Kinase Atlas

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:23326516). 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.

Site	Maximum Consensus Site Population	Minimum Consensus Site Population	Median Consensus Site Population
MPP	24	24	24.0
DFG	5	5	5.0
EDI	4	4	4.0
MT3	2	2	2.0
ATP	19	8	13.5

PDB ID	Maximum Consensus Site Population
PDB ID	MPP site	DFG site	PIF site	DRS site	DEF site	EDI site	MT3 site	AAS site	LBP site	CMP site	PDIG site	ATP site	PMP site
Total Druggable Structures per Site	1	0	0	0	0	0	0	0	0	0	0	1	0
1LUF	24	5	0	0	0	4	2	0	0	0	0	19	0

Q62838