ID:MUSK_HUMAN DESCRIPTION: RecName: Full=Muscle, skeletal receptor tyrosine-protein kinase; EC=2.7.10.1; AltName: Full=Muscle-specific tyrosine-protein kinase receptor; Short=MuSK; Short=Muscle-specific kinase receptor; Flags: Precursor; 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. 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). CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. ENZYME REGULATION: Positively regulated by CK2 (By similarity). SUBUNIT: 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). SUBCELLULAR LOCATION: Cell junction, synapse, postsynaptic cell membrane; Single-pass type I membrane protein (Probable). Note=Localizes to the postsynaptic cell membrane of the neuromuscular junction (Probable). PTM: Ubiquitinated by PDZRN3. Ubiquitination promotes endocytosis and lysosomal degradation (By similarity). PTM: Phosphorylated. Phosphorylation is induced by AGRIN. Autophosphorylation at Tyr-554 is required for interaction with DOK7 which in turn stimulates the phosphorylation and the activation of MUSK. DISEASE: Defects in MUSK is a cause of congenital myasthenic syndrome with acetylcholine receptor deficiency (CMS-ACHRD) [MIM:608931]. A postsynaptic congenital myasthenic syndrome. Mutations underlying AChR deficiency cause a 'loss of function' and show recessive inheritance. Note=MUSK mutations lead to decreased agrin-dependent AChR aggregation, a critical step in the formation of the neuromuscular junction. SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein kinase family. SIMILARITY: Contains 1 FZ (frizzled) domain. SIMILARITY: Contains 3 Ig-like C2-type (immunoglobulin-like) domains. SIMILARITY: Contains 1 protein kinase domain. SEQUENCE CAUTION: Sequence=CAH69977.1; Type=Erroneous gene model prediction; Sequence=CAH69978.1; Type=Erroneous gene model prediction; Sequence=CAI17349.1; Type=Erroneous gene model prediction; Sequence=CAI17350.1; Type=Erroneous gene model prediction; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/MUSK"; WEB RESOURCE: Name=Wikipedia; Note=MuSK entry; URL="http://en.wikipedia.org/wiki/MuSK_protein";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on O15146
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
BioCarta from NCI Cancer Genome Anatomy Project h_agrPathway - Agrin in Postsynaptic Differentiation h_achPathway - Role of nicotinic acetylcholine receptors in the regulation of apoptosis
Reactome (by CSHL, EBI, and GO)
Protein O15146 (Reactome details) participates in the following event(s):
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
