Overview
| Uniprot ID | O15146 |
| Protein Name | Muscle, skeletal receptor tyrosine-protein kinase |
| Gene Name | MUSK |
| Organism | Homo sapiens |
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 287 |
YTCIATNKHGEKFST |
| 291 |
ATNKHGEKFSTAKAA |
| 296 |
GEKFSTAKAAATISI |
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)
Protein Sequence
10
MRELVNIPLV
20
HILTLVAFSG
30
TEKLPKAPVI
40
TTPLETVDAL
50
VEEVATFMCA
60
VESYPQPEIS
70
WTRNKILIKL
80
FDTRYSIREN
90
GQLLTILSVE
100
DSDDGIYCCT
110
ANNGVGGAVE
120
SCGALQVKMK
130
PKITRPPINV
140
KIIEGLKAVL
150
PCTTMGNPKP
160
SVSWIKGDSP
170
LRENSRIAVL
180
ESGSLRIHNV
190
QKEDAGQYRC
200
VAKNSLGTAY
210
SKVVKLEVEV
220
FARILRAPES
230
HNVTFGSFVT
240
LHCTATGIPV
250
PTITWIENGN
260
AVSSGSIQES
270
VKDRVIDSRL
280
QLFITKPGLY
290
TCIATNKHGE
300
KFSTAKAAAT
310
ISIAEWSKPQ
320
KDNKGYCAQY
330
RGEVCNAVLA
340
KDALVFLNTS
350
YADPEEAQEL
360
LVHTAWNELK
370
VVSPVCRPAA
380
EALLCNHIFQ
390
ECSPGVVPTP
400
IPICREYCLA
410
VKELFCAKEW
420
LVMEEKTHRG
430
LYRSEMHLLS
440
VPECSKLPSM
450
HWDPTACARL
460
PHLDYNKENL
470
KTFPPMTSSK
480
PSVDIPNLPS
490
SSSSSFSVSP
500
TYSMTVIISI
510
MSSFAIFVLL
520
TITTLYCCRR
530
RKQWKNKKRE
540
SAAVTLTTLP
550
SELLLDRLHP
560
NPMYQRMPLL
570
LNPKLLSLEY
580
PRNNIEYVRD
590
IGEGAFGRVF
600
QARAPGLLPY
610
EPFTMVAVKM
620
LKEEASADMQ
630
ADFQREAALM
640
AEFDNPNIVK
650
LLGVCAVGKP
660
MCLLFEYMAY
670
GDLNEFLRSM
680
SPHTVCSLSH
690
SDLSMRAQVS
700
SPGPPPLSCA
710
EQLCIARQVA
720
AGMAYLSERK
730
FVHRDLATRN
740
CLVGENMVVK
750
IADFGLSRNI
760
YSADYYKANE
770
NDAIPIRWMP
780
PESIFYNRYT
790
TESDVWAYGV
800
VLWEIFSYGL
810
QPYYGMAHEE
820
VIYYVRDGNI
830
LSCPENCPVE
840
LYNLMRLCWS
850
KLPADRPSFT
860
SIHRILERMC
ERAEGTVSV
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0031594 |
neuromuscular junction |
| Cellular Component |
GO:0005886 |
plasma membrane |
| Cellular Component |
GO:0045211 |
postsynaptic membrane |
| Cellular Component |
GO:0043235 |
receptor complex |
| Molecular Function |
GO:0005524 |
ATP binding |
| Molecular Function |
GO:0046872 |
metal ion binding |
| Molecular Function |
GO:0004713 |
protein tyrosine kinase activity |
| Molecular Function |
GO:0004714 |
transmembrane receptor protein tyrosine kinase activity |
| Molecular Function |
GO:0017147 |
Wnt-protein binding |
| Biological Process |
GO:0030154 |
cell differentiation |
| Biological Process |
GO:0007169 |
cell surface receptor protein tyrosine kinase signaling pathway |
| Biological Process |
GO:0007613 |
memory |
| Biological Process |
GO:0007528 |
neuromuscular junction development |
| Biological Process |
GO:0010628 |
positive regulation of gene expression |
| Biological Process |
GO:2000541 |
positive regulation of protein geranylgeranylation |
| Biological Process |
GO:0001934 |
positive regulation of protein phosphorylation |
| Biological Process |
GO:0008582 |
regulation of synaptic assembly at neuromuscular junction |
| Biological Process |
GO:0071340 |
skeletal muscle acetylcholine-gated channel clustering |
Reference
[1] Yan M, Tu H, Tang S, Gai Z, Shi Q et al.. Lactylated Proteomic Analysis Reveals Functional Implications of Lysine Lactylation In Asthenozoospermia.. Mol Cell Proteomics 24(12):101439. 2025 Dec. PMID: 41192556.