ID MUSK_HUMAN Reviewed; 869 AA.
AC O15146; Q32MJ8; Q32MJ9; Q5VZW7; Q5VZW8;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 27-MAR-2024, entry version 196.
DE RecName: Full=Muscle, skeletal receptor tyrosine-protein kinase;
DE EC=2.7.10.1 {ECO:0000269|PubMed:25029443};
DE AltName: Full=Muscle-specific tyrosine-protein kinase receptor;
DE Short=MuSK;
DE Short=Muscle-specific kinase receptor;
DE Flags: Precursor;
GN Name=MUSK;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND ALTERNATIVE SPLICING (ISOFORMS
RP 2 AND 3).
RX PubMed=7546737; DOI=10.1016/0896-6273(95)90146-9;
RA Valenzuela D.M., Stitt T.N., DiStefano P.S., Rojas E., Mattsson K.,
RA Compton D.L., Nunez L., Park J.S., Stark J.L., Gies D.R., Thomas S.,
RA LeBeau M.M., Fernald A.A., Copeland N.G., Jenkins N.A., Burden S.J.,
RA Glass D.J., Yancopoulos G.D.;
RT "Receptor tyrosine kinase specific for the skeletal muscle lineage:
RT expression in embryonic muscle, at the neuromuscular junction, and after
RT injury.";
RL Neuron 15:573-584(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP INTERACTION WITH DOK7.
RX PubMed=20603078; DOI=10.1016/j.molcel.2010.06.007;
RA Bergamin E., Hallock P.T., Burden S.J., Hubbard S.R.;
RT "The cytoplasmic adaptor protein Dok7 activates the receptor tyrosine
RT kinase MuSK via dimerization.";
RL Mol. Cell 39:100-109(2010).
RN [5]
RP NEDDYLATION.
RX PubMed=20596523; DOI=10.1371/journal.pone.0011332;
RA Del Rincon S.V., Rogers J., Widschwendter M., Sun D., Sieburg H.B.,
RA Spruck C.;
RT "Development and validation of a method for profiling post-translational
RT modification activities using protein microarrays.";
RL PLoS ONE 5:E11332-E11332(2010).
RN [6]
RP CATALYTIC ACTIVITY, COFACTOR, PHOSPHORYLATION, AND MUTAGENESIS OF GLY-584;
RP LYS-609 AND ASP-743.
RX PubMed=25029443; DOI=10.1371/journal.pone.0102695;
RA Bainbridge T.W., DeAlmeida V.I., Izrael-Tomasevic A., Chalouni C., Pan B.,
RA Goldsmith J., Schoen A.P., Quinones G.A., Kelly R., Lill J.R., Sandoval W.,
RA Costa M., Polakis P., Arnott D., Rubinfeld B., Ernst J.A.;
RT "Evolutionary divergence in the catalytic activity of the CAM-1, ROR1 and
RT ROR2 kinase domains.";
RL PLoS ONE 9:E102695-E102695(2014).
RN [7]
RP VARIANT CMS9 MET-790, AND INVOLVEMENT IN CMS9.
RX PubMed=15496425; DOI=10.1093/hmg/ddh333;
RA Chevessier F., Faraut B., Ravel-Chapuis A., Richard P., Gaudon K.,
RA Bauche S., Prioleau C., Herbst R., Goillot E., Ioos C., Azulay J.-P.,
RA Attarian S., Leroy J.-P., Fournier E., Legay C., Schaeffer L., Koenig J.,
RA Fardeau M., Eymard B., Pouget J., Hantai D.;
RT "MUSK, a new target for mutations causing congenital myasthenic syndrome.";
RL Hum. Mol. Genet. 13:3229-3240(2004).
RN [8]
RP VARIANTS [LARGE SCALE ANALYSIS] GLY-27; MET-100; GLU-107; GLY-159; SER-222;
RP ILE-413; PHE-629; ALA-644; SER-664; LEU-696; ASP-782; SER-819; LEU-829 AND
RP HIS-858.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
RN [9]
RP VARIANT CMS9 ARG-344.
RX PubMed=19949040; DOI=10.1212/wnl.0b013e3181c3fce9;
RA Mihaylova V., Salih M.A., Mukhtar M.M., Abuzeid H.A., El-Sadig S.M.,
RA von der Hagen M., Huebner A., Nurnberg G., Abicht A., Muller J.S.,
RA Lochmuller H., Guergueltcheva V.;
RT "Refinement of the clinical phenotype in musk-related congenital myasthenic
RT syndromes.";
RL Neurology 73:1926-1928(2009).
RN [10]
RP VARIANTS CMS9 ILE-605 AND VAL-727, AND CHARACTERIZATION OF VARIANTS CMS9
RP ILE-605 AND VAL-727.
RX PubMed=20371544; DOI=10.1093/hmg/ddq110;
RA Maselli R.A., Arredondo J., Cagney O., Ng J.J., Anderson J.A., Williams C.,
RA Gerke B.J., Soliven B., Wollmann R.L.;
RT "Mutations in MUSK causing congenital myasthenic syndrome impair MuSK-Dok-7
RT interaction.";
RL Hum. Mol. Genet. 19:2370-2379(2010).
RN [11]
RP VARIANT CMS9 VAL-835, AND SUBCELLULAR LOCATION.
RX PubMed=23326516; DOI=10.1371/journal.pone.0053826;
RA Ben Ammar A., Soltanzadeh P., Bauche S., Richard P., Goillot E., Herbst R.,
RA Gaudon K., Huze C., Schaeffer L., Yamanashi Y., Higuchi O., Taly A.,
RA Koenig J., Leroy J.P., Hentati F., Najmabadi H., Kahrizi K., Ilkhani M.,
RA Fardeau M., Eymard B., Hantai D.;
RT "A mutation causes MuSK reduced sensitivity to agrin and congenital
RT myasthenia.";
RL PLoS ONE 8:E53826-E53826(2013).
RN [12]
RP VARIANT FADS1 THR-575, INVOLVEMENT IN FADS1, CHARACTERIZATION OF VARIANT
RP FADS1 THR-575, AND FUNCTION.
RX PubMed=25537362; DOI=10.1038/ejhg.2014.273;
RA Tan-Sindhunata M.B., Mathijssen I.B., Smit M., Baas F., de Vries J.I.,
RA van der Voorn J.P., Kluijt I., Hagen M.A., Blom E.W., Sistermans E.,
RA Meijers-Heijboer H., Waisfisz Q., Weiss M.M., Groffen A.J.;
RT "Identification of a Dutch founder mutation in MUSK causing fetal akinesia
RT deformation sequence.";
RL Eur. J. Hum. Genet. 23:1151-1157(2015).
RN [13]
RP VARIANT CMS9 GLU-38.
RX PubMed=24183479; DOI=10.1016/j.nmd.2013.08.002;
RA Gallenmuller C., Muller-Felber W., Dusl M., Stucka R., Guergueltcheva V.,
RA Blaschek A., von der Hagen M., Huebner A., Muller J.S., Lochmuller H.,
RA Abicht A.;
RT "Salbutamol-responsive limb-girdle congenital myasthenic syndrome due to a
RT novel missense mutation and heteroallelic deletion in MUSK.";
RL Neuromuscul. Disord. 24:31-35(2014).
RN [14]
RP INVOLVEMENT IN FADS1.
RX PubMed=25612909; DOI=10.1136/jmedgenet-2014-102730;
RA Wilbe M., Ekvall S., Eurenius K., Ericson K., Casar-Borota O., Klar J.,
RA Dahl N., Ameur A., Anneren G., Bondeson M.L.;
RT "MuSK: a new target for lethal fetal akinesia deformation sequence
RT (FADS).";
RL J. Med. Genet. 52:195-202(2015).
CC -!- FUNCTION: Receptor tyrosine kinase which plays a central role in the
CC formation and the maintenance of the neuromuscular junction (NMJ), the
CC synapse between the motor neuron and the skeletal muscle
CC (PubMed:25537362). Recruitment of AGRIN by LRP4 to the MUSK signaling
CC complex induces phosphorylation and activation of MUSK, the kinase of
CC the complex. The activation of MUSK in myotubes regulates the formation
CC of NMJs through the regulation of different processes including the
CC specific expression of genes in subsynaptic nuclei, the reorganization
CC of the actin cytoskeleton and the clustering of the acetylcholine
CC receptors (AChR) in the postsynaptic membrane. May regulate AChR
CC phosphorylation and clustering through activation of ABL1 and Src
CC family kinases which in turn regulate MUSK. DVL1 and PAK1 that form a
CC ternary complex with MUSK are also important for MUSK-dependent
CC regulation of AChR clustering. May positively regulate Rho family
CC GTPases through FNTA. Mediates the phosphorylation of FNTA which
CC promotes prenylation, recruitment to membranes and activation of RAC1 a
CC regulator of the actin cytoskeleton and of gene expression. Other
CC effectors of the MUSK signaling include DNAJA3 which functions
CC downstream of MUSK. May also play a role within the central nervous
CC system by mediating cholinergic responses, synaptic plasticity and
CC memory formation (By similarity). {ECO:0000250,
CC ECO:0000269|PubMed:25537362}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028,
CC ECO:0000269|PubMed:25029443};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:25029443};
CC -!- ACTIVITY REGULATION: Positively regulated by CK2. {ECO:0000250}.
CC -!- SUBUNIT: Monomer (By similarity). Homodimer (Probable). Interacts with
CC LRP4; the heterodimer forms an AGRIN receptor complex that binds AGRIN
CC resulting in activation of MUSK (By similarity). Forms a heterotetramer
CC composed of 2 DOK7 and 2 MUSK molecules which facilitates MUSK trans-
CC autophosphorylation on tyrosine residue and activation. Interacts (via
CC cytoplasmic part) with DOK7 (via IRS-type PTB domain); requires MUSK
CC phosphorylation. Interacts with DVL1 (via DEP domain); the interaction
CC is direct and mediates the formation of a DVL1, MUSK and PAK1 ternary
CC complex involved in AChR clustering (By similarity). Interacts with
CC PDZRN3; this interaction is enhanced by agrin (By similarity).
CC Interacts with FNTA; the interaction is direct and mediates AGRIN-
CC induced phosphorylation and activation of FNTA (By similarity).
CC Interacts with CSNK2B; mediates regulation by CK2 (By similarity).
CC Interacts (via the cytoplasmic domain) with DNAJA3 (By similarity).
CC Interacts with NSF; may regulate MUSK endocytosis and activity (By
CC similarity). Interacts with CAV3; may regulate MUSK signaling (By
CC similarity). Interacts with RNF31 (By similarity).
CC {ECO:0000250|UniProtKB:Q62838, ECO:0000305}.
CC -!- INTERACTION:
CC O15146; Q16543: CDC37; NbExp=3; IntAct=EBI-6423196, EBI-295634;
CC O15146; P08238: HSP90AB1; NbExp=2; IntAct=EBI-6423196, EBI-352572;
CC O15146; P62258: YWHAE; NbExp=2; IntAct=EBI-6423196, EBI-356498;
CC -!- SUBCELLULAR LOCATION: Postsynaptic cell membrane
CC {ECO:0000269|PubMed:23326516}; Single-pass type I membrane protein
CC {ECO:0000305}. Note=Colocalizes with acetylcholine receptors (AChR) to
CC the postsynaptic cell membrane of the neuromuscular junction.
CC {ECO:0000269|PubMed:23326516}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=O15146-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O15146-2; Sequence=VSP_035958, VSP_035959, VSP_035960;
CC Name=3;
CC IsoId=O15146-3; Sequence=VSP_035959, VSP_035960;
CC -!- PTM: Ubiquitinated by PDZRN3. Ubiquitination promotes endocytosis and
CC lysosomal degradation (By similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylated (By similarity). Phosphorylation is induced by
CC AGRIN in a LRP4-dependent manner (By similarity). Autophosphorylated
CC (PubMed:25029443). Autophosphorylation at Tyr-554 is required for
CC interaction with DOK7 which in turn stimulates the phosphorylation and
CC the activation of MUSK (By similarity). {ECO:0000250|UniProtKB:Q61006,
CC ECO:0000269|PubMed:25029443}.
CC -!- PTM: Neddylated. {ECO:0000269|PubMed:20596523}.
CC -!- DISEASE: Myasthenic syndrome, congenital, 9, associated with
CC acetylcholine receptor deficiency (CMS9) [MIM:616325]: A form of
CC congenital myasthenic syndrome, a group of disorders characterized by
CC failure of neuromuscular transmission, including pre-synaptic,
CC synaptic, and post-synaptic disorders that are not of autoimmune
CC origin. Clinical features are easy fatigability and muscle weakness
CC affecting the axial and limb muscles (with hypotonia in early-onset
CC forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and
CC the facial and bulbar musculature (affecting sucking and swallowing,
CC and leading to dysphonia). The symptoms fluctuate and worsen with
CC physical effort. CMS9 is a disorder of postsynaptic neuromuscular
CC transmission, due to deficiency of AChR at the endplate that results in
CC low amplitude of the miniature endplate potential and current.
CC {ECO:0000269|PubMed:15496425, ECO:0000269|PubMed:19949040,
CC ECO:0000269|PubMed:20371544, ECO:0000269|PubMed:23326516,
CC ECO:0000269|PubMed:24183479}. Note=The disease is caused by variants
CC affecting the gene represented in this entry. MUSK mutations lead to
CC decreased agrin-dependent AChR aggregation, a critical step in the
CC formation of the neuromuscular junction.
CC -!- DISEASE: Fetal akinesia deformation sequence 1 (FADS1) [MIM:208150]: A
CC clinically and genetically heterogeneous group of disorders with
CC congenital malformations related to impaired fetal movement. Clinical
CC features include fetal akinesia, intrauterine growth retardation,
CC polyhydramnios, arthrogryposis, pulmonary hypoplasia, craniofacial
CC abnormalities, and cryptorchidism. FADS1 inheritance is autosomal
CC recessive. {ECO:0000269|PubMed:25537362, ECO:0000269|PubMed:25612909}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=MuSK entry;
CC URL="https://en.wikipedia.org/wiki/MuSK_protein";
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DR EMBL; AF006464; AAB63044.1; -; mRNA.
DR EMBL; AL157881; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL513328; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC109098; AAI09099.1; -; mRNA.
DR EMBL; BC109099; AAI09100.1; -; mRNA.
DR CCDS; CCDS48005.1; -. [O15146-1]
DR CCDS; CCDS75874.1; -. [O15146-2]
DR RefSeq; NP_001159752.1; NM_001166280.1. [O15146-2]
DR RefSeq; NP_001159753.1; NM_001166281.1. [O15146-3]
DR RefSeq; NP_005583.1; NM_005592.3. [O15146-1]
DR PDB; 8S9P; EM; 3.80 A; C=1-869.
DR PDBsum; 8S9P; -.
DR AlphaFoldDB; O15146; -.
DR EMDB; EMD-40241; -.
DR SMR; O15146; -.
DR BioGRID; 110679; 73.
DR IntAct; O15146; 67.
DR MINT; O15146; -.
DR STRING; 9606.ENSP00000363571; -.
DR BindingDB; O15146; -.
DR ChEMBL; CHEMBL5684; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; O15146; -.
DR GuidetoPHARMACOLOGY; 1847; -.
DR TCDB; 8.A.23.1.29; the basigin (basigin) family.
DR GlyCosmos; O15146; 2 sites, No reported glycans.
DR GlyGen; O15146; 3 sites, 1 O-linked glycan (1 site).
DR iPTMnet; O15146; -.
DR PhosphoSitePlus; O15146; -.
DR BioMuta; MUSK; -.
DR jPOST; O15146; -.
DR MassIVE; O15146; -.
DR PaxDb; 9606-ENSP00000363571; -.
DR PeptideAtlas; O15146; -.
DR Antibodypedia; 29502; 540 antibodies from 34 providers.
DR DNASU; 4593; -.
DR Ensembl; ENST00000189978.10; ENSP00000189978.6; ENSG00000030304.15. [O15146-2]
DR Ensembl; ENST00000374448.9; ENSP00000363571.4; ENSG00000030304.15. [O15146-1]
DR GeneID; 4593; -.
DR KEGG; hsa:4593; -.
DR MANE-Select; ENST00000374448.9; ENSP00000363571.4; NM_005592.4; NP_005583.1.
DR UCSC; uc064vai.1; human. [O15146-1]
DR AGR; HGNC:7525; -.
DR CTD; 4593; -.
DR DisGeNET; 4593; -.
DR GeneCards; MUSK; -.
DR GeneReviews; MUSK; -.
DR HGNC; HGNC:7525; MUSK.
DR HPA; ENSG00000030304; Tissue enhanced (skeletal).
DR MalaCards; MUSK; -.
DR MIM; 208150; phenotype.
DR MIM; 601296; gene.
DR MIM; 616325; phenotype.
DR neXtProt; NX_O15146; -.
DR OpenTargets; ENSG00000030304; -.
DR Orphanet; 994; Fetal akinesia deformation sequence.
DR Orphanet; 98913; Postsynaptic congenital myasthenic syndromes.
DR PharmGKB; PA31326; -.
DR VEuPathDB; HostDB:ENSG00000030304; -.
DR eggNOG; KOG1026; Eukaryota.
DR GeneTree; ENSGT00940000158226; -.
DR HOGENOM; CLU_000288_30_5_1; -.
DR InParanoid; O15146; -.
DR OMA; KNNHPIM; -.
DR OrthoDB; 1614410at2759; -.
DR PhylomeDB; O15146; -.
DR TreeFam; TF106465; -.
DR PathwayCommons; O15146; -.
DR Reactome; R-HSA-3000178; ECM proteoglycans.
DR SignaLink; O15146; -.
DR SIGNOR; O15146; -.
DR BioGRID-ORCS; 4593; 8 hits in 1181 CRISPR screens.
DR ChiTaRS; MUSK; human.
DR GenomeRNAi; 4593; -.
DR Pharos; O15146; Tchem.
DR PRO; PR:O15146; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; O15146; Protein.
DR Bgee; ENSG00000030304; Expressed in male germ line stem cell (sensu Vertebrata) in testis and 106 other cell types or tissues.
DR ExpressionAtlas; O15146; baseline and differential.
DR Genevisible; O15146; HS.
DR GO; GO:0031594; C:neuromuscular junction; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0045211; C:postsynaptic membrane; ISS:UniProtKB.
DR GO; GO:0043235; C:receptor complex; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004713; F:protein tyrosine kinase activity; ISS:UniProtKB.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0017147; F:Wnt-protein binding; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0007613; P:memory; ISS:UniProtKB.
DR GO; GO:0007528; P:neuromuscular junction development; IDA:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IBA:GO_Central.
DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IBA:GO_Central.
DR GO; GO:2000541; P:positive regulation of protein geranylgeranylation; ISS:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0008582; P:regulation of synaptic assembly at neuromuscular junction; ISS:UniProtKB.
DR GO; GO:0071340; P:skeletal muscle acetylcholine-gated channel clustering; ISS:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR CDD; cd20970; IgI_1_MuSK; 1.
DR CDD; cd20968; IgI_2_MuSK; 1.
DR CDD; cd05050; PTKc_Musk; 1.
DR Gene3D; 1.10.2000.10; Frizzled cysteine-rich domain; 1.
DR Gene3D; 2.60.40.10; Immunoglobulins; 3.
DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR InterPro; IPR020067; Frizzled_dom.
DR InterPro; IPR036790; Frizzled_dom_sf.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR013098; Ig_I-set.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR PANTHER; PTHR24416:SF317; MUSCLE, SKELETAL RECEPTOR TYROSINE-PROTEIN KINASE; 1.
DR PANTHER; PTHR24416; TYROSINE-PROTEIN KINASE RECEPTOR; 1.
DR Pfam; PF01392; Fz; 1.
DR Pfam; PF07679; I-set; 2.
DR Pfam; PF13927; Ig_3; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PIRSF; PIRSF000615; TyrPK_CSF1-R; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00409; IG; 3.
DR SMART; SM00408; IGc2; 3.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF48726; Immunoglobulin; 3.
DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR PROSITE; PS50038; FZ; 1.
DR PROSITE; PS50835; IG_LIKE; 3.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Cell membrane;
KW Congenital myasthenic syndrome; Developmental protein; Differentiation;
KW Disease variant; Disulfide bond; Glycoprotein; Immunoglobulin domain;
KW Kinase; Magnesium; Membrane; Metal-binding; Muscle protein;
KW Nucleotide-binding; Phosphoprotein; Postsynaptic cell membrane; Receptor;
KW Reference proteome; Repeat; Signal; Synapse; Transferase; Transmembrane;
KW Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..869
FT /note="Muscle, skeletal receptor tyrosine-protein kinase"
FT /id="PRO_0000024446"
FT TOPO_DOM 24..495
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 496..516
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 517..869
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 28..116
FT /note="Ig-like 1"
FT DOMAIN 121..205
FT /note="Ig-like 2"
FT DOMAIN 212..302
FT /note="Ig-like 3"
FT DOMAIN 312..450
FT /note="FZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DOMAIN 575..856
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 725
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 581..589
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 609
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 554
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q61006"
FT MOD_RES 681
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000250|UniProtKB:Q61006"
FT MOD_RES 698
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000250|UniProtKB:Q61006"
FT MOD_RES 755
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q62838"
FT CARBOHYD 222
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 338
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
FT DISULFID 49..99
FT /evidence="ECO:0000250"
FT DISULFID 98..112
FT /evidence="ECO:0000250"
FT DISULFID 142..190
FT /evidence="ECO:0000250"
FT DISULFID 233..282
FT /evidence="ECO:0000250"
FT DISULFID 317..382
FT /evidence="ECO:0000250"
FT DISULFID 325..375
FT /evidence="ECO:0000250"
FT DISULFID 366..406
FT /evidence="ECO:0000250"
FT DISULFID 394..447
FT /evidence="ECO:0000250"
FT DISULFID 398..434
FT /evidence="ECO:0000250"
FT VAR_SEQ 209
FT /note="E -> EEESEPEQDTK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_035958"
FT VAR_SEQ 307..394
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_035959"
FT VAR_SEQ 454..462
FT /note="DYNKENLKT -> A (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_035960"
FT VARIANT 27
FT /note="A -> G (in dbSNP:rs56054734)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041748"
FT VARIANT 38
FT /note="D -> E (in CMS9; dbSNP:rs775587809)"
FT /evidence="ECO:0000269|PubMed:24183479"
FT /id="VAR_072785"
FT VARIANT 100
FT /note="T -> M (in dbSNP:rs35142681)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041749"
FT VARIANT 107
FT /note="G -> E (in dbSNP:rs55786136)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041750"
FT VARIANT 159
FT /note="S -> G (in dbSNP:rs35176182)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041751"
FT VARIANT 222
FT /note="N -> S (in dbSNP:rs55826142)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041752"
FT VARIANT 344
FT /note="P -> R (in CMS9; dbSNP:rs387906803)"
FT /evidence="ECO:0000269|PubMed:19949040"
FT /id="VAR_072786"
FT VARIANT 413
FT /note="M -> I (in dbSNP:rs2274419)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_021930"
FT VARIANT 575
FT /note="I -> T (in FADS1; reduces agrin-dependent AChR
FT aggregation and tyrosine kinase activity in developing
FT neuromuscular junction; dbSNP:rs751889864)"
FT /evidence="ECO:0000269|PubMed:25537362"
FT /id="VAR_072787"
FT VARIANT 605
FT /note="M -> I (in CMS9; affects interaction with DOK7 and
FT impairs MUSK phosphorylation; altered AChR clustering;
FT dbSNP:rs766640370)"
FT /evidence="ECO:0000269|PubMed:20371544"
FT /id="VAR_066604"
FT VARIANT 629
FT /note="L -> F (in dbSNP:rs34267283)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041753"
FT VARIANT 644
FT /note="V -> A (in dbSNP:rs41279055)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041754"
FT VARIANT 664
FT /note="N -> S (in dbSNP:rs55963442)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041755"
FT VARIANT 696
FT /note="P -> L (in dbSNP:rs56126328)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041756"
FT VARIANT 727
FT /note="A -> V (in CMS9; affects interaction with DOK7 and
FT impairs MUSK phosphorylation; altered AChR clustering;
FT dbSNP:rs397515450)"
FT /evidence="ECO:0000269|PubMed:20371544"
FT /id="VAR_066605"
FT VARIANT 782
FT /note="E -> D (in dbSNP:rs34614566)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041757"
FT VARIANT 790
FT /note="V -> M (in CMS9; does not affect catalytic kinase
FT activity; reduces protein expression and stability;
FT dbSNP:rs199476083)"
FT /evidence="ECO:0000269|PubMed:15496425"
FT /id="VAR_023046"
FT VARIANT 819
FT /note="N -> S (in a lung neuroendocrine carcinoma sample;
FT somatic mutation; dbSNP:rs757577755)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041758"
FT VARIANT 829
FT /note="V -> L (in dbSNP:rs578430)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_033837"
FT VARIANT 835
FT /note="M -> V (in CMS9; reduces AChR aggregation in
FT developing neuromuscular junction)"
FT /evidence="ECO:0000269|PubMed:23326516"
FT /id="VAR_072788"
FT VARIANT 858
FT /note="R -> H (in dbSNP:rs34115159)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041759"
FT MUTAGEN 584
FT /note="G->C,D: Mild decrease in kinase activity."
FT /evidence="ECO:0000269|PubMed:25029443"
FT MUTAGEN 609
FT /note="K->R: Severe loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:25029443"
FT MUTAGEN 743
FT /note="D->N: Severe loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:25029443"
SQ SEQUENCE 869 AA; 97056 MW; 3DDC20E179FA010C CRC64;
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
//
