Muscle, skeletal receptor tyrosine-protein kinase

Details

Name
Muscle, skeletal receptor tyrosine-protein kinase
Synonyms
  • 2.7.10.1
  • Muscle-specific kinase receptor
  • Muscle-specific tyrosine-protein kinase receptor
  • MuSK
Gene Name
MUSK
Organism
Humans
Amino acid sequence
>lcl|BSEQ0051860|Muscle, skeletal receptor tyrosine-protein kinase
MRELVNIPLVHILTLVAFSGTEKLPKAPVITTPLETVDALVEEVATFMCAVESYPQPEIS
WTRNKILIKLFDTRYSIRENGQLLTILSVEDSDDGIYCCTANNGVGGAVESCGALQVKMK
PKITRPPINVKIIEGLKAVLPCTTMGNPKPSVSWIKGDSPLRENSRIAVLESGSLRIHNV
QKEDAGQYRCVAKNSLGTAYSKVVKLEVEVFARILRAPESHNVTFGSFVTLHCTATGIPV
PTITWIENGNAVSSGSIQESVKDRVIDSRLQLFITKPGLYTCIATNKHGEKFSTAKAAAT
ISIAEWSKPQKDNKGYCAQYRGEVCNAVLAKDALVFLNTSYADPEEAQELLVHTAWNELK
VVSPVCRPAAEALLCNHIFQECSPGVVPTPIPICREYCLAVKELFCAKEWLVMEEKTHRG
LYRSEMHLLSVPECSKLPSMHWDPTACARLPHLDYNKENLKTFPPMTSSKPSVDIPNLPS
SSSSSFSVSPTYSMTVIISIMSSFAIFVLLTITTLYCCRRRKQWKNKKRESAAVTLTTLP
SELLLDRLHPNPMYQRMPLLLNPKLLSLEYPRNNIEYVRDIGEGAFGRVFQARAPGLLPY
EPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMAY
GDLNEFLRSMSPHTVCSLSHSDLSMRAQVSSPGPPPLSCAEQLCIARQVAAGMAYLSERK
FVHRDLATRNCLVGENMVVKIADFGLSRNIYSADYYKANENDAIPIRWMPPESIFYNRYT
TESDVWAYGVVLWEIFSYGLQPYYGMAHEEVIYYVRDGNILSCPENCPVELYNLMRLCWS
KLPADRPSFTSIHRILERMCERAEGTVSV
Number of residues
869
Molecular Weight
97055.3
Theoretical pI
Not Available
GO Classification
Functions
ATP binding / metal ion binding / protein tyrosine kinase activity / transmembrane receptor protein tyrosine kinase activity
Processes
cell differentiation / memory / multicellular organism development / neuromuscular junction development / positive regulation of gene expression / positive regulation of protein geranylgeranylation / positive regulation of protein phosphorylation / protein autophosphorylation / regulation of synaptic growth at neuromuscular junction / skeletal muscle acetylcholine-gated channel clustering / transmembrane receptor protein tyrosine kinase signaling pathway
Components
cell junction / integral component of plasma membrane / neuromuscular junction / postsynaptic membrane / receptor complex
General 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 within the central nervous system by mediating cholinergic responses, synaptic plasticity and memory formation (By similarity).
Specific Function
Atp binding
Pfam Domain Function
Transmembrane Regions
496-516
Cellular Location
Cell junction
Gene sequence
>lcl|BSEQ0051861|Muscle, skeletal receptor tyrosine-protein kinase (MUSK)
ATGAGAGAGCTCGTCAACATTCCACTGGTACATATTCTTACTCTGGTTGCCTTCAGCGGA
ACTGAGAAACTTCCAAAAGCTCCTGTCATCACCACTCCTCTTGAAACAGTGGATGCCTTA
GTTGAAGAAGTGGCTACTTTCATGTGTGCAGTGGAATCCTACCCCCAGCCTGAGATTTCC
TGGACTAGAAATAAAATTCTCATTAAACTCTTTGACACCCGGTACAGCATCCGGGAGAAT
GGGCAGCTCCTCACCATCCTGAGTGTGGAAGACAGTGATGATGGCATTTACTGCTGCACG
GCCAACAATGGTGTGGGAGGAGCTGTGGAGAGTTGTGGAGCCCTGCAAGTGAAGATGAAA
CCTAAAATAACTCGTCCTCCCATAAATGTGAAAATAATAGAGGGATTAAAAGCAGTCCTA
CCATGTACTACAATGGGTAATCCCAAACCATCAGTGTCTTGGATAAAGGGAGACAGCCCT
CTCAGGGAAAATTCCCGAATTGCAGTTCTTGAATCTGGGAGCTTGAGGATTCATAACGTA
CAAAAGGAAGATGCAGGACAGTATCGATGTGTGGCAAAAAACAGCCTCGGGACAGCATAT
TCCAAAGTGGTGAAGCTGGAAGTTGAGGTTTTTGCCAGGATCCTGCGGGCTCCTGAATCC
CACAATGTCACCTTTGGCTCCTTTGTGACCCTGCACTGTACAGCAACAGGCATTCCTGTC
CCCACCATCACCTGGATTGAAAACGGAAATGCTGTTTCTTCTGGGTCCATTCAAGAGAGT
GTGAAAGACCGAGTGATTGACTCAAGACTGCAGCTGTTTATCACCAAGCCAGGACTCTAC
ACATGCATAGCTACCAATAAGCATGGGGAGAAGTTCAGTACTGCCAAGGCTGCAGCCACC
ATCAGCATAGCAGAATGGAGTAAACCACAGAAAGATAACAAAGGCTACTGCGCCCAGTAC
AGAGGGGAGGTGTGTAATGCAGTCCTGGCAAAAGATGCTCTTGTTTTTCTCAACACCTCC
TATGCGGACCCTGAGGAGGCCCAAGAGCTACTGGTCCACACGGCCTGGAATGAACTGAAA
GTAGTGAGCCCAGTCTGCCGGCCAGCTGCTGAGGCTTTGTTGTGTAACCACATCTTCCAG
GAGTGCAGTCCTGGAGTAGTGCCTACTCCTATTCCCATTTGCAGAGAGTACTGCTTGGCA
GTAAAGGAGCTCTTCTGCGCAAAAGAATGGCTGGTAATGGAAGAGAAGACCCACAGAGGA
CTCTACAGATCCGAGATGCATTTGCTGTCCGTGCCAGAATGCAGCAAGCTTCCCAGCATG
CATTGGGACCCCACGGCCTGTGCCAGACTGCCACATCTAGATTATAACAAAGAAAACCTA
AAAACATTCCCACCAATGACGTCCTCAAAGCCAAGTGTGGACATTCCAAATCTGCCTTCC
TCCTCCTCTTCTTCCTTCTCTGTCTCACCTACATACTCCATGACTGTAATAATCTCCATC
ATGTCCAGCTTTGCAATATTTGTGCTTCTTACCATAACTACTCTCTATTGCTGCCGAAGA
AGAAAACAATGGAAAAATAAGAAAAGAGAATCAGCAGCAGTAACCCTCACCACACTGCCT
TCTGAGCTCTTACTAGATAGACTTCATCCCAACCCCATGTACCAGAGGATGCCGCTCCTT
CTGAACCCCAAATTGCTCAGCCTGGAGTATCCAAGGAATAACATTGAATATGTGAGAGAC
ATCGGAGAGGGAGCGTTTGGAAGGGTGTTTCAAGCAAGGGCACCAGGCTTACTTCCCTAT
GAACCTTTCACTATGGTGGCAGTAAAGATGCTCAAAGAAGAAGCCTCGGCAGATATGCAA
GCGGACTTTCAGAGGGAGGCAGCCCTCATGGCAGAATTTGACAACCCTAACATTGTGAAG
CTATTAGGAGTGTGTGCTGTCGGGAAGCCAATGTGCCTGCTCTTTGAATACATGGCCTAT
GGTGACCTCAATGAGTTCCTCCGCAGCATGTCCCCTCACACCGTGTGCAGCCTCAGTCAC
AGTGACTTGTCTATGAGGGCTCAGGTCTCCAGCCCTGGGCCCCCACCCCTCTCCTGTGCT
GAGCAGCTTTGCATTGCCAGGCAGGTGGCAGCTGGCATGGCTTACCTCTCAGAACGTAAG
TTTGTTCACCGAGATTTAGCCACCAGGAACTGCCTGGTGGGCGAGAACATGGTGGTGAAA
ATTGCCGACTTTGGCCTCTCCAGGAACATCTACTCAGCAGACTACTACAAAGCTAATGAA
AACGACGCTATCCCTATCCGTTGGATGCCACCAGAGTCCATTTTTTATAACCGCTACACT
ACAGAGTCTGATGTGTGGGCCTATGGCGTGGTCCTCTGGGAGATCTTCTCCTATGGCCTG
CAGCCCTACTATGGGATGGCCCATGAGGAGGTCATTTACTACGTGCGAGATGGCAACATC
CTCTCCTGCCCTGAGAACTGCCCCGTGGAGCTGTACAATCTCATGCGTCTATGTTGGAGC
AAGCTGCCTGCAGACAGACCCAGTTTCACCAGTATTCACCGAATTCTGGAACGCATGTGT
GAGAGGGCAGAGGGAACTGTGAGTGTCTAA
Chromosome Location
9
Locus
9q31.3
External Identifiers
ResourceLink
UniProtKB IDO15146
UniProtKB Entry NameMUSK_HUMAN
HGNC IDHGNC:7525
General References
  1. Valenzuela DM, Stitt TN, DiStefano PS, Rojas E, Mattsson K, Compton DL, Nunez L, Park JS, Stark JL, Gies DR, et al.: Receptor tyrosine kinase specific for the skeletal muscle lineage: expression in embryonic muscle, at the neuromuscular junction, and after injury. Neuron. 1995 Sep;15(3):573-84. [Article]
  2. Humphray SJ, Oliver K, Hunt AR, Plumb RW, Loveland JE, Howe KL, Andrews TD, Searle S, Hunt SE, Scott CE, Jones MC, Ainscough R, Almeida JP, Ambrose KD, Ashwell RI, Babbage AK, Babbage S, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beasley H, Beasley O, Bird CP, Bray-Allen S, Brown AJ, Brown JY, Burford D, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Chen Y, Clarke G, Clark SY, Clee CM, Clegg S, Collier RE, Corby N, Crosier M, Cummings AT, Davies J, Dhami P, Dunn M, Dutta I, Dyer LW, Earthrowl ME, Faulkner L, Fleming CJ, Frankish A, Frankland JA, French L, Fricker DG, Garner P, Garnett J, Ghori J, Gilbert JG, Glison C, Grafham DV, Gribble S, Griffiths C, Griffiths-Jones S, Grocock R, Guy J, Hall RE, Hammond S, Harley JL, Harrison ES, Hart EA, Heath PD, Henderson CD, Hopkins BL, Howard PJ, Howden PJ, Huckle E, Johnson C, Johnson D, Joy AA, Kay M, Keenan S, Kershaw JK, Kimberley AM, King A, Knights A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd C, Lloyd DM, Lovell J, Martin S, Mashreghi-Mohammadi M, Matthews L, McLaren S, McLay KE, McMurray A, Milne S, Nickerson T, Nisbett J, Nordsiek G, Pearce AV, Peck AI, Porter KM, Pandian R, Pelan S, Phillimore B, Povey S, Ramsey Y, Rand V, Scharfe M, Sehra HK, Shownkeen R, Sims SK, Skuce CD, Smith M, Steward CA, Swarbreck D, Sycamore N, Tester J, Thorpe A, Tracey A, Tromans A, Thomas DW, Wall M, Wallis JM, West AP, Whitehead SL, Willey DL, Williams SA, Wilming L, Wray PW, Young L, Ashurst JL, Coulson A, Blocker H, Durbin R, Sulston JE, Hubbard T, Jackson MJ, Bentley DR, Beck S, Rogers J, Dunham I: DNA sequence and analysis of human chromosome 9. Nature. 2004 May 27;429(6990):369-74. [Article]
  3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  4. Bergamin E, Hallock PT, Burden SJ, Hubbard SR: The cytoplasmic adaptor protein Dok7 activates the receptor tyrosine kinase MuSK via dimerization. Mol Cell. 2010 Jul 9;39(1):100-9. doi: 10.1016/j.molcel.2010.06.007. [Article]
  5. Del Rincon SV, Rogers J, Widschwendter M, Sun D, Sieburg HB, Spruck C: Development and validation of a method for profiling post-translational modification activities using protein microarrays. PLoS One. 2010 Jun 28;5(6):e11332. doi: 10.1371/journal.pone.0011332. [Article]
  6. Bainbridge TW, DeAlmeida VI, Izrael-Tomasevic A, Chalouni C, Pan B, Goldsmith J, Schoen AP, Quinones GA, Kelly R, Lill JR, Sandoval W, Costa M, Polakis P, Arnott D, Rubinfeld B, Ernst JA: Evolutionary divergence in the catalytic activity of the CAM-1, ROR1 and ROR2 kinase domains. PLoS One. 2014 Jul 16;9(7):e102695. doi: 10.1371/journal.pone.0102695. eCollection 2014. [Article]
  7. Chevessier F, Faraut B, Ravel-Chapuis A, Richard P, Gaudon K, Bauche S, Prioleau C, Herbst R, Goillot E, Ioos C, Azulay JP, Attarian S, Leroy JP, Fournier E, Legay C, Schaeffer L, Koenig J, Fardeau M, Eymard B, Pouget J, Hantai D: MUSK, a new target for mutations causing congenital myasthenic syndrome. Hum Mol Genet. 2004 Dec 15;13(24):3229-40. Epub 2004 Oct 20. [Article]
  8. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. [Article]
  9. Mihaylova V, Salih MA, Mukhtar MM, Abuzeid HA, El-Sadig SM, von der Hagen M, Huebner A, Nurnberg G, Abicht A, Muller JS, Lochmuller H, Guergueltcheva V: Refinement of the clinical phenotype in musk-related congenital myasthenic syndromes. Neurology. 2009 Dec 1;73(22):1926-8. doi: 10.1212/WNL.0b013e3181c3fce9. [Article]
  10. Maselli RA, Arredondo J, Cagney O, Ng JJ, Anderson JA, Williams C, Gerke BJ, Soliven B, Wollmann RL: Mutations in MUSK causing congenital myasthenic syndrome impair MuSK-Dok-7 interaction. Hum Mol Genet. 2010 Jun 15;19(12):2370-9. doi: 10.1093/hmg/ddq110. Epub 2010 Apr 6. [Article]
  11. Ben Ammar A, Soltanzadeh P, Bauche S, Richard P, Goillot E, Herbst R, Gaudon K, Huze C, Schaeffer L, Yamanashi Y, Higuchi O, Taly A, Koenig J, Leroy JP, Hentati F, Najmabadi H, Kahrizi K, Ilkhani M, Fardeau M, Eymard B, Hantai D: A mutation causes MuSK reduced sensitivity to agrin and congenital myasthenia. PLoS One. 2013;8(1):e53826. doi: 10.1371/journal.pone.0053826. Epub 2013 Jan 9. [Article]
  12. Tan-Sindhunata MB, Mathijssen IB, Smit M, Baas F, de Vries JI, van der Voorn JP, Kluijt I, Hagen MA, Blom EW, Sistermans E, Meijers-Heijboer H, Waisfisz Q, Weiss MM, Groffen AJ: Identification of a Dutch founder mutation in MUSK causing fetal akinesia deformation sequence. Eur J Hum Genet. 2015 Sep;23(9):1151-7. doi: 10.1038/ejhg.2014.273. Epub 2014 Dec 24. [Article]
  13. Gallenmuller C, Muller-Felber W, Dusl M, Stucka R, Guergueltcheva V, Blaschek A, von der Hagen M, Huebner A, Muller JS, Lochmuller H, Abicht A: Salbutamol-responsive limb-girdle congenital myasthenic syndrome due to a novel missense mutation and heteroallelic deletion in MUSK. Neuromuscul Disord. 2014 Jan;24(1):31-5. doi: 10.1016/j.nmd.2013.08.002. Epub 2013 Aug 7. [Article]
  14. Wilbe M, Ekvall S, Eurenius K, Ericson K, Casar-Borota O, Klar J, Dahl N, Ameur A, Anneren G, Bondeson ML: MuSK: a new target for lethal fetal akinesia deformation sequence (FADS). J Med Genet. 2015 Mar;52(3):195-202. doi: 10.1136/jmedgenet-2014-102730. Epub 2015 Jan 22. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails