myosin light chain kinase 2

Target id: 1553

Nomenclature: myosin light chain kinase 2

Abbreviated Name: skMLCK

Family: Myosin Light Chain Kinase (MLCK) family

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

   GtoImmuPdb view: OFF :     Currently no data for myosin light chain kinase 2 in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 596 20q13.31 MYLK2 myosin light chain kinase 2
Mouse - 613 2 Mylk2 myosin, light polypeptide kinase 2, skeletal muscle
Rat - 610 3q41 Mylk2 myosin light chain kinase 2
Previous and Unofficial Names
myosin light chain kinase 2, skeletal/cardiac muscle | MLCK2 (skeletal muscle isoform) | KMLC | myosin, light polypeptide kinase 2, skeletal muscle | myosin
Database Links
BRENDA
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  The complex between Ca-Calmodulin and skeletal muscle myosin light chain kinase from combination of NMR and aqueous and contrast-matched SAXS data
PDB Id:  2LV6
Resolution:  0.0Å
Species:  Human
References:  4
Enzyme Reaction
EC Number: 2.7.11.18

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

Activators
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Reference
calmodulin {Sp: Human} Hs Activation - - 5
[5]
Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
GSK2606414 Hs Inhibition 6.2 pIC50 2
pIC50 6.2 (IC50 7.01x10-7 M) [2]
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: 3,6

Key to terms and symbols Click column headers to sort
Target used in screen: MYLK2
Ligand Sp. Type Action Affinity Units
tozasertib Hs Inhibitor Inhibition 7.4 pKd
sunitinib Hs Inhibitor Inhibition 7.3 pKd
KW-2449 Hs Inhibitor Inhibition 7.3 pKd
lestaurtinib Hs Inhibitor Inhibition 7.3 pKd
staurosporine Hs Inhibitor Inhibition 7.2 pKd
dovitinib Hs Inhibitor Inhibition 7.0 pKd
SU-14813 Hs Inhibitor Inhibition 6.7 pKd
PD-173955 Hs Inhibitor Inhibition 6.7 pKd
AST-487 Hs Inhibitor Inhibition 6.5 pKd
PHA-665752 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/MLCK2(MYLK2)
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
JAK3 inhibitor VI Hs Inhibitor Inhibition 5.8
dovitinib Hs Inhibitor Inhibition 5.9
K-252a Hs Inhibitor Inhibition 6.2
staurosporine Hs Inhibitor Inhibition 7.6
sunitinib Hs Inhibitor Inhibition 7.7
SB 218078 Hs Inhibitor Inhibition 7.8
dorsomorphin Hs Inhibitor Inhibition 9.3
SU11652 Hs Inhibitor Inhibition 10.0
PKR inhibitor Hs Inhibitor Inhibition 12.0
GSK-3 inhibitor IX Hs Inhibitor Inhibition 17.6
Displaying the top 10 most potent ligands  View all ligands in screen »
Clinically-Relevant Mutations and Pathophysiology
Disease:  Cardiomyopathy, familial hypertrophic, 1; CMH1
Synonyms: Familial hypertrophic cardiomyopathy [Disease Ontology: DOID:11986]
Familial isolated hypertrophic cardiomyopathy [Orphanet: ORPHA155]
Disease Ontology: DOID:11986
OMIM: 192600
Orphanet: ORPHA155

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. Axten JM, Medina JR, Feng Y, Shu A, Romeril SP, Grant SW, Li WH, Heerding DA, Minthorn E, Mencken T et al.. (2012) Discovery of 7-methyl-5-(1-{[3-(trifluoromethyl)phenyl]acetyl}-2,3-dihydro-1H-indol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (GSK2606414), a potent and selective first-in-class inhibitor of protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK). J. Med. Chem., 55 (16): 7193-207. [PMID:22827572]

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. Grishaev A, Anthis NJ, Clore GM. (2012) Contrast-matched small-angle X-ray scattering from a heavy-atom-labeled protein in structure determination: application to a lead-substituted calmodulin-peptide complex. J. Am. Chem. Soc., 134 (36): 14686-9. [PMID:22908850]

5. Hathaway DR, Adelstein RS. (1979) Human platelet myosin light chain kinase requires the calcium-binding protein calmodulin for activity. Proc. Natl. Acad. Sci. U.S.A., 76 (4): 1653-7. [PMID:156362]

6. 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

Myosin Light Chain Kinase (MLCK) family: myosin light chain kinase 2. Last modified on 18/02/2015. Accessed on 19/08/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1553.