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myosin light chain kinase

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Target id: 1552

Nomenclature: myosin light chain kinase

Abbreviated Name: smMLCK

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 - 1914 3q21.1 MYLK myosin light chain kinase
Mouse - 1941 16 B3 Mylk myosin, light polypeptide kinase
Rat - 1961 11q22 Mylk myosin light chain kinase
Previous and Unofficial Names Click here for help
MLCK108 | MLCK210 | telokin | MLCK1 (smooth muscle and non-muscle isoform) | myosin
Database Links Click here for help
Alphafold Q15746 (Hs), Q6PDN3 (Mm)
BRENDA 2.7.11.18
CATH/Gene3D 2.60.40.10
ChEMBL Target CHEMBL2428 (Hs)
Ensembl Gene ENSG00000065534 (Hs), ENSMUSG00000022836 (Mm), ENSRNOG00000002215 (Rn)
Entrez Gene 4638 (Hs), 107589 (Mm), 288057 (Rn)
Human Protein Atlas ENSG00000065534 (Hs)
KEGG Enzyme 2.7.11.18
KEGG Gene hsa:4638 (Hs), mmu:107589 (Mm), rno:288057 (Rn)
OMIM 600922 (Hs)
Orphanet ORPHA246653 (Hs)
Pharos Q15746 (Hs)
RefSeq Nucleotide NM_053025 (Hs), NM_139300 (Mm), NM_001105874 (Rn)
RefSeq Protein NP_444253 (Hs), NP_647461 (Mm), NP_001099344 (Rn)
UniProtKB Q15746 (Hs), Q6PDN3 (Mm)
Wikipedia MYLK (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Calmodulin complexed with calmodulin-binding peptide from smooth muscle myosin light chain kinase- solution NMR
PDB Id:  2K0F
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
RKI-1447 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.8 pIC50 7
⤷ pIC50 7.8 (IC50 1.563x10-8 M) [7]
MLCK inhibitor peptide 18 Peptide Primary target of this compound Ggal Inhibition 7.3 pIC50 6
⤷ pIC50 7.3 (IC50 5x10-8 M) [6]
View species-specific inhibitor tables
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: MYLK
Ligand Sp. Type Action Value Parameter
GSK-1838705A Small molecule or natural product Hs Inhibitor Inhibition 8.0 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.9 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.8 pKd
BI-2536 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.0 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.7 pKd
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.6 pKd
ruboxistaurin Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.5 pKd
PP-242 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 6.4 pKd
ruxolitinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.4 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: 1,3
Key to terms and symbols Click column headers to sort
Target used in screen: MLCK/MLCK(MYLK)
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 2.2 0.0 0.5
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 4.0 90.0 65.0
K-252a Small molecule or natural product Hs Inhibitor Inhibition 6.4 1.0 2.0
JAK inhibitor I Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 9.0 2.0 4.0
isogranulatimide Small molecule or natural product Hs Inhibitor Inhibition 15.5 11.0 8.0
SU11652 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 17.6 9.0 3.0
GF109203X Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 23.2 20.0 7.0
Gö 6976 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 24.6 16.0 11.0
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 25.6
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 27.3 13.0 10.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Aortic aneurysm, familial thoracic 7; AAT7
Synonyms: Familial thoracic aortic aneurysm and aortic dissection [Orphanet: ORPHA91387]
thoracic aortic aneurysm
Disease Ontology: DOID:14004
OMIM: 613780
Orphanet: ORPHA91387

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. 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]

4. Gsponer J, Christodoulou J, Cavalli A, Bui JM, Richter B, Dobson CM, Vendruscolo M. (2008) A coupled equilibrium shift mechanism in calmodulin-mediated signal transduction. Structure, 16 (5): 736-46. [PMID:18462678]

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. Lukas TJ, Mirzoeva S, Slomczynska U, Watterson DM. (1999) Identification of novel classes of protein kinase inhibitors using combinatorial peptide chemistry based on functional genomics knowledge. J Med Chem, 42 (5): 910-9. [PMID:10072688]

7. Pireddu R, Forinash KD, Sun NN, Martin MP, Sung SS, Alexander B, Zhu JY, Guida WC, Schönbrunn E, Sebti SM et al.. (2012) Pyridylthiazole-based ureas as inhibitors of Rho associated protein kinases (ROCK1 and 2). Medchemcomm, 3 (6): 699-709. [PMID:23275831]

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

Myosin Light Chain Kinase (MLCK) family: myosin light chain kinase. Last modified on 03/11/2016. Accessed on 16/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=1552.