MUSK_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: MUSK_HUMAN
• UniProt AC: O15146
• Protein Name: Muscle, skeletal receptor tyrosine-protein kinase
• Gene Name: MUSK
• Organism: Homo sapiens (Human).
• Sequence Length: 869
• Subcellular Localization: Cell junction, synapse, postsynaptic cell membrane ; Single-pass type I membrane protein . Colocalizes with acetylcholine receptors (AChR) 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. [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 within the central nervous system by mediating cholinergic responses, synaptic plasticity and memory formation (By similarity]
• Protein Sequence: MRELVNIPLVHILTLVAFSGTEKLPKAPVITTPLETVDALVEEVATFMCAVESYPQPEISWTRNKILIKLFDTRYSIRENGQLLTILSVEDSDDGIYCCTANNGVGGAVESCGALQVKMKPKITRPPINVKIIEGLKAVLPCTTMGNPKPSVSWIKGDSPLRENSRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGTAYSKVVKLEVEVFARILRAPESHNVTFGSFVTLHCTATGIPVPTITWIENGNAVSSGSIQESVKDRVIDSRLQLFITKPGLYTCIATNKHGEKFSTAKAAATISIAEWSKPQKDNKGYCAQYRGEVCNAVLAKDALVFLNTSYADPEEAQELLVHTAWNELKVVSPVCRPAAEALLCNHIFQECSPGVVPTPIPICREYCLAVKELFCAKEWLVMEEKTHRGLYRSEMHLLSVPECSKLPSMHWDPTACARLPHLDYNKENLKTFPPMTSSKPSVDIPNLPSSSSSSFSVSPTYSMTVIISIMSSFAIFVLLTITTLYCCRRRKQWKNKKRESAAVTLTTLPSELLLDRLHPNPMYQRMPLLLNPKLLSLEYPRNNIEYVRDIGEGAFGRVFQARAPGLLPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMAYGDLNEFLRSMSPHTVCSLSHSDLSMRAQVSSPGPPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGENMVVKIADFGLSRNIYSADYYKANENDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHEEVIYYVRDGNILSCPENCPVELYNLMRLCWSKLPADRPSFTSIHRILERMCERAEGTVSV

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
14	Phosphorylation	IPLVHILTLVAFSGT CCHHHHHHHHHCCCC	20.70	24043423
19	Phosphorylation	ILTLVAFSGTEKLPK HHHHHHCCCCCCCCC	34.76	24043423
21	Phosphorylation	TLVAFSGTEKLPKAP HHHHCCCCCCCCCCC	28.84	24043423
31	Phosphorylation	LPKAPVITTPLETVD CCCCCEECCCHHHHH	23.69	-
76	Phosphorylation	KLFDTRYSIRENGQL HHHCCCEEEECCCEE	16.33	24719451
153	Phosphorylation	GNPKPSVSWIKGDSP CCCCCCCCCCCCCCC	27.67	28961369
195	Phosphorylation	YRCVAKNSLGTAYSK EEEEEECCCCCCHHH	27.72	25219547
198	Phosphorylation	VAKNSLGTAYSKVVK EEECCCCCCHHHHEE	27.93	25219547
200	Phosphorylation	KNSLGTAYSKVVKLE ECCCCCCHHHHEEHH	14.63	25219547
201	Phosphorylation	NSLGTAYSKVVKLEV CCCCCCHHHHEEHHH	19.26	25219547
222	N-linked_Glycosylation	LRAPESHNVTFGSFV HCCCHHCCCCCCEEE	43.75	UniProtKB CARBOHYD
275	Phosphorylation	SRLQLFITKPGLYTC HCCEEEEECCCEEEE	24.69	29978859
280	Phosphorylation	FITKPGLYTCIATNK EEECCCEEEEEEECC	12.89	29978859
281	Phosphorylation	ITKPGLYTCIATNKH EECCCEEEEEEECCC	11.50	29978859
285	Phosphorylation	GLYTCIATNKHGEKF CEEEEEEECCCCCCC	25.53	29978859
293	Phosphorylation	NKHGEKFSTAKAAAT CCCCCCCCCCHHHHE	38.22	-
294	Phosphorylation	KHGEKFSTAKAAATI CCCCCCCCCHHHHEE	35.00	-
316	Phosphorylation	PQKDNKGYCAQYRGE CCCCCCCCCHHHHHH	6.04	29759185
320	Phosphorylation	NKGYCAQYRGEVCNA CCCCCHHHHHHHHHH	11.32	29759185
338	N-linked_Glycosylation	KDALVFLNTSYADPE HCEEEEEECCCCCHH	18.60	UniProtKB CARBOHYD
339	Phosphorylation	DALVFLNTSYADPEE CEEEEEECCCCCHHH	25.84	26074081
340	Phosphorylation	ALVFLNTSYADPEEA EEEEEECCCCCHHHH	19.76	26074081
341	Phosphorylation	LVFLNTSYADPEEAQ EEEEECCCCCHHHHH	17.00	26074081
417	Phosphorylation	WLVMEEKTHRGLYRS HHHCCCCCCCCCCCC	21.78	24719451
424	Phosphorylation	THRGLYRSEMHLLSV CCCCCCCCCCEEECC	26.22	-
430	Phosphorylation	RSEMHLLSVPECSKL CCCCEEECCCCHHCC	41.82	-
435	Phosphorylation	LLSVPECSKLPSMHW EECCCCHHCCCCCCC	35.25	24719451
554	Phosphorylation	RLHPNPMYQRMPLLL CCCCCCHHHCCCCHH	8.33	10781064
577	Phosphorylation	YPRNNIEYVRDIGEG CCCCCCEEEEECCCC	9.29	10781064
681	Phosphorylation	TVCSLSHSDLSMRAQ CEEECCCCHHHHEEE	36.55	-
698	Phosphorylation	SPGPPPLSCAEQLCI CCCCCCCCHHHHHHH	19.63	-
751	Phosphorylation	FGLSRNIYSADYYKA HCCCCCEECCCCCCC	11.01	10781064
755	Phosphorylation	RNIYSADYYKANEND CCEECCCCCCCCCCC	13.44	10781064
756	Phosphorylation	NIYSADYYKANENDA CEECCCCCCCCCCCC	12.27	10781064
813	Phosphorylation	MAHEEVIYYVRDGNI CCCCEEEEEEECCCE	10.90	10781064

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
681	S	Phosphorylation	Kinase	CK2	-	Uniprot
698	S	Phosphorylation	Kinase	CK2	-	Uniprot
-	K	Ubiquitination	E3 ubiquitin ligase	PDZRN3	Q9UPQ7	PMID:17576800

Functions of PTM Sites

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

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_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
SYNE1_HUMAN	SYNE1	physical	10878022
PZRN3_HUMAN	PDZRN3	physical	17576800
ADA30_HUMAN	ADAM30	physical	28514442
DJC13_HUMAN	DNAJC13	physical	28514442
RBNS5_HUMAN	RBSN	physical	28514442
ILKAP_HUMAN	ILKAP	physical	28065597
STYX_HUMAN	STYX	physical	28065597

Drug and Disease Associations

• Kegg Disease
• H00770: Congenital myasthenic syndrome
• OMIM Disease
• 616325: Myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency (CMS9)
• 208150: Fetal akinesia deformation sequence (FADS)
• Kegg Drug
• There are no disease associations of PTM sites.
• DrugBank
• There are no disease associations of PTM sites.