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Overview

Uniprot IDO15146
Protein NameMuscle, skeletal receptor tyrosine-protein kinase
Gene NameMUSK
OrganismHomo 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.