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protein kinase, cAMP-dependent, catalytic, alpha subunit

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Target not currently curated in GtoImmuPdb

Target id: 1476

Nomenclature: protein kinase, cAMP-dependent, catalytic, alpha subunit

Abbreviated Name: PKACa

Family: Protein kinase A (PKA) family

Contents:

Quaternary Structure: Complexes
protein kinase A
Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 351 19p13.12 PRKACA protein kinase cAMP-activated catalytic subunit alpha
Mouse - 351 8 C2 Prkaca protein kinase, cAMP dependent, catalytic, alpha
Rat - 351 19q11 Prkaca protein kinase cAMP-activated catalytic subunit alpha
Previous and Unofficial Names Click here for help
cAMP-dependent protein kinase catalytic subunit C alpha | Cs-PKA | PKA C-alpha | PKCA1 | Pkaca | protein kinase, cAMP-dependent, catalytic, alpha | protein kinase, cAMP-dependent, alpha catalytic subunit | protein kinase, cAMP dependent, catalytic, alpha | protein kinase
Database Links Click here for help
Alphafold P17612 (Hs), P05132 (Mm), P27791 (Rn)
BRENDA 2.7.11.11
ChEMBL Target CHEMBL4101 (Hs), CHEMBL3390 (Rn)
Ensembl Gene ENSG00000072062 (Hs), ENSMUSG00000005469 (Mm), ENSRNOG00000005257 (Rn)
Entrez Gene 5566 (Hs), 18747 (Mm), 25636 (Rn)
Human Protein Atlas ENSG00000072062 (Hs)
KEGG Enzyme 2.7.11.11
KEGG Gene hsa:5566 (Hs), mmu:18747 (Mm), rno:25636 (Rn)
OMIM 601639 (Hs)
Pharos P17612 (Hs)
RefSeq Nucleotide NM_002730 (Hs), NM_008854 (Mm), NM_001100922 (Rn)
RefSeq Protein NP_002721 (Hs), NP_032880 (Mm), NP_001094392 (Rn)
SynPHARM 80427 (in complex with H-89)
UniProtKB P17612 (Hs), P05132 (Mm), P27791 (Rn)
Wikipedia PRKACA (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Complex of PKA with the bisubstrate protein kinase inhibitor ARC-1039
PDB Id:  3AGL
Resolution:  2.1Å
Species:  Human
References:  7
Enzyme Reaction Click here for help
EC Number: 2.7.11.11

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

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
GSK690693 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.7 pKd 3
⤷ pKd 7.7 (Kd 1.9x10-8 M) [3]
H-89 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inhibition 7.3 pKi 2
⤷ pKi 7.3 (Ki 4.8x10-8 M) [2]
aplithianine A Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.1 pIC50 4
⤷ pIC50 7.1 (IC50 8.4x10-8 M) [4]
ripasudil Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 5.7 pIC50 6
⤷ pIC50 5.7 (IC50 2.1x10-6 M) [6]
Inhibitor Comments
The data for H-89 provided here is derived from [2], but species and PKA subunit information is from BindingDB's entry for this ligand.
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: 3,8
Key to terms and symbols Click column headers to sort
Target used in screen: PKAC-alpha
Ligand Sp. Type Action Value Parameter
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.7 pKd
GSK690693 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.7 pKd
A-674563 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 6.7 pKd
enzastaurin Small molecule or natural product Hs Inhibitor Inhibition 6.5 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.2 pKd
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.1 pKd
SB203580 Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition <5.5 pKd
erlotinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition <5.5 pKd
crizotinib Small molecule or natural product Approved drug Ligand has a PDB structure 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: 1,5
Key to terms and symbols Click column headers to sort
Target used in screen: PKA/PKA
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 1.9 0.5 2.5
H-89 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 10.5 2.0 6.0
K-252a Small molecule or natural product Hs Inhibitor Inhibition 18.0 7.0 3.0
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 34.0 13.0 10.0
PKR inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 40.1 25.0 5.0
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 44.7 70.0 68.0
PP1 analog II Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 54.3 34.0 8.0
GF109203X Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 72.0 60.0 20.0
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 73.8
PDK1/Akt/Flt dual pathway inhibitor Small molecule or natural product Hs Inhibitor Inhibition 76.6 95.0 82.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Immune regulation
Immuno Process:  Cytokine production & signalling
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. Chijiwa T, Mishima A, Hagiwara M, Sano M, Hayashi K, Inoue T, Naito K, Toshioka T, Hidaka H. (1990) Inhibition of forskolin-induced neurite outgrowth and protein phosphorylation by a newly synthesized selective inhibitor of cyclic AMP-dependent protein kinase, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89), of PC12D pheochromocytoma cells. J Biol Chem, 265 (9): 5267-72. [PMID:2156866]

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. Du L, Wilson BAP, Li N, Shah R, Dalilian M, Wang D, Smith EA, Wamiru A, Goncharova EI, Zhang P et al.. (2023) Discovery and Synthesis of a Naturally Derived Protein Kinase Inhibitor that Selectively Inhibits Distinct Classes of Serine/Threonine Kinases. J Nat Prod, 86 (10): 2283-2293. [PMID:37843072]

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. Isobe T, Mizuno K, Kaneko Y, Ohta M, Koide T, Tanabe S. (2014) Effects of K-115, a rho-kinase inhibitor, on aqueous humor dynamics in rabbits. Curr Eye Res, 39 (8): 813-22. [PMID:24502505]

7. Pflug A, Rogozina J, Lavogina D, Enkvist E, Uri A, Engh RA, Bossemeyer D. (2010) Diversity of bisubstrate binding modes of adenosine analogue-oligoarginine conjugates in protein kinase a and implications for protein substrate interactions. J Mol Biol, 403 (1): 66-77. [PMID:20732331]

8. 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

Protein kinase A (PKA) family: protein kinase, cAMP-dependent, catalytic, alpha subunit. Last modified on 11/01/2024. Accessed on 16/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1476.