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protein kinase C epsilon

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 1486

Nomenclature: protein kinase C epsilon

Abbreviated Name: PKCε

Family: Eta subfamily

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 737 2p21 PRKCE protein kinase C epsilon
Mouse - 737 17 E4 Prkce protein kinase C, epsilon
Rat - 737 6q12 Prkce protein kinase C, epsilon
Previous and Unofficial Names Click here for help
nPKC-epsilon | PKCepsilon | protein kinase C, epsilon | protein kinase C
Database Links Click here for help
Alphafold Q02156 (Hs), P16054 (Mm), P09216 (Rn)
BRENDA 2.7.11.13
CATH/Gene3D 2.60.40.150
ChEMBL Target CHEMBL3582 (Hs), CHEMBL4366 (Mm), CHEMBL3424 (Rn)
Ensembl Gene ENSG00000171132 (Hs), ENSMUSG00000045038 (Mm), ENSRNOG00000015603 (Rn)
Entrez Gene 5581 (Hs), 18754 (Mm), 29340 (Rn)
Human Protein Atlas ENSG00000171132 (Hs)
KEGG Enzyme 2.7.11.13
KEGG Gene hsa:5581 (Hs), mmu:18754 (Mm), rno:29340 (Rn)
OMIM 176975 (Hs)
Pharos Q02156 (Hs)
RefSeq Nucleotide NM_005400 (Hs), NM_011104 (Mm), NM_017171 (Rn)
RefSeq Protein NP_005391 (Hs), NP_035234 (Mm), NP_058867 (Rn)
UniProtKB Q02156 (Hs), P16054 (Mm), P09216 (Rn)
Wikipedia PRKCE (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  STRUCTURE OF THE C2 DOMAIN FROM NOVEL PROTEIN KINASE C EPSILON
PDB Id:  1GMI
Resolution:  1.7Å
Species:  Human
References:  10
Enzyme Reaction Click here for help
EC Number: 2.7.11.13

Download all structure-activity data for this target as a CSV file go icon to follow link

Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
ingenol mebutate Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Activation 9.8 pKi 8
⤷ pKi 9.8 (Ki 1.71x10-10 M) [8]
10-Me-Aplog-1 Small molecule or natural product Click here for species-specific activity table Hs Activation 8.7 pKi 9
⤷ pKi 8.7 (Ki 2x10-9 M) [9]
Description: Binding affinity for the C1B domain of PKCε, determined by inhibition of [3H]PDBu binding
RasGRP activator 1 Small molecule or natural product Click here for species-specific activity table Hs Binding 7.7 pKi 7
⤷ pKi 7.7 (Ki 2.11x10-8 M) [7]
Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
sotrastaurin Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.2 pIC50 12
⤷ pIC50 8.2 (IC50 6.2x10-9 M) [12]
balanol Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.7 pIC50 4
⤷ pIC50 7.7 (IC50 2x10-8 M) [4]
chelerythrine Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.6 pIC50 5
⤷ pIC50 7.6 (IC50 2.4x10-8 M) [5]
Ro-32-0432 Small molecule or natural product Primary target of this compound Mm Inhibition 7.0 pIC50 2,13
⤷ pIC50 7.0 (IC50 1.08x10-7 M) [2,13]
Y27632 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.5 pIC50 15
⤷ pIC50 6.5 (IC50 3.35x10-7 M) [15]
7-hydroxystaurosporine Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.3 pIC50 11
⤷ pIC50 6.3 (IC50 5.3x10-7 M) [11]
View species-specific inhibitor tables
DiscoveRx KINOMEscan® screen Click here for help
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
http://www.discoverx.com/services/drug-discovery-development-services/kinase-profiling/kinomescan
Reference: 3,14
Key to terms and symbols Click column headers to sort
Target used in screen: PRKCE
Ligand Sp. Type Action Value Parameter
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 9.6 pKd
GSK690693 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.3 pKd
enzastaurin Small molecule or natural product Hs Inhibitor Inhibition 8.1 pKd
PP-242 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.1 pKd
ruboxistaurin Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.0 pKd
A-674563 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.0 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.8 pKd
alvocidib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.4 pKd
ruxolitinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.3 pKd
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.3 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen Click here for help
A screen profiling 158 kinase inhibitors (Calbiochem Protein Kinase Inhibitor Library I and II, catalogue numbers 539744 and 539745) for their inhibitory activity at 1µM and 10µM against 234 human recombinant kinases using the EMD Millipore KinaseProfilerTM service.

A screen profiling the inhibitory activity of 178 commercially available kinase inhibitors at 0.5µM against a panel of 300 recombinant protein kinases using the Reaction Biology Corporation Kinase HotspotSM platform.

http://www.millipore.com/techpublications/tech1/pf3036
http://www.reactionbiology.com/webapps/main/pages/kinase.aspx

Reference: 1,6
Key to terms and symbols Click column headers to sort
Target used in screen: PKCε/PKCepsilon
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
GF109203X Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 0.5 10.0 1.0
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 0.8 1.0 -0.5
Ro-32-0432 Small molecule or natural product Hs Inhibitor Inhibition 2.7
K-252a Small molecule or natural product Hs Inhibitor Inhibition 10.6 51.0 10.0
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 10.7 42.0 14.0
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 11.5 30.0 8.0
PKCbeta inhibitor Small molecule or natural product Hs Inhibitor Inhibition 12.8 21.0 3.0
Gö 6983 Small molecule or natural product Hs Inhibitor Inhibition 14.6 3.0 0.0
PKR inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 19.5 27.0 9.0
bisindolylmaleimide IV Small molecule or natural product Hs Inhibitor Inhibition 24.0 63.0 21.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
PKCε is included in GtoImmuPdb based on its GO immune process associations.
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Immune regulation
Immuno Process:  Cellular signalling

References

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1. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR. (2011) Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat Biotechnol, 29 (11): 1039-45. [PMID:22037377]

2. Birchall AM, Bishop J, Bradshaw D, Cline A, Coffey J, Elliott LH, Gibson VM, Greenham A, Hallam TJ, Harris W et al.. (1994) Ro 32-0432, a selective and orally active inhibitor of protein kinase C prevents T-cell activation. J Pharmacol Exp Ther, 268 (2): 922-9. [PMID:8114006]

3. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011) Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol, 29 (11): 1046-51. [PMID:22037378]

4. Defauw JM, Murphy MM, Jagdmann Jr GE, Hu H, Lampe JW, Hollinshead SP, Mitchell TJ, Crane HM, Heerding JM, Mendoza JS et al.. (1996) Synthesis and protein kinase C inhibitory activities of acyclic balanol analogs that are highly selective for protein kinase C over protein kinase A. J Med Chem, 39 (26): 5215-27. [PMID:8978850]

5. Fedorov O, Marsden B, Pogacic V, Rellos P, Müller S, Bullock AN, Schwaller J, Sundström M, Knapp S. (2007) A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. Proc Natl Acad Sci USA, 104 (51): 20523-8. [PMID:18077363]

6. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ. (2013) A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. Biochem J, 451 (2): 313-28. [PMID:23398362]

7. Garcia LC, Donadío LG, Mann E, Kolusheva S, Kedei N, Lewin NE, Hill CS, Kelsey JS, Yang J, Esch TE et al.. (2014) Synthesis, biological, and biophysical studies of DAG-indololactones designed as selective activators of RasGRP. Bioorg Med Chem, 22 (12): 3123-40. [PMID:24794745]

8. Kedei N, Lundberg DJ, Toth A, Welburn P, Garfield SH, Blumberg PM. (2004) Characterization of the interaction of ingenol 3-angelate with protein kinase C. Cancer Res, 64 (9): 3243-55. [PMID:15126366]

9. Kikumori M, Yanagita RC, Tokuda H, Suzuki N, Nagai H, Suenaga K, Irie K. (2012) Structure-activity studies on the spiroketal moiety of a simplified analogue of debromoaplysiatoxin with antiproliferative activity. J Med Chem, 55 (11): 5614-26. [PMID:22625994]

10. Ochoa WF, Garcia-Garcia J, Fita I, Corbalan-Garcia S, Verdaguer N, Gomez-Fernandez JC. (2001) Structure of the C2 domain from novel protein kinase Cepsilon. A membrane binding model for Ca(2+)-independent C2 domains. J Mol Biol, 311 (4): 837-49. [PMID:11518534]

11. Seynaeve CM, Kazanietz MG, Blumberg PM, Sausville EA, Worland PJ. (1994) Differential inhibition of protein kinase C isozymes by UCN-01, a staurosporine analogue. Mol Pharmacol, 45 (6): 1207-14. [PMID:8022414]

12. Wagner J, von Matt P, Sedrani R, Albert R, Cooke N, Ehrhardt C, Geiser M, Rummel G, Stark W, Strauss A et al.. (2009) 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. J Med Chem, 52 (20): 6193-6. [PMID:19827831]

13. Wilkinson SE, Parker PJ, Nixon JS. (1993) Isoenzyme specificity of bisindolylmaleimides, selective inhibitors of protein kinase C. Biochem J, 294 ( Pt 2): 335-7. [PMID:8373348]

14. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010) Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. Chem Biol, 17 (11): 1241-9. [PMID:21095574]

15. Wu F, Büttner FH, Chen R, Hickey E, Jakes S, Kaplita P, Kashem MA, Kerr S, Kugler S, Paw Z et al.. (2010) Substituted 2H-isoquinolin-1-one as potent Rho-Kinase inhibitors. Part 1: Hit-to-lead account. Bioorg Med Chem Lett, 20 (11): 3235-9. [PMID:20462760]

How to cite this page

Eta subfamily: protein kinase C epsilon. Last modified on 06/06/2024. Accessed on 08/10/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=1486.