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Aliases for MUSK Gene

Aliases for MUSK Gene

  • Muscle Associated Receptor Tyrosine Kinase 2 3
  • Muscle, Skeletal, Receptor Tyrosine Kinase 2 3 5
  • Muscle-Specific Tyrosine-Protein Kinase Receptor 3 4
  • Muscle-Specific Kinase Receptor 3 4
  • EC 2.7.10.1 4 63
  • EC 2.7.10 63
  • FADS 3
  • CMS9 3
  • MuSK 4

External Ids for MUSK Gene

Previous GeneCards Identifiers for MUSK Gene

  • GC09P104229
  • GC09P105163
  • GC09P106888
  • GC09P108810
  • GC09P110510
  • GC09P112470
  • GC09P113431
  • GC09P083032

Summaries for MUSK Gene

Entrez Gene Summary for MUSK Gene

  • 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]

GeneCards Summary for MUSK Gene

MUSK (Muscle Associated Receptor Tyrosine Kinase) is a Protein Coding gene. Diseases associated with MUSK include fetal akinesia deformation sequence and myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency. Among its related pathways are Degradation of the extracellular matrix and ERK Signaling. GO annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is ALK.

UniProtKB/Swiss-Prot for MUSK Gene

  • 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).

No data available for Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for MUSK Gene

Genomics for MUSK Gene

Regulatory Elements for MUSK Gene

Promoters for MUSK Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around MUSK on UCSC Golden Path with GeneCards custom track

Genomic Location for MUSK Gene

Chromosome:
9
Start:
110,668,545 bp from pter
End:
110,806,542 bp from pter
Size:
137,998 bases
Orientation:
Plus strand

Genomic View for MUSK Gene

Genes around MUSK on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MUSK Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for MUSK Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MUSK Gene

Proteins for MUSK Gene

  • Protein details for MUSK Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O15146-MUSK_HUMAN
    Recommended name:
    Muscle, skeletal receptor tyrosine-protein kinase
    Protein Accession:
    O15146
    Secondary Accessions:
    • Q32MJ8
    • Q32MJ9
    • Q5VZW7
    • Q5VZW8

    Protein attributes for MUSK Gene

    Size:
    869 amino acids
    Molecular mass:
    97056 Da
    Cofactor:
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Quaternary structure:
    • Monomer (By similarity). Homodimer (Probable). Interacts with LRP4; the heterodimer forms an AGRIN receptor complex that binds AGRIN resulting in activation of MUSK (By similarity). Forms a heterotetramer composed of 2 DOK7 and 2 MUSK molecules which facilitates MUSK trans-autophosphorylation on tyrosine residue and activation. Interacts (via cytoplasmic part) with DOK7 (via IRS-type PTB domain); requires MUSK phosphorylation. Interacts with DVL1 (via DEP domain); the interaction is direct and mediates the formation of a DVL1, MUSK and PAK1 ternary complex involved in AChR clustering (By similarity). Interacts with PDZRN3; this interaction is enhanced by agrin (By similarity). Interacts with FNTA; the interaction is direct and mediates AGRIN-induced phosphorylation and activation of FNTA (By similarity). Interacts with CSNK2B; mediates regulation by CK2 (By similarity). Interacts (via the cytoplasmic domain) with DNAJA3 (By similarity). Interacts with NSF; may regulate MUSK endocytosis and activity (By similarity). Interacts with CAV3; may regulate MUSK signaling (By similarity). Interacts with RNF31 (By similarity).
    SequenceCaution:
    • Sequence=CAH69977.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=CAH69978.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=CAI17349.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=CAI17350.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};

    Alternative splice isoforms for MUSK Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for MUSK Gene

Proteomics data for MUSK Gene at MOPED

Post-translational modifications for MUSK Gene

  • Neddylated.
  • Phosphorylated. Phosphorylation is induced by AGRIN in a LRP4-dependent manner (By similarity). Autophosphorylated (PubMed:25029443). Autophosphorylation at Tyr-554 is required for interaction with DOK7 which in turn stimulates the phosphorylation and the activation of MUSK (By similarity).
  • Ubiquitinated by PDZRN3. Ubiquitination promotes endocytosis and lysosomal degradation (By similarity).
  • Glycosylation at Asn 222 and Asn 338
  • Modification sites at PhosphoSitePlus

Other Protein References for MUSK Gene

Antibody Products

Domains & Families for MUSK Gene

Suggested Antigen Peptide Sequences for MUSK Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

O15146

UniProtKB/Swiss-Prot:

MUSK_HUMAN :
  • Contains 1 FZ (frizzled) domain.
  • Belongs to the protein kinase superfamily. Tyr protein kinase family.
Domain:
  • Contains 1 FZ (frizzled) domain.
  • Contains 3 Ig-like C2-type (immunoglobulin-like) domains.
  • Contains 1 protein kinase domain.
Family:
  • Belongs to the protein kinase superfamily. Tyr protein kinase family.
genes like me logo Genes that share domains with MUSK: view

Function for MUSK Gene

Molecular function for MUSK Gene

GENATLAS Biochemistry:
skeletal muscle specific receptor tyrosine kinase,expressed in early myotomes and developing muscle and at the neuromuscular junction in mature muscle
UniProtKB/Swiss-Prot CatalyticActivity:
ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
UniProtKB/Swiss-Prot EnzymeRegulation:
Positively regulated by CK2.
UniProtKB/Swiss-Prot Function:
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).

Enzyme Numbers (IUBMB) for MUSK Gene

Gene Ontology (GO) - Molecular Function for MUSK Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004672 protein kinase activity IEA --
GO:0004713 protein tyrosine kinase activity IEA,ISS --
genes like me logo Genes that share ontologies with MUSK: view
genes like me logo Genes that share phenotypes with MUSK: view

Human Phenotype Ontology for MUSK Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for MUSK Gene

MGI Knock Outs for MUSK:

Animal Model Products

No data available for miRNA , Transcription Factor Targets and HOMER Transcription for MUSK Gene

Localization for MUSK Gene

Subcellular locations from UniProtKB/Swiss-Prot for MUSK Gene

Cell junction, synapse, postsynaptic cell membrane; Single-pass type I membrane protein. Note=Colocalizes with acetylcholine receptors (AChR) to the postsynaptic cell membrane of the neuromuscular junction. {ECO:0000269 PubMed:23326516}.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for MUSK Gene COMPARTMENTS Subcellular localization image for MUSK gene
Compartment Confidence
plasma membrane 5
extracellular 2
cytoskeleton 1
endoplasmic reticulum 1
peroxisome 1

Gene Ontology (GO) - Cellular Components for MUSK Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with MUSK: view

Pathways & Interactions for MUSK Gene

genes like me logo Genes that share pathways with MUSK: view

SIGNOR curated interactions for MUSK Gene

Activates:
Is activated by:

Gene Ontology (GO) - Biological Process for MUSK Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001934 positive regulation of protein phosphorylation ISS --
GO:0007613 memory ISS --
GO:0010628 positive regulation of gene expression ISS --
GO:0018108 peptidyl-tyrosine phosphorylation IEA,ISS --
GO:0030154 cell differentiation IEA --
genes like me logo Genes that share ontologies with MUSK: view

Drugs & Compounds for MUSK Gene

(10) Drugs for MUSK Gene - From: Novoseek and HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Adenosine triphosphate Approved Nutra 0

(4) Additional Compounds for MUSK Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • Adenosindiphosphorsaeure
  • Adenosine 5'-pyrophosphate
  • Adenosine diphosphate
  • Adenosine pyrophosphate
  • Adenosine-5'-diphosphate
Full agonist, Agonist 58-64-0
genes like me logo Genes that share compounds with MUSK: view

Transcripts for MUSK Gene

mRNA/cDNA for MUSK Gene

(8) REFSEQ mRNAs :
(4) Additional mRNA sequences :
(1) Selected AceView cDNA sequences:
(7) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for MUSK Gene

Muscle, skeletal, receptor tyrosine kinase:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for MUSK Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14a · 14b ^ 15
SP1: - -
SP2: - - -
SP3: - - - -
SP4: - -

Relevant External Links for MUSK Gene

GeneLoc Exon Structure for
MUSK
ECgene alternative splicing isoforms for
MUSK

Expression for MUSK Gene

mRNA expression in normal human tissues for MUSK Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for MUSK Gene

This gene is overexpressed in Muscle - Skeletal (x12.0) and Small Intestine - Terminal Ileum (x4.5).

Protein differential expression in normal tissues from HIPED for MUSK Gene

This gene is overexpressed in Testis (35.0) and Pancreatic juice (28.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for MUSK Gene



SOURCE GeneReport for Unigene cluster for MUSK Gene Hs.521653

genes like me logo Genes that share expression patterns with MUSK: view

Protein tissue co-expression partners for MUSK Gene

Primer Products

In Situ Assay Products

No data available for mRNA Expression by UniProt/SwissProt for MUSK Gene

Orthologs for MUSK Gene

This gene was present in the common ancestor of animals.

Orthologs for MUSK Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia MUSK 35
  • 90.6 (n)
  • 94.02 (a)
MUSK 36
  • 82 (a)
OneToOne
dog
(Canis familiaris)
Mammalia MUSK 35
  • 86.71 (n)
  • 91.86 (a)
mouse
(Mus musculus)
Mammalia Musk 35
  • 87.75 (n)
  • 92.86 (a)
Musk 16
Musk 36
  • 91 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia MUSK 35
  • 99.58 (n)
  • 99.77 (a)
MUSK 36
  • 99 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Musk 35
  • 88.63 (n)
  • 93.55 (a)
oppossum
(Monodelphis domestica)
Mammalia MUSK 36
  • 83 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia MUSK 36
  • 80 (a)
OneToOne
chicken
(Gallus gallus)
Aves MUSK 35
  • 74.94 (n)
  • 78.09 (a)
MUSK 36
  • 71 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia MUSK 36
  • 70 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia musk 35
  • 70.29 (n)
  • 73.03 (a)
African clawed frog
(Xenopus laevis)
Amphibia musk-A 35
zebrafish
(Danio rerio)
Actinopterygii musk 35
  • 61.43 (n)
  • 61.94 (a)
musk 36
  • 58 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta Nrk 37
  • 59 (a)
Nrk 35
  • 56.35 (n)
  • 54.29 (a)
Nrk 36
  • 37 (a)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP006988 35
  • 54.43 (n)
  • 49.91 (a)
worm
(Caenorhabditis elegans)
Secernentea kin-23 37
  • 33 (a)
Species with no ortholog for MUSK:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for MUSK Gene

ENSEMBL:
Gene Tree for MUSK (if available)
TreeFam:
Gene Tree for MUSK (if available)

Paralogs for MUSK Gene

Paralogs for MUSK Gene

genes like me logo Genes that share paralogs with MUSK: view

Variants for MUSK Gene

Sequence variations from dbSNP and Humsavar for MUSK Gene

SNP ID Clin Chr 09 pos Sequence Context AA Info Type
rs2274419 - 110,775,842(-) TCTTC(C/T)ATTAC reference, missense
VAR_023046 Myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency (CMS9)
rs578430 - 110,800,863(+) GCCCC(A/C/G/T)TGGAG reference, missense
rs56054734 - 110,682,674(+) TTCAG(C/G)TCCTG reference, missense
rs35142681 - 110,687,209(+) CTGCA(C/T)GGCCA reference, missense

Structural Variations from Database of Genomic Variants (DGV) for MUSK Gene

Variant ID Type Subtype PubMed ID
nsv466482 CNV Gain 19166990
esv2665360 CNV Deletion 23128226
esv2614598 CNV Deletion 19546169
esv2298654 CNV Deletion 18987734
esv2738927 CNV Deletion 23290073
esv1003568 CNV Deletion 20482838
nsv436600 CNV Deletion 17901297
esv994960 CNV Loss 20482838
esv2677020 CNV Deletion 23128226
esv999248 CNV Loss 20482838
esv28185 CNV Loss 19812545
esv2738928 CNV Deletion 23290073
nsv893718 CNV Gain 21882294
nsv893719 CNV Gain 21882294
esv271869 CNV Insertion 20981092
esv272528 CNV Insertion 20981092
nsv510201 CNV Loss 20534489

Variation tolerance for MUSK Gene

Residual Variation Intolerance Score: 77.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 6.77; 78.97% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for MUSK Gene

HapMap Linkage Disequilibrium report
MUSK
Human Gene Mutation Database (HGMD)
MUSK

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MUSK Gene

Disorders for MUSK Gene

MalaCards: The human disease database

(16) MalaCards diseases for MUSK Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search MUSK in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

MUSK_HUMAN
  • Fetal akinesia deformation sequence (FADS) [MIM:208150]: A clinically and genetically heterogeneous group of disorders with congenital malformations related to impaired fetal movement. Clinical features include fetal akinesia, intrauterine growth retardation, polyhydramnios, arthrogryposis, pulmonary hypoplasia, craniofacial abnormalities, and cryptorchidism. {ECO:0000269 PubMed:25537362, ECO:0000269 PubMed:25612909}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency (CMS9) [MIM:616325]: A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS9 is a disorder of postsynaptic neuromuscular transmission, due to deficiency of AChR at the endplate that results in low amplitude of the miniature endplate potential and current. {ECO:0000269 PubMed:15496425, ECO:0000269 PubMed:19949040, ECO:0000269 PubMed:20371544, ECO:0000269 PubMed:23326516, ECO:0000269 PubMed:24183479}. Note=The disease is caused by mutations affecting the gene represented in this entry. MUSK mutations lead to decreased agrin-dependent AChR aggregation, a critical step in the formation of the neuromuscular junction.

Relevant External Links for MUSK

Genetic Association Database (GAD)
MUSK
Human Genome Epidemiology (HuGE) Navigator
MUSK
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
MUSK
genes like me logo Genes that share disorders with MUSK: view

No data available for Genatlas for MUSK Gene

Publications for MUSK Gene

  1. Receptor tyrosine kinase specific for the skeletal muscle lineage: expression in embryonic muscle, at the neuromuscular junction, and after injury. (PMID: 7546737) Valenzuela D.M. … Yancopoulos G.D. (Neuron 1995) 2 3 4 23 67
  2. Mutations in MUSK causing congenital myasthenic syndrome impair MuSK- Dok-7 interaction. (PMID: 20371544) Maselli R.A. … Wollmann R.L. (Hum. Mol. Genet. 2010) 3 23
  3. [Seronegative myasthenia and myasthenia gravis with anti-MuSK antibody: a retrospective study of 20 cases]. (PMID: 19327804) Aubert S. … Pouget J. (Rev. Neurol. (Paris) 2009) 3 23
  4. The effect of plasma from muscle-specific tyrosine kinase myasthenia patients on regenerating endplates. (PMID: 19745065) ter Beek W.P. … Molenaar P.C. (Am. J. Pathol. 2009) 3 23
  5. Mutations causing DOK7 congenital myasthenia ablate functional motifs in Dok-7. (PMID: 18165682) Hamuro J. … Yamanashi Y. (J. Biol. Chem. 2008) 3 23

Products for MUSK Gene

Sources for MUSK Gene

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