Tchem MUSK Muscle, skeletal receptor tyrosine-protein kinase

Protein Classes

DTO Classes

Protein / Kinase / Protein Kinase / Tk Group / Musk Family / Muscle, Skeletal Receptor Tyrosine-protein Kinase

Protein Summary

Description

Receptor tyrosine kinase which plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ), the synapse between the motor neuron and the skeletal muscle (PubMed:25537362). Recruitment of AGRIN by LRP4 to the MUSK signaling complex induces phosphorylation and activation of MUSK, the kinase of the complex. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. May regulate AChR phosphorylation and clustering through activation of ABL1 and Src family kinases which in turn regulate MUSK. DVL1 and PAK1 that form a ternary complex with MUSK are also important for MUSK-dependent regulation of AChR clustering. May positively regulate Rho family GTPases through FNTA. Mediates the phosphorylation of FNTA which promotes prenylation, recruitment to membranes and activation of RAC1 a regulator of the actin cytoskeleton and of gene expression. Other effectors of the MUSK signaling include DNAJA3 which functions downstream of MUSK. May also play a role within the central nervous system by mediating cholinergic responses, synaptic plasticity and memory formation (By similarity). This gene encodes a muscle-specific tyrosine kinase receptor. The encoded protein may play a role in clustering of the acetylcholine receptor in the postsynaptic neuromuscular junction. Mutations in this gene have been associated with congenital myasthenic syndrome. Alternatively spliced transcript variants have been described.[provided by RefSeq, Oct 2009]

Uniprot Accession IDs

• O15146
• Q32MJ8
• Q32MJ9
• Q5VZW7
• Q5VZW8

Gene Name

• MUSK

Ensembl ID

• ENST00000189978
• ENSP00000189978
• ENSG00000030304
• ENST00000374448
• ENSP00000363571

Symbol

• CMS9
• FADS

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
protein domain	1
molecular function	0.98
biological process	0.82
trait	0.75
kinase perturbation	0.71

Related Tools

ProKinO

The ProKinO is a protein kinase-specific ontology, which provides a controlled vocabulary of terms, their hierarchy, and relationships unifying sequence, structure, function, mutation and pathway information on kinases.

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Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 725.21   (req: < 5)

Gene RIFs: 42   (req: <= 3)

Antibodies: 447   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 725.21   (req: >= 5)

Gene RIFs: 42   (req: > 3)

Antibodies: 447   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 20

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 6

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Active Ligands (6)

Explore Active Ligands

1 – 6 of 6

CHEMBL388978

MUSKTchem Kinase

IC50 : 8.42

CHEMBL1230609

MUSKTchem Kinase

Kd : 7.89

CHEMBL574738

MUSKTchem Kinase

Kd : 8.51

CHEMBL223360

MUSKTchem Kinase

Kd : 8

CHEMBL248757

MUSKTchem Kinase

Ki : 5.78000021

CHEMBL1774056

MUSKTchem Kinase

IC50 : 6.6500001

GWAS Traits (1)

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
heel bone mineral density	EFO_0009270	2	2	3		84.7

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
heel bone mineral density	EFO_0009270	3		84.7

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Orthologs (13)

1 – 5 of 13

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	muscle associated receptor tyrosine kinase	VGNC:10127	464653
Macaque	muscle associated receptor tyrosine kinase		709397
Mouse	muscle, skeletal, receptor tyrosine kinase	MGI:103581	18198
Rat	muscle associated receptor tyrosine kinase	RGD:3211	81725
Horse	muscle associated receptor tyrosine kinase	VGNC:20446	100058619

Species	Name	OMA	EggNOG	Inparanoid
Chimp	muscle associated receptor tyrosine kinase
Macaque	muscle associated receptor tyrosine kinase
Mouse	muscle, skeletal, receptor tyrosine kinase
Rat	muscle associated receptor tyrosine kinase
Horse	muscle associated receptor tyrosine kinase

Protein Structure (0 Structures, 1 AlphaFold Model)

Representation

  axes   backbone   ball+stick   cartoon   rocket   rope   spacefill

Color Scheme

  target   atomindex   bfactor   chainname   electrostatic   element   hydrophobicity   resname   sstruc

AF-O15146-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

Pathways (2)

Reactome (2)

ECM proteoglycans (R-HSA-3000178)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	ECM proteoglycans	56 targets	R-HSA-3000178
Reactome	Extracellular matrix organization	297 targets	R-HSA-1474244

Name	Explore in Pharos	Explore in Source
ECM proteoglycans	56 targets	R-HSA-3000178
Extracellular matrix organization	297 targets	R-HSA-1474244

Gene Ontology Terms (26)

Functions (6)

Components (6)

Processes (14)

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Items per page:

10

1 – 6 of 6

GO Term	Evidence	Assigned by
transmembrane receptor protein tyrosine kinase activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
transmembrane signaling receptor activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
Wnt-protein binding	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
protein tyrosine kinase activity	Inferred from Sequence or structural Similarity (ISS)	UniProtKB
ATP binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW
metal ion binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

Protein-Protein Interactions (120)

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1 – 10 of 120

• See Interactions on String-DB

ADAM30

Tdark

Family: Enzyme

Novelty: 0.25395428

p_int: 0.999999779

p_ni: 2.18e-7

p_wrong: 2e-9

Score: 0.215

Data Source: BioPlex,STRINGDB

DNAJC13

Tbio

Novelty: 0.03251995

p_int: 0.989026376

p_ni: 0.010973624

Score: 0.247

Data Source: BioPlex,STRINGDB

RBSN

Tbio

Novelty: 0.0046123

p_int: 0.872421843

p_ni: 0.127296834

p_wrong: 0.000281323

Score: 0.352

Data Source: BioPlex,STRINGDB

AGRN

Tbio

Novelty: 0.00156441

Score: 0.997

Data Source: Reactome,STRINGDB

RAPSN

Tbio

Novelty: 0.00565077

Score: 0.997

Data Source: STRINGDB

LRP4

Tbio

Novelty: 0.01336125

Score: 0.991

Data Source: Reactome,STRINGDB

DOK7

Tbio

Novelty: 0.01360545

Score: 0.99

Data Source: STRINGDB

DVL1

Tchem

Novelty: 0.00356876

Score: 0.966

Data Source: STRINGDB

COLQ

Tbio

Family: Enzyme

Novelty: 0.01414634

Score: 0.966

Data Source: STRINGDB

CHRNB1

Tclin

Family: IC

Novelty: 0.04777051

Score: 0.958

Data Source: STRINGDB

Publication Statistics

PubMed Score  725.21

PubMed score by year

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PubTator Score  298.66

PubTator score by year

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Patents

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Amino Acid Sequence

Residue Counts

Protein Sequence

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Ortholog Sequence Conservation

WebLogo Color Code

PolarG S T Y C

NeutralQ N

BasicK R H

AcidicD E

HydrophobicA V L I P W F M

Compare across kinases on ProKinO

Structural Annotations

Find similar targets by:

UniProt Keyword Find Similar Targets

Alternative splicing
ATP-binding
Cell junction
Cell membrane
Complete proteome
Congenital myasthenic syndrome
Developmental protein
Differentiation
Disease mutation
Disulfide bond

GWAS Trait Find Similar Targets

heel bone mineral density

MGI Phenotype Find Similar Targets

behavior/neurological phenotype
cellular phenotype
growth/size/body region phenotype
homeostasis/metabolism phenotype
integument phenotype
mortality/aging
muscle phenotype
nervous system phenotype
respiratory system phenotype
skeleton phenotype