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protein kinase C eta

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 1487

Nomenclature: protein kinase C eta

Abbreviated Name: PKCη

Family: Eta subfamily

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 683 14q23.1 PRKCH protein kinase C eta
Mouse - 683 12 C3 Prkch protein kinase C, eta
Rat - 683 6q24 Prkch protein kinase C, eta
Previous and Unofficial Names Click here for help
PKCL | PKC-L | PRKCL | Pkch | protein kinase C, eta | protein kinase C
Database Links Click here for help
Alphafold P24723 (Hs), P23298 (Mm), Q64617 (Rn)
BRENDA 2.7.11.13
CATH/Gene3D 2.60.40.150
ChEMBL Target CHEMBL3616 (Hs), CHEMBL4992 (Mm)
Ensembl Gene ENSG00000027075 (Hs), ENSMUSG00000021108 (Mm), ENSRNOG00000004873 (Rn)
Entrez Gene 5583 (Hs), 18755 (Mm), 81749 (Rn)
Human Protein Atlas ENSG00000027075 (Hs)
KEGG Enzyme 2.7.11.13
KEGG Gene hsa:5583 (Hs), mmu:18755 (Mm), rno:81749 (Rn)
OMIM 605437 (Hs)
Pharos P24723 (Hs)
RefSeq Nucleotide NM_006255 (Hs), NM_008856 (Mm), NM_031085 (Rn)
RefSeq Protein NP_006246 (Hs), NP_032882 (Mm), NP_112347 (Rn)
UniProtKB P24723 (Hs), P23298 (Mm), Q64617 (Rn)
Wikipedia PRKCH (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Human protein kinase C, eta
PDB Id:  2FK9
Resolution:  1.75Å
Species:  Human
References:  7
Image of receptor 3D structure from RCSB PDB
Description:  PKC eta kinase in complex with a naphthyridine
PDB Id:  3TXO
Resolution:  2.05Å
Species:  Human
References:  8
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
10-Me-Aplog-1 Small molecule or natural product Click here for species-specific activity table Hs Activation 9.4 pKi 5
⤷ pKi 9.4 (Ki 4.5x10-10 M) [5]
Description: Binding affinity for the C1B domain of PKCη, determined by inhibition of [3H]PDBu binding
Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
balanol Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.5 pIC50 3
⤷ pIC50 8.5 (IC50 3x10-9 M) [3]
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 9
⤷ pIC50 8.2 (IC50 6.1x10-9 M) [9]
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: 2,10
Key to terms and symbols Click column headers to sort
Target used in screen: PRKCH
Ligand Sp. Type Action Value Parameter
GSK690693 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.6 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.3 pKd
A-674563 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.0 pKd
enzastaurin Small molecule or natural product Hs Inhibitor Inhibition 7.3 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.8 pKd
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.5 pKd
alvocidib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.5 pKd
PP-242 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.1 pKd
ruboxistaurin Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 5.7 pKd
SB203580 Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition <5.5 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: 1,4
Key to terms and symbols Click column headers to sort
Target used in screen: PKCη/PKCeta
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 0.4 2.5 0.0
Gö 6983 Small molecule or natural product Hs Inhibitor Inhibition 6.8 10.0 2.0
GF109203X Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.7 9.0 1.0
Ro-32-0432 Small molecule or natural product Hs Inhibitor Inhibition 7.8
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 20.4 84.0 29.0
K-252a Small molecule or natural product Hs Inhibitor Inhibition 20.5 36.0 7.0
PKCbeta inhibitor Small molecule or natural product Hs Inhibitor Inhibition 29.7 15.0 2.0
Rho kinase inhibitor IV Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 34.4 27.0 4.0
Gö 6976 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 35.3 72.0 60.0
PKR inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 41.2 23.0 5.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
PKCη is included in GtoImmuPdb based on the involvement of other PKC isozymes in immune processes.
Immuno Process Associations
Immuno Process:  Immune regulation
Immuno Process:  Cellular signalling
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Stroke, ischemic
Synonyms: Cerebral infarction
Cerebrovascular accident [Disease Ontology: DOID:3455]
Disease Ontology: DOID:3455
OMIM: 601367
Comments:  A non-synonymous SNP in PRKCH causes susceptibility to cerebral infarction.
References:  6
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human V374I 1425G>A 6

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. 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]

3. 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]

4. 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]

5. 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]

6. Kubo M, Hata J, Ninomiya T, Matsuda K, Yonemoto K, Nakano T, Matsushita T, Yamazaki K, Ohnishi Y, Saito S et al.. (2007) A nonsynonymous SNP in PRKCH (protein kinase C eta) increases the risk of cerebral infarction. Nat Genet, 39 (2): 212-7. [PMID:17206144]

7. Littler DR, Walker JR, She YM, Finerty PJ, Newman EM, Dhe-Paganon S. (2006) Structure of human protein kinase C eta (PKCeta) C2 domain and identification of phosphorylation sites. Biochem Biophys Res Commun, 349 (4): 1182-9. [PMID:16973127]

8. van Eis MJ, Evenou JP, Floersheim P, Gaul C, Cowan-Jacob SW, Monovich L, Rummel G, Schuler W, Stark W, Strauss A et al.. (2011) 2,6-Naphthyridines as potent and selective inhibitors of the novel protein kinase C isozymes. Bioorg Med Chem Lett, 21 (24): 7367-72. [PMID:22078216]

9. 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]

10. 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]

How to cite this page

Eta subfamily: protein kinase C eta. Last modified on 06/06/2024. Accessed on 05/10/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=1487.