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calcium/calmodulin-dependent protein kinase II alpha subunit

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Target not currently curated in GtoImmuPdb

Target id: 1555

Nomenclature: calcium/calmodulin-dependent protein kinase II alpha subunit

Abbreviated Name: CaMK2α

Family: CAMK2 family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 478 5q32 CAMK2A calcium/calmodulin dependent protein kinase II alpha
Mouse - 478 18 34.41 cM Camk2a calcium/calmodulin-dependent protein kinase II alpha
Rat - 478 18q12.1 Camk2a calcium/calmodulin-dependent protein kinase II alpha
Previous and Unofficial Names Click here for help
CaM kinase II alpha subunit | CaMK-II alpha subunit | alpha CaM kinase II | PK2CDD | PKCCD | CaMKII
Database Links Click here for help
Alphafold Q9UQM7 (Hs), P11798 (Mm), P11275 (Rn)
BRENDA 2.7.11.17
ChEMBL Target CHEMBL4147 (Hs), CHEMBL2359 (Rn)
Ensembl Gene ENSG00000070808 (Hs), ENSMUSG00000024617 (Mm), ENSRNOG00000018712 (Rn)
Entrez Gene 815 (Hs), 12322 (Mm), 25400 (Rn)
Human Protein Atlas ENSG00000070808 (Hs)
KEGG Enzyme 2.7.11.17
KEGG Gene hsa:815 (Hs), mmu:12322 (Mm), rno:25400 (Rn)
OMIM 114078 (Hs)
Pharos Q9UQM7 (Hs)
RefSeq Nucleotide NM_015981 (Hs), NM_177407 (Mm), NM_012920 (Rn)
RefSeq Protein NP_057065 (Hs), NP_803126 (Mm), NP_037052 (Rn)
UniProtKB Q9UQM7 (Hs), P11798 (Mm), P11275 (Rn)
Wikipedia CAMK2A (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  STRUCTURE OF HUMAN CALCIUM CALMODULIN DEPENDENT PROTEIN KINASE TYPE II ALPHA (CAMK2A) IN COMPLEX WITH INDIRUBIN E804
PDB Id:  2VZ6
Resolution:  2.3Å
Species:  Human
References:  6
Enzyme Reaction Click here for help
EC Number: 2.7.11.17

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
KN-93 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Mm Inhibition 5.8 – 6.4 pIC50 3,7
⤷ pIC50 5.8 – 6.4 (IC50 1.6x10-6 – 3.7x10-7 M) [3,7]
Description: Assayed using purified mouse CaMKiiα subunit (Komiya et al, 2011).
KN-93 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Rn Inhibition 5.1 pIC50 5
⤷ pIC50 5.1 (IC50 8.4x10-6 M) [5]
Description: Assay performed using a truncated, recombinant rat CAMKIIalpha subunit, expressed in and purified from Sf9 cells.
View species-specific inhibitor tables
Inhibitor Comments
KN-93 is a calmodulin-competitive inhibitor of CaMKII phosphorylating activity [7].
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: 2,8
Key to terms and symbols Click column headers to sort
Target used in screen: CAMK2A
Ligand Sp. Type Action Value Parameter
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 9.8 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.0 pKd
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.7 pKd
ruxolitinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.3 pKd
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 7.1 pKd
fedratinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.5 pKd
A-674563 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.5 pKd
SU-14813 Small molecule or natural product Hs Inhibitor Inhibition 6.5 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.0 pKd
GSK-461364A Small molecule or natural product Hs Inhibitor Inhibition 6.0 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
Key to terms and symbols Click column headers to sort
Target used in screen: nd/CAMK2a
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 0.5
K-252a Small molecule or natural product Hs Inhibitor Inhibition 0.8
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 2.8
SU11652 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 3.6
indirubin derivative E804 Small molecule or natural product Hs Inhibitor Inhibition 12.2
GSK-3 inhibitor IX Small molecule or natural product Hs Inhibitor Inhibition 13.9
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 14.3
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 14.5
JAK3 inhibitor VI Small molecule or natural product Hs Inhibitor Inhibition 16.8
Gö 6976 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 19.1
Displaying the top 10 most potent ligands  View all ligands in screen »
General Comments
Using photoaffinity labeling, chemoproteomics and x-ray crystallography, CaMKIIα has been identified as a specific high-affinity molecular target for the natural substance γ-hydroxybutyric acid (γ-hydroxybutyrate; GHB) and related compounds [4]. GHB-like ligand interactions with CaMKIIα induce a neuroprotective effect.

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. Komiya M, Asano S, Koike N, Koga E, Igarashi J, Nakatani S, Isobe Y. (2011) Structure and activity relationship of 2-(substituted benzoyl)-hydroxyindoles as novel CaMKII inhibitors. Bioorg Med Chem Lett, 21 (5): 1456-8. [PMID:21292482]

4. Leurs U, Klein AB, McSpadden ED, Griem-Krey N, Solbak SMØ, Houlton J, Villumsen IS, Vogensen SB, Hamborg L, Gauger SJ et al.. (2021) GHB analogs confer neuroprotection through specific interaction with the CaMKIIα hub domain. Proc Natl Acad Sci U S A, 118 (31). [PMID:34330837]

5. Mirzoeva S, Sawkar A, Zasadzki M, Guo L, Velentza AV, Dunlap V, Bourguignon JJ, Ramstrom H, Haiech J, Van Eldik LJ et al.. (2002) Discovery of a 3-amino-6-phenyl-pyridazine derivative as a new synthetic antineuroinflammatory compound. J Med Chem, 31 (45): 563-6. [PMID:11806708]

6. Rellos P, Pike AC, Niesen FH, Salah E, Lee WH, von Delft F, Knapp S. (2010) Structure of the CaMKIIdelta/calmodulin complex reveals the molecular mechanism of CaMKII kinase activation. PLoS Biol, 8 (7): e1000426. [PMID:20668654]

7. Sumi M, Kiuchi K, Ishikawa T, Ishii A, Hagiwara M, Nagatsu T, Hidaka H. (1991) The newly synthesized selective Ca2+/calmodulin dependent protein kinase II inhibitor KN-93 reduces dopamine contents in PC12h cells. Biochem Biophys Res Commun, 181 (3): 968-75. [PMID:1662507]

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

CAMK2 family: calcium/calmodulin-dependent protein kinase II alpha subunit. Last modified on 01/05/2023. Accessed on 04/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=1555.