calcium/calmodulin-dependent protein kinase II alpha subunit | CAMK2 family | IUPHAR/BPS Guide to PHARMACOLOGY

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calcium/calmodulin-dependent protein kinase II alpha subunit

Target not currently curated in GtoImmuPdb

Target id: 1555

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

Abbreviated Name: CaMK2α

Family: CAMK2 family

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 - 489 5 CAMK2A calcium/calmodulin dependent protein kinase II alpha
Mouse - 478 18 Camk2a calcium/calmodulin-dependent protein kinase II alpha
Rat - 478 18q11 Camk2a calcium/calmodulin-dependent protein kinase II alpha
Previous and Unofficial Names
CaM kinase II alpha subunit | CaMK-II alpha subunit | alpha CaM kinase II | PK2CDD | PKCCD | CaMKII
Database Links
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
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:  5
Enzyme Reaction
EC Number: 2.7.11.17

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

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
KN-93 Mm Inhibition 5.8 – 6.4 pIC50 3,6
⤷ pIC50 5.8 – 6.4 (IC50 1.6x10-6 – 3.7x10-7 M) [3,6]
Description: Assayed using purified mouse CaMKiiα subunit (Komiya et al, 2011).
KN-93 Rn Inhibition 5.1 pIC50 4
⤷ pIC50 5.1 (IC50 8.4x10-6 M) [4]
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 [6].
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: 2,7
Key to terms and symbols Click column headers to sort
Target used in screen: CAMK2A
Ligand Sp. Type Action Value Parameter
staurosporine Hs Inhibitor Inhibition 9.8 pKd
lestaurtinib Hs Inhibitor Inhibition 8.0 pKd
midostaurin Hs Inhibitor Inhibition 7.7 pKd
ruxolitinib Hs Inhibitor Inhibition 7.3 pKd
sunitinib Hs Inhibitor Inhibition 7.1 pKd
fedratinib Hs Inhibitor Inhibition 6.5 pKd
A-674563 Hs Inhibitor Inhibition 6.5 pKd
SU-14813 Hs Inhibitor Inhibition 6.5 pKd
NVP-TAE684 Hs Inhibitor Inhibition 6.0 pKd
GSK-461364A 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
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 Hs Inhibitor Inhibition 0.5
K-252a Hs Inhibitor Inhibition 0.8
SB 218078 Hs Inhibitor Inhibition 2.8
SU11652 Hs Inhibitor Inhibition 3.6
indirubin derivative E804 Hs Inhibitor Inhibition 12.2
GSK-3 inhibitor IX Hs Inhibitor Inhibition 13.9
Cdk1/2 inhibitor III Hs Inhibitor Inhibition 14.3
sunitinib Hs Inhibitor Inhibition 14.5
JAK3 inhibitor VI Hs Inhibitor Inhibition 16.8
Gö 6976 Hs Inhibitor Inhibition 19.1
Displaying the top 10 most potent ligands  View all ligands in screen »
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 1 GO processes
GO:0060333 interferon-gamma-mediated signaling pathway TAS
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 1 GO processes
GO:0060333 interferon-gamma-mediated signaling pathway TAS

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. 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]

5. 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]

6. 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]

7. 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 23/10/2014. Accessed on 26/05/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1555.