|MUSK_HUMAN » Muscle, skeletal receptor tyrosine protein kinase » Muscle-specific tyrosine protein kinase receptor;Muscle-specific kinase receptor; MuSK;|
|Hydrophobic Thickness||32.0 ± 1.4 Å|
|Tilt Angle||0 ± 3°|
|Links||UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC, HMDB|
|TM Segments||494-517 (490-521)|
|UniProt annotation for MUSK_HUMAN » Muscle, skeletal receptor tyrosine protein kinase|
|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). 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). CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. ENZYME REGULATION: Positively regulated by CK2. SUBUNIT: Monomer (By similarity). Homodimer (Probable). Interacts with LRP4; the heterodimer forms an AGRIN receptor complex that binds AGRIN resulting in activation of MUSK (By similarity). Forms a heterotetramer composed of 2 DOK7 and 2 MUSK molecules which facilitates MUSK trans-autophosphorylation on tyrosine residue and activation. Interacts (via cytoplasmic part) with DOK7 (via IRS- type PTB domain); requires MUSK phosphorylation. Interacts with DVL1 (via DEP domain); the interaction is direct and mediates the formation of a DVL1, MUSK and PAK1 ternary complex involved in AChR clustering (By similarity). Interacts with PDZRN3; this interaction is enhanced by agrin (By similarity). Interacts with FNTA; the interaction is direct and mediates AGRIN-induced phosphorylation and activation of FNTA (By similarity). Interacts with CSNK2B; mediates regulation by CK2 (By similarity). Interacts (via the cytoplasmic domain) with DNAJA3 (By similarity). Interacts with NSF; may regulate MUSK endocytosis and activity (By similarity). Interacts with CAV3; may regulate MUSK signaling (By similarity). Interacts with RNF31 (By similarity). DISEASE: Myasthenic syndrome, congenital, associated with acetylcholine receptor deficiency (CMS-ACHRD) OMIM: A post-synaptic congenital myasthenic syndrome. Congenital myasthenic syndromes (CMS) are inherited disorders of neuromuscular transmission that stem from mutations in presynaptic, synaptic, or postsynaptic proteins. mutations affecting the gene represented in this entry. MUSK mutations lead to decreased agrin-dependent AChR aggregation, a critical step in the formation of the neuromuscular junction. DISEASE: Fetal akinesia deformation sequence (FADS) OMIM: A clinically and genetically heterogeneous group of disorders with congenital malformations related to impaired fetal movement. Clinical features include fetal akinesia, intrauterine growth retardation, polyhydramnios, arthrogryposis, pulmonary hypoplasia, craniofacial abnormalities, and cryptorchidism. Note=The disease is caused by mutations affecting the gene represented in this entry.|
|UniProt features for MUSK_HUMAN » Muscle, skeletal receptor tyrosine protein kinase|
SIGNAL 1 23 Potential. |
CHAIN 24 869 Muscle, skeletal receptor tyrosine- protein kinase.
DOMAIN 28 116 Ig-like 1.
DOMAIN 121 205 Ig-like 2.
DOMAIN 212 302 Ig-like 3.
DOMAIN 312 450 FZ.
DOMAIN 575 856 Protein kinase.
ACT_SITE 725 725 Proton acceptor (By similarity).
DISULFID 49 99 By similarity.
DISULFID 98 112 By similarity.
DISULFID 142 190 By similarity.
DISULFID 233 282 By similarity.
DISULFID 317 382 By similarity.
DISULFID 325 375 By similarity.
DISULFID 366 406 By similarity.
DISULFID 394 447 By similarity.
DISULFID 398 434 By similarity.
|Amino Acid Sequence for MUSK_HUMAN » Muscle, skeletal receptor tyrosine protein kinase|
|MRELVNIPLV HILTLVAFSG TEKLPKAPVI TTPLETVDAL VEEVATFMCA VESYPQPEIS WTRNKILIKL FDTRYSIREN GQLLTILSVE DSDDGIYCCT ANNGVGGAVE SCGALQVKMK PKITRPPINV KIIEGLKAVL PCTTMGNPKP SVSWIKGDSP LRENSRIAVL ESGSLRIHNV QKEDAGQYRC VAKNSLGTAY SKVVKLEVEV FARILRAPES HNVTFGSFVT LHCTATGIPV PTITWIENGN AVSSGSIQES VKDRVIDSRL QLFITKPGLY TCIATNKHGE KFSTAKAAAT ISIAEWSKPQ KDNKGYCAQY RGEVCNAVLA KDALVFLNTS YADPEEAQEL LVHTAWNELK VVSPVCRPAA EALLCNHIFQ ECSPGVVPTP IPICREYCLA VKELFCAKEW LVMEEKTHRG LYRSEMHLLS VPECSKLPSM HWDPTACARL PHLDYNKENL KTFPPMTSSK PSVDIPNLPS SSSSSFSVSP TYSMTVIISI MSSFAIFVLL TITTLYCCRR RKQWKNKKRE SAAVTLTTLP SELLLDRLHP NPMYQRMPLL LNPKLLSLEY PRNNIEYVRD IGEGAFGRVF QARAPGLLPY EPFTMVAVKM LKEEASADMQ ADFQREAALM AEFDNPNIVK LLGVCAVGKP MCLLFEYMAY GDLNEFLRSM SPHTVCSLSH SDLSMRAQVS SPGPPPLSCA EQLCIARQVA AGMAYLSERK FVHRDLATRN CLVGENMVVK IADFGLSRNI YSADYYKANE NDAIPIRWMP PESIFYNRYT TESDVWAYGV VLWEIFSYGL QPYYGMAHEE VIYYVRDGNI LSCPENCPVE LYNLMRLCWS KLPADRPSFT SIHRILERMC ERAEGTVSV|