PRKCE

Summary

PRKCE (protein kinase C epsilon, HGNC:9401) is a protein-coding gene on chromosome 2p21, encoding Protein kinase C epsilon type (Q02156). Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays essential roles in the regulation of multiple cellular processes linked to cytoskeletal proteins, such as cell adhesion, motility, migration and cell cycle, functions….

Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and the second messenger diacylglycerol. PKC family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. PKC family members also serve as major receptors for phorbol esters, a class of tumor promoters. Each member of the PKC family has a specific expression profile and is believed to play a distinct role in cells. The protein encoded by this gene is one of the PKC family members. This kinase has been shown to be involved in many different cellular functions, such as neuron channel activation, apoptosis, cardioprotection from ischemia, heat shock response, as well as insulin exocytosis. Knockout studies in mice suggest that this kinase is important for lipopolysaccharide (LPS)-mediated signaling in activated macrophages and may also play a role in controlling anxiety-like behavior.

Source: NCBI Gene 5581 — RefSeq curated summary.

At a glance

• GWAS associations: 91 (top 1% of genes corpus-wide)
• Clinical variants (ClinVar): 68 total — 1 pathogenic, 1 likely-pathogenic
• Regional missense constraint (gnomAD): 3 of 11 regions constrained (≈16% of expected missense variation)
• GTEx eGene: eQTL in 26 tissues, sQTL in 21 (q < 0.05)
• Drug target: yes — 1 curated mechanism-of-action drug; 21 molecules with ChEMBL bioactivity (top 2% of genes corpus-wide)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.28 (highly constrained)
• MANE Select transcript: NM_005400
• Notable: 68 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9401
Approved symbol	PRKCE
Name	protein kinase C epsilon
Location	2p21
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000171132
Ensembl biotype	protein_coding
OMIM	176975
Entrez	5581

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 12 protein_coding_CDS_not_defined, 10 protein_coding

MANE Select: ENST00000306156

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 2, TSL 3: 6, TSL 4: 2, TSL 5: 3

ENST00000306156, ENST00000394874, ENST00000421201, ENST00000462720, ENST00000467135, ENST00000469753, ENST00000472021, ENST00000476675, ENST00000480453, ENST00000480633, ENST00000485176, ENST00000489067, ENST00000494472, ENST00000497602, ENST00000498388, ENST00000872579, ENST00000986780, ENST00001051924, ENST00001107163, ENST00001127648, ENST00001127649, ENST00001144333

RefSeq mRNA: 1 — MANE Select: NM_005400 NM_005400

CCDS: CCDS1824

Canonical transcript exons

ENST00000306156 — 15 exons

Exon	Start	End
ENSE00001169438	46151041	46151229
ENSE00001169459	46007462	46007661
ENSE00001169464	46004542	46004638
ENSE00001169474	45984551	45984680
ENSE00001326267	46184735	46187990
ENSE00001779178	46010344	46010517
ENSE00001829860	45651675	45652448
ENSE00003488235	45980296	45980381
ENSE00003507286	46159606	46159752
ENSE00003509073	46086208	46086362
ENSE00003621522	45976429	45976588
ENSE00003625267	45843000	45843063
ENSE00003632577	45978976	45979010
ENSE00003649344	46001404	46001546
ENSE00003678245	46145093	46145231

Expression profiles

Bgee: expression breadth ubiquitous, 233 present calls, max score 96.63.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.1985 / max 222.6898, expressed in 1696 samples.

Highest expression (Bgee): buccal mucosa cell, sural nerve, lateral nuclear group of thalamus, parietal lobe, postcentral gyrus.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PRKCE is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 26 tissues and its splicing (sQTL) in 21 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 47 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	sqtl	2.3e-30	+0.90	2:45701491:G:A
Cells Cultured fibroblasts	sqtl	1.2e-18	+0.60	2:45844464:A:T
Muscle Skeletal	eqtl	7.9e-15	-0.28	2:45718265:A:G
Esophagus Mucosa	sqtl	8.5e-15	-0.60	2:45848722:AC:A
Nerve Tibial	sqtl	4.4e-14	+0.60	2:45844464:A:T
Lung	sqtl	1.2e-13	-0.67	2:45844464:A:T
Whole Blood	sqtl	3.8e-13	-0.55	2:45849406:T:C
Adipose Subcutaneous	sqtl	1.5e-12	-0.51	2:45849899:C:T
Cells EBV-transformed lymphocytes	sqtl	2.3e-10	-0.74	2:45844464:A:T
Whole Blood	eqtl	2.0e-09	+0.18	2:45656458:G:C
Stomach	sqtl	1.6e-07	+0.61	2:45849899:C:T
Thyroid	sqtl	4.3e-07	-0.45	2:45848722:AC:A
Colon Transverse	sqtl	2.2e-05	+0.48	2:45844464:A:T
Pituitary	sqtl	3.6e-05	+0.59	2:45844464:A:T
Testis	eqtl	4.1e-05	-0.21	2:46015835:A:G
Breast Mammary Tissue	sqtl	5.9e-05	-0.49	2:45846957:T:A
Esophagus Muscularis	sqtl	1.3e-04	+0.41	2:45849899:C:T
Brain Cerebellar Hemisphere	eqtl	1.7e-04	+0.19	2:45754891:G:A
Heart Atrial Appendage	sqtl	1.8e-04	+0.51	2:45848722:AC:A
Cells Cultured fibroblasts	eqtl	1.8e-04	+0.12	2:45750933:A:G

FANTOM5 promoters

9 alternative TSS:

Promoter ID	TPM avg	Samples expressed
20039	7.4348	1551
20038	3.2826	1182
20051	1.3922	379
202178	0.5233	287
20040	0.3959	163
20052	0.1135	52
202179	0.0441	13
20043	0.0063	3
20047	0.0057	3

Top tissues by expression

showing 100 of 291 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	96.63	gold quality
sural nerve	UBERON:0015488	94.88	gold quality
lateral nuclear group of thalamus	UBERON:0002736	94.53	gold quality
parietal lobe	UBERON:0001872	93.96	gold quality
postcentral gyrus	UBERON:0002581	93.57	gold quality
right lung	UBERON:0002167	93.43	gold quality
middle temporal gyrus	UBERON:0002771	93.42	gold quality
cortical plate	UBERON:0005343	93.01	gold quality
sperm	CL:0000019	92.95	gold quality
superior frontal gyrus	UBERON:0002661	91.79	gold quality
entorhinal cortex	UBERON:0002728	91.76	gold quality
pons	UBERON:0000988	91.09	gold quality
prefrontal cortex	UBERON:0000451	91.02	gold quality
Brodmann (1909) area 23	UBERON:0013554	90.24	gold quality
male germ cell	CL:0000015	89.88	gold quality
occipital lobe	UBERON:0002021	89.80	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	89.43	gold quality
primary visual cortex	UBERON:0002436	89.38	gold quality
upper lobe of left lung	UBERON:0008952	88.57	gold quality
frontal cortex	UBERON:0001870	88.36	gold quality
left testis	UBERON:0004533	88.23	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.16	gold quality
upper lobe of lung	UBERON:0008948	88.12	gold quality
right testis	UBERON:0004534	88.10	gold quality
neocortex	UBERON:0001950	87.98	gold quality
cerebellar cortex	UBERON:0002129	87.97	gold quality
cerebral cortex	UBERON:0000956	87.90	gold quality
cerebellar hemisphere	UBERON:0002245	87.90	gold quality
dorsal root ganglion	UBERON:0000044	87.25	gold quality
Ammon’s horn	UBERON:0001954	87.21	gold quality
temporal lobe	UBERON:0001871	87.08	gold quality
cerebellum	UBERON:0002037	86.78	gold quality
cingulate cortex	UBERON:0003027	86.68	gold quality
anterior cingulate cortex	UBERON:0009835	86.44	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.41	gold quality
right frontal lobe	UBERON:0002810	86.33	gold quality
testis	UBERON:0000473	85.84	gold quality
trigeminal ganglion	UBERON:0001675	85.66	gold quality
telencephalon	UBERON:0001893	85.57	gold quality
colonic epithelium	UBERON:0000397	85.30	gold quality
corpus callosum	UBERON:0002336	84.73	gold quality
endothelial cell	CL:0000115	84.70	gold quality
lower lobe of lung	UBERON:0008949	84.29	silver quality
calcaneal tendon	UBERON:0003701	84.21	gold quality
forebrain	UBERON:0001890	84.09	gold quality
superior vestibular nucleus	UBERON:0007227	84.08	gold quality
amygdala	UBERON:0001876	83.89	gold quality
brain	UBERON:0000955	83.68	gold quality
central nervous system	UBERON:0001017	83.30	gold quality
renal medulla	UBERON:0000362	82.62	gold quality
cerebellar vermis	UBERON:0004720	82.58	gold quality
ventral tegmental area	UBERON:0002691	82.15	silver quality
lung	UBERON:0002048	82.09	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.99	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	81.76	gold quality
lateral globus pallidus	UBERON:0002476	81.38	gold quality
islet of Langerhans	UBERON:0000006	80.80	gold quality
adult organism	UBERON:0007023	80.53	gold quality
nucleus accumbens	UBERON:0001882	80.00	gold quality
bronchial epithelial cell	CL:0002328	79.96	gold quality
caudate nucleus	UBERON:0001873	79.56	gold quality
dorsal plus ventral thalamus	UBERON:0001897	79.17	silver quality
gastrocnemius	UBERON:0001388	79.00	gold quality
muscle of leg	UBERON:0001383	78.81	gold quality
stromal cell of endometrium	CL:0002255	78.78	gold quality
monocyte	CL:0000576	78.65	gold quality
mononuclear cell	CL:0000842	78.56	gold quality
putamen	UBERON:0001874	78.48	gold quality
leukocyte	CL:0000738	78.38	gold quality
mucosa of paranasal sinus	UBERON:0005030	78.34	silver quality
inferior vagus X ganglion	UBERON:0005363	78.24	silver quality
adult mammalian kidney	UBERON:0000082	77.82	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.75	gold quality
tonsil	UBERON:0002372	77.51	gold quality
subthalamic nucleus	UBERON:0001906	77.49	silver quality
lower esophagus mucosa	UBERON:0035834	77.31	gold quality
right lobe of liver	UBERON:0001114	77.26	gold quality
tendon	UBERON:0000043	77.21	gold quality
hindlimb stylopod muscle	UBERON:0004252	77.11	gold quality
hypothalamus	UBERON:0001898	77.02	gold quality
medulla oblongata	UBERON:0001896	76.90	silver quality
substantia nigra pars compacta	UBERON:0001965	76.78	silver quality
muscle layer of sigmoid colon	UBERON:0035805	76.54	gold quality
right atrium auricular region	UBERON:0006631	76.00	gold quality
lymph node	UBERON:0000029	75.91	gold quality
liver	UBERON:0002107	75.77	gold quality
epithelium of bronchus	UBERON:0002031	75.52	gold quality
pancreas	UBERON:0001264	75.43	gold quality
bronchus	UBERON:0002185	75.39	gold quality
anatomical system	UBERON:0000467	75.38	gold quality
stomach	UBERON:0000945	75.35	gold quality
material anatomical entity	UBERON:0000465	75.25	gold quality
multicellular organism	UBERON:0000468	75.25	gold quality
ventricular zone	UBERON:0003053	75.25	gold quality
decidua	UBERON:0002450	75.07	gold quality
metanephros cortex	UBERON:0010533	75.02	gold quality
ectocervix	UBERON:0012249	74.99	gold quality
cardiac atrium	UBERON:0002081	74.95	gold quality
adrenal tissue	UBERON:0018303	74.85	gold quality
heart left ventricle	UBERON:0002084	74.76	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-25	yes	36.89
E-CURD-119	yes	17.41
E-ANND-3	yes	13.59

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Postcentral gyrus	tissue	157.9
Hippocampus	tissue	144.2	medium
Frontal cortex	tissue	119.2
Hippocampal formation	tissue	117.5
Caudate putamen	tissue	114.5
Cerebral cortex	tissue	84.0	high
Somatosensory cortex	tissue	84.0
Motor cortex	tissue	83.2
Prefrontal cortex	tissue	82.6
Entorhinal cortex	tissue	81.5
Occipital cortex	tissue	79.3
Temporal cortex	tissue	77.5
Retrosplenial and cingulate cortex	tissue	77.0
Amygdala	tissue	73.1
Insular cortex	tissue	70.7
Retrosplenial cortex	tissue	70.3
Olfactory bulb	tissue	67.0
Cerebellum	tissue	55.1	low
Putamen	tissue	54.5
Basal ganglia	tissue	53.6	medium
Ventral forebrain	tissue	47.1
Septum	tissue	47.0
Thalamus	tissue	45.3
Nucleus accumbens	tissue	42.9
Superior colliculi	tissue	38.0
Locus coeruleus	tissue	36.7
Pons	tissue	34.5
Midbrain	tissue	31.8
Hypothalamus	tissue	28.9
Choroid plexus	tissue	24.4
Medulla oblongata	tissue	19.5
Periaqueductal gray	tissue	19.2
Spinal cord	tissue	17.2
Substantia nigra	tissue	17.1
Retina	tissue	14.3
Liver	tissue	11.7	not detected
Lung	tissue	10.7	not detected
Corpus callosum	tissue	9.8
Kidney	tissue	9.4	high
Parathyroid gland	tissue	8.9	low
Placenta	tissue	7.8	not detected
Bone marrow	tissue	7.6	not detected
Heart muscle	tissue	5.8	not detected
Skeletal muscle	tissue	5.8	not detected
Testis	tissue	5.6	low
Lymph node	tissue	5.4	not detected
Fallopian tube	tissue	5.3	not detected
Adrenal gland	tissue	5.2	low
Tongue	tissue	5.0
Pituitary gland	tissue	4.7
Urinary bladder	tissue	4.6	not detected
Thyroid gland	tissue	4.6	not detected
Cervix	tissue	4.4	not detected
Adipose tissue	tissue	4.0	not detected
Smooth muscle	tissue	3.9	low
Endometrium 1	tissue	3.9	not detected
Tonsil	tissue	3.9	not detected
Spleen	tissue	3.7	not detected
Appendix	tissue	3.5	not detected
Colon	tissue	3.3	low

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Posterior cingulate cortex (161.3), Hippocampus, CA1 (155.3), Dentate gyrus (153.3), Hippocampus, CA3 (140.4), Precentral gyrus (138.6).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, BHLHE40, CREB1, EGR1, FOS, JUN, NFKB, PAX5, PPARG, SP1, STAT1, ZHX2

miRNA regulators (miRDB)

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

showing 30 of 210 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4282	99.99	75.36	6408
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-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.278, missense Z 4.93 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000306156 splits into 11 regions with different missense tolerance; 3 are missense-constrained (≈16% 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
2:45,652,101–45,843,047	100 / 177.1	0.56	no
2:45,843,048–45,976,474	33 / 33.7	0.98	no
2:45,976,475–45,980,358	29 / 96.2	0.30	yes (p 7.2e-12)
2:45,980,359–45,984,564	18 / 17.4	1.04	no
2:45,984,565–46,004,567	55 / 128.1	0.43	no
2:46,004,568–46,007,635	117 / 104.8	1.12	no
2:46,007,636–46,086,357	89 / 154.1	0.58	no
2:46,086,358–46,145,193	15 / 42.2	0.36	yes (p 2.9e-05)
2:46,145,194–46,145,231	0 / 16.6	0.00	yes (p 4.7e-05)
2:46,151,041–46,184,782	72 / 166.0	0.43	no
2:46,184,783–46,184,878	45 / 39.1	1.15	no

Literature-anchored findings (GeneRIF, showing 40)

• Isoforms of protein kinase C and their distribution in human adrenal cortex and tumors (PMID:11740573)
• PKCepsilon mediates neurite induction by increased association to the cytoskeleton during neuronal differentiation. (PMID:11809819)
• 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)
• Direct phosphorylation of capsaicin receptor VR1 by protein kinase Cepsilon and identification of two target serine residues (PMID:11884385)
• The anchoring protein RACK1 links protein kinase Cepsilon to integrin beta chains. (PMID:11934885)
• Protein kinase C epsilon-dependent regulation of cystic fibrosis transmembrane regulator involves binding to a receptor for activated C kinase (RACK1) and RACK1 binding to Na+/H+ exchange regulatory factor. (PMID:11956211)
• The contribution of PKCepsilon kinase activity in controlling the phosphorylation of Thr(566) and Ser(729)of PKCE. (PMID:11964154)
• No thyroid papillary carcinoma, follicular adenoma, or anaplastic carcinoma harbored the PKCalpha 881A>G mutation. (PMID:11994357)
• Critical role of diacylglycerol- and phospholipid-regulated protein kinase C epsilon in induction of low-density lipoprotein receptor transcription in response to depletion of cholesterol. (PMID:11997513)
• 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)
• promotes survival of lung cancer cells by suppressing apoptosis through dysregulation of the mitochondrial caspase pathway (PMID:12121973)
• role in regulating caveolin-1 expression and secretion (PMID:12185081)
• activation inhibited TNF-induced apoptosis in MCF-7 cells (PMID:12198125)
• Protein kinase C-epsilon mediates bradykinin-induced cyclooxygenase-2 expression in human airway smooth muscle cells (PMID:12205039)
• PKCepsilon-mediated inhibition of Cl-/OH- exchange activity in Caco-2 cells (PMID:12372810)
• PKCepsilon as the key isoform responsible for actin disruption in T84 cells (PMID:12372816)
• Protein kinase C epsilon plays a role in lipopolysaccharide-induced IL-12 synthesis in monocyte-derived dendritic cells. (PMID:12385023)
• absence of protein kinase C-epsilon allows increased expression of potassium(V) channels (like Kv3.1b) to occur in pulmonary artery smooth muscle cells, which likely contributes to decreased hypoxic pulmonary vasoconstriction (PMID:12505875)
• selective modulation of novel PKC epsilon may regulate TNF-R1 signaling in intestinal epithelium. (PMID:12505880)
• Il-2 and polysaccharide K increased expression of protein kinase C epsilon. (PMID:12536241)
• 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)
• our data suggest that an association of PKCepsilon with Bax may neutralize apoptotic signals propagated through a mitochondrial death-signaling pathway. (PMID:12970744)
• PKC-epsilon is specifically required in the signaling pathway leading to the induction of hsp90 beta gene in response to heat shock. (PMID:14532285)
• PKC epsilon (epsilon) was recently found to be a critical component of TLR-4 signaling pathway and thereby to play a key role in macrophage and dendritic cell (DC) activation in response to LPS [review] (PMID:14643884)
• PKCdelta and PKCepsilon may offer novel targets for development of cancer preventive or therapeutic agents that selectively inactivate PKCepsilon or stimulate PKCdelta. (PMID:14656938)
• A putative Rac1/Cdc42/PKC-alpha pathway is convergent with the PKC-epsilon/MEK1/2 pathway in terms of the activation of JNK by PMA. (PMID:14709334)
• Induction of neurites by the regulatory domain of PKCE is counteracted by PKC catalytic activity and RhoA GTP-binding protein metabolism. (PMID:14720513)
• intramolecular within epsilon PKC is critical and rate limiting in the process of PKC translocation (PMID:14739299)
• protein kinase Cepsilon has a role in phosphorylation of the activation loop of protein kinase D (PMID:15190080)
• Results suggest that the involvement of protein kinase C alpha in carbachol-induced soluble amyloid precursor protein (sAPPalpha) release is negligible, but PKC epsilon may be important in coupling cholinergic receptors with APP metabolism. (PMID:15233804)
• Use of PKC agonists and isozyme-specific pseudosubstrate peptide antagonists suggested a role for PKCalpha and -epsilon in VEGF-mediated DAF up-regulation, mediating A cytoprotective pathway in ECs. (PMID:15284224)
• PKCepsilon plays a critical role in the regulation of ADAM12 cell-surface expression (PMID:15364951)
• a mutually reinforcing signaling loop sustains the activation of beta1 integrins, PKCepsilon, and PKB/Akt in adherent prostate cancer cells (PMID:15467757)
• We analyzed the dependence of the expression of some selected protein kinase C isoenzymes on the availability and/or action of androgens. (PMID:15499829)
• central role of PKC isoforms and the negative regulatory function of c-Src in the control of stromelysin 3 expression (PMID:15509588)
• PAR1 seems to be the responsible receptor for thrombin-induced migration and adhesion of human colon carcinoma cells including PKCepsilon as an essential signal transducer (PMID:15559761)
• diacylglycerol-responsive PKC isoforms differentially influence CaR agonist-induced release of Ca2+ from internal stores (PMID:15572354)
• two fatty acids inhibited the phorbol 12-myristate 13-acetate (PMA)-induced plasma membrane translocation of protein kinase C (PKC)-alpha and -epsilon (PMID:15627650)
• DGK interacts selectively with and is phosphorylated by PKCepsilon and -eta and peptide agonist-induced selective activation of PKCepsilon directly leads to DGK translocation (PMID:15632189)
• Results demonstrate that a branched signaling pathway involving MEK, ERK, PKCepsilon, PKCalpha, and caveolin-1 regulates collagen expression in normal lung tissue and is perturbed during fibrosis. (PMID:15691837)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	prkcea	ENSDARG00000003008
danio_rerio	prkceb	ENSDARG00000069928
mus_musculus	Prkce	ENSMUSG00000045038
rattus_norvegicus	Prkce	ENSRNOG00000015603
drosophila_melanogaster	Pkc53E	FBGN0003091
drosophila_melanogaster	inaC	FBGN0004784
drosophila_melanogaster	Pkn	FBGN0020621
drosophila_melanogaster	Pkcdelta	FBGN0287828
caenorhabditis_elegans		WBGENE00004033
caenorhabditis_elegans		WBGENE00006599
caenorhabditis_elegans		WBGENE00009793

Paralogs (9): PRKCH (ENSG00000027075), PKN2 (ENSG00000065243), PRKCZ (ENSG00000067606), PKN1 (ENSG00000123143), PRKCG (ENSG00000126583), PRKCA (ENSG00000154229), PKN3 (ENSG00000160447), PRKCI (ENSG00000163558), PRKCB (ENSG00000166501)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:97599) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 15 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal uterus morphology	1
dilated uterus	1
decreased body size	1
reduced female fertility	1
increased susceptibility to bacterial infection	1
increased myocardial infarct size	1
decreased T cell proliferation	1
decreased NK cell number	1
decreased dendritic cell number	1
decreased circulating tumor necrosis factor level	1
decreased tumor necrosis factor secretion	1
decreased circulating interleukin-1 beta level	1
decreased total body fat amount	1
decreased macrophage nitric oxide production	1
decreased macrophage apoptosis	1

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	Q5R7A7	100.0%	Diamond
Oryctolagus cuniculus	P05772	99.4%	Diamond
Macaca fascicularis	Q4R4U2	99.4%	Diamond
Bos taurus	P05126	99.3%	Diamond
Xenopus tropicalis	Q5BKK4	99.0%	Diamond
Xenopus laevis	Q6GPN6	98.8%	Diamond
Drosophila sechellia	B4I4Y1	98.1%	Diamond
Drosophila simulans	B4R0A5	98.1%	Diamond
Drosophila yakuba	B4PRE2	97.6%	Diamond
Drosophila erecta	B3NYS4	97.1%	Diamond
Gallus gallus	Q6U1I9	95.8%	Diamond
Sus scrofa	M3TYT0	94.8%	Diamond
Mesocricetus auratus	Q64398	94.2%	Diamond
Caenorhabditis briggsae	A8WUG4	93.5%	Diamond
AKT8 murine leukemia virus	P31748	100.0%	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
PRKCE-AS1	ncRNA	105374580
EPAS1	protein-coding	2034
LINC01820	ncRNA	105374582
SRBD1	protein-coding	55133
LINC01121	ncRNA	400952

Protein

Protein identifiers

Protein kinase C epsilon type — Q02156 (reviewed: Q02156)

Alternative names: nPKC-epsilon

All UniProt accessions (4): C9JR22, Q02156, E9PBI2, L7RTI5

UniProt curated annotations — full annotation on UniProt →

Function. Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays essential roles in the regulation of multiple cellular processes linked to cytoskeletal proteins, such as cell adhesion, motility, migration and cell cycle, functions in neuron growth and ion channel regulation, and is involved in immune response, cancer cell invasion and regulation of apoptosis. Mediates cell adhesion to the extracellular matrix via integrin-dependent signaling, by mediating angiotensin-2-induced activation of integrin beta-1 (ITGB1) in cardiac fibroblasts. Phosphorylates MARCKS, which phosphorylates and activates PTK2/FAK, leading to the spread of cardiomyocytes. Involved in the control of the directional transport of ITGB1 in mesenchymal cells by phosphorylating vimentin (VIM), an intermediate filament (IF) protein. In epithelial cells, associates with and phosphorylates keratin-8 (KRT8), which induces targeting of desmoplakin at desmosomes and regulates cell-cell contact. Phosphorylates IQGAP1, which binds to CDC42, mediating epithelial cell-cell detachment prior to migration. In HeLa cells, contributes to hepatocyte growth factor (HGF)-induced cell migration, and in human corneal epithelial cells, plays a critical role in wound healing after activation by HGF. During cytokinesis, forms a complex with YWHAB, which is crucial for daughter cell separation, and facilitates abscission by a mechanism which may implicate the regulation of RHOA. In cardiac myocytes, regulates myofilament function and excitation coupling at the Z-lines, where it is indirectly associated with F-actin via interaction with COPB1. During endothelin-induced cardiomyocyte hypertrophy, mediates activation of PTK2/FAK, which is critical for cardiomyocyte survival and regulation of sarcomere length. Plays a role in the pathogenesis of dilated cardiomyopathy via persistent phosphorylation of troponin I (TNNI3). Involved in nerve growth factor (NFG)-induced neurite outgrowth and neuron morphological change independently of its kinase activity, by inhibition of RHOA pathway, activation of CDC42 and cytoskeletal rearrangement. May be involved in presynaptic facilitation by mediating phorbol ester-induced synaptic potentiation. Phosphorylates gamma-aminobutyric acid receptor subunit gamma-2 (GABRG2), which reduces the response of GABA receptors to ethanol and benzodiazepines and may mediate acute tolerance to the intoxicating effects of ethanol. Upon PMA treatment, phosphorylates the capsaicin- and heat-activated cation channel TRPV1, which is required for bradykinin-induced sensitization of the heat response in nociceptive neurons. Is able to form a complex with PDLIM5 and N-type calcium channel, and may enhance channel activities and potentiates fast synaptic transmission by phosphorylating the pore-forming alpha subunit CACNA1B (CaV2.2). In prostate cancer cells, interacts with and phosphorylates STAT3, which increases DNA-binding and transcriptional activity of STAT3 and seems to be essential for prostate cancer cell invasion. Downstream of TLR4, plays an important role in the lipopolysaccharide (LPS)-induced immune response by phosphorylating and activating TICAM2/TRAM, which in turn activates the transcription factor IRF3 and subsequent cytokines production. In differentiating erythroid progenitors, is regulated by EPO and controls the protection against the TNFSF10/TRAIL-mediated apoptosis, via BCL2. May be involved in the regulation of the insulin-induced phosphorylation and activation of AKT1. Phosphorylates NLRP5/MATER and may thereby modulate AKT pathway activation in cumulus cells. Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking.

Subunit / interactions. Forms a ternary complex with TRIM63 and RACK1/GN2BL1. Can form a complex with PDLIM5 and N-type calcium channel. Interacts with COPB1. Interacts with DGKQ. Interacts with STAT3. Interacts with YWHAB. Interacts with HSP90AB1; promotes functional activation in a heat shock-dependent manner. Interacts (via phorbol-ester/DAG-type 2 domain) with PRPH and VIM. Interacts with NLRP5/MATER. Interacts with PRKCH upstream open reading frame 2; the interaction leads to inhibition of kinase activity.

Subcellular location. Cytoplasm. Cytoskeleton. Cell membrane. Perinuclear region. Nucleus.

Tissue specificity. Expressed in cumulus cells (at protein level).

Post-translational modifications. Phosphorylation on Thr-566 by PDPK1 triggers autophosphorylation on Ser-729. Phosphorylation in the hinge domain at Ser-350 by MAPK11 or MAPK14, Ser-346 by GSK3B and Ser-368 by autophosphorylation is required for interaction with YWHAB. In response to growth factors, phosphorylated at Thr-703 and Ser-729 by the mTORC2 complex, promoting autophosphorylation and activation of PRKCE.

Activity regulation. Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are calcium-insensitive, but activated by diacylglycerol (DAG) and phosphatidylserine. Three specific sites; Thr-566 (activation loop of the kinase domain), Thr-710 (turn motif) and Ser-729 (hydrophobic region), need to be phosphorylated for its full activation. 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 and the C2 domain is a non-calcium binding domain.

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

RefSeq proteins (1): NP_005391* (*=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
IPR027274	PKC_epsilon	Family
IPR034669	nPKC_epsilon	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR046349	C1-like_sf	Homologous_superfamily

Pfam: PF00069, PF00130, PF00168, PF00433

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-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 (38 total): modified residue 16, sequence variant 5, mutagenesis site 5, domain 3, binding site 2, zinc finger region 2, region of interest 2, chain 1, short sequence motif 1, active site 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
2WH0	Recognition of an intrachain tandem 14-3-3 binding site within protein kinase C epsilon	X-RAY DIFFRACTION	2.25
5LIH	Structure of a peptide-substrate bound to PKCiota core kinase domain	X-RAY DIFFRACTION	3.25

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q02156-F1	80.45	0.47

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Kinases, AGC Ser/Thr protein kinases, Predicted intracellular proteins, Cancer-related genes, Candidate cancer biomarkers, FDA approved drug targets, Small molecule drugs

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; intermediate filaments; plasma membrane; vesicles

Antibody reliability (HPA): IH enhanced · IF supported

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)

Position	Role
532	proton acceptor

Ligand- & substrate-binding residues (2)

Position	Role
414–422	ATP
437	ATP

Post-translational modifications (16)

Type	Positions
Phosphoserine	62, 234, 316, 329, 337, 346, 350, 368, 388, 729
Phosphothreonine	228, 309, 349, 566, 703, 710

Mutagenesis-validated functional residues (5)

Position	Phenotype
437	abolishes activity and s-729 phosphorylation.
566	abolishes phosphorylation by pdpk1/pdk1, and s-729 phosphorylation.
566	no effect on s-729 phosphorylation.
710	no effect on activity; no effect on s-729 phosphorylation.
729	enhances t-566 dephosphorylation.

Function

Pathways and Gene Ontology

Reactome pathways

4 curated (TAS) of 17; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

17 pathways:

ID	Pathway	Evidence
R-HSA-1489509	DAG and IP3 signaling	curated
R-HSA-114508	Effects of PIP2 hydrolysis	curated
R-HSA-2029485	Role of phospholipids in phagocytosis	curated
R-HSA-1250196	SHC1 events in ERBB2 signaling	curated
R-HSA-2029480	Fcgamma receptor (FCGR) dependent phagocytosis	—
R-HSA-416476	G alpha (q) signalling events	—
R-HSA-418597	G alpha (z) signalling events	electronic
R-HSA-388396	GPCR downstream signalling	—
R-HSA-109582	Hemostasis	—
R-HSA-168256	Immune System	—
R-HSA-168249	Innate Immune System	—
R-HSA-9006925	Intracellular signaling by second messengers	—
R-HSA-76002	Platelet activation, signaling and aggregation	—
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	—

MSigDB gene sets: 581 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_RESPONSE_TO_ETHANOL, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, TAATAAT_MIR126, REACTOME_INNATE_IMMUNE_SYSTEM, BENPORATH_ES_WITH_H3K27ME3, GOBP_BEHAVIOR, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_NEGATIVE_REGULATION_OF_SODIUM_ION_TRANSPORT, GOBP_RESPONSE_TO_PROSTAGLANDIN_E, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, REACTOME_G_ALPHA_Z_SIGNALLING_EVENTS

GO Biological Process (24): apoptotic process (GO:0006915), cell adhesion (GO:0007155), signal transduction (GO:0007165), toxin catabolic process (GO:0009407), positive regulation of epithelial cell migration (GO:0010634), positive regulation of fibroblast migration (GO:0010763), positive regulation of actin filament polymerization (GO:0030838), negative regulation of protein ubiquitination (GO:0031397), lipopolysaccharide-mediated signaling pathway (GO:0031663), positive regulation of cytokinesis (GO:0032467), positive regulation of superoxide anion generation (GO:0032930), regulation of actin cytoskeleton organization (GO:0032956), intracellular signal transduction (GO:0035556), TRAM-dependent toll-like receptor 4 signaling pathway (GO:0035669), Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096), xenobiotic catabolic process (GO:0042178), cell division (GO:0051301), positive regulation of wound healing (GO:0090303), negative regulation of sodium ion transmembrane transport (GO:1902306), positive regulation of protein localization to plasma membrane (GO:1903078), immune system process (GO:0002376), protein phosphorylation (GO:0006468), regulation of metal ion transport (GO:0010959), regulation of monoatomic cation transmembrane transport (GO:1904062)

GO Molecular Function (18): actin monomer binding (GO:0003785), protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), diacylglycerol-dependent serine/threonine kinase activity (GO:0004697), diacylglycerol-dependent, calcium-independent serine/threonine kinase activity (GO:0004699), ATP binding (GO:0005524), enzyme activator activity (GO:0008047), zinc ion binding (GO:0008270), enzyme binding (GO:0019899), signaling receptor activator activity (GO:0030546), ethanol binding (GO:0035276), 14-3-3 protein binding (GO:0071889), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (12): nucleus (GO:0005634), cytoplasm (GO:0005737), mitochondrion (GO:0005739), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), intermediate filament cytoskeleton (GO:0045111), perinuclear region of cytoplasm (GO:0048471), cell periphery (GO:0071944), cytoskeleton (GO:0005856), membrane (GO:0016020)

Reactome top-level categories

12 top-level categories:

Category	Pathways
Signal Transduction	3
GPCR downstream signalling	2
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
Signaling by Receptor Tyrosine Kinases	1
Immune System	1
Innate Immune System	1
Signaling by GPCR	1
Hemostasis	1

GO top-level categories

showing 60 of 86 GO namespaces:

Category	Terms
cellular anatomical structure	5
cytoplasm	5
intracellular membrane-bounded organelle	4
cellular process	3
catabolic process	2
positive regulation of cell migration	2
intracellular anatomical structure	2
protein kinase activity	2
anion binding	2
catalytic activity	2
molecular function activator activity	2
protein binding	2
endomembrane system	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
toxin metabolic process	1
detoxification	1
epithelial cell migration	1
regulation of epithelial cell migration	1
fibroblast migration	1
regulation of fibroblast migration	1
actin filament polymerization	1
regulation of actin filament polymerization	1
positive regulation of protein polymerization	1
positive regulation of cytoskeleton organization	1
positive regulation of supramolecular fiber organization	1
protein ubiquitination	1
regulation of protein ubiquitination	1
negative regulation of protein modification by small protein conjugation or removal	1
cell surface receptor signaling pathway	1
cellular response to lipopolysaccharide	1
cytokinesis	1
regulation of cytokinesis	1
positive regulation of cell division	1
positive regulation of cell cycle process	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
signal transduction	1
toll-like receptor 4 signaling pathway	1
TRAM-dependent toll-like receptor signaling pathway	1
Fc receptor mediated stimulatory signaling pathway	1
phagocytosis	1
Fc-gamma receptor signaling pathway	1
xenobiotic metabolic process	1
wound healing	1
regulation of wound healing	1
positive regulation of response to wounding	1
negative regulation of sodium ion transport	1
sodium ion transmembrane transport	1
regulation of sodium ion transmembrane transport	1
negative regulation of cation transmembrane transport	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 16 of 54 annotations. The rest are phylogenetic / computational / electronic (IEA).

16 experimentally-supported GO terms:

GO term	NS	Evidence
positive regulation of cytokinesis	BP	mutant phenotype
positive regulation of epithelial cell migration	BP	mutant phenotype
positive regulation of wound healing	BP	mutant phenotype
regulation of actin cytoskeleton organization	BP	direct assay
toxin catabolic process	BP	direct assay
xenobiotic catabolic process	BP	mutant phenotype
cytoplasm	CC	direct assay
cytosol	CC	direct assay
endoplasmic reticulum	CC	direct assay
intermediate filament cytoskeleton	CC	direct assay
plasma membrane	CC	direct assay
diacylglycerol-dependent, calcium-independent serine/threonine kinase activity	MF	direct assay
enzyme activator activity	MF	mutant phenotype
enzyme binding	MF	physical interaction
protein kinase activity	MF	direct assay
protein serine/threonine kinase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,472 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRKCE	CACNA1B	Q00975	687
PRKCE	COPB2	P35606	650
PRKCE	IRS2	Q9Y4H2	558
PRKCE	ELOVL6	Q9H5J4	548
PRKCE	SIRT3	Q9NTG7	543
PRKCE	RACK1	P25388	539
PRKCE	ECE1	P42892	527
PRKCE	ECE2	P0DPD6	520
PRKCE	TRPV1	Q8NER1	518
PRKCE	TRPA1	O75762	510
PRKCE	PIRT	P0C851	497
PRKCE	A0A0A0MSP3	A0A0A0MSP3	496
PRKCE	EEF1AKMT4-ECE2	P0DPD8	493
PRKCE	GRHL3	Q8TE85	492
PRKCE	SLC9A8	Q9Y2E8	486

IntAct

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

26 partners by confidence:

Partner	Interaction type	MIscore	Records
YWHAZ	direct interaction	0.730	5
HSP90AB1	physical association	0.640	2
BRAF	physical association	0.590	3
APP	physical association	0.560	3
SNCA	physical association	0.560	3
YWHAE	physical association	0.560	2
PRKCA	physical association	0.560	1
SFN	physical association	0.560	1
EGFR	physical association	0.550	2
MAPKAP1	physical association	0.520	2
PECAM1	direct interaction	0.440	1
PKM	phosphorylation reaction	0.440	1
PRKD1	phosphorylation reaction	0.440	1
TICAM2	phosphorylation reaction	0.440	1
UGT1A7	phosphorylation reaction	0.440	1
IL32	physical association	0.400	2
RPS6KA2	physical association	0.400	2
BAX	physical association	0.400	1
PDPK1	physical association	0.400	1
PPP1R15A	physical association	0.400	1
CST4	association	0.350	1
PAPSS1	association	0.350	1
PRPSAP2	association	0.350	1
SRP54	association	0.350	1
DSP	physical association	0.000	1
MAP4K4	physical association	0.000	1

BioGRID (176 interactions; top human partners by supporting records): GNB2L1 (Far Western; 4 records), RAD9A (Affinity Capture-Western; 4 records), EGFR (Two-hybrid; 3 records), HSP90AA1 (Affinity Capture-Western; 3 records), HSP90AB1 (Affinity Capture-MS; 3 records), VDAC1 (Affinity Capture-Western; 3 records), YWHAZ (Affinity Capture-MS; 3 records), ACTA1 (Affinity Capture-Western; 2 records), BAD (Affinity Capture-Western; 2 records), BRAF (Affinity Capture-Western; 2 records), CDC37 (Affinity Capture-MS; 2 records), CFTR (Affinity Capture-Western; 2 records), COPB2 (Affinity Capture-Western; 2 records), IKBKB (Affinity Capture-Western; 2 records), IL32 (Affinity Capture-Western; 2 records)

SIGNOR signaling

showing 42 of 86 signaling interactions:

A	Effect	B	Mechanism
PDPK1	up-regulates	PRKCE	phosphorylation
PRKCE	down-regulates	PRKCE	phosphorylation
PRKCE	up-regulates	IQGAP1	phosphorylation
PRKCE	up-regulates	CHAT	phosphorylation
PRKCE	up-regulates	STAT3	phosphorylation
PRKCE	up-regulates	GJA1	phosphorylation
PRKCE	up-regulates	TICAM2	phosphorylation
PRKCE	down-regulates	KIR3DL1	phosphorylation
PRKCE	down-regulates	BAD	phosphorylation
PRKCE	down-regulates	CTNND1	phosphorylation
PRKCE	up-regulates	OCLN	phosphorylation
GSK3B	up-regulates	PRKCE	phosphorylation
“bisindolylmaleimide i”	down-regulates	PRKCE	“chemical inhibition”
3-(1-methyl-3-indolyl)-4-[1-[1-(2-pyridinylmethyl)-4-piperidinyl]-3-indolyl]pyrrole-2,5-dione	down-regulates	PRKCE	“chemical inhibition”
PRKCE	up-regulates	ATF2	phosphorylation
PRKCE	up-regulates	FGFR1	phosphorylation
PRKCE	up-regulates	FGFR2	phosphorylation
1,2-diacyl-sn-glycerol	“up-regulates activity”	PRKCE	binding
PRKCE	unknown	OPRD1	phosphorylation
PRKCE	“up-regulates activity”	SLC4A3	phosphorylation
PRKCE	“up-regulates activity”	TRPV1	phosphorylation
PRKCE	“up-regulates activity”	PPP1R14A	phosphorylation
PRKCE	“down-regulates activity”	NOS3	phosphorylation
PRKCE	“up-regulates activity”	NLRP5	phosphorylation
TRIM41	“down-regulates quantity by destabilization”	PRKCE	polyubiquitination
PRKCE	“up-regulates activity”	MIIP	phosphorylation
PRKCE	“down-regulates quantity by destabilization”	NREP	phosphorylation
mTORC2	“up-regulates activity”	PRKCE	phosphorylation
MAPKAP1	“up-regulates activity”	PRKCE	binding
PRKCE	“up-regulates activity”	GLS	phosphorylation
PRKCE	“up-regulates activity”	NANOG	phosphorylation
PRKCE	“up-regulates activity”	NSF	phosphorylation
PRKCE	“up-regulates activity”	IKBKB	phosphorylation
PRKCE	“down-regulates activity”	GSK3B	phosphorylation
PRKCE	“up-regulates activity”	KAT5	phosphorylation
PRKCE	“up-regulates activity”	RHOA	phosphorylation
PRKCE	“down-regulates quantity”	STXBP1	phosphorylation
PRKCE	“up-regulates quantity”	DLG4	phosphorylation
PRKCE	up-regulates	PRKD2	phosphorylation
PRKCE	unknown	RPS6KB2	phosphorylation
PRKCE	“up-regulates activity”	SHC1	phosphorylation
PRKCE	“down-regulates activity”	GJA1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 26 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
Apoptosis	5	36.5×	2e-05
Programmed Cell Death	5	31.8×	4e-05
Transcriptional Regulation by TP53	5	13.5×	1e-03
Signaling by Receptor Tyrosine Kinases	5	11.2×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	5	15.7×	1e-03
protein phosphorylation	5	13.6×	2e-03
negative regulation of apoptotic process	7	9.7×	9e-04
intracellular signal transduction	6	9.2×	2e-03

Disease & clinical

Genetic variants

Variant evidence for PRKCE: 68 ClinVar records (2 pathogenic / likely pathogenic); 2 PharmGKB clinical annotations; 91 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	41
Likely benign	3
Benign	4

Top pathogenic / likely-pathogenic (2)

Showing all 2 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
453227	NM_005400.3(PRKCE):c.1795G>A (p.Glu599Lys)	Pathogenic	criteria provided, single submitter	2
4071986	NM_005400.3(PRKCE):c.982G>C (p.Glu328Gln)	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore PRKCE’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; 35 predictions of 3,370):

Position(s)	Effect	Δscore	Sites
2:45652449–45652450	donor_loss	1.0000	5
2:45842998–45842999	acceptor_loss	1.0000	5
2:45976410	acceptor_gain	1.0000
2:45976416	acceptor_gain	1.0000
2:45976427–45976428	acceptor_loss	1.0000	6
2:45976589–45976590	donor_loss	1.0000	5
2:45980294–45980295	acceptor_loss	1.0000	6
2:45980382–45980383	donor_loss	1.0000	4
2:46001391	acceptor_gain	1.0000
2:46001401	acceptor_gain	1.0000

AlphaMissense

2,935 missense substitutions predicted likely pathogenic (of 4,898 scored), across 575 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M495	9	0.998	1.000
M553	9	0.998	1.000
M486	9	0.994	1.000
M600	9	0.991	1.000
M173	9	0.969	0.997
D449	8	1.000	1.000
D493	8	1.000	1.000
D532	8	1.000	1.000
D536	8	1.000	1.000
N537	8	1.000	1.000
D550	8	1.000	1.000
D589	8	1.000	1.000
H170	8	0.999	1.000
H209	8	0.999	1.000
H281	8	0.999	1.000
F419	8	0.999	1.000
D572	8	0.999	1.000
F607	8	0.999	1.000
F698	8	0.999	1.000
D699	8	0.999	1.000

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	1.41e-10
Rectum Adenocarcinoma (TCGA)	unfavorable	0.000847

Disease associations

OMIM: gene MIM:176975 | disease phenotypes:

GWAS associations

showing 30 of 91 associations:

Study	Trait	p-value
GCST90002384_345	Hemoglobin	2e-237
GCST010083_53	Hemoglobin levels	2e-182
GCST90002383_326	Hematocrit	2e-168
GCST90002403_570	Red blood cell count	1e-117
GCST004604_24	Hematocrit	7e-95
GCST90002383_324	Hematocrit	5e-88
GCST004615_78	Hemoglobin concentration	1e-85
GCST004601_65	Red blood cell count	4e-66
GCST90002384_344	Hemoglobin	1e-53
GCST90002403_569	Red blood cell count	1e-39
GCST004601_63	Red blood cell count	2e-39
GCST005994_19	Hematocrit	3e-39
GCST005996_14	Red blood cell count	1e-36
GCST90002403_521	Red blood cell count	2e-33
GCST005995_7	Hemoglobin	3e-32
GCST90002383_196	Hematocrit	4e-32
GCST90002384_517	Hemoglobin	1e-27
GCST006979_977	Heel bone mineral density	5e-25
GCST004601_64	Red blood cell count	1e-24
GCST90002384_516	Hemoglobin	3e-22
GCST90002402_429	Platelet count	4e-21
GCST004005_5	Hemoglobin levels	1e-20
GCST004003_6	Hematocrit	1e-19
GCST001765_17	Red blood cell traits	3e-19
GCST90002383_194	Hematocrit	7e-19
GCST90002403_568	Red blood cell count	4e-18
GCST004412_1	Craniofacial microsomia	1e-17
GCST007269_44	Pulse pressure	2e-17
GCST90002400_90	Plateletcrit	2e-17
GCST90002384_346	Hemoglobin	2e-16

EFO canonical traits (from GWAS)

25 canonical traits:

EFO ID	Trait name
EFO:0004509	hemoglobin measurement
EFO:0004348	hematocrit
EFO:0004305	erythrocyte count
EFO:0004321	attempted suicide
EFO:0005276	hydroxy-leucine measurement
EFO:0006995	response to diisocyanate
EFO:0005921	FEV change measurement
EFO:0007707	cerebral amyloid deposition measurement
EFO:0007893	alpha-carotene measurement
EFO:0005763	pulse pressure measurement
EFO:0006336	diastolic blood pressure
EFO:0007986	reticulocyte count
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0009270	heel bone mineral density
EFO:0006335	systolic blood pressure
EFO:0008392	triiodothyronine measurement
EFO:0004338	body weight
EFO:0004340	body mass index
EFO:0010543	uridine diphosphate galactose measurement
EFO:0010544	uridine diphosphate glucose measurement
EFO:0004980	appendicular lean mass
EFO:0005091	monocyte count
EFO:0007985	platelet crit
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2093867 (PROTEIN FAMILY), CHEMBL2096620 (PROTEIN FAMILY), CHEMBL3582 (SINGLE PROTEIN)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the PRKCE 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
KAI-1678	Unknown	2

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 405,912 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

21 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL288441	BOSUTINIB	4	12,869
CHEMBL1287853	FEDRATINIB	4	3,770
CHEMBL1863513	INGENOL MEBUTATE	4	1,527
CHEMBL608533	MIDOSTAURIN	4	7,641
CHEMBL1789941	RUXOLITINIB	4	12,161
CHEMBL83	TAMOXIFEN	4	173,287
CHEMBL428690	ALVOCIDIB	3	28,145
CHEMBL140	CURCUMIN	3	95,185
CHEMBL300138	ENZASTAURIN	3	3,401
CHEMBL2107337	ENZASTAURIN HYDROCHLORIDE	3	552
CHEMBL38380	FASUDIL	3	12,137
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3	78
CHEMBL265502	SURAMIN	3	37,133
CHEMBL3982723	DAROVASERTIB	2	503
CHEMBL28509	EDELFOSINE	2	10,657
CHEMBL279115	PHORBOL MYRISTATE ACETATE	2	1,427
CHEMBL565612	SOTRASTAURIN	2	1,414
CHEMBL574737	UCN-01	2	2,319
CHEMBL3137336	UPROSERTIB	2	1,706
CHEMBL494089	GSK-690693	1

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

2 annotations by evidence level (1 strongest → 4):

Variant	Association	Level	Drugs	Phenotypes
rs11125035	Toxicity	3	radiotherapy
rs11125039	Toxicity	3	sorafenib	Hypertension

PharmGKB variants

2 variants:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs11125035	PRKCE	3	3.00	1	radiotherapy
rs11125039	PRKCE	3	2.50	1	sorafenib

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

5 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs6720975	donepezil, galantamine, rivastigmine	Efficacy	Allele T is associated with increased response to donepezil, galantamine and rivastigmine in people with Alzheimer Disease as compared to allele C.	PMID:23374588
rs940052	radiotherapy	Toxicity	Allele G is associated with decreased risk of Esophagitis when treated with radiotherapy as compared to allele A.	PMID:25054431
rs11125035	radiotherapy	Toxicity	Allele T is associated with decreased risk of Esophagitis when treated with radiotherapy as compared to allele A.	PMID:25054431
rs11125039	sorafenib	Toxicity	Allele G is associated with increased risk of Hypertension when treated with sorafenib in people with Carcinoma, Renal Cell as compared to allele A.	PMID:35484400
rs2278773	perphenazine	Efficacy	Allele C is associated with response to perphenazine in people with Schizophrenia.	PMID:22920393

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Eta subfamily

Most potent curated ligand interactions (9 total), top 9:

Ligand	Action	Affinity	Parameter
ingenol mebutate	Activation	9.77	pKi
10-Me-Aplog-1	Activation	8.7	pKi
sotrastaurin	Inhibition	8.21	pIC50
balanol	Inhibition	7.7	pIC50
RasGRP activator 1	Binding	7.68	pKi
chelerythrine	Inhibition	7.62	pIC50
Ro-32-0432	Inhibition	6.97	pIC50
ninvosudil	Inhibition	6.47	pIC50
7-hydroxystaurosporine	Inhibition	6.28	pIC50

Binding affinities (BindingDB)

624 measured of 862 human assays (883 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
CHEMBL4528495	IC50	0.15 nM
CHEMBL4538431	IC50	0.17 nM
CHEMBL4443190	IC50	0.18 nM
CHEMBL3741746	EC50	0.19 nM
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
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
Bryostatin	KD	0.44 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
maleimide derivative, 12	IC50	0.9 nM
CHEMBL2153750	IC50	1 nM
DEMETHOXYDEBROMOAPLYSIATOXIN	KI	1 nM
Compound K-252a(epi)	IC50	1.2 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
maleimide derivative, 10	IC50	2.2 nM
CHEMBL83790	IC50	2.2 nM
CHEMBL4083319	IC50	2.7 nM
CHEMBL4101316	IC50	2.8 nM
2-{3-[2-Benzo[b]thiophen-2-yl-3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl)-indol-1-yl]-propyl}-isothiourea	IC50	3 nM
CHEMBL2071201	IC50	3 nM
corilagin	EC50	3.2 nM
CHEMBL4089217	IC50	3.4 nM
CEP-701	KD	3.4 nM
CHEMBL2153747	IC50	3.6 nM
CHEMBL2153749	IC50	3.6 nM
CHEMBL4064291	IC50	3.7 nM
23-ethyl-17,20-dioxa-4,14,23,26-tetraazahexacyclo[24.6.1.17,14.02,6.08,13.027,32]tetratriaconta-1(33),2(6),7(34),8(13),9,11,27(32),28,30-nonaene-3,5-dione	IC50	4 nM
CHEMBL2153755	IC50	4.5 nM
Z-[2-(Hydroxymethyl)-4-(3-methylbutylidene)-5-oxo-2-(2,3-dihydrofuryl)]methyl 5-Methyl-3-(2-methylpropyl)hexanoate	KI	4.7 nM
CHEMBL4089665	IC50	4.7 nM
CHEMBL2148108	KI	4.7 nM
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	IC50	5.6 nM	US-8822500: Tyrosine kinase inhibitors
17,23-dimethyl-20-oxa-4,14,17,23,26-pentaazahexacyclo[24.6.1.17,14.02,6.08,13.027,32]tetratriaconta-1(33),2(6),7(34),8(13),9,11,27(32),28,30-nonaene-3,5-dione	IC50	6 nM
CHEMBL2151412	IC50	6.4 nM
Staurosporine, 8	IC50	6.5 nM
maleimide derivative, 11	IC50	7.1 nM

ChEMBL bioactivities

783 potent at pChembl≥5 of 909 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
9.85	IC50	0.143	nM	STAUROSPORINE
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
9.70	IC50	0.198	nM	STAUROSPORINE
9.66	Kd	0.22	nM	CHEMBL27768
9.66	IC50	0.22	nM	CHEMBL4435580
9.60	Kd	0.25	nM	STAUROSPORINE
9.54	IC50	0.286	nM	STAUROSPORINE
9.44	IC50	0.36	nM	CHEMBL4587471
9.43	Kd	0.37	nM	CHEMBL337834
9.35	Ki	0.45	nM	PHORBOL MYRISTATE ACETATE
9.33	Ki	0.47	nM	CHEMBL399981
9.26	EC50	0.55	nM	CHEMBL4587471
9.26	Ki	0.55	nM	CHEMBL337834
9.24	Ki	0.58	nM	CHEMBL265998
9.23	Kd	0.59	nM	CHEMBL27768
9.22	IC50	0.6	nM	STAUROSPORINE
9.22	EC50	0.6	nM	CHEMBL4575056
9.20	Ki	0.63	nM	DEBROMOAPLYSIATOXIN
9.15	IC50	0.7	nM	CHEMBL2151411
9.09	Kd	0.81	nM	CHEMBL27768
9.05	IC50	0.9	nM	CHEMBL1996510
9.00	Ki	1	nM	CHEMBL2326002
9.00	IC50	1	nM	STAUROSPORINE
9.00	Ki	1	nM	CHEMBL285801
8.99	Ki	1.03	nM	CHEMBL137386
8.92	Ki	1.21	nM	CHEMBL3393748
8.89	Ki	1.3	nM	DEMETHOXYDEBROMOAPLYSIATOXIN
8.89	Ki	1.3	nM	APLYSIATOXIN
8.87	Ki	1.35	nM	CHEMBL27768
8.85	Ki	1.43	nM	CHEMBL137386
8.82	Kd	1.5	nM	CHEMBL27768
8.82	IC50	1.5	nM	STAUROSPORINE
8.80	IC50	1.6	nM	CHEMBL1080994
8.77	IC50	1.7	nM	CHEMBL291126
8.72	Ki	1.89	nM	CHEMBL137386
8.70	IC50	2	nM	CHEMBL162621
8.70	IC50	2	nM	STAUROSPORINE
8.70	Ki	2	nM	CHEMBL2148108
8.70	IC50	2	nM	CHEMBL2153750
8.70	IC50	2	nM	CHEMBL1084411
8.67	Ki	2.14	nM	CHEMBL3393741
8.66	Ki	2.17	nM	CHEMBL3289012
8.66	IC50	2.2	nM	CHEMBL83790

PubChem BioAssay actives

622 with measured affinity, of 2353 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
[(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	1189624: Displacement of [20-3H] phorbol 12, 13-dibutylate from recombinant PKCepsilon (unknown origin) in presence of 100 ug/ml 100% phosphatidylserine	kd	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
[(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	218937: Inhibition of [3H]-phorbol 12,13-dibutyrate (PDBu) binding to human recombinant protein kinase C epsilon	ki	0.0004	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	163699: Binding affinity for human Protein kinase C epsilon	kd	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	312188: Displacement of [3H]PDBu from PKCepsilon 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	163849: Displacement of 3[H]PDBu from Protein kinase C epsilon C1b domain	ki	0.0006	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	687833: Inhibition of [3H]PDBu binding to PKCepsilon C1B domain	ki	0.0006	uM
3-(7-methyl-1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione	690001: Inhibition of PKCepsilon by scintillation proximity assay	ic50	0.0007	uM
3-(1H-indol-3-yl)-4-(2-piperazin-1-ylquinazolin-4-yl)pyrrole-2,5-dione	690001: Inhibition of PKCepsilon by scintillation proximity assay	ic50	0.0009	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	163837: Displacement of [3H]- PDBu from recombinant PKC epsilon expressed in baculovirus	ki	0.0010	uM
(2R)-2-[(2S)-4-[3-chloro-5-fluoro-6-(2H-pyrazolo[3,4-b]pyridin-3-yl)-2-pyridinyl]piperazin-2-yl]-3-methylbutan-2-ol	728534: Inhibition of PKC epsilon (unknown origin)	ki	0.0010	uM
[(4E)-2-(hydroxymethyl)-4-[5-methyl-3-(2-methylpropyl)hexylidene]-5-oxooxolan-2-yl]methyl 2,2-dimethylpropanoate	1189624: Displacement of [20-3H] phorbol 12, 13-dibutylate from recombinant PKCepsilon (unknown origin) in presence of 100 ug/ml 100% phosphatidylserine	ki	0.0010	uM
[(4E)-2-(hydroxymethyl)-4-(3-methylbutylidene)-5-oxooxolan-2-yl]methyl 5-methyl-3-(2-methylpropyl)hexanoate	1189624: Displacement of [20-3H] phorbol 12, 13-dibutylate from recombinant PKCepsilon (unknown origin) in presence of 100 ug/ml 100% phosphatidylserine	ki	0.0012	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	517267: Inhibition of [3H]PDBu binding to PKCepsilon C1B peptide	ki	0.0013	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	768062: Displacement of [3H]PDBu from PKCepsilon C1B domain (unknown origin)	ki	0.0013	uM
4-[(4-methyl-1H-indol-5-yl)amino]-5-[(E)-2-[3-(4-methylpiperazin-1-yl)sulfonylphenyl]ethenyl]pyridine-3-carbonitrile	469099: Inhibition of PKCepsilon	ic50	0.0016	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
4-[(4-methyl-1H-indol-5-yl)amino]-5-[(E)-2-[6-[(4-methylpiperazin-1-yl)methyl]-2-pyridinyl]ethenyl]pyridine-3-carbonitrile	463342: Inhibition of PKCepsilon	ic50	0.0020	uM
3-[6-fluoro-2-(4-methylpiperazin-1-yl)quinazolin-4-yl]-4-(1H-indol-3-yl)pyrrole-2,5-dione	690001: Inhibition of PKCepsilon by scintillation proximity assay	ic50	0.0020	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	687833: Inhibition of [3H]PDBu binding to PKCepsilon C1B domain	ki	0.0020	uM
[(4E)-2-(hydroxymethyl)-4-(3-methylbutylidene)-5-oxooxolan-2-yl]methyl (9E,12E)-octadeca-9,12-dienoate	1189624: Displacement of [20-3H] phorbol 12, 13-dibutylate from recombinant PKCepsilon (unknown origin) in presence of 100 ug/ml 100% phosphatidylserine	ki	0.0021	uM
[(4E)-2-(hydroxymethyl)-4-[(1-methylindol-5-yl)methylidene]-5-oxooxolan-2-yl]methyl 2-propylpentanoate	1152263: Displacement of [3H]PDBu from recombinant human PKC-epsilon after 5 mins by scintillation counting analysis in presence of phosphatidylserine	ki	0.0022	uM
[(4Z)-2-(hydroxymethyl)-4-(3-methylbutylidene)-5-oxooxolan-2-yl]methyl 5-methyl-3-(2-methylpropyl)hexanoate	1189624: Displacement of [20-3H] phorbol 12, 13-dibutylate from recombinant PKCepsilon (unknown origin) in presence of 100 ug/ml 100% phosphatidylserine	ki	0.0024	uM
4-[(4-methyl-1H-indol-5-yl)amino]-5-[5-[(4-methylpiperazin-1-yl)methyl]-1-benzofuran-2-yl]pyridine-3-carbonitrile	447961: Inhibition of PKCepsilon by IMAP fluorescence polarization technology	ic50	0.0025	uM
4-[(4-methyl-1H-indol-5-yl)amino]-5-[(E)-4-piperazin-1-ylbut-1-enyl]pyridine-3-carbonitrile	453670: Inhibition of PKCepsilon by fluorescence polarization assay	ic50	0.0025	uM
[(4E)-4-[(4-chlorophenyl)methylidene]-2-(hydroxymethyl)-5-oxooxolan-2-yl]methyl 2,2-dimethylpropanoate	1505437: Displacement of [3H]PDBu from full length recombinant human PKCepsilon expressed in baculovirus expression system after 5 mins by scintillation counting	ki	0.0026	uM
3-amino-N-[3-(4-amino-4-methylpiperidin-1-yl)-2-pyridinyl]-6-[3-(trifluoromethyl)-2-pyridinyl]pyrazine-2-carboxamide	2098509: Inhibition of PKCepsilon (unknown origin)	ic50	0.0029	uM
3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione	1902443: Inhibition of PKCepsilon (unknown origin) by IMAP kinase assay	ic50	0.0032	uM
3-(1-methylindol-3-yl)-4-(2-piperazin-1-ylquinazolin-4-yl)pyrrole-2,5-dione	690001: Inhibition of PKCepsilon by scintillation proximity assay	ic50	0.0038	uM
3-[6-chloro-2-(4-methylpiperazin-1-yl)quinazolin-4-yl]-4-(1H-indol-3-yl)pyrrole-2,5-dione	690001: Inhibition of PKCepsilon by scintillation proximity assay	ic50	0.0039	uM
[(4E)-2-(hydroxymethyl)-4-[(9Z,12Z)-octadeca-9,12-dienylidene]-5-oxooxolan-2-yl]methyl 2,2-dimethylpropanoate	1189624: Displacement of [20-3H] phorbol 12, 13-dibutylate from recombinant PKCepsilon (unknown origin) in presence of 100 ug/ml 100% phosphatidylserine	ki	0.0041	uM
3-(1H-indol-3-yl)-4-[3-(4-methylpiperazin-1-yl)isoquinolin-1-yl]pyrrole-2,5-dione	690001: Inhibition of PKCepsilon by scintillation proximity assay	ic50	0.0043	uM
3-[2-chloro-6-[(dimethylamino)methyl]naphthalen-1-yl]-4-(1H-indol-3-yl)pyrrole-2,5-dione	1437220: Inhibition of PKCepsilon (unknown origin) after 60 mins in presence of [gamma33P]ATP by scintillation proximity assay	ic50	0.0043	uM
[(4E)-2-(hydroxymethyl)-4-(3-methylbutylidene)-5-oxooxolan-2-yl]methyl octadec-9-ynoate	1189624: Displacement of [20-3H] phorbol 12, 13-dibutylate from recombinant PKCepsilon (unknown origin) in presence of 100 ug/ml 100% phosphatidylserine	ki	0.0048	uM
N’-(3-pyridin-4-yl-2,6-naphthyridin-1-yl)ethane-1,2-diamine	688997: Inhibition of recombinant human PKCepsilon assessed as [33P]-ATP incorporation into tridecapeptide substrate after 60 mins by scintillation proximity assay	ic50	0.0050	uM
(2S)-1-N-(3-pyridin-4-yl-2,6-naphthyridin-1-yl)propane-1,2-diamine	688997: Inhibition of recombinant human PKCepsilon assessed as [33P]-ATP incorporation into tridecapeptide substrate after 60 mins by scintillation proximity assay	ic50	0.0050	uM
[(4Z)-2-(hydroxymethyl)-4-[(9Z,12Z)-octadeca-9,12-dienylidene]-5-oxooxolan-2-yl]methyl 2,2-dimethylpropanoate	1189624: Displacement of [20-3H] phorbol 12, 13-dibutylate from recombinant PKCepsilon (unknown origin) in presence of 100 ug/ml 100% phosphatidylserine	ki	0.0051	uM
[(4E)-2-(hydroxymethyl)-4-(3-methylbutylidene)-5-oxooxolan-2-yl]methyl octadeca-9,11-diynoate	1189624: Displacement of [20-3H] phorbol 12, 13-dibutylate from recombinant PKCepsilon (unknown origin) in presence of 100 ug/ml 100% phosphatidylserine	ki	0.0052	uM
4-[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-[[(3S)-piperidin-3-yl]methoxy]imidazo[4,5-c]pyridin-4-yl]-2-methylbut-3-yn-2-ol	625014: Binding constant for PRKCE kinase domain	kd	0.0053	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
[(4E)-2-(hydroxymethyl)-4-(3-methylbutylidene)-5-oxooxolan-2-yl]methyl 8-[2-[(2-pentylcyclopropyl)methyl]cyclopropyl]octanoate	1189624: Displacement of [20-3H] phorbol 12, 13-dibutylate from recombinant PKCepsilon (unknown origin) in presence of 100 ug/ml 100% phosphatidylserine	ki	0.0055	uM
3-[3-[2-(dimethylamino)ethoxy]naphthalen-1-yl]-4-(1H-indol-3-yl)pyrrole-2,5-dione	1799253: Protein Kinase Assays from Article 10.1021/jm901108b: “Discovery of 3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione (AEB071), a potent and selective inhibitor of protein kinase C isotypes.”	ic50	0.0055	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tetradecanoylphorbol Acetate	increases activity, increases localization, affects reaction, increases expression, affects localization (+1 more)	4
Aflatoxin B1	affects methylation, decreases expression, decreases methylation	4
trichostatin A	affects cotreatment, increases expression	3
Benzo(a)pyrene	decreases methylation, affects methylation, decreases expression	3
Curcumin	decreases expression, decreases reaction, increases expression, decreases response to substance	3
Estradiol	affects cotreatment, decreases expression, affects binding, increases reaction, increases expression	3
bisphenol A	increases expression, decreases methylation	2
Arsenic	decreases expression, increases abundance, affects methylation	2
Calcium	increases abundance, increases activity, increases reaction, increases phosphorylation, decreases reaction (+1 more)	2
Formaldehyde	decreases expression	2
Thiram	increases expression, decreases activity	2
Valproic Acid	affects cotreatment, increases expression	2
Palmitic Acid	increases phosphorylation	2
FR900359	affects phosphorylation	1
methyleugenol	decreases expression	1
diphenyleneiodonium	affects localization, decreases reaction	1
gingerol	affects reaction, increases expression	1
morin	decreases expression	1
methylparaben	decreases expression	1
chelerythrine	decreases reaction, increases phosphorylation	1
mono-(2-ethylhexyl)phthalate	increases expression, affects reaction	1
sodium arsenite	decreases expression, increases abundance	1
cobaltous chloride	decreases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	decreases expression	1
aflatoxin B2	decreases methylation	1
puag-haad	increases expression, decreases reaction	1
droloxifene	affects localization	1
di-n-butylphosphoric acid	affects expression	1
bisindolylmaleimide I	decreases expression, decreases reaction, increases expression	1

ChEMBL screening assays

722 unique, capped per target: 707 binding, 14 functional, 1 admet

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*
CHEMBL4048341	ADMET	Inhibition of partial length wild type human PRKCE expressed in mammalian expression system at 0.5 uM by KINOMEscan method relative to control	Discovery and Preclinical Development of IIIM-290, an Orally Active Potent Cyclin-Dependent Kinase Inhibitor. — *J Med Chem*

Cellosaurus cell lines

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

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

Cellosaurus	Name	Category	Sex
CVCL_D7YH	Ubigene A-549 PRKCE KO	Cancer cell line	Male
CVCL_D8TX	Ubigene HCT 116 PRKCE KO	Cancer cell line	Male
CVCL_D9PM	Ubigene HEK293 PRKCE KO	Transformed cell line	Female
CVCL_E0LW	Ubigene HeLa PRKCE KO	Cancer cell line	Female
CVCL_TG84	HAP1 PRKCE (-) 1	Cancer cell line	Male
CVCL_TG85	HAP1 PRKCE (-) 2	Cancer cell line	Male
CVCL_TG86	HAP1 PRKCE (-) 3	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 PRKCE across ~30M SureChEMBL compounds — explore on Sugi Predict.