muscle associated receptor tyrosine kinase | Type IX RTKs: MuSK | IUPHAR/BPS Guide to PHARMACOLOGY

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muscle associated receptor tyrosine kinase

Target not currently curated in GtoImmuPdb

Target id: 1847

Nomenclature: muscle associated receptor tyrosine kinase

Abbreviated Name: MuSK

Family: Type IX RTKs: MuSK

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

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 869 9q31.3-q32 MUSK muscle associated receptor tyrosine kinase
Mouse 1 893 4 Musk muscle, skeletal, receptor tyrosine kinase
Rat 1 868 5q24 Musk muscle associated receptor tyrosine kinase
Previous and Unofficial Names
Nsk1 | muscle specific kinase (neural fold/somite kinase 1) | muscle-specific tyrosine protein kinase receptor | MDK4 | Nsk2 | Nsk3 | muscle, skeletal, receptor tyrosine kinase | muscle
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of the MuSK Tyrosine Kinase: Insights into Receptor Autoregulation
PDB Id:  1LUF
Resolution:  2.05Å
Species:  Rat
References:  5
Enzyme Reaction
EC Number: 2.7.10.1

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
compound 25 [PMID: 17935989] Hs Inhibition 5.8 pKi 4
pKi 5.8 (Ki 1.65x10-6 M) [4]
compound 1d [PMID: 21493067] Hs Inhibition 6.7 pIC50 6
pIC50 6.7 (IC50 2.24x10-7 M) [6]
Inhibitor Comments
Compound 25 [PMID 17935989] is a CHK1 inhibitor and interacts with MUSK as an off-target. Inhibiton of CHK1 is >400 times more potent than inhibition of MUSK [4]. Similarly MUSK is an off-target of the JAK2 inhibitor compound 1d [PMID 21493067] [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: MUSK
Ligand Sp. Type Action Value Parameter
AST-487 Hs Inhibitor Inhibition 8.5 pKd
linifanib Hs Inhibitor Inhibition 8.0 pKd
foretinib Hs Inhibitor Inhibition 7.9 pKd
staurosporine Hs Inhibitor Inhibition 7.1 pKd
SU-14813 Hs Inhibitor Inhibition 7.0 pKd
tamatinib Hs Inhibitor Inhibition 7.0 pKd
sorafenib Hs Inhibitor Inhibition 6.9 pKd
KW-2449 Hs Inhibitor Inhibition 6.7 pKd
crizotinib Hs Inhibitor Inhibition 6.6 pKd
NVP-TAE684 Hs Inhibitor Inhibition 6.6 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: 1,3

Key to terms and symbols Click column headers to sort
Target used in screen: MuSK/MUSK
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
K-252a Hs Inhibitor Inhibition 6.1 18.0 2.0
JAK3 inhibitor VI Hs Inhibitor Inhibition 6.1 25.0 2.0
Cdk1/2 inhibitor III Hs Inhibitor Inhibition 8.0 0.0 0.0
staurosporine Hs Inhibitor Inhibition 12.2 -1.0 0.5
JNK inhibitor V Hs Inhibitor Inhibition 14.8 90.0 50.0
PI 3-Kg inhibitor Hs Inhibitor Inhibition 16.2 90.0 75.0
PKR inhibitor Hs Inhibitor Inhibition 21.6 53.0 11.0
SB 218078 Hs Inhibitor Inhibition 25.8 103.0 93.0
Cdc2-like kinase inhibitor Hs Inhibitor Inhibition 28.4 82.0 75.0
Gö 6976 Hs Inhibitor Inhibition 34.8 32.0 37.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Clinically-Relevant Mutations and Pathophysiology
Disease:  Myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency; CMS9
Synonyms: Congenital myasthenic syndrome [Orphanet: ORPHA590] [Disease Ontology: DOID:3635]
Postsynaptic congenital myasthenic syndromes [Orphanet: ORPHA98913]
Disease Ontology: DOID:3635
OMIM: 616325
Orphanet: ORPHA590, ORPHA98913

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. Tao ZF, Chen Z, Bui MH, Kovar P, Johnson E, Bouska J, Zhang H, Rosenberg S, Sowin T, Lin NH. (2007) Macrocyclic ureas as potent and selective Chk1 inhibitors: an improved synthesis, kinome profiling, structure-activity relationships, and preliminary pharmacokinetics. Bioorg. Med. Chem. Lett., 17 (23): 6593-601. [PMID:17935989]

5. Till JH, Becerra M, Watty A, Lu Y, Ma Y, Neubert TA, Burden SJ, Hubbard SR. (2002) Crystal structure of the MuSK tyrosine kinase: insights into receptor autoregulation. Structure, 10 (9): 1187-96. [PMID:12220490]

6. Wang T, Ioannidis S, Almeida L, Block MH, Davies AM, Lamb ML, Scott DA, Su M, Zhang HJ, Alimzhanov M et al.. (2011) In vitro and in vivo evaluation of 6-aminopyrazolyl-pyridine-3-carbonitriles as JAK2 kinase inhibitors. Bioorg. Med. Chem. Lett., 21 (10): 2958-61. [PMID:21493067]

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

Type IX RTKs: MuSK: muscle associated receptor tyrosine kinase. Last modified on 05/05/2015. Accessed on 08/12/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1847.