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. 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. ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-[protein] Positively regulated by CK2. Monomer. Homodimer (Probable). Interacts with LRP4; the heterodimer forms an AGRIN receptor complex that binds AGRIN resulting in activation of MUSK. 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. Interacts with PDZRN3; this interaction is enhanced by agrin. Interacts with FNTA; the interaction is direct and mediates AGRIN-induced phosphorylation and activation of FNTA. Interacts with CSNK2B; mediates regulation by CK2. Interacts (via the cytoplasmic domain) with DNAJA3. Interacts with NSF; may regulate MUSK endocytosis and activity. Interacts with CAV3; may regulate MUSK signaling. Interacts with RNF31. Localizes to the postsynaptic cell membrane of the neuromuscular junction. Expressed preferentially in skeletal muscle. Skeletal myogenesis is a major site of expression during normal embryogenesis. In addition, the ganglia of the developing peripheral nervous system and various embryonic epithelia, including those of kidney, lung and gut are also sites of expression. Ubiquitinated by PDZRN3. Ubiquitination promotes endocytosis and lysosomal degradation. Phosphorylated (PubMed:16818610). Phosphorylation is induced by AGRIN (PubMed:8653787, PubMed:18848351). Autophosphorylated. Autophosphorylation at Tyr-553 is required for interaction with DOK7 which in turn stimulates the phosphorylation and the activation of MUSK (PubMed:16794080, PubMed:20603078). Neddylated. Mice die perinatally being unable to take a breath and to respond to tail or leg pinch. Despite the presence of apparently normal skeletal muscle, the absence of differentiated nerve terminals is sufficient to account for this phenotype. Every aspect of NMJ formation examined is absent in these mice. Branches of the main intramuscular nerve do not establish normal contacts with the muscle, do not form correctly positioned or specialized nerve terminals, and are apparently not given appropriate signals to stop their wandering aimlessly across the muscle. Furthermore, postsynaptic differentiation is absent, muscle-derived proteins normally localized to the synaptic basal lamina or the postsynaptic membrane being uniformly distributed in myofibers. Belongs to the protein kinase superfamily. Tyr protein kinase family.