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FLASH GENE
Symbol MUSK contributors: mct/pgu - updated : 08-07-2015
HGNC name muscle, skeletal, receptor tyrosine kinase
HGNC id 7525
Corresponding disease
CMS1D congenital myasthenic syndrome, 1D
FADSL fetal akinesia deformation sequence lethal
Location 9q31.3      Physical location : 113.431.050 - 113.563.278
Synonym name
  • protein-tyrosine kinase
  • muscle-specific kinase receptor
  • Synonym symbol(s) MGC126323, MGC126324, CMS9
    EC.number 2.7.10.1
    DNA
    TYPE functioning gene
    STRUCTURE 132.23 kb     15 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    15 - 2764 96.9 869 - 2008 18165682
    13 - 2496 - 783 - 2008 18165682
    12 - 2466 86.3 773 - 2008 18165682
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivemouth    
    Nervousbrainlimbic systemhippocampus   Homo sapiens
     brainforebraincerebral cortex   Homo sapiens
     brainhindbraincerebellum   Homo sapiens
    Olfactory (smell)olfactory bulb     Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, fetal
    Text early myotomes and developing muscle
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • the most N-terminal Ig-like domain is essential for AGRN to stimulate MUSK phosphorylation
  • a large ectodomain which comprises three immunoglobulin-like domains and a cysteine-rich domain (Fz-CRD) related to those in Frizzled proteins, the receptors for Wnts
  • a spacer between domains 3 and 4, containing 6 conserved cysteines
  • a kringle domain
  • a soluble extracellular domain that potentiates Agrin-binding to LRP4-expressing cells
  • HOMOLOGY
    Homologene
    FAMILY
  • protein kinase superfamily
  • Tyr protein kinase family
  • CATEGORY enzyme , receptor membrane
    SUBCELLULAR LOCALIZATION     plasma membrane,junction
    basic FUNCTION
  • playing an essential role in stabilizing the muscle prepattern, and has a potent role in regulating the formation of synapses
  • initial step in postsynaptic differentiation and formation of an end-plate band in cooperation with rapsyn
  • essential receptor tyrosine kinase for the establishment and maintenance of the neuromuscular junction (NMJ)
  • essential to initiate AChR clustering but also to restrict approaching growth cones to the muscle center, thereby coordinating pre- and postsynaptic development
  • recruits docking protein-7 (DOK7), an adaptor protein that is expressed selectively in muscle (
  • transmembrane tyrosine kinase vital for forming and maintaining the mammalian neuromuscular junction
  • its activation initiates complex intracellular signalling events that coordinate the local synthesis and assembly of synaptic proteins
  • LRP4 and MUSK act as scaffolds for multiple binding partners, resulting in a complex and dynamic network of interacting proteins that is required for ACHR clustering
  • receptor tyrosine kinase that plays a central signaling role in the formation of neuromuscular junctions (NMJs)
  • uses both classical and nonclassical endosomal pathways that involve a variety of different components of the endosomal machinery
  • role of MUSK as a tyrosine kinase that orchestrates neuromuscular synaptogenesis
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS development
    text muscle development
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • rapsyn
  • LRP4 and MUSK can interact and form a complex
  • associate with SHC4 via its PTB domain (undergo tyrosine phosphorylation downstream of activated MUSK)
  • PDZRN3 binds to MUSK and promotes its ubiquitination
  • MUSK-interacting protein DOK7 is essential for neuromuscular synaptogenesis, although the mechanisms by which DOK7 regulates MUSK activity and promotes synapse formation have been unclear
  • AGRN binds LRP4 and stimulates further MUSK phosphorylation, stabilizing nascent synapses
  • LRP4 is a cis-acting ligand for MUSK, whereas AGRN functions as an allosteric and paracrine regulator to promote association between LRP4 and MUSK
  • is a WNT4 receptor (WNT4 not only interacts with MUSK ectodomain but also mediates MUSK activation)
  • LRP4 acts bi-directionally and coordinates synapse formation by binding AGRN, activating MUSK and stimulating postsynaptic differentiation
  • ligand for MUSK is LRP4, a transmembrane protein in muscle, whose binding affinity for MUSK is potentiated by agrin, a neuronally derived heparan-sulfate proteoglycan 9)
  • DOK7, a cytoplasmic adaptor protein, is also required for MUSK activation 9)
  • MUSK activation by DOK7 mildly affects the localization of MUSK on the cell surface but has no effect on the rate of MUSK internalization
  • MUSK activator agrin plays another role essential for the postnatal maintenance, but not for embryonic formation, of NMJs and also for the postnatal, but not prenatal, midmuscle localization of postsynaptic specializations
  • DOK7 is essential for activation of the receptor kinase MUSK, which governs NMJ formation
  • cell & other
    REGULATION
    activated by AGRN to cluster acetylcholine receptors
    activation of muscle-specific receptor tyrosine kinase and binding to dystroglycan are regulated by alternative mRNA splicing of agrin AGRN)
    LRP4 (low-density lipoprotein receptor-related protein-4)
    ASSOCIATED DISORDERS
    corresponding disease(s) CMS1D , FADSL
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS