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muscle associated receptor tyrosine kinase

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Target not currently curated in GtoImmuPdb

Target id: 1847

Nomenclature: muscle associated receptor tyrosine kinase

Abbreviated Name: MuSK

Family: Type IX RTKs: MuSK

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 869 9q31.3 MUSK muscle associated receptor tyrosine kinase
Mouse 1 868 4 31.87 cM Musk muscle, skeletal, receptor tyrosine kinase
Rat 1 868 5q24 Musk muscle associated receptor tyrosine kinase
Previous and Unofficial Names Click here for help
muscle specific kinase (neural fold/somite kinase 1) | muscle-specific tyrosine protein kinase receptor | Nsk1 | MDK4 | Nsk2 | Nsk3 | muscle, skeletal, receptor tyrosine kinase | muscle
Database Links Click here for help
Alphafold O15146 (Hs), Q61006 (Mm), Q62838 (Rn)
BRENDA 2.7.10.1
CATH/Gene3D 1.10.2000.10, 2.60.40.10
ChEMBL Target CHEMBL5684 (Hs)
Ensembl Gene ENSG00000030304 (Hs), ENSMUSG00000057280 (Mm), ENSRNOG00000033567 (Rn)
Entrez Gene 4593 (Hs), 18198 (Mm), 81725 (Rn)
Human Protein Atlas ENSG00000030304 (Hs)
KEGG Enzyme 2.7.10.1
KEGG Gene hsa:4593 (Hs), mmu:18198 (Mm), rno:81725 (Rn)
OMIM 601296 (Hs)
Orphanet ORPHA160311 (Hs)
Pharos O15146 (Hs)
RefSeq Nucleotide NM_001166280 (Hs), NM_001037127 (Mm), NM_031061 (Rn)
RefSeq Protein NP_005583 (Hs), NP_001032207 (Mm), NP_001159468 (Mm), NP_035074 (Mm), NP_001032204 (Mm), NP_001032205 (Mm), NP_001032206 (Mm), NP_112323 (Rn)
UniProtKB O15146 (Hs), Q61006 (Mm), Q62838 (Rn)
Wikipedia MUSK (Hs)
Selected 3D Structures Click here for help
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 Click here for help
EC Number: 2.7.10.1

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

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] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.8 pKi 4
⤷ pKi 5.8 (Ki 1.65x10-6 M) [4]
compound 1d [PMID: 21493067] Small molecule or natural product Click here for species-specific activity table 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 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: 2,7
Key to terms and symbols Click column headers to sort
Target used in screen: MUSK
Ligand Sp. Type Action Value Parameter
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 8.5 pKd
linifanib Small molecule or natural product Hs Inhibitor Inhibition 8.0 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.9 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.1 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.0 pKd
SU-14813 Small molecule or natural product Hs Inhibitor Inhibition 7.0 pKd
sorafenib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.9 pKd
KW-2449 Small molecule or natural product Hs Inhibitor Inhibition 6.7 pKd
crizotinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.6 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure 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 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: MuSK/MUSK
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
K-252a Small molecule or natural product Hs Inhibitor Inhibition 6.1 18.0 2.0
JAK3 inhibitor VI Small molecule or natural product Hs Inhibitor Inhibition 6.1 25.0 2.0
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.0 0.0 0.0
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 12.2 -1.0 0.5
JNK inhibitor V Small molecule or natural product Hs Inhibitor Inhibition 14.8 90.0 50.0
PI 3-Kg inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 16.2 90.0 75.0
PKR inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 21.6 53.0 11.0
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 25.8 103.0 93.0
Cdc2-like kinase inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 28.4 82.0 75.0
Gö 6976 Small molecule or natural product Ligand has a PDB structure 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 Click here for help
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 18/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1847.