InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: MUSK

Summary

InnateDB Protein

IDBP-80518.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

MUSK

Protein Name

muscle, skeletal, receptor tyrosine kinase

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000363571

InnateDB Gene

IDBG-80516 (MUSK)

Protein Structure

UniProt Annotation

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). {ECO:0000250}.

Subcellular Localization

Cell junction, synapse, postsynaptic cell membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Note=Localizes to the postsynaptic cell membrane of the neuromuscular junction. {ECO:0000305}.

Disease Associations

Myasthenic syndrome, congenital, associated with acetylcholine receptor deficiency (CMS-ACHRD) [MIM:608931]: A post-synaptic congenital myasthenic syndrome. Congenital myasthenic syndromes (CMS) are inherited disorders of neuromuscular transmission that stem from mutations in presynaptic, synaptic, or postsynaptic proteins. {ECO:0000269PubMed:15496425, ECO:0000269PubMed:20371544}. Note=The disease is caused by mutations 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.

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 9 experimentally validated interaction(s) in this database.
They are also associated with 5 interaction(s) predicted by orthology.

Experimentally validated
Total	9 [view]
Protein-Protein	9 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	5 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0004714	transmembrane receptor protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0030165	PDZ domain binding

Biological Process

GO:0001934	positive regulation of protein phosphorylation
GO:0006355	regulation of transcription, DNA-templated
GO:0006468	protein phosphorylation
GO:0007169	transmembrane receptor protein tyrosine kinase signaling pathway
GO:0007275	multicellular organismal development
GO:0007528	neuromuscular junction development
GO:0007613	memory
GO:0008582	regulation of synaptic growth at neuromuscular junction
GO:0010628	positive regulation of gene expression
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0030154	cell differentiation
GO:0030198	extracellular matrix organization
GO:0043113	receptor clustering
GO:0043525	positive regulation of neuron apoptotic process
GO:0046777	protein autophosphorylation
GO:0071340	skeletal muscle acetylcholine-gated channel clustering
GO:2000541	positive regulation of protein geranylgeranylation

Cellular Component

GO:0005886	plasma membrane
GO:0005887	integral component of plasma membrane
GO:0030054	cell junction
GO:0031594	neuromuscular junction
GO:0043235	receptor complex
GO:0045211	postsynaptic membrane

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR003598 Immunoglobulin subtype 2
IPR003599 Immunoglobulin subtype
IPR007110 Immunoglobulin-like domain
IPR011009 Protein kinase-like domain
IPR013098 Immunoglobulin I-set
IPR013106 Immunoglobulin V-set domain
IPR013151 Immunoglobulin
IPR020067 Frizzled domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714
PF07679
PF07686
PF00047
PF01392

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00408
SM00409
SM00063
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt