	1138942: Binding affinity to PKC-delta C1B domain (unknown origin)	kd	0.0002	uM
(1S,3R,4S,5S,9R,13S,14R)-13-hydroxy-9-[(1R)-1-hydroxyethyl]-3-[(2S,5S)-5-(3-hydroxyphenyl)-5-methoxypentan-2-yl]-4,14,16,16-tetramethyl-2,6,10,17-tetraoxatricyclo[11.3.1.11,5]octadecane-7,11-dione	687832: Inhibition of [3H]PDBu binding to PKCdelta C1B domain	ki	0.0002	uM
[(1R,6R,13R,14R,15S)-13-butanoyloxy-1,6-dihydroxy-4,12,12,15-tetramethyl-5,8-dioxo-14-tetracyclo[8.5.0.02,6.011,13]pentadec-3-enyl] butanoate	1799804: Binding Assay from Article 10.1074/jbc.M707463200: “Characterization of the interaction of phorbol esters with the C1 domain of MRCK (myotonic dystrophy kinase-related Cdc42 binding kinase) alpha/beta.”	kd	0.0002	uM
(1S,3R,4S,5S,9R,13S,14R)-13-hydroxy-9-[(1R)-1-hydroxyethyl]-3-[(2S)-5-(3-hydroxyphenyl)pentan-2-yl]-4,14,16,16-tetramethyl-2,6,10,17-tetraoxatricyclo[11.3.1.11,5]octadecane-7,11-dione	768063: Displacement of [3H]PDBu from PKCdelta C1B domain (unknown origin)	ki	0.0003	uM
(6S,9S,14R,17R)-17-ethenyl-6-(hydroxymethyl)-10,14,17-trimethyl-9,14-di(propan-2-yl)-2,7,10-triazatetracyclo[9.7.1.04,19.013,18]nonadeca-1(18),3,11(19),12-tetraen-8-one	163528: Displacement of [3H]PDBu from recombinant Protein kinase C delta	ki	0.0003	uM
3-(1H-indol-3-yl)-4-(2-piperazin-1-ylquinazolin-4-yl)pyrrole-2,5-dione	690000: Inhibition of PKCdelta by scintillation proximity assay	ic50	0.0004	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
(1S,3R,4S,5S,9R,13S,14R)-3-[(2S,5S)-5-(2-bromo-5-hydroxyphenyl)-5-methoxypentan-2-yl]-13-hydroxy-9-[(1R)-1-hydroxyethyl]-4,14,16,16-tetramethyl-2,6,10,17-tetraoxatricyclo[11.3.1.11,5]octadecane-7,11-dione	517266: Inhibition of [3H]PDBu binding to PKC delta C1B peptide	ki	0.0004	uM
[(1S,3S,5Z,7R,8E,11S,12S,13E,15S,17R,21R,23R,25S)-25-acetyloxy-1,11,21-trihydroxy-17-[(1R)-1-hydroxyethyl]-5,13-bis(2-methoxy-2-oxoethylidene)-10,10,26,26-tetramethyl-19-oxo-18,27,28,29-tetraoxatetracyclo[21.3.1.13,7.111,15]nonacos-8-en-12-yl] (2E,4E)-octa-2,4-dienoate	374768: Displacement of [3H]PDBu from human recombinant PKCdelta expressed in Sf9 cells by liquid scintillation counting	ki	0.0004	uM
(10S,13S)-3-hexyl-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	312187: Displacement of [3H]PDBu from PKCdelta C1B domain	ki	0.0005	uM
(1R,3R,4R,5S,9R,13R)-9-(hydroxymethyl)-3-[4-(3-hydroxyphenyl)butyl]-4,16,16-trimethyl-2,6,10,17-tetraoxatricyclo[11.3.1.11,5]octadecane-7,11-dione	687832: Inhibition of [3H]PDBu binding to PKCdelta C1B domain	ki	0.0005	uM
[(1R,2R,6S,10S,11R,13S,14R,15R)-13-butanoyloxy-1-hydroxy-8-(hydroxymethyl)-4,12,12,15-tetramethyl-5-oxo-14-tetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dienyl] butanoate	163680: Displacement of 3[H]PDBu from Protein kinase C delta C1b domain	ki	0.0006	uM
3-[6-fluoro-2-(4-methylpiperazin-1-yl)quinazolin-4-yl]-4-(1H-indol-3-yl)pyrrole-2,5-dione	690000: Inhibition of PKCdelta by scintillation proximity assay	ic50	0.0006	uM
(2S,5S)-2-decyl-5-(hydroxymethyl)-1-methyl-2,4,5,6-tetrahydro-1,4-benzodiazocin-3-one	155742: Binding affinity for human recombinant protein kinase C delta	ki	0.0008	uM
(10S,13S)-13-(hydroxymethyl)-9-methyl-5-octyl-10-propan-2-yl-3,9,12-triazatricyclo[6.6.1.04,15]pentadeca-1,4,6,8(15)-tetraen-11-one	163526: Displacement of [3H]- PDBu from recombinant PKC delta expressed in baculovirus	ki	0.0008	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	220518: Inhibition of [3H]-phorbol 12,13-dibutyrate (PDBu) binding to human recombinant protein kinase C delta	ki	0.0008	uM
(2S,5S)-5-(hydroxymethyl)-1-methyl-2-tetradecyl-2,4,5,6-tetrahydro-1,4-benzodiazocin-3-one	155742: Binding affinity for human recombinant protein kinase C delta	ki	0.0008	uM
(2S,5S)-2-dodecyl-5-(hydroxymethyl)-1-methyl-2,4,5,6-tetrahydro-1,4-benzodiazocin-3-one	155742: Binding affinity for human recombinant protein kinase C delta	ki	0.0008	uM
2-[2,6-dihydroxy-4-[2-[(4-hydroxybenzoyl)amino]cyclopentyl]oxycarbonylbenzoyl]-3-hydroxybenzoic acid	163378: Evaluated against recombinant human Protein kinase C delta	ic50	0.0009	uM
[(4E)-2-(hydroxymethyl)-4-[5-methyl-3-(2-methylpropyl)hexylidene]-5-oxooxolan-2-yl]methyl 2,2-dimethylpropanoate	238839: Binding affinity for isolated C1b domain of protein kinase C-delta	ki	0.0009	uM
N-[(2S,5S)-5-(hydroxymethyl)-1-methyl-3-oxo-2-propan-2-yl-2,4,5,6-tetrahydro-1,4-benzodiazocin-8-yl]-N’-[(2S,5S)-5-(hydroxymethyl)-1-methyl-3-oxo-2-propan-2-yl-2,4,5,6-tetrahydro-1,4-benzodiazocin-9-yl]tetradecanediamide	163510: Binding affinity for human Protein kinase C delta	kd	0.0010	uM
2-[2,6-dihydroxy-4-[(1R,2R)-2-[(4-hydroxybenzoyl)amino]cyclopentyl]oxycarbonylbenzoyl]-3-hydroxybenzoic acid	163505: Inhibitory concentration against recombinant human Protein kinase C delta isozyme	ic50	0.0010	uM
3-(1-methylindol-3-yl)-4-(2-piperazin-1-ylquinazolin-4-yl)pyrrole-2,5-dione	690000: Inhibition of PKCdelta by scintillation proximity assay	ic50	0.0010	uM
3-[6-chloro-2-(4-methylpiperazin-1-yl)quinazolin-4-yl]-4-(1H-indol-3-yl)pyrrole-2,5-dione	690000: Inhibition of PKCdelta by scintillation proximity assay	ic50	0.0012	uM
[(4Z)-2-(hydroxymethyl)-4-[5-methyl-3-(2-methylpropyl)hexylidene]-5-oxooxolan-2-yl]methyl 2,2-dimethylpropanoate	1799804: Binding Assay from Article 10.1074/jbc.M707463200: “Characterization of the interaction of phorbol esters with the C1 domain of MRCK (myotonic dystrophy kinase-related Cdc42 binding kinase) alpha/beta.”	ki	0.0012	uM
[(1S,17R,19S,21E,22S)-8-(2,6-dimethoxyphenyl)-1-hydroxy-17-(hydroxymethyl)-21-(2-methoxy-2-oxoethylidene)-2,2-dimethyl-5,15-dioxo-4,12,16,23-tetraoxatricyclo[17.3.1.06,11]tricosa-6(11),7,9-trien-22-yl] octanoate	1634646: Inhibition of [3H]PDBu binding to recombinant full length human PKCdelta expressed in baculovirus expression system incubated for 5 mins by scintillation counting method	ki	0.0013	uM
3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione	1437219: Inhibition of PKCdelta (unknown origin) after 60 mins in presence of [gamma33P]ATP by scintillation proximity assay	ic50	0.0013	uM
(1S,3R,5R,9R,13R)-3-[4-(3-hydroxy-4-iodophenyl)butyl]-9-(hydroxymethyl)-16,16-dimethyl-2,6,10,17-tetraoxatricyclo[11.3.1.11,5]octadecane-7,11-dione	746975: Inhibition of [3H]PDBu binding to PKCdelta-C1B domain peptide (unknown origin)	ki	0.0013	uM
[(4E)-2-(hydroxymethyl)-4-[(4-hydroxyphenyl)methylidene]-5-oxooxolan-2-yl]methyl 4-methyl-3-propan-2-ylpentanoate	265548: Binding affinity to PKCdeltaC1b in presence of phospholipid	ki	0.0014	uM
[(4Z)-4-[[4-(dimethylamino)phenyl]methylidene]-2-(hydroxymethyl)-5-oxooxolan-2-yl]methyl 4-nitrobenzoate	1799804: Binding Assay from Article 10.1074/jbc.M707463200: “Characterization of the interaction of phorbol esters with the C1 domain of MRCK (myotonic dystrophy kinase-related Cdc42 binding kinase) alpha/beta.”	ki	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
3-(1H-indol-3-yl)-4-[3-(4-methylpiperazin-1-yl)isoquinolin-1-yl]pyrrole-2,5-dione	690000: Inhibition of PKCdelta by scintillation proximity assay	ic50	0.0018	uM
(2S,5S)-9-decyl-5-(hydroxymethyl)-1-methyl-2-propan-2-yl-2,4,5,6-tetrahydro-1,4-benzodiazocin-3-one	163511: Displacement of [3H]-PDBu from human recombinant Protein kinase C delta	ki	0.0018	uM
[(1S,17R,19S,21E,22S)-8-[2,6-di(propan-2-yloxy)phenyl]-1-hydroxy-17-(hydroxymethyl)-21-(2-methoxy-2-oxoethylidene)-2,2-dimethyl-5,15-dioxo-4,12,16,23-tetraoxatricyclo[17.3.1.06,11]tricosa-6(11),7,9-trien-22-yl] octanoate	1634646: Inhibition of [3H]PDBu binding to recombinant full length human PKCdelta expressed in baculovirus expression system incubated for 5 mins by scintillation counting method	ki	0.0019	uM
[(1R,3S,7S,8E,11S,12S,13E,17R,21R,23S)-11,21-dihydroxy-17-[(1R)-1-hydroxyethyl]-13-(2-methoxy-2-oxoethylidene)-10,10-dimethyl-19-oxo-6,18,27,28,29-pentaoxatetracyclo[21.3.1.13,7.111,15]nonacos-8-en-12-yl] octanoate	163677: Displacement of [3H]PDBu from protein kinase C delta C1b domain	ki	0.0025	uM
4-[(4-methyl-1H-indol-5-yl)amino]-5-[(E)-4-(4-methylpiperazin-1-yl)but-1-enyl]pyridine-3-carbonitrile	1799293: PKC IMAP Kinase Assay from Article 10.1016/j.bmc.2009.10.020: “5-Vinyl-3-pyridinecarbonitrile inhibitors of PKCtheta: optimization of enzymatic and functional activity.”	ic50	0.0025	uM
3-(5-chloro-1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione	690000: Inhibition of PKCdelta by scintillation proximity assay	ic50	0.0025	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] 2-(methylamino)benzoate	1063167: Activation of PKCdelta (unknown origin) after 40 mins	ec50	0.0025	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tetradecanoylphorbol Acetate	affects cotreatment, increases expression, increases localization, decreases expression, affects phosphorylation (+8 more)	18
rottlerin	decreases response to substance, decreases reaction, increases phosphorylation, increases activity, increases cleavage (+3 more)	8
Tretinoin	decreases reaction, increases expression, affects reaction, increases activity, affects expression (+2 more)	7
sodium arsenite	decreases reaction, decreases phosphorylation, increases reaction, increases phosphorylation, decreases expression (+2 more)	6
Quercetin	affects localization, decreases reaction, increases phosphorylation, increases activity, increases localization (+2 more)	4
bisindolylmaleimide I	decreases reaction, increases expression, decreases expression, affects phosphorylation, affects reaction	3
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	increases cleavage, increases reaction, increases ubiquitination, increases phosphorylation, decreases reaction (+1 more)	3
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	affects localization, decreases reaction, increases phosphorylation, increases activity, increases localization (+2 more)	3
Curcumin	increases reaction, increases expression, affects reaction, decreases reaction, increases phosphorylation	3
Estradiol	affects cotreatment, decreases expression	3
diphenyleneiodonium	affects localization, decreases reaction, increases localization	2
bisphenol B	decreases expression, increases expression	2
NSC606985	increases activity, increases cleavage, increases reaction, affects reaction, decreases expression (+1 more)	2
Bortezomib	affects cotreatment, increases activity, increases cleavage, increases reaction	2
Wortmannin	increases activity, increases localization, decreases reaction, increases phosphorylation	2
Arsenic Trioxide	affects cotreatment, increases activity, increases cleavage	2
Acetylcysteine	decreases reaction, increases phosphorylation, increases localization	2
Cisplatin	affects expression, affects cotreatment, increases expression	2
Doxorubicin	increases response to substance, decreases reaction, increases cleavage, increases reaction, increases activity	2
Glutathione	decreases reaction, increases phosphorylation	2
Plant Extracts	affects cotreatment, increases expression, increases activity	2
1-Methyl-4-phenylpyridinium	decreases expression, increases expression	2
Aflatoxin B1	increases expression	2
FR900359	affects phosphorylation	1
daidzein	decreases expression	1
triphenyl phosphate	affects expression	1
2-amino-4-hydroxy-6-formylpteridine	affects localization	1
bisphenol A	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
2-butenal	increases expression, increases reaction	1

ChEMBL screening assays

804 unique, capped per target: 790 binding, 14 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

5 cell lines: 4 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2C5	Abcam HeLa PRKCD KO	Cancer cell line	Female
CVCL_B3EV	Abcam HEK293T PRKCD KO	Transformed cell line	Female
CVCL_D1U3	Abcam U-87MG PRKCD KO	Cancer cell line	Male
CVCL_TG82	HAP1 PRKCD (-) 1	Cancer cell line	Male
CVCL_TG83	HAP1 PRKCD (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for PRKCD across ~30M SureChEMBL compounds — explore on Sugi Predict.