Recombinant Human Muscle, Skeletal Receptor Tyrosine-Protein Kinase (MUSK) Protein (His), Active

Name: Recombinant Human Muscle, Skeletal Receptor Tyrosine-Protein Kinase (MUSK) Protein (His), Active
Brand: Beta LifeScience
SKU: BLC-06113P
Availability: InStock

Greater than 90% as determined by SDS-PAGE.

Activity Measured by ADP-Glo Kinase detection kit. The EC 50 of MUSK is 2.65-3.58 μg/ml.

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Product Overview

Description	Recombinant Human Muscle, Skeletal Receptor Tyrosine-Protein Kinase (MUSK) Protein (His), Active is produced by our E.coli expression system. This is a extracellular protein.
Purity	Greater than 90% as determined by SDS-PAGE.
Activity	Measured by ADP-Glo Kinase detection kit. The EC50 of MUSK is 2.65-3.58 μg/ml.
Uniprotkb	O15146
Target Symbol	MUSK
Synonyms	MUSK; Muscle, skeletal receptor tyrosine-protein kinase; Muscle-specific tyrosine-protein kinase receptor; MuSK; Muscle-specific kinase receptor
Species	Homo sapiens (Human)
Expression System	in vitro E.coli expression system
Tag	N-6His
Target Protein Sequence	LPKAPVITTPLETVDALVEEVATFMCAVESYPQPEISWTRNKILIKLFDTRYSIRENGQLLTILSVEDSDDGIYCCTANNGVGGAVESCGALQVKMKPKITRPPINVKIIEGLKAVLPCTTMGNPKPSVSWIKGDSPLRENSRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGTAYSKVVKLEVEEESEPEQDTKVFARILRAPESHNVTFGSFVTLHCTATGIPVPTITWIENGNAVSSGSIQESVKDRVIDSRLQLFITKPGLYTCIATNKHGEKFSTAKAAATISIAEWREYCLAVKELFCAKEWLVMEEKTHRGLYRSEMHLLSVPECSKLPSMHWDPTACARLPHLAFPPMTSSKPSVDIPNLPSSSSSSFSVSPTYSMTVIISIMSSFAIFVLLTITTLYCCRRRKQWKNKKRESAAVTLTTLPSELLLDRLHPNPMYQRMPLLLNPKLLSLEYPRNNIEYVRDI
Expression Range	24-495aa
Protein Length	Extracellular Domain
Mol. Weight	56.5kDa
Research Area	Signal Transduction
Form	Liquid or Lyophilized powder
Buffer	Liquid form: default storage buffer is Tris/PBS-based buffer, 5%-50% glycerol. Lyophilized powder form: the buffer before lyophilization is Tris/PBS-based buffer, 6% Trehalose, pH 8.0.
Reconstitution	Briefly centrifuged the vial prior to opening to bring the contents to the bottom. Reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL. It is recommended to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20°C/-80°C. The default final concentration of glycerol is 50%.
Storage	1. Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. 2. Avoid repeated freeze-thaw cycles. 3. Store working aliquots at 4°C for up to one week. 4. In general, protein in liquid form is stable for up to 6 months at -20°C/-80°C. Protein in lyophilized powder form is stable for up to 12 months at -20°C/-80°C.
Notes	Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.

Target Details

Target 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. 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.
Subcellular Location	Cell junction, synapse, postsynaptic cell membrane; Single-pass type I membrane protein.
Protein Families	Protein kinase superfamily, Tyr protein kinase family
Database References	HGNC: 7525 OMIM: 208150 KEGG: hsa:4593 STRING: 9606.ENSP00000363571 UniGene: PMID: 27601729 Classical electromyography revealed the presence of myopathic changes more frequently in MuSK myasthenia gravis compared to acetylcholine receptor myasthenia gravis PMID: 26778359 A Dutch founder mutation in MUSK causing fetal akinesia deformation sequence has been found in 14 fetuses. PMID: 25537362 To our knowledge, this is the first report showing that a mutation in MuSK is associated with Fetal akinesia deformation sequence syndrome PMID: 25612909 Immunosuppression attenuates the Th1 response in AChR-myasthenia gravis (MG) and MuSK-MG, but otherwise modulates immune responses in AChR-MG and MuSK-MG patients differentially. PMID: 25893403 HnRNP C, YB-1 and hnRNP L coordinately enhance skipping of human MUSK exon 10 to generate a Wnt-insensitive MuSK isoform. PMID: 25354590 MuSK myasthenia gravis IgG4 disrupts the interaction of LRP4 with MuSK but both IgG4 and IgG1-3 can disperse preformed agrin-independent AChR clusters PMID: 24244707 [review] Recent discovery of two novel target proteins (MuSK and LRP4) has reduced the percentage of patients without known autoantibodies, although there are still some seronegative myasthenia gravis patients. PMID: 24530233 Identification of a novel missense mutation c.114T > A; p.Asp38Glu heteroallelic to a genomic deletion encompassing exons 2-3 of MUSK that explain a limb-girdle congenital myasthenic syndrome in two affected brothers of a Turkish family. PMID: 24183479 HEp-2 M4 cells revealed a high specificity for the detection of MuSK autoantibodies from 25 patient sera. PMID: 24416182 This study provides a replication of the highly significant associations of both HLA-DRB1( )16,-DRB1( )14 and -DQB1( *)05 with MuSK-MG. PMID: 23993985 pathogenic IgG4 antibodies to MuSK bind to a structural epitope in the first Ig-like domain of MuSK, prevent binding between MuSK and Lrp4, and inhibit Agrin-stimulated MuSK phosphorylation. PMID: 24297891 We proved that the missense mutations in ColQ-CTD cause endplate AChE deficiency by compromising ColQ-MuSK interaction at the NMJ. PMID: 23553736 MUSK is associated with a small but variable subgroup of distinct phenotypes in Thai patients with myasthenia gravis who have MUSK autoantibodies. PMID: 23352351 MUSK antibodies may induce phenotypically disruptive actions at the neuromuscular junction by binding acetylcholinesterase (AChE) via its collagen tail, producing a reduction in synaptic AChE activity. PMID: 23720161 MuSK is activated in a complex spatio-temporal manner to cluster acetylcholine receptors on the postsynaptic (muscle) side of the synapse and to induce differentiation of the nerve terminal on the presynaptic side. (Review) PMID: 23467009 We report a novel mutation in MUSK leading to a Congenital myasthenic syndromes PMID: 23326516 MuSK kinase activity is necessary for substrate-dependent acetylcholine receptor cluster formation PMID: 22210232 Two family cases are reported that transmit MuSK antibody myasthenia gravis to the offspring by different maternal mechanisms. PMID: 21386774 The ability of immobilized MuSK extracellular domain to remove practically all anti-MuSK antibodies from patients' sera should prove invaluable for development of an antigen-specific therapeutic approach for MuSK myasthenia gravis. PMID: 21993075 Lrp4 is a cis-acting ligand for MuSK PMID: 21969364 The importance of MuSK as a synapse organiser is highlighted by cases of autoimmune myasthenia gravis in which MuSK autoantibodies can deplete MuSK from the postsynaptic membrane, leading to complete disassembly of the adult neuromuscular junction. PMID: 20974278 these findings demonstrate that missense mutations in MUSK can result in a severe form of congenital myasthenic syndrome and indicate that the inability of MuSK mutants to interact with Dok-7. PMID: 20371544 Anti-MuSK protein positive patients have more predominantly bulbar involvement and had more severe myasthenia gravis. PMID: 19327804 analysis of regulation of MuSK expression by a novel signaling pathway PMID: 12885777 Missense mutation does not affect MuSK catalytic kinase activity but diminishes expression and stability. PMID: 15496425 Thus, an agrin/MuSK complex may form part of a motor neuron stop signal involved in "reverse signaling" to the motor neuron. PMID: 15691710 A low-molecular weight isoform of muscle-specific receptor tyrosine kinase in human sperm localized in the flagellar mid-piece region. PMID: 16487930 Dok-7 is essential for neuromuscular synaptogenesis through its interaction with MuSK PMID: 16794080 Altogether, these results indicate that anti-MuSK Abs could be pathogenic by contributing to the muscle atrophy in MuSK+ MG patients. PMID: 16857268 muscle-specific receptor tyrosine kinase activation and binding to dystroglycan are regulated by alternative mRNA splicing of agrin PMID: 17012237 Testing of human myotubes for the presence and activation of MuSK by exposing them to laminin. PMID: 17192614 We describe a case of epileptic seizures secondary to myasthenia gravis caused by autoantibodies to the MUSK receptor. These autoantibodies affected the brain as well. PMID: 17661994 the COOH-terminal NES and Src homology 2 target motifs play key roles in Dok-7/MuSK signaling for neuromuscular synaptogenesis. PMID: 18165682 We describe a transient neonatal myasthenic syndrome with anti-musk antibodies. PMID: 18378885 IgG from anti-MuSK-positive patients can cause myasthenia gravis when injected into mice. PMID: 18384168 single-fiber electromyography of distal limb muscles tends to have a lower yield of abnormality in MuSK-antibody-positive patients than either acetylcholine receptor-antibody-positive or seronegative myasthenia gravis PMID: 18567855 Thymectomy is mostly considered scarcely effective; however, at present, no firm conclusions can be drawn on its role in the treatment of this form of myasthenia gravis PMID: 18567856 Anti-MuSK antibodies influence the activity of MuSK molecules without reducing their number, thereby diminishing the size of the endplate and affecting the functioning of acetylcholine receptors. PMID: 19745065 This study report a family known so far with a congenital myasthenic syndromes due to a mutation in the MUSK gene. PMID: 19949040

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Proteins are sensitive to heat, and freeze-drying can preserve the activity of the majority of proteins. It improves protein stability, extends storage time, and reduces shipping costs. However, freeze-drying can also lead to the loss of the active portion of the protein and cause aggregation and denaturation issues. Nonetheless, these adverse effects can be minimized by incorporating protective agents such as stabilizers, additives, and excipients, and by carefully controlling various lyophilization conditions.

Commonly used protectant include saccharides, polyols, polymers, surfactants, some proteins and amino acids etc. We usually add 8% (mass ratio by volume) of trehalose and mannitol as lyoprotectant. Trehalose can significantly prevent the alter of the protein secondary structure, the extension and aggregation of proteins during freeze-drying process; mannitol is also a universal applied protectant and fillers, which can reduce the aggregation of certain proteins after lyophilization.

Our protein products do not contain carrier protein or other additives (such as bovine serum albumin (BSA), human serum albumin (HSA) and sucrose, etc., and when lyophilized with the solution with the lowest salt content, they often cannot form A white grid structure, but a small amount of protein is deposited in the tube during the freeze-drying process, forming a thin or invisible transparent protein layer.

Reminder: Before opening the tube cap, we recommend that you quickly centrifuge for 20-30 seconds in a small centrifuge, so that the protein attached to the tube cap or the tube wall can be aggregated at the bottom of the tube. Our quality control procedures ensure that each tube contains the correct amount of protein, and although sometimes you can't see the protein powder, the amount of protein in the tube is still very precise.

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