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myosin light chain kinase 2

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Target id: 1553

Nomenclature: myosin light chain kinase 2

Abbreviated Name: skMLCK

Family: Myosin Light Chain Kinase (MLCK) family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 596 20q11.21 MYLK2 myosin light chain kinase 2
Mouse - 613 2 H1 Mylk2 myosin, light polypeptide kinase 2, skeletal muscle
Rat - 610 3q41 Mylk2 myosin light chain kinase 2
Previous and Unofficial Names Click here for help
myosin light chain kinase 2, skeletal/cardiac muscle | MLCK2 (skeletal muscle isoform) | KMLC | myosin, light polypeptide kinase 2, skeletal muscle | myosin
Database Links Click here for help
Alphafold Q9H1R3 (Hs), Q8VCR8 (Mm), P20689 (Rn)
BRENDA 2.7.11.18
ChEMBL Target CHEMBL2777 (Hs)
Ensembl Gene ENSG00000101306 (Hs), ENSMUSG00000027470 (Mm), ENSRNOG00000008235 (Rn)
Entrez Gene 85366 (Hs), 228785 (Mm), 117558 (Rn)
Human Protein Atlas ENSG00000101306 (Hs)
KEGG Enzyme 2.7.11.18
KEGG Gene hsa:85366 (Hs), mmu:228785 (Mm), rno:117558 (Rn)
OMIM 606566 (Hs)
Pharos Q9H1R3 (Hs)
RefSeq Nucleotide NM_033118 (Hs), NM_001081044 (Mm), NM_057209 (Rn)
RefSeq Protein NP_149109 (Hs), NP_001074513 (Mm), NP_476557 (Rn)
UniProtKB Q9H1R3 (Hs), Q8VCR8 (Mm), P20689 (Rn)
Wikipedia MYLK2 (Hs)
Selected 3D Structures Click here for help
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 Click here for help
EC Number: 2.7.11.18

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

Activators
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
calmodulin {Sp: Human} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Activation - - 5
⤷ [5]
Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
GSK2606414 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.2 pIC50 2
⤷ pIC50 6.2 (IC50 7.01x10-7 M) [2]
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: 3,6
Key to terms and symbols Click column headers to sort
Target used in screen: MYLK2
Ligand Sp. Type Action Value Parameter
tozasertib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.4 pKd
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 7.3 pKd
KW-2449 Small molecule or natural product Hs Inhibitor Inhibition 7.3 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.3 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.2 pKd
dovitinib Small molecule or natural product Hs Inhibitor Inhibition 7.0 pKd
PD-173955 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.7 pKd
SU-14813 Small molecule or natural product Hs Inhibitor Inhibition 6.7 pKd
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 6.5 pKd
PHA-665752 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/MLCK2(MYLK2)
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
JAK3 inhibitor VI Small molecule or natural product Hs Inhibitor Inhibition 5.8
dovitinib Small molecule or natural product Hs Inhibitor Inhibition 5.9
K-252a Small molecule or natural product Hs Inhibitor Inhibition 6.2
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.6
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 7.7
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 7.8
dorsomorphin Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 9.3
SU11652 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 10.0
PKR inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 12.0
GSK-3 inhibitor IX Small molecule or natural product Hs Inhibitor Inhibition 17.6
Displaying the top 10 most potent ligands  View all ligands in screen »
Clinically-Relevant Mutations and Pathophysiology Click here for help
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 USA, 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 18/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=1553.