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protein kinase C gamma

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 1484

Nomenclature: protein kinase C gamma

Abbreviated Name: PKCγ

Family: Alpha subfamily

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 697 19q13.42 PRKCG protein kinase C gamma
Mouse - 697 7 1.93 cM Prkcg protein kinase C, gamma
Rat - 697 1q12 Prkcg protein kinase C, gamma
Previous and Unofficial Names Click here for help
PKCC | SCA14 | PKC-gamma | PKCI | Prkcc | protein kinase C, gamma | protein kinase C
Database Links Click here for help
Alphafold P05129 (Hs), P63318 (Mm), P63319 (Rn)
BRENDA 2.7.11.13
CATH/Gene3D 2.60.40.150
ChEMBL Target CHEMBL2938 (Hs), CHEMBL3604 (Rn)
Ensembl Gene ENSG00000126583 (Hs), ENSMUSG00000078816 (Mm), ENSRNOG00000054371 (Rn)
Entrez Gene 5582 (Hs), 18752 (Mm), 24681 (Rn)
Human Protein Atlas ENSG00000126583 (Hs)
KEGG Enzyme 2.7.11.13
KEGG Gene hsa:5582 (Hs), mmu:18752 (Mm), rno:24681 (Rn)
OMIM 176980 (Hs)
Orphanet ORPHA118014 (Hs)
Pharos P05129 (Hs)
RefSeq Nucleotide NM_002739 (Hs), NM_011102 (Mm), NM_012628 (Rn)
RefSeq Protein NP_002730 (Hs), NP_035232 (Mm), NP_036760 (Rn)
UniProtKB P05129 (Hs), P63318 (Mm), P63319 (Rn)
Wikipedia PRKCG (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Solution structure of the phorbol esters/diacylglycerol binding domain of protein kinase C gamma
PDB Id:  2E73
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 Click here for species-specific activity table Ligand has a PDB structure Hs Activation 9.8 pKi 8
⤷ pKi 9.8 (Ki 1.62x10-10 M) [8]
10-Me-Aplog-1 Small molecule or natural product Click here for species-specific activity table Hs Activation 8.3 pKi 9
⤷ pKi 8.3 (Ki 5.5x10-9 M) [9]
Description: Binding affinity for the C1A domain of PKCγ, 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
Gö 6983 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.2 pIC50 6
⤷ pIC50 8.2 (IC50 6x10-9 M) [6]
balanol Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.0 pIC50 3
⤷ pIC50 8.0 (IC50 1x10-8 M) [3]
GF109203X Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Bt Inhibition 7.7 pIC50 11
⤷ pIC50 7.7 (IC50 2x10-8 M) [11]
7-hydroxystaurosporine Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.5 pIC50 10
⤷ pIC50 7.5 (IC50 3x10-8 M) [10]
Ro-32-0432 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Bt Inhibition 7.4 – 7.4 pIC50 2,12
⤷ pIC50 7.4 – 7.4 (IC50 3.7x10-8 – 3.65x10-8 M) [2,12]
ruboxistaurin Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.5 pIC50 7
⤷ pIC50 6.5 (IC50 3x10-7 M) [7]
enzastaurin Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.7 pIC50 4
⤷ pIC50 5.7 (IC50 2x10-6 M) [4]
View species-specific inhibitor tables
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: 1,5
Key to terms and symbols Click column headers to sort
Target used in screen: PKCγ/PKCg
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 -3.2 1.5 1.0
Ro-32-0432 Small molecule or natural product Hs Inhibitor Inhibition 6.9
GF109203X Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 17.6 1.0 1.0
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 32.8 92.0 96.0
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 35.6 15.0 6.0
K-252a Small molecule or natural product Hs Inhibitor Inhibition 40.2 19.0 2.0
PKCbeta inhibitor Small molecule or natural product Hs Inhibitor Inhibition 51.6 8.0 2.0
Gö 6983 Small molecule or natural product Hs Inhibitor Inhibition 54.0 3.0 0.0
PDK1/Akt/Flt dual pathway inhibitor Small molecule or natural product Hs Inhibitor Inhibition 59.3 113.0 95.0
Gö 6976 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 72.1 9.0 16.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
PKCγ is included in GtoImmuPdb based on the involvement of other PKC isozymes in immune processes.
Immuno Process Associations
Immuno Process:  Cellular signalling
Immuno Process:  Inflammation
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Spinocerebellar ataxia 14; SCA14
Synonyms: Spinocerebellar ataxia [Disease Ontology: DOID:1441]
Disease Ontology: DOID:1441
OMIM: 605361
Orphanet: ORPHA98763

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. 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. 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]

5. 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]

6. 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]

7. 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]

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. 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]

11. Toullec D, Pianetti P, Coste H, Bellevergue P, Grand-Perret T, Ajakane M, Baudet V, Boissin P, Boursier E, Loriolle F et al.. (1991) The bisindolylmaleimide GF 109203X is a potent and selective inhibitor of protein kinase C. J Biol Chem, 266 (24): 15771-81. [PMID:1874734]

12. 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]

How to cite this page

Alpha subfamily: protein kinase C gamma. Last modified on 06/06/2024. Accessed on 13/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=1484.