MUSK_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: MUSK_MOUSE
• UniProt AC: Q61006
• Protein Name: Muscle, skeletal receptor tyrosine-protein kinase
• Gene Name: Musk
• Organism: Mus musculus (Mouse).
• Sequence Length: 868
• Subcellular Localization: Cell junction, synapse, postsynaptic cell membrane ; Single-pass type I membrane protein . Localizes to the postsynaptic cell membrane of the neuromuscular junction.
• Protein Description: 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..
• Protein Sequence: MRELVNIPLLQMLTLVAFSGTEKLPKAPVITTPLETVDALVEEVATFMCAVESYPQPEISWTRNKILIKLFDTRYSIRENGQLLTILSVEDSDDGIYCCIANNGVGGAVESCGALQVKMKPKITRPPINVKIIEGLKAVLPCTTMGNPKPSVSWIKGDNALRENSRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGTAYSKLVKLEVEVFARILRAPESHNVTFGSFVTLRCTAIGIPVPTISWIENGNAVSSGSIQESVKDRVIDSRLQLFITKPGLYTCIATNKHGEKFSTAKAAATVSIAEWSKSQKDSQGYCAQYRGEVCDAVLAKDALVFFNTSYRDPEDAQELLIHTAWNELKAVSPLCRPAAEALLCNHLFQECSPGVVPTPMPICREYCLAVKELFCAKEWQAMEGKAHRGLYRSGMHLLPVPECSKLPSMHRDPTACTRLPYLDYKKENITTFPSITSSRPSADIPNLPASTSSFAVSPAYSMTVIISIVSSFALFALLTIATLYCCRRRKEWKNKKRESTAVTLTTLPSELLLDRLHPNPMYQRMPLLLNPKLLSLEYPRNNIEYVRDIGEGAFGRVFQARAPGLLPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMAYGDLNEFLRSMSPHTVCSLSHSDLSTRARVSSPGPPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGETMVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHEEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQRMCERAEGTVGV

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
188	Phosphorylation	QKEDAGQYRCVAKNS CHHHCCCEEEEEECC	12.69	20139300
198	Phosphorylation	VAKNSLGTAYSKLVK EEECCCCHHHHHHHH	27.93	20139300
222	N-linked_Glycosylation	LRAPESHNVTFGSFV HCCCHHCCCCCCEEE	43.75	-
338	N-linked_Glycosylation	KDALVFFNTSYRDPE CCEEEEEECCCCCHH	19.36	-
422	Phosphorylation	GKAHRGLYRSGMHLL CCCCCCHHHCCCEEE	12.93	-
424	Phosphorylation	AHRGLYRSGMHLLPV CCCCHHHCCCEEECC	27.23	-
459	N-linked_Glycosylation	YLDYKKENITTFPSI CCCCCCCCCCCCCCC	45.87	-
553	Phosphorylation	RLHPNPMYQRMPLLL CCCCCCHHHCCCCHH	8.33	16794080
678	Phosphorylation	PHTVCSLSHSDLSTR CCCEEECCCCCCCCC	12.49	24899341
680	Phosphorylation	TVCSLSHSDLSTRAR CEEECCCCCCCCCCC	36.55	16818610
689	Phosphorylation	LSTRARVSSPGPPPL CCCCCCCCCCCCCCC	25.84	26239621
690	Phosphorylation	STRARVSSPGPPPLS CCCCCCCCCCCCCCC	30.90	26239621
697	Phosphorylation	SPGPPPLSCAEQLCI CCCCCCCCHHHHHHH	19.63	26239621
754	Phosphorylation	RNIYSADYYKADGND CCEEECCEEECCCCC	13.44	-

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
553	Y	Phosphorylation	Kinase	MUSK	Q61006	GPS
680	S	Phosphorylation	Kinase	CSNK2A1	P68400	GPS
680	S	Phosphorylation	Kinase	CK2	-	Uniprot
697	S	Phosphorylation	Kinase	CSNK2A1	P68400	GPS
697	S	Phosphorylation	Kinase	CK2	-	Uniprot
-	K	Ubiquitination	E3 ubiquitin ligase	Pdzrn3	Q69ZS0	PMID:22199232

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of MUSK_MOUSE !!

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Oops, there are no SNP-PTM records of MUSK_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
DVL1_MOUSE	Dvl1	physical	12165471
MUSK_MOUSE	Musk	physical	16794080
DOK7_HUMAN	DOK7	physical	16794080

Drug and Disease Associations

• Kegg Drug
• DrugBank
• There are no disease associations of PTM sites.

Related Literatures of Post-Translational Modification

Phosphorylation

"The cytoplasmic adaptor protein Dok7 activates the receptor tyrosinekinase MuSK via dimerization.";
Bergamin E., Hallock P.T., Burden S.J., Hubbard S.R.;
Mol. Cell 39:100-109(2010).
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 544-556 IN COMPLEX WITH DOK7,INTERACTION WITH DOK7, AND AUTOPHOSPHORYLATION AT TYR-553.
PubMed: 20603078

"The muscle protein Dok-7 is essential for neuromuscularsynaptogenesis.";
Okada K., Inoue A., Okada M., Murata Y., Kakuta S., Jigami T.,Kubo S., Shiraishi H., Eguchi K., Motomura M., Akiyama T., Iwakura Y.,Higuchi O., Yamanashi Y.;
Science 312:1802-1805(2006).
Cited for: INTERACTION WITH DOK7, AUTOPHOSPHORYLATION AT TYR-553, AND MUTAGENESISOF TYR-553.
PubMed: 16794080