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protein kinase C delta

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 1485

Nomenclature: protein kinase C delta

Abbreviated Name: PKCδ

Family: Delta subfamily

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 676 3p21.1 PRKCD protein kinase C delta
Mouse - 674 14 18.82 cM Prkcd protein kinase C, delta
Rat - 673 16p16 Prkcd protein kinase C, delta
Previous and Unofficial Names Click here for help
nPKC-delta | PKCdelta | protein kinase C, delta | protein kinase C
Database Links Click here for help
Alphafold Q05655 (Hs), P28867 (Mm), P09215 (Rn)
BRENDA 2.7.11.13
CATH/Gene3D 2.60.40.150
ChEMBL Target CHEMBL2996 (Hs), CHEMBL2560 (Mm), CHEMBL3633 (Rn)
Ensembl Gene ENSG00000163932 (Hs), ENSMUSG00000021948 (Mm), ENSRNOG00000016346 (Rn)
Entrez Gene 5580 (Hs), 18753 (Mm), 170538 (Rn)
Human Protein Atlas ENSG00000163932 (Hs)
KEGG Enzyme 2.7.11.13
KEGG Gene hsa:5580 (Hs), mmu:18753 (Mm), rno:170538 (Rn)
OMIM 176977 (Hs)
Orphanet ORPHA332077 (Hs)
Pharos Q05655 (Hs)
RefSeq Nucleotide NM_006254 (Hs), NM_011103 (Mm), NM_133307 (Rn)
RefSeq Protein NP_006245 (Hs), NP_035233 (Mm), NP_579841 (Rn)
UniProtKB Q05655 (Hs), P28867 (Mm), P09215 (Rn)
Wikipedia PRKCD (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Solution structure of the first Phorbol esters/diacylglycerol binding domain of human Protein kinase C, delta
PDB Id:  2YUU
Resolution:  0.0Å
Species:  Human
References: 
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 Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Activation 9.4 pKi 10
⤷ pKi 9.4 (Ki 3.76x10-10 M) [10]
10-Me-Aplog-1 Small molecule or natural product Click here for species-specific activity table Hs Activation 9.3 pKi 11
⤷ pKi 9.3 (Ki 4.6x10-10 M) [11]
Description: Binding affinity for the C1B domain of PKCδ, 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
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 8.9 pIC50 17
⤷ pIC50 8.9 (IC50 1.3x10-9 M) [17]
Gö 6983 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.0 pIC50 7
⤷ pIC50 8.0 (IC50 1x10-8 M) [7]
balanol Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.8 pIC50 4
⤷ pIC50 7.8 (IC50 1.6x10-8 M) [4]
compound 23 [PMID: 35816678] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.2 pIC50 13
⤷ pIC50 7.2 (IC50 7.1x10-8 M) [13]
ruboxistaurin Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.6 pIC50 9
⤷ pIC50 6.6 (IC50 2.5x10-7 M) [9]
7-hydroxystaurosporine Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.2 pIC50 15
⤷ pIC50 6.2 (IC50 5.9x10-7 M) [15]
enzastaurin Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.0 pIC50 5
⤷ pIC50 6.0 (IC50 1x10-6 M) [5]
rottlerin Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.5 pIC50 8
⤷ pIC50 5.5 (IC50 3.02x10-6 M) [8]
CC-90005 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.3 pIC50 14
⤷ pIC50 5.3 (IC50 4.44x10-6 M) [14]
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: 3,18
Key to terms and symbols Click column headers to sort
Target used in screen: PRKCD
Ligand Sp. Type Action Value Parameter
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.8 pKd
ruboxistaurin Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.4 pKd
enzastaurin Small molecule or natural product Hs Inhibitor Inhibition 7.6 pKd
A-674563 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.6 pKd
GSK690693 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.3 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.6 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 6.2 pKd
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 5.8 pKd
tofacitinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 5.7 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: PKCδ/PKCd
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
Gö 6983 Small molecule or natural product Hs Inhibitor Inhibition 1.7 3.0 -1.0
GF109203X Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 4.7 2.0 -1.0
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 5.6 0.5 0.5
Ro-32-0432 Small molecule or natural product Hs Inhibitor Inhibition 8.1
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 10.9 21.0 9.0
K-252a Small molecule or natural product Hs Inhibitor Inhibition 12.6 18.0 3.0
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 19.0 103.0 92.0
PKCbeta inhibitor Small molecule or natural product Hs Inhibitor Inhibition 19.3 8.0 2.0
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 22.2 10.0 9.0
Rho kinase inhibitor IV Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 22.4 7.0 3.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
PKCδ is included in GtoImmuPdb based on its GO immune process associations.
Immuno Process Associations
Immuno Process:  Inflammation
Comment:  Neutrophil chemotaxis (GO:0030593)
References:  16
Immuno Process:  Immune regulation
Immuno Process:  Cytokine production & signalling
Immuno Process:  T cell (activation)
Immuno Process:  B cell (activation)
Immuno Process:  Cellular signalling
Comment:  Neutrophil chemotaxis (GO:0030593)
References:  16
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Autoimmune lymphoproliferative syndrome, type III; ALPS3
Synonyms: Autoimmune lymphoproliferative syndrome [Orphanet: ORPHA3261] [Disease Ontology: DOID:6688]
Disease Ontology: DOID:6688
OMIM: 615559
Orphanet: ORPHA3261
References:  12
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human R614W c.1840C>T This deleterious homozygous mutation results in loss of function of the protein 12
Disease:  Autosomal recessive systemic lupus erythematosus
Orphanet: ORPHA300345
References:  2
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human G510S 1528G>A 2

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. Belot A, Kasher PR, Trotter EW, Foray AP, Debaud AL, Rice GI, Szynkiewicz M, Zabot MT, Rouvet I, Bhaskar SS et al.. (2013) Protein kinase cδ deficiency causes mendelian systemic lupus erythematosus with B cell-defective apoptosis and hyperproliferation. Arthritis Rheum, 65 (8): 2161-71. [PMID:23666743]

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. Faul MM, Gillig JR, Jirousek MR, Ballas LM, Schotten T, Kahl A, Mohr M. (2003) Acyclic N-(azacycloalkyl)bisindolylmaleimides: isozyme selective inhibitors of PKCbeta. Bioorg Med Chem Lett, 13 (11): 1857-9. [PMID:12749884]

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. Gschwendt M, Dieterich S, Rennecke J, Kittstein W, Mueller HJ, Johannes FJ. (1996) Inhibition of protein kinase C mu by various inhibitors. Differentiation from protein kinase c isoenzymes. FEBS Lett, 392 (2): 77-80. [PMID:8772178]

8. Gschwendt M, Müller HJ, Kielbassa K, Zang R, Kittstein W, Rincke G, Marks F. (1994) Rottlerin, a novel protein kinase inhibitor. Biochem Biophys Res Commun, 199 (1): 93-8. [PMID:8123051]

9. Jirousek MR, Gillig JR, Gonzalez CM, Heath WF, McDonald JH, Neel DA, Rito CJ, Singh U, Stramm LE, Melikian-Badalian A et al.. (1996) (S)-13-[(dimethylamino)methyl]-10,11,14,15-tetrahydro-4,9:16, 21-dimetheno-1H, 13H-dibenzo[e,k]pyrrolo[3,4-h][1,4,13]oxadiazacyclohexadecene-1,3(2H)-d ione (LY333531) and related analogues: isozyme selective inhibitors of protein kinase C beta. J Med Chem, 39 (14): 2664-71. [PMID:8709095]

10. 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]

11. 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]

12. Kuehn HS, Niemela JE, Rangel-Santos A, Zhang M, Pittaluga S, Stoddard JL, Hussey AA, Evbuomwan MO, Priel DA, Kuhns DB et al.. (2013) Loss-of-function of the protein kinase C δ (PKCδ) causes a B-cell lymphoproliferative syndrome in humans. Blood, 121 (16): 3117-25. [PMID:23430113]

13. Ladduwahetty T, Lee MR, Maillard MC, Cachope R, Todd D, Barnes M, Beaumont V, Chauhan A, Gallati C, Haughan AF et al.. (2022) Identification of a Potent, Selective, and Brain-Penetrant Rho Kinase Inhibitor and its Activity in a Mouse Model of Huntington's Disease. J Med Chem, 65 (14): 9819-9845. [PMID:35816678]

14. Papa P, Whitefield B, Mortensen DS, Cashion D, Huang D, Torres E, Parnes J, Sapienza J, Hansen J, Correa M et al.. (2021) Discovery of the Selective Protein Kinase C-θ Kinase Inhibitor, CC-90005. J Med Chem, 64 (16): 11886-11903. [PMID:34355886]

15. 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]

16. Uddin M, Seumois G, Lau LC, Davies DE, Djukanovic R. (2006) Activation of neutrophils by the repairing epithelium is regulated via PI3-kinase/Akt/PKCdelta-mediated signals. Thorax (BTS suppl 2), 61 (ii9): S21. DOI: 10.1136/thx.2007.080325

17. 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]

18. 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]

Contributors

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How to cite this page

Mohib Uddin.
Delta subfamily: protein kinase C delta. Last modified on 06/06/2024. Accessed on 13/10/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1485.