PRKCB

Summary

PRKCB (protein kinase C beta, HGNC:9395) is a protein-coding gene on chromosome 16p12.2-p12.1, encoding Protein kinase C beta type (P05771). Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase involved in various cellular processes such as regulation of the B-cell receptor (BCR) signalosome, oxidative stress-induced apoptosis, androgen receptor-dependent transcription r….

Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and 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 protein kinase has been reported to be involved in many different cellular functions, such as B cell activation, apoptosis induction, endothelial cell proliferation, and intestinal sugar absorption. Studies in mice also suggest that this kinase may also regulate neuronal functions and correlate fear-induced conflict behavior after stress. Alternatively spliced transcript variants encoding distinct isoforms have been reported.

Source: NCBI Gene 5579 — RefSeq curated summary.

At a glance

• GWAS associations: 23
• Clinical variants (ClinVar): 83 total — 1 pathogenic
• Regional missense constraint (gnomAD): 1 of 6 regions constrained (≈3% of expected missense variation)
• GTEx eGene: eQTL in 26 tissues, sQTL in 3 (q < 0.05)
• Drug target: yes — 2 curated mechanism-of-action drugs; 28 molecules with ChEMBL bioactivity (top 1% of genes corpus-wide)
• Cancer driver (intOGen): activating (oncogene-like) across 4 cancer types (inferred from mutation patterns)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.24 (highly constrained)
• MANE Select transcript: NM_002738
• Notable: 83 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9395
Approved symbol	PRKCB
Name	protein kinase C beta
Location	16p12.2-p12.1
Locus type	gene with protein product
Status	Approved
Aliases	PKCβ
Ensembl gene	ENSG00000166501
Ensembl biotype	protein_coding
OMIM	176970
Entrez	5579

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 15 protein_coding, 10 nonsense_mediated_decay, 4 protein_coding_CDS_not_defined, 3 retained_intron

MANE Select: ENST00000643927

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

ENST00000643927, ENST00000321728, ENST00000463752, ENST00000466124, ENST00000472066, ENST00000482000, ENST00000486868, ENST00000487674, ENST00000498058, ENST00000498739, ENST00000645517, ENST00000647422, ENST00000867666, ENST00000914401, ENST00000965655, ENST00000965656, ENST00000965657, ENST00000965658, ENST00000965659, ENST00000997925, ENST00001025368, ENST00001025369, ENST00001025370, ENST00001025371, ENST00001025372, ENST00001025373, ENST00001025374, ENST00001025375, ENST00001025378, ENST00001127399, ENST00001127400, ENST00001136749

RefSeq mRNA: 2 — MANE Select: NM_002738 NM_002738, NM_212535

CCDS: CCDS10618, CCDS10619

Canonical transcript exons

ENST00000643927 — 17 exons

Exon	Start	End
ENSE00001103616	24172270	24172361
ENSE00001103624	24174518	24174580
ENSE00001122545	24112973	24113069
ENSE00001242743	24191090	24191230
ENSE00001242785	24123835	24123981
ENSE00001242819	24032136	24032247
ENSE00001301256	24214658	24220611
ENSE00001400169	23835983	23836348
ENSE00001678439	23837375	23837406
ENSE00001699103	23988508	23988590
ENSE00001772524	24154684	24154857
ENSE00003463142	24094163	24094297
ENSE00003545547	24092791	24092947
ENSE00003552034	24035419	24035547
ENSE00003612107	24185460	24185567
ENSE00003633639	24185111	24185191
ENSE00003686275	24180790	24180928

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 99.27.

FANTOM5 (CAGE): breadth broad, TPM avg 58.3826 / max 2260.9711, expressed in 840 samples.

Highest expression (Bgee): middle temporal gyrus, orbitofrontal cortex, frontal pole, Brodmann (1909) area 23, Brodmann (1909) area 46.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PRKCB is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 26 tissues and its splicing (sQTL) in 3 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 29 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Artery Tibial	eqtl	2.6e-73	-0.59	16:23914030:G:A
Esophagus Muscularis	eqtl	2.9e-51	+0.67	16:23862880:A:T
Brain Cerebellar Hemisphere	eqtl	4.2e-27	-1.33	16:23998804:G:T
Colon Sigmoid	eqtl	1.2e-26	+0.56	16:23860077:C:T
Whole Blood	eqtl	1.5e-24	+0.16	16:23849686:CT:C
Esophagus Gastroesophageal Junction	eqtl	3.0e-24	+0.49	16:23860300:C:T
Brain Cerebellum	eqtl	2.1e-21	-1.35	16:23998804:G:T
Whole Blood	sqtl	7.3e-19	-1.48	16:24214944:T:A
Artery Aorta	eqtl	7.8e-17	+0.45	16:23874207:C:T
Adipose Subcutaneous	eqtl	4.3e-11	+0.22	16:23855702:G:C
Cells EBV-transformed lymphocytes	sqtl	4.3e-10	-1.66	16:24214944:T:A
Colon Transverse	eqtl	5.1e-10	+0.26	16:23860300:C:T
Nerve Tibial	eqtl	2.4e-09	+0.26	16:23927177:TTCCAGGACTAAATGATA:T
Breast Mammary Tissue	eqtl	1.7e-08	+0.23	16:23853269:T:C
Adrenal Gland	eqtl	3.1e-08	+0.34	16:23853269:T:C
Prostate	eqtl	2.3e-07	+0.27	16:23872157:A:G
Cells EBV-transformed lymphocytes	eqtl	2.8e-07	+0.33	16:23821145:A:G
Spleen	sqtl	4.8e-05	-1.65	16:24207784:T:G
Testis	eqtl	2.6e-04	+0.23	16:23831800:G:T
Heart Left Ventricle	eqtl	1.1e-03	+0.29	16:23843107:A:G

FANTOM5 promoters

showing 10 of 16 alternative TSS:

Promoter ID	TPM avg	Samples expressed
153180	53.1947	832
153179	1.3590	471
153182	0.7616	167
153181	0.7269	174
153196	0.6659	117
153207	0.4033	93
153178	0.2944	72
153208	0.2362	58
153206	0.2186	68
153197	0.1261	67

Top tissues by expression

showing 100 of 287 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	99.27	gold quality
orbitofrontal cortex	UBERON:0004167	99.26	gold quality
frontal pole	UBERON:0002795	99.12	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.97	gold quality
Brodmann (1909) area 46	UBERON:0006483	98.95	gold quality
superior frontal gyrus	UBERON:0002661	98.86	gold quality
Brodmann (1909) area 10	UBERON:0013541	98.70	gold quality
parietal lobe	UBERON:0001872	98.67	gold quality
CA1 field of hippocampus	UBERON:0003881	98.53	gold quality
postcentral gyrus	UBERON:0002581	98.48	gold quality
lateral globus pallidus	UBERON:0002476	98.44	gold quality
occipital lobe	UBERON:0002021	98.26	gold quality
middle frontal gyrus	UBERON:0002702	98.05	gold quality
primary visual cortex	UBERON:0002436	97.96	gold quality
prefrontal cortex	UBERON:0000451	97.48	gold quality
endothelial cell	CL:0000115	97.37	gold quality
pons	UBERON:0000988	97.35	gold quality
entorhinal cortex	UBERON:0002728	97.33	gold quality
frontal cortex	UBERON:0001870	97.15	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.99	gold quality
blood	UBERON:0000178	96.81	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.64	gold quality
bone marrow cell	CL:0002092	96.63	gold quality
mononuclear cell	CL:0000842	96.41	gold quality
monocyte	CL:0000576	96.37	gold quality
leukocyte	CL:0000738	96.35	gold quality
neocortex	UBERON:0001950	96.35	gold quality
cerebral cortex	UBERON:0000956	95.75	gold quality
cingulate cortex	UBERON:0003027	95.71	gold quality
anterior cingulate cortex	UBERON:0009835	95.68	gold quality
putamen	UBERON:0001874	95.39	gold quality
right frontal lobe	UBERON:0002810	95.18	gold quality
telencephalon	UBERON:0001893	94.96	gold quality
caudate nucleus	UBERON:0001873	94.82	gold quality
bone marrow	UBERON:0002371	94.00	gold quality
granulocyte	CL:0000094	93.97	gold quality
nucleus accumbens	UBERON:0001882	93.91	gold quality
saphenous vein	UBERON:0007318	93.90	gold quality
paraflocculus	UBERON:0005351	93.46	gold quality
lymph node	UBERON:0000029	93.16	gold quality
trabecular bone tissue	UBERON:0002483	92.70	gold quality
Ammon’s horn	UBERON:0001954	92.44	gold quality
lateral nuclear group of thalamus	UBERON:0002736	92.29	gold quality
vermiform appendix	UBERON:0001154	92.05	gold quality
adult organism	UBERON:0007023	91.24	gold quality
superior vestibular nucleus	UBERON:0007227	91.13	gold quality
thymus	UBERON:0002370	91.10	gold quality
ventral tegmental area	UBERON:0002691	91.03	gold quality
buccal mucosa cell	CL:0002336	91.02	gold quality
temporal lobe	UBERON:0001871	90.98	gold quality
spleen	UBERON:0002106	90.69	gold quality
medulla oblongata	UBERON:0001896	90.67	gold quality
forebrain	UBERON:0001890	90.54	gold quality
corpus callosum	UBERON:0002336	90.51	gold quality
caecum	UBERON:0001153	90.40	gold quality
dorsal plus ventral thalamus	UBERON:0001897	90.20	gold quality
brain	UBERON:0000955	89.90	gold quality
epithelium of nasopharynx	UBERON:0001951	89.69	gold quality
central nervous system	UBERON:0001017	89.68	gold quality
substantia nigra pars compacta	UBERON:0001965	89.20	gold quality
subthalamic nucleus	UBERON:0001906	89.09	gold quality
inferior vagus X ganglion	UBERON:0005363	88.96	gold quality
pigmented layer of retina	UBERON:0001782	87.71	gold quality
nipple	UBERON:0002030	87.58	gold quality
cerebellum	UBERON:0002037	87.23	gold quality
cerebellar vermis	UBERON:0004720	87.06	gold quality
substantia nigra pars reticulata	UBERON:0001966	87.04	gold quality
dorsal root ganglion	UBERON:0000044	86.80	gold quality
cerebellar cortex	UBERON:0002129	86.53	gold quality
cerebellar hemisphere	UBERON:0002245	86.49	gold quality
amygdala	UBERON:0001876	86.21	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.04	gold quality
colonic epithelium	UBERON:0000397	85.44	gold quality
midbrain	UBERON:0001891	85.37	gold quality
tonsil	UBERON:0002372	85.15	gold quality
substantia nigra	UBERON:0002038	84.66	gold quality
trigeminal ganglion	UBERON:0001675	84.02	gold quality
periodontal ligament	UBERON:0008266	83.78	gold quality
superficial temporal artery	UBERON:0001614	83.55	gold quality
ileal mucosa	UBERON:0000331	83.29	gold quality
spinal cord	UBERON:0002240	82.80	gold quality
globus pallidus	UBERON:0001875	82.51	gold quality
hypothalamus	UBERON:0001898	82.40	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	82.39	gold quality
pylorus	UBERON:0001166	81.81	gold quality
urethra	UBERON:0000057	81.59	gold quality
seminal vesicle	UBERON:0000998	81.57	gold quality
cortical plate	UBERON:0005343	80.99	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.82	gold quality
lower lobe of lung	UBERON:0008949	80.21	gold quality
small intestine Peyer’s patch	UBERON:0003454	79.96	gold quality
cardia of stomach	UBERON:0001162	79.68	gold quality
medial globus pallidus	UBERON:0002477	79.37	gold quality
sural nerve	UBERON:0015488	79.22	gold quality
small intestine	UBERON:0002108	79.21	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	78.96	gold quality
male germ cell	CL:0000015	78.95	silver quality
inferior olivary complex	UBERON:0002127	78.93	gold quality
urinary bladder	UBERON:0001255	78.87	gold quality
sperm	CL:0000019	78.85	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	2550.33
E-HCAD-25	yes	87.05
E-HCAD-35	yes	39.20
E-MTAB-6701	yes	16.28
E-GEOD-137537	yes	14.57
E-HCAD-10	yes	13.51
E-MTAB-8498	yes	11.89
E-CURD-119	yes	5.83
E-MTAB-6678	yes	5.35
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Caudate putamen	tissue	326.9
Putamen	tissue	281.1
Basal ganglia	tissue	252.8	medium
Postcentral gyrus	tissue	248.4
Frontal cortex	tissue	227.8
Cerebral cortex	tissue	205.2	medium
Motor cortex	tissue	205.2
Somatosensory cortex	tissue	184.7
Occipital cortex	tissue	180.7
Prefrontal cortex	tissue	179.4
Retrosplenial and cingulate cortex	tissue	166.4
Retrosplenial cortex	tissue	165.9
Hippocampal formation	tissue	150.4
Entorhinal cortex	tissue	150.4
Ventral forebrain	tissue	141.0
Insular cortex	tissue	139.7
Temporal cortex	tissue	139.6
Nucleus accumbens	tissue	115.5
Septum	tissue	83.4
Amygdala	tissue	79.7
Hippocampus	tissue	72.1	medium
Midbrain	tissue	62.0
Thalamus	tissue	61.5
Pons	tissue	58.3
Cerebellum	tissue	45.4	medium
Superior colliculi	tissue	44.2
Lymph node	tissue	44.0	high
Thymus	tissue	43.9
Hypothalamus	tissue	43.7
Spleen	tissue	43.6	high
Substantia nigra	tissue	39.6
Tonsil	tissue	37.5	high
Olfactory bulb	tissue	36.0
Medulla oblongata	tissue	33.9
Corpus callosum	tissue	33.0
Periaqueductal gray	tissue	32.4
Bone marrow	tissue	30.3	not detected
Spinal cord	tissue	29.7
Appendix	tissue	29.0	low
Locus coeruleus	tissue	26.5
Retina	tissue	16.9
Choroid plexus	tissue	11.2
Seminal vesicle	tissue	9.6	not detected
Urinary bladder	tissue	8.1	not detected
Testis	tissue	7.9	medium
Prostate	tissue	6.8	not detected
Smooth muscle	tissue	6.7	not detected
Lung	tissue	6.3	not detected
Duodenum	tissue	5.6	not detected
Small intestine	tissue	5.3	not detected
Skin 1	tissue	5.2	not detected
Colon	tissue	5.2	not detected
Rectum	tissue	4.8	not detected
Stomach 1	tissue	4.3	not detected
Thyroid gland	tissue	4.2	low
Gallbladder	tissue	4.2	not detected
Adipose tissue	tissue	4.1	not detected
Cervix	tissue	4.0	not detected
Liver	tissue	4.0	not detected
Endometrium 1	tissue	3.5	not detected

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Precentral gyrus (192.5), Precentral gyrus, middle (173.1), Caudate nucleus (172.3), Paracentral lobule, anterior (171.6), Frontal eye field (165.7).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FLI1, MAZ, MITF, NFKB, PROX1, RUNX1, SP1, SP3, STAT3

miRNA regulators (miRDB)

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

showing 30 of 53 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-199A-3P	99.75	70.48	929
HSA-MIR-199B-3P	99.75	70.48	929

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.241, missense Z 4.79 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000643927 splits into 6 regions with different missense tolerance; 1 is missense-constrained (≈3% 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
16:23,836,176–23,836,218	33 / 21.9	1.50	no
16:23,836,219–24,113,030	184 / 362.9	0.51	no
16:24,113,031–24,154,714	80 / 89.4	0.90	no
16:24,154,715–24,185,157	106 / 214.0	0.50	no
16:24,185,158–24,185,497	2 / 27.0	0.07	yes (p 1.5e-06)
16:24,185,498–24,214,813	104 / 160.5	0.65	no

Literature-anchored findings (GeneRIF, showing 40)

• Investigation of the inhibitory effects of chelerythrine chloride on the translocation of the protein kinase C betaI, betaII, zeta in human neutrophils (PMID:11765038)
• PKC-beta 1 when activated enhances calcium flux and protects the assembly of the F-actin cytoskeleton in intestinal monolayers against oxidants. (PMID:12023512)
• A method that uses liquid chromatography electrospray ionization-mass spectrometry to quantify site-specific protein phosphorylation was used to measure the time-dependent increase of phosphorylation by PRKCB2 at a PKC-preferred site, Ser44. (PMID:12033257)
• PKC beta II 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)
• The turn motif is a phosphorylation switch that regulates binding of Hsp70. (PMID:12080070)
• 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)
• Nephroprotective actions of the ACE inhibitor lisinopril in experimental diabetes mellitus were associated with and thus could be mediated in part by inhibition of diabetes-induced activation of PKC beta isoenzymes in the renal cortex. (PMID:12435880)
• PKCbeta has a role in in the chemotactic response of human monocytes to MCP-1 (PMID:12724308)
• elevated glucose increases the activity of core 2 GlcNAc-T and adhesion of human leukocytes to retinal capillary endothelial cells, in a dose-dependent manner, through diabetes-activated serine/threonine protein kinase C beta2 dependent phosphorylation (PMID:12765965)
• DNA sequence differences in the promoter of PRKCB1 contribute to diabetic nephropathy susceptibility in type I diabetes mellitus (PMID:12874455)
• data indicate a highly specific function of PKCbeta for regulation of TCR-CD28 induced-signaling, IL-2 gene expression and secretion in Jurkat T cells (PMID:12917261)
• PKCalpha and betaII have roles in the regulation of membrane recycling (PMID:14527960)
• protein kinase Cbeta is a direct, downstream target of RUNX1 (PMID:14561740)
• EGF-mediated protection against oxidant disruption of the intestinal barrier function requires PKC-beta1 activation and NF-kappaB suppression. (PMID:14602581)
• These results suggest that phosphorylation of tyrosinase by PKC-beta induces a complex formation between tyrosinase and TRP-1. (PMID:14623273)
• PKCbetaII induces cell invasion through a Ras/Mek-, PKC iota/Rac 1-dependent signaling pathway (PMID:15037605)
• phospholipase D causes translocation of protein kinase C (PKC)betaII but not PKCbetaI to a juxtanuclear subset of recycling endosomes (PMID:15067001)
• RACK-I anchors activated PKC-beta on the melanosome membrane, allowing PKC-beta to phosphorylate tyrosinase (PMID:15252133)
• Protein kinase CbetaII regulates its own expression in rat intestinal epithelial cells and the colonic epithelium in vivo. (PMID:15322124)
• PKC-MAPK pathway mRNAs plays an important role in the development and/or progression of early tissue damage in diabetic nephropathy (PMID:15327405)
• results showed that PKC beta(II) and delta isozymes are essential for the activation of IL-10 production in human monocytes following stimulation by HIV-1 Tat protein (PMID:15488737)
• We analyzed the dependence of the expression of some selected protein kinase C isoenzymes on the availability and/or action of androgens. (PMID:15499829)
• juxtanuclear translocation of protein kinase C betaII is selectively inhibited by a negative feedback mechanism involving ceramide formed from the salvage pathway (PMID:15546881)
• Chemotaxis to PDGF-BB in 25 mmol/L glucose is PKCbetaII-dependent and requires activation of both the PI3K and MAPK pathways. (PMID:15591231)
• PKCbetaII is regulated by PI 3-kinase in HT29 cells (PMID:15647851)
• the level of Smad6s can alter the level of TGF-beta and the subsequent induction of PAI-1 via a FoxD1 transcription site (PMID:15716278)
• This evidence supports that the Hal gene is turned on by glucocorticoids and by glucagon either via PKC or PKA, but prefers the PKA pathway. (PMID:15741241)
• Inhibition of protein phosphatase 2A increased phosphorylation at Ser660 that determines calcium sensitivity and activity of protein kinase c betaII isoform (PMID:15880462)
• Regulation of protein kinase C betaII expression and signaling play critical roles in mediating progenitor to dendritic cell differentiation (PMID:15917249)
• PRKCB1 gene on chromosome 16p may be involved in the etiology of autism. (PMID:16027742)
• The data do not support a strong association between single nucleotide polymorphism of PRKCB and spina bifida risk. (PMID:16080189)
• Furthermore, curcumin strongly repressed the PMA-induced phosphorylation of ERK, JNK, and p38 MAP kinase, which were dependent on the PKC pathway (PMID:16102725)
• Acrosomal exocytosis is regulated through the PKC-mediated phosphorylation of conserved threonines in the polybasic regions of synaptotagmin VI. (PMID:16111671)
• Data show that activity of protein kinase B in hormone-dependent mammary tumors was significantly higher than in tumor tissue from patients with negative receptor status. (PMID:16224561)
• A novel mechanism by which ROS can initiate cell death through the activation of PKC-betaI is reported. (PMID:16236825)
• Protein kinase C can inactivate TRPC3 indirectly by activating protein kinase G, and directly by phosphorylation on Ser-712. (PMID:16331690)
• Protein kinase Calpha, betaI, and betaII isozymes regulate cytokine production in mast cells through MEKK2/ERK5-dependent and -independent pathways. (PMID:16430878)
• Subcellular localization of protein kinase C (PKC)-beta, CD81, and LFA-1 was determined in T lymphocytes. (PMID:16472601)
• increased expression of PKC-alpha and -betaI leads to increased total classical PKC kinase activity; increased activity of the isoenzymes plays a role in accelerated growth of TCC. In carcinoma tissue, PKC expression and activity are under strict control. (PMID:16517978)
• study indicates that PRKCB1 is a predictor for worsening of kidney disease in Japanese subjects with type 2 diabetes (PMID:16567829)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	prkcba	ENSDARG00000008723
danio_rerio	prkcbb	ENSDARG00000022254
mus_musculus	Prkcb	ENSMUSG00000052889
rattus_norvegicus	Prkcb	ENSRNOG00000012061
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), PRKCE (ENSG00000171132)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:97596) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 15 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased IgM level	8
decreased B-1 B cell number	3
impaired humoral immune response	3
abnormal humoral immune response	2
decreased B cell proliferation	2
decreased B-1a cell number	2
decreased IgG3 level	2
decreased response to antigen	2
abnormal cued conditioning behavior	1
abnormal contextual conditioning behavior	1
abnormal vascular wound healing	1
increased T cell number	1
decreased B cell number	1
increased CD4-positive, alpha-beta T cell number	1
increased CD8-positive, alpha-beta T cell number	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
Bos taurus	P05131	99.4%	Diamond
Sus scrofa	P05383	99.4%	Diamond
Oryctolagus cuniculus	P05772	99.4%	Diamond
Macaca fascicularis	Q4R4U2	99.4%	Diamond
Xenopus tropicalis	Q5BKK4	99.0%	Diamond
Xenopus laevis	Q6GPN6	98.8%	Diamond
Gallus gallus	Q6U1I9	95.8%	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
CACNG3	protein-coding	10368
LINC02194	ncRNA	105371142
ERN2	protein-coding	10595
PLK1	protein-coding	5347
CHP2	protein-coding	63928
MIR1273H	ncRNA	102466247
PALB2	protein-coding	79728
DCTN5	protein-coding	84516

Protein

Protein identifiers

Protein kinase C beta type — P05771 (reviewed: P05771)

All UniProt accessions (4): P05771, H3BV73, I3L148, I3L1Z0

UniProt curated annotations — full annotation on UniProt →

Function. Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase involved in various cellular processes such as regulation of the B-cell receptor (BCR) signalosome, oxidative stress-induced apoptosis, androgen receptor-dependent transcription regulation, insulin signaling and endothelial cells proliferation. Plays a key role in B-cell activation by regulating BCR-induced NF-kappa-B activation. Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11/CARMA1 at ‘Ser-559’, ‘Ser-644’ and ‘Ser-652’. Phosphorylation induces CARD11/CARMA1 association with lipid rafts and recruitment of the BCL10-MALT1 complex as well as MAP3K7/TAK1, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1. Plays a direct role in the negative feedback regulation of the BCR signaling, by down-modulating BTK function via direct phosphorylation of BTK at ‘Ser-180’, which results in the alteration of BTK plasma membrane localization and in turn inhibition of BTK activity. Involved in apoptosis following oxidative damage: in case of oxidative conditions, specifically phosphorylates ‘Ser-36’ of isoform p66Shc of SHC1, leading to mitochondrial accumulation of p66Shc, where p66Shc acts as a reactive oxygen species producer. Acts as a coactivator of androgen receptor (AR)-dependent transcription, by being recruited to AR target genes and specifically mediating phosphorylation of ‘Thr-6’ of histone H3 (H3T6ph), a specific tag for epigenetic transcriptional activation that prevents demethylation of histone H3 ‘Lys-4’ (H3K4me) by LSD1/KDM1A. In insulin signaling, may function downstream of IRS1 in muscle cells and mediate insulin-dependent DNA synthesis through the RAF1-MAPK/ERK signaling cascade. Participates in the regulation of glucose transport in adipocytes by negatively modulating the insulin-stimulated translocation of the glucose transporter SLC2A4/GLUT4. Phosphorylates SLC2A1/GLUT1, promoting glucose uptake by SLC2A1/GLUT1. Under high glucose in pancreatic beta-cells, is probably involved in the inhibition of the insulin gene transcription, via regulation of MYC expression. In endothelial cells, activation of PRKCB induces increased phosphorylation of RB1, increased VEGFA-induced cell proliferation, and inhibits PI3K/AKT-dependent nitric oxide synthase (NOS3/eNOS) regulation by insulin, which causes endothelial dysfunction. Also involved in triglyceride homeostasis. Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription. Phosphorylates KLHL3 in response to angiotensin II signaling, decreasing the interaction between KLHL3 and WNK4. Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking. Acts as an activator of ferroptosis by mediating phosphorylation and activation of ACSL4. Also stimulates ferroptosis propagation by catalyzing phosphorylation of FOXK1, thereby promoting LGALS13 secretion.

Subunit / interactions. Interacts with PDPK1/PDK1. Interacts in vitro with PRKCBP1. Interacts with PHLPP1 and PHLPP2; both proteins mediate its dephosphorylation. Interacts with KDM1A/LSD1, PKN1 and AR.

Subcellular location. Cytoplasm. Nucleus. Membrane.

Post-translational modifications. Phosphorylation on Thr-500 within the activation loop renders it competent to autophosphorylate. Subsequent autophosphorylation of Thr-642 maintains catalytic competence, and autophosphorylation on Ser-661 appears to release the kinase into the cytosol. Autophosphorylation on other sites i.e. in the N-terminal and hinge regions have no effect on enzyme activity. Phosphorylation at Tyr-662 by SYK induces binding with GRB2 and contributes to the activation of MAPK/ERK signaling cascade.

Activity regulation. Classical (or conventional) PKCs (PRKCA, PRKCB and PRKCG) are activated by calcium and diacylglycerol (DAG) in the presence of phosphatidylserine. Three specific sites; Thr-500 (activation loop of the kinase domain), Thr-642 (turn motif) and Ser-661 (hydrophobic region), need to be phosphorylated for its full activation. Specifically inhibited by enzastaurin (LY317615).

Cofactor. Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2 domain.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P05771-1	Beta-I, PRKCB1	yes
P05771-2	Beta-II, PRKCB2

RefSeq proteins (2): NP_002729, NP_997700 (=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
IPR014375	Protein_kinase_C_a/b/g	Family
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR017892	Pkinase_C	Domain
IPR020454	DAG/PE-bd	Domain
IPR034664	cPKC-beta	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 (120 total): strand 34, helix 29, modified residue 17, binding site 16, turn 8, domain 3, sequence variant 3, zinc finger region 2, region of interest 2, initiator methionine 1, chain 1, active site 1, splice variant 1, sequence conflict 1, compositionally biased region 1

Structure

Experimental structures (PDB)

8 structures by resolution:

PDB	Title	Method	Resolution (Å)
9C5F	Crystal Structure Analysis of human PRKCB	X-RAY DIFFRACTION	2.41
2I0E	Structure of catalytic domain of human protein kinase C beta II complexed with a …	X-RAY DIFFRACTION	2.6
8SE3	Structure of Full-length Human Protein Kinase C Beta 1 (PKCBI) in the Active Conformation	X-RAY DIFFRACTION	2.6
8SE4	Structure of Full-length Human Protein Kinase C Beta 1 (PKCBI) in the Active and Inactive …	X-RAY DIFFRACTION	2.68
8SE2	Structure of Full-length Human Protein Kinase C Beta 1 (PKCBI) in the Active and Inactive …	X-RAY DIFFRACTION	2.95
8SE1	Structure of Full-length Human Protein Kinase C Beta 2 (PKCBII) in the Inactive …	X-RAY DIFFRACTION	3.32
9S9T	Structure of human PKCBeta Kinase domain with Ruboxistaurin, D427N mutant	X-RAY DIFFRACTION	3.42
8SG2	BIVALENT INTERACTIONS OF PIN1 WITH THE C-TERMINAL TAIL OF PKC	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P05771-F1	85.95	0.62

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Kinases, AGC Ser/Thr protein kinases, Transporters, Accessory Factors Involved in Transport, Predicted intracellular proteins, Plasma proteins, RAS pathway related proteins, Cancer-related genes, Candidate cancer biomarkers, FDA approved drug targets, Small molecule drugs

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; cytosol

Antibody reliability (HPA): IH approved · 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
466	proton acceptor

Ligand- & substrate-binding residues (16)

Position	Role
186	Ca(2+)
187	Ca(2+)
193	Ca(2+)
246	Ca(2+)
247	Ca(2+)
248	Ca(2+)
251	Ca(2+)
252	Ca(2+)
254	Ca(2+)
348–356	ATP
371	ATP

Post-translational modifications (17)

Type	Positions
Phosphothreonine	641, 17, 250, 314, 324, 500, 504, 635, 642
Phosphoserine	660, 11, 16, 206, 311, 661
N-acetylalanine	2
Phosphotyrosine	662

Function

Pathways and Gene Ontology

Reactome pathways

9 curated (TAS) of 42; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

42 pathways:

ID	Pathway	Evidence
R-HSA-1169091	Activation of NF-kappaB in B cells	curated
R-HSA-4419969	Depolymerization of the Nuclear Lamina	curated
R-HSA-114516	Disinhibition of SNARE formation	curated
R-HSA-5668599	RHO GTPases Activate NADPH Oxidases	curated
R-HSA-8939246	RUNX1 regulates transcription of genes involved in differentiation of myeloid cells	curated
R-HSA-76005	Response to elevated platelet cytosolic Ca2+	curated
R-HSA-416993	Trafficking of GluR2-containing AMPA receptors	curated
R-HSA-5218921	VEGFR2 mediated cell proliferation	curated
R-HSA-5099900	WNT5A-dependent internalization of FZD4	curated
R-HSA-1280218	Adaptive Immune System	—
R-HSA-3858494	Beta-catenin independent WNT signaling	—
R-HSA-1640170	Cell Cycle	—
R-HSA-69278	Cell Cycle, Mitotic	—
R-HSA-1168372	Downstream signaling events of B Cell Receptor (BCR)	—
R-HSA-418597	G alpha (z) signalling events	electronic
R-HSA-388396	GPCR downstream signalling	—
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-212436	Generic Transcription Pathway	—
R-HSA-399721	Glutamate binding, activation of AMPA receptors and synaptic plasticity	—
R-HSA-109582	Hemostasis	—
R-HSA-168256	Immune System	—
R-HSA-68886	M Phase	—
R-HSA-68875	Mitotic Prophase	—
R-HSA-112316	Neuronal System	—
R-HSA-112314	Neurotransmitter receptors and postsynaptic signal transmission	—
R-HSA-2980766	Nuclear Envelope Breakdown	—
R-HSA-4086400	PCP/CE pathway	—
R-HSA-76002	Platelet activation, signaling and aggregation	—
R-HSA-195258	RHO GTPase Effectors	—
R-HSA-73857	RNA Polymerase II Transcription	—
R-HSA-162582	Signal Transduction	—
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-195721	Signaling by WNT	—
R-HSA-983705	Signaling by the B Cell Receptor (BCR)	—
R-HSA-399719	Trafficking of AMPA receptors	—
R-HSA-8878171	Transcriptional regulation by RUNX1	—
R-HSA-112315	Transmission across Chemical Synapses	—
R-HSA-4420097	VEGFA-VEGFR2 Pathway	—

MSigDB gene sets: 681 (showing top): RNGTGGGC_UNKNOWN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_CARBOHYDRATE_TRANSPORT, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, BENPORATH_ES_WITH_H3K27ME3, BIOCARTA_EDG1_PATHWAY, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, BASSO_B_LYMPHOCYTE_NETWORK, GOBP_B_CELL_ACTIVATION, GOBP_MEMBRANE_DISASSEMBLY, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, REACTOME_G_ALPHA_Z_SIGNALLING_EVENTS, HOFMANN_CELL_LYMPHOMA_UP, KEGG_MAPK_SIGNALING_PATHWAY

GO Biological Process (26): adaptive immune response (GO:0002250), DNA-templated transcription (GO:0006351), regulation of transcription by RNA polymerase II (GO:0006357), protein phosphorylation (GO:0006468), apoptotic process (GO:0006915), mitotic nuclear membrane disassembly (GO:0007077), signal transduction (GO:0007165), phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway (GO:0007207), regulation of D-glucose transmembrane transport (GO:0010827), negative regulation of D-glucose transmembrane transport (GO:0010829), positive regulation of vascular endothelial growth factor receptor signaling pathway (GO:0030949), intracellular signal transduction (GO:0035556), B cell activation (GO:0042113), lipoprotein transport (GO:0042953), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), positive regulation of angiogenesis (GO:0045766), negative regulation of insulin receptor signaling pathway (GO:0046627), B cell receptor signaling pathway (GO:0050853), protein kinase C signaling (GO:0070528), positive regulation of ferroptosis (GO:0160020), regulation of synaptic vesicle exocytosis (GO:2000300), immune system process (GO:0002376), chromatin organization (GO:0006325), chromatin remodeling (GO:0006338), positive regulation of DNA-templated transcription (GO:0045893), regulation of transport (GO:0051049)

GO Molecular Function (19): chromatin binding (GO:0003682), transcription coactivator activity (GO:0003713), protein serine/threonine kinase activity (GO:0004674), diacylglycerol-dependent serine/threonine kinase activity (GO:0004697), calcium,diacylglycerol-dependent serine/threonine kinase activity (GO:0004698), protein kinase C binding (GO:0005080), calcium channel regulator activity (GO:0005246), ATP binding (GO:0005524), zinc ion binding (GO:0008270), histone H3T6 kinase activity (GO:0035403), histone binding (GO:0042393), nuclear androgen receptor binding (GO:0050681), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (10): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), spectrin (GO:0008091), calyx of Held (GO:0044305), extracellular exosome (GO:0070062), presynaptic cytosol (GO:0099523), membrane (GO:0016020)

Reactome top-level categories

15 top-level categories:

Category	Pathways
Response to elevated platelet cytosolic Ca2+	1
Downstream signaling events of B Cell Receptor (BCR)	1
Trafficking of AMPA receptors	1
GPCR downstream signalling	1
Nuclear Envelope Breakdown	1
PCP/CE pathway	1
VEGFA-VEGFR2 Pathway	1
RHO GTPase Effectors	1
Platelet activation, signaling and aggregation	1
Transcriptional regulation by RUNX1	1
Transmission across Chemical Synapses	1
Neuronal System	1
Signaling by the B Cell Receptor (BCR)	1
Immune System	1
Signaling by Receptor Tyrosine Kinases	1

GO top-level categories

showing 60 of 84 GO namespaces:

Category	Terms
cellular anatomical structure	4
D-glucose transmembrane transport	2
intracellular anatomical structure	2
binding	2
protein kinase activity	2
protein serine/threonine kinase activity	2
immune response	1
gene expression	1
RNA biosynthetic process	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
phosphorylation	1
protein modification process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
mitotic cell cycle	1
nuclear membrane disassembly	1
mitotic cell cycle process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
phospholipase C-activating G protein-coupled receptor signaling pathway	1
G protein-coupled acetylcholine receptor signaling pathway	1
regulation of transmembrane transport	1
regulation of D-glucose transmembrane transport	1
negative regulation of transmembrane transport	1
positive regulation of signal transduction	1
regulation of vascular endothelial growth factor receptor signaling pathway	1
vascular endothelial growth factor receptor signaling pathway	1
signal transduction	1
lymphocyte activation	1
protein transport	1
lipoprotein localization	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
angiogenesis	1
regulation of angiogenesis	1
positive regulation of vasculature development	1
insulin receptor signaling pathway	1
negative regulation of signal transduction	1
regulation of insulin receptor signaling pathway	1
negative regulation of cellular response to insulin stimulus	1
antigen receptor-mediated signaling pathway	1
intracellular signal transduction	1
positive regulation of programmed cell death	1
ferroptosis	1
regulation of ferroptosis	1
transcription coregulator activity	1
positive regulation of DNA-templated transcription	1
diacylglycerol-dependent serine/threonine kinase activity	1
calcium-dependent protein serine/threonine kinase activity	1
protein kinase binding	1
calcium channel activity	1
ion channel regulator activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 17 of 55 annotations. The rest are phylogenetic / computational / electronic (IEA).

17 experimentally-supported GO terms:

GO term	NS	Evidence
positive regulation of ferroptosis	BP	direct assay
protein kinase C signaling	BP	direct assay
regulation of D-glucose transmembrane transport	BP	direct assay
regulation of transcription by RNA polymerase II	BP	mutant phenotype
cytoplasm	CC	direct assay
extracellular exosome	CC	high-throughput assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
plasma membrane	CC	direct assay
calcium,diacylglycerol-dependent serine/threonine kinase activity	MF	direct assay
chromatin binding	MF	direct assay
histone H3T6 kinase activity	MF	direct assay
histone binding	MF	direct assay
nuclear androgen receptor binding	MF	direct assay
protein kinase C binding	MF	physical interaction
protein serine/threonine kinase activity	MF	direct assay
transcription coactivator activity	MF	mutant phenotype

Protein interactions and networks

IntAct

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

18 partners by confidence:

Partner	Interaction type	MIscore	Records
SHCBP1	physical association	0.560	2
AKT1	physical association	0.550	1
PRKCD	association	0.530	2
PRKCA	association	0.530	1
TINF2	physical association	0.510	2
PRL1	direct interaction	0.440	1
HSP90AB1	physical association	0.400	1
TERF1	physical association	0.370	1
CHEK1	association	0.350	1
DELEC1	association	0.350	1
HNRNPDL	association	0.350	1
MTCL3	association	0.350	1
PRKCG	association	0.350	1
RDH14	association	0.350	1
CHUK	proximity	0.270	1
GSK3B	proximity	0.270	1
IKBKB	proximity	0.270	1
FMR1	physical association	0.000	1

BioGRID (260 interactions; top human partners by supporting records): GNB2L1 (Affinity Capture-Western; 6 records), ADRBK1 (Affinity Capture-Western; 5 records), PRKCA (Affinity Capture-MS; 5 records), RBCK1 (Biochemical Activity; 5 records), ARRB2 (Affinity Capture-Western; 4 records), CARD11 (Affinity Capture-Western; 4 records), PDPK1 (Reconstituted Complex; 4 records), AKT1 (Two-hybrid; 3 records), DDX58 (Biochemical Activity; 3 records), RNF31 (Affinity Capture-Western; 3 records), TRIM41 (Affinity Capture-Western; 3 records), ACSL4 (Affinity Capture-Western; 2 records), BLVRA (Biochemical Activity; 2 records), CLTC (Affinity Capture-Western; 2 records), GNB1 (Affinity Capture-Western; 2 records)

SIGNOR signaling

showing 43 of 140 signaling interactions:

A	Effect	B	Mechanism
PRKCB	down-regulates	GSK3A	phosphorylation
PDPK1	up-regulates	PRKCB	phosphorylation
PRKCB	up-regulates	CHAT	phosphorylation
PRKCB	down-regulates	TNNI3	phosphorylation
PRKCB	“up-regulates activity”	PRKCB	phosphorylation
PRKCB	up-regulates	PRKCB	phosphorylation
PRKCB	down-regulates	C5AR1	phosphorylation
BLVRA	up-regulates	PRKCB	phosphorylation
PRKCB	down-regulates	ORAI1	phosphorylation
PRKCB	“up-regulates activity”	ILF3	phosphorylation
PRKCB	down-regulates	IBTK	phosphorylation
“bisindolylmaleimide i”	down-regulates	PRKCB	“chemical inhibition”
3-(1-methyl-3-indolyl)-4-[1-[1-(2-pyridinylmethyl)-4-piperidinyl]-3-indolyl]pyrrole-2,5-dione	down-regulates	PRKCB	“chemical inhibition”
DVL1P1	up-regulates	PRKCB	binding
PRKCB	up-regulates	ANXA1	phosphorylation
PHLPP2	“down-regulates quantity”	PRKCB	dephosphorylation
PHLPP1	“down-regulates quantity”	PRKCB	dephosphorylation
1,2-diacyl-sn-glycerol	“up-regulates activity”	PRKCB	binding
PHLPP1	“down-regulates quantity by destabilization”	PRKCB	dephosphorylation
PHLPP2	“down-regulates quantity by destabilization”	PRKCB	dephosphorylation
PRKCB	unknown	LMNB1	phosphorylation
PRKCB	“down-regulates activity”	CYTH2	phosphorylation
PRKCB	unknown	CD5	phosphorylation
PRKCB	unknown	PA2G4	phosphorylation
PRKCB	“down-regulates activity”	BTK	phosphorylation
PRKCB	unknown	ITGB2	phosphorylation
PRKCB	unknown	PTPN11	phosphorylation
PRKCB	“down-regulates activity”	CASR	phosphorylation
PRKCB	“up-regulates activity”	TOP2A	phosphorylation
PRKCB	“up-regulates activity”	PSEN1	phosphorylation
PRKCB	“down-regulates activity”	EIF6	phosphorylation
PRKCB	“down-regulates activity”	HABP4	phosphorylation
PRKCB	“down-regulates activity”	NOS3	phosphorylation
LUBAC	“down-regulates quantity by destabilization”	PRKCB	polyubiquitination
TRIM41	“down-regulates quantity by destabilization”	PRKCB	polyubiquitination
PRKCB	“up-regulates activity”		phosphorylation
PRKCB	“up-regulates activity”	ICOSLG	phosphorylation
PRKCB	“up-regulates quantity by stabilization”	CFLAR	phosphorylation
PRKCB	“up-regulates activity”	TP73	phosphorylation
PRKCB	“up-regulates activity”	PIK3CG	phosphorylation
PRKCB	“up-regulates activity”	TRPV1	phosphorylation
TRPV1	“up-regulates activity”	PRKCB	binding
PRKCB	“up-regulates quantity”	MSX2	phosphorylation

Protein complexes (CORUM) (2)

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

2 complexes by size:

Complex	Subunits	Members
★ EGFR-ERBB3-LYN-PAG1-PRKCB-RACK1 complex	6	EGFR, ERBB3, LYN, PAG1, PRKCB, RACK1
★ KCNA5-KCNAB1-RACK1 complex	5	KCNA5, KCNAB1, PRKCB, PRKCQ, RACK1

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 18 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.

GO biological processes:

GO term	Partners	Fold	FDR
protein phosphorylation	6	25.5×	9e-06
intracellular signal transduction	5	11.9×	2e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 4 cancer types — DLBCLNOS, HNSC, PRAD, STAD.

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 PRKCB: 83 ClinVar records (1 pathogenic / likely pathogenic); 1 CIViC cancer variant; 2 PharmGKB clinical annotations; 23 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	44
Likely benign	8
Benign	8

Top pathogenic / likely-pathogenic (1)

Showing all 1 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
224499	NM_002738.7(PRKCB):c.275G>T (p.Gly92Val)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore PRKCB’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; 30 predictions of 1,735):

Position(s)	Effect	Δscore	Sites
16:24032127–24032128	acceptor_gain	1.0000	2
16:24035416	acceptor_gain	1.0000
16:24035417–24035418	acceptor_loss	1.0000	6
16:24035529	donor_gain	1.0000
16:24035548–24035549	donor_loss	1.0000	2
16:24092789–24092790	acceptor_loss	1.0000	4
16:24092949	donor_loss	1.0000	2
16:24094158	acceptor_gain	1.0000
16:24094161–24094162	acceptor_loss	1.0000	6
16:24094298–24094299	donor_loss	1.0000	5

AlphaMissense

2,872 missense substitutions predicted likely pathogenic (of 4,527 scored), across 532 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
M487	9	0.991	1.000
M429	9	0.987	1.000
M186	9	0.982	0.999
M534	9	0.974	1.000
M420	9	0.972	0.999
M256	9	0.943	0.999
D246	8	1.000	1.000
D248	8	1.000	1.000
D466	8	1.000	1.000
D470	8	1.000	1.000
N471	8	1.000	1.000
D484	8	1.000	1.000
H37	8	0.999	1.000
H75	8	0.999	1.000
D187	8	0.999	1.000
D254	8	0.999	1.000
D383	8	0.999	1.000
D427	8	0.999	1.000
F501	8	0.999	1.000
F353	8	0.998	1.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

1 prognostic cancer types:

Cancer	Prognostic	p-value
Lung Adenocarcinoma (TCGA)	favorable	4.4e-05

Disease associations

OMIM: gene MIM:176970 | disease phenotypes:

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (1 panels, 0 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

1 panels:

Panel	Rating
Familial Meniere Disease	amber

GWAS associations

23 associations:

Study	Trait	p-value
GCST011956_157	Systemic lupus erythematosus	1e-12
GCST90002388_351	Lymphocyte count	7e-12
GCST001725_51	Inflammatory bowel disease	1e-9
GCST011494_14	Daytime nap	2e-9
GCST005537_140	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	3e-9
GCST90002388_350	Lymphocyte count	3e-9
GCST004145_9	Primary biliary cholangitis	4e-9
GCST004131_75	Inflammatory bowel disease	2e-7
GCST004133_48	Ulcerative colitis	2e-7
GCST003265_68	Post bronchodilator FEV1/FVC ratio in COPD	6e-7
GCST003265_67	Post bronchodilator FEV1/FVC ratio in COPD	7e-7
GCST003265_66	Post bronchodilator FEV1/FVC ratio in COPD	9e-7
GCST002936_28	Cadmium levels	1e-6
GCST003265_114	Post bronchodilator FEV1/FVC ratio in COPD	1e-6
GCST003265_65	Post bronchodilator FEV1/FVC ratio in COPD	1e-6
GCST003265_323	Post bronchodilator FEV1/FVC ratio in COPD	2e-6
GCST006585_1787	Blood protein levels	2e-6
GCST003265_113	Post bronchodilator FEV1/FVC ratio in COPD	3e-6
GCST003265_322	Post bronchodilator FEV1/FVC ratio in COPD	3e-6
GCST001454_14	Rheumatoid arthritis	4e-6
GCST90006998_7	Gut microbiota relative abundance (Dorea)	4e-6
GCST006914_6	Sleep duration	6e-6
GCST009378_20	Bone mineral content	9e-6

EFO canonical traits (from GWAS)

5 canonical traits:

EFO ID	Trait name
EFO:0004713	FEV/FVC ratio
EFO:0007621	bone mineral content measurement
EFO:0007828	daytime rest measurement
EFO:0004587	lymphocyte count
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2093867 (PROTEIN FAMILY), CHEMBL2096620 (PROTEIN FAMILY), CHEMBL3045 (SINGLE PROTEIN), CHEMBL3137267 (PROTEIN FAMILY)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the PRKCB 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.

2 curated-mechanism drugs:

Drug	Modality	Max phase
ENZASTAURIN	Small molecule	3
RUBOXISTAURIN	Small molecule	3

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 301,840 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

28 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL3301610	ABEMACICLIB	4	7,497
CHEMBL2105759	BARICITINIB	4	7,117
CHEMBL2325741	CAPIVASERTIB	4	2,281
CHEMBL1863513	INGENOL MEBUTATE	4	1,527
CHEMBL608533	MIDOSTAURIN	4	7,641
CHEMBL2035187	PACRITINIB	4	3,544
CHEMBL83	TAMOXIFEN	4	173,287
CHEMBL300138	ENZASTAURIN	3	3,401
CHEMBL2107337	ENZASTAURIN HYDROCHLORIDE	3	552
CHEMBL91829	RUBOXISTAURIN	3	78
CHEMBL2219422	AFURESERTIB	3	1,534
CHEMBL428690	ALVOCIDIB	3	28,145
CHEMBL38380	FASUDIL	3	12,137
CHEMBL265502	SURAMIN	3	37,133
CHEMBL495727	AT-9283	2	1,442
CHEMBL3982723	DAROVASERTIB	2	503
CHEMBL3039513	DECERNOTINIB	2	1,509
CHEMBL103667	DORAMAPIMOD	2	1,746
CHEMBL28509	EDELFOSINE	2	10,657
CHEMBL362558	LY-2090314	2	109
CHEMBL279115	PHORBOL MYRISTATE ACETATE	2
CHEMBL565612	SOTRASTAURIN	2
CHEMBL574737	UCN-01	2
CHEMBL3137336	UPROSERTIB	2
CHEMBL1944698	ZOTIRACICLIB	2
CHEMBL494089	GSK-690693	1
CHEMBL3128043	PF-03758309	1
CHEMBL571948	Y-39983	1

CIViC curated variants (1)

Named clinical variants curated in CIViC for this gene (the catalogue beneath the predictive evidence above):

D427N.

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

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

Variant	Association	Level	Drugs	Phenotypes
rs11649514	Toxicity	3	atenolol	Hyperglycemia
rs9922316	Other	3	dexmedetomidine

PharmGKB variants

2 variants:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs9922316	PRKCB	3	1.50	1	dexmedetomidine
rs11649514	PRKCB	3	2.50	1	atenolol

PharmGKB variant annotations

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

2 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs11649514	atenolol	Toxicity, Other	Genotypes GT + TT is associated with increased likelihood of Hyperglycemia when treated with atenolol in people with Essential hypertension as compared to genotype GG.	PMID:26946962
rs9922316	dexmedetomidine	Other	Allele T is associated with increased dexmedetomidine ED50 values for drug-induced dorsal hand vein (DHV) constriction when exposed to dexmedetomidine in healthy individuals as compared to allele G.	PMID:23337848

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Alpha subfamily

Most potent curated ligand interactions (13 total), top 13:

Ligand	Action	Affinity	Parameter
ingenol mebutate	Activation	9.98	pKi
sotrastaurin	Inhibition	8.7	pIC50
PKCbeta inhibitor	Inhibition	8.3	pIC50
ruboxistaurin	Inhibition	8.23	pIC50
Gö 6983	Inhibition	8.15	pIC50
balanol	Inhibition	8.0	pIC50
10-Me-Aplog-1	Activation	7.92	pKi
GF109203X	Inhibition	7.8	pIC50
7-hydroxystaurosporine	Inhibition	7.54	pIC50
enzastaurin	Inhibition	7.52	pIC50
Ro-32-0432	Inhibition	7.52	pIC50
bisindolylmaleimide IV	Inhibition	6.67	pIC50
CGP53353	Inhibition	6.4	pIC50

Binding affinities (BindingDB)

887 measured of 1107 human assays (1143 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
CHEMBL4528495	IC50	0.15 nM
[3-[[5-fluoro-2-(2,2,2-trifluoroethoxy)pyrimidin-4-yl]amino]-6,6-dimethyl-1,4-dihydropyrrolo[3,4-d]pyrazol-5-yl]-[(2S,5R)-2,4,5-trimethylpiperazin-1-yl]methanone	KI	0.165 nM	US-117808
CHEMBL4538431	IC50	0.17 nM
CHEMBL4443190	IC50	0.18 nM
[3-[[5-fluoro-2-(2,2,2-trifluoroethoxy)pyrimidin-4-yl]amino]-6,6-dimethyl-1,4-dihydropyrrolo[3,4-d]pyrazol-5-yl]-[(2S)-2,4,5,5-tetramethylpiperazin-1-yl]methanone	KI	0.181 nM	US-117808
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
[3-[[5-fluoro-2-(2,2,2-trifluoroethoxy)pyrimidin-4-yl]amino]-6,6-dimethyl-1,4-dihydropyrrolo[3,4-d]pyrazol-5-yl]-[(2S,5R)-4-(3-methoxypropyl)-2,5-dimethylpiperazin-1-yl]methanone	KI	0.376 nM	US-117808
Aplysiatoxin	KI	0.4 nM
CHEMBL2151411	IC50	0.4 nM
Bryostatin	KD	0.44 nM
(2S)-1-[[4-(difluoromethyl)-6-(2-methyl-4-pyridinyl)-3-pyridinyl]oxy]-2,4-dimethylpentan-2-amine	IC50	0.5 nM	US-10155760: Biaryl kinase inhibitors
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
[3-[(2-ethoxy-5-fluoropyrimidin-4-yl)amino]-6,6-dimethyl-1,4-dihydropyrrolo[3,4-d]pyrazol-5-yl]-[(2S,5R)-4-(3-methoxypropyl)-2,5-dimethylpiperazin-1-yl]methanone	KI	0.683 nM	US-117808
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
maleimide derivative, 12	IC50	0.9 nM
[3-[(2-ethoxy-5-fluoropyrimidin-4-yl)amino]-6,6-dimethyl-1,2,3,3a,4,6a-hexahydropyrrolo[3,4-c]pyrazol-5-yl]-[(2S)-2,4,5,5-tetramethylpiperazin-1-yl]methanone	KI	0.912 nM	US-117808
N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methylthieno[3,2-d]pyrimidin-4-yl)amino]-1,4-dihydropyrrolo[3,4-d]pyrazole-5-carboxamide	IC50	1 nM	US-8530652: Pyrrolopyrazoles, potent kinase inhibitors
CHEMBL2153750	IC50	1 nM
DEMETHOXYDEBROMOAPLYSIATOXIN	KI	1 nM
5-{[(8S)-6,8-dimethyl-6,9-diazaspiro[4.5]dec-9-yl]carbonyl}-N-(5-fluoro-2-methylpyrimidin-4-yl)-6,6-dimethyl-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazol-3-amine	KI	1.01 nM	US-117808
[3-[(2-ethoxy-5-fluoropyrimidin-4-yl)amino]-6,6-dimethyl-1,2,3,3a,4,6a-hexahydropyrrolo[3,4-c]pyrazol-5-yl]-[(2S,5R)-2,4,5-trimethylpiperazin-1-yl]methanone	KI	1.12 nM	US-117808
[3-[(3-fluoro-6-methyl-2-pyridinyl)amino]-6,6-dimethyl-1,2,3,3a,4,6a-hexahydropyrrolo[3,4-c]pyrazol-5-yl]-[(2S)-2,4,5,5-tetramethylpiperazin-1-yl]methanone	KI	1.17 nM	US-117808
Compound K-252a(epi)	IC50	1.2 nM
CHEMBL2151415	IC50	1.4 nM
CHEMBL2153748	IC50	1.4 nM
CHEMBL2236794	IC50	1.4 nM
6,6-dimethyl-8-(1-(oxetan-3-yl)piperidin-4-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile	IC50	1.5 nM
[3-[(2-ethyl-5-fluoropyrimidin-4-yl)amino]-6,6-dimethyl-1,4-dihydropyrrolo[3,4-d]pyrazol-5-yl]-[(2S,5R)-4-(3-methoxypropyl)-2,5-dimethylpiperazin-1-yl]methanone	KI	1.64 nM	US-117808
N-[5-[(2S,5R)-2,5-dimethyl-4-(oxan-4-yl)piperazine-1-carbonyl]-6,6-dimethyl-1,4-dihydropyrrolo[3,4-d]pyrazol-3-yl]pyridine-2-carboxamide	KI	1.7 nM	US-8999981: 3-amido-pyrrolo[3,4-C]pyrazole-5(1H, 4H,6H) carbaldehyde derivatives
CHEMBL2153751	IC50	1.7 nM
(4-fluoro-1-methylpiperidin-4-yl)-[3-[[5-fluoro-2-(2,2,2-trifluoroethoxy)pyrimidin-4-yl]amino]-6,6-dimethyl-1,4-dihydropyrrolo[3,4-d]pyrazol-5-yl]methanone	KI	1.71 nM	US-117808
[3-[(5-fluoro-2-propylpyrimidin-4-yl)amino]-6,6-dimethyl-1,4-dihydropyrrolo[3,4-d]pyrazol-5-yl]-[(2S)-2,4,5,5-tetramethylpiperazin-1-yl]methanone	KI	1.73 nM	US-117808
CHEMBL4085837	IC50	1.8 nM
N-[5-[(2S,5R)-2,5-dimethyl-4-(oxan-4-ylmethyl)piperazine-1-carbonyl]-6,6-dimethyl-1,4-dihydropyrrolo[3,4-d]pyrazol-3-yl]pyridine-2-carboxamide	KI	1.9 nM	US-8999981: 3-amido-pyrrolo[3,4-C]pyrazole-5(1H, 4H,6H) carbaldehyde derivatives
CHEMBL2236799	IC50	2 nM
[3-[[2-(ethylamino)-5-fluoropyrimidin-4-yl]amino]-6,6-dimethyl-1,4-dihydropyrrolo[3,4-d]pyrazol-5-yl]-[(2S,5R)-2,4,5-trimethylpiperazin-1-yl]methanone	KI	2.03 nM	US-117808
[3-[[5-fluoro-2-(methoxymethyl)pyrimidin-4-yl]amino]-6,6-dimethyl-1,2,3,3a,4,6a-hexahydropyrrolo[3,4-c]pyrazol-5-yl]-[(2S)-2,4,5,5-tetramethylpiperazin-1-yl]methanone	KI	2.1 nM	US-117808
[3-[(6-ethoxy-3-fluoro-2-pyridinyl)amino]-6,6-dimethyl-1,2,3,3a,4,6a-hexahydropyrrolo[3,4-c]pyrazol-5-yl]-[(2S,5R)-4-ethyl-2,5-dimethylpiperazin-1-yl]methanone	KI	2.11 nM	US-117808

ChEMBL bioactivities

1326 potent at pChembl≥5 of 1440 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	EC50	0.1	nM	CHEMBL3926213
9.89	IC50	0.13	nM	CHEMBL3741746
9.85	IC50	0.14	nM	CHEMBL4575056
9.82	IC50	0.15	nM	CHEMBL4528495
9.78	Ki	0.165	nM	CHEMBL5764715
9.77	Ki	0.17	nM	DEBROMOAPLYSIATOXIN
9.77	IC50	0.17	nM	CHEMBL4538431
9.74	IC50	0.18	nM	CHEMBL4443190
9.74	Ki	0.181	nM	CHEMBL5992520
9.72	EC50	0.19	nM	CHEMBL3741746
9.72	Kd	0.19	nM	CHEMBL337834
9.70	IC50	0.2	nM	CHEMBL2151411
9.70	EC50	0.2	nM	CHEMBL4113544
9.66	IC50	0.22	nM	CHEMBL4435580
9.44	IC50	0.36	nM	CHEMBL4587471
9.43	Ki	0.376	nM	CHEMBL6057218
9.40	Ki	0.4	nM	CHEMBL285801
9.35	Ki	0.45	nM	APLYSIATOXIN
9.30	Ki	0.5	nM	CHEMBL4077967
9.26	EC50	0.55	nM	CHEMBL4587471
9.22	IC50	0.6	nM	CHEMBL1996510
9.22	EC50	0.6	nM	CHEMBL4575056
9.22	IC50	0.6	nM	STAUROSPORINE
9.19	IC50	0.64	nM	SOTRASTAURIN
9.17	Ki	0.683	nM	CHEMBL5912753
9.15	IC50	0.7	nM	CHEMBL4102228
9.10	EC50	0.8	nM	CHEMBL4115540
9.04	Ki	0.912	nM	CHEMBL6041594
9.00	IC50	1	nM	STAUROSPORINE
9.00	Ki	1.01	nM	CHEMBL5988431
8.95	Ki	1.12	nM	CHEMBL6049355
8.93	Ki	1.17	nM	CHEMBL5769039
8.92	IC50	1.2	nM	CHEMBL2153750
8.89	Kd	1.3	nM	CHEMBL27768
8.88	Kd	1.31	nM	CHEMBL27768
8.87	Kd	1.34	nM	CHEMBL27768
8.85	IC50	1.4	nM	CHEMBL2151415
8.85	IC50	1.413	nM	CHEMBL2236794
8.85	IC50	1.4	nM	CHEMBL2236794
8.85	IC50	1.4	nM	CHEMBL4072879
8.85	Ki	1.42	nM	CHEMBL337834
8.84	IC50	1.44	nM	STAUROSPORINE
8.82	Ki	1.5	nM	DEMETHOXYDEBROMOAPLYSIATOXIN
8.80	IC50	1.6	nM	GF-109203
8.79	Ki	1.64	nM	CHEMBL5902043
8.77	Ki	1.7	nM	CHEMBL3662851
8.77	IC50	1.7	nM	CHEMBL291126
8.77	Ki	1.71	nM	CHEMBL5924468

PubChem BioAssay actives

746 with measured affinity, of 3234 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
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	163205: Binding affinity for human PKC beta-1	kd	0.0002	uM
3-(7-methyl-1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione	689999: Inhibition of PKCbeta-1 by scintillation proximity assay	ic50	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	687830: Inhibition of [3H]PDBu binding to PKCbeta C1A domain	ki	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
(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	163193: Displacement of [3H]- PDBu from recombinant PKC beta expressed in baculovirus	ki	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	517263: Inhibition of [3H]PDBu binding to PKC beta C1A peptide	ki	0.0004	uM
3-[2-chloro-7-[(dimethylamino)methyl]naphthalen-1-yl]-4-(1-methylindol-3-yl)pyrrole-2,5-dione	1437231: Reversible competitive inhibition of PKCbeta1 (unknown origin)	ki	0.0005	uM
3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione	1902439: Inhibition of PKCbeta1 (unknown origin) by IMAP kinase assay	ic50	0.0006	uM
3-(1H-indol-3-yl)-4-(2-piperazin-1-ylquinazolin-4-yl)pyrrole-2,5-dione	689999: Inhibition of PKCbeta-1 by scintillation proximity assay	ic50	0.0006	uM
3-[2-chloro-7-[(dimethylamino)methyl]naphthalen-1-yl]-4-(1H-indol-3-yl)pyrrole-2,5-dione	1437218: Inhibition of PKCbeta1 (unknown origin) after 60 mins in presence of [gamma33P]ATP by scintillation proximity assay	ic50	0.0007	uM
3-[6-fluoro-2-(4-methylpiperazin-1-yl)quinazolin-4-yl]-4-(1H-indol-3-yl)pyrrole-2,5-dione	689999: Inhibition of PKCbeta-1 by scintillation proximity assay	ic50	0.0012	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	163363: Binding affinity for Protein kinase C beta C1a domain	kd	0.0013	uM
3-[2-chloro-7-(methylaminomethyl)naphthalen-1-yl]-4-(1-methylindol-3-yl)pyrrole-2,5-dione	1437218: Inhibition of PKCbeta1 (unknown origin) after 60 mins in presence of [gamma33P]ATP by scintillation proximity assay	ic50	0.0014	uM
3-(1-methylindol-3-yl)-4-(2-piperazin-1-ylquinazolin-4-yl)pyrrole-2,5-dione	689999: Inhibition of PKCbeta-1 by scintillation proximity assay	ic50	0.0014	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	768065: Displacement of [3H]PDBu from PKCbeta C1A domain (unknown origin)	ki	0.0015	uM
3-[1-[3-(dimethylamino)propyl]indol-3-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	0.0016	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
[(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	220908: Inhibition of [3H]-phorbol 12,13-dibutyrate (PDBu) binding to human recombinant protein kinase C beta	ki	0.0018	uM
3-(1H-indol-3-yl)-4-[3-(4-methylpiperazin-1-yl)naphthalen-1-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	0.0018	uM
2-[2,6-dihydroxy-4-[(3R,4R)-3-[(4-hydroxybenzoyl)amino]azepan-4-yl]oxycarbonylbenzoyl]-3-hydroxybenzoic acid	1315726: Binding affinity to PKCbeta2 (unknown origin) using Lys-Arg-Thr-Leu-Arg-Arg as substrate after 8 mins in presence of [gamma-32P]ATP by liquid scintillation spectrometry	kd	0.0018	uM
3-(1H-indol-3-yl)-4-[3-(4-methylpiperazin-1-yl)isoquinolin-1-yl]pyrrole-2,5-dione	689999: Inhibition of PKCbeta-1 by scintillation proximity assay	ic50	0.0020	uM
2-[4-[(1R,2R,4R)-4-amino-2-[(4-hydroxybenzoyl)amino]cyclopentyl]oxycarbonyl-2,6-dihydroxybenzoyl]-3-hydroxybenzoic acid	163351: Inhibitory concentration against recombinant human Protein kinase C beta 2 isozyme	ic50	0.0020	uM
3-[7-(azetidin-1-ylmethyl)-2-chloronaphthalen-1-yl]-4-(1-methylindol-3-yl)pyrrole-2,5-dione	1437218: Inhibition of PKCbeta1 (unknown origin) after 60 mins in presence of [gamma33P]ATP by scintillation proximity assay	ic50	0.0020	uM
3-(23-methyl-14-oxo-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4,6,8,10,15,17,19,21-nonaen-3-yl)propanenitrile	325569: Inhibition of PKCbeta	ic50	0.0020	uM
3-[3-(4-anilino-2,5-dioxopyrrol-3-yl)indol-1-yl]propyl carbamimidothioate;hydrobromide	241463: Inhibitory concentration against recombinant human Protein kinase C beta 2	ic50	0.0020	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	0.0021	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	163372: Displacement of 3[H]PDBu from Protein kinase C beta C1b domain	ki	0.0022	uM
3-[2-chloro-7-[(propan-2-ylamino)methyl]naphthalen-1-yl]-4-(1-methylindol-3-yl)pyrrole-2,5-dione	1437218: Inhibition of PKCbeta1 (unknown origin) after 60 mins in presence of [gamma33P]ATP by scintillation proximity assay	ic50	0.0029	uM
2-[2,6-dihydroxy-4-[(1R,2R,4S)-2-[(4-hydroxybenzoyl)amino]-4-(hydroxymethyl)cyclopentyl]oxycarbonylbenzoyl]-3-hydroxybenzoic acid	163351: Inhibitory concentration against recombinant human Protein kinase C beta 2 isozyme	ic50	0.0030	uM
2-[2,6-dihydroxy-4-[2-[(4-hydroxyphenyl)methyl]cyclopentyl]oxycarbonylbenzoyl]-3-hydroxybenzoic acid	163340: Evaluated against recombinant human Protein kinase C beta 2	ic50	0.0030	uM
2-[2,6-dihydroxy-4-[(1R,2S)-2-[(4-hydroxyphenyl)methyl]cyclopentyl]oxycarbonylbenzoyl]-3-hydroxybenzoic acid	1795485: PKC assay from Article 10.1021/jm960581w: “Synthesis and protein kinase C inhibitory activities of acyclic balanol analogs that are highly selective for protein kinase C over protein kinase A.”	ic50	0.0030	uM
3-[2-chloro-7-[(2-methoxyethylamino)methyl]naphthalen-1-yl]-4-(1-methylindol-3-yl)pyrrole-2,5-dione	1437218: Inhibition of PKCbeta1 (unknown origin) after 60 mins in presence of [gamma33P]ATP by scintillation proximity assay	ic50	0.0031	uM
3-[7-(aminomethyl)-2-chloronaphthalen-1-yl]-4-(1-methylindol-3-yl)pyrrole-2,5-dione	1437218: Inhibition of PKCbeta1 (unknown origin) after 60 mins in presence of [gamma33P]ATP by scintillation proximity assay	ic50	0.0033	uM
3-[2-chloro-6-[(dimethylamino)methyl]naphthalen-1-yl]-4-(1H-indol-3-yl)pyrrole-2,5-dione	1437218: Inhibition of PKCbeta1 (unknown origin) after 60 mins in presence of [gamma33P]ATP by scintillation proximity assay	ic50	0.0034	uM
3-(1H-indol-3-yl)-4-[5-methyl-2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione	689999: Inhibition of PKCbeta-1 by scintillation proximity assay	ic50	0.0038	uM
3-[1-[3-(dimethylamino)propyl]indazol-3-yl]-4-(1-quinolin-3-ylindol-3-yl)pyrrole-2,5-dione	241735: Inhibition of human Protein kinase C beta 2 using [gamma-33P]-ATP	ic50	0.0040	uM
2-[4-[(1R,2R,4S)-4-(aminomethyl)-2-[(4-hydroxybenzoyl)amino]cyclopentyl]oxycarbonyl-2,6-dihydroxybenzoyl]-3-hydroxybenzoic acid	163200: Inhibitory concentration against recombinant human Protein kinase C beta 1 isozyme	ic50	0.0040	uM
[2-(hydroxymethyl)-5-oxo-4-propan-2-ylideneoxolan-2-yl]methyl 4-[2-(4-methylphenyl)ethynyl]benzoate	350005: Displacement of [3H]PDBu form human PKCbeta in presence of phosphatidylserine	ki	0.0041	uM
(18S)-18-[(dimethylamino)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.17,14.02,6.08,13.022,27]nonacosa-1(28),2(6),7(29),8,10,12,22,24,26-nonaene-3,5-dione;methanesulfonic acid	163199: Inhibition of Protein kinase C beta 1	ic50	0.0047	uM
(18S)-18-[(dimethylamino)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.17,14.02,6.08,13.022,27]nonacosa-1(28),2(6),7(29),8,10,12,22,24,26-nonaene-3,5-dione	1397956: Inhibition of DAG-activated human PKCbeta1 after 10 mins in presence of [32P]ATP by beta scintillation counting method	ic50	0.0047	uM
3-[1-[3-(dimethylamino)propyl]indazol-3-yl]-4-(1-naphthalen-2-ylindol-3-yl)pyrrole-2,5-dione	241735: Inhibition of human Protein kinase C beta 2 using [gamma-33P]-ATP	ic50	0.0050	uM
(18S)-18-(methylaminomethyl)-17-oxa-4,14,21-triazahexacyclo[19.6.1.17,14.02,6.08,13.022,27]nonacosa-1(28),2(6),7(29),8,10,12,22,24,26-nonaene-3,5-dione	163197: Inhibition of Protein kinase C beta 1	ic50	0.0050	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tetradecanoylphorbol Acetate	increases abundance, increases activity, increases localization, affects reaction, increases reaction (+6 more)	11
Valproic Acid	affects methylation, affects cotreatment, increases expression, affects expression	9
Tretinoin	increases expression, increases reaction, increases phosphorylation	5
Arsenic Trioxide	decreases expression, increases expression, affects response to substance, increases reaction	4
Resveratrol	decreases reaction, increases activity, increases phosphorylation, affects cotreatment, decreases expression	3
Air Pollutants	increases expression, affects expression, increases abundance	3
Benzo(a)pyrene	decreases expression, decreases methylation, increases methylation, increases expression	3
Glucose	increases expression, increases activity, increases phosphorylation, decreases reaction	3
Ozone	affects expression, increases abundance, increases expression	3
mercuric bromide	decreases expression, affects cotreatment	2
Bandrowski’s base	increases expression, affects reaction	2
entinostat	affects cotreatment, increases expression	2
(+)-JQ1 compound	decreases expression	2
Decitabine	affects expression, decreases reaction, increases expression	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Copper	affects binding, decreases expression, affects cotreatment	2
Deoxycholic Acid	decreases reaction, increases expression, increases activity	2
Metformin	increases expression, decreases expression, decreases reaction	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tetrachlorodibenzodioxin	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
Particulate Matter	increases expression, decreases expression, affects cotreatment, increases abundance	2
FR900359	increases phosphorylation	1
quinone	increases expression	1
methylmercuric chloride	decreases expression	1
naringenin	affects localization, decreases reaction	1
bis(tri-n-butyltin)oxide	increases expression	1

ChEMBL screening assays

973 unique, capped per target: 951 binding, 21 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*
CHEMBL4424904	ADMET	Inhibition of human N-terminal His6-tagged (2 to end residues) PKCbeta expressed in baculovirus infected Sf21 insect cells using Histone H1 as substrate	Optimization of an azetidine series as inhibitors of colony stimulating factor-1 receptor (CSF-1R) Type II to lead to the clinical candidate JTE-952. — *Bioorg Med Chem Lett*

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_B8N5	Abcam HCT 116 PRKCB KO	Cancer cell line	Male
CVCL_B9AQ	Abcam MCF-7 PRKCB KO	Cancer cell line	Female
CVCL_B9QE	Abcam A-549 PRKCB KO	Cancer cell line	Male
CVCL_D9PL	Ubigene HEK293 PRKCB KO	Transformed cell line	Female
CVCL_E0LV	Ubigene HeLa PRKCB KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Predicted chemistry — Sugi Predict

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