MUSK
entrez
4593
canonical
uniprot
O15146
canonical
ensembl
ENSG00000030304
resolver
ensp
ENSP00000189978
resolver
ensp
ENSP00000363571
resolver
ensp
ENSP00000393608
resolver
enst
ENST00000416899
resolver
genesymbol
MUSK
resolver
hgnc
HGNC:7525
resolver
uniprot
A0A087WSY1
resolver
uniprot
Q32MJ8
resolver
uniprot
Q32MJ9
resolver
uniprot
Q5VZW7
resolver
uniprot
Q5VZW8
resolver
uniprot_entry
A0A087WSY1_HUMAN
resolver
uniprot_entry
MUSK_HUMAN
resolver
uniprot_sec
Q32MJ8
resolver
uniprot_sec
Q32MJ9
resolver
uniprot_sec
Q5VZW7
resolver
uniprot_sec
Q5VZW8
resolver
activity_regulation
ACTIVITY REGULATION: Positively regulated by CK2. {ECO:0000250}.
uniprot
proteins
amino_acid_sequence
MRELVNIPLVHILTLVAFSGTEKLPKAPVITTPLETVDALVEEVATFMCAVESYPQPEISWTRNKILIKLFDTRYSIRENGQLLTILSVEDSDDGIYCCTANNGVGGAVESCGALQVKMKPKITRPPINVKIIEGLKAVLPCTTMGNPKPSVSWIKGDSPLRENSRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGTAYSKVVKLEVEVFARILRAPESHNVTFGSFVTLHCTATGIPVPTITWIENGNAVSSGSIQESVKDRVIDSRLQLFITKPGLYTCIATNKHGEKFSTAKAAATISIAEWSKPQKDNKGYCAQYRGEVCNAVLAKDALVFLNTSYADPEEAQELLVHTAWNELKVVSPVCRPAAEALLCNHIFQECSPGVVPTPIPICREYCLAVKELFCAKEWLVMEEKTHRGLYRSEMHLLSVPECSKLPSMHWDPTACARLPHLDYNKENLKTFPPMTSSKPSVDIPNLPSSSSSSFSVSPTYSMTVIISIMSSFAIFVLLTITTLYCCRRRKQWKNKKRESAAVTLTTLPSELLLDRLHPNPMYQRMPLLLNPKLLSLEYPRNNIEYVRDIGEGAFGRVFQARAPGLLPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMAYGDLNEFLRSMSPHTVCSLSHSDLSMRAQVSSPGPPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGENMVVKIADFGLSRNIYSADYYKANENDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHEEVIYYVRDGNILSCPENCPVELYNLMRLCWSKLPADRPSFTSIHRILERMCERAEGTVSV
uniprot
proteins
disease_involvement
DISEASE: 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 variants 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.; DISEASE: Fetal akinesia deformation sequence 1 (FADS1) [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. FADS1 inheritance is autosomal recessive. {ECO:0000269|PubMed:25537362, ECO:0000269|PubMed:25612909}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.7.10.1
uniprot
proteins
function
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 in acetylcholinesterase (AChE) localization at the neuromuscular junctions (NMJ) via its interaction wit COLQ (By similarity). May also play a role within the central nervous system by mediating cholinergic responses, synaptic plasticity and memory formation (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:Q62838, ECO:0000269|PubMed:25537362}.
uniprot
proteins
mass_dalton
97056
uniprot
proteins
mutagenesis
MUTAGEN 584; /note="G->C,D: Mild decrease in kinase activity."; /evidence="ECO:0000269|PubMed:25029443"; MUTAGEN 609; /note="K->R: Severe loss of kinase activity."; /evidence="ECO:0000269|PubMed:25029443"; MUTAGEN 743; /note="D->N: Severe loss of kinase activity."; /evidence="ECO:0000269|PubMed:25029443
uniprot
proteins
post_translational_modification
PTM: Ubiquitinated by PDZRN3. Ubiquitination promotes endocytosis and lysosomal degradation (By similarity). {ECO:0000250}.; PTM: 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). {ECO:0000250|UniProtKB:Q61006, ECO:0000269|PubMed:25029443}.; PTM: Neddylated. {ECO:0000269|PubMed:20596523}.
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
Tyr protein kinase family
uniprot
proteins
pubmed
15164053
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15496425
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
19949040
uniprot
proteins
pubmed
20371544
uniprot
proteins
pubmed
20596523
uniprot
proteins
pubmed
20603078
uniprot
proteins
pubmed
23326516
uniprot
proteins
pubmed
24183479
uniprot
proteins
pubmed
25029443
uniprot
proteins
pubmed
25537362
uniprot
proteins
pubmed
25612909
uniprot
proteins
pubmed
7546737
uniprot
proteins
sequence_length
869
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Postsynaptic cell membrane {ECO:0000269|PubMed:23326516}; Single-pass type I membrane protein {ECO:0000305}. Note=Colocalizes with acetylcholine receptors (AChR) to the postsynaptic cell membrane of the neuromuscular junction. {ECO:0000269|PubMed:23326516}.
uniprot
proteins
transmembrane_region
TRANSMEM 496..516; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins