protein kinase C delta

Target id: 1485

Nomenclature: protein kinase C delta

Abbreviated Name: PKCδ

Family: Delta subfamily

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

Contents:

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 676 3p21.31 PRKCD protein kinase C delta
Mouse - 674 14 Prkcd protein kinase C, delta
Rat - 673 16p16 Prkcd protein kinase C, delta
Previous and Unofficial Names
nPKC-delta
PKCdelta
protein kinase C, delta
protein kinase C
Database Links
BRENDA 2.7.11.13
Ensembl Gene ENSG00000163932 (Hs), ENSMUSG00000021948 (Mm), ENSRNOG00000016346 (Rn)
Entrez Gene 5580 (Hs), 18753 (Mm), 170538 (Rn)
ExplorEnz 2.7.11.13
GeneCards PRKCD (Hs)
GenitoUrinary Development Molecular Anatomy Project Prkcd (Mm)
HomoloGene 55963 (Hs)
Human Protein Reference Database 01501 (Hs)
InterPro Q05655 (Hs), P28867 (Mm), P09215 (Rn)
KEGG Enzyme 2.7.11.13
KEGG Gene hsa:5580 (Hs), mmu:18753 (Mm), rno:170538 (Rn)
NeXtProt Q05655 (Hs)
OMIM 176977 (Hs)
Orphanet ORPHA332077 (Hs)
PhosphoSitePlus Q05655 (Hs), P28867 (Mm), P09215 (Rn)
RefSeq Nucleotide NM_006254 (Hs), NM_011103 (Mm), NM_133307 (Rn)
RefSeq Protein NP_006245 (Hs), NP_035233 (Mm), NP_579841 (Rn)
TreeFam PRKCD
UniGene Hs.155342 (Hs)
UniProtKB Q05655 (Hs), P28867 (Mm), P09215 (Rn)
Wikipedia PRKCD (Hs)
Selected 3D Structures
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
EC Number: 2.7.11.13

Download all structure-activity data for this target as a CSV file

Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
ingenol mebutate Hs Activation 9.4 pKi 9
pKi 9.4 (Ki 3.76x10-10 M) [9]
Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
sotrastaurin Hs Inhibition 8.9 pIC50 12
pIC50 8.9 (IC50 1.3x10-9 M) [12]
Gö 6983 Hs Inhibition 8.0 pIC50 7
pIC50 8.0 (IC50 1x10-8 M) [7]
balanol Hs Inhibition 7.8 pIC50 4
pIC50 7.8 (IC50 1.6x10-8 M) [4]
ruboxistaurin Hs Inhibition 6.6 pIC50 8
pIC50 6.6 (IC50 2.5x10-7 M) [8]
7-hydroxystaurosporine Hs Inhibition 6.2 pIC50 11
pIC50 6.2 (IC50 5.9x10-7 M) [11]
enzastaurin Hs Inhibition 6.0 pIC50 5
pIC50 6.0 (IC50 1x10-6 M) [5]
DiscoveRx KINOMEscan® screen
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: 3,13
Key to terms and symbols Click column headers to sort
Target used in screen: PRKCD
Ligand Sp. Type Action Affinity Units
staurosporine Hs Inhibitor Inhibition 8.8 pKd
ruboxistaurin Hs Inhibitor Inhibition 8.4 pKd
enzastaurin Hs Inhibitor Inhibition 7.6 pKd
A-674563 Hs Inhibitor Inhibition 7.6 pKd
GSK690693 Hs Inhibitor Inhibition 7.3 pKd
lestaurtinib Hs Inhibitor Inhibition 6.6 pKd
midostaurin Hs Inhibitor Inhibition 6.5 pKd
alvocidib Hs Inhibitor Inhibition 6.2 pKd
bosutinib Hs Inhibitor Inhibition 5.8 pKd
tofacitinib 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
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 Hs Inhibitor Inhibition 1.7 3.0 -1.0
GF109203X Hs Inhibitor Inhibition 4.7 2.0 -1.0
staurosporine Hs Inhibitor Inhibition 5.6 0.5 0.5
Ro-32-0432 Hs Inhibitor Inhibition 8.1
midostaurin Hs Inhibitor Inhibition 10.9 21.0 9.0
K-252a Hs Inhibitor Inhibition 12.6 18.0 3.0
SB 218078 Hs Inhibitor Inhibition 19.0 103.0 92.0
PKCbeta inhibitor Hs Inhibitor Inhibition 19.3 8.0 2.0
Cdk1/2 inhibitor III Hs Inhibitor Inhibition 22.2 10.0 9.0
Rho kinase inhibitor IV Hs Inhibitor Inhibition 22.4 7.0 3.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Clinically-Relevant Mutations and Pathophysiology
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:  10
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 10
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

Show »

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. 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]

9. 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]

10. 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]

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. 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

Delta subfamily: protein kinase C delta. Last modified on 30/03/2016. Accessed on 01/10/2016. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1485.