MUSK

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]

Muscle Associated Receptor Tyrosine Kinase

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).

Cell differentiation Source: UniProtKB-KW
Memory Source: UniProtKB
Neuromuscular junction development Source: UniProtKB
Positive regulation of gene expression Source: UniProtKB
Positive regulation of kinase activity Source: GO_Central
Positive regulation of protein geranylgeranylation Source: UniProtKB
Positive regulation of protein phosphorylation Source: UniProtKB
Protein autophosphorylation Source: UniProtKB
Regulation of synaptic assembly at neuromuscular junction Source: UniProtKB
Skeletal muscle acetylcholine-gated channel clustering Source: UniProtKB
Transmembrane receptor protein tyrosine kinase signaling pathway Source: GO_Central

Plasma membrane
postsynaptic cell membrane
Note: Colocalizes with acetylcholine receptors (AChR) to the postsynaptic cell membrane of the neuromuscular junction.

Myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency (CMS9):
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.
Fetal akinesia deformation sequence 1 (FADS1):
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. FADS1 inheritance is autosomal recessive.

Extracellular: 24-495
Helical: 496-516
Cytoplasmic: 517-869

Ubiquitinated by PDZRN3. Ubiquitination promotes endocytosis and lysosomal degradation (By similarity).
Phosphorylated (By similarity). 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).
Neddylated.